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Background Ulcerative colitis (UC) is the large intestine disease that results in chronic inflammation and ulcers in the colon. Rg3-enriched Korean red ginseng extract (Rg3-RGE) is known for its pharmacological activities. Persicaria tinctoria (PT) is also used in the treatment of various inflammatory diseases. The aim of this study is to investigate the attenuating effects of Rg3-RGE with PT on oxazolone (OXA)-induced UC in mice. Methods A total of six groups of mice including control group, OXA (as model group, 1.5%) group, sulfasalazine (75 mg/kg) group, Rg3-RGE (20 mg/kg) group, PT (300 mg/kg) group, and Rg3-RGE (10 mg/kg) with PT (150 mg/kg) group. Data on the colon length, body weight, disease activity index (DAI), histological changes, nitric oxide (NO) assay, Real-time PCR of inflammatory factors, ELISA of inflammatory factors, Western blot, and flow cytometry analysis were obtained. Results Overall, the combination treatment of Rg3-RGE and PT significantly improved the colon length and body weight and decreased the DAI in mice compared with the treatment with OXA. Additionally, the histological injury was also reduced by the combination treatment. Moreover, the NO production level and inflammatory mediators and cytokines were significantly downregulated in the Rg3-RGE with the PT group compared with the model group. Also, NLR family pyrin domain containing 3 (NLRP3) inflammasome and nuclear factor kappa B (NF-κB) were suppressed in the combination treatment group compared with the OXA group. Furthermore, the number of immune cell subtypes of CD4+ T-helper cells, CD19+ B-cells, and CD4+ and CD25+ regulatory T-cells (Tregs) was improved in the Rg3-RGE with the PT group compared with the OXA group. Conclusion Overall, the mixture of Rg3-RGE and PT is an effective therapeutic treatment for UC.

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.

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.

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.

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

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.

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.

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.

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.

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.

Prostate-specific membrane antigen (PSMA), also known as glutamate carboxypeptidase II, is a potential target protein for imaging and treatment of patients with prostate cancer because of its overexpression during metastasis. Various PSMA-targeted imaging and therapeutic probes have been designed and synthesized based on the Lys-urea-Glu motif. Structural modifications have been made exclusively in the linker region, while maintaining the Lys-urea-Glu structure that interacts with S1 and S1ʹ pockets. This review includes WIPO-listed patents (from January 2017 to June 2020) reporting PSMA-targeted probes based on the Lys-urea-Glu or Glu-urea-Glu structure. : PSMA-targeted imaging agents labeled with radionuclides such as fluorine-18, copper-64, gallium-68, and technetium-99m have been successfully translated into clinical phase for the early diagnosis of metastatic prostate cancer. Recently, PSMA-targeted therapeutic agents labeled with iodine-131, lutetium-177, astatine-211, and lead-212 have also been developed with notable progress. Most PSMA-targeted agents are based on the Lys-urea-Glu or Glu-urea-Glu structure, demonstrate strong PSMA-binding affinity in nanomolar range, and achieve diverse structural modifications in the non-pharmacophore pocket. By exploiting the S1 accessory pocket or the tunnel region of the PSMA active site, the in vivo efficacy and pharmacokinetic profiles of the PMSA-targeted agents can be effectively modulated.

Aims This study aimed to elucidate the risk for stroke and systemic embolism (SE) in patients with atrial fibrillation and heart failure (HF) according to HF type. Methods and results A total of 10 780 patients with atrial fibrillation were enrolled in a multicentre prospective registry and divided according to HF type: no‐HF, HF with preserved ejection fraction (EF) (HFpEF), HF with mid‐range EF (HFmrEF), and HF with reduced EF (HFrEF). Each group included 237 age‐matched and sex‐matched patients (age, 69.0 ± 10.3 years; men, 69.6%). The baseline characteristics, cumulative incidence, and hazard ratios for stroke/SE and major bleeding were compared across the groups. Patients with HF accounted for 10.3% of the total population; HFpEF, HFmrEF, and HFrEF represented 43.7%, 23.6%, and 32.7% of the patients with HF, respectively. The CHA2DS2‐VASc score was significantly higher in the HFpEF, HFmrEF, and HFrEF groups than in the no‐HF group. The annual stroke/SE incidence rates were 2.8%, 0.7%, 1.1%, and 0.9% in the HFpEF, HFmrEF, HFrEF, and no‐HF groups, respectively. The cumulative incidence of stroke/SE was significantly highest in the HFpEF group at 22.8 ± 10.0 months (P = 0.020). The stroke/SE risk was higher in the HFpEF group than in the HFmrEF and HFrEF groups (hazard ratio, 3.192; 95% confidence interval, 1.039–9.810; P = 0.043). E/e' value was an independent risk factor for stroke/SE. There were no significant differences in the incidence of major bleeding across the groups. Conclusions The stroke/SE risk was the highest in the HFpEF group and comparable between the HFmrEF and HFrEF groups.

Background Complementary and alternative medicine (CAM) has been frequently used and its use continues to increase in lung cancer patients, despite insufficient scientific evidence. We analyzed the current status of the awareness and use of CAM in Korean lung cancer patients. Methods This study was a prospective survey-based study performed at seven medical centers in South Korea between August 2019 and October 2019. The survey included general patient characteristics, and the awareness and use of CAM. We analyzed the differences in the clinical parameters between patients aware and not aware of CAM and between CAM non-users and users. Results A total of 434 patients were included in this study. Among them, 68.8% of the patients responded that they were aware of CAM, and 30.9% of the patients said they experienced CAM. In univariate analysis, patients aware of CAM were younger with poor performance status, patients with advanced-stage lung cancer, those who received more systemic therapy, and those who received CCRT. By multiple logistic regression, younger age, poor performance status, advanced stage, and prior CCRT were independent risk factors for CAM awareness. There were no significant differences in the general characteristics and cancer-associated clinical parameters between CAM non-users and users. Conclusions More lung cancer patients with younger age, poor performance status, advanced stage, and prior CCRT were aware of CAM. There were no significantly different characteristics between CAM users and non-users.

ObjectiveTo compare P2Y12 inhibitor monotherapy after 3-month dual antiplatelet therapy (DAPT) with 12-month DAPT according to the type of P2Y12 inhibitor in patients undergoing percutaneous coronary intervention (PCI).MethodsThe Smart Angioplasty Research Team: Comparison Between P2Y12 Antagonist Monotherapy vs Dual Antiplatelet Therapy in Patients Undergoing Implantation of Coronary Drug-Eluting Stents (SMART-CHOICE) randomised trial compared 3-month DAPT followed by P2Y12 inhibitor monotherapy with 12-month DAPT. In this trial, 2993 patients undergoing successful PCI with drug-eluting stent were enrolled in Korea. As a prespecified analysis, P2Y12 inhibitor monotherapy after 3-month DAPT versus 12-month DAPT were compared among patients receiving clopidogrel and those receiving potent P2Y12 inhibitor (ticagrelor or prasugrel), respectively. The primary endpoint was a composite of all-cause death, myocardial infarction or stroke at 12 months after the index procedure.ResultsAmong 2993 patients (mean age 64 years), 58.2% presented with acute coronary syndrome. Clopidogrel was prescribed in 2312 patients (77.2%) and a potent P2Y12 inhibitor in 681 (22.8%). There were no significant differences in the primary endpoint between the P2Y12 inhibitor monotherapy group and the DAPT group among patients receiving clopidogrel (3.0% vs 3.0%; HR: 1.02; 95% CI 0.64 to 1.65; p=0.93) as well as among patients receiving potent P2Y12 inhibitors (2.4% vs 0.7%; HR: 3.37; 95% CI 0.77 to 14.78; p=0.11; interaction p=0.1). Among patients receiving clopidogrel, P2Y12 inhibitor monotherapy compared with DAPT showed consistent treatment effects across various subgroups for the primary endpoint. Among patients receiving potent P2Y12 inhibitors, the rate of bleeding (Bleeding Academic Research Consortium types 2– 5) was significantly lower in the P2Y12 inhibitor monotherapy group than in the DAPT group (1.5% vs 5.0%; HR: 0.33; 95% CI 0.12 to 0.87; p=0.03).ConclusionsCompared with 12-month DAPT, clopidogrel monotherapy after 3-month DAPT showed comparable cardiovascular outcomes in patients undergoing PCI.Trial registration numberNCT02079194.

A hypertrophic scar is a common dermal fibroproliferative lesion usually treated with topical silicone. Verapamil, a type of calcium channel blocker, is considered a candidate drug for the treatment of hypertrophic scars. Here, we report that the addition of verapamil to topical silicone gel enhances treatment outcomes of hypertrophic scars. Upon creation of hypertrophic scars with the rabbit ear model, varying concentrations of verapamil‐added silicone gel (0.1, 1, and 10 mg/g) were applied daily for 28 days. After the animals were euthanised, microscopic measurement was performed for (a) scar elevation index (SEI), (b) fibroblast count, and (c) capillary count. On gross analysis, features of hypertrophic scars were significantly alleviated in the verapamil‐added groups. On histologic examination, verapamil‐added groups showed (a) reduced SEI (1.93 (1.79‐2.67) for control vs 1.34 (1.21‐1.51) for silicone only and 1.13 (1.01‐1.65) for verapamil‐added silicone), (b) fibroblast count 700.5 (599.5‐838.5) for control, 613.25 (461‐762.5) for silicone only, and 347.33 (182.5‐527) for verapamil‐added silicone), and (c) capillary formation (52 (35.5‐96.5) for control, 46 (28‐64.5) for silicone only, and 39.83(24‐70) for verapamil‐added silicone) (Kruskal‐Wallis test, P

Aims For the effective production of 146S particles, which determines foot-and-mouth disease (FMD) vaccine efficacy, we aimed to identify the optimal medium that is easy-to-use, productive, and economically affordable for the large-scale production of FMD vaccine. Methods and results Nine combinations of cell growth media and replacement media were tested for virus propagation. Apart from the replacement strategy, we tested a simple addition strategy involving the addition of 30% v/v of fresh medium to the total spent medium using the Cellvento BHK-200 (Vento). Unlike other tested media that produced poor yields of 146S particles when the spent media were not eliminated, Vento exhibited high productivity with the 30% addition strategy. Conclusions Considering its lower price and media consumption compared to those of other media that require media replacement, the 30% addition strategy of Vento is highly effective. Further, owing to its simple application strategy, it makes the scale-up process easy and helps in saving the time and labor involved in spent media removal. Significance and impact of the study Through the first comparative assessment of commercial media for the 146S particle recovery, this study suggests the best practical medium for the industrial-scale production of FMD vaccines.

OBJECTIVES Surgical resection is the best option for the treatment of early-stage lung cancer. However, older patients are less likely to receive curative treatment. Therefore, we compared long-term survival rates between surgical resection and stereotactic ablative radiotherapy (SABR) for the treatment of early-stage lung cancer in older patients. METHODS From 2013 to 2016, 272 patients aged ≥75 years with clinical stage I lung cancer underwent surgical resection (n = 191) or SABR (n = 81). A propensity score-matched analysis was performed. Overall survival, cumulative incidence of cancer-related death and recurrence were compared between the 2 groups. RESULTS In the matched cohort, 48 well-balanced pairs were extracted. An overall survival benefit was associated with surgery (surgery vs SABR = 65.9% vs 40.3%; P = 0.034); however, there was no significant difference in the cumulative incidence of cancer-related death (P = 0.089) or recurrence (P = 0.111) between the 2 groups. Systemic dissemination was the dominant pattern of progression in both groups. The 3-year cumulative incidence of regional recurrence was significantly higher in the SABR group compared to the surgery group (surgery vs SABR = 0% vs 11.4%, P = 0.046). CONCLUSIONS Surgical resection with mediastinal lymph node dissection provides better long-term survival compared to SABR in older patients with stage I lung cancer. Surgery should be considered for older patients aged ≥75 years who are appropriate candidates for surgery. SABR remains an alternative treatment with comparable cancer-related death and recurrence for patients unsuitable for surgery.

OBJECTIVES To identify whether the prognostic implications of Vasoactive Inotropic Score according to use of mechanical circulatory support differ in the treatment of acute myocardial infarction complicated by cardiogenic shock. DESIGN A multicenter retrospective and prospective observational cohort study. SETTING/PATIENT The REtrospective and prospective observational Study to investigate Clinical oUtcomes and Efficacy registry includes 1,247 patients with cardiogenic shock from 12 centers in Korea. A total of 836 patients with acute myocardial infarction complicated by cardiogenic shock were finally selected, and the study population was stratified by quartiles of Vasoactive Inotropic Score ( 90) for the present study. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Primary endpoint was in-hospital mortality and secondary endpoint was follow-up mortality. Among the study population, 326 patients (39.0%) received medical treatment alone, 218 (26.1%) received intra-aortic balloon pump, and 292 (34.9%) received extracorporeal membrane oxygenation. In-hospital mortality occurred in 305 patients (36.5%) and was significantly higher in patients with higher Vasoactive Inotropic Score (15.6%, 20.8%, 40.2%, and 67.3%, for 90; p < 0.001). Vasoactive Inotropic Score showed better ability to predict in-hospital mortality in acute myocardial infarction patients with cardiogenic shock who received medical treatment alone (area under the curve: 0.797; 95% CI, 0.728-0.865) than in those who received intra-aortic balloon pump (area under the curve, 0.704; 95% CI, 0.625-0.783) or extracorporeal membrane oxygenation (area under the curve, 0.644; 95% CI, 0.580-0.709). The best cutoff value of Vasoactive Inotropic Score for the prediction of in-hospital mortality also differed according to the use of mechanical circulatory support (16.5, 40.1, and 84.0 for medical treatment alone, intra-aortic balloon pump, and extracorporeal membrane oxygenation, respectively). There was a significant interaction between Vasoactive Inotropic Score as a continuous value and the use of mechanical circulatory support including intra-aortic balloon pump (interaction-p = 0.006) and extracorporeal membrane oxygenation (interaction-p < 0.001) for all-cause mortality during follow-up. CONCLUSIONS High Vasoactive Inotropic Score was associated with significantly higher in-hospital and follow-up mortality in patients with acute myocardial infarction complicated by cardiogenic shock. The predictive value of Vasoactive Inotropic Score for mortality was significantly higher in acute myocardial infarction patients with cardiogenic shock treated by medical treatment alone than in those treated by mechanical circulatory support such as intra-aortic balloon pump or extracorporeal membrane oxygenation.

The prognosis of patients with node-negative T1b tumors according to human epidermal growth factor receptor 2 (HER2) status is not known. This group of patients has not been studied in the available randomized trials. The objective of this study was to evaluate the survival of patients in a monoethnic group diagnosed with T1b lymph node-negative breast cancer depending on HER2 status. We analyzed 3110 patients with T1bN0M0 breast cancer whose data were deposited into the Korean Breast Cancer Society Registry database between 2000 and 2009. Overall survival (OS) and breast cancer-specific survival (BCSS) were compared according to HER2 status. Among all patients, 494 (15.9%) had HER2-positive breast cancer. At a mean follow-up of 93 months, 108 deaths and 86 breast cancer-specific deaths were noted among all patients. There was no significant difference in OS between the HER2-negative and HER2-positive groups (p = 0.103). The same result was observed for BCSS. However, in the subgroup of estrogen receptor (ER)-positive women, HER2-negative patients had a better BCSS prognosis than HER2-positive patients (p = 0.025). Multivariate analysis also indicated a significant difference in BCSS in the ER-positive subgroup (HR 2.60; 95% CI 1.15–5.87; p = 0.021). This study analyzed a large nationwide and monoethnic cohort and found a significant difference only in BCSS in the ER-positive subgroup according to HER2 status. Anti-HER2 therapy may be considered in HER2-positive and ER-positive patients with small, node-negative breast cancer.

Background/Aims: Comparative occurrence of ischemic stroke for rhythm versus rate control strategy in patients with non-valvular atrial fibrillation (NVAF) is still inconclusive. The purpose of this study was to investigate whether the rhythm control strategy is associated with a lower risk of ischemic stroke compared to the rate control strategy in NVAF patients. Methods: The CODE-AF registry prospectively enrolled 6,280 consecutive pa tients who were treated for NVAF at 10 tertiary referral centers in South Korea. Of these, 2,513 NVAF patients (age, 67 ± 10 years; male, 61.8%) were clinically followed up for over 1-year and divided into rate and rhythm control groups. Results: Those treated with the rhythm control strategy were younger and had less proportions of underlying disease compared to those treated with the rate control strategy. After the propensity matching analysis, those treated with the rhythm control strategy had similar baseline characteristics including the CHA2DS2-VASC score compared to those treated with the rate control strategy. The rate of oral anticoagulation, all bleeding, and hospitalization were also simi larly between the two groups. The incidence rate of ischemic stroke in the rhythm control group was significantly lower than in the rate control group (0.7 vs. 6.9 per 1,000 person-years, p = 0.011). Conclusions: The rhythm control strategy demonstrated a beneficial effect to lower the risk of ischemic stroke during a 1-year follow-up compared to the rate control strategy.

Rationale: Chemoradiation (CRT) is commonly used as an adjuvant or neoadjuvant treatment for colorectal cancer (CRC) patients. However, resistant cells manage to survive and propagate after CRT, increasing the risk of recurrence. Thus, better understanding the mechanism of resistant cancer cells is required to achieve better clinical outcomes. Methods: Here, we explored gene expression profiling of CRC patient tumors to identify therapy resistance genes and discovered that protein tyrosine phosphatase receptor type C (PTPRC), which encodes CD45, was increased in remnant tumor tissues after CRT and correlated with metastasis. Through multiple validations using patient tumors and CRC cell lines, we found for the first time the increase of CD45 expression in CRC (EpCAM+) epithelial cells surviving after CRT. Thus, we investigated the biological role and downstream events of CD45 were explored in human CRC cells and CRC mouse models. Results: Increased CD45 expression in cancer cells in pretreated primary tumors accounts for poor regression and recurrence-free survival in CRT-treated patients. High CD45 expression promotes CRC cell survival upon 5-fluorouracil or radiation treatment, while CD45 depletion sensitizes CRC cells to CRT. Intriguingly, CD45 is preferentially expressed in cancer stem-like cells (CSCs), as determined by spheroid culture and the expression of CSC markers, and is required for the distinct functions of CSCs, such as cancer initiation, repopulation, and metastasis. Mechanistically, CD45 phosphatase activity promotes Wnt transcriptional activity by stabilizing the β-catenin protein, which collectively enhances stemness and the therapy-resistant phenotype. Conclusions: Our results highlight a novel function of CD45 as a mediator of CRT resistance and provide a potential therapy strategy for CRC therapy.

Background The impact of the changes in the obesity status on mortality has not been established; thus, we investigated the long-term influence of body fat (BF) changes on all-cause deaths and cardiovascular outcomes in a general population. Methods A total of 8374 participants were observed for 12 years. BF was measured at least two times using a bioimpedance method. The causes of death were acquired from the nationwide database. A major adverse cardiovascular event (MACE) was defined as a composite of myocardial infarction, coronary artery disease, stroke, and cardiovascular death. Standard deviations (SDs) were derived using a local regression model corresponding to the time elapsed between the initial and final BF measurements (SDT) and were used to standardize the changes in BF (ΔBF/SDT). Results The incidence rates of all-cause death, cardiovascular death, and MACE were the highest in the participants with ΔBF/SDT

A wide range of studies have steadily pointed out the relation of oxidative stress to the primary and secondary causes of human disease and aging. As such, there have been multiple misconceptions about oxidative stress. Most of reactive oxygen species (ROS) generated from chronic diseases cause oxidative damage to cell membrane lipids and proteins. ROS production is increased by abnormal stimulation inside and outside in the body, and even though ROS are generated in cells in response to abnormal metabolic processes such as disease, it does not mean that they directly contribute to the pathogenesis of a disease. Therefore, the focus of treatment should not be on ROS production itself but on the prevention and treatment of diseases linked to ROS production, including types 1 and 2 diabetes, cancer, heart disease, schizophrenia, Parkinson's disease, and Alzheimer's disease. In this regard, Korean Red Ginseng (KRG) has been traditionally utilized to help prevent and treat diseases such as diabetes, cancer, inflammation, nervous system diseases, cardiovascular disease, and hyperlipidemia. Therefore, this review was intended to summarize in vivo animal and human clinical studies on the antioxidant activities of KRG and its components, ginsenosides.

Background Mutation analysis of circulating tumor DNA (ctDNA) is used for diagnosing lung cancer. This trial aimed to assess the efficacy of afatinib in treatment‐naïve patients with lung cancer harboring epidermal growth factor receptor mutations (EGFRm, exon 19 deletions or exon 21 point mutations) detected based on ctDNA. Methods The primary objective was the objective response rate (ORR) in the response evaluable (RE) population. EGFRm analysis of ctDNA was performed using PANA Mutype. Of the 331 patients screened, ctDNA was positive in 21% (68/331) in the detection of activating EGFRm. Among 81 subjects with tumor EGFRm, 48 showed matched EGFRm in their ctDNA (59% sensitivity). Results Therapy with afatinib 40 mg was initiated in 21 (female, 17; adenocarcinoma, 20) patients (intention‐to‐treat, ITT); dose modifications were made in 15 (71%). The ORR was 74% in the RE population (14/19); 11 patients showed EGFRm only in ctDNA (Group A), whereas 10 exhibited the same EGFRm in their ctDNA and tumor DNA (Group B). There was no significant difference in ORR between Groups A and B (80% and 67% RE, respectively). Median progression‐free survival (PFS) was 12.0 months, and no significant difference was observed according to the final afatinib dose, type of EGFRm, and Group A versus B. After progression, T790M mutation was found in 40% (6/15) of patients, and osimertinib was used as a second‐line treatment. Conclusions Afatinib showed similar ORR and PFS in patients with lung cancer harboring EGFRm in their ctDNA regardless of tumor EGFRm results. Key points Significant findings of the study Afatinib showed favorable ORR and PFS regardless of the tumor EGFR mutation status results, similar to the findings of previous trials assessing afatinib as first‐line treatment of EGFR‐mutated non‐small cell lung cancer based on tumor genotyping. What this study adds Our findings emphasize that the survival benefit of afatinib treatment can be achieved not only by appropriate dose reduction with frequent and detailed monitoring of toxicities, but also by using noninvasive (ctDNA) assays in a real‐world setting., Afatinib showed favorable ORR and PFS regardless of the tumor EGFR mutation status results, similar to the findings of previous trials assessing afatinib as first‐line treatment of EGFR‐mutated NSCLC based on tumor genotyping. The survival benefit of afatinib treatment can be achieved not only by appropriate dose reduction with frequent and detailed monitoring of toxicities, but also by using noninvasive (ctDNA) assays in a real‐world setting

Background This study identified predictors of hospital mortality after successful weaning of patients with cardiogenic shock off venoarterial (VA) extracorporeal membrane oxygenation (ECMO) support.Methods and Results:Adult patients who received peripheral VA ECMO from January 2012 to April 2017 were reviewed retrospectively. After excluding patients who died on ECMO support, predictors for survival to discharge were investigated in patients who were successfully weaned off ECMO. Of 191 patients successfully weaned off ECMO, 143 (74.9%) survived to discharge. The prevalence of a history of stroke and coronary artery disease, as well as ECMO-related complications, including newly developed stroke and sepsis, was a higher in patients who did not survive to discharge than in those who did. On the day of ECMO weaning, Sequential Organ Failure Assessment score and serum lactate were higher in patients who did not survive to discharge, although there was no significant difference in blood pressure and the use of vasoactive drugs between the 2 groups. On multivariable analysis, stroke and sepsis during ECMO support, a lower Glasgow Coma Scale and acute kidney injury requiring continuous renal replacement therapy after weaning were significant predictors for in-hospital mortality. Conclusions Complications that occurred during ECMO and the presence of extracardiac organ dysfunction after weaning were associated with in-hospital mortality in patients with cardiogenic shock who were successfully weaned off ECMO.

Aims The aim of this study is to determine the relationship between alcohol consumption and atrial fibrillation (AF)-related adverse events in the AF population. Methods and results A total of 9411 patients with nonvalvular AF in a prospective observational registry were categorized into four groups according to the amount of alcohol consumption—abstainer-rare, light ( Conclusion Our findings suggest that heavy alcohol consumption increases the risk of adverse events in patients with AF, whereas light or moderate alcohol consumption does not.

BACKGROUND Choriocarcinoma is an infrequent entity and the most aggressive subtype of germ-cell tumors. Because of early metastatic spread and rapid disease progression, choriocarcinoma patients display poor prognosis. Although etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine (EMA-CO) regimen is widely used to treat gestational trophoblastic tumors in females, its role in treating male choriocarcinoma is seldom reported. CASE SUMMARY A 32-year-old man was diagnosed with burned-out primary germ cell tumors (GCT) with retroperitoneum, liver and lung metastases. Biopsy of the liver revealed pure choriocarcinoma. The patient received bleomycin, etoposide, and cisplatin chemotherapy. After two cycles of treatment, response evaluation revealed the mixed response. EMA-CO regimen was used in the second-line therapy. After eight cycles, the patient showed a potentially resectable state and thus, all residual masses were surgically removed. The patient was completely cured, and 10 years later, he is leading a healthy life without complications. CONCLUSION This paper is the first case of high-risk nonseminomatous GCT in a male patient to be successfully treated with the EMA-CO regimen. The EMA-CO regimen can be used actively in patients with high-risk nonseminomatous GCT.

Background Complete resection is a standard treatment for patients with Masaoka-Koga stages II and III thymoma, however the role of postoperative radiotherapy (PORT) is controversial. We analyzed data collected from 4 Korean hospitals to determine the effectiveness of PORT in stage II and III thymoma patients. Methods Between January 2000 and December 2013, 1,663 patients underwent surgery for thymic tumors at the 4 hospitals. Among them, 668 patients (527 with stage II and 141 with stage III) were investigated, among whom, 443 received PORT (335 with stage II and 108 with stage III). Propensity score matching (PSM) was performed, and 404 patients (346 with stage II and 58 with stage III) were selected. Results Perioperative characteristics were similar in the PORT and non-PORT groups after PSM. On survival analysis of stage II patients, the PORT and non-PORT groups showed no difference in either 5-year recurrence-free survival (RFS) (96.3% vs. 96.6%, P=0.622) or 5-year overall survival (OS) (94.6% vs. 93.8%, P=0.839). However, among stage III patients, the PORT group showed significantly better 5-year RFS (75.7% vs. 50.1%, P=0.040) and 5-year OS (86.5% vs. 54.7%, P=0.001). On multivariate Cox regression analysis, PORT was a significant positive prognostic factor in terms of both RFS (P=0.005) and OS (P=0.004) in patients with stage III thymomas, but not in those with stage II disease (P=0.987 and 0.968, respectively). Conclusions PORT improved the RFS and OS in stage III thymoma patients, but showed no survival benefit in stage II patients.

Background Ulcerative colitis (UC) is a commonly encountered large intestine disease in the contemporary world that terminates into colorectal cancer; therefore, the timely treatment of UC is of major concern. Panax ginseng Meyer is an extensively consumed herbal commodity in South East Asian countries, especially Korea. It exhibits a wide range of biologically beneficial qualities for almost head-to-toe ailments in the body. Epimedium koreanum Nakai (EKN) is also a widely used traditional Korean herbal medicine used for treating infertility, rheumatism, and cardiovascular diseases. Materials and methods Separately the anti-inflammatory activities of both red ginseng extracts (RGEs) and EKNs had been demonstrated in the past in various inflammatory models; however, we sought to unravel the anti-inflammatory activities of the combination of these two extracts in dextran sulfate sodium (DSS)-induced ulcerative colitis in mice model because the allopathic remedies for UC involve more side effects than benefits. Results Our results have shown that the combination of RGE + EKN synergistically alleviated the macroscopic lesions in DSS-induced colitic mice such as colon shortening, hematochezia, and weight loss. Moreover, it restored the histopathological lesions in mice and decreased the levels of pro-inflammatory mediators and cytokines through the repression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP-3) expression. In vitro, this combination also reduced the magnitude of nitric acid (NO), pro-inflammatory mediators and cytokine through NF-κB and mitogen-activated protein kinase (MAPK) pathways in RAW 264.7 mouse macrophage cells. Conclusion In the light of these findings, we can endorse this combination extract as a functional food for the prophylactic as well as therapeutic treatment of UC in humans together with allopathic remedies.

Air embolism is a rare, fatal complication of computed tomography (CT)‐guided transthoracic needle biopsy (TTNB) of the lung. Here, we report a patient who developed an air embolism after CT‐guided TTNB, which led to ST‐elevation myocardial infarction and acute cerebral ischemia. The patient recovered completely without critical sequelae and was diagnosed with adenocarcinoma harboring activating epidermal growth factor receptor (EGFR) mutation. The patient responded to subsequent treatment with gefitinib. Key points Signficant findings of the study Air embolism is a rare, fatal complication of CT‐guided transthoracic lung biopsy. Only a few cases have been previously reported where myocardial and cerebral infarction occurred after TTNB, demonstrated not only on CT scan, but also electrocardiogram and electroencephalogram. What this study adds Detection of driver gene mutation is crucial for planning lung cancer treatment. Despite the need for tissue biopsy, air embolism propagation to vital organs could result in severe end‐organ damage and multidisciplinary approaches are needed to improve initial outcomes., Systemic air embolism developed after CT‐guided TTNB, leading to ST‐elevation, myocardial infarction and acute ischemic stroke. The patient recovered completely without sequelae and was diagnosed with adenocarcinoma harboring activating EGFR mutation. Treatment with gefitinib showed a response.

This study examined several trauma scoring systems that serve as the basis for applying the Secondary Assessment of Victim Endpoint (SAVE) severity classification to propose a method that can be applied during triage. By using an exploratory method, data collected from different trauma scoring systems was qualitatively evaluated. First, it was confirmed that the survival risk ratio (SRR) of the International Classification of Disease-based Injury Severity Score (ICISS) can be used for SAVE severity classification. Second, the Korean Trauma Data Bank (KTDB) of the Central Emergency Medical Center does not indicate the SRR of each injury according to the Korean standard classification of disease and cause of death (KCD). Third, the SRR of injuries, from data acquired from the United States can be used for classification of SAVE severity classification. Fourth, the addition of SRR from the KCD to the KTDB can be used for SAVE severity classification.

BACKGROUND Carotid blowout syndrome (CBS) is a rupture of the carotid artery and is mainly caused by radiation and resection of head and neck cancers or direct tumor invasion of the carotid artery wall. It is a life-threatening clinical situation. There is no established and effective mode of management of CBS. Furthermore, there is no established preceding sign or symptom; therefore, preventive efforts are not clinically meaningful. CASE SUMMARY We described two cases of CBS that occurred in patients with head and neck cancer after definitive chemoradiotherapy (CRT) using three-dimensional conformal intensity-modulated radiation therapy. Two men aged 61 and 56 years with locally advanced head and neck cancer were treated with definitive CRT. After completing CRT, both of them achieved complete remission. Subsequently, they had persistent severe pain in the oropharyngeal mucosal region and the irradiated neck despite the use of opioid analgesics and rehabilitation for relief of contracted skin. However, continuous follow-up imaging studies showed no evidence of cancer recurrence. Eleven to twelve months after completing CRT, the patients visited the emergency room complaining about massive oronasal bleeding. Angiograms showed rupture of carotid artery pseudoaneurysms on the irradiated side. Despite attempting to secure hemostasis with carotid arterial stent insertion and coil embolization, both patients died because of repeated bleeding from the pseudoaneurysms. CONCLUSION In patients with persistent pain in irradiated sites, clinicians should be suspicious of progressing or impending CBS, even in the three-dimensional conformal intensity-modulated radiation therapy era.