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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

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.

Background: Hydroxychloroquine has recently received attention as a treatment for COVID-19. However, hydroxychloroquine may prolong the QTc interval, thus increasing the risk of life-threatening arrhythmia. Many patients with COVID-19 have comorbidities, necessitating the use of several drugs simultaneously with hydroxychloroquine. However, the risk of QT prolongation due to drug-drug interactions (DDIs) between hydroxychloroquine and these co-medications has not been identified. Therefore, it is necessary to investigate the risk of QT interval prolongation due to DDIs between hydroxychloroquine and frequently used concurrent drugs.Methods and Results: Using 447,632 patients and 1,040,752 electrocardiograms, we investigated the risk of QT prolongation due to DDIs between hydroxychloroquine and 118 concurrent drugs frequently used in real-world practice. In the analysis, we observed that 11 drugs (trimebutine, tacrolimus, tramadol, rosuvastatin, ciclosporin, sulfasalazine, rofecoxib, diltiazem, piperacillin/tazobactam, and isoniazid) show DDIs with hydroxychloroquine in the direction of QT prolongation.Conclusions: We found 11 drugs that show significant (p

Objectives Biosignal data include important physiological information. For that reason, many devices and systems have been developed, but there has not been enough consideration of how to collect and integrate raw data from multiple systems. To overcome this limitation, we have developed a system for collecting and integrating biosignal data from two patient monitoring systems. Methods We developed an interface to extract biosignal data from Nihon Kohden and Philips monitoring systems. The Nihon Kohden system has a central server for the temporary storage of raw waveform data, which can be requested using the HL7 protocol. However, the Philips system used in our hospital cannot save raw waveform data. Therefore, our system was connected to monitoring devices using the RS232 protocol. After collection, the data were transformed and stored in a unified format. Results From September 2016 to August 2017, we collected approximately 117 patient-years of waveform data from 1,268 patients in 79 beds of five intensive care units. Because the two systems use the same data storage format, the application software could be run without compatibility issues. Conclusions Our system collects biosignal data from different systems in a unified format. The data collected by the system can be used to develop algorithms or applications without the need to consider the source of the data.

Type 2 diabetes mellitus is a major concern globally and well known for increasing risk of complications. However, diabetes complications often remain undiagnosed and untreated in a large number of high-risk patients. In this study based on claims data collected in South Korea, we aimed to explore the diagnostic progression and sex- and age-related differences among patients with type 2 diabetes using time-considered patterns of the incidence of comorbidities that evolved after a diagnosis of type 2 diabetes. This study compared 164,593 patients who met the full criteria for type 2 diabetes with age group-, sex-, encounter type-, and diagnosis date-matched controls who had not been diagnosed with type 2 diabetes. We identified 76,423 significant trajectories of four diagnoses from the dataset. The top 30 trajectories with the highest average relative risks comprised microvascular, macrovascular, and miscellaneous complications. Compared with the trajectories of male groups, those of female groups included relatively fewer second-order nodes and contained hubs. Moreover, the trajectories of male groups contained diagnoses belonging to various categories. Our trajectories provide additional information about sex- and age-related differences in the risks of complications and identifying sequential relationships between type 2 diabetes and potentially complications.

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.

Background: In COPD, coronary artery disease (CAD) is a frequent co-morbidity and cardiovascular disease is the most common cause of death. When coronary angiography was performed, the Gensini score is used for the assessment of CAD severity. This study was performed to evaluate the clinical impact of Gensini score in COPD. Methods: We retrospectively reviewed 191 patients with COPD (male 90.1%, mean age 68.5 ± 8.9 years, smoker 86.2%) who had undergone coronary angiography in Ajou University Hospital from Jan 2000 to Dec 2012. The extent of CAD in the entire coronary arterial tree was assessed by Gensini score. Comparative analyses between high Gensini group (≥4 points; median value or more) and low Gensini group ( Results: High Gensini group was more frequently associated with triple vessel CAD (37.2% vs. 1.0%, p 1 (66.4 ± 16.9 vs 64. 9 ± 19.0, p=0.583) and prevalence of hypertension (59.6% vs. 57.7%, p=0.796) did not differ between two groups. High Gensini group was independently related to triple vessel CAD (OR 3.51, 95% CI 1.77 – 6.94) and myocardial infarction (OR 5.38, 95% CI 1.83 – 15.82). Conclusion: Our data suggest that high Gensini score in COPD was independently associated with cardiac co-morbidities such as triple vessel CAD and myocardial infarction.

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

Beijing strain of Mycobacterium tuberculosis (M. tb) is characterized by a high incidence of transmission, relapse, and drug resistance. This study aimed to determine host immune responses to antigens derived from the Beijing/K strain which has been highly prevalent in tuberculosis (TB) outbreaks in South Korea.We recruited 52 TB patients and 96 healthy subjects comprising 31 individuals with latent TB infection (LTBI) and 65 TB-naïve controls based on QuantiFERON-TB Gold In-Tube (QFT-IT) tests. Blood samples were obtained for diluted whole-blood assays, multiplex bead arrays, ELISpot assays, and HLA typing. Molecular genotyping of M. tb was performed using clinical isolates.Active TB and LTBI groups were differentiated by TNF-α concentrations induced by the Beijing/K strain-derived antigens, MTBK_24790 and MTBK_24800 (P 0.001). MTBK_24800-induced IFN-γ and CXCL10 concentrations discriminated the TB-infected groups from TB-naïve controls (P 0.001). IFN-γ-producing T cells were generated in 87.2% of TB patients in response to MTBK_24800 peptide antigens. The major immunogenic epitope was at C-terminal of the antigen, and predominantly recognized by HLA-DR4 and -DQ4.Measurement of IFN-γ, CXCL10, and TNF-α concentrations induced by MTBK_24790 and MTBK_24800 may contribute to improved diagnosis of TB and vaccine development in regions where the Beijing/K strain is endemic.

Background: The T-helper type 1(Th1) lymphocytes is important in pathogenesis of tuberculosis. So, we evaluated for significance of interferon (IFN)-γ and IFN-inducible chemokines in pleural effusions. Methods: A total of 276 subjects were enrolled. The study population comprised 80 patients with tuberculous effusions, 68 patients with malignant effusions, 53 patients with parapneumonic effusions, 27 patients with transudates, and 48 patients with miscellaneous effusions. In serum and effusion samples from patients with pleural effusions, the levels of IFN-γ, IFN-inducible T-cell alpha chemoattractant (I-TAC) and monokine induced by IFN-γ (MIG) were measured by enzyme-linked immunosorbent assay (ELISA) and the levels of adenosine deaminase (ADA) were measured by colorimetry. Receiver operating characteristic (ROC) analysis was performed. Results: The levels of IFN-γ, I-TAC, MIG and ADA in the pleural effusions were significantly increased in the tuberculous effusions ( p Conclusions: All the IFN-γinducible chemokines along with and ADA showed high discriminating powers for tuberculous effusion, especially IFN-γ in effusion, and MIG in serum. Those chemokines can be useful surrogate markers in diagnosis of pleural effusion.