Development of Machine Learning Model for VO2max Estimation Using a Patch-Type Single-Lead ECG Monitoring Device in Lung Resection Candidates.

A cardiopulmonary exercise test (CPET) is essential for lung resection. However, performing a CPET can be challenging. This study aimed to develop a machine learning model to estimate maximal oxygen consumption (VO2max) using data collected through a patch-type single-lead electrocardiogram (ECG) monitoring device in candidates for lung resection. This prospective, single-center study included 42 patients who underwent a CPET at a tertiary teaching hospital from October 2021 to July 2022. During the CPET, a single-lead ECG monitoring device was applied to all patients, and the results obtained from the machine-learning algorithm using the information extracted from the ECG patch were compared with the CPET results. According to the Bland-Altman plot of measured and estimated VO2max, the VO2max values obtained from the machine learning model and the FRIEND equation showed lower differences from the reference value (bias: -0.33 mL·kg-1·min-1, bias: 0.30 mL·kg-1·min-1, respectively). In subgroup analysis, the developed model demonstrated greater consistency when applied to different maximal stage levels and sexes. In conclusion, our model provides a closer estimation of VO2max values measured using a CPET than existing equations. This model may be a promising tool for estimating VO2max and assessing cardiopulmonary reserve in lung resection candidates when a CPET is not feasible.

Development of a Machine Learning Model for Predicting Weaning Outcomes Based Solely on Continuous Ventilator Parameters during Spontaneous Breathing Trials.

Discontinuing mechanical ventilation remains challenging. We developed a machine learning model to predict weaning outcomes using only continuous monitoring parameters obtained from ventilators during spontaneous breathing trials (SBTs). Patients who received mechanical ventilation in the medical intensive care unit at a tertiary university hospital from 2019-2021 were included in this study. During the SBTs, three waveforms and 25 numerical data were collected as input variables. The proposed convolutional neural network (CNN)-based weaning prediction model extracts features from input data with diverse lengths. Among 138 enrolled patients, 35 (25.4%) experienced weaning failure. The dataset was randomly divided into training and test sets (8:2 ratio). The area under the receiver operating characteristic curve for weaning success by the prediction model was 0.912 (95% confidence interval [CI], 0.795-1.000), with an area under the precision-recall curve of 0.767 (95% CI, 0.434-0.983). Furthermore, we used gradient-weighted class activation mapping technology to provide visual explanations of the model's prediction, highlighting influential features. This tool can assist medical staff by providing intuitive information regarding readiness for extubation without requiring any additional data collection other than SBT data. The proposed predictive model can assist clinicians in making ventilator weaning decisions in real time, thereby improving patient outcomes.

Enhancing the interferon-γ release assay through omission of nil and mitogen values.

PURPOSE: To address the limited utility of the interferon (IFN)-γ release assay (IGRA) caused by its variability and inconsistency. METHODS: This retrospective cohort study was based on data obtained between 2011 and 2019. QuantiFERON-TB Gold-In-Tube was used to measure IFN-γ levels in nil, tuberculosis (TB) antigen, and mitogen tubes. RESULTS: Of 9,378 cases, 431 had active TB. The non-TB group comprised 1,513 IGRA-positive, 7,202 IGRA-negative, and 232 IGRA-indeterminate cases. Nil-tube IFN-γ levels were significantly higher in the active TB group (median = 0.18 IU/mL; interquartile range: 0.09-0.45 IU/mL) than in the IGRA-positive non-TB (0.11 IU/mL; 0.06-0.23 IU/mL) and IGRA-negative non-TB (0.09 IU/mL; 0.05-0.15 IU/mL) groups (P < 0.0001). From receiver operating characteristic analysis, TB antigen tube IFN-γ levels had higher diagnostic utility for active TB than TB antigen minus nil values. In a logistic regression analysis, active TB was the main driver of higher nil values. In the active TB group, after reclassifying the results based on a TB antigen tube IFN-γ level of 0.48 IU/mL, 14/36 cases with negative results and 15/19 cases with indeterminate results became positive, while 1/376 cases with positive results became negative. Overall, the sensitivity for detecting active TB improved from 87.2 to 93.7%. CONCLUSION: The results of our comprehensive assessment can aid in IGRA interpretation. Since nil values are governed by TB infection rather than reflecting background noise, TB antigen tube IFN-γ levels should be used without subtracting nil values. Despite indeterminate results, TB antigen tube IFN-γ levels can be informative.

Infectivity of Coronavirus Disease 2019: A Prospective Cohort Study in the Korean Metropolitan Area.

BACKGROUND: Although several characteristics of coronavirus disease 2019 (COVID-19), an ongoing pandemic disease, have been identified, data on the infectivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are limited. METHODS: This prospective cohort study was conducted to analyze the infectivity of SARS-CoV-2 based on data of all patients diagnosed with COVID-19 confirmed using real-time polymerase chain reaction test from January to April 2020 in Gyeonggi-do, the largest province in Korea. RESULTS: Of the 502 patients, 298 consisting of 106 clusters with 5,909 contacts were included. Of these, 277 (93.0%) were symptomatic, and the most common symptoms were cough, fever, sputum, sore throat, and headache. A total of 94 patients (31.5%) had pneumonia, while 8 (2.7%) died during the follow-up period. The secondary attack rate (SAR) in the study population was 3.5% (204/5,909). In exposure settings, the SAR was higher in religious gathering (13.5% [95% confidence interval, 10.7-16.8%]), workplaces (8.49% [95% CI, 6.08-11.74%]), and schools (6.38% [95% CI, 3.39-11.69%]) than in health care facilities (1.92% [95% CI, 1.45-2.55%]). Sore throat at any period, dyspnea at diagnosis or any period, lower cycle threshold value in the lower respiratory tract samples, leukocytosis, and higher bilirubin levels were associated with higher infectivity of COVID-19. The presence of symptoms was not related to the infectivity. CONCLUSION: In establishing the infection control strategies for COVID-19, the variables associated with high infectivity may be considered.

Short-Term Air Pollution Exposure and Risk of Acute Exacerbation of Chronic Obstructive Pulmonary Disease in Korea: A National Time-Stratified Case-Crossover Study.

We investigated the association between short-term exposure to air pollution and the risk of acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) in seven metropolitan cities in Korea. We used national health insurance claims data to identify AE-COPD cases in 2015. We estimated short-term exposure to particulate matter (PM) with a diameter of ≤2.5 µm (PM2.5), PM with diameters of ≤10 µm (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3) obtained from the Ministry of Environment. We conducted a time-stratified, case-crossover study to evaluate the effect of short-term exposure to air pollution on hospital visits for AE-COPD, using a conditional logistic regression model. The risk of hospital visits for AE-COPD was significantly associated with interquartile range increases in PM10 in a cumulative lag model (lag 0-2, 0.35%, 95% confidence interval (CI) 0.06-0.65%; lag 0-3, 0.39%, 95% CI 0.01-0.77%). The associations were higher among patients who were men, aged 40-64 years, with low household income, and with a history of asthma. However, other air pollutants were not significantly associated with the risk of hospital visits for AE-COPD. Short-term exposure to air pollution, especially PM10, increases the risk of hospital visits for AE-COPD.

Aerosolized antibiotics in the treatment of hospital-acquired pneumonia/ventilator-associated pneumonia.

Aerosolized antibiotics are being increasingly used to treat respiratory infections, especially those caused by drug-resistant pathogens. Their use in the treatment of hospital-acquired pneumonia and ventilator-associated pneumonia in critically ill patients is especially significant. They are also used as an efficient alternative to overcome the issues caused by systemic administration of antibiotics, including the occurrence of drug-resistant strains, drug toxicity, and insufficient drug concentration at the target site. However, the rationale for the use of aerosolized antibiotics is limited owing to their insufficient efficacy and the potential for underestimated risks of developing side effects. Despite the lack of availability of high-quality evidence, the use of aerosolized antibiotics is considered as an attractive alternative treatment approach, especially in patients with multidrug-resistant pathogens. In this review, we have discussed the effectiveness and side effects of aerosolized antibiotics as well as the latest advancements in this field and usage in the Republic of Korea.

Interferon-γ-Inducible Chemokines as Prognostic Markers for Lung Cancer.

Interferon (IFN)-γ-inducible chemokines in the CXCR3/ligand axis are involved in cell-mediated immunity and play a significant role in the progression of cancer. We enrolled patients with lung cancer (n = 144) and healthy volunteers as the controls (n = 140). Initial blood samples were collected and concentrations of IFN-γ and IFN-γ-inducible chemokines CXCL9, CXCL10, and CXCL11 were measured using enzyme-linked immunosorbent assay. Of patients with lung cancer, 125 had non-small cell lung cancer (NSCLC) and 19 had small cell lung cancer. The area under the curve (AUC) (95% CI) of CXCL9 was 0.83 (0.80-0.89) for differentiating lung cancer patients from controls. The levels of all the markers were significantly higher in NSCLC patients with stage IV than in those with stages I-III. A Kaplan-Meier survival analysis showed that NSCLC cancer patients with higher levels of all markers showed poorer survival than those with lower levels. In Cox multivariate analysis of patients with NSCLC, independent prognostic factors for overall survival were CXCL9 and CXCL11. CXCL9 was the only independent prognostic factor for cancer-specific survival. Serum IFN-γ-inducible chemokines may be useful as clinical markers of metastasis and prognosis in NSCLC, and CXCL9 levels showed the most significant results.

Assessment of medical students' clinical performance using high-fidelity simulation: comparison of peer and instructor assessment.

BACKGROUND: High-fidelity simulators are highly useful in assessing clinical competency; they enable reliable and valid evaluation. Recently, the importance of peer assessment has been highlighted in healthcare education, and studies using peer assessment in healthcare, such as medicine, nursing, dentistry, and pharmacy, have examined the value of peer assessment. This study aimed to analyze inter-rater reliability between peers and instructors and examine differences in scores between peers and instructors in the assessment of high-fidelity-simulation-based clinical performance by medical students. METHODS: This study analyzed the results of two clinical performance assessments of 34 groups of fifth-year students at Ajou University School of Medicine in 2020. This study utilized a modified Queen's Simulation Assessment Tool to measure four categories: primary assessment, diagnostic actions, therapeutic actions, and communication. In order to estimate inter-rater reliability, this study calculated the intraclass correlation coefficient and used the Bland and Altman method to analyze agreement between raters. A t-test was conducted to analyze the differences in evaluation scores between colleagues and faculty members. Group differences in assessment scores between peers and instructors were analyzed using the independent t-test. RESULTS: Overall inter-rater reliability of clinical performance assessments was high. In addition, there were no significant differences in overall assessment scores between peers and instructors in the areas of primary assessment, diagnostic actions, therapeutic actions, and communication. CONCLUSIONS: The results indicated that peer assessment can be used as a reliable assessment method compared to instructor assessment when evaluating clinical competency using high-fidelity simulators. Efforts should be made to enable medical students to actively participate in the evaluation process as fellow assessors in high-fidelity-simulation-based assessment of clinical performance in situations similar to real clinical settings.

Biosignal-Based Digital Biomarkers for Prediction of Ventilator Weaning Success.

We evaluated new features from biosignals comprising diverse physiological response information to predict the outcome of weaning from mechanical ventilation (MV). We enrolled 89 patients who were candidates for weaning from MV in the intensive care unit and collected continuous biosignal data: electrocardiogram (ECG), respiratory impedance, photoplethysmogram (PPG), arterial blood pressure, and ventilator parameters during a spontaneous breathing trial (SBT). We compared the collected biosignal data's variability between patients who successfully discontinued MV (n = 67) and patients who did not (n = 22). To evaluate the usefulness of the identified factors for predicting weaning success, we developed a machine learning model and evaluated its performance by bootstrapping. The following markers were different between the weaning success and failure groups: the ratio of standard deviations between the short-term and long-term heart rate variability in a Poincaré plot, sample entropy of ECG and PPG, α values of ECG, and respiratory impedance in the detrended fluctuation analysis. The area under the receiver operating characteristic curve of the model was 0.81 (95% confidence interval: 0.70-0.92). This combination of the biosignal data-based markers obtained during SBTs provides a promising tool to assist clinicians in determining the optimal extubation time.

TB Antigen-Stimulated CXCR3 Ligand Assay for Diagnosis of Tuberculous Lymphadenitis.

The diagnosis of tuberculous lymphadenitis (TB-LAP) is challenging. We evaluated the role of blood CXC chemokine receptor 3 (CXCR3) ligands in its diagnosis. A total of 65 lymphadenopathy patients were enrolled and lymph node sampling was performed. We also recruited 113 control subjects, consisting of 27 with positive results and 86 with negative results, in the interferon (IFN)-γ release assay (IGRA). In all study subjects, whole-blood samples were collected using the IGRA methodology. After incubation, plasma levels of IFN-γ and two CXCR3 ligands, IFN-inducible T-cell a chemoattractant (I-TAC) and monokine induced by IFN-γ (MIG), were measured using immunoassay. Fifty-three TB-LAP patients were enrolled. TB antigen-stimulated IFN-γ, I-TAC, and MIG levels were all significantly higher in the TB-LAP patients than in the controls and non-TB-LAP patients. The levels of I-TAC and MIG, but not IFN-γ, showed significant differences between the TB-LAP patients and IGRA-positive controls. Area under the receiver operating characteristic curves (AUROCs) of IFN-γ, I-TAC, and MIG were 0.955, 0.958, and 0.959, respectively, for differentiating TB-LAP from control group, and were 0.912, 0.956, and 0.936, respectively, for differentiating TB-LAP from non-TB-LAP. In conclusion, the TB antigen-stimulated MIG and I-TAC could be useful biomarkers in the diagnosis of TB-LAP.

Effects of high-fidelity simulation education on medical students' anxiety and confidence.

INTRODUCTION: Psychological factors such as anxiety and confidence that students have in the patient care situation are important in that this affects the actual clinical performance. Students who are just starting clinical practice have a lack of clinical knowledge, skill proficiency, and patient communication skills, so they experience anxiety and lack of confidence in clinical setting. Practice in a safe environment, such as simulation education, can help students perform more settled and competently in patient care. The purpose of this study was to analyze the effect of high-fidelity simulation experience on anxiety and confidence in medical students. MATERIALS AND METHODS: This study enrolled 37 5th-year students at Ajou University School of Medicine in 2020. Two simulation trainings were implemented, and a survey was conducted to measure students' level of anxiety and confidence before and after each simulation. Based on the research data, a paired t-test was conducted to compare these variables before and after the simulation, and whether this was their first or second simulation experience. RESULTS: Students had a significantly lower level of anxiety and a significantly higher level of confidence after the simulation than before. In addition, after one simulation experience, students had less anxiety and more confidence before the second simulation compared to those without simulation experience. CONCLUSIONS: We confirmed that medical students need to be repeatedly exposed to simulation education experiences in order to have a sense of psychological stability and to competently deliver medical treatment in a clinical setting. There is a practical limitation in that medical students do not have enough opportunities to meet the patients during clinical practice in hospitals. Therefore, in order to produce excellent doctors, students should have the expanded opportunities to experience simulation education so they can experience real-world medical conditions.

Risk of QT prolongation through drug interactions between hydroxychloroquine and concomitant drugs prescribed in real world practice.

Hydroxychloroquine has recently received attention as a treatment for COVID-19. However, it may prolong the QTc interval. Furthermore, when hydroxychloroquine is administered concomitantly with other drugs, it can exacerbate the risk of QT prolongation. Nevertheless, the risk of QT prolongation due to drug-drug interactions (DDIs) between hydroxychloroquine and concomitant medications has not yet been identified. To evaluate the risk of QT prolongation due to DDIs between hydroxychloroquine and 118 concurrent drugs frequently used in real-world practice, we analyzed the electrocardiogram results obtained for 447,632 patients and their relevant electronic health records in a tertiary teaching hospital in Korea from 1996 to 2018. We repeated the case-control analysis for each drug. In each analysis, we performed multiple logistic regression and calculated the odds ratio (OR) for each target drug, hydroxychloroquine, and the interaction terms between those two drugs. The DDIs were observed in 12 drugs (trimebutine, tacrolimus, tramadol, rosuvastatin, cyclosporin, sulfasalazine, rofecoxib, diltiazem, piperacillin/tazobactam, isoniazid, clarithromycin, and furosemide), all with a p value of < 0.05 (OR 1.70-17.85). In conclusion, we found 12 drugs that showed DDIs with hydroxychloroquine in the direction of increasing QT prolongation.

Beneficial Function of Taurine on Bone Metabolism in Alcohol-Fed OVX Rat Model.

The present study investigates the effects of taurine on bone markers and bone mineral density (BMD) in alcohol-fed ovariectomized (OVX) rat model. We divided twenty four rats into Sham and OVX groups. These two groups were thereafter subdivided into two groups: control and experimental diet containing 2 g/kg of taurine. BMD and bone mineral content (BMC) were estimated by PIXImus. As bone markers, we measured serum calcium, phosphorus, ALP activity, osteocalcin and urine calcium, phosphorus and DPD crosslinks value. The results were as follows: weight gain showed no significant difference and serum calcium concentration was in normal range. Urine DPD crosslink value was significantly decreased in taurine-fed group (p < 0.05). Serum ALP activity and osteocalcin levels, and urine phosphorus concentration did not show any differences among groups. Also the mineral density and content of spinal and femural bone did not show any differences among groups. However, the femur BMD was significantly increased in taurine-fed group (p < 0.05). In conclusion, taurine supplemented diets may have positive results on bone metabolism in alcohol-fed OVX rat model.

Effects of Taurine and Vitamin D on Antioxidant Enzyme Activity and Lipids Profiles in Rats Fed Diet Deficient Calcium.

Calcium deficiency is a worldwide problem affecting both developed and developing countries. The deficiency in calcium leads to a marked decrease of superoxide dismutase. It is known that vitamin D protects cells against oxidative damages while taurine plays an anti-inflammatory and antioxidant role. In this study, we examined whether vitamin D and taurine supplementation had a protective effect on oxidative stress in rats fed calcium deficient diet. Female SD rats (mean weight 60 ∼ 70 g) were divided into four groups; control, taurine, vitamin D, taurine + vitamin D for 6 weeks (taurine: 2 g/100 g diet, vitamin D: 0.5 mg/100 g diet). We then analyzed the level of triglyceride (TG), total cholesterol (TC), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C) in serum and level of TC, TG in liver. We investigated antioxidative enzyme activities such as catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px). We observed that weight gain was not significantly different in the experimental groups. Food efficiency ratio (FER) was significantly higher in the normal control group than the taurine and vitamin D groups (p < 0.05). The level of liver TC was significantly lower in taurine, vitamin D, taurine + vitamin D groups than control group (p < 0.05). The concentration of malondialdehyde (MDA) was significantly lower in the taurine group than the control group. The activity of SOD was higher in taurine group than other experimental groups (p < 0.05), but GSH-Px and CAT were not significantly different. In conclusion, taurine has a positive effect on SOD activity but not on vitamin D. Also taurine and vitamin D have a protective effect as observed in liver TC in rats fed with a diet which lacks calcium.

The Usefulness of Serum CXCR3 Ligands for Evaluating the Early Treatment Response in Tuberculosis: A Longitudinal Cohort Study.

Cell-mediated immunity plays an important role in the pathobiology of tuberculosis (TB). The ligands for CXC chemokine receptor 3 (CXCR3) activate the T-helper type 1 lymphocyte pathway. The CXCR3 ligands are reportedly useful clinical markers for the diagnosis and follow-up of TB. The objective of this study was to assess the utility of CXCR3 ligands for evaluating early treatment responses in TB.We recruited 88 patients who underwent antituberculous chemotherapy. The serum levels of interferon (IFN)-γ and the CXCR3 ligands CXCL9 (monokine induced by IFN-γ [MIG]), CXCL10 (IFN-γ-inducible 10-kDa protein [IP-10]), and CXCL11 (IFN-inducible T-cell α chemoattractant [I-TAC]) were measured before and 2 months after the start of treatment. Treatment responses were divided into "fast" and "slow" based on the clinical, radiological, and bacteriological improvement at 2 months. A change in level of 20% or more at 2 months was defined as "significant."In patients with treatment success, 58 patients exhibited a fast response and 20 patients exhibited a slow response. Treatment failure occurred in 5 patients, and the diagnoses were changed to non-TB diseases in 5 patients. The levels of all CXCR3 ligands significantly decreased in the fast-response group (P < 0.01) but did not decrease in the other groups. IFN-γ levels showed no significant changes. The ability of significant decreases in marker levels to predict a fast response was evaluated. CXCL9 showed a sensitivity of 83%, and CXCL10 showed a specificity of 100%. Use of various combinations of CXCR3 ligands resulted in improvements in sensitivity (88%-93%), while specificity (92%-96%) was similar to that using single CXCR3 ligands. The decreases in CXCR3 ligand levels were less marked in the 2-month Mycobacterium tuberculosis culture-positive group than in the culture-negative group. There were significant differences in treatment outcomes in terms of 2-month culture positivity (P < 0.001), the significance of CXCL9 decreases (P < 0.01), and the significance of CXCL11 decreases (P < 0.05).In conclusion, CXCR3 ligands may be useful surrogate markers for the evaluation of early treatment response and showed utility as indicators of possible treatment failure in TB.

Independent risk factors for mortality in patients with chronic obstructive pulmonary disease who undergo comprehensive cardiac evaluations.

BACKGROUND: Cardiovascular disease is the most common cause of death in chronic obstructive pulmonary disease (COPD). However, the impact of cardiovascular comorbidities on the prognosis of COPD is not well known. OBJECTIVES: This study was performed to investigate the effects of cardiovascular comorbidities on the prognosis of COPD. METHODS: We enlisted 229 patients with COPD who underwent comprehensive cardiac evaluations including coronary angiography and echocardiography at Ajou University Hospital between January 2000 and December 2012. Survival analyses were performed in this retrospective cohort. RESULTS: Kaplan-Meier analyses showed that COPD patients without left heart failure (mean survival = 12.5 ± 0.7 years) survived longer than COPD patients with left heart failure (mean survival = 6.7 ± 1.4 years; p = 0.003), and the survival period of nonanemic COPD patients (mean survival = 13.8 ± 0.8 years) was longer than that of anemic COPD patients (mean survival = 8.3 ± 0.8 years; p < 0.001). The survival period in COPD with coronary artery disease (CAD; mean survival = 11.37 ± 0.64 years) was not different from that in COPD without CAD (mean survival = 11.98 ± 0.98 years; p = 0.703). According to a multivariate Cox regression model, a lower hemoglobin level, a lower left ventricular ejection fraction, and the forced expiratory volume in 1 s (FEV1) were independently associated with higher mortality in the total COPD group (p < 0.05). CONCLUSIONS: Hemoglobin levels and left ventricular ejection fraction along with a lower FEV1 were identified as independent risk factors for mortality in COPD patients who underwent comprehensive cardiac evaluations, suggesting that multidisciplinary approaches are required in the care of COPD.

Effects of Rubus coreanus-Cheonggukjang on Bone Mineral Density and Bone Mineral Content in Growing Rats.

The purpose of the present study was to investigate the bone-conserving effects of Rubus coreanus-Cheonggukjang (RC-CGJ) supplemented with more intensified phytochemicals compared to general Cheonggukjang (CGJ) in growing rats. Eighteen rats were divided into 3 treatment groups (Control, CGJ, and RC-CGJ) and were given experimental diets for 9 weeks. All of the rats in this study were fed a AIN-93G-based diet. Both CGJ groups were fed with 33.1% CGJ and RC-CGJ powder, respectively. The results of this study indicate that weight gain, mean food intake, and food efficiency ratio were not significantly different by the experimental diets among all groups. Spine bone mineral density (BMD) and femur BMD were not significantly different by the experimental diets. Spine bone mineral content (BMC) was significantly higher in the RC-CGJ and CGJ groups than in the control group, regardless of CGJ type. The femur BMC of the CGJ supplemented group was significantly higher compared with the control group and the RC-CGJ group. Compared with the control group, spine BMD and femur BMD per weight were markedly increased in the RC-CGJ and CGJ group regardless of CGJ type. Also, spine BMC per weight was significantly higher in the RC-CGJ group than in the CGJ group. However, femur BMC per weight was significantly higher in the CGJ group than in the RC-CGJ group. It can be concluded that RC-CGJ and CGJ supplemented diets have more beneficial effects on spine and femur peak bone mass in growing rats.

A TB antigen-stimulated CXCR3 ligand assay for the diagnosis of active pulmonary TB.

BACKGROUND: The ligands for CXC chemokine receptor 3 (CXCR3) recruit T-helper type 1 cells, which play a major role in cell-mediated immunity in TB. METHODS: A total of 409 subjects were enrolled. The study population comprised 186 patients with active TB, 58 patients with non-TB pulmonary diseases, 50 control subjects with a positive interferon (IFN)-γ release assay (IGRA) result, and 115 control subjects with a negative IGRA result. Whole-blood samples were collected using IGRA methodology. After incubation, plasma IFN-γ levels and two CXCR3 ligands, IFN-inducible T-cell α-chemoattractant (I-TAC, CXCL11) and monokine induced by IFN-γ (MIG, CXCL9), were measured by enzyme-linked immunosorbent assay. Receiver operating characteristic (ROC) analysis was performed. Sensitivity and specificity were based on cutoff values selected to maximize the Youden index. RESULTS: The TB antigen-stimulated levels of IFN-γ, I-TAC, and MIG were significantly increased in the active pulmonary TB group compared with all other groups. From ROC analysis, for the diagnosis of active TB, I-TAC and MIG outperformed IFN-γ in all comparisons with the IGRA-positive and -negative control groups and the non-TB pulmonary disease group. The areas under the curve (95% CI) for differentiating active pulmonary TB from all other groups were 0.893 (0.864-0.924) for IFN-γ, 0.962 (0.946-0.978) for I-TAC, and 0.944 (0.922-0.965) for MIG. Sensitivity and specificity were 90.3% and 90.7%, respectively, for I-TAC; 92.5% and 85.2% for MIG; and 84.9% and 79.8% for IFN-γ. CONCLUSIONS: TB antigen-stimulated assays of I-TAC and MIG may be useful surrogate markers in the diagnosis of active pulmonary TB.

The significance of caspase-cleaved cytokeratin 18 in pleural effusion.

BACKGROUND: Apoptosis plays a role in the development of pleural effusion. Caspase-cleaved cytokeratin 18, a marker for epithelial cell apoptosis, was evaluated in pleural effusion. METHODS: A total of 79 patients with pleural effusion were enrolled. The underlying causes were lung cancer (n=24), parapneumonic effusion (n=15), tuberculous effusion (n=28), and transudates (n=12). The levels of M30, an epitope of caspase-cleaved cytokeratin 18, were measured in blood and pleural fluids using enzyme-linked immunosorbent assay along with routine cellular and biochemical parameters. The expression of M30 was evaluated in the pleural tissues using immunohistochemistry for M30. RESULTS: The M30 levels in pleural fluid were significantly higher in patients with tuberculosis (2,632.1±1,467.3 U/mL) than in patients with lung cancer (956.5±618.5 U/mL), parapneumonic effusion (689.9±413.6 U/mL), and transudates (273.6±144.5 U/mL; all p<0.01). The serum levels were not significantly different among the disease groups. Based on receiver operating characteristics analysis, the area under the curve of M30 for differentiating tuberculous pleural effusion from all other effusions was 0.93. In the immunohistochemical analysis of M30, all pathologic types of cancer cells showed moderate to high expression, and the epithelioid cells in granulomas showed high expression in tuberculous pleural tissues. CONCLUSION: Caspase-cleaved cytokeratin 18 was most prominently observed in tuberculous pleural effusion and showed utility as a clinical marker. The main source of M30 was found to be the epithelioid cells of granulomas in tuberculous pleural tissues.

Consideration of additional factors in Sequential Organ Failure Assessment score.

PURPOSE: The Sequential Organ Failure Assessment (SOFA) score, originally developed to assess organ failure status, is widely used as a prognostic indicator in intensive care unit patients. Additional prognostic factors, such as age and comorbidities, may complement the predictive performance of the SOFA. METHODS: In total, 1049 consecutive patients were enrolled prospectively. SOFA and other admission-based intensive care unit scores were recorded during the first 24 hours. A complemented SOFA (cSOFA) score model was constructed by adding age and comorbidity scores to the original SOFA score, based on logistic regression analysis. The predictive performance was evaluated with regard to hospital mortality by receiver operating characteristics analysis. The Hosmer-Lemeshow goodness-of-fit test was used to assess calibration of the model, and leave-one-out cross-validation was performed. RESULTS: The cSOFA score (maximum 30 points) was calculated as the SOFA score (24 points) + age score (2 points) + comorbidity score (4 points). The cSOFA score model showed satisfactory calibration and cross-validation performance. The AUC (95% CI) of the cSOFA score (0.812 [0.787-0.835]) was higher than the SOFA score (0.743 [0.715-0.769], P < .0001). CONCLUSION: The performance of the SOFA score to predict hospital mortality can be improved by considering age and comorbidity factors.