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: This study investigates the long-term efficacy and safety of evogliptin add-on therapy in patients with inadequately controlled type 2 diabetes mellitus (T2DM) previously received dapagliflozin and metformin (DAPA/MET) combination. Methods: In this multicenter randomized placebo-controlled phase 3 trial, patients with glycosylated hemoglobin (HbA1c) levels 7.0% to 10.5% (n=283) previously used DAPA 10 mg plus MET (≥1,000 mg) were randomly assigned to the evogliptin 5 mg once daily or placebo group (1:1). The primary endpoint was the difference in the HbA1c level from baseline at week 24, and exploratory endpoints included the efficacy and safety of evogliptin over 52 weeks (trial registration: ClinicalTrials.gov NCT04170998). Results: Evogliptin add-on to DAPA/MET therapy was superior in HbA1c reduction compared to placebo at weeks 24 and 52 (least square [LS] mean difference, –0.65% and –0.55%; 95% confidence interval [CI], –0.79 to –0.51 and –0.71 to –0.39; P<0.0001). The proportion of patients achieving HbA1c <7% was higher in the triple combination group at week 52 (32.14% vs. 8.51% in placebo; odds ratio, 5.62; P<0.0001). Evogliptin significantly reduced the fasting glucose levels and mean daily glucose levels with improvement in homeostatic model assessment of β-cell function (LS mean difference, 9.04; 95% CI, 1.86 to 16.21; P=0.0138). Adverse events were similar between the groups, and no serious adverse drug reactions were reported in the evogliptin group. Conclusion Long-term triple combination with evogliptin added to DAPA/MET showed superior HbA1c reduction and glycemic control compared to placebo at 52 weeks and was well tolerated.

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: To report a case of continuously progressive abducens palsy after transarterial coil embolization.Case summary: A 42-year-old male was referred to the clinic due to binocular horizontal diplopia. The patient had a history of left direct carotid cavernous fistula (CCF) after head trauma, and his ocular symptoms developed 15 months after coil embolization for CCF. Visual acuity and pupil reaction of both eyes were normal. The ocular motility examination showed 14 prism diopters (PD) of left esotropia in the primary gaze with abduction limitation; therefore, the patient was diagnosed with left abducens palsy. There was no evidence of fistula recanalization or new abnormal lesions in follow-up brain imaging. After strabismus was stabilized with 35 PD of esotropia, strabismus surgery including left medial rectus muscle recession and lateral rectus resection was performed, and ocular alignment was normalized in the primary position. However, 2 years after surgery, left abducens palsy recurred and abduction limitation worsened to -4 over 10 months. Finally, the patient underwent superior rectus transposition and medial rectus re-recession, which improved his ocular alignment at primary position. Binocular diplopia was resolved at primary position. Conclusions Late-onset abducens palsy can occur after coil embolization and is likely to continue to progress. Because spontaneous regression is rare in late-onset palsy compared with acute-onset palsy, surgery should be considered when the strabismus becomes stabilized.

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: To report a case of continuously progressive abducens palsy after transarterial coil embolization.Case summary: A 42-year-old male was referred to the clinic due to binocular horizontal diplopia. The patient had a history of left direct carotid cavernous fistula (CCF) after head trauma, and his ocular symptoms developed 15 months after coil embolization for CCF. Visual acuity and pupil reaction of both eyes were normal. The ocular motility examination showed 14 prism diopters (PD) of left esotropia in the primary gaze with abduction limitation; therefore, the patient was diagnosed with left abducens palsy. There was no evidence of fistula recanalization or new abnormal lesions in follow-up brain imaging. After strabismus was stabilized with 35 PD of esotropia, strabismus surgery including left medial rectus muscle recession and lateral rectus resection was performed, and ocular alignment was normalized in the primary position. However, 2 years after surgery, left abducens palsy recurred and abduction limitation worsened to -4 over 10 months. Finally, the patient underwent superior rectus transposition and medial rectus re-recession, which improved his ocular alignment at primary position. Binocular diplopia was resolved at primary position. Conclusions Late-onset abducens palsy can occur after coil embolization and is likely to continue to progress. Because spontaneous regression is rare in late-onset palsy compared with acute-onset palsy, surgery should be considered when the strabismus becomes stabilized.

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: 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.