Metastasis is the main cause of tumor-related death, and the dispersal of tumor cells through the circulatory system is a critical step in the metastatic process. Early detection and analysis of ...circulating tumor cells (CTCs) is therefore important for early diagnosis, prognosis, and effective treatment of cancer, enabling favorable clinical outcomes in cancer patients. Accurate and reliable methods for isolating and detecting CTCs are necessary to obtain this clinical information. Over the past two decades, microfluidic technologies have demonstrated great potential for isolating and detecting CTCs from blood. The present paper reviews current advanced microfluidic technologies for isolating CTCs based on various biological and physical principles, and discusses their fundamental advantages and drawbacks for subsequent cellular and molecular assays. Owing to significant genetic heterogeneity among CTCs, microfluidic technologies for isolating individual CTCs have recently been developed. We discuss these single-cell isolation methods, as well as approaches to overcoming the limitations of current microfluidic CTC isolation technologies. Finally, we provide an overview of future innovative microfluidic platforms.
Aims
To evaluate the effects of initiating sodium‐glucose cotransporter‐2 (SGLT2) inhibitors on cardiorenal outcomes and mortality compared to dipeptidyl peptidase‐4 (DPP‐4) inhibitors as active ...comparators in patients diagnosed with type 2 diabetes with a history of percutaneous coronary intervention (PCI).
Materials and Methods
We used an active‐comparator, new‐user design and nationwide data from the National Health Insurance Service in South Korea from 2014 to 2019. Of the 56 392 patients who underwent PCI, 4610 new SGLT2 inhibitor users were paired 1:1 with DPP‐4 inhibitor users for analysis using propensity‐score matching.
Results
During 13 708.59 person‐years of follow‐up, the initiation of SGLT2 inhibitors, compared with the initiation of DPP‐4 inhibitors, was associated with a significantly lower risk of composite repeat revascularization, myocardial infarction, stroke, heart failure (HF), all‐cause death and end‐stage renal disease (ESRD). The beneficial effects of SGLT2 inhibitor use were consistent with the components of stroke, HF, all‐cause death and ESRD. In the cohort that included health examination data, including anthropometric and metabolic factors, new use of SGLT2 inhibitors was associated with a significantly lower risk of HF (hazard ratio HR 0.574, 95% confidence interval CI 0.36–0.915), all‐cause death (HR 0.731, 95% CI 0.567–0.942), and ESRD (HR 0.076, 95% CI 0.018–0.319). The effects of SGLT2 inhibitor use were consistent regardless of the timing of the previous PCI.
Conclusions
The initiation of SGLT2 inhibitors in patients with type 2 diabetes and a history of PCI was significantly associated with a reduced risk of cardiorenal consequences and mortality, irrespective of time since the last PCI.
Adult women experience several changes in physiological status, such as pregnancy and childbirth, during their life cycle. This study analyses the association between birth-related factors (the ...number of childbirths, abortions and miscarriages) and periodontitis using data from the Korea National Health and Nutrition Examination Survey, which represents Korean adults.
The study used data from Korea National Health and Nutrition Examination Survey VI and VII (2013-2018) and included 10,072 women 19 years or older, with no missing data on the variables assessed. Periodontitis was defined according to the Community Periodontal Index (CPI) criteria. Multiple logistic regression analysis, adjusting for age, household income, education, alcohol consumption, smoking, stress, body mass index, waist circumference, hypertension, diabetes mellitus, an oral examination within 1 year, daily tooth brushing frequency, hygiene products and self-perceived oral health as identified via logistic regression analyses, was performed to determine the association between birth-related variables and periodontitis.
In the crude model, the odds ratio (OR) showed a significantly increased risk of periodontitis (CPI ≥ 3) and severe periodontitis (CPI = 4) based on the number of childbirths, abortions and miscarriages (p < .05). After covariate adjustment, periodontitis (CPI ≥ 3) was associated with the number of childbirths (1: OR = 1.92; 95% confidence interval CI: 1.47-2.50; 2: OR = 2.03; 95% CI: 1.57-2.61; ≥3: OR = 2.11; 95% CI: 1.60-2.78). Furthermore, severe periodontitis (CPI = 4) was also associated with the number of childbirths (1: OR = 2.33; 95% CI: 1.24-4.38; 2: OR = 2.99; 95% CI: 1.62-5.52; ≥3: OR = 3.34; 95% CI: 1.79-6.21).
The findings of this large-scale, nationally representative study suggest that the number of childbirths is associated with the severity of periodontitis. However, the relationship between the number of abortions and miscarriages and periodontitis (CPI ≥ 3) or severe periodontitis (CPI = 4) is not significant.
We aimed to isolate circulating tumor cells (CTCs) using a microfluidic technique with a novel lateral magnetophoretic microseparator. Prostate cancer–specific gene expressions were evaluated using ...mRNA from the isolated CTCs. A CTC‐based multigene model was then developed for identifying advanced prostate cancer. Peripheral blood samples were obtained from five healthy donors and patients with localized prostate cancer (26 cases), metastatic hormone‐sensitive prostate cancer (mHSPC, 10 cases), and metastatic castration‐resistant prostate cancer (mCRPC, 28 cases). CTC recovery rate and purity (enriched CTCs/total cells) were evaluated according to cancer stage. The areas under the curves of the six gene expressions were used to evaluate whether multigene models could identify mHSPC or mCRPC. The number of CTCs and their purity increased at more advanced cancer stages. In mHSPC/mCRPC cases, the specimens had an average of 27.5 CTCs/mL blood, which was 4.2 × higher than the isolation rate for localized disease. The CTC purity increased from 2.1% for localized disease to 3.8% for mHSPC and 6.7% for mCRPC, with increased CTC expression of the genes encoding prostate‐specific antigen (PSA), prostate‐specific membrane antigen (PSMA), and cytokeratin 19 (KRT19). All disease stages exhibited expression of the genes encoding androgen receptor (AR) and epithelial cell adhesion molecule (EpCAM), although expression of the AR‐V7 variant was relatively rare. Relative to each gene alone, the multigene model had better accuracy for predicting advanced prostate cancer. Our lateral magnetophoretic microseparator can be used for identifying prostate cancer biomarkers. In addition, CTC‐based genetic signatures may guide the early diagnosis of advanced prostate cancer.
CTCs have useful biological information for understanding the prostate cancer aggressiveness. CTC‐based gene signatures have potential for early diagnosis of metastatic prostate cancer. Multigene profile (AR, AR‐V7, PSA, PSMA, EpCAM, and KRT19) may guide the diagnosis and treatment of metastatic prostate cancer.
Necrotizing fasciitis (NF) is a serious skin and soft tissue infection causing high mortality. Investigating region specific epidemiologic factors associated with NF is important for establishing ...appropriate treatment strategies. This multicenter study was done to provide an update of the microbial etiology, clinical characteristics, and outcomes of NF in Korea.
A retrospective cohort of adult patients with NF was established using patient data from 13 general hospitals between January 2012 and December 2015 in Korea. We evaluated microbial etiology and clinical characteristics to identify risk factors associated with in-hospital mortality; analyses were performed using binary logistic regression models.
A total of 161 patients with NF were included. The most common underlying disease was diabetes mellitus (66 cases, 41.0%). A total of 148 organisms were isolated from 119 (73.9%) patients. Enteric Gram-negative organisms (36 patients) were the most common pathogen, followed by Staphylococcus aureus (30 patients) and streptococci (28 patients). Methicillin-resistant Staphylococcus aureus (MRSA) was identified in 6.2% (10/161) of patients. Of 37 enteric Gram-negative isolates tested, 26 (70.3%) isolates were susceptible to ceftriaxone. The in-hospital mortality rate was 22.4%. Intensive care unit admission, septic shock, and Gram-negative organism infections were significantly associated with in-hospital mortality, and surgery was not a favorable prognostic factor.
As initial empirical antibiotics, glycopeptides against MRSA and broad-spectrum antibiotics against third-generation cephalosporin-resistant organisms should be considered for patients with community-onset NF in Korea.
Aim
This study aimed to investigate the effects of repeated detection of non‐alcoholic fatty liver disease (NAFLD) on the incidence risk of type 2 diabetes in young adults.
Materials and Methods
In ...this nationwide population‐based observational study using data from the Korean National Health Insurance Service, approximately 1 125 015 young adults aged 20‐39 years who underwent health screening four times between 2009 and 2013 were included. NAFLD was defined as a fatty liver index (FLI) of ≥60. Repeated detection of NAFLD scores was defined as the number of times the participants met the criteria for NAFLD (0‐4). To account for the degree of repeated detection of NAFLD, weighted repeated NAFLD scores were scaled as a sum by assigning points (0 points for FLI <30, 1 point for 30 ≤ FLI < 60, and 2 points for FLI ≥60) ranging from 0 to 8 points.
Results
The multivariable‐adjusted hazard ratios of type 2 diabetes associated with repeated detection of NAFLD scores of 1, 2, 3 and 4 were 2.74 (95% confidence interval 2.57‐2.921), 3.45 (3.221‐3.694), 4.588 (4.303‐4.892) and 6.126 (5.77‐6.504), respectively. The incidence risk of type 2 diabetes increased significantly with repeated detection of the NAFLD score. In the analysis of the weighted repeated NAFLD score, the hazard ratios for the incidence of type 2 diabetes showed a significant continuous positive linear association with increasing scores.
Conclusions
Repeated detection of NAFLD influenced the incidence risk of type 2 diabetes in young adults, and a higher degree of repeated detection of NAFLD was independently associated with the risk of type 2 diabetes in young adults.
Aims
We aimed to investigate weight change in patients with new‐onset type 2 diabetes mellitus and the association of weight loss on diabetes remission in Korean adults.
Materials and Methods
We used ...the health examination database of the Korean National Health Insurance Service. Patients diagnosed with type 2 diabetes mellitus from 2009 to 2012 were enrolled and followed to 2017. The baseline body weight was measured at the health examination closest to the time the patient was enrolled, and the change was calculated by examining the weight measured at the subsequent examination within 2 years. Remission was defined as fasting blood glucose less than 126 mg/dl at two or more consecutive health examinations after stopping medication.
Results
In total, 114, 874 patients with new‐onset type 2 diabetes mellitus were analysed. Of these, 23 156 (20.2%) lost more than 5% of their body weight, and 2429 (2.1%) achieved remission. The adjusted odds ratio for remission in the weight loss group was 2.56 (95% confidence interval 2.35‐2.79) compared with the group with stable body weight. Sensitivity analysis according to the degree of weight change showed that the greater weight loss, the higher the likelihood of remission. In the subgroup analysis, the effects of weight loss on remission were significantly greater in subgroups of age <65 years, male sex and body mass index >25.
Conclusion
Weight loss within the first 2 years of treating type 2 diabetes mellitus was associated with diabetes remission. Physicians should pay more attention to weight management in new‐onset type 2 diabetes mellitus, particularly for young and obese individuals.
The outbreak of coronavirus disease 2019 (COVID-19), which began in December 2019, is still ongoing in Korea, with >9,000 confirmed cases as of March 25, 2020. COVID-19 is a severe acute respiratory ...syndrome Coronavirus 2 (SARS-CoV-2) infection, and real-time reverse transcription-PCR is currently the most reliable diagnostic method for COVID-19 around the world. Korean Society for Laboratory Medicine and the Korea Centers for Disease Prevention and Control propose guidelines for diagnosing COVID-19 in clinical laboratories in Korea. These guidelines are based on other related domestic and international guidelines, as well as expert opinions and include the selection of test subjects, selection of specimens, diagnostic methods, interpretation of test results, and biosafety.
: Although melatonin has a variety of biological actions such as antitumor, antiangiogenic, and antioxidant activities, the osteogenic mechanism of melatonin still remains unclear. Thus, in the ...present study, the molecular mechanism of melatonin was elucidated in the differentiation of mouse osteoblastic MC3T3‐E1 cells. Melatonin enhanced osteoblastic differentiation and mineralization compared to untreated controls in preosteoblastic MC3T3‐E1 cells. Also, melatonin increased wound healing and dose‐dependently activated osteogenesis markers such as runt‐related transcription factor 2 (Runx2), osteocalcin (OCN), bone morphogenic protein (BMP)‐2 and ‐4 in MC3T3‐E1 cells. Of note, melatonin activated Wnt 5 α/β, β‐catenin and the phosphorylation of c‐Jun N‐terminal kinase (JNK), and extracellular signal‐regulated kinase (ERK) in a time‐dependent manner while it attenuated phosphorylation of glycogen synthase kinase 3 beta (GSK‐3β) in MC3T3‐E1 cells. Consistently, confocal microscope observation revealed that BMP inhibitor Noggin blocked melatonin‐induced nuclear localization of β‐catenin. Furthermore, Western blotting showed that Noggin reversed activation of β‐catenin and Wnt5 α/β and suppression of GSK‐3β induced by melatonin in MC3T3‐E1 cells, which was similarly induced by ERK inhibitor PD98059. Overall, these findings demonstrate that melatonin promotes osteoblastic differentiation and mineralization in MC3T3‐E1 cells via the BMP/ERK/Wnt pathways.
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