Population pharmacokinetic model of rifampicin for personalized tuberculosis pharmacotherapy: Effects of SLCO1B1 polymorphisms on drug exposure.

BACKGROUND: Rifampicin (RIF) exhibits high pharmacokinetic (PK) variability among individuals; a low plasma concentration might result in unfavorable treatment outcomes and drug resistance. This study evaluated the contributions of non- and genetic factors to the interindividual variability of RIF exposure, then suggested initial doses for patients with different weight bands. METHODS: This multicenter prospective cohort study in Korea analyzed demographic and clinical data, the solute carrier organic anion transporter family member 1B1 (SLCO1B1) genotypes, and RIF concentrations. Population PK modeling and simulations were conducted using nonlinear mixed-effect modeling. RESULTS: In total, 879 tuberculosis (TB) patients were divided into a training dataset (510 patients) and a test dataset (359 patients). A one-compartment model with allometric scaling for effect of body size best described the RIF PKs. The apparent clearance (CL/F) was 16.6% higher among patients in the SLCO1B1 rs4149056 wild-type group than among patients in variant group, significantly decreasing RIF exposure in the wild-type group. The developed model showed better predictive performance compared with previously reported models. We also suggested that patients with body weights of <40 kg, 40-55 kg, 55-70 kg, and >70 kg patients receive RIF doses of 450, 600, 750, and 1050 mg/day, respectively. CONCLUSIONS: Total body weight and SLCO1B1 rs4149056 genotypes were the most significant covariates that affected RIF CL/F variability in Korean TB patients. We suggest initial doses of RIF based on World Health Organization weight-band classifications. The model may be implemented in treatment monitoring for TB patients.

Current status and trends of pulmonary rehabilitation in South Korea: National level data analysis using Health Insurance Review and Assessment Service (HIRA) database from 2016 to 2018.

In South Korea, there are few studies to understand the current status of pulmonary rehabilitation in clinical practice and develop it. This study aimed to assess the current status and annual changes in the number and pattern of prescriptions for pulmonary rehabilitation before and after its insurance coverage. The trends of pulmonary rehabilitation before and after its insurance coverage commencement were evaluated using the data of 24,380 patients during the 3-year period from 2016 to 2018 that were archived by the National Health Information Database of the Health Insurance Review and Assessment Service in South Korea. The annual total number of patients who received pulmonary rehabilitation was stratified by the type of prescription, sex, age, type of insurance, medical institution, and region. In addition, the frequencies of pulmonary rehabilitation for various diagnoses were investigated using the major codes of the Korean Standard Classification of Disease. The patients who received pulmonary rehabilitation increased by approximately 2 times from 5936 in 2016 (before insurance coverage) to 10,474 in 2019. Before 2017, most patients underwent simple pulmonary rehabilitation coded as MM290. However, since the insurance coverage of rehabilitation exercise for pulmonary disease (MM440), the proportions of patients receiving them increased. Men underwent pulmonary rehabilitation more often than women, and >70% of the patients were aged >60 years. Most patients received pulmonary rehabilitation at tertiary hospitals in Seoul. In 2016, pulmonary rehabilitation was prescribed more frequently for cerebral infarction; after 2017, it was prescribed more frequently for lung cancer. This study summarized the current status and trends of pulmonary rehabilitation in South Korea before and after National Health Insurance Service coverage, which commenced on January 1, 2017. A significant increase in the number of pulmonary rehabilitations was confirmed after the insurance coverage.

Transbronchial Lung Cryobiopsy for Diagnosing Interstitial Lung Disease: A Retrospective Single-Center Experience.

BACKGROUND: An accurate diagnosis in patients with interstitial lung diseases (ILDs) by multidisciplinary discussion (MDD) based on histopathologic information is essential for optimal treatment. Transbronchial lung cryobiopsy (TBLC) has increasingly been used as a diagnostic alternative to surgical lung biopsy. This study aimed to evaluate the appropriate methods of TBLC in patients with ILD in Korea. METHODS: A total of 27 patients who underwent TBLC were included. TBLC procedure details and clinical MDD diagnosis using TBLC histopathologic information were retrospectively analyzed. RESULTS: All procedures were performed under general anesthesia with the fluoroscopic guidance in the operation room using flexible bronchoscopy and endobronchial balloon blocker. The median procedure duration was less than 30 minutes, and the median number of biopsies per participant was 2. Most of the bleeding after TBLC was not severe, and the rate of pneumothorax was 25.9%. The most common histopathologic pattern was alternative (48.2%), followed by indeterminate (33.3%) and usual interstitial pneumonia (UIP)/probable UIP (18.5%). In the MDD after TBLC, the most common diagnosis was idiopathic pulmonary fibrosis (33.3%), followed by smoking-related ILD (25.9%), nonspecific interstitial pneumonia (18.6%), unclassifiable-ILD (14.8%), and others (7.4%). CONCLUSION: This first single-center experience showed that TBLC using a flexible bronchoscopy and endobronchial balloon blocker with the fluoroscopic guidance under general anesthesia may be a safe and adequate diagnostic method for ILD patients in Korea. The diagnostic yield of MDD was 85.2%. Further studies are needed to evaluate the diagnostic yield and confidence of TBLC.

Clinical outcomes of hyperprogression based on volumetry in non-small cell lung cancer after immune checkpoint inhibitor treatment.

BACKGROUND: Hyperprogressive disease (HPD) is a novel pattern of the treatment course after immune checkpoint inhibitor (ICI) therapy in patients with non-small cell lung cancer (NSCLC). This study aimed to investigate the clinical characteristics, outcomes, and associated factors of HPD using a semiautomatic volume measurement. METHODS: This retrospective study enrolled patients with recurrent and/or metastatic NSCLC treated with ICIs between January 2015 and August 2019 at eight tertiary centers in Korea. HPD was defined according to the tumor growth kinetics and time to treatment failure. Tumor volume was measured using a semiautomatic software. RESULTS: A total of 219 NSCLC patients with 35 HPD by volumetric measurement (HPDv) (15.9%) were enrolled. The median duration of overall survival (OS) and OS after ICI treatment (ICI-OS) were 34.5 and 18.4 months, respectively. HPDv patients had significantly worse progression-free survival (PFS) than progressive disease patients without HPDv (1.16 vs. 1.82 months, p-value <0.001). ICI-OS did not significantly differ between patients with HPDv and those without HPDv (2.66 vs. 5.4 months, p = 0.105). PD-L1 expression lower than 50%, more than three metastatic sites, neutrophil-to-lymphocyte ratio equal to or higher than 3.3, and hemoglobin level lower than 10 were found to be associated with HPDv. CONCLUSIONS: There is no standardized definition of HPD. However, defining HPD in NSCLC patients treated with ICI using a semiautomatic volume measurement software is feasible.

The current status and outcomes of in-hospital P2Y12 receptor inhibitor switching in Korean patients with acute myocardial infarction.

BACKGROUND/AIMS: While switching strategies of P2Y12 receptor inhibitors (RIs) have sometimes been used in acute myocardial infarction (AMI) patients, the current status of in-hospital P2Y12RI switching remains unknown. METHODS: Overall, 8,476 AMI patients who underwent successful revascularization from Korea Acute Myocardial Infarction Registry-National Institute of Health (KAMIR-NIH) were divided according to in-hospital P2Y12RI strategies, and net adverse cardiovascular events (NACEs), defined as a composite of cardiac death, non-fatal myocardial infarction (MI), stroke, or thrombolysis in myocardial infarction (TIMI) major bleeding during hospitalization were compared. RESULTS: Patients with in-hospital P2Y12RI switching accounted for 16.5%, of which 867 patients were switched from clopidogrel to potent P2Y12RI (C-P) and 532 patients from potent P2Y12RI to clopidogrel (P-C). There were no differences in NACEs among the unchanged clopidogrel, the unchanged potent P2Y12RIs, and the P2Y12RI switching groups. However, compared to the unchanged clopidogrel group, the C-P group had a higher incidence of non-fatal MI, and the P-C group had a higher incidence of TIMI major bleeding. In clinical events of in-hospital P2Y12RI switching, 90.9% of non-fatal MI occurred during pre-switching clopidogrel administration, 60.7% of TIMI major bleeding was related to pre-switching P2Y12RIs, and 71.4% of TIMI major bleeding was related to potent P2Y12RIs. Only 21.6% of the P2Y12RI switching group switched to P2Y12RIs after a loading dose (LD); however, there were no differences in clinical events between patients with and without LD. CONCLUSION: In-hospital P2Y12RI switching occurred occasionally, but had relatively similar clinical outcomes compared to unchanged P2Y12RIs in Korean AMI patients. Non-fatal MI and bleeding appeared to be mainly related to pre-switching P2Y12RIs.

Clinical Outcomes of Ticagrelor in Korean Patients with Acute Myocardial Infarction without High Bleeding Risk.

BACKGROUND: Although ticagrelor is known to increase the bleeding risk compared to clopidogrel in East Asian patients, its clinical benefits in patients with acute myocardial infarction (AMI) without high bleeding risk (HBR) remains unknown. METHODS: A total of 7,348 patients who underwent successful percutaneous coronary intervention (PCI) from the Korea Acute Myocardial Infarction Registry-National Institute of Health (KAMIR-NIH), between November 2011 and December 2015, were divided into two groups according to the Academic Research Consortium for HBR criteria (KAMIR-HBR, 2,469 patients; KAMIR-non HBR, 4,879 patients). We compared in-hospital major adverse cardiovascular events (MACEs, defined as a composite of cardiac death, non-fatal myocardial infarction, or stroke), and the thrombolysis in myocardial infarction (TIMI) major bleeding between ticagrelor and clopidogrel in the KAMIR-HBR and the KAMIR-non HBR groups, respectively. RESULTS: After propensity score matching, ticagrelor had a higher incidence of in-hospital TIMI major bleeding than clopidogrel in all patients (odds ratio [OR], 1.683; 95% confidence interval [CI], 1.010-2.805; P = 0.046) and the KAMIR-HBR group (OR, 3.460; 95% CI, 1.374-8.714; P = 0.008). However, there was no significant difference in in-hospital TIMI major bleeding between ticagrelor and clopidogrel in the KAMIR-non HBR group (OR, 1.436; 95% CI, 0.722-2.855; P = 0.303). No differences were observed in the cumulative incidences of in-hospital and 6-month MACEs between ticagrelor and clopidogrel in both groups. CONCLUSIONS: The bleeding risk of ticagrelor was attenuated in Korean patients with AMI without HBR. Appropriate patient selection could reduce in-hospital bleeding complications associated with ticagrelor in Korean patients with AMI who underwent successful PCI.

The role of interleukin-6 as a prognostic biomarker for predicting acute exacerbation in interstitial lung diseases.

BACKGROUND: Interstitial lung diseases (ILDs) are chronic, parenchymal lung diseases with a variable clinical course and a poor prognosis. Within various clinical courses, acute exacerbation (AE) is a devastating condition with significant morbidity and high mortality. The aim of this study was to investigate the role of interleukin-6 (IL-6) to predict AE and prognosis in patients with ILD. METHODS: Eighty-three patients who were diagnosed with ILD from 2016 to 2019 at the Haeundae Paik Hospital, Busan, South Korea, were included and their clinical data were retrospectively analyzed. RESULTS: The median follow-up period was 20 months. The mean age was 68.1 years and 65.1% of the patients were men with 60.2% of patients being ever-smokers. Among ILDs, idiopathic pulmonary fibrosis was the most common disease (68.7%), followed by connective tissue disease-associated ILD (14.5%), cryptogenic organizing pneumonia (9.6%), and nonspecific interstitial pneumonia (6.0%). The serum levels of IL-6 were measured at diagnosis with ILD and sequentially at follow-up visits. During the follow-ups, 15 (18.1%) patients experienced an acute exacerbation (AE) of ILD and among them, four (26.7%) patients died. In the multivariable analysis, high levels of IL-6 (OR 1.014, 95% CI: 1.001-1.027, p = 0.036) along with lower baseline saturations of peripheral oxygen (SpO2) were independent risk factors for AE. In the receiver operating characteristic curve analysis, the area under the curve was 0.815 (p < 0.001) and the optimal cut-off value of serum IL-6 to predict AE was 25.20 pg/mL with a sensitivity of 66.7% and specificity of 80.6%. In the multivariable Cox analysis, a high level of serum IL-6 (HR 1.007, 95% CI: 1.001-1.014, p = 0.018) was only an independent risk factor for mortality in ILD patients. CONCLUSIONS: In our study, a high level of serum IL-6 is a useful biomarker to predict AE and poor prognosis in patients with ILD.

Prognostic Factors of Second-line Immune Checkpoint Inhibitors in Patients With Advanced-stage Non-Small Cell Lung Cancer: A Multicenter, Retrospective Study.

OBJECTIVES: Immune checkpoint inhibitors (ICIs) targeting the programmed cell death receptor-1 and its ligand have achieved impressive success in treating patients with advanced-stage non-small cell lung cancer (NSCLC) after failed first-line cytotoxic chemotherapy. However, knowledge on clinical biomarkers that could help select patients who will respond well to second-line ICI therapy is limited. PATIENTS AND METHODS: Medical records of patients with NSCLC treated with first-line platinum-based chemotherapy and subsequent second-line ICI were collected from 6 medical centers between January 2018 and June 2020. Clinical information, pathologic variables, and radiologic findings of the data collected were reviewed. The patients were followed up until the date of the last visit, the death of any cause, or the end of data recording (December 31, 2020). RESULTS: A total of 181 patients with NSCLC were treated with second-line ICI following first-line platinum-based doublet chemotherapy. The median progression-free survival was 2.0 months (interquartile range, 1.0 to 5.5 mo), and the median overall survival was 12.0 months (interquartile range, 6.0 to 20.0 mo). Low body mass index (BMI) was independently associated with progression-free survival (odds ratio [OR], 0.826; 95% confidence interval [CI], 0.723-0.945; P=0.005). Similarly, a low BMI (OR, 0.839; 95% CI, 0.740-0.952; P=0.005) and a high number of metastatic organs (OR, 1.682; 95% CI, 1.156-2.448; P=0.007) were independently associated with the overall survival after second-line ICI therapy. CONCLUSION: BMI and the number of metastatic sites were significantly associated with second-line ICI therapy outcomes in patients with NSCLC receiving first-line platinum-based chemotherapy.

Practical guidance for P2Y12 inhibitors in acute myocardial infarction undergoing percutaneous coronary intervention.

AIMS: Potent P2Y12 inhibitors for dual antiplatelet therapy (DAPT) is crucial for managing acute myocardial infarction; however, the selection of drugs is based on limited clinical information such as age and body weight. The current study sought to develop and validate a new risk scoring system that can be used to guide the selection of potent P2Y12 inhibitors by balancing ischaemic benefit and bleeding risk. METHODS AND RESULTS: Derivation cohort of 10 687 patients who participated in the Korea Acute Myocardial Infarction Registry-National Institutes of Health study was used to construct a new scoring system. We combined the ischaemic and bleeding models to establish a simple clinical prediction score. Among the low score group (n = 1764), the observed bleeding risk (8.7% vs. 4.4%, P < 0.001) due to potent P2Y12 inhibitors exceeded ischaemic benefit (1.3% vs. 2.2%, P = 0.185) during 12 months. Conversely, the high score group (n = 1898) showed an overall benefit from taking potent P2Y12 inhibitors from the standpoint of observed ischaemic (17.1% vs. 8.6%, P < 0.001) and bleeding events (10.1% vs. 6.8%, P = 0.073). The performance of ischaemic [integrated area under the curve (iAUC) = 0.809] and bleeding model (iAUC = 0.655) was deemed to be acceptable. CONCLUSION: The new scoring system is a useful clinical tool for guiding DAPT by balancing ischaemic benefit and bleeding risk, especially among Asian populations. Further validation studies with other cohorts will be required to verify that the new system meets the needs of real clinical practice.

Unilateral pleuroparenchymal fibroelastosis as a rare form of idiopathic interstitial pneumonia: A case report.

BACKGROUND: Pleuroparenchymal fibroelastosis (PPFE) is a rare idiopathic interstitial pneumonia characterized by predominantly upper lobe involvement with pleural fibrosis and subjacent parenchymal fibrosis. Recently, there have been increasing reports of PPFE, and PPFE might coexist with other interstitial lung diseases in the lower lobe and upper lobe. However, cases of unilateral PPFE are scarce. CASE SUMMARY: A 75-year-old Korean male presented to our hospital with chronic dry cough and exertional dyspnea. The patient's symptoms started 6 mo previously and had been gradually worsening. At the time of presentation, he felt dyspnea when walking at his own pace. Radiologic findings suggested PPFE, but the lesion was localized in the upper lobe of the right lung. After multidisciplinary discussion, a transbronchial lung biopsy in the right upper lobe revealed collapsed alveoli with parenchymal fibroelastosis, and elastic van Gieson staining demonstrated septal elastosis with intra-alveolar collagenosis, which met the histopathologic criteria of definite PPFE. After multidisciplinary discussion in an experienced interstitial lung disease center, we confirmed the diagnosis of unilateral PPFE. Furthermore, we confirmed the progression of PPFE on radiologic findings during the follow-up period. CONCLUSION: Clinicians should consider PPFE, even in cases with unilateral, predominantly upper lung involvement in interstitial lung disease patients through multidisciplinary discussion.

KMBARC registry: protocol for a multicentre observational cohort study on non-cystic fibrosis bronchiectasis in Korea.

INTRODUCTION: Despite the significant disease burden of bronchiectasis in Korea, no large-scale, representative prospective cohort studies have been conducted to evaluate the clinical characteristics of Korean patients with bronchiectasis, indicating an urgent need for cohort studies on bronchiectasis. METHODS AND ANALYSIS: The Korean Multicenter Bronchiectasis Audit and Research Collaboration (KMBARC) is a prospective, non-interventional observational cohort study on bronchiectasis in Korea. The inclusion criteria of this registry are as follows: (1) adult patients (aged ≥18 years) with or without respiratory symptoms (cough, chronic sputum and/or recurrent respiratory infection) and chest computed tomography revealing bronchiectasis affecting one or more lobes and (2) stable status at the time of registration: patients with bronchiectasis who were admitted for a respiratory aetiology can be enrolled at least 4 weeks after hospital discharge. The exclusion criteria are as follows: (1) bronchiectasis due to cystic fibrosis; (2) traction bronchiectasis associated with interstitial lung disease; (3) patients actively being treated for pneumonia, pulmonary tuberculosis or non-tuberculous mycobacterial infection; (4) patients who are unable or unwilling to provide informed consent; and (5) pregnant patients. Although the KMBARC questionnaires for baseline and annual follow-up data are similar to the European Multicentre Bronchiectasis Audit and Research Collaboration questionnaires, KMBARC has distinctive features such as use of Bronchiectasis Health Questionnaires, measurement with fatigue and depression scales, blood tests, use of consensus definition of exacerbations and information on emergency room or hospitalisation.We aim to recruit at least 1200 patients over the study period from more than 26 hospitals in South Korea. Patients will undergo a detailed baseline and yearly assessment for up to 5 years. The study objectives of the KMBARC registry are as follows: (1) uncovering the natural course of bronchiectasis; (2) aiding in establishing evidence-based bronchiectasis guidelines in Korea; and (3) encouraging and facilitating studies on bronchiectasis in Korea. ETHICS AND DISSEMINATION: This study received necessary approval from the Institutional Review Boards of all participating institutions. The Asan Medical Center Institutional Review Board gave overall approval for the study. Results will be disseminated via peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: KCT0003088.

Diagnostic Agreement of Quantitative Flow Ratio With Fractional Flow Reserve and Instantaneous Wave-Free Ratio.

Background Quantitative flow ratio ( QFR ) has a high diagnostic accuracy in assessing functional stenoses relevance, as judged by fractional flow reserve ( FFR ). However, its diagnostic performance has not been thoroughly evaluated using instantaneous wave-free ratio ( iFR ) or coronary flow reserve as the reference standard. This study sought to evaluate the diagnostic performance of QFR using other reference standards beyond FFR . Methods and Results We analyzed 182 patients (253 vessels) with stable ischemic heart disease and 82 patients (105 nonculprit vessels) with acute myocardial infarction in whom coronary stenoses were assessed with FFR , iFR, and coronary flow reserve. Contrast QFR analysis of interrogated vessels was performed in blinded fashion by a core laboratory, and its diagnostic performance was evaluated with respect to the other invasive physiological indices. Mean percentage diameter stenosis, FFR , iFR , coronary flow reserve, and QFR were 53.1±19.0%, 0.80±0.13, 0.88±0.12, 3.14±1.30, and 0.81±0.14, respectively. QFR showed higher correlation ( r=0.863 with FFR versus 0.740 with iFR , P<0.001), diagnostic accuracy (90.8% versus 81.3%, P<0.001), and discriminant function (area under the curve=0.953 versus 0.880, P<0.001) when FFR was used as a reference standard than when iFR was used as the reference standard. However, when coronary flow reserve was used as an independent reference standard, FFR , iFR , and QFR showed modest discriminant function (area under the curve=0.682, 0.765, and 0.677, respectively) and there were no significant differences in diagnostic accuracy among FFR , iFR , and QFR (65.4%, 70.6%, and 64.9%; all P values in pairwise comparisons >0.05, overall comparison P=0.061). Conclusions QFR has a high correlation and agreement with respect to both FFR and iFR , although it is better when FFR is used as the comparator. As a pressure-derived index not depending on wire or adenosine, QFR might be a promising tool for improving the adoption rate of physiology-based revascularization in clinical practice.

Potential Therapeutic Strategy in Chronic Obstructive Pulmonary Disease Using Pioglitazone-Augmented Wharton's Jelly-Derived Mesenchymal Stem Cells.

BACKGROUND: A recent study reported that mesenchymal stem cells possess potential cellular therapeutic properties for treating patients with chronic obstructive pulmonary disease, which is characterized by emphysema. We examined the potential therapeutic effect of Wharton's Jelly-derived mesenchymal stem cells (WJMSCs), following pretreatment with pioglitazone, in lung regeneration mouse emphysema models. METHODS: We used two mouse emphysema models, an elastase-induced model and a cigarette smoke-induced model. We intravenously injected WJMSCs (1×104/mouse) to mice, pretreated or not, with pioglitazone for 7 days. We measured the emphysema severity by mean linear intercepts (MLI) analysis using lung histology. RESULTS: Pioglitazone pretreated WJMSCs (pioWJMSCs) were associated with greater lung regeneration than non-augmented WJMSCs in the two mouse emphysema models. In the elastase-induced emphysema model, the MLIs were 59.02±2.42 µm (n=6), 72.80±2.87 µm (n=6), for pioWJMSCs injected mice, and non-augmented WJMSCs injected mice, respectively (p<0.01). Both pioWJMSCs and non-augmented WJMSCs showed regenerative effects in the cigarette smoke emphysema model (MLIs were 41.25±0.98 [n=6] for WJMSCs and38.97±0.61 µm [n=6] for pioWJMSCs) compared to smoking control mice (51.65±1.36 µm, n=6). The mean improvement of MLI appeared numerically better in pioWJMSCs than in non-augmented WJMSCs injected mice, but the difference did not reach the level of statistical significance (p=0.071). CONCLUSION: PioWJMSCs may produce greater lung regeneration, compared to non-augmented WJMSCs, in a mouse emphysema model.

Masked inherited primary arrhythmia syndromes in sudden cardiac death patients accompanied by coronary vasospasm.

BACKGROUND/AIMS: Coronary vasospasms are one of the important causes of sudden cardiac death (SCD). Provocation of coronary vasospasms can be useful, though some results may lead to false positives, with patients potentially experiencing recurrent SCD despite appropriate medical treatments. We hypothesized that it is not coronary vasospasms but inherited primary arrhythmia syndromes (IPAS) that underlie the development of SCD. METHODS: We analyzed 74 consecutive patients (3.8%) who survived out-of-hospital cardiac arrest among 1,986 patients who had angiographically proven coronary vasospasms. Electrical abnormalities were evaluated in serial follow-up electrocardiograms (ECGs) during and after the index event for a 3.9 years median follow-up. Major clinical events were defined as the composite of death and recurrent SCD events. RESULTS: Forty five patients (60.8%) displayed electrocardiographic abnormalities suggesting IPAS: Brugada type patterns in six (8.2%), arrhythmogenic right ventricular dysplasia patterns in three (4.1%), long QT syndrome pattern in one (2.2%), and early repolarization in 38 (51.4%). Patients having major clinical events showed more frequent Brugada type patterns, early repolarization, and more diffuse multivessel coronary vasospasms. Brugada type pattern ECGs (adjusted hazard ratio [HR], 4.22; 95% confidence interval [CI], 1.16 to 15.99; p = 0.034), and early repolarization (HR, 2.97; 95% CI, 1.09 to 8.10; p = 0.034) were ultimately associated with an increased risk of mortality. CONCLUSIONS: Even though a number of aborted SCD survivors have coronary vasospasms, some also have IPAS, which has the potential to cause SCD. Therefore, meticulous evaluations and follow-ups for IPAS are required in those patients.

Effects of ticagrelor on neointimal hyperplasia and endothelial function, compared with clopidogrel and prasugrel, in a porcine coronary stent restenosis model.

BACKGROUND: Several investigations have been conducted to evaluate the off-target effects of ticagrelor. The aim of the present study was to evaluate the off-target effects of ticagrelor such as neointimal formation and endothelial function after drug-eluting stent implantation in a porcine restenosis model. METHODS: A total of 30 pigs were randomly allocated based on the following P2Y12 inhibitor: (1) clopidogrel 300mg loading plus 75mg maintenance (n=10); (2) prasugrel 60mg loading plus 10mg maintenance (n=10); (3) ticagrelor 180mg loading plus 180mg maintenance (n=10). In each group, zotarolimus-eluting stents were implanted in the proximal portion of the left anterior descending artery and left circumflex artery. One month after stenting, the animals underwent follow-up angiography, endothelial function assessment, optical coherence tomography (OCT) and histopathological analysis. RESULTS: Regarding vasomotor responses to acetylcholine infusion, there were significant vasoconstrictions to maximal acetylcholine infusion in the clopidogrel and prasugrel group compared with those in the ticagrelor group. The mean neointimal area were significantly lower in the ticagrelor group (1.0±0.3 by OCT, 0.9±0.3 by histology), than in the clopidogrel (1.8±0.7, p=0.003, 1.6±0.8, p=0.030) and prasugrel (1.8±0.5, p=0.001, 1.5±0.5, p=0.019) groups. Percentages of moderate to dense peri-strut inflammatory cell infiltration were significantly lower in the ticagrelor group (9.0%) compared with the clopidogrel (17.3%, p<0.001) and prasugrel groups (15.7%, p=0.002). There were no significant differences in all findings between clopidogrel and prasugrel groups. CONCLUSIONS: Compared to clopidogrel and prasugrel, ticagrelor reduced neointimal formation, endothelial dysfunction, and peri-strut inflammation.

Tracheal Involvement in Crohn Disease: the First Case in Korea.

Respiratory involvement in Crohn disease (CD) is rare condition with only about a dozen reported cases. We report the first case of CD with tracheal involvement in Korea. An 18-year-old woman with CD was hospitalized because of coughing, dyspnea, and fever sustained for 3 weeks. Because she had stridor in her neck, we performed computed tomography of the neck, which showed circumferential wall thickening of the larynx and hypopharynx. Bronchoscopy revealed mucosal irregularity, ulceration, and exudates debris in the proximal trachea, and bronchial biopsy revealed chronic inflammation with granulation tissue. Based on these findings, we suspected CD with tracheal involvement and began administering intravenous methylprednisolone at 1 mg/kg per day, after which her symptoms and bronchoscopic findings improved.

Modified one-day etoposide and cisplatin combination for previously untreated extensive-disease small-cell lung cancer: A retrospective evaluation of 36 cases.

The combination of etoposide and cisplatin (EP) remains one of the standard first-line treatments for extensive-disease small-cell lung cancer (ED-SCLC) We devised a one-day modified EP regimen for better tolerance and convenience by modifying the dose and schedule of conventional EP with administration over 3-5 consecutive days. The modified EP consists of two infusions of etoposide (120 mg/m2 each) and 60 mg/m2 of cisplatin on day 1 of a 21-day cycle and a maximum of 6 cycles of treatment. A total of 36 consecutive ED-SCLC patients were treated with the modified EP as first-line therapy and retrospectively reviewed to assess the efficacy and safety of this regimen. Of the 36 patients, 24 exhibited confirmed objective tumor response (overall response rate of 66%, with a complete response rate of 3% and a partial response rate of 63%). The median overall survival (OS) was 11.8 months [95% confidence interval (CI): 7.9-15.3] and the progression-free survival (PFS) was 7.3 months (95% CI: 5.2-9.7). The survival estimates at 1 year were 35 and 17% for OS and PFS, respectively. The chemotherapy treatment was well tolerated, with only one case of grade 4 non-hematological adverse events, no grade 4 hematological toxicities and no treatment-related deaths. The mean relative dose intensity of etoposide and cisplatin was measured to be 94.7 and 98.5% of the planned dose, respectively. Therefore, the modified EP warrants further clinical research regarding its effectiveness, toxicity profile and convenience of administration. Prospective randomized clinical trials are required to determine the therapeutic role of the modified EP as first-line treatment in patients with ED-SCLC.

Predictors of Plaque Progression in Hypertensive Angina Patients with Achieved Low-Density Lipoprotein Cholesterol Less Than 70 mg/dL after Rosuvastatin Treatment.

We evaluated the impact of achieved low-density lipoprotein cholesterol (LDL-C) concentrations <70 mg/dL on plaque progression in statin-treated hypertensive angina patients by use of virtual histology-intravascular ultrasound (VH-IVUS). The effects of 10 mg of rosuvastatin on plaque progression were evaluated in 78 patients who achieved LDL-C <70 mg/dL with statin treatment. The patients were divided into plaque progressors (n=30) and plaque regressors (n=40) on the basis of the baseline minimum lumen area (MLA) site at the 9-month follow-up. The prevalence of chronic kidney disease (CKD) [creatinine clearance (CrCl) <60 mL/min)] and current smoking was higher in progressors than in regressors (90.0% vs. 31.3%, p<0.001, and 40.0% vs. 12.5%, p=0.005, respectively). Baseline CrCl was significantly lower and baseline apolipoprotein (apo) B/A1 was significantly higher in progressors than in regressors (21±13 mL/min vs. 70±20 mL/min, p<0.001, and 0.77±0.23 vs. 0.65±0.16, p=0.011, respectively). Absolute and relative fibrotic areas at the MLA site increased in progressors; by contrast, these areas decreased in regressors from baseline to follow-up. CKD [odds ratio (OR): 2.13, 95% confidence interval (CI): 1.77-2.53, p=0.013], smoking (OR: 1.76, 95% CI: 1.23-2.22, p=0.038), and apoB/A1 (OR: 1.25, 95% CI: 1.12-1.40, p=0.023), but not any VH-IVUS parameters, were independent predictors of plaque progression at follow-up. In conclusion, clinical factors including CKD, smoking, and apoB/A1 rather than plaque components detected by VH-IVUS are associated with plaque progression in hypertensive angina patients who achieve very low LDL-C after statin treatment.

Stanford type A aortic dissection secondary to infectious aortitis: a case report.

Nowadays, infectious aortitis has become a rare disease thanks to antibiotics, but remains life-threatening. We present a case of a patient with acupuncture-induced infectious aortitis leading to aortic dissection. Chest computed-tomogram scan revealed Stanford type A dissection with pericardial effusion. Under the impression of an impending rupture, emergent surgery was performed. During surgery, infectious aortitis was identified incidentally, so she underwent resection of the infected aorta including surrounding tissues. Then the ascending aorta and hemi-arch were replaced with a prosthetic graft as an in situ fashion. The resected tissue and blood cultures revealed Staphylococcus aureus, so prolonged antibiotherapy was prescribed.