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Polylactic acid (PLA) has garnered attention for use in interim dental restorations due to its biocompatibility, biodegradability, low cost, ease of fabrication, and moderate strength. However, its performance under intraoral conditions, particularly under heat and moisture, remains underexplored. This study evaluated the mechanical properties of PLA interim crowns compared with those of polymethylmethacrylate (PMMA) and bisphenol crowns under simulated intraoral conditions with thermocycling. Three CAD/CAM polymers-PMMA (milling), PLA (fused deposition), and bisphenol (stereolithography)-were tested for fracture resistance, hardness, and surface roughness. For fracture strength, 25 crowns from each group were cemented onto dies. The Shore D hardness and surface roughness were measured on round discs before and after 10,000 thermocycles (5°C/55°C). The surface topography was assessed via scanning electron microscopy. PMMA exhibited the highest fracture strength (2787.93 N), followed by bisphenol (2165.47 N) and PLA (2088.78 N), with no significant difference between the latter two. PMMA and bisphenol showed vertical fractures and cracks, whereas PLA showed crown tearing or die deformation. Bisphenol had the highest Shore D hardness, followed by PMMA and PLA, with no significant changes after thermocycling. The surface roughness (Ra) was lowest for bisphenol and similar between PMMA and PLA. The roughness (Rz) increased from bisphenol to PMMA to PLA. The roughness of the PMMA remained unchanged after thermocycling, whereas the Ra but not the Rz of the PLA increased. Bisphenol showed a significant increase in both Ra and Rz (p

Abstract Background Phlegm is prevalent symptom in patients with chronic obstructive pulmonary disease (COPD). Few studies have investigated the effectiveness of N-acetylcysteine (NAC) nebulizer therapy in COPD patients. We evaluated the effect of nebulized NAC on the improvement of phlegm symptom in COPD patients. Methods This was a 12-week, prospective, single-arm, open-label, phase IV multi-center trial (NCT05102305, Registration Date: 20-October-2021). We enrolled patients aged ≥ 40 years with post bronchodilator forced expiratory volume in one second/forced vital capacity (FEV1/FVC)

Abstract The lack of an appropriate preclinical model of metabolic dysfunction-associated steatotic liver disease (MASLD) that recapitulates the whole disease spectrum impedes exploration of disease pathophysiology and the development of effective treatment strategies. Here, we develop a mouse model (Streptozotocin with high-fat diet, STZ + HFD) that gradually develops fatty liver, metabolic dysfunction-associated steatohepatitis (MASH), hepatic fibrosis, and hepatocellular carcinoma (HCC) in the context of metabolic dysfunction. The hepatic transcriptomic features of STZ + HFD mice closely reflect those of patients with obesity accompanying type 2 diabetes mellitus, MASH, and MASLD-related HCC. Dietary changes and tirzepatide administration alleviate MASH, hepatic fibrosis, and hepatic tumorigenesis in STZ + HFD mice. In conclusion, a murine model recapitulating the main histopathologic, transcriptomic, and metabolic alterations observed in MASLD patients is successfully established.

Background The mechanisms leading to lung fibrosis are still under investigation. This study aimed to demonstrate whether antacids could prevent the development of interstitial lung disease (ILD). Methods This population-based longitudinal cohort study was conducted between January 2006 and December 2010 in South Korea. Eligible subjects were ≥40 years of age, exposed to proton pump inhibitors (PPI)±histamine-2 receptor antagonists (H-2 blockers) or H-2 blockers only, and had no history of ILD between 2004 and 2005. Exposure to antacids was defined as the administration of either PPI or H-2 receptor antagonists for >14 days, whereas underexposure was defined as antacid treatment administered for less than 14 days. Newly developed ILDs, including idiopathic pulmonary fibrosis (IPF), were counted during the 5-year observation period. The association between antacid exposure and ILD development was evaluated using adjusted Cox regression models with variables, such as age, sex, smoking history, and comorbidities. Results The incidence rates of ILD with/without antacid use were 43.2 and 33.8/100,000 person-years, respectively and those of IPF were 14.9 and 22.9/100,000 person-years, respectively. In multivariable analysis, exposure to antacid before the diagnosis of ILD was independently associated with a reduced development of ILD (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.45 to 0.71; p

BackgroundPirfenidone is an antifibrotic medication approved for idiopathic pulmonary fibrosis (IPF). Fybro®, a generic version of pirfenidone developed in South Korea, gained approval and is available in 200 mg and in higher-dose formulations of 400 and 600 mg. This real-world prospective cohort study investigated the safety and effectiveness of Fybro®.MethodsA nationwide observational study was conducted in patients with IPF. Patients were followed up for 6 months, with a subset of patients being followed up for 12 months. Data on lung function and adverse events were collected. Patient adherence to fewer-pill (400 and/or 600 mg tablets) and multiple-pill (200 mg tablets) regimens were compared.ResultsOf the 359 enrolled patients, 352 received pirfenidone (Fybro®) at least once and were included in the analysis. The mean age was 69.0 years and 82.4% of patients were male. The median treatment duration was 186.0 days. A total of 253 patients (71.9%) experienced adverse events, with decreased appetite being the most common (16.5%). The adjusted decline rates in lung function were −1.5% and −2.2% predicted per year for forced vital capacity and diffusing capacity, respectively. No significant differences were observed based on the pirfenidone dose. For a daily intake of 1,200 or 1800 mg of pirfenidone, a significantly longer duration of drug administration was observed with the fewer-pill regimen than with multiple-pill regimen.ConclusionThe safety and effectiveness of Fybro® observed in this real-world cohort study are consistent with previous studies. Using higher-strength tablets to reduce pill burden may improve medication adherence.

Background Mechanical power (MP) has been reported to be associated with clinical outcomes. Because the original MP equation is derived from paralyzed patients under volume-controlled ventilation, its application in practice could be limited in patients receiving pressure-controlled ventilation (PCV). Recently, a simplified equation for patients under PCV was developed. We investigated the association between MP and intensive care unit (ICU) mortality. Methods We conducted a retrospective analysis of Korean data from the Fourth International Study of Mechanical Ventilation. We extracted data of patients under PCV on day 1 and calculated MP using the following simplified equation: MPPCV = 0.098 ∙ respiratory rate ∙ tidal volume ∙ (ΔPinsp + positive end-expiratory pressure), where ΔPinsp is the change in airway pressure during inspiration. Patients were divided into survivors and non-survivors and then compared. Multivariable logistic regression was performed to determine association between MPPCV and ICU mortality. The interaction of MPPCV and use of neuromuscular blocking agent (NMBA) was also analyzed. Results A total of 125 patients was eligible for final analysis, of whom 38 died in the ICU. MPPCV was higher in non-survivors (17.6 vs. 26.3 J/min, P

Abstract Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is currently the leading cause of chronic liver disease worldwide. Metabolic Dysfunction-Associated Steatohepatitis (MASH), an advanced form of MASLD, can progress to liver fibrosis, cirrhosis, and hepatocellular carcinoma. Based on recent findings by our team that liver 5HT2A knockout male mice suppressed steatosis and reduced fibrosis-related gene expression, we developed a peripheral 5HT2A antagonist, compound 11c for MASH. It shows good in vitro activity, stability, and in vivo pharmacokinetics (PK) in rats and dogs. Compound 11c also shows good in vivo efficacy in a diet-induced obesity (DIO) male mice model and in a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) male mice model, effectively improving histologic features of MASH and fibrosis. According to the tissue distribution study using [14C]-labeled 11c, the compound was determined to be a peripheral 5HT2A antagonist. Collectively, first-in-class compound 11c shows promise as a therapeutic agent for the treatment of MASLD and MASH.

PurposeTo assess the association between pattern changes in hemoglobin levels over time and the incidence of dementia using trajectories in females aged 55-79 years.Materials and methodsWe conducted a retrospective cohort study using females of aged 55-79 years from the National Health Insurance Service National Health Screening Cohort in Korea. To identify hemoglobin trajectories over eight years (2002-2009), we performed a three-step approach comprising measures of change, factor analysis, and cluster analysis. Univariate and multivariate Cox proportional hazard models were used to assess the associations between hemoglobin trajectories and the incidence of dementia.ResultsWe included 20,195 of 235,742 female participants. New dementia (N = 2664) was developed during follow-up period (2010-2015). Five hemoglobin trajectories were identified: high, mid, low, increasing, and decreasing. With high as a reference, the hazard ratios (HRs) for low and decreasing trajectories were significant, 1.28 (95% confidence interval [CI], 1.13-1.45) and 1.21 (95% CI, 1.10-1.34) in univariate models, respectively. However, only the HR for the decreasing trajectory was significant, 1.12 (95% CI, 1.01-1.24) after adjustment for confounders.ConclusionThe decreasing trajectory of hemoglobin levels within the normal range was associated with dementia. Even females aged 55-79 years without anemia might be vulnerable to dementia development risk.

Background Patients with coronavirus disease 2019 (COVID-19) infections often have macrovascular or microvascular thrombosis and inflammation, which are known to be associated with a poor prognosis. Heparin has been hypothesized that administration of heparin with treatment dose rather than prophylactic dose for prevention of deep vein thrombosis in COVID-19 patients. Methods Studies comparing therapeutic or intermediate anticoagulation with prophylactic anticoagulation in COVID-19 patients were eligible. Mortality, thromboembolic events, and bleeding were the primary outcomes. PubMed, Embase, the Cochrane Library, and KMbase were searched up to July 2021. A meta-analysis was performed using random-effect model. Subgroup analysis was conducted according to disease severity. Results Six randomized controlled trials (RCTs) with 4,678 patients and four cohort studies with 1,080 patients were included in this review. In the RCTs, the therapeutic or intermediate anticoagulation was associated with significant reductions in the occurrence of thromboembolic events (5 studies, n=4,664; relative risk [RR], 0.72; P=0.01), and a significant increase in bleeding events (5 studies, n=4,667; RR, 1.88; P=0.004). In the moderate patients, therapeutic or intermediate anticoagulation was more beneficial than prophylactic anticoagulation in terms of thromboembolic events, but showed significantly higher bleeding events. In the severe patients, the incidence of thromboembolic and bleeding events in the therapeutic or intermediate. Conclusions The study findings suggest that prophylactic anticoagulant treatment should be used in patients with moderate and severe COVID-19 infection groups. Further studies are needed to determine more individualized anticoagulation guidance for all COVID-19 patients.

Abstract Background Prone position has already been demonstrated to improve survival in non-COVID acute respiratory distress syndrome and has been widely performed in COVID-19 patients with respiratory failure, both in non-intubated and intubated patients. However, the beneficial effect of the prone position in COVID-19 pneumonia still remains controversial. Therefore, we aimed to evaluate the effectiveness and safety of the prone position compared with the non-prone in non-intubated and intubated COVID-19 patients, respectively. Methods We searched the MEDLINE, EMBASE, and Cochrane databases, as well as one Korean domestic database, on July 9, 2021, and updated the search 9 times to September 14, 2022. Studies that compared prone and non-prone positions in patients with COVID-19 were eligible for inclusion. The primary outcomes were mortality, need for intubation, and adverse events. Results Of the 1259 records identified, 9 randomized controlled trials (RCTs) and 23 nonrandomized studies (NRSs) were eligible. In the non-intubated patients, the prone position reduced the intubation rate compared with the non-prone position in 6 RCTs (n = 2156, RR 0.81, P = 0.0002) and in 18 NRSs (n = 3374, RR 0.65, P = 0.002). In the subgroup analysis according to the oxygen delivery method, the results were constant only in the HFNC or NIV subgroup. For mortality, RCTs reported no difference between prone and non-prone groups, but in NRSs, the prone position had a significant advantage in mortality [18 NRSs, n = 3361, relative risk (RR) 0.56, P

Abstract Background Evidence regarding the timing of the application of mechanical ventilation among patients with severe coronavirus disease (COVID-19) is insufficient. This systematic review and meta-analysis aimed to evaluate the effectiveness of early intubation compared to late intubation in patients with severe and critical COVID-19. Methods For this study, we searched the MEDLINE, EMBASE, and Cochrane databases as well as one Korean domestic database on July 15, 2021. We updated the search monthly from September 10, 2021 to February 10, 2022. Studies that compared early intubation with late intubation in patients with severe COVID-19 were eligible for inclusion. Relative risk (RR) and mean difference (MD) were calculated as measures of effect using the random-effects model for the pooled estimates of in-hospital mortality, intensive care unit (ICU) length of stay (LOS), duration of mechanical ventilation (MV), hospital LOS, ICU-free days, and ventilator-free days. Subgroup analysis was performed based on the definition of early intubation and the index time. To assess the risk of bias in the included studies, we used the Risk of Bias Assessment tool for Non-randomized studies 2.0. Results Of the 1523 records identified, 12 cohort studies, involving 2843 patients with severe COVID-19 were eligible. There were no differences in in-hospital mortality (8 studies, n = 795; RR 0.91, 95% CI 0.75–1.10, P = 0.32, I 2 = 33%), LOS in the ICU (9 studies, n = 978; MD −1.77 days, 95% CI −4.61 to 1.07 days, P = 0.22, I 2 = 78%), MV duration (9 studies, n = 1,066; MD −0.03 day, 95% CI −1.79 to 1.72 days, P = 0.97, I 2 = 49%), ICU-free days (1 study, n = 32; 0 day vs. 0 day; P = 0.39), and ventilator-free days (4 studies, n = 344; MD 0.94 day, 95% CI −4.56 to 6.43 days, P = 0.74, I 2 = 54%) between the early and late intubation groups. However, the early intubation group had significant advantage in terms of hospital LOS (6 studies, n = 738; MD −4.32 days, 95% CI −7.20 to −1.44 days, P = 0.003, I 2 = 45%). Conclusion This study showed no significant difference in both primary and secondary outcomes between the early intubation and late intubation groups. Trial registration This study was registered in the Prospective Register of Systematic Reviews on 16 February, 2022 (registration number CRD42022311122).

Background/Aims The treatment of epidermal growth factor receptor (EGFR)-mutated lung cancer cases has shown remarkable development in the past two decades. However, there have been limited studies comparing the prognostic effects of EGFR-tyrosine kinase inhibitor (TKI) and other treatment modalities. Therefore, we compared the survival outcomes of patients treated with EGFR-TKIs versus those treated with other treatment modalities. Methods Patient data were collected from the Korean National Health Insurance Database, National Health Insurance Service-National Sample Cohort 2002 to 2015, which was released by the Korean National Health Insurance Service in 2015. The lung cancer group included patients (n = 2,003) initially diagnosed with lung cancer between January 2010 and December 2013. The main outcome was all-cause mortality. A Cox proportional hazard regression analysis was used to calculate the relative risk of mortality. Results Among the newly diagnosed lung cancer cases, 1,004 (50.1%) were included in the analysis. A 15.1-month median survival benefit was observed in the EGFR-TKI group than that of the multimodality therapy group. The risk of mortality was as follows: EGFR-TKI treatment group (n = 142; hazard ratio [HR], 5.29; 95% confidence interval [CI], 3.57 to 7.86) and multimodality therapy group (n = 326; HR, 7.42; 95% CI, 5.19 to 10.63) compared to surgery only (n = 275). Conclusions Patients with advanced lung cancer harbouring EGFR mutations treated with EGFR-TKIs showed better median survival and lower risk of mortality than those in the multimodality therapy group. In the case of EGFR-mutated advanced lung cancer, there is room for downstaging in the TNM classification.

Background/Aims There are few studies describing contemporary status of mechanical ventilation in Korea. We investigated changes in management and outcome of mechanical ventilation in Korea. Methods International, prospective observational cohort studies have been conducted every 6 years since 1998. Korean intensive care units (ICUs) participated in 2010 and 2016 cohorts. We compared 2016 and 2010 Korean data. Results Two hundred and twenty-six patients from 18 ICUs and 275 patients from 12 ICUs enrolled in 2016 and 2010, respectively. In 2016 compared to 2010, use of non-invasive ventilation outside ICU increased (10.2% vs. 2.5%, p = 0.001). Pressure-control ventilation was the most common mode in both groups. Initial tidal volume (7.1 mL/kg vs. 7.4 mL/kg, p = 0.372) and positive end-expiratory pressure (6 cmH2O vs. 6 cmH2O, p = 0.141) were similar, but peak pressure (22 cmH2O vs. 24 cmH2O, p = 0.011) was lower in 2016. More patients received sedatives (70.7% vs. 57.0%, p = 0.002) and analgesics (86.5% vs. 51.1%, p < 0.001) in 2016. The awakening (48.4% vs. 31.0%, p = 0.002) was more frequently attempted in 2016. The accidental extubation rate decreased to one tenth of what it was in 2010 (1.1% vs. 10.2%, p < 0.001). The ICU mortality did not change (31.4% vs. 35.6%, p = 0.343) but ICU length of stay showed a decreasing trend (9 days vs. 10 days, p = 0.054) in 2016. Conclusions There were temporal changes in care of patients on mechanical ventilation including better control of pain and agitation, and active attempt of awakening.

Statement of problem: Biomaterials, including polymethyl methacrylate (PMMA) and bisacrylate, have been widely used as conventional interim materials and may exhibit cytotoxicity or systemic toxicity. Purpose: This study was designed to compare the mechanical properties of polylactic acid (PLA) as an alternative to conventional dental polymers for computer-aided design and manufacturing (CAD/CAM). Material and methods: Four groups (n = 20 per group) of CAD/CAM polymers were assessed. Specimens of PLA (PLA Mill) and PMMA (PMMA Mill) for subtractive manufacturing, PLA for fused deposition modeling (PLA FDM), and bisphenol for additive manufacturing by stereolithography (Bisphenol SLA) were fabricated into 2-mm-wide, 2-mm-thick and 25-mm-long specimens using a milling machine, an FDM printer, and an SLA printer, respectively.The flexural strength (FS) and elastic modulus (EM) were calculated. The surface roughness and Shore D hardness were analyzed with a 3D optical surface roughness analyzer and a Shore durometer, respectively. Results: PLA Mill showed the lowest FS (64.9 ± 8.28), followed by PLA FDM (104.27 ± 4.42 MPa), PMMA Mill (139.2 ± 20.95 MPa), and Bisphenol SLA (171.56 ± 15.38 MPa), with statistically significant differences. PLA FDM showed the highest EM, followed by PLA Mill, Bisphenol SLA, and PMMA Mill. Significant differences were observed not only between PMMA Mill and Bisphenol SLA but also between PLA FDM and PLA Mill. The lowest Shore D hardness was observed for PLA FDM, followed by PLA Mill, PMMA Mill, and Bisphenol SLA, which showed the highest value among the 4 groups, with significance. The highest values for the surface roughness parameters were observed for PLA Mill, and the lowest were observed for Bisphenol SLA. Conclusions: Among the tested CAD/CAM polymers, Bisphenol SLA was the most durable material, and the mechanical properties of PLA FDM were within the clinically acceptable range.

Purpose: This study aimed to compare the characteristics of venous thromboembolic disease (VTE) in Korean to Caucasian population. Materials and Methods : XALIA-LEA and XALIA were phase IV non-interventional prospective studies with identical designs that investigated the effect of rivaroxaban versus standard anticoagulation for VTE. Koreans accounted for the largest proportion of the overall enrolled population of XALIA-LEA. However, in the XALIA study, most patients were Caucasian. Therefore, Korean data from XALIA-LEA and Caucasian data from XALIA were used in this study. This study compared the clinical characteristics and primary outcomes of the XALIA program, including major bleeding, recurrent VTE, and all-cause mortality. Results : The Korean population was older, was less obese, and had more active cancer at baseline than the Caucasian population. Provoked VTE was more common in the Korean population. Interestingly, Koreans showed less accompanying thrombophilia than Caucasians, and factor V Leiden mutations were not detected. Korean analyses comparing the effects of rivaroxaban and standard anticoagulation with primary outcomes showed a lower incidence of major bleeding, recurrent VTE, and all-cause mortality with rivaroxaban. Similar results were obtained in the propensity score matching analysis. Conclusion : Characteristic differences were found between Korean and Caucasian VTE patients. Despite these ethnic differences, the effectiveness and safety of rivaroxaban therapy in these patients were consistent.

Idiopathic pulmonary fibrosis (IPF) was considered untreatable until the development of therapeutic drugs and diagnostic technology that made it possible to slow the progression of IPF. In 2014, pirfenidone and nintedanib were approved simultaneously as therapeutic drugs for patients with IPF. These drugs have proven effective in reducing further progression of pulmonary fibrosis, acute exacerbation, and mortality and have consistent effects regardless of the severity of IPF. The indications of nintedanib and pirfenidone are gradually expanding for various other diseases that cause pulmonary fibrosis. Currently, IPF pathogenesis is associated with the type 2 alveolar epithelium and repeated or persistent damage to its cells. Such damage may induce an abnormal wound healing response, causing fibrosis rather than repair. Several promising drugs have been developed for reducing or reversing fibrosis, each with a different molecular target implicated in pulmonary fibrosis. Due to the heterogeneous mechanisms underlying pulmonary fibrosis, future disease management is likely to comprise combinations of therapies targeting a range of disease mechanisms.

Abstract The purpose of the study was to compare clinical characteristics and mortality among adults infected with human coronaviruses (HCoV) 229E and OC43. We conducted a retrospective cohort study of adults (≥ 18 years) admitted to the ward of a university teaching hospital for suspected viral infection from October 2012 to December 2017. Multiplex real-time polymerase chain reaction (PCR) was used to test for respiratory viruses. Multivariate logistic regression was used to compare mortality among patients with HCoV 229E and HCoV OC43 infections. The main outcome was 30-day all-cause mortality. Of 8071 patients tested, 1689 were found to have a respiratory virus infection. Of these patients, 133 had HCoV infection, including 12 mixed infections, 44 HCoV 229E infections, and 77 HCoV OC43 infections. HCoV 229E infections peaked in January and February, while HCoV OC43 infections occurred throughout the year. The 30-day all-cause mortality was 25.0% among patients with HCoV 229E infection, and 9.1% among patients with HCoV OC43 infection (adjusted odds ratio: 3.58, 95% confidence interval: 1.19–10.75). Infections with HCoVs 229E and OC43 appear to have different seasonal patterns, and HCoV 229E might be more virulent than HCoV OC43.

Background The use of sedative drugs may be an important therapeutic intervention during noninvasive ventilation (NIV) in intensive care units (ICUs). The purpose of this study was to assess the current application of analgosedation in NIV and its impact on clinical outcomes in Korean ICUs. Methods Twenty Korean ICUs participated in the study, and data was collected on NIV use during the period between June 2017 and February 2018. Demographic data from all adult patients, NIV clinical parameters, and hospital mortality were included. Results A total of 155 patients treated with NIV in the ICUs were included, of whom 26 received pain and sedation therapy (sedation group) and 129 did not (control group). The primary cause of ICU admission was due to acute exacerbation of obstructed lung disease (45.7%) in the control group and pneumonia treatment (53.8%) in the sedation group. In addition, causes of NIV application included acute hypercapnic respiratory failure in the control group (62.8%) and post-extubation respiratory failure in the sedation group (57.7%). Arterial partial pressure of carbon dioxide (PaCO2) levels before and after 2 hours of NIV treatment were significantly decreased in both groups: from 61.9±23.8 mm Hg to 54.9±17.6 mm Hg in the control group (P

Background/Aims Seasonal variation is an environmental factor proposed to affect the incidence of venous thromboembolism (VTE). However, VTE seasonal variation is not well studied in Asian populations, which have different genetic determinants of VTE compared to Westerners. The present study aimed at investigating seasonal variation of VTE occurrence and the effect of various demographic factors (i.e., age, sex, and co-morbidities) on variation. Methods VTE seasonal variation was evaluated in 59,626 index cases (from January 2009 to December 2013) in the Korean Health Insurance Review and Assessment Service database. We quantified and compared VTE occurrence across four seasons, and additionally assessed monthly through a chronobiological analysis. Results VTE incidence varied both seasonally and monthly, with new cases peaking in the winter (January and February) and the lowest incidence in the summer (August and September). After adjusting for sex, age, type of VTE, and combined cancer diagnosis, winter remained a significant independent factor driving VTE incidence. Additionally, seasonal variation was prominent in patients aged 60 years or older and in patients with pulmonary embolism, but not so prominent in patients of aged less than 60 years and patients with deep vein thrombosis. Conclusions Seasonal variation was a weak but independent contributor to VTE incidence in a Korean population diagnosed from 2009 to 2013, especially in those individuals with old age or suffering from a pulmonary embolism.

Kidney disease: The flaw behind a faulty filter A genetic mutation associated with kidney disease impairs the maturation and migration of cells that filter waste products out of the blood. Tiny tendrils from kidney cells called podocytes establish a tight meshwork that keeps blood proteins in circulation while allowing unwanted contaminants to pass through. Mutations in the PLCE1 gene disrupt this filter, leading to a disorder called nephrotic syndrome Researchers led by Heon Yung Gee at Yonsei University College of Medicine, Seoul, South Korea, have uncovered mechanisms underlying this malfunction. Working with cultured podocytes, they showed that loss of PLCE1 impairs cell migration, potentially undermining their ability to form a meshwork. The researchers also found that the protein encoded by PLCE1 interacts with other molecules that promote cell division and maturation, revealing another mechanism by which mutations could contribute to loss of podocyte function.

Background Information about the epidemiology of venous thromboembolism (VTE) recurrence in Korea is lacking. The purpose of this study was to investigate VTE cumulative recurrence rates and identify risk factors for VTE recurrence among Korean adults. Methods A retrospective cohort study was conducted on adult patients (≥18 years) admitted to a university teaching hospital for pulmonary embolism (PE) from 2005 to 2013. The main outcome of interest was a recurrence of VTE. We used Cox proportional hazard regression analyses to calculate the relative risk of VTE recurrence. Results Five-year cumulative incidence of recurrent VTE events was 21.5% (95% confidence interval [CI], 17.7–25.4) in all cases of PE; 17% after provoked and 27% after unprovoked PE. Multivariate analysis showed that body mass index (BMI) of ≥25 (hazard ratio [HR], 2.02; 95% CI, 1.17–3.46; p=0.01) and longer anticoagulation therapy duration (HR, 0.90; 95% CI, 0.84–0.96; p

Background/Aims Limited data are available regarding the efficacy of rivaroxaban for the treatment of cancer-associated venous thromboembolism (VTE). The aim of this study was to evaluate the effectiveness and safety of rivaroxaban for the treatment of VTE in active cancer patients. Methods In this prospective, multicenter, open-label trial (NCT01989845), we enrolled patients with active cancer and objectively diagnosed lower-extremity deep vein thrombosis, pulmonary embolism (PE), or both from November 2013 to June 2016. Active cancer was defined as a histologically confirmed malignancy, which was diagnosed or treated within the previous 6 months, or as a recurrent/metastatic cancer. Patients received oral rivaroxaban 15 mg twice daily for first 3 weeks, followed by 20 mg once daily for 6 months. The primary outcome was the symptomatic recurrent VTE and the secondary outcomes included any recurrent VTE, major or clinically relevant non-major (CRNM) bleeding events, and overall mortality. All study outcomes were validated by blinded central adjudication. Results Of 124 patients enrolled, 110 (88.7%) had solid cancer, 93 (75.0%) had metastatic disease, and 110 (88.7%) were receiving chemotherapy or radiotherapy. During the 6-month study period, seven patients experienced symptomatic recurrent VTE (cumulative incidence, 5.9%), and two patients experienced incidental recurrent PE (cumulative incidence of any recurrent VTE, 7.6%). Major bleeding events occurred in six patients (cumulative incidence, 5.3%) and CRNM bleeding events in 11 patients (cumulative incidence, 10.2%). Twenty-eight patients (overall mortality, 24.0%) died. Conclusions Rivaroxaban is effective and safe for the treatment of VTE in patients with active cancer.

Background Mortality rates associated with sepsis have increased progressively in Korea, but domestic epidemiologic data remain limited. The objective of this study was to investigate the characteristics, management and clinical outcomes of sepsis patients in Korea. Methods This study is a multicenter retrospective cohort study. A total of 64,021 adult patients who visited an emergency department (ED) within one of the 19 participating hospitals during a 1-month period were screened for eligibility. Among these, patients diagnosed with sepsis based on the third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) were included in the study. Results Using the Sepsis-3 criteria, 977 sepsis patients were identified, among which 36.5% presented with septic shock. The respiratory system (61.8%) was the most common site of infection. The pathogen involved was identified in 444 patients (45.5%) and multi-drug resistance (MDR) pathogens were isolated in 171 patients. Empiric antibiotic therapy was appropriate in 68.6% of patients, but the appropriateness was significantly reduced in infections associated with MDR pathogens as compared with non-MDR pathogens (58.8% vs. 76.0%, P

Background Data on noninvasive ventilation (NIV) use in intensive care units (ICUs) are very limited in South Korea. Methods A prospective observational study was performed in 20 ICUs of university-affiliated hospitals from June 2017 to February 2018. Adult patients (age>18 years) who were admitted to the ICU and received NIV treatment for acute respiratory failure were included. Results A total of 156 patients treated with NIV were enrolled (mean age, 71.9±11.6 years). The most common indications for NIV were acute hypercapnic respiratory failure (AHRF, n=89) and post-extubation respiratory failure (n=44). The main device for NIV was an invasive mechanical ventilator with an NIV module (61.5%), and the majority of patients (87.2%) used an oronasal mask. After the exclusion of 32 do-not-resuscitate patients, NIV success rate was 68.5% (85/124); ICU and hospital mortality rates were 8.9% and 15.3%, respectively. However, the success rate was lower in patients with de novo respiratory failure (27.3%) compared to that of patients with AHRF (72.8%) or post-extubation respiratory failure (75.0%). In multivariate analysis, immunocompromised state, de novo respiratory failure, post-NIV (2 hours) respiratory rate, NIV mode (i.e., non-pressure support ventilation mode), and the change of NIV device were significantly associated with a lower success rate of NIV. Conclusion AHRF and post-extubation respiratory failure were the most common indications for NIV in Korean ICUs. Overall NIV success was achieved in 68.5% of patients, with the lowest rate in patients with de novo respiratory failure.

Abstract Background Connective tissue disease associated with interstitial lung disease (CTD-ILD) and interstitial lung disease (ILD) alone have same pathological and imaging backgrounds. However, the differences between lung cancer development and the mortality risk between these two conditions are unclear. Incidence of primary lung cancer and all-cause mortality were studied between interstitial lung disease patients with and without connective tissue disease. Methods Data were extracted from the Korean National Health Insurance Research Database in 2009. A total of 12,787 cases of ILD without idiopathic pulmonary fibrosis and 2491 cases of CTD-ILD were diagnosed in 2009. The cohort was followed up until June 30, 2014. Incident lung cancers and all-cause mortality were ascertained. Results The overall incidence of lung cancer was 165.7 and 161.8 per 10,000 person-years in the CTD-ILD and ILD-only, respectively (rate ratio, 1.08; 95% confidence interval, 0.89–1.30). CTD-ILD patients in the 40–49 and 50–59 years old age groups had lung cancer incidence rates of 92.5 and 139.2, which were 2.0 and 1.7 times higher than those in the ILD-only, respectively. All-cause mortality was significantly higher in the CTD-ILD group compared to ILD-only group in patients aged 50–79 years. All-cause mortality of women in the 50–59, 60–69 and 70–79 age groups was 2.0, 1.8, and 1.4 times higher in the CTD-ILD group than in the ILD-only group, respectively. Conclusions CTD-ILD patients aged

Background Obstructive airway disease patients with increased variability of airflow and incompletely reversible airflow obstruction are often categorized as having asthma–chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS). ACOS is heterogeneous with two sub-phenotypes: asthma-ACOS and COPD-ACOS. The objective of this study was to determine the difference in risk of exacerbation between the two sub-phenotypes of ACOS. Methods A total of 223 patients exhibiting incompletely reversible airflow obstruction with increased variability (spirometrically defined ACOS) were enrolled. These patients were divided into asthma-ACOS and COPD-ACOS according to their physician's diagnosis and smoking history of 10 pack-years. Within-group comparisons were made for asthma-ACOS versus COPD-ACOS and light smokers versus heavy smokers. Results Compared to patients with COPD-ACOS, patients with asthma-ACOS experienced exacerbation more often despite their younger age, history of light smoking, and better lung function. While the light-smoking group showed better lung function, they made unscheduled outpatient clinic visits more frequently. On multivariate analysis, asthma-ACOS and poor inhaler compliance were significantly associated with more than two unscheduled clinic visits during the previous year. Conclusion Spirometrically defined ACOS includes heterogeneous subgroups with different clinical features. Phenotyping of ACOS by physician's diagnosis could be significant in predicting future risk of exacerbation.

Background The objective of this study was to investigate the characteristics and clinical outcomes of critically ill cancer patients admitted to intensive care units (ICUs) in Korea. Methods This was a retrospective cohort study that analyzed prospective collected data from the Validation of Simplified Acute Physiology Score 3 (SAPS3) in Korean ICU (VSKI) study, which is a nationwide, multicenter, and prospective study that considered 5,063 patients from 22 ICUs in Korea over a period of 7 months. Among them, patients older than 18 years of age who were diagnosed with solid or hematologic malignancies prior to admission to the ICU were included in the present study. Results During the study period, a total of 1,762 cancer patients were admitted to the ICUs and 833 of them were deemed eligible for analysis. Six hundred fifty-eight (79%) had solid tumors and 175 (21%) had hematologic malignancies, respectively. Respiratory problems (30.1%) was the most common reason leading to ICU admission. Patients with hematologic malignancies had higher Sequential Organ Failure Assessment (12 vs. 8, P

Abstract Background Understanding the risk factors that are associated with the development of interstitial lung disease might have an important role in understanding the pathogenetic mechanism of interstitial lung disease as well as prevention. We aimed to determine independent risk factors of interstitial lung disease development. Methods This was a retrospective cohort study with nationwide population-based 9-year longitudinal data. We selected subjects who were aged > 40 years at cohort entry and with a self-reported history of cigarette smoking. Cases were selected based on International Classification of Diseases codes. A cohort of 312,519 subjects were followed until December 2013. We used Cox regression analysis to calculate the hazard ratios (HRs) for interstitial lung disease development. Results Interstitial lung disease developed in 1972 of the 312,519 subjects during the 9-year period. Smoking (HR: 1.2; 95% confidence interval [CI]: 1.1–1.4), hepatitis C (HR: 1.6; 95% CI: 1.1–2.3), history of tuberculosis (HR: 1.5; 95% CI: 1.1–1.9), history of pneumonia (HR: 1.6; 95% CI: 1.3–2.0), and chronic obstructive pulmonary disease (HR: 1.8; 95% CI: 1.6–2.1), men (HR: 1.9; 95% CI: 1.7–2.1) were significantly associated with the development of interstitial lung disease. The risk of interstitial lung disease development increases with age, and the risk was 6.9 times higher (95% CI: 5.9–8.0) in those aged over 70 than in their forties. Conclusions Smoking, hepatitis C, history of tuberculosis, history of pneumonia, chronic obstructive pulmonary disease, male sex, and older age were significantly associated with interstitial lung disease development.

Abstract Background Respiratory syncytial virus (RSV) infection constitutes a substantial disease burden in the general population. However, the risk of death for RSV infection has been rarely evaluated with confounders or comorbidities adjusted. We aimed to evaluate whether RSV infection is associated with higher mortality than seasonal influenza after adjusting for confounders and comorbidities and the effect of oseltamivir on the mortality in patients with influenza infection. Methods A retrospective cohort study was conducted on adult (≥18 years) patients admitted to the emergency department and ward of a university teaching hospital for suspected viral infection during 2013–2015 (N = 3743). RSV infection was diagnosed by multiplex PCR (N = 87). Adults hospitalized for seasonal influenza during the study period were enrolled as a comparison group (n = 312). The main outcome was 20-day all-cause mortality.We used Cox proportional hazard regression analyses to calculate the relative risk of death. Results Adult patients were less likely to be diagnosed with RSV than with influenza (2.3 vs 8.3%, respectively), were older and more likely to be diagnosed with pneumonia, chronic obstructive pulmonary disease, hypoxemia, and bacterial co-infection. In patients with RSV infection, the 20-day all-cause mortality was higher than that for influenza, (18.4 vs 6.7%, respectively). RSV infection showed significantly higher risk of death compared to the seasonal influenza group, with hazard ratio, 2.32 (95% CI, 1.17–4.58). Oseltamivir had no significant effect on mortality in patients with influenza. Conclusions RSV infection was significantly associated with a higher risk of death than seasonal influenza, adjusted for potential confounders and comorbidities.

There is no well-stated practical guideline for mechanically ventilated patients with or without acute respiratory distress syndrome (ARDS). We generate strong (1) and weak (2) grade of recommendations based on high (A), moderate (B) and low (C) grade in the quality of evidence. In patients with ARDS, we recommend low tidal volume ventilation (1A) and prone position if it is not contraindicated (1B) to reduce their mortality. However, we did not support high-frequency oscillatory ventilation (1B) and inhaled nitric oxide (1A) as a standard treatment. We also suggest high positive end-expiratory pressure (2B), extracorporeal membrane oxygenation as a rescue therapy (2C), and neuromuscular blockage for 48 hours after starting mechanical ventilation (2B). The application of recruitment maneuver may reduce mortality (2B), however, the use of systemic steroids cannot reduce mortality (2B). In mechanically ventilated patients, we recommend light sedation (1B) and low tidal volume even without ARDS (1B) and suggest lung protective ventilation strategy during the operation to lower the incidence of lung complications including ARDS (2B). Early tracheostomy in mechanically ventilated patients can be performed only in limited patients (2A). In conclusion, of 12 recommendations, nine were in the management of ARDS, and three for mechanically ventilated patients.

Severe acute respiratory infections (SARI) remain one of the leading causes of mortality around the world in all age groups. There is large global variation in epidemiology, clinical management and outcomes, including mortality. We performed a short period observational data collection in critical care units distributed globally during regional peak SARI seasons from 1 January 2016 until 31 August 2017, using standardised data collection tools. Data were collected for 1 week on all admitted patients who met the inclusion criteria for SARI, with follow-up to hospital discharge. Proportions of patients across regions were compared for microbiology, management strategies and outcomes. Regions were divided geographically and economically according to World Bank definitions. Data were collected for 682 patients from 95 hospitals and 23 countries. The overall mortality was 9.5%. Of the patients, 21.7% were children, with case fatality proportions of 1% for those less than 5 years. The highest mortality was in those above 60 years, at 18.6%. Case fatality varied by region: East Asia and Pacific 10.2% (21 of 206), Sub-Saharan Africa 4.3% (8 of 188), South Asia 0% (0 of 35), North America 13.6% (25 of 184), and Europe and Central Asia 14.3% (9 of 63). Mortality in low-income and low-middle-income countries combined was 4% as compared with 14% in high-income countries. Organ dysfunction scores calculated on presentation in 560 patients where full data were available revealed Sequential Organ Failure Assessment (SOFA) scores on presentation were significantly associated with mortality and hospital length of stay. Patients in East Asia and Pacific (48%) and North America (24%) had the highest SOFA scores of >12. Multivariable analysis demonstrated that initial SOFA score and age were independent predictors of hospital survival. There was variability across regions and income groupings for the critical care management and outcomes of SARI. Intensive care unit-specific factors, geography and management features were less reliable than baseline severity for predicting ultimate outcome. These findings may help in planning future outbreak severity assessments, but more globally representative data are required.

Pneumonia severity index (PSI) is an important scoring system that can assess the severity of community acquired pneumonia and determine admission status. However, there is a lack of research on whether this scoring system can be applied to viral community acquired pneumonia. The purpose of this study was to evaluate the usefulness of PSI in viral community acquired pneumonia. This retrospective cohort study included 1,434 adult patients (aged ≥18 years) who were admitted to the emergency department of a university hospital during 2013-2015 because of community-acquired pneumonia. Viral infections were diagnosed by multiplex PCR. Patients diagnosed with non-viral community-acquired pneumonia were included in the control group (N = 1,173). The main outcome was 30-day all-cause mortality. multivariate Cox regression analyses were performed to calculate the risk of death. Respiratory viruses were detected in 261 (18.2%) patients with community-acquired pneumonia. Two types of respiratory viruses were detected in 7 cases. Of the 254 cases detected with only one virus, 62 were influenza A, 18 were influenza B, 65 were rhinovirus, 35 were respiratory syncytial virus, 25 were metapneumovirus, 20 were parainfluenza, 17 were coronavirus, 7 were bocavirus, and 5 were adenovirus. Mortality was not significantly different between patients with respiratory virus and those without respiratory virus; the 30-day all-cause mortality rates were 20.3% and 22.4%, respectively (P = 0.45). Mortality rate increased with an increasing PSI score with or without respiratory viral infection. Pulmonary severity index was significantly associated with mortality adjusted for respiratory virus detection (hazard ratio = 1.024, 95% confidence interval = 1.020-1.028). Pneumonia severity index score is an important factor for assessing the prognosis of patients with community-acquired pneumonia, regardless of respiratory virus detection.

Zinc finger MYND-type-containing 10 (ZMYND10), a cytoplasmic protein expressed in ciliated cells, causes primary ciliary dyskinesia (PCD) when mutated; however, its function is poorly understood. Therefore, in this study, we examined the roles of ZMYND10 using Zmynd10-/-mice exhibiting typical PCD phenotypes, including hydrocephalus and laterality defects. In these mutants, morphology, the number of motile cilia, and the 9+2 axoneme structure were normal; however, inner and outer dynein arms (IDA and ODA, respectively) were absent. ZMYND10 interacted with ODA components and proteins, including LRRC6, DYX1C1, and C21ORF59, implicated in the cytoplasmic pre-assembly of DAs, whose levels were significantly reduced in Zmynd10-/-mice. LRRC6 and DNAI1 were more stable when co-expressed with ZYMND10 than when expressed alone. DNAI2, which did not interact with ZMYND10, was not stabilized by co-expression with ZMYND10 alone, but was stabilized by co-expression with DNAI1 and ZMYND10, suggesting that ZMYND10 stabilized DNAI1, which subsequently stabilized DNAI2. Together, these results demonstrated that ZMYND10 regulated the early stage of DA cytoplasmic pre-assembly by stabilizing DNAI1.

The incidence of venous thromboembolism (VTE) is lower in Asian populations than in Western populations. The objective of the present study was to evaluate the annual age- and sex-adjusted incidence (ASR) of VTE from 2009 to 2013 in South Korea. In addition, annual change in the pattern of VTE treatment during the study period was estimated because a new direct oral anticoagulant (DOAC) had become available and was covered by health insurance in Korea beginning in January 2013. VTE cases from 2009 to 2013 were retrospectively identified based on both diagnostic and medication codes of anticoagulants used for initial treatment using the Korean Health Insurance Review and Assessment Service (HIRA) databases. The incidence of VTE increased yearly. It was significantly higher in the older population than in the younger population, and it was higher in females than in males. In 2009, ASRs of VTE, deep vein thrombosis, and pulmonary embolism were 21.3, 8.1, and 13.2 cases per 100,000 individuals, respectively in 2009. These increased to 29.2, 12.7, and 16.6 cases per 100,000, respectively, in 2013. Prescription rates of warfarin and low-molecular-weight heparin decreased with the introduction of a new anticoagulant in 2013. The proportion of subjects who underwent mechanical procedures decreased annually. The ASR of VTE in Korea continuously increased from 2009 to 2013, reflecting an increased awareness and detection of VTE as well as improved survival of patients with cancer and other morbidities. Following its introduction, DOAC rapidly replaced other anticoagulants for the treatment of VTE.

Kr-pok (kidney cancer-related POZ domain and Krüppel-like protein) is a new proto-oncogenic POZ-domain transcription factor. Fatty acid synthase gene (FASN) encodes one of the key enzymes in fatty acids synthesis and is the only enzyme that synthesizes fatty acids in cancer cells. Sp1 and SREBP-1c are the two major transcription activators of FASN. We investigated whether Kr-pok modulates transcription of the FASN. FASN expression is significantly decreased in Kr-pok knockout murine embryonic fibroblasts. Coimmunoprecipitation, GST fusion protein pull-down, and immunocytochemistry assays show that the zinc-finger domain of Kr-pok interacts directly with the bZIP DNA binding domain of SREBP-1. Electrophoretic mobility shift assay, oligonucleotide pull-down, and chromatin immunoprecipitation assays showed that Kr-pok changes the transcription factor binding dynamics of Sp1 and SREBP-1c to the SRE/E-box elements of the proximal promoter. We found that Kr-pok expression increased during 3T3-L1 preadipocyte differentiation and that FASN expression is decreased by the knockdown of Kr-pok. Kr-pok facilitates the SREBP-1c-mediated preadipocyte differentiation and/or fatty acid synthesis. Kr-pok may act as an important regulator of fatty acid synthesis and may induce rapid cancer cell proliferation by increasing palmitate synthesis.

BACKGROUND: The level of body mass index (BMI) that is associated with the lowest mortality in critically ill patients in Asian populations is uncertain. We aimed to examine the association of BMI with hospital mortality in critically ill patients in Korea. METHODS: We conducted a prospective multicenter cohort study of 3,655 critically ill patients in 22 intensive care units (ICUs) in Korea. BMI was categorized into five groups:

Aberrant activation of the Wnt pathway contributes to human cancer progression. Antagonists that interfere with Wnt ligand/receptor interactions can be useful in cancer treatments. In this study, we evaluated the therapeutic potential of a soluble Wnt receptor decoy in cancer gene therapy. We designed a Wnt antagonist sLRP6E1E2, and generated a replication-incompetent adenovirus (Ad), dE1-k35/sLRP6E1E2, and a replication-competent oncolytic Ad, RdB-k35/sLRP6E1E2, both expressing sLRP6E1E2. sLRP6E1E2 prevented Wnt-mediated stabilization of cytoplasmic β-catenin, decreased Wnt/β-catenin signaling and cell proliferation via the mitogen-activated protein kinase, and phosphatidylinositol 3-kinase pathways. sLRP6E1E2 induced apoptosis, cytochrome c release, and increased cleavage of PARP and caspase-3. sLRP6E1E2 suppressed growth of the human lung tumor xenograft, and reduced motility and invasion of cancer cells. In addition, sLRP6E1E2 upregulated expression of epithelial marker genes, while sLRP6E1E2 downregulated mesenchymal marker genes. Taken together, sLRP6E1E2, by inhibiting interaction between Wnt and its receptor, suppressed Wnt-induced cell proliferation and epithelial-to-mesenchymal transition.