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Purpose Acute promyelocytic leukemia (APL) is a rare disease in children and there are some different characteristics between children and adult. We aimed to evaluate incidence, clinical characteristics and treatment outcomes of pediatric APL in Korea.Materials and Methods Seventy-nine pediatric APL patients diagnosed from January 2009 to December 2016 in 16 tertiary medical centers in Korea were reviewed retrospectively.Results Of 801 acute myeloid leukemia children, 79 (9.9%) were diagnosed with APL. The median age at diagnosis was 10.6 years (range, 1.3 to 18.0). Male and female ratio was 1:0.93. Thirty patients (38.0%) had white blood cell (WBC) count greater than 10×109/L at diagnosis. All patients received induction therapy consisting of all-trans retinoic acid and chemotherapy. Five patients (6.6%) died during induction chemotherapy and 66 patients (86.8%) achieved complete remission (CR) after induction chemotherapy. The causes of death were three intracranial hemorrhage, one cerebral infarction, and one sepsis. Five patients (7.1%) suffered a relapse during or after maintenance chemotherapy. The estimated 4-year event-free survival and overall survival (OS) rates were 82.1%±4.4%, 89.7%±5.1%, respectively. The 4-year OS was significantly higher in patients with initial WBC < 10×109/L than in those with initial WBC ≥ 10×109/L (p=0.020).Conclusion This study showed that the CR rates and survival outcomes in Korean pediatric APL patients were relatively good. The initial WBC count was the most important prognostic factor and most causes of death were related to serious bleeding in the early stage of treatment.

Traditionally, Asian ginseng or Korean ginseng, Panax ginseng has long been used in Korea and China to treat various diseases. The main active components of Panax ginseng is ginsenoside, which is known to have various pharmacological treatment effects such as antioxidant, vascular easing, anti-allergic, anti-inflammatory, anti-diabetes, and anticancer. Most reactive oxygen species (ROS) cause chronic diseases such as myocardial symptoms and cause fatal oxidative damage to cell membrane lipids and proteins. Therefore, many studies that inhibit the production of oxidative stress have been conducted in various fields of physiology, pathophysiology, medicine and health, and disease. Recently, ginseng or ginsenosides have been known to act as antioxidants in vitro and in vivo results, which have a beneficial effect on preventing cardiovascular disease. The current review aims to provide mechanisms and inform precious information on the effects of ginseng and ginsenosides on the prevention of oxidative stress and cardiovascular disease in animals and clinical trials.

Background: It remains unclear whether P2Y 12 monotherapy, especially clopidogrel, following short-duration dual antiplatelet therapy (DAPT) is associated with favorable outcomes in patients undergoing complex percutaneous coronary intervention (PCI). Therefore, this study analyzed the efficacy and safety of P2Y 12 inhibitor monotherapy, mostly clopidogrel (78%), in complex PCI following short-term DAPT. Methods: The post-hoc analysis of the SMART-CHOICE trial involving 2,993 patients included 498 cases of complex PCIs, defined by at least one of the following features: 3 vessels treated, ≥ 3 stents implanted, ≥ 3 lesions treated, bifurcation with ≥ 2 stents implanted, and a total stent length of ≥ 60 mm. The primary endpoint was major adverse cardiac and cerebrovascular event (MACCE), defined as the composite of all-cause death, myocardial infarction, and stroke. The primary safety endpoint included bleeding, defined as Bleeding Academic Research Consortium (BARC) types 2 to 5. Results: Complex PCI group had a higher risk of MACCE (4.0% vs. 2.3%, hazard ratio [HR] = 1.74, 95% confidence interval [CI]: 1.05–2.89, p = 0.033) and a similar risk of BARC types 2–5 bleeding (2.6% vs. 2.6%, HR = 1.02, 95% CI: 0.56–1.86, p = 0.939) compared with those without complex PCIs. Patients undergoing complex PCIs, followed by P2Y 12 inhibitor monotherapy and 12 months of DAPT exhibited similar rates of MACCE (3.8% vs. 4.2%, HR = 0.92, 95% CI: 0.38–2.21, p = 0.853). Conclusions: P2Y 12 inhibitor monotherapy, mostly clopidogrel, following 3 months of DAPT did not increase ischemic events in patients with complex PCIs.

Purpose: Sphingosine kinase is a lipid kinase that phosphorylates sphingosine to generate sphingosine 1-phosphate (S1P). S1P regulates pancreatic islet β-cell endoplasmic reticulum stress and proliferation. Type 1 and type 2 diabetes share some key pathogenic processes. In this study, we investigated whether secretion of insulin and production of S1P is altered in alloxan and glucose-treated cells from the rat pancreatic β-cell line RIN-5F.Methods: RIN-5F cells were treated with 2 mM alloxan and 20 mM glucose for 6 hours or 24 hours before being evaluated by enzyme linked immunosorbent assay (ELISA) and Western blotting.Results: Insulin secretion and expression was higher in RIN-5F cells treated with glucose compared to control cells. In contrast, alloxan treatment did not affect insulin secretion and expression in RIN-5F cells. Interestingly, compared with normal control levels, S1P/EDG-5 was increased in both alloxan and glucose-treated pancreatic β cell than normal control. Mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) inhibition strongly decreased the expression of insulin and S1P in glucose- or alloxan-treated RIN-5F cells.Conclusion: We observe that production of S1P is increased in both diabetic cell models. In addition, MAPK/ERK signaling regulates secretion of insulin and S1P expression in pancreatic β-cells. Based on the literature and our findings, S1P may be a promising agent for the treatment of insulin-related disorders.

This paper presents the systems of the CANYVAL-C mission—a mission that demonstrates the concept of a virtual space telescope for a solar science mission, which is achieved by using two CubeSats (1U: Timon, 2U: Pumbaa). The aim of the mission is to capture images of the solar corona by performing precise formation flying. Two CubeSat systems were developed for this investigation: a 1U CubeSat and a 2U CubeSat. The 1U CubeSat can take several pictures of the solar corona, whereas the 2U CubeSat blocks the sunlight with its payload, which is called the Occulter. To accomplish the goal of this mission, precise guidance, navigation, and control technologies have been developed and verified through numerical simulations and the hardware-in-the loop simulations. Flight models of the two CubeSats were developed with end-to-end testing and environmental testing to ensure the feasibility of the mission operations under practical limitations. The two CubeSats are scheduled to launch and be in operation in the first half of 2021.

Objectives: This evidence-based design clinical trial assessed the feasibility of a multisensory environment (MSE) using aromatherapy, color-changing lights, and music as a behavioral intervention to calm Veterans with dementia during assisted bathing to improve the patient experience. Background: The number of Veterans with dementia is growing rapidly, along with the associated debilitating behavior challenges. The severity of these distressed behaviors that predominantly occur at bath time often necessitates costly, dangerous sedatives. Feasibility studies of nonpharmacological behavioral interventions during bathing for people with dementia are urgently needed, and research supports MSE as a viable solution. Method: Using an A–B, multiple baselines across participants design, this study tracked operational behaviors of four Veterans with dementia during bathing without and with an MSE intervention. Sessions were provided and recorded by a dedicated team of five nurses, so the study team could analyze the Veterans’ operational behaviors to understand the impact of individualized MSE during both baseline and intervention phases. Results: The results support the feasibility of MSE as a helpful, nonpharmacological behavioral intervention for Veterans with dementia during bathing. All participants experienced an overall increase in duration of positive operational behaviors and an overall decrease in duration of negative operational behaviors. Conclusions: Healthcare environments are integral components in dementia care and the use of MSE within the bathing setting appears to improve not only operational behaviors but the overall bathing experience.

Objective Recent studies have reported that thyroid hormone levels are associated with metabolic syndrome (MetS) even in euthyroid subjects. However, the association between thyroid autoimmunity and MetS is uncertain. This study aimed to investigate the relationship between thyroid autoimmunity and MetS in a large cohort study of euthyroid subjects. Methods A total of 4775 participants aged ≥19 years from the Korea National Health and Nutrition Examination Survey VI (2013–2015) with anti-thyroid peroxidase antibody (TPOAb) results and normal thyroid functions were included in this study. Subjects were grouped according to thyroid autoimmunity (positivity of TPOAb). We estimated the odds ratios (ORs) for MetS according to TPOAb positivity using logistic regression models, adjusted for potential confounders. Results Of the study subjects, 25% (n = 1206) were diagnosed with MetS. Subjects with MetS showed higher median TPOAb levels (6.3 vs 6.8 IU/mL, P < 0.001) and higher positivity of TPOAb (5 vs 7%, P = 0.002) than those without MetS. There was a significant difference in prevalence of MetS depending on the TPOAb positivity (25% vs 33%, P = 0.002). Subjects with TPOAb positive had a significantly greater risk of abdominal obesity (OR 1.675, 95% CI: 1.302–2.154, P < 0.001), low high-density lipoprotein cholesterol (OR: 1.603, 95% CI: 1.244–2.066, P < 0.001) and elevated blood pressure (OR: 1.418, 95% CI: 1.099–1.829, P = 0.007) as compared to those with TPOAb negative. Positivity of TPOAb was a significant risk factor for MetS even after adjusting for confounding variables including age, sex, household income, education, smoking, alcohol consumption, walking activity, thyroid-stimulating hormone and free thyroxine (OR: 1.389, 95% CI: 1.048–1.841, P = 0.022). Conclusion In euthyroid subjects, thyroid autoimmunity is associated with MetS. Further large longitudinal studies are needed to clarify causality.

Gallbladder paraganglioma (GP) is a rare tumor, with only 12 cases reported in the literature to date. Due to its rarity, clinical information of GP is insufficient. We present a case of GP in a 48-year-old female along with a literature review of all GP cases described to date. A 48-year-old female presented with intermittent right upper abdominal pain. Preoperative imaging revealed a hematoma in the gallbladder lumen without any definite etiology. Laparoscopic cholecystectomy was performed. Gross examination of the gallbladder revealed multiple small stones and a large hematoma as well as a 1.6-cm-sized polypoid mass at the gallbladder fundus. Microscopic study of the polypoid mass showed a zellballen appearance. Immunohistochemical analysis revealed that the mass was positive for synaptophysin, CD56, and chromogranin, suggesting GP. GP is difficult to diagnose because of non-specific clinical findings. Almost all GP cases are diagnosed based on histologic findings after cholecystectomy. Simple cholecystectomy was performed as a treatment in all reported cases of GP, including our case. There was no postoperative tumor recurrence or metastasis after surgery.

Background: Glycated hemoglobin (HbA1c), which reflects the patient's blood sugar level, can only be measured in a hospital setting. Therefore, we developed a model predicting HbA1c using personal information and self-monitoring of blood glucose (SMBG) data solely obtained by a patient.Methods: Leave-one-out cross-validation (LOOCV) was performed at two university hospitals. After measuring the baseline HbA1c level before SMBG (Pre_HbA1c), the SMBG was recorded over a 3-month period. Based on these data, an HbA1c prediction model was developed, and the actual HbA1c value was measured after 3 months. The HbA1c values of the prediction model and actual HbA1c values were compared. Personal information was used in addition to SMBG data to develop the HbA1c predictive model.Results: Thirty model training sessions and evaluations were conducted using LOOCV. The average mean absolute error of the 30 models was 0.659 (range, 0.005–2.654). Pre_HbA1c had the greatest influence on HbA1c prediction after 3 months, followed by post-breakfast blood glucose level, oral hypoglycemic agent use, fasting glucose level, height, and weight, while insulin use had a limited effect on HbA1c values.Conclusions: The patient's SMBG data and personal information strongly influenced the HbA1c predictive model. In the future, it will be necessary to develop sophisticated predictive models using large samples for stable SMBG in patients.

Recently, there has been a great interest for realizing flexible, cheap, smart, and disposable bioelectronics and implantable electronic systems that can collect various types of in vivo biological...

BACKGROUND The survival rate of aneurysmal subarachnoid hemorrhage (aSAH) has gradually increased, leading to more clinical cases of de novo intracranial aneurysms (DNIAs). OBJECTIVE To identify the characteristics of patients with DNIA growth or rupture. METHODS We included 1601 patients with aSAH treated by clipping from January 1993 to May 2010. According to the inclusion and exclusion criteria, 233 patients had no DNIAs, and 63 patients had 77 DNIAs. We assessed the incidence rate of DNIAs and risk factors for DNIA formation. After dichotomizing the DNIA group into the heed (patients with DNIA rupture or growth) and stable groups (patients without DNIA growth), we assessed the risk factors for DNIA growth or rupture. RESULTS The total follow-up period was 4427.9 patient-years. The incidence rate per patient-year was 1.42%. Age ≤50 yr, family history of aneurysm, and multiplicity at initial aSAH were significant risk factors for DNIA formation. Multivariate regression analysis revealed that female sex (odds ratio [OR], 5.566; 95% confidence interval [CI], 1.241-24.952), duration from initial aSAH to DNIA detection

Background: In general, a 2-cm surgical margin is recommended for limited resection to obtain equivalent oncologic outcomes to lobectomy for lung cancer. This study aimed to examine the patterns of recurrence and prognostic factors for recurrence in patients with a close parenchymal resection margin. Methods: From January 2009 to April 2017, 156 patients with stage I lung cancer who underwent segmentectomy with a close resection margin (

OBJECTIVES The current understanding of pulmonary invasive mucinous adenocarcinoma is largely based on studies of advanced stage patients and data about early-stage invasive mucinous adenocarcinoma are sparse. We evaluated the radiological and clinical features of screening-detected early-stage invasive mucinous adenocarcinoma (SD-IMA). METHODS Data from 91 patients who underwent surgical treatment for SD-IMA (≤3 cm) from 2013 to 2019 were reviewed retrospectively. Data on radiological characteristics, clinicopathological findings, recurrence and survival were obtained. Disease-free survival rate was analysed. RESULTS Radiologically, SD-IMAs presented as a pure ground-glass nodule (6.6%), part-solid nodule (38.5%) or solid (54.9%). Dominant locations were both lower lobes (74.7%) and peripheral area (93.4%). The sensitivity of percutaneous needle biopsy was 78.1% (25/32). Lobectomy was performed in 70 (76.9%) patients, and sublobar resection in 21 (23.1%) patients. Seventy-three (80.2%), 15 (16.5%) and 3 (3.3%) patients had pathological stage IA, IB and IIB or above, respectively. Seven patients developed recurrence, and 3 died due to disease progression. Pleural seeding developed exclusively in 2 patients who underwent needle biopsy. The 5-year disease-free survival rate was 89.4%. The disease-free survival rates at 5 years were 86.3% in the lobectomy group and 100% in the sublobar resection group. CONCLUSIONS SD-IMAs were mostly radiologically invasive nodules. SD-IMAs showed favourable prognosis after surgical treatment., Invasive mucinous adenocarcinoma (IMA), which accounts for 5% of pulmonary adenocarcinomas, has different characteristics than non-mucinous adenocarcinoma (NMA) in terms of histology, genetics and clinical features.

We aimed to compare the short- and long-term outcomes between robotic esophagectomy (RE) and open esophagectomy (OE) in patients with esophageal squamous cell carcinoma (ESCC). Among the patients who underwent esophagectomy for ESCC from 2008 to 2017, 402 patients (n = 178 in RE and n = 224 in OE) were enrolled and, after propensity-score matching, 136 patients in each group were selected. The total rate of complications was comparable, whereas the rate of major complications was higher in OE (p

Per the well-known resistance of hepatitis B virus to nucleoside/nucleotide analogs, alternative treatment options with higher resistance barriers have been approved for use in both treatment-naïve and lamivudine-resistant hepatitis B virus infections. This phase I study was conducted in adults with normal and impaired renal function to evaluate the effect of renal impairment on the pharmacokinetics of besifovir, a prodrug of an acyclic nucleotide phosphonate, that is mainly cleared via renal excretion. An open-label, single-dose parallel-group clinical study was conducted in subjects with normal renal function and mild, moderate, and severe renal impairment. Subjects received a single oral dose of besifovir dipivoxil 150 mg, and serial blood and urine samples were collected for up to 72 hours after dosing to assess the pharmacokinetic characteristics of besifovir. The extent of plasma exposure of besifovir, detected as its major and active metabolites, LB80331 and LB80317, respectively, increased with worsening renal function. Compared to the subjects with normal renal function, the mean areas under the concentration-time curves of LB80331 increased by 1.5-, 2.5-, and 4.5-fold in subjects with mild, moderate, and severe impairment, respectively. LB80317 showed a 1.8-, 3.2-, and 6.2-fold increase in subjects with mild, moderate, and severe renal impairment compared to those with normal function. The ratios of LB80331 renal clearance and the average estimated glomerular filtration rate of each renal impairment group with respect to the normal group were similar. The increase in plasma exposure and decrease in renal clearance suggest the need to adjust dosage regimens in patients with moderate to severe renal impairment.

Whether moderate-intensity statins plus ezetimibe could be an alternative to high-intensity statins in patients with atherosclerotic cardiovascular disease is unclear. We compared the risk of adverse cardiovascular events in patients receiving moderate-intensity statins plus ezetimibe vs. high-intensity statins after a coronary revascularization procedure using data from a large cohort study. Population-based cohort study using nationwide medical insurance data from Korea. Study participants (n = 20,070) underwent percutaneous coronary intervention or coronary artery bypass graft surgery between January 1, 2015, and December 31, 2016, and received moderate-intensity statins (atorvastatin 10–20 mg or rosuvastatin 5–10 mg) plus ezetimibe (n = 922) or high-intensity statins (atorvastatin 40–80 mg or rosuvastatin 20 mg; n = 19,148). The primary outcome was a composite of cardiovascular mortality, hospitalization for myocardial infarction (MI), hospitalization for stroke, or revascularization. At 12 months, the incidence rates of the primary outcome were 138.0 vs. 154.0 per 1000 person-years in the moderate-intensity stains plus ezetimibe and the high-intensity statins group, respectively. The fully adjusted hazard ratio [HR] for the primary outcome was 1.11 (95% confidence interval [CI] 0.86–1.42; p = 0.43). The multivariable-adjusted HR for a composite of cardiovascular mortality, hospitalization for MI, or hospitalization for stroke was 1.05 (95% CI 0.74–1.47; p = 0.80). During follow-up, the proportion of patients maintaining their initial lipid-lowering therapy was significantly higher in the moderate-intensity statins plus ezetimibe group than in the high-intensity statins group. Patients undergoing a coronary revascularization procedure who received moderate-intensity statins plus ezetimibe showed similar rates of major adverse cardiovascular events as patients who received high-intensity statins.

PURPOSE Adjuvant chemotherapy after D2 gastrectomy is standard for resectable locally advanced gastric cancer (LAGC) in Asia. Based on positive findings for perioperative chemotherapy in European phase III studies, the phase III PRODIGY study (ClinicalTrials.gov identifier: NCT01515748 ) investigated whether neoadjuvant docetaxel, oxaliplatin, and S-1 (DOS) followed by surgery and adjuvant S-1 could improve outcomes versus standard treatment in Korean patients with resectable LAGC. PATIENTS AND METHODS Patients 20-75 years of age, with Eastern Cooperative Oncology Group performance status 0-1, and with histologically confirmed primary gastric or gastroesophageal junction adenocarcinoma (clinical TNM staging: T2-3N+ or T4Nany) were randomly assigned to D2 surgery followed by adjuvant S-1 (40-60 mg orally twice a day, days 1-28 every 6 weeks for eight cycles; SC group) or neoadjuvant DOS (docetaxel 50 mg/m2, oxaliplatin 100 mg/m2 intravenously day 1, S-1 40 mg/m2 orally twice a day, days 1-14 every 3 weeks for three cycles) before D2 surgery, followed by adjuvant S-1 (CSC group). The primary objective was progression-free survival (PFS) with CSC versus SC. Two sensitivity analyses were performed: intent-to-treat and landmark PFS analysis. RESULTS Between January 18, 2012, and January 2, 2017, 266 patients were randomly assigned to CSC and 264 to SC at 18 Korean study sites; 238 and 246 patients, respectively, were treated (full analysis set). Follow-up was ongoing in 176 patients at data cutoff (January 21, 2019; median follow-up 38.6 months [interquartile range, 23.5-62.1]). CSC improved PFS versus SC (adjusted hazard ratio, 0.70; 95% CI, 0.52 to 0.95; stratified log-rank P = .023). Sensitivity analyses confirmed these findings. Treatments were well tolerated. Two grade 5 adverse events (febrile neutropenia and dyspnea) occurred during neoadjuvant treatment. CONCLUSION PRODIGY showed that neoadjuvant DOS chemotherapy, as part of perioperative chemotherapy, is effective and tolerable in Korean patients with LAGC.

Background There remain concerns about the safety and functional benefit of laparoscopic pylorus-preserving gastrectomy (LPPG) compared with laparoscopic distal gastrectomy (LDG). This study evaluated short-term outcomes of a randomized clinical trial (RCT) comparing LPPG with LDG for gastric cancer. Methods The Korean Laparoendoscopic Gastrointestinal Surgery Study (KLASS)-04 trial was an investigator-initiated, open-label, parallel-assigned, superiority, multicentre RCT in Korea. Patients with cT1N0M0 cancer located in the middle third of the stomach at least 5 cm from the pylorus were randomized to undergo LPPG or LDG. Participants, care givers and those assessing the outcomes were not blinded to group assignment. Outcomes were 30-day postoperative morbidity rate and death at 90 days. Results Some 256 patients from nine institutions were randomized (LPPG 129 patients, LDG 127 patients) between July 2015 and July 2017 and outcomes for 253 patients were analysed. Postoperative complications within 30 days were seen in 19.3 and 15.5 per cent in the LPPG and LDG groups respectively (P = 0·419). Postoperative pyloric stenosis was observed in nine (7.2 per cent) and two (1·5 per cent) patients in the LPPG and LDG groups (P = 0·026) respectively. In multivariable analysis higher BMI was a risk factor for postoperative complications (odds ratio 1·17, 95 per cent c.i. 1·04 to 1·32; P = 0·011). Death at 90 days was zero in both groups. Conclusion Postoperative complications and mortality was comparable in patients undergoing LPPG and LDG. Registration number: NCT02595086 (http://www.clinicaltrials.gov).

This study sought to evaluate clinical implications of the residual fractional flow reserve (FFR) gradient after angiographically successful percutaneous coronary intervention (PCI).Recent studies have demonstrated FFR measured after PCI is associated with clinical outcome after PCI. Although post-PCI FFR pull back tracings provide clinically relevant information on the residual FFR gradient, there are no objective criteria for assessing post-PCI FFR pull back tracings.A total of 492 patients who underwent angiographically successful PCI and post-PCI FFR measurement with pull back tracings were analyzed. The presence of the major residual FFR gradient after PCI was assessed by both conventional visual interpretation of the pull back tracings and objective analysis using the instantaneous FFR gradient per unit time (dFFR(t)/dt) with a cutoff value of dFFR(t)/dt ≥0.035. Classification agreement between 2 independent operators for the presence of the major residual FFR gradient was compared before and after providing dFFR(t)/dt results. Target vessel failure (TVF), a composite of cardiac death, target vessel myocardial infarction, or clinically driven target vessel revascularization at 2 years, was compared according to the presence of the major residual FFR gradient.Among the study population, 33.9% had the major residual FFR gradient defined by dFFR(t)/dt. The classification agreement between operators' assessments for the major residual FFR gradient increased with dFFR(t)/dt results compared with conventional visual assessment (Cohen's kappa = 0.633 to 0.819; P 0.001; intraclass correlation coefficient: 0.776 to 0.901; P 0.001). Patients with major residual FFR gradient were associated with a higher risk of TVF at 2 years than those without major residual FFR gradient (9.0% vs 2.2%; P 0.001). Inclusion of the major residual FFR gradient to a clinical prediction model significantly increased discrimination and reclassification ability (C-index = 0.539 vs 0.771; P = 0.006; net reclassification improvement = 0.668; P = 0.007; integrated discrimination improvement = 0.033; P = 0.017) for TVF at 2 years. The presence of the major residual FFR gradient was independently associated with TVF at 2 years, regardless of post-PCI FFR or percent FFR increase (adjusted hazard ratio: 3.930; 95% confidence interval: 1.353-11.420; P = 0.012).Objective analysis of post-PCI FFR pull back tracings using dFFR(t)/dt improved classification agreement on the presence of the major residual FFR gradient among operators. Presence of the major residual FFR gradient defined by dFFR(t)/dt after angiographically successful PCI was independently associated with an increased risk of TVF at 2 years. (Automated Algorithm Detecting Physiologic Major Stenosis and Its Relationship with Post-PCI Clinical Outcomes [Algorithm-PCI]; NCT04304677; Influence of FFR on the Clinical Outcome After Percutaneous Coronary Intervention [COE-PERSPECTIVE]; NCT01873560).

Author's summary This prospective, multi-center, randomized, comparative, and pivotal clinical study in patients with coronary artery occlusive disease was conducted to evaluate the safety and efficacy of D+Storm™ drug-eluting stent (DES), a sirolimus-eluting stent coated with polylactic acid and ascorbic acid. Our results showed that in-segment late lumen loss of D+Storm™ DES group was non-inferior to BioMatrix Flex™ DES group and the total procedural success rate of D+Storm™ DES group was 100%. In addition, the safety of the D+Storm™ DES group at 36 weeks was also demonstrated in this study., Background and Objectives This clinical trial was conducted to evaluate the safety and efficacy of D+Storm™ drug-eluting stent (DES) and BioMatrix Flex™ DES. Methods This study was a multicenter, subject-single-blind, randomized, and confirmed comparative clinical trial. According to the inclusion criteria, those diagnosed with stable angina, unstable angina, silent ischemia, or non-ST-segment myocardial infarction were selected among patients with coronary artery stenosis as subjects. Among the subjects with 50% stenosis on coronary angiography, the experiment was performed on those who had a lesion with reference vessel 2.5–4.0 mm in diameter and ≤40 mm in length. The primary endpoint was an in-segment late loss and the secondary endpoints were in-stent late lumen loss, stent malapposition, the incidence of mortality, myocardial infarction, reoperation, and stent thrombosis at 36 weeks. Results 57 patients in the D+Storm™ DES group and 55 patients in the BioMatrix Flex™ DES group were enrolled in the study. Fifty-seven patients in the D+Storm™ DES group and Fifty-five patients in the BioMatrix Flex™ DES group were enrolled in the study. An average of in-segment late lumen loss was 0.08±0.13 mm in the D+Storm™ DES group and 0.14±0.32 mm in the BioMatrix Flex™ DES group with no significant difference between the 2 groups (p=0.879). In addition, there was no significant difference in adverse events between D+Storm™ DES and BioMatrix Flex™ DES. Conclusions This study demonstrated the clinical effectiveness and safety of D+Storm™ DES implantation in patients with coronary artery disease over a 36-week follow-up period.

OBJECTIVES Data regarding acute severe hypertension, a life-threatening condition encountered in the emergency department, are limited. We aimed to identify the characteristics, practice patterns, and outcomes of patients with acute severe hypertension in the emergency department. METHODS This cross-sectional study at a tertiary referral centre included patients aged at least 18 years who were admitted to the emergency department between January 2016 and December 2019 for acute severe hypertension, which was defined as SBP at least 180 mmHg and/or DBP at least 100 mmHg. RESULTS Of 172 105 patients who visited the emergency department, 10 219 (5.9%) had acute severe hypertension. Of them, 2506 (24.5%) patients had acute hypertension-mediated organ damage (HMOD), and these patients had more cardiovascular risk factors than did patients without HMOD. Additionally, 4137 (40.5%) patients were admitted, and nine (0.1%) died in the emergency department. The overall 3-month, 1-year, and 3-year mortality rates were 4.8, 8.8, and 13.9%, respectively. In patients with HMOD, the 1-year mortality rate was 26.9%, and patients lost to follow-up had a significantly higher 1-year mortality rate than those who were followed up (21.3 vs. 10.5%, respectively, P

Introduction and objectives There are no guidelines regarding the most appropriate approach for provisional side branch (SB) intervention in left main (LM) bifurcation lesions. Methods The present prospective, randomized, open-label, multicenter trial compared conservative vs aggressive strategies for provisional SB intervention during LM bifurcation treatment. Although the trial was designed to enroll 700 patients, it was prematurely terminated due to slow enrollment. For 160 non-true bifurcation lesions, a 1-stent technique without kissing balloon inflation was applied in the conservative strategy, whereas a 1-stent technique with mandatory kissing balloon inflation was applied in the aggressive strategy. For 46 true bifurcation lesions, a stepwise approach was applied in the conservative strategy (after main vessel stenting, SB ballooning when residual stenosis > 75%; then, SB stenting if residual stenosis > 50% or there was a dissection). An elective 2-stent technique was applied in the aggressive strategy. The primary outcome was a 1-year target lesion failure (TLF) composite of cardiac death, myocardial infarction, or target lesion revascularization . Results Among non-true bifurcation lesions, the conservative strategy group used a smaller amount of contrast dye than the aggressive strategy group. There were no significant differences in 1-year TLF between the 2 strategies among non-true bifurcation lesions (6.5% vs 4.9%; HR, 1.31; 95%CI, 0.35-4.88; P = .687) and true bifurcation lesions (17.6% vs 21.7%; HR, 0.76; 95%CI, 0.20-2.83; P = .683). Conclusions In patients with a LM bifurcation lesion, conservative and aggressive strategies for a provisional SB approach have similar 1-year TLF rates.

Background The long-term outcomes of robotic thymectomy for thymic epithelial tumors (TETs) are not well known, even though the early postoperative outcomes have improved. This study aimed to report the long-term survival and recurrence in patients with TETs who underwent robotic thymectomies. Methods A total of 158 patients who underwent robotic thymectomy for TET and who were followed-up for more than 1 year were included in the study. The median follow-up time was 43 (interquartile range, 40) months, and 156 (98%) patients were followed completely until the end of the study period. Results The mean age of the patients was 55.7 ± 12.7 years, and the mean size of the tumor was 4.6 ± 2.1 cm. There was no postoperative mortality and postoperative complications occurred in 7 (4.4%) patients. The median length of the postoperative hospital stay was 2 (interquartile range, 1-20) days. Thymoma was the most common cell type (n = 132, 84%), and thymic carcinoma (n = 24, 15%) and neuroendocrine tumors (n = 2, 1%) were the next most common types. Advanced stages more than stage III were identified in 15 patients (stage IIIA: n = 7, 4%; stage IVA: n = 5, 3%; and stage IVB: n = 3, 2%). The 5-year disease-specific survival was 100% in thymoma and 95% in thymic carcinoma. The 5-year recurrence-free survival was 94% in thymoma and 79% in thymic carcinoma. Conclusions Robotic thymectomy could achieve favorable long-term survival and recurrence rates, comparable to open or thoracoscopic thymectomy.

Objectives The aim of this study was to explore if right ventricular (RV) contractile function and its coupling to pulmonary circulation (PC) were associated with successful weaning from venoarterial−extracorporeal membrane oxygenation (VA-ECMO) at maintenance of pump flow. Background Limited data are available on predictors of successful weaning from VA-ECMO. Methods A total of 79 patients with cardiogenic shock underwent transthoracic echocardiography to evaluate weaning from ECMO and were prospectively enrolled between 2016 and 2019. The noninvasively measured RV-PC coupling index was acquired by indexing tricuspid annular S' velocity, tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), and RV free-wall longitudinal strain (FWLS) to right ventricular systolic pressure (RVSP). Results Transthoracic echocardiography was performed at a median 3.0 days (range 1 to 6 days) after ECMO initiation at a median ECMO flow of 3.2 l/min (range 3.0 to 3.6 l/min). The RV-PC coupling matrix, tricuspid annular S'/RVSP, TAPSE/RVSP, and RV FWLS/RVSP exhibited satisfactory predictive performances for predicting successful weaning from ECMO. Using the best cutoff values derived from the area under the receiver-operator characteristic curve, tricuspid annular S'/RVSP demonstrated a significantly better predictive performance than conventional echocardiographic parameters (left ventricular ejection fraction >20%, left ventricular outflow tract time-velocity integral ≥10 cm, and mitral annular S' ≥6 cm/s). Conclusions Echocardiographic RV-PC coupling metrics exhibited a significantly better performance for predicting successful weaning from VA ECMO compared with conventional echocardiographic criteria at maintenance of pump flow.

Tet methylcytosine dioxygenase 2 (TET2) is one of the most frequently mutated genes in myelodysplastic syndrome (MDS). TET2 is known to involve a demethylation process, and the loss of TET2 is thought to cause DNA hypermethylation. Loss of TET2 function is known to be caused by genetic mutations and miRNA, such as miR-22. We analyzed 41 MDS patients receiving hypomethylating therapy (HMT) to assess whether TET2 mutation status and miR-22 expression status were associated with their clinical characteristics and treatment outcomes. Responsiveness to HMT was not affected by both TET2 mutation (odds ratio (OR) 0.900, p = 0.909) and high miR-22 expression (OR 1.548, p = 0.631). There was a tendency for TET2 mutation to be associated with lower-risk disease based on IPSS (Gamma = −0.674, p = 0.073), lower leukemic transformation (OR 0.170, p = 0.040) and longer survival (Hazard ratio 0.354, p = 0.059). Although high miR-22 expression also showed a similar tendency, this tendency was weaker than that of TET2 mutation. In summary, the loss of TET2 function, including both TET2 mutation and high miR-22 expression, was not a good biomarker for predicting the response to HMT but may be associated with lower-risk disease based on IPSS, lower leukemic transformation and longer survival.

Fetal health monitoring during pregnancy has become a necessary procedure. Fetal heart rate (FHR) monitoring can determine fetal development or presence of heart disease and evaluate fetal well-being. The FHR measurement uses typically an acoustic probe-based Doppler ultrasound. Doppler ultrasound method transmits a continuous wave signal to the abdomen of a pregnant woman to receive a reflected signal from the fetal heart. Periodic displacement of the heart tissue produces the Doppler effect and the phase change of the reflected wave is proportional to the velocity of the fetal heart. The reflected signal is modulated into a phase signal and the received signal is demodulated to detect the heart rate. The current clinician system consists of a single probe and requires the probe to be manipulated to the optimal position to measure FHR. The system is highly dependent on trained diagnostic experts. The movement of the pregnant woman and the fetus leads to the misaligned acoustic beam which degrades the reliability of the measurement. This work presents a detection and tracking system using a Doppler signal to compensate for the target's movement. The system is implemented by integrating multi-channel probes interfaced to a Doppler signal converter with a 2-degree of freedom (DOF) motor device. This work describes the characteristics of two key components: Doppler signals of multi-channel probes according to the direction of the acoustic beam and the algorithm with a 2-DOF tracking system.

The aim of this study was to evaluate prognostic implications of physiological 2-dimensional disease patterns on the basis of distribution and local severity of coronary atherosclerosis determined by quantitative flow ratio (QFR) virtual pull back.The beneficial effect of percutaneous coronary intervention (PCI) is determined by physiological distribution and local severity of coronary atherosclerosis.The study population included 341 patients who underwent angiographically successful PCI and post-PCI fractional flow reserve (FFR) measurement. Using pre-PCI virtual pull backs of QFR, physiological distribution was determined by pull back pressure gradient index, with a cutoff value of 0.78 to define predominant focal versus diffuse disease. Physiological local severity was assessed by instantaneous QFR gradient per unit length, with a cutoff value of ≥0.025/mm to define a major gradient. Suboptimal post-PCI physiological results were defined as both post-PCI FFR ≤0.85 and percentage FFR increase ≤15%. Clinical outcome was assessed by target vessel failure (TVF) at 2 years.QFR pull back pressure gradient index was correlated with post-PCI FFR (R = 0.423; P 0.001), and instantaneous QFR gradient per unit length was correlated with percentage FFR increase (R = 0.370; P 0.001). Using the 2 QFR-derived indexes, disease patterns were classified into 4 categories: predominant focal disease with and without major gradient (group 1 [n = 150] and group 2 [n = 21], respectively) and predominant diffuse disease with and without major gradient (group 3 [n = 115] and group 4 [n = 55], respectively). Proportions of suboptimal post-PCI physiological results were significantly different according to the 4 disease patterns (18.7%, 23.8%, 22.6%, and 56.4% from group 1 to group 4, respectively; P 0.001). Cumulative incidence of TVF after PCI was significantly higher in patients with predominant diffuse disease (8.1% in group 3 and 9.9% in group 4 vs 1.4% in group 1 and 0.0% in group 2; overall P = 0.024).Both physiological distribution and local severity of coronary atherosclerosis could be characterized without pressure-wire pull backs, which determined post-PCI physiological results. After successful PCI, TVF risk was determined mainly by the physiological distribution of coronary atherosclerosis. (Automated Algorithm Detecting Physiologic Major Stenosis and Its Relationship With Post-PCI Clinical Outcomes [Algorithm-PCI], NCT04304677; Influence of FFR on the Clinical Outcome After Percutaneous Coronary Intervention [PERSPECTIVE], NCT01873560).

There are several types of minimally invasive approaches for thymectomy, of which the transpleural approach by video-assisted thoracoscopic surgery is particularly useful. In this approach, thymectomy is performed from either side of the thoracic cage. Thoracic surgeons should be familiar with the principles of the procedure, the anatomy of the region, and surgical strategies for successful thymectomy. The details of transpleural thymectomy are discussed herein.

BACKGROUND Electromagnetic interference (EMI), means disturbance to the operation of implanted electrical devices caused by external sources. If cardiac pacemaker is implanted into the body, the risk of EMI should be considered when performing neuromuscular electrical stimulation (NMES). So far, no case has been reported that clinical magnets are used to safely manage the EMI risk of patients with cardiac pacemaker in NMES. CASE SUMMARY A 72-year-old male with swallowing disorder due to pure motor lacunar syndrome was transferred to rehabilitation department six days after the symptom onset. EMI risk needed be considered when implementing NMES on pharyngeal muscles, since cardiac pacemaker was implanted on his left chest due to the sick sinus syndrome. In the first NMES, the function of the pacemaker was directly monitored using telemetric instruments. From the second day, by a simple method of placing a magnet on the pacemaker, we chose to move the pacemaker into a mode that the device was not influenced by external stimulus. This magnet method has been used repeatedly for a year for the safe NMES treatment. We could remove Levin tube four months after the initial symptom and dysphagia related symptoms had not been noted during two-year follow-up period. CONCLUSION This report is the first case of dysphagia rehabilitation that EMI risk was handled using mode change of pacemaker with magnet. This method is unfamiliar to doctors, but safe and easy approach. This paper could be guidance for clinicians who need to treat patients with EMI risk.

Objectives The optimal sequence for the administration of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for treating non‐small cell lung cancer (NSCLC) is still unclear. This study aimed to evaluate the efficacy of sequential afatinib and osimertinib treatment in patients with NSCLC harboring EGFR mutations. Materials and methods Electronic records of patients with EGFR‐mutated NSCLC, who were administered afatinib and osimertinib (group A) or other chemotherapy (group B) between October 2014 and 2019, across 16 hospitals in South Korea were reviewed. The primary outcome, time on treatment (TOT), secondary outcome, and overall survival (OS) were estimated using the Kaplan–Meier method and log‐rank test. Multivariate analyses were performed using the Cox proportional hazards model. Results Of the 737 patients who received frontline afatinib treatment, 324 with complete records were selected (group A: 126, group B: 198). All patients in group A were T790M positive after afatinib, while patients in group B were all negative or unknown. The median TOT was 35.4 months (95% confidence interval [CI]: 27.7−45.6) in group A and 20.8 months (95% CI: 19.4−24.0) in group B. The median TOT with afatinib was 13.0 months (95% CI: 12.0−13.9) overall and 15.7 months (95% CI: 13.9−17.3) in group A. The 2‐ and 3‐year survival rates were 86.0 and 69.3% in group A and 75.9 and 55.3% in group B, respectively. Conclusion Sequential afatinib and osimertinib treatment resulted in better survival rates than treatment with afatinib followed by other chemotherapies., Our study evaluated the real‐world efficacy of sequential treatment of afatinib and osimertinib, and compared it with other chemotherapies as a second‐line treatment. Promising real‐world data on first‐line afatinib and second‐line osimertinib may maximize sustained clinical benefit with avoiding chemotherapy and may warrant consideration, though tailored personalized approaches are necessary.

This study aimed to demonstrate pharmacokinetic (PK) equivalence of a single dose of the proposed adalimumab biosimilar CT‐P17 to United States‐licensed adalimumab (US‐adalimumab) and European Union‐approved adalimumab (EU‐adalimumab). This double‐blind, parallel‐group, phase I trial (clinicaltrials.gov NCT03970824) was conducted at 10 hospitals (Republic of Korea), in which healthy subjects (1:1:1) were randomized to receive a single 40 mg (100 mg/ml) subcutaneous injection of CT‐P17, US‐adalimumab, or EU‐adalimumab. Primary end points were PK equivalence in terms of: area under the concentration–time curve from time zero to infinity (AUC0–inf); AUC from time zero to the last quantifiable concentration (AUC0–last); and maximum serum concentration (Cmax). PK equivalence was concluded if 90% confidence intervals (CIs) for percent ratios of geometric least squares means (GLSMs) for pairwise comparisons were within the equivalence margin of 80–125%. Additional PK end points, safety, and immunogenicity were evaluated. Of the 312 subjects who were randomized (103 CT‐P17; 103 US‐adalimumab; 106 EU‐adalimumab), 308 subjects received study drug. AUC0–inf, AUC0–last, and Cmax were equivalent among CT‐P17, US‐adalimumab, and EU‐adalimumab, because 90% CIs for the ratios of GLSMs were within the 80–125% equivalence margin for each pairwise comparison. Secondary PK end points, safety, and immunogenicity were similar between treatment groups. In conclusion, PK equivalence for single‐dose administration of CT‐P17, EU‐adalimumab, and US‐adalimumab was demonstrated in healthy adults. Safety and immunogenicity profiles were comparable between treatment groups and consistent with previous reports for adalimumab biosimilars.

In medicine, X-ray imaging has to have stable image quality while minimizing radiation exposure. In recent digital radiography (DR), the radiation exposure and image quality are controlled by employing automatic exposure control (AEC) technology. In such an environment, the technology needs the capability of accurately classifying the level of radiation exposure despite statistical X-ray fluctuations. Therefore, the purpose of this study was to implement a radiation exposure classifier that could objectively determine the level using the deep neural network (DNN) method. Datasets containing 2000 images were used for training and validation of the DNN. This was done by changing the sensitivity of the AEC of the DR system to S200, S400, S800, and S1000. The changes in sensitivity generated four groups of 500 X-ray images each: overexposure, normal exposure (2), normal exposure (1), and underexposure. The results showed a classification accuracy of 93.83% and a loss 38.9%. In conclusion, through deep learning with X-ray images, an objective radiation exposure classifier was implemented and is expected to be used for the AEC of DR systems and to improve diagnostic accuracy.

Spermatocytic tumor is a rare testicular tumor, which is originated from gonocytes. It is characterized by the histological feature of tripartite which is composed of large, medium, and lymphocyte-like small cells. It is well-known that spematocytic tumor is benign, thus a good prognosis is expected after simple resection. Metastatic spermatocytic tumor is extremely rare and usually accompanied by histological variants including sarcomatous changes and anaplastic variants. In this case, however, we report a canine metastatic spermatocytic tumor without prominent sarcomatous changes and anaplastic variants. The mass was composed of three kinds of cells including large, medium, and small cells with high pleomorphism. The neoplastic cells had an indistinct cytoplasmic border and mitotic figures were frequently observed. The primary spermatocytic tumor metastasized to the abdominal organs one month after the resection, and the dog died 13 months after the surgery. Thus, careful follow-up is recommended after surgical resection of canine spermatocytic tumor even though metastasis in spermatocytic tumors is rare. Spermatocitni tumor je redak tumor testisa, koji potiče od gonocita. Karakteriše ga histološki nalaz tri morfološka tipa ćelija, a sastoji se od velikih, srednjih i limfocitima sličnih malih ć elija. Dobro je poznato da je spermatocitni tumor benignog ponašanja pa se očekuje dobra prognoza nakon jednostavne resekcije. Metastatski spermatocitni tumor izuzetno je redak i obično je prać en histološkim varijacijama, uključujuć i sarkomatozne i anaplastične promene. U ovom slučaju, međutim, opisan je metastatski spermatocitni tumor bez izraženih sarkomatoznih promena i anaplastičnih varijanti. Masa se sastojala od tri vrste ć elija, uključujuć i velike, srednje i male ć elije sa visokim pleomorfi zmom. Neoplastične ć elije su imale nejasnu citoplazmatsku granicu i često su primeć ene mitotičke fi gure. Primarni spermatocitni tumor metastazirao je na trbušne organe mesec dana nakon resekcije, a pas je uginuo 13 meseci nakon operacije. Stoga se preporučuje pažljivo prać enje nakon hirurške resekcije spermatocitnog tumora mada su metastaze u spermatocitnim tumorima retke.

Renal fibrosis is a progressive and chronic process that influences kidneys with chronic kidney disease (CKD), irrespective of cause, leading to irreversible failure of renal function and end-stage kidney disease. Among the signaling related to renal fibrosis, transforming growth factor-β1 (TGF-β1) signaling is a major pathway that induces the activation of myofibroblasts and the production of extracellular matrix (ECM) molecules. Apamin, a component of bee venom (BV), has been studied in relation to various diseases. However, the effect of apamin on renal interstitial fibrosis has not been investigated. The aim of this study was to estimate the beneficial effect of apamin in unilateral ureteral obstruction (UUO)-induced renal fibrosis and TGF-β1-induced renal fibroblast activation. This study revealed that obstructive kidney injury induced an inflammatory response, tubular atrophy, and ECM accumulation. However, apamin treatment suppressed the increased expression of fibrotic-related genes, including α-SMA, vimentin, and fibronectin. Administration of apamin also attenuated the renal tubular cells injury and tubular atrophy. In addition, apamin attenuated fibroblast activation, ECM synthesis, and inflammatory cytokines such as TNF-α, IL-1β, and IL-6 by suppressing the TGF-β1-canonical and non-canonical signaling pathways. This study showed that apamin inhibits UUO-induced renal fibrosis in vivo and TGF-β1-induced renal fibroblasts activation in vitro. Apamin inhibited the inflammatory response, tubular atrophy, ECM accumulation, fibroblast activation, and renal interstitial fibrosis through suppression of TGF-β1/Smad2/3 and STAT3 signaling pathways. These results suggest that apamin might be a potential therapeutic agent for renal fibrosis. KEY MESSAGES: UUO injury can induce renal dysfunction; however, apamin administration prevents renal failure in UUO mice. Apamin inhibited renal inflammatory response and ECM deposition in UUO-injured mice. Apamin suppressed the activation of myofibroblasts in vivo and in vitro. Apamin has the anti-fibrotic effect on renal fibrosis via regulation of TGF-β1 canonical and non-canonical signaling.

Background In estrogen receptor (ER)-positive breast cancer (BC), young age is associated with poor prognosis. While very young patients respond better to chemotherapy, chemotherapy is less effective in ER-positive tumors than in ER-negative tumors. The authors tried to evaluate chemotherapy response of very young patients with ER-positive BC by pathologic complete response (pCR) after neoadjuvant chemotherapy excluding the effect of endocrine treatment to the extent possible. Methods We collected individual patient data from 1992 to 2013 from the Korean Breast Cancer Society (KBCS). Total 1048 ER-positive and 797 ER-negative patients aged Results The proportion of patients aged P = 0.001). Breast conservation rates were not significantly different according to age (44.2% vs. 46.8% in ER-positive group, 55.2% vs. 48.0% in ER-negative group). pCR rate was not different according to age in ER-positive group (P = 0.71) but significantly better in patients aged P = 0.009). After adjusting for confounding variables, young patients maintained the higher probability of pCR than older patients in ER-negative tumors. However, pCR rate did not differ according to age in ER-positive tumors. In multivariate analysis, young age (P = 0.003, HR = 1.98) and there was only one event in a few patients achieved pCR in ER-positive group. Conclusions Chemotherapy response based on pCR was not better in young patients ( Trial registration Retrospectively registered.