Background: It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia. Methods: This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment. Results: After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. −0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (−55.20% vs. −7.69%, P<0.001) without previously unknown adverse drug events. Conclusion The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin’s preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.

Background: Preeclampsia (PE) is known to arise from insufficient trophoblast invasion as uterine spiral arteries lack remodeling. A significant reduction in placental perfusion induces an ischemic placental microenvironment due to reduced oxygen delivery to the placenta and fetus, leading to oxidative stress. Mitochondria are involved in the regulation of cellular metabolism and the production of reactive oxygen species (ROS). NME/NM23 nuceloside diphosphate kinase 4 (NME4) gene is known to have the ability to supply nucleotide triphosphate and deoxynucleotide triphosphate for replication and transcription of mitochondria. Our study aimed to investigate changes in NME4 expression in PE using trophoblast stem-like cells (TSLCs) from induced pluripotent stem cells (iPSCs) as a model of early pregnancy and peripheral blood mononuclear cells (PBMNCs) as a model of late preterm pregnancy. Methods: Transcriptome analysis using TSLCs was performed to identify the candidate gene associated with the possible pathophysiology of PE. Then, the expression of NME4 associated with mitochondrial function, p53 associated with cell death, and thioredoxin (TRX) linked to ROS were investigated through qRT-PCR, western blotting and deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick end labelling (TUNEL) assay. Results: In patients with PE, NME4 was significantly downregulated in TSLCs but upregulated in PBMNCs. p53 was shown to be upregulated in TSLCs and PBMNCs of PE. In addition, western blot analysis confirmed that TRX expression had the tendency to increase in TSLCs of PE. Similarly, TUNEL analysis confirmed that the dead cells were higher in PE than in normal pregnancy. Conclusion Our study showed that the expression of the NME4 differed between models of early and late preterm pregnancy of PE, and suggests that this expression pattern may be a potential biomarker for early diagnosis of PE.

Sarcopenia is a progressive and generalized loss of skeletal muscle mass and function. The prevalence of sarcopenia was reported to be up to 29% in older persons in the community healthcare setting. Sarcopenia diagnosis is confirmed by the presence of low muscle mass plus low muscle strength or low physical performance. Sarcopenia management options include non-pharmacological and pharmacological approaches. Non-pharmacological approaches include resistance exercise and adequate nutrition. Of the two, resistance exercise is the standard non-pharmacological treatment approach for sarcopenia with significant positive evidence. Some dietary approaches such as adequate intake of protein, vitamin D, antioxidant nutrients, and long-chain polyunsaturated fatty acid have been shown to have positive effects against sarcopenia. Currently, no specific drugs have been approved by the Food and Drug Administration for the treatment of sarcopenia. However, several agents, including growth hormone, anabolic or androgenic steroids, selective androgenic receptor modulators, protein anabolic agents, appetite stimulants, myostatin inhibitors, activating II receptor drugs, β-receptor blockers, angiotensin-converting enzyme inhibitors, and troponin activators, are recommended and have been shown to have variable efficacy. Future research should focus on sarcopenia biological pathway and improved diagnostic approaches such as biomarkers for early detection, development of consistently pre-eminent treatment methods for severe sarcopenia patients, and establishing sensitive measures for predicting sarcopenia treatment response.

: Immune checkpoint inhibitors (ICIs) are approved for treating non-small-cell lung cancer (NSCLC); however, the safety and efficacy of combined ICI and Gamma Knife radiosurgery (GKS) treatment remain undefined. In this study, we retrospectively analyzed patients treated with ICIs with or without GKS at our institute to manage patients with brain metastases from NSCLC. Methods : We retrospectively reviewed medical records of patients with brain metastases from NSCLC treated with ICIs between January 2015 and December 2017. Of 134 patients, 77 were assessable for brain responses and categorized into three groups as follows : group A, ICI alone (n=26); group B, ICI with concurrent GKS within 14 days (n=24); and group C, ICI with non-concurrent GKS (n=27). Results : The median follow-up duration after brain metastasis diagnosis was 19.1 months (range, 1–77). At the last follow-up, 53 patients (68.8%) died, 20 were alive, and four were lost to follow-up. The estimated median overall survival (OS) of all patients from the date of brain metastasis diagnosis was 20.0 months (95% confidence interval, 12.5–27.7) (10.0, 22.5, and 42.1 months in groups A, B, and C, respectively). The OS was shorter in group A than in group C (p=0.001). The intracranial disease progression-free survival (p=0.569), local progression-free survival (p=0.457), and complication rates did not significantly differ among the groups. Twelve patients showed leptomeningeal seeding (LMS) during follow-up. The 1-year LMS-free rate in treated with ICI alone group (69.1%) was significantly lower than that in treated with GKS before ICI treatment or within 14 days group (93.2%) (p=0.004). Conclusion : GKS with ICI showed no favorable OS outcome in treating brain metastasis from NSCLC. However, GKS with ICI did not increase the risk of complications. Furthermore, compared with ICI alone, GKS with ICI may be associated with a reduced incidence of LMS. Further understanding of the mechanism, which remains unknown, may help improve the quality of life of patients with brain metastasis.

We performed a point seroprevalence survey of measles among healthcare workers (HCWs) at two Korean teaching hospitals in 2019. A total of 2,830 HCWs underwent an antibody test.The overall seropositivity of measles was 93.1%. The seroprevalence of measles was lowest in HCWs aged 20 - 24 years (81.2%), followed by those aged 25 - 29 years (90.1%). The rates of anti-measles IgG positivity were significantly different between the two hospitals (97.0% vs.89.4%, P <0.001). These results suggest that the seropositivity of measles in HCWs may differ depending on the hospital's vaccination policy.

Purpose: The purpose is to estimate the degree of normalization of C-reactive protein (CRP) at 2 weeks and 4 weeks after uncomplicated total knee arthroplasty (TKA) using computer navigation. We also wish to determine whether the degree of normalization of CRP at 2 and 4 weeks differs after TKA performed in one knee and after TKA performed sequentially in both knees. We also want to analyze the patient factors that may influence the normalization of CRP. Methods: We studied 400 knees who underwent primary computer-navigated TKA for treatment of advanced osteoarthritis: the TKAs were all performed by the same surgeon. We retrospectively analyzed CRP levels during the preoperative period, the early postoperative period (5–7 days), the 2-week postoperative period (12–14 days), and the 4-week postoperative period (25–30 days). We have assumed gender, age, body mass index (BMI), staged bilateral TKA, and preoperative CRP as the potential patient factors associated with CRP normalization. Results: In unilateral TKA, CRP was normalized in 94 cases (34.3%) and in 219 cases (81.4%) within 2 weeks and 4 weeks after surgery, respectively. In second-knee, staged bilateral TKA, CRP was normalized in 46 cases (35.1%) and in 104 cases (79.4%) within 2 weeks and 4 weeks after surgery, respectively. There were no statistical differences between unilateral TKA and second-knee, staged bilateral TKA during the 2-week postoperative and the 4-week postoperative period. Compared to women, men were 1.99 times less likely to have normalized CRP at 2 weeks after surgery (P = 0.02). Conclusion CRP was less likely to normalize during the 2-week postoperative period in men than it is in women, while there was no difference between men and women in the normalization of CRP during the 4-week postoperative period. There were no statistical differences in the course of CRP levels after unilateral TKA and staged bilateral TKA during the 2-week postoperative and the 4-week postoperative period.

Purpose: The purpose is to estimate the degree of normalization of C-reactive protein (CRP) at 2 weeks and 4 weeks after uncomplicated total knee arthroplasty (TKA) using computer navigation. We also wish to determine whether the degree of normalization of CRP at 2 and 4 weeks differs after TKA performed in one knee and after TKA performed sequentially in both knees. We also want to analyze the patient factors that may influence the normalization of CRP. Methods: We studied 400 knees who underwent primary computer-navigated TKA for treatment of advanced osteoarthritis: the TKAs were all performed by the same surgeon. We retrospectively analyzed CRP levels during the preoperative period, the early postoperative period (5–7 days), the 2-week postoperative period (12–14 days), and the 4-week postoperative period (25–30 days). We have assumed gender, age, body mass index (BMI), staged bilateral TKA, and preoperative CRP as the potential patient factors associated with CRP normalization. Results: In unilateral TKA, CRP was normalized in 94 cases (34.3%) and in 219 cases (81.4%) within 2 weeks and 4 weeks after surgery, respectively. In second-knee, staged bilateral TKA, CRP was normalized in 46 cases (35.1%) and in 104 cases (79.4%) within 2 weeks and 4 weeks after surgery, respectively. There were no statistical differences between unilateral TKA and second-knee, staged bilateral TKA during the 2-week postoperative and the 4-week postoperative period. Compared to women, men were 1.99 times less likely to have normalized CRP at 2 weeks after surgery (P = 0.02). Conclusion CRP was less likely to normalize during the 2-week postoperative period in men than it is in women, while there was no difference between men and women in the normalization of CRP during the 4-week postoperative period. There were no statistical differences in the course of CRP levels after unilateral TKA and staged bilateral TKA during the 2-week postoperative and the 4-week postoperative period.

Background: The aim of this study was to evaluate the difference between the planned and verified actual values in total knee arthroplasty (TKA) performed using a navigation system. Methods: Sixty patients who underwent primary TKA for knee pain from March 2018 to July 2018 were included in this study.All patients underwent TKA using the latest version of a computer navigation system (Kick ver. 2.6). All TKA procedures were performed by the same surgeon. The appropriateness of the use of navigation system in each of the several steps during the operation was investigated. Implant size was assessed using a preoperative template and after registration of landmarks with the navigation system. Intraoperative measurement was conducted using a femoral sizing implant apparatus. The difference between the planned value based on the navigation system and the actual cutting value was investigated. Intraoperatively confirmed hip-knee-ankle angle was also compared to the angle measured at postoperative 3 months. Results: The average time spent on the registration process was 242 seconds (range, 205–345 seconds). Intraoperative femoral component size tended to be smaller than the size recommended by the navigation system. A significant difference between the planned distal femoral cutting level (9.08 ± 0.40 mm) and the verified actual cutting level (9.87 ± 1.39 mm) was identified (p < 0.05).The difference between the planned lateral and medial tibial resection levels (10.12 ± 0.34 mm and 4.47 ± 2.17 mm, respectively) and the verified actual lateral and medial tibial resection levels (9.07 ± 1.45 mm and 3.48 ± 2.00 mm, respectively) was statistically significant. Distal femoral cutting angle in sagittal plane was significantly different but femoral and tibial cutting angles showed no significant difference between the planned and verified values. At full extension, the average coronal alignment of the implant recorded after insertion of the actual implant using the navigation system was 0.23° ± 0.51° varus and showed no significant difference from the alignment measured at postoperative 3 months (0.45° ± 0.58°). Conclusions When performing navigation-assisted TKA, surgeons should aware that frequent errors can occur on the femoral cutting level, tibial cutting level, and implant sizing despite its reported advantage in defining the mechanical limb axis.

BACKGROUND: Cardiovascular risk remains increased despite optimal low density lipoprotein cholesterol (LDL-C) level induced by intensive statin therapy. Therefore, recent guidelines recommend non-high density lipoprotein cholesterol (non-HDL-C) as a secondary target for preventing cardiovascular events. The aim of this study was to assess the efficacy and tolerability of omega-3 fatty acids (OM3-FAs) in combination with atorvastatin compared to atorvastatin alone in patients with mixed dyslipidemia. METHODS: This randomized, double-blind, placebo-controlled, parallel-group, and phase III multicenter study included adults with fasting triglyceride (TG) levels ≥200 and <500 mg/dL and LDL-C levels <110 mg/dL. Eligible subjects were randomized to ATOMEGA (OM3-FAs 4,000 mg plus atorvastatin calcium 20 mg) or atorvastatin 20 mg plus placebo groups. The primary efficacy endpoints were the percent changes in TG and non-HDL-C levels from baseline at the end of treatment. RESULTS: After 8 weeks of treatment, the percent changes from baseline in TG (−29.8% vs. 3.6%, P<0.001) and non-HDL-C (−10.1% vs. 4.9%, P<0.001) levels were significantly greater in the ATOMEGA group (n=97) than in the atorvastatin group (n=103). Moreover, the proportion of total subjects reaching TG target of <200 mg/dL in the ATOMEGA group was significantly higher than that in the atorvastatin group (62.9% vs. 22.3%, P<0.001). The incidence of adverse events did not differ between the two groups. CONCLUSION The addition of OM3-FAs to atorvastatin improved TG and non-HDL-C levels to a significant extent compared to atorvastatin alone in subjects with residual hypertriglyceridemia.

Purpose: Post-fracture sleeping disorders can lead to a deterioration of mental and physical health and delay recovery to pre-fracture status. Here, an analysis was conducted to determine if sleep disturbance is a risk factor for delirium in patients older than 60 years of age with surgically treated proximal femoral fractures. Materials and Methods: This retrospective study included 316 patients with surgically treated proximal femoral fractures between January 2014 and December 2016; 33 patients were removed from analysis due to exclusion criteria. Confirmation of delirium was made by a neurologist upon consultation for cognitive impairment and sleeping disorders were confirmed by a doctor or nurse based on the Pittsburgh sleep quality index. Potential risk factors other than a sleep disorder (e.g., history of cognitive impairment, medical illness, preoperational levels of albumin and hemoglobin, transfusion) were also analyzed as variables for the development of delirium. Results: The sensitivity and specificity of a sleeping disorder as a risk factor for the development of delirium were 0.75 and 0.76, respectively; the positive and negative predictive values were 0.64 and 0.93, respectively. A sleeping disorder was significantly related to the development of the delirium (odds ratio adjusted for age, sex and body mass index was 5.78, P<0.01). In those with a history of cognitive impairment, the adjusted odds ratio for the development of delirium was 6.03 (P<0.01). Conclusion Sleeping disorders occurring after a surgically repaired proximal femoral fracture in patients 60 years of age or older could be an independent predictive factor of delirium.