Objective: To evaluate the effects of Catalpa bignonioides fruit extract on the promotion of muscle growth and muscular capacity in vitro and in vivo. Methods: Cell viability was measured using the 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide assay. Cell proliferation was assessed using a 5-bromo-2’-deoxyuridine (BrdU) assay kit. Western blot analysis was performed to determine the protein expressions of related factors. The effects of Catalpa bignonioides extract were investigated in mice using the treadmill exhaustion test and whole-limb grip strength assay. Chemical composition analysis was performed using high-performance liquid chromatography (HPLC). Results: Catalpa bignonioides extract increased the proliferation of C2C12 mouse myoblasts by activating the Akt/mTOR signaling pathway. It also induced metabolic changes, increasing the number of mitochondria and glucose metabolism by phosphorylating adenosine monophosphate-activated protein kinase. In an in vivo study, the extract-treated mice showed improved motor abilities, such as muscular endurance and grip strength. Additionally, HPLC analysis showed that vanillic acid may be the main component of the Catalpa bignonioides extract that enhanced muscle strength. Conclusions: Catalpa bignonioides improves exercise performance through regulation of growth and metabolism in skeletal muscles, suggesting its potential as an effective natural agent for improving muscular strength.

Although gemcitabine-based regimens are widely used as an effective treatment for pancreatic cancer, acquired resistance to gemcitabine has become an increasingly common problem. Therefore, a novel therapeutic strategy to treat gemcitabine-resistant pancreatic cancer is urgently required. Piceamycin has been reported to exhibit antiproliferative activity against various cancer cells; however, its underlying molecular mechanism for anticancer activity in pancreatic cancer cells remains unexplored. Therefore, the present study evaluated the antiproliferation activity of piceamycin in a gemcitabine-resistant pancreatic cancer cell line and patient-derived pancreatic cancer organoids. Piceamycin effectively inhibited the proliferation and suppressed the expression of alpha-actinin-4, a gene that plays a pivotal role in tumorigenesis and metastasis of various cancers, in gemcitabine-resistant cells. Long-term exposure to piceamycin induced cell cycle arrest at the G0/G1 phase and caused apoptosis. Piceamycin alsoinhibited the invasion and migration of gemcitabine-resistant cells by modulating focal adhesion and epithelial-mesenchymal transition biomarkers. Moreover, the combination of piceamycin and gemcitabine exhibited a synergistic antiproliferative activity in gemcitabine-resistant cells. Piceamycin also effectively inhibited patient-derived pancreatic cancer organoid growth and induced apoptosis in the organoids. Taken together, these findings demonstrate that piceamycin may be an effective agent for overcoming gemcitabine resistance in pancreatic cancer.

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: Coronary artery disease patients undergoing percutaneous coronary intervention (PCI) often exhibit reduced left ventricular ejection fraction (LVEF). However, the impact of LV dysfunction status in conjunction with platelet reactivity on clinical outcomes has not been previously investigated. Methods: From the multicenter PTRG-DES (Platelet function and genoType-Related long-term prognosis in DES-treated patients) consortium, the patients were classified as preserved-EF (PEF: LVEF ≥ 50%) and reduced-EF (REF: LVEF< 5 0%) group by echocardiography. Platelet reactivity was measured using VerifyNow P2Y 12 assay and high platelet reactivity (HPR) was defined as PRU ≥ 252. The major adverse cardiac and cerebrovascular events (MACCEs) were a composite of death, myocardial infarction, stent thrombosis and stroke at 5 years after PCI. Major bleeding was defined as Bleeding Academic Research Consortium bleeding types 3–5. Results: A total of 13,160 patients from PTRG-DES, 9,319 (79.6%) patients with the results of both PRU and LVEF were analyzed. The incidence of MACCE and major bleeding was higher in REF group as compared with PEF group (MACCEs: hazard ratio [HR] 2.17, P < 0.001, 95% confidence interval [CI] 1.85–2.55; major bleeding: HR 1.78, P < 0.001, 95% CI 1.39–2.78).The highest rate of MACCEs was found in patients with REF and HPR, and the difference between the groups was statistically significant (HR 3.14 in REF(+)/HPR(+) vs. PEF(+)/HPR(-) group,P <0.01, 95% CI 2.51–3.91). The frequency of major bleeding was not associated with the HPR in either group. Conclusion LV dysfunction was associated with an increased incidence of MACCEs and major bleeding in patients who underwent PCI. The HPR status further exhibited significant increase of MACCEs in patients with LV dysfunction in a large, real-world registry.Trial Registration: ClinicalTrials.gov Identifier: NCT04734028

Isolated extramedullary relapse (EMR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acute myeloid leukemia (AML) is relatively rare and the clinical significance is still not well characterized, particularly in children. During or after chemotherapy, an uncommon event termed lineage switch, in which the lineage at onset of leukemia converts to another lineage at a later time, is observed in a subset of leukemia patients, but it is a rare event. We report a 10-year-old boy with isolated mediastinal EMR after allo-HSCT for AML who subsequently experienced BM relapse with the cell lineage switching from AML to T-cell acute lymphoblastic leukemia.

Purpose: To derive the optimized intraocular lens (IOL) constants from automated and manifest refraction after cataract surgery in Korean patients, and to evaluate whether there is a difference in optimized IOL constants according to the refraction method. Methods: This retrospective multicenter cohort study enrolled 4,103 eyes of 4,103 patients who underwent phacoemulsification and in-the-bag IOL implantation at 18 institutes. Optimized IOL constants for the SRK/T, Holladay, Hoffer Q, and Haigis formulas were calculated via autorefraction or manifest refraction of samples using the same biometry and IOL. The IOL constants derived from autorefraction and manifest refraction were compared. Results: Of the 4,103 eyes, the majority (62.9%) were measured with an IOLMaster 500 followed by an IOLMaster 700 (15.2%). A total of 33 types of IOLs were used, and the Tecnis ZCB00 was the most frequently used (53.0%). There was no statistically significant difference in IOL constants derived from autorefraction and manifest refraction when IOL constants were optimized with a large number of study subjects. On the other hand, optimized IOL constants derived from autorefraction were significantly smaller than those from manifest refraction when the number of subjects was small. Conclusions It became possible to use the IOL constants optimized from Koreans to calculate the IOL power. However, if the IOL constant is optimized using autorefraction in a small sample group, the IOL constant tends to be small, which may lead to refractive error after surgery.

Given the progressive improvements in antithrombotic strategies, management of cardiovascular disease has become sophisticated/refined. However, the optimal perioperative management of antithrombotic therapy in patients with acute coronary syndrome or who are scheduled for percutaneous coronary intervention remains unclear. Assessments of the thrombotic and hemorrhagic risks are essential to reduce the rates of mortality and major cardiac events. However, the existing guidelines do not mention these topics. This case-based consensus document deals with common clinical scenarios and offers evidence-based guidelines for individualized perioperative management of antithrombotic therapy in the real world.

The prevalence of ischemic heart disease is steadily growing as populations age. Antithrombotic treatment is a key therapeutic modality for the prevention of secondary cerebro-cardiovascular disease. Patients with acute coronary syndrome or who are undergoing percutaneous coronary intervention must be treated with dual antiplatelet therapy for a mandatory period. The optimal perioperative antithrombotic regimen remains debatable; antithrombotics can cause bleeding. Inadequate antithrombotic regimens are associated with perioperative ischemic events, but continuation of therapy may increase the risks of perioperative hemorrhagic complications (including mortality). Many guidelines on the perioperative management of antithrombotic agents have been established by academic societies. However, the existing guidelines do not cover all specialties, nor do they describe the thrombotic and hemorrhagic risks associated with various surgical interventions. Moreover, few practical recommendations on the modification of antithrombotic regimens in patients who require non-deferrable interventions/surgeries or procedures associated with a high risk of hemorrhage have appeared. Therefore, cardiologists, specialists performing invasive procedures, surgeons, dentists, and anesthesiologists have not come to a consensus on optimal perioperative antithrombotic regimens. The Korean Platelet-Thrombosis Research Group presented a positioning paper on perioperative antithrombotic management. We here discuss commonly encountered clinical scenarios and engage in evidence-based discussion to assist individualized, perioperative antithrombotic management in clinical practice.

Purpose: To report a case of a successful secondary Descemet membrane endothelial keratoplasty in failed penetrating keratoplasty. Case summary: A 46-year-old male with keratoconus in both of his eyes underwent penetrating keratoplasty in his right eye 30 years ago and in his left eye 14 years ago. From one and a half year ago, the patient’s visual acuity decreased in his left eye due to graft failure. For treatment, secondary Descemet membrane endothelial keratoplasty was performed. Partial detachment of Descemet membrane was observed at 13 days after the operation, and an additional air injection was performed. At 8 months after the operation, the patient’s uncorrected visual acuity improved to 0.5 and the cornea maintained its clearance without rejection. Conclusions Secondary Descemet membrane endothelial keratoplasty was successfully performed in a patient with failed penetrating keratoplasty.

Purpose: This study was performed to compare the oncologic outcomes between nonradical management and total mesorectal excision in good responders after chemoradiotherapy. Methods: We analyzed 75 patients, who underwent 14 watch-and-wait, 30 local excision, and 31 total mesorectal excision, in ycT0–1N0M0 based on magnetic resonance imaging after chemoradiotherapy for advanced mid-to-low rectal cancer in 3 referral hospitals. The nonradical management group underwent surveillance with additional sigmoidoscopy and rectal magnetic resonance imaging every 3–6 months within the first 2 years. Results: Nonradical management group had more low-lying tumors (P < 0.001) and less lymph node metastasis based on magnetic resonance imaging (P = 0.004). However, cT stage, ycT, and ycN stage were not different between the 2 groups. With a median follow-up period of 64.7 months, the 5-year locoregional failure rate was higher in the nonradical management group than in the total mesorectal excision group (16.7% vs. 0%, P = 0.013). However, the 5-year overall survival and disease-free survival rates of the nonradical management and total mesorectal excision groups were not different (95.2% vs. 93.5%, P = 0.467; 76.4% vs. 83.6%, P = 0.665; respectively). Conclusion This study shows that nonradical management for ycT0–1N0 mid-to-low rectal cancer may be an alternative treatment to total mesorectal excision under proper surveillance and management for oncologic events.