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Cardiovascular diseases can affect the clinical course of coronavirus disease 2019 (COVID-19); however, evaluation of COVID-19 contribution to prognosis for each individual disease, such as heart failure, is lacking in South Korea. Therefore, this study aimed to investigate COVID-19 patients with heart failure by matching them with patients with heart failure only and those with COVID-19 only. We performed a nationwide population-based retrospective study using data from the National Health Insurance System. Based on patients with heart failure and COVID-19, up to 1:3 propensity score matching procedures were performed for patients with heart failure only and those with COVID-19 only. The outcome was the composite of complications. After matching, a multivariable-adjusted conditional logistic regression analysis was performed. The number of patients was 317 for heart failure and COVID-19, 951 for heart failure only, and 884 for COVID-19 only. The adjusted odds ratio (OR) and 95% confidence interval (CI) for the composite of complications of patients with heart failure and COVID-19 compared with those with heart failure only was 3.511 (2.501-4.928), and compared with those with COVID-19 only, they were 1.626 (1.112-2.376). In patients with heart failure and COVID-19, age per 10 years increase and diabetes were significant variables with the adjusted OR (95% CI) [2.206 (1.704-2.856) for age and 2.345 (1.244-4.420) for diabetes] for complications. This study demonstrated that patients with both heart failure and COVID-19 in South Korea are associated with a poor prognosis. Patients with heart failure require more surveillance and precautions for COVID-19, as recommended by the Center for Disease Control and Prevention.

Hemoglobin level determines blood viscosity and as hemoglobin level rises, blood pressure rises. However, hemoglobin level in individuals is not fixed and change in hemoglobin is affected by various clinical conditions. The purpose of this study is to investigate whether the hemoglobin variability affects the development of hypertension using Korean cohort database. This study was conducted with 94,798 adults (age ≥ 40 years) who visited the health screening in 2006 or 2007 (index year) and had at least 3 health screenings from 2002 to 2007. Hemoglobin variability was assessed by 3 indices of coefficient of variation (CV), standard deviation, and variability independent of the mean. Cox proportional hazard regression analysis was performed for each index of quartile groups (Q1–Q4). A total of 29,145 participants (30.7%) had the incidence of hypertension during a median follow-up of 7.4 ± 2.5 years. In the multivariable adjusted model, the hazard ratio and 95% confidence interval for incidence of hypertension of Q2, Q3, and Q4 compared with Q1 of hemoglobin variability CV were 1.014 [0.981–1.047], 1.064 [1.030–1.099] and 1.094 [1.059–1.131] respectively. The results were consistent in various sensitivity and subgroup analyses. This study showed that hemoglobin variability could be associated with hypertension development.

Hemoglobin variability is known to be associated with mortality in patients with chronic renal failure and cardiovascular disease. However, the effect of hemoglobin variability on mortality in the general population has not yet been studied. We aimed to investigate the association between hemoglobin variability and mortality using Korean cohort from National Health Insurance Service-Health Screening 2002–2015 database. This study was conducted on 182,757 adults who underwent more than 4 health screenings from 2002 to 2009. Hemoglobin variability was assessed by 3 indices of coefficient of variation (CV), standard deviation (SD), and variability independent of the mean (VIM). Cox proportional hazard regression analysis was performed for each index of quartile groups (Q1–Q4). The hazard ratio and 95% confidence interval^l for all-cause mortality comparing Q2, Q3 and Q4 with Q1 of hemoglobin variability CV in the multivariable adjusted model were 1.07 [0.96–1.20], 1.18 [1.06–1.31] and 1.43 [1.29–1.58] respectively. As the 5% CV, SD, and VIM increased, the hazard ratio for mortality increased by 1.08 [1.06–1.10] in the multivariable adjusted model. Hemoglobin variability is not only important predictor in patients with chronic renal failure and cardiovascular disease but could also be considered as a useful predictor of mortality in the general population.

Several studies reported that aspirin can potentially help prevent infection and serious complications of coronavirus disease (COVID-19), but no study has elucidated a definitive association between aspirin and COVID-19. This study aims to investigate the association between aspirin and COVID-19.This case-control study used demographic, clinical, and health screening laboratory test data collected from the National Health Insurance Service database. Patients who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection until June 4, 2020, were matched with control patients using propensity score matching according to their SARS-CoV-2 status, the composite of complications, and death. The composite of complications included intensive care unit admission, use of vasopressors, high-flow oxygen therapy, renal replacement therapy, extracorporeal membrane oxygenation, and death. Exposure to aspirin was defined as having a prescription for aspirin for more than 14 days, including the index date. After matching, multivariable-adjusted conditional logistic regression analysis was performed. To confirm the robustness of this study, we used 2 study groups, 3 propensity score matching methods, and 3 models for conditional logistic regression analyses.The crude odds ratio and 95% confidence interval for SARS-CoV-2 infection between the groups without and with exposure to aspirin were 1.21 (1.04-1.41), but the adjusted odds ratios (95% confidence interval) were not significant. There was no association between aspirin exposure and COVID-19 status. Multiple statistical analyses, including subgroup analysis, revealed consistent results. Furthermore, the results of analysis for complications and death were not significant. Aspirin exposure was not associated with COVID-19-related complications and mortality in COVID-19 patients.In this nationwide population-based case-control study, aspirin use was not associated with SARS-CoV-2 infection or related complications. With several ongoing randomized controlled trials of aspirin in COVID-19 patients, more studies would be able to confirm the effectiveness of aspirin in COVID-19.

Purpose: On the basis that spironolactone is involved in ACE2 expression and TMPRSS2 activity, previous studies have suggested that spironolactone may influence the infectivity of COVID-19. Research has suggested that cell entry of SARS-CoV-2, the virus that induces COVID-19, is associated with the ACE2 receptor and TMPRSS2. The purpose of this study was to investigate whether spironolactone has a protective effect against COVID-19 and the development of associated complications in patients with liver cirrhosis.Methods: We conducted a nationwide case-control study on liver cirrhosis patients with or without COVID-19 from the population-based data acquired from the National Health Insurance Systems of Republic of Korea. After 1:5 case-control matching, multivariable adjusted conditional logistic regression analysis was performed.Results: Among the patients with liver cirrhosis, the case group with COVID-19 was found to be significantly less exposed to spironolactone compared with the control group without COVID-19. The adjusted odds ratio (OR) and 95% confidence interval (CI) between the two groups was 0.20 (0.07–0.54). In addition, regardless of cumulative dose of spironolactone, exposure to spironolactone was associated with lower COVID-19 infection. In terms of the development of complications due to COVID-19, spironolactone did not show any significant association between the patients with and without complications (P = 0.43). The adjusted OR and 95% CI between the two groups was 1.714 (0.246–11.938).Conclusion: We conclude that spironolactone may reduce susceptibility to COVID-19 but does not affect the development of its associated complications; however, further studies are needed to confirm the exact association between spironolactone and COVID-19 infection.

Chronic kidney disease–mineral bone disorder (CKD-MBD) is the most common complication in CKD patients. Although there is a consensus on treatment guidelines for CKD-MBD, it remains uncertain whether these treatment recommendations reflect actual practice. Therefore, the aim of this study was to investigate the CKD-MBD medication trend in real-world practice. This was a retrospective and observational study using a 12-year period database transformed into a common data model from three tertiary university hospitals. Study populations were subjects initially diagnosed as CKD. The date of diagnosis was designated as the index date. New patients were categorized year to year from 2008 to 2019 with a fixed observation period of 365 days to check the prescription of CKD-MBD medications including calcium-containing phosphate binder, noncalcium-containing phosphate binder, aluminium hydroxide, vitamin D receptor activator (VDRA), and cinacalcet. The numbers of CKD patients in the three hospitals were 7555, 2424, and 5351, respectively. The proportion for patients with CKD-MBD medication prescription decreased yearly regardless of hospital and CKD stage ( p for trend < 0.05). The use of aluminium hydroxide disappeared steadily while the use of VDRA increased annually in all settings. Despite these changes in prescription patterns, the mean value for CKD-MBD-related serologic markers was almost within target range. The proportion of the population within the target value was not significantly changed. Irrespective of hospital and CKD stage, similar trends of prescription for CKD-MBD medications were observed in real-world practice. Further research with a distributed network study may be helpful to understand medication trends in CKD-MBD treatment.

Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are antidiabetic drugs that improve cardiovascular outcomes. Hemoglobin and hematocrit values increase after SGLT-2 inhibitor administration. Although these factors increase blood viscosity and the risk of cardiovascular disease, SGLT-2 inhibitors have protective effects on the cardiovascular system. The mechanisms for this paradoxical phenomenon remain unclear, and the effect of SGLT-2 inhibitors on hemorheology has not been studied. We evaluated the hemorheological parameters of 63 patients of whom 38 received metformin with a dipeptidyl peptidase 4 (DPP-4) inhibitor, while 25 received metformin with SGLT-2 inhibitor. Blood viscosity was measured using a cone-and-plate viscometer, erythrocyte aggregation was measured using a modified erythrocyte sedimentation rate method, and erythrocyte membrane fluctuation was measured as deformability, using a diffraction optical tomography. Both blood viscosity and erythrocyte aggregation increased in the SGLT-2 inhibitor group, although erythrocyte deformability was significantly improved compared with that of the DPP-4 inhibitor group (DPP-4 inhibitor 43.71 ± 5.13 nm; SGLT-2 inhibitor 53.88 ± 4.88 nm; p

Background/Aims Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, there have been concerns about the association between exposure to renin-angiotensin-aldosterone system (RAAS) inhibitors and the risk and severity of COVID-19. Methods We performed a case-control study that utilized up-to-date data on the South Korean population provided by the Korean National Health Insurance System. Of the 62,909 patients with hypertension or heart failure tested for COVID-19, there were 1,644 (2.6%) confirmed cases. After case-control matching, multivariable-adjusted conditional logistic regression analysis was performed. Results Comparison between patients exposed to RAAS inhibitors and those not exposed to RAAS inhibitors revealed that the adjusted odds ratio (OR) and 95% confidence interval (CI) for COVID-19 infection and death were 0.981 (95% CI, 0.849 to 1.135) and 0.875 (95% CI, 0.548 to 1.396), respectively. Subgroup analysis for the major confounders, age and region of diagnosis, resulted in OR of 0.912 (95% CI, 0.751 to 1.108) and 0.942 (95% CI, 0.791 to 1.121), respectively. Conclusions The present study demonstrated no evidence of association between RAAS inhibitor exposure and risk and severity of COVID-19.

The severe acute respiratory syndrome coronavirus 2 is known to infect host cells by interacting with ACE2 (angiotensin-converting enzyme 2) expressed in the respiratory epithelium. There have been concerns on whether alterations of ACE2 expression by renin-angiotensin-aldosterone system (RAAS) inhibitors would contribute to the infectivity and severity of coronavirus disease 2019 (COVID-19). We performed a case-control study to investigate the association between RAAS inhibitors and risk and severity of COVID-19 infection in South Korea using the population-based data provided by the Korean National Health Insurance System. Of 16 281 subjects with hypertension, there were 950 (5.8%) confirmed COVID-19 cases. After case-control matching, multivariable-adjusted conditional logistic regression analysis was performed. The adjusted odds ratio and 95% CIs for COVID-19 infection and long-term hospitalization comparing exposure to RAAS inhibitors and nonexposure to RAAS inhibitors was 1.161 (0.958–1.407) and 0.863 (0.533–1.397), respectively. When comparing exposure to RAAS inhibitors and nonexposure to RAAS inhibitors for intensive care unit admission, high-flow oxygen therapy, and death, the adjusted odds ratios (95% CIs) were 1.515 (0.402–5.701), 0.663 (0.272–1.619), and 1.363 (0.513–3.662), respectively. In all analyses, P values were not significant ( P >0.05). The present study demonstrates the absence of an identifiable association between the exposure to RAAS inhibitors and risk and severity of COVID-19 infection, supporting the current medical guidelines and recommendations that patients should not discontinue RAAS inhibitors out of a concern that they are at increased risk for infection or severe illness of COVID-19.

Cancer is a dynamic disease involving constant changes. With these changes, cancer cells become heterogeneous, resulting in varying sensitivity to chemotherapy. The heterogeneity of cancer cells plays a key role in chemotherapy resistance and cancer recurrence. Therefore, for effective treatment, cancer cells need to be analyzed at the single-cell level by monitoring various proteins and investigating their heterogeneity. We propose a microfluidic chip for a single-cell proteomics assay that is capable of analyzing complex cellular signaling systems to reveal the heterogeneity of cancer cells. The single-cell assay chip comprises (i) microchambers (n = 1376) for manipulating single cancer cells, (ii) micropumps for rapid single-cell lysis, and (iii) barcode immunosensors for detecting nine different secretory and intracellular proteins to reveal the correlation among cancer-related proteins. Using this chip, the single-cell proteomics of a lung cancer cell line, which may be easily masked in bulk analysis, were evaluated. By comparing changes in the level of protein secretion and heterogeneity in response to combinations of four anti-cancer drugs, this study suggests a new method for selecting the best combination of anti-cancer drugs. Subsequent preclinical and clinical trials should enable this platform to become applicable for patient-customized therapies.

Pneumonia is related to oral health of the elderly and intensive care unit patients. However, studies on the relationship between overall oral health and pneumonia in the general population have been limited. The purpose of this study was to investigate the association between oral health and pneumonia using a nationwide population-based Korean cohort database. Data from 122,251 participants who underwent health screening and oral examinations in 2004 or 2005 were analyzed. Cox proportional hazard regression analysis was performed to evaluate the association between oral health and pneumonia. The risk of pneumonia increased significantly in groups with a higher number of dental caries and missing teeth, with respective adjusted hazard ratios (HRs) and 95% confidence interval (CI) of 1.265 (1.086–1.473; p = 0.0025) and 1.218 (1.113–1.332; p

The available data on the association between micronutrients in the blood and non-alcoholic fatty liver disease (NAFLD) are limited. To investigate the clinical implications of this relationship, we sought to identify the difference in the serum levels of vitamins A and E according to NAFLD status using data from the seventh Korea National Health and Nutrition Examination Survey. In this cross-sectional study of the Korean population, NAFLD and its severity were defined using prediction models. Differences in the prevalence and severity of NAFLD were analyzed according to serum retinol (vitamin A) and alpha (α)-tocopherol (vitamin E) levels. Serum levels of retinol and α-tocopherol were positively correlated with the prevalence of NAFLD. In most prediction models of the NAFLD subjects, serum retinol deficiency was significantly correlated with advanced fibrosis, while serum α-tocopherol levels did not differ between individuals with or without advanced fibrosis. Similar trends were also noted with cholesterol-adjusted levels of α-tocopherol. In summary, while circulating concentrations of retinol and α-tocopherol were positively associated with the presence of NAFLD, advanced liver fibrosis was only correlated with serum retinol levels. Our findings could provide insight into NAFLD patient care at a micronutrient level.

Electrical methods are among the primarily studied non-invasive glucose measurement techniques; however, various factors affect the accuracy of the sensors used. Of these, the temperature is a critical factor; hence, the effects of temperature on the electrical properties of blood components are investigated in this study. Furthermore, the changes in the electrical properties of blood according to the glucose level are corrected by considering the effects of temperature on the electrical properties. An impedance sensor is developed and used to measure whole blood impedance in 10 healthy participants at various temperatures and glucose levels. Subsequently, the conductivities of the plasma and cytoplasm were extracted. Changes in the electrical properties of the blood components are then analyzed using linear regression and repeated measures ANOVA. The electrical conductivities of plasma and cytoplasm increased with increasing temperatures (plasma: 0.0397 (slope), 0.7814 (R2), cytoplasm: 0.014 (slope), 0.694 (R2)). At three values of increasing glucose levels (85.4, 158.1, and 271.8 mg/dL), the electrical conductivities of the plasma and cytoplasm decreased. These tendencies are more significant upon temperature corrections (p-values; plasma: 0.001, 0.001, cytoplasm: 0.003, 0.002). The relationships between temperature and electrical conductivity changes can thus be used for temperature corrections in blood glucose measurement.

Individuals with intermediate to high cardiac risk for major noncardiac surgery suffer from perioperative myocardial ischemic injury. The purpose of this study was to evaluate the long-term impact of postoperative cardiac troponin elevation on clinical outcome after major noncardiac surgery.Patients (n = 750) aged ≥ 50 years who underwent major noncardiac surgery were eligible for the study. Postoperative cardiac troponin-I data were collected retrospectively and consecutively. The primary outcome measure was allcause mortality. The median follow-up period was 1727 days in all patients.Among 750 patients, 92 (12.2%) showed elevated postoperative troponin-I above 0.10 ng/mL. Operative mortality was 4.1% (31 subjects), and patients with troponin-I elevation showed a higher operative mortality rate (RR: 4.23, 95% CI: 2.67-11.31, P < 0.001). In multivariate Cox regression analysis, a troponin-I concentration above 0.10 ng/mL was associated with all-cause mortality (RR: 1.73, 95% CI: 1.27-2.36, P < 0.001). It should be noted that there was a significant difference between patients with elevated and non-elevated troponin-I in the rate of mortality until 6 months. However, these differences disappeared after 6 months.An elevated troponin-I level conferred an increase in mortality during the 7 year follow-up period after major noncardiac surgery. This difference in mortality was mainly derived from the result within the first 6 months.