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BackgroundSepsis, characterized by a dysregulated host response to infection, often leads to organ dysfunction, and vascular endothelial dysfunction plays a central role. The erythropoietin-producing hepatocellular carcinoma (Eph)A2 receptor is associated with increased vascular permeability; however, the developmental endothelial locus-1 (Del-1), has contrasting effects on endothelial function. Hence, we examined their potential as biomarkers of sepsis.MethodsIn total, 117 participants, including 20 healthy controls, 21 patients with systemic inflammatory response syndrome (SIRS), and 76 patients with sepsis, were enrolled in this study. Sepsis severity was assessed using the Acute Physiology and Chronic Health Evaluation (APACHE) II and the Sequential Organ Failure Assessment (SOFA) scores.ResultsThe Median plasma EphA2 levels increased progressively from healthy controls to SIRS and sepsis cases (154.29, 293.52, and 554.24 pg/mL; all p

Background/Aims Intensive care unit (ICU) quality is largely determined by the mortality rate. Therefore, we aimed to develop and validate a novel prognostic model for predicting mortality in Korean ICUs, using national insurance claims data. Methods Data were obtained from the health insurance claims database maintained by the Health Insurance Review and Assessment Service of South Korea. From patients who underwent the third ICU adequacy evaluation, 42,489 cases were enrolled and randomly divided into the derivation and validation cohorts. Using the models derived from the derivation cohort, we analyzed whether they accurately predicted death in the validation cohort. The models were verified using data from one general and two tertiary hospitals. Results Two severity correction models were created from the derivation cohort data, by applying variables selected through statistical analysis, through clinical consensus, and from performing multiple logistic regression analysis. Model 1 included six categorical variables (age, sex, Charlson comorbidity index, ventilator use, hemodialysis or continuous renal replacement therapy, and vasopressor use). Model 2 additionally included presence/absence of ICU specialists and nursing grades. In external validation, the performance of models 1 and 2 for predicting in-hospital and ICU mortality was not inferior to that of pre-existing scoring systems. Conclusions The novel and simple models could predict in-hospital and ICU mortality and were not inferior compared to the pre-existing scoring systems.

IntroductionEnd-stage lung disease causes cardiac remodeling and induces electrocardiogram (ECG) changes. On the other way, whether lung transplantation (LTx) in end-stage lung disease patients are associated with ECG change is unknown. The object of this study was to investigate ECG changes before and after LTx in end-stage lung disease patients and whether these changes had clinical significance.MethodThis was a single-center retrospective cohort study of 280 end-stage lung disease patients who consecutively underwent LTx at a tertiary referral hospital. ECG findings before LTx and within 1 week and 1, 3, and 6 months after LTx were obtained and analyzed. To find clinical meaning, the ECG at 1 month after LTx was analyzed according to 1-year survival (survivor vs non-survivor groups). Survival data were estimated using the Kaplan–Meier method.ResultsSignificant differences were observed in the PR interval, QRS duration, QT interval, QTc interval, and heart rate before LTx and 1 month after LTx; the PR interval, QRS duration, QTc interval, and heart rate were decreased. Particularly, the QTc interval was significantly decreased 1 month after LTx, whereas there was no significant change in the QTc interval from 1 to 6 months thereafter. The PR interval, QT interval, QTc interval, and heart rate were significantly different between the survivor and non-survivor groups. The serial changes in QTc interval before LTx and 1 and 3 months after LTx were also significantly different between the survivor and non-survivor groups (p = 0.040 after adjusting for age and body mass index). Upon dividing the patients based on the range of QTc interval change ≤ -8 ms, >-8–10 ms, >10–35 ms, >35 ms), the survival rate was significantly lower in the group whose QTc interval at 1 month after LTx decreased by > 35 m (p = 0.019).ConclusionLTx in patients with end-stage lung disease may induce ECG changes. Patients whose QTc interval at 1 month after LTx decreased by > 35 ms have a significantly higher 1-year mortality rate. Hence, these ECG changes may have clinical and prognostic significance.

Abstract Background Whether COVID-19-induced acute respiratory distress syndrome (ARDS) should be approached differently in terms of mechanical ventilation therapy compared to other virus-induced ARDS is debatable. Therefore, we aimed to ascertain whether the respiratory mechanical characteristics of COVID-19-induced ARDS differ from those of influenza A induced ARDS, in order to establish a rationale for mechanical ventilation therapy in COVID-19-induced ARDS. Methods This was a retrospective cohort study comparing patients with COVID-19-induced ARDS and influenza A induced ARDS. We included intensive care unit (ICU) patients with COVID-19 or Influenza A aged ≥ 19, who were diagnosed with ARDS according to the Berlin definition between January 2015 and July 2021. Ventilation parameters for respiratory mechanics were collected at specific times on days one, three, and seven after intubation. Results The median age of the 87 participants was 71.0 (62.0–78.0) years old, and 63.2% were male. The ratio of partial pressure of oxygen in arterial blood to the fractional of inspiratory oxygen concentration in COVID-19-induced ARDS was lower than that in influenza A induced ARDS during the initial stages of mechanical ventilation (influenza A induced ARDS 216.1 vs. COVID-19-induced ARDS 167.9, p = 0.009, day 1). The positive end expiratory pressure remained consistently higher in the COVID-19 group throughout the follow-up period (7.0 vs. 10.0, p

Abstract Background In the global trend of population aging, age is one of the significant factors to be considered in critically ill patients. However, the impact of age on clinical outcomes and long-term prognosis in this population varies across different studies. Methods We conducted a retrospective cohort analysis for patients admitted to the medical intensive care unit (ICU) (30 beds) between January 2017 and December 2020 at the tertiary referral hospital in Korea. Patients were classified into three groups according to age:

Abstract Sepsis is a dysregulated immune response to infection that leads to organ dysfunction and is associated with a high incidence and mortality rate. The lack of reliable biomarkers for diagnosing and prognosis of sepsis is a major challenge in its management. We aimed to investigate the potential of three-dimensional label-free CD8 + T cell morphology as a biomarker for sepsis. This study included three-time points in the sepsis recovery cohort (N = 8) and healthy controls (N = 20). Morphological features and spatial distribution within cells were compared among the patients’ statuses. We developed a deep learning model to predict the diagnosis and prognosis of sepsis using the internal cell morphology. Correlation between the morphological features and clinical indices were analysed. Cell morphological features and spatial distribution differed significantly between patients with sepsis and healthy controls and between the survival and non-survival groups. The model for predicting the diagnosis and prognosis of sepsis showed an area under the receiver operating characteristic curve of nearly 100% with only a few cells, and a strong correlation between the morphological features and clinical indices was observed. Our study highlights the potential of three-dimensional label-free CD8 + T cell morphology as a promising biomarker for sepsis. This approach is rapid, requires a minimum amount of blood samples, and has the potential to provide valuable information for the early diagnosis and prognosis of sepsis.

Abstract We aimed to describe the clinical features of lymphangioleiomyomatosis (LAM) in Korean patients and identify factors associated with progressive disease (PD). Clinical features of 54 patients with definite or probable LAM from 2005 to 2018 were retrospectively analysed. Common features were pneumothorax (66.7%) and abdominal lymphadenopathy (50.0%). Twenty-three (42.6%) patients were initially treated with mechanistic target of rapamycin (mTOR) inhibitors. Lung transplantation (LT) was performed in 13 (24.1%) patients. Grouped based on the annual decline in forced expiratory volume in 1 s (FEV1) from baseline and LT, 36 (66.7%) patients exhibited stable disease (SD). All six deaths (11.1%) occurred in PD. Proportion of SD was higher in those treated initially with mTOR inhibitors than in those under observation (p = 0.043). Univariate analysis revealed sirolimus use, and baseline forced vital capacity, FEV1, and diffusing capacity of the lungs for carbon monoxide are associated with PD. Multivariate analysis showed that only sirolimus use (odds ratio 0.141, 95% confidence interval 0.021–0.949, p = 0.044) reduced PD. Kaplan–Meier analysis estimates overall survival of 92.0% and 74.7% at 5 and 10 years, respectively. A considerable proportion of LAM patients remain clinically stable without treatment. LT is an increasingly viable option for patients with severe lung function decline.

Abstract Background Diagnostic cutoff points for sarcopenia in chest computed tomography (CT) have not been established although CT is widely used for investigating skeletal muscles. This study aimed to determine reference values for sarcopenia of thoracic skeletal muscles acquired from chest CT scans and to analyse variables related to sarcopenia using the cutoff values determined in a general Asian population. Methods We retrospectively reviewed chest CT scans of 4470 participants (mean age 54.8 ± 9.9 years, 65.8% male) performed at a check‐up centre in South Korea (January 2016–August 2017). To determine cutoffs, 335 participants aged 19–39 years (mean age 35.2 ± 3.6 years, 75.2% male) were selected as the healthy and younger reference group, and 4135 participants aged ≥40 years (mean age 56.4 ± 8.4 years, 65.1% male) were selected as the study group. We measured the following: cross‐sectional area (CSA) of the pectoralis, intercostalis, paraspinal, serratus, and latissimus muscles at the 4th vertebral region (T4CSA); T4CSA divided by height2 (T4MI); pectoralis muscle area (PMCSA); and PMCSA divided by height2 (PMI) at the 4th vertebral region. Sarcopenia cutoff was defined as sex‐specific values of less than −2 SD below the mean from the reference group. Results In the reference group, T4CSA, T4MI, PMCSA, and PMI cutoffs for sarcopenia were 100.06cm2, 33.69cm2/m2, 29.00cm2, and 10.17cm2/m2 in male, and 66.93cm2, 26.01cm2/m2, 18.29cm2, and 7.31cm2/m2 in female, respectively. The prevalence of sarcopenia in the study group measured with T4CSA, T4MI, PMCSA and PMI cutoffs were 11.4%, 8.7%, 8.5%, and 10.1%, respectively. Correlations were observed between appendicular skeletal mass divided by height2 measured by bioelectrical impedance analysis (BIA) and T4CSA (r = 0.82; P

Abstract Background For patients with acute respiratory distress syndrome, a ventilator is essential to supply oxygen to tissues, but it may also cause lung damage. In this study, we investigated the role of NOX4 using NOX4 knockout (KO) mice and NOX4 inhibitors in a ventilator-induced lung injury (VILI) model. Methods Wild-type (WT) male C57BL/6J mice and NOX4 knockout (KO) male mice were divided into five groups: (1) control group; (2) high tidal ventilation (HTV) group: WT mice + HTV ± DMSO; (3) NOX4 KO group; (4) NOX4 KO with HTV group; (5) NOX4 inhibitor group: WT mice + HTV + NOX4 inhibitor. In the VILI model, the supine position was maintained at 24 mL/kg volume, 0 cm H2O PEEP, 100/min respiratory rate, and 0.21 inspired oxygen fraction. In the NOX4 inhibitor group, 50 μL anti-GKT 137831 inhibitor was injected intraperitoneally, 2 h after ventilator use. After 5 h of HTV, mice in the ventilator group were euthanized, and their lung tissues were obtained for further analysis. In addition, the relationship between EphA2 (which is related to lung injury) and NOX4 was investigated using EphA2 KO mice, and NOX4 and EphA2 levels in the bronchoalveolar lavage fluid (BALF) of 38 patients with pneumonia were examined. Results Cell counts from BALFs were significantly lower in the NOX4 KO with HTV group (p

Abstract In elderly ICU patients, the prevalence of skeletal muscle loss is high. Longitudinal effect of thoracic muscles, especially in elderly ICU patients, are unclear although skeletal muscle loss is related with the short- and long-term outcomes. This study aimed to evaluate whether pectoralis muscle mass loss could be a predictor of prognosis in elderly ICU patients. We retrospectively evaluated 190 elderly (age > 70 years) patients admitted to the ICU. We measured the cross-sectional area (CSA) of the pectoralis muscle (PMCSA) at the fourth vertebral region. CT scans within two days before ICU admission were used for analysis. Mortality, prolonged mechanical ventilation, and longitudinal changes in Sequential Organ Failure Assessment (SOFA) scores were examined. PMCSA below median was significantly related with prolonged ventilation (odds ratio 2.92) and a higher SOFA scores during the ICU stay (estimated mean = 0.94). PMCSA below median was a significant risk for hospital mortality (hazards ratio 2.06). In elderly ICU patients, a low ICU admission PMCSA was associated with prolonged ventilation, higher SOFA score during the ICU stay, and higher mortality. Adding thoracic skeletal muscle CSA at the time of ICU admission into consideration in deciding the therapeutic intensity in elderly ICU patients may help in making medical decisions.

Background: Studies on the risk and protective factors for lung function decline and mortality in rheumatoid arthritis–related interstitial lung disease (RA-ILD) are limited. Objectives: We aimed to investigate clinical factors and medication uses associated with lung function decline and mortality in RA-ILD. Methods: This retrospective cohort study examined the medical records of patients with RA-ILD who visited Severance Hospital between January 2006 and December 2019. We selected 170 patients with RA-ILD who had undergone at least one spirometry test and chest computed tomography scan. An absolute decline of ⩾10% in the functional vital capacity (FVC) was defined as significant decline in pulmonary function. Data for analysis were retrieved from electronic medical records. Results: Ninety patients (52.9%) were female; the mean age was 64.0 ± 10.2 years. Multivariate logistic regression showed that a high erythrocyte sediment rate level at baseline [odds ratio (OR) = 3.056; 95% confidence interval (CI) = 1.183–7.890] and methotrexate (MTX) use (OR = 0.269; 95% CI = 0.094–0.769) were risk and protective factors for lung function decline, respectively. Multivariate Cox regression analysis indicated that age ⩾65 years (OR = 2.723; 95% CI = 1.142–6.491), radiologic pattern of usual interstitial pneumonia (UIP) or probable UIP (OR = 3.948; 95% CI = 1.522–10.242), baseline functional vital capacity (FVC) % predicted (OR = 0.971; 95% CI = 0.948–0.994), and MTX use (OR = 0.284; 95% CI = 0.091–0.880) were predictive of mortality. Conclusion: We identified risk and protective factors for lung function decline and mortality in patients with RA-ILD. MTX use was associated with favorable outcome in terms of both lung function and mortality in our cohort.

Abstract Interstitial lung disease (ILD), particularly idiopathic pulmonary fibrosis (IPF), has a poor prognosis. Corticosteroids are widely used in the treatment of acute exacerbation of ILD (AE-ILD). This study aimed to clarify the causes of AE-ILD, determine the efficacy of corticosteroids for treating AE-ILD, and detect differences in the mortality rate among subgroups of ILD. This was an observational retrospective single-center study. Patients with ILD who presented to the emergency department with acute respiratory symptoms from January 1, 2016, to December 31, 2018, were included. Patients with AE-ILD were classified into two groups depending on the prednisolone dose: low dose (0 to 1.0 mg/kg) or high dose (> 1.0 mg/kg). Mortality rates between patients with and without IPF were compared. This study included 182 patients with AE-ILD, including IPF (n = 117) and non-IPF (n = 65). Multivariate Cox regression analysis showed that corticosteroid dose (HR: 0.221, CI: 0.102–0.408, P 1 mg/kg prednisolone) in patients with AE-non-IPF-ILD. However, this was not the case in patients with AE-IPF.

Background Flexible bronchoscopy is one of the essential procedures for the diagnosis and treatment of pulmonary diseases. The purpose of this study was to identify the risk factors associated with the occurrence of hypoxia in adults undergoing flexible bronchoscopy under sedation. Methods We retrospectively analyzed 2,520 patients who underwent flexible bronchoscopy under sedation at our tertiary care university hospital in South Korea January 1, 2013–December 31, 2014. Hypoxia was defined as more than 5%-point reduction in the baseline percutaneous oxygen saturation (SpO2) or SpO2 1 minute during the procedure. Results The mean age was 64.7±13.5, and 565 patients developed hypoxia during the procedure. The mean sedation duration and midazolam dose for sedation were 31.1 minutes and 3.9 mg, respectively. The bivariate analysis showed that older age, a low forced expiratory volume in one second (FEV1), use of endobronchial ultrasound, the duration of sedation, and the midazolam dose were associated with the occurrence of hypoxia during the procedure, while the multivariate analysis found that age >60 (odds ratio [OR], 1.32), a low FEV1 (OR, 0.99), and a longer duration of sedation (>40 minutes; OR, 1.33) were significant risk factors. Conclusion The findings suggest that patients older than age 60 and those with a low FEV1 tend to develop hypoxia during the bronchoscopy under sedation. Also, longer duration of sedation (>40 minutes) was a significant risk factor for hypoxia.

Abstract Sepsis remains a critical problem with high mortality worldwide, but there is still a lack of reliable biomarkers. We aimed to evaluate the serum lysophosphatidylcholine (LPC) 16:0 as a biomarker of sepsis using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Patients admitted to intensive care unit at Severance Hospital from March 2017 through June 2018 were prospectively enrolled. The inclusion criteria were the fulfillment of at least two criteria of systemic inflammatory response syndrome (SIRS) or the presence of sepsis. Of the 127 patients, 14 had non-infectious SIRS, 41 had sepsis, and 72 had septic shock. The mean serum LPC 16:0 concentration (µmol/L) in non-infectious SIRS was significantly higher than in patients with sepsis and septic shock (101.1 vs. 48.92, p

Objectives: Related innate immune system activation and diagnostic factors of sepsis are not fully understood. The aim of this study was to analyze the clinical value of full-length tryptophanyl-tRNA synthetase (WRS) induced through inflammatory stimuli for the detection of sepsis and prediction of mortality in critically ill patients. Methods: This was a retrospective analysis of blood samples collected prospectively from patients in the medical intensive care unit (ICU) at Yonsei University College of Medicine, from March 2015 to June 2018. The ability of WRS to detect sepsis and predict mortality were compared to those of procalcitonin (PCT), C-reactive protein (CRP), and interleukin 6 (IL-6), and with Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores. Results: A total of 241 study patients were enrolled, of whom 190 (78.8%) had been diagnosed with sepsis on ICU admission. The areas under the receiver operating characteristics curves (AUROCs) for sepsis discrimination with WRS, PCT, CRP, and IL-6 levels, and SOFA and APACHE II scores were 0.864, 0.727, 0.625, 0.651, 0.840, and 0.754, respectively. The prediction of 28-day mortality in patients with sepsis using WRS levels was possible and non-inferior to that with the SOFA score. Conclusions: WRS secreted early in sepsis may be useful not only for the early detection of sepsis, but also for the prediction of mortality in critically ill patients.

Background Sepsis-induced cardiomyopathy (SIC) occurs frequently in critically ill patients, but the clinical features and prognostic impact of SIC on sepsis outcome remain controversial. Here, we investigated the predictors and outcomes of SIC. Methods Patients admitted to a single medical intensive care unit from June 2016 to September 2017 were retrospectively reviewed. SIC was diagnosed by ejection fraction (EF)

Background: Hyperbilirubinemia and hypoalbuminemia are frequently appeared and associated with poor prognosis in critically ill patients. We aim to evaluate the association between the bilirubin to albumin ratio and prognosis in intensive care unit (ICU) patients. Methods: This was a retrospective study of 731 patients who were admitted to the medical intensive care unit (MICU) at a tertiary-care center from July 2015 to September 2017. We analyzed the bilirubin to albumin ratio on admission to the MICU, including clinical characteristics and other examinations. Results: The overall 28-day survival of MICU patients was 69.1%. On univariate analysis, Acute Physiology and Chronic Health Evaluation (APACHE) II score (P

Background: Tuberculosis (TB) causes undernutrition, and it has a long recovery time after treatment. It is accompanied by adverse health outcomes, such as sarcopenia. Objective: We aimed to evaluate the prevalence of sarcopenia and its association with protein and total energy intakes among Korean TB survivors. Methods: Data of the population-based Korea National Health and Nutrition Examination Survey (2008–2011) were analyzed, including 9,203 participants aged ⩾ 40 years. We used three definitions for sarcopenia-appendicular skeletal muscle mass (ASM, kg) divided by body mass index (BMI, kg/m 2 ), weight (kg), or height squared (m 2 ). Daily protein and total energy intakes were estimated with a 24-h recall method. Multiple logistic regression was used to evaluate the association between dietary protein/total energy intake and sarcopenia among TB survivors. Results: The prevalence of sarcopenia was 11.2%, 10.7%, and 24.3% among TB survivors with sarcopenia defined by ASM divided by BMI, weight, and height squared, respectively. The prevalence of sarcopenia among TB survivors was higher than among those without TB. After adjusting for age, weight, sex, education level, employment status, smoking status, and drinking status, sufficient protein and total energy intakes were associated with a lower risk of sarcopenia in TB survivors. Conclusion: The prevalence of sarcopenia was higher in TB survivors than in those without TB. We suggest consuming sufficient protein intake along with increasing total energy intake in TB survivors.

BackgroundIn the era of artificial intelligence, event prediction models are abundant. However, considering the limitation of the electronic medical record–based model, including the temporally skewed prediction and the record itself, these models could be delayed or could yield errors. ObjectiveIn this study, we aim to develop multiple event prediction models in intensive care units to overcome their temporal skewness and evaluate their robustness against delayed and erroneous input. MethodsA total of 21,738 patients were included in the development cohort. Three events—death, sepsis, and acute kidney injury—were predicted. To overcome the temporal skewness, we developed three models for each event, which predicted the events in advance of three prespecified timepoints. Additionally, to evaluate the robustness against input error and delays, we added simulated errors and delayed input and calculated changes in the area under the receiver operating characteristic curve (AUROC) values. ResultsMost of the AUROC and area under the precision-recall curve values of each model were higher than those of the conventional scores, as well as other machine learning models previously used. In the error input experiment, except for our proposed model, an increase in the noise added to the model lowered the resulting AUROC value. However, the delayed input did not show the performance decreased in this experiment. ConclusionsFor a prediction model that was applicable in the real world, we considered not only performance but also temporal skewness, delayed input, and input error.

Abstract Background In many clinical disorders, there is a relationship between the ratio of the diameter of the main pulmonary artery (mPA) to that of the aorta (Ao) on chest computed tomography (CT). The aim of this study was to determine if the mPA/Ao ratio at diagnosis is associated with the clinical characteristics and outcomes in patients with idiopathic pulmonary fibrosis (IPF). Methods We retrospectively reviewed the diameters of the pulmonary artery and aorta on chest CT, clinical characteristics, and results of other examinations in 303 patients at the time of initial diagnosis of IPF at our tertiary care center between 2011 and 2015. The primary outcomes were death and lung transplantation. The patients were followed up until June 2017. Results One hundred and eight patients (35.6%) died and 58 (19.1%) underwent lung transplantation during follow-up. The mean mPA and Ao diameters were 28.3 mm and 34.0 mm, respectively, and the mean mPA/Ao ratio was 0.84. Thirty-one patients (10.2%) had an mPA/Ao ratio > 1.0 and 182 (60.1%) had an mPA/Ao ratio > 0.8. Patients with an mPA/Ao ratio > 0.8 had a lower DLco value than those with an mPA/Ao ratio ≤ 0.8. In Kaplan-Meier analysis, patients with an mPA/Ao ratio > 1.0 or > 0.8 had worse outcomes than those with an mPA/Ao ratio ≤ 1.0 and ≤ 0.8, respectively. Conclusions A higher mPA/Ao ratio based on 1.0 and 0.8 is associated with unfavorable prognosis in patients with IPF.

Background/Aims Delayed diagnosis and treatment of smear-negative pulmonary tuberculosis (TB) are major concerns for TB control. We evaluated characteristics of patients with smear-negative pulmonary TB who received a delayed diagnosis and identified risk factors that may have contributed to this delay. Methods We reviewed medical records of patients with smear-negative culture-positive pulmonary TB treated at a tertiary care hospital in South Korea between January 2017 and December 2018. Patients who initiated anti-TB treatment after positive cultures were included in the missed TB group, and those who initiated empirical treatment before positive cultures were included in the control group. Results Of 220 patients included, 117 (53.2%) and 103 (46.8%) were in the missed TB and control groups, respectively. Patients in the missed TB group were older (p = 0.001) and had a higher mean body mass index (BMI) (p = 0.019). Comorbidities (66.9% vs. 46.6%, p = 0.003) and immunocompromised patients (33.1% vs. 20.4%, p = 0.035) were more common in the missed TB group than in the control group. Old age (odds ratio [OR], 1.030; 95% confidence interval [CI], 1.012 to 1.048; p = 0.001), high BMI (OR, 1.114; 95% CI, 1.004 to 1.237; p = 0.042), and negative polymerase chain reaction (PCR) results (OR, 9.551; 95% CI, 4.925 to 18.521; p < 0.001) were associated with delayed diagnosis. Conclusions In more than half of patients with smear-negative pulmonary TB, the diagnosis was delayed. Patients with delayed TB diagnosis were older, had higher BMI, and negative PCR results.

Background Transforming growth factor β (TGF-β), retinoic acid (RA), p38 mitogen-activated protein kinase (MAPK), and MEK signaling play critical roles in cell differentiation, proliferation, and apoptosis. We investigated the effect of RA and the role of these signaling molecules on the phosphorylation of Smad2/3 (p-Smad2/3) induced by TGF-β1. Methods A549 epithelial cells and CCD-11Lu fibroblasts were incubated and stimulated with or without all-trans RA (ATRA) and TGF-β1 and with MAPK or MEK inhibitors. The levels of p-Smad2/3 were analyzed by western blotting. For animal models, we studied three experimental mouse groups: control, bleomycin, and bleomycin+ATRA group. Changes in histopathology, lung injury score, and levels of TGF-β1 and Smad3 were evaluated at 1 and 3 weeks. Results When A549 cells were pre-stimulated with TGF-β1 prior to RA treatment, RA completely inhibited the p-Smad2/3. However, when A549 cells were pre-treated with RA prior to TGF-β1 stimulation, RA did not completely suppress the p-Smad2/3. When A549 cells were pre-treated with MAPK inhibitor, TGF-β1 failed to phosphorylate Smad2/3. In fibroblasts, p38 MAPK inhibitor suppressed TGF-β1-induced p-Smad2. In a bleomycin-induced lung injury mouse model, RA decreased the expression of TGF-β1 and Smad3 at 1 and 3 weeks. Conclusion RA had inhibitory effects on the phosphorylation of Smad induced by TGF-β1 in vitro, and RA also decreased the expression of TGF-β1 at 1 and 3 weeks in vivo. Furthermore, pre-treatment with a MAPK inhibitor showed a preventative effect on TGF-β1/Smad phosphorylation in epithelial cells. As a result, a combination of RA and MAPK inhibitors may suppress the TGF-β1-induced lung injury and fibrosis.

Background An automatic alarm system was developed was developed for unexpected vital sign instability in admitted patients to reduce staffing needs and costs related to rapid response teams. This was a pilot study of the automatic alarm system, the medical emergency system (MES), and the aim of this study was to determine the effectiveness of the MES before expanding this system to all departments. Methods This retrospective, observational study compared the performance of patients admitted to the pulmonary department at a single center using patient data from three 3-month periods (before implementation of the MES, December 2013-February 2014; after implementation of the MES, December 2014-February 2015 and December 2015-February 2016). Results A total of 571 patients were admitted to the pulmonary department during the three observation periods. During this pilot study, the MES automatically issued 568 alarms for 415 admitted patients. There was no significant difference in the rate of cardiopulmonary resuscitation (CPR) before and after application of the MES. The mortality rate also did not change. However, it appeared that CPR was prevented in four patients admitted from the general ward to the intensive care unit (ICU) during MES implementation. The median length of hospital stay and median length of ICU stay were not significantly different before and after MES implementation. Conclusions Although we did not find a significant improvement in outcomes upon MES implementation, the CPR rate and mortality rate did not increase despite increased comorbidities. This was a small pilot study and, based on these results, we believe that the MES may have significant effects in longer-term and larger-scale studies.

Background The renin-angiotensin-aldosterone system is closely associated with volume status and vascular tone in septic shock. The present study aimed to assess whether plasma renin activity (PRA) and plasma aldosterone concentration (PAC) measurements compared with conventional severity indicators are associated with mortality in patients with septic shock. Methods We evaluated 105 patients who were admitted for septic shock. Plasma levels of the biomarkers PRA and PAC, the PAC/PRA ratio, C-reactive protein (CRP) level, and cortisol level on days 1, 3, and 7 were serially measured. During the intensive care unit stay, relevant clinical information and laboratory results were recorded. Results Patients were divided into two groups according to 28-day mortality: survivors (n = 59) and non-survivors (n = 46). The survivor group showed lower PRA, PAC, Acute Physiologic and Chronic Health Evaluation (APACHE) II score, and Sequential Organ Failure Assessment (SOFA) score than did the non-survivor group (all P < 0.05). The SOFA score was positively correlated with PRA (r = 0.373, P < 0.001) and PAC (r = 0.316, P = 0.001). According to receiver operating characteristic analysis, the areas under the curve of PRA and PAC to predict 28-day mortality were 0.69 (95% confidence interval [CI], 0.58 to 0.79; P = 0.001) and 0.67 (95% CI, 0.56 to 0.77; P = 0.003), respectively, similar to the APACHE II scores and SOFA scores. In particular, the group with PRA value ≥3.5 ng ml-1 h-1 on day 1 showed significantly greater mortality than did the group with PRA value

Onodera's prognostic nutritional index (PNI) is useful in predicting prognosis of various diseases. But the usefulness of PNI in non-surgical patients has not been sufficiently proven yet. In patients with mycobacterium avium complex pulmonary disease (MAC-PD), malnutrition is an important factor that affects the quality of life and morbidity. Here, we aimed to evaluate whether PNI is related with clinical outcomes in MAC-PD patients. We examined 663 patients diagnosed with MAC-PD between May 2005 and November 2017. PNI score was calculated at the time of diagnosis and treatment initiation, and patients were divided into malnutrition and non-malnutrition groups according to a cut-off PNI score of 45. As the recommended duration of treatment for MAC-PD is 12 months following sputum conversion, treatment duration less than 12 months was defined as treatment intolerance. Survivals were compared with the log-rank test. Multivariate logistic regression and multivariate Cox proportional hazards models were used to estimate the odds ratio (OR) and hazards ratio (HR) for treatment intolerance and mortality, respectively. Of the 306 patients that received treatment, 193 received treatment longer than 12 months. In the multivariable logistic regression model, malnutrition at the time of treatment initiation was related with treatment intolerance (OR: 2.559, 95% confidence interval [CI]: 1.414-4.634, P = 0.002). Patients in the malnutrition group at the time of diagnosis exhibited lower survival (P

Background Despite many ongoing, prospective studies on the topic, sepsis still remains one of the main causes of death in hospital. The hormone insulin-like growth factor 1 (IGF-1) has a similar molecular structure to that of insulin. IGF-1 exerts anabolic effects and plays important roles in both normal physiology and pathologic processes. Previous studies have observed low serum IGF-1 level in patients with critical illnesses. Here, we evaluated changes in IGF-1 level based on survival of septic patients. Methods We evaluated 140 patients with sepsis and septic shock (21 with sepsis and 119 with septic shock) admitted to the intensive care unit of a university-affiliated hospital in Korea. Serum IGF-1 level was measured on days 0, 1, 3, and 7. Patients with liver disease were excluded from this study. All data were analyzed using SPSS version 20 (SPSS Inc., Chicago, IL, USA). Results Patients with septic shock had significantly lower serum IGF-1 level on days 1 and 3 than patients without septic shock (p = 0.002 and p = 0.007, respectively). Generally, there was a negative relationship between IGF-1 and serum cortisol levels; however, this relationship was only significant on day 3 (p = 0.029). Furthermore, renin showed significantly negative correlation with IGF-1 on day 3 (p = 0.038). IGF-1 level did not show significant difference between survivors and non-survivors. Conclusions Our results showed that IGF-1 was associated with septic shock, and that the IGF-1 axis is severely disrupted in septic patients. Additionally, serum cortisol and renin levels were associated with IGF-1 level.

Severe hyperammonemia can occur as a result of inherited or acquired liver enzyme defects in the urea cycle, among which ornithine transcarbamylase deficiency (OTCD) is the most common form. We report a very rare case of a 45-year-old Korean male who was admitted to the intensive care unit (ICU) due to severe septic shock with acute respiratory failure caused by Pneumocystis jiroveci pneumonia. During his ICU stay with ventilator care, the patient suffered from marked hyperammonemia (>1,700 μg/dL) with abrupt mental change leading to life-threatening cerebral edema. Despite every effort including continuous renal replacement therapy and use of a molecular adsorbent recirculating system (extracorporeal liver support–albumin dialysis) to lower his serum ammonia level, the patient was not recovered. The lethal hyperammonemia in the patient was later proven to be a manifestation of acquired liver enzyme defect known as OTCD, which is triggered by serious catabolic conditions, such as severe septic shock with acute respiratory failure.

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.

OBJECTIVES Previous studies have shown relatively low correlations between self-reported and accelerometer-assessed physical activity (PA). However, this association differs by socio-demographic factors, and this relationship has not been fully investigated in the general population. Thus, we investigated the correlation between self-reported and accelerometer-assessed PA and whether it differed by demographic and socioeconomic factors among the Korean general population. METHODS This cross-sectional study included 623 participants (203 men and 420 women) aged 30 to 64 years, who completed a PA questionnaire and wore a wrist-worn accelerometer on the non-dominant wrist for 7 days. We examined the agreement for metabolic equivalent task minutes per week (MET-min/wk) between the 2 measures and calculated Spearman correlation coefficients according to demographic and socioeconomic factors. RESULTS The kappa coefficient between tertiles of self-reported and accelerometer-assessed total MET-min/wk was 0.16 in the total population, suggesting overall poor agreement. The correlation coefficient between the 2 measurements was 0.26 (p

Increased serum CA 19-9 levels in patients with nonmalignant diseases have been investigated in previous reports. This study evaluates the clinical significance of serum CA 19-9 elevation in pulmonary nontuberculous mycobacterial disease and pulmonary tuberculosis. The median CA 19-9 level was higher in patients with pulmonary nontuberculous mycobacterial disease than in patients with pulmonary tuberculosis (pulmonary nontuberculous mycobacterial disease: 13.80, tuberculosis: 5.85, p

BACKGROUND:Pneumocystis jirovecii pneumonia (PCP) is often fatal in human immunodeficiency (HIV)-negative patients and typically presents with respiratory insufficiency. Predicting treatment failure is challenging. This study aimed to identify prognostic factors and examine PCP polymerase chain reaction (PCR)-negative conversion in non-HIV PCP patients with respiratory failure. METHOD:We retrospectively enrolled 81 non-HIV patients diagnosed with and treated for PCP with respiratory failure in the intensive care unit at a tertiary hospital over a 3-year period. PCP was diagnosed via nested PCR-mediated detection of Pneumocystis jirovecii in induced sputum samples, endotracheal aspirates, and bronchoalveolar lavage fluids. PCP PCR was performed weekly to check for negative conversion. RESULTS:The overall survival rate was 35.8%. Seventy-four patients (91.3%) required mechanical ventilation, and 6 (7.4%) required high-flow nasal oxygen treatment. The PCP PCR-negative conversion rate was 70.5% (survivors, 97%; non-survivors, 63.5%); the median time to conversion was 10 (7.0-14.0) days. On univariate analysis, the APACHE II score (p < 0.001), renal failure requiring renal replacement therapy (p = 0.04), PCP PCR-negative conversion (p = 0.003), and the PaO2/FiO2 ratio (first 24 hours) (p < 0.001) significantly correlated with mortality. On multivariate analysis, PCP PCR-negative conversion (hazard ratio, 0.433; 95% confidence interval, 0.203-0.928; p = 0.031) and the PaO2/FiO2 ratio (first 24 hours) (hazard ratio, 0.988; 95% confidence interval, 0.983-0.993; p < 0.001) independently predicted prognosis. CONCLUSIONS:Determination of PCP PCR-negative conversion and PaO2/FiO2 ratios may help physicians predict treatment failure and mortality in non-HIV PCP patients with respiratory failure.

BACKGROUND:The ratio of the diameter of the main pulmonary artery (mPA) to the diameter of the aorta (Ao) on chest computed tomography is associated with diverse clinical conditions. Herein, we determined the functional and prognostic implications of the mPA/Ao ratio in Korean chronic obstructive pulmonary disease (COPD) patients. METHODS:The study population comprised 226 chronic obstructive pulmonary disease patients from the Korean Obstructive Lung Disease cohort who underwent chest computed tomography. We analyzed the relationships between the clinical characteristics, including pulmonary function, echocardiography findings, St. George's Respiratory Questionnaire, 6-minute walking (6MW) distance, and exacerbation with the mPA, Ao, and mPA/Ao ratio. RESULTS:The mean age was 65.8 years, and 219 (96.9%) patients were male. The mean FEV1% predicted and FEV1/FVC ratio were 61.2% and 47.3%, respectively. The mean mPA and Ao were 23.7 and 36.4 mm, respectively, and the mPA/Ao ratio was 0.66. The mPA/Ao ratio correlated negatively with the 6MW distance (G = -0.133, P = 0.025) and positively with the right ventricular pressure (G = 0.323, P = 0.001). After adjustment for potential confounders, the mPA/Ao ratio was significantly associated with 6MW distance (β = -107.7, P = 0.017). Moreover, an mPA/Ao ratio >0.8 was a significant predictor of exacerbation at the 1-year (odds ratio 2.12, 95% confidence interval 1.27-3.52) and 3-year follow-ups (odds ratio 2.04, 95% confidence interval 1.42-2.90). CONCLUSIONS:The mPA/Ao ratio is an independent predictor of exercise capacity and an mPA/Ao ratio >0.8 is a significant risk factor of COPD exacerbation.

Purpose: Isoniazid (INH) mono-resistant tuberculosis (Hr-TB) is a highly prevalent type of drug-resistant TB, possibly associated with unfavorable treatment outcomes. However, definitive guidelines on an optimal treatment regimen and duration for Hr-TB are currently under discussion. We evaluated the characteristics and treatment outcomes of Hr-TB patients. Materials and Methods: We retrospectively reviewed the medical records of Hr-TB patients treated at a South Korean tertiary referral hospital from January 2005 to December 2018. Results: We included 195 Hr-TB patients. 113 (57.9%) were male, and the median age was 56.6 [interquartile range, 40.2-68.6] years. Mutations in katG were the most frequent [54 (56.3%)], followed by those in the inhA [34 (35.4%)]. Favorable and unfavorable outcomes were noted in 164 (84.1%) and 31 (15.9%) patients, respectively. Smoking history [odds ratio (OR)=5.606, 95% confidence interval (CI): 1.695-18.543, p=0.005], low albumin level (OR=0.246, 95% CI: 0.104-0.578, p=0.001), and positive acid-fast bacilli culture at 2 months (OR=7.853, 95% CI: 1.246-49.506, p=0.028) were associated with unfavorable outcomes. Conclusion: A tailored strategy targeting high-risk patients is imperative for improved treatment outcomes. Further research on the rapid and accurate detection of resistance to INH and other companion drugs is warranted. [ABSTRACT FROM AUTHOR]