Fetuin as a potential serum biomarker to detect subclinical shedder of bovine paratuberculosis.

Paratuberculosis (PTB) is a chronic contagious granulomatous enteritis of wild and domestic ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP). PTB causes considerable economic losses to the dairy industry through decreased milk production and premature culling. PTB-affected cattle undergo a subclinical stage without clinical signs and initiate fecal shedding of MAP into the environment. Current diagnostic tools have low sensitivity for the detection of subclinical PTB infection. Therefore, alternative diagnostic tools are required to improve the diagnostic sensitivity of subclinical PTB infection. In this study, we performed ELISA for three previously identified host biomarkers (fetuin, alpha-1-acid glycoprotein, and apolipoprotein) and analyzed their diagnostic performance with conventional PTB diagnostic methods. We observed that serum fetuin levels were significantly lowered in the subclinical shedder and clinical shedder groups than in the healthy control group, indicating its potential utility as a diagnostic biomarker for bovine PTB. Also, fetuin showed an excellent discriminatory power with an AUC = 0.949, a sensitivity of 92.6%, and a specificity of 94.4% for the detection of subclinical MAP infection. In conclusion, our results demonstrated that fetuin could be used as a diagnostic biomarker for enhancing the diagnostic sensitivity for the detection of subclinical MAP infections that are difficult to detect based on current diagnostic methods.

Beneficial Effect of Left Ventricular Remodeling after Early Change of Sacubitril/Valsartan in Patients with Nonischemic Dilated Cardiomyopathy.

Background and Objectives: Evidence for effectiveness of early change from angiotensin II receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors (ACEIs) to sacubitril/valsartan is lacking. We aimed to investigate whether early changes to sacubitril/valsartan could improve outcomes in patients with nonischemic dilated cardiomyopathy (DCM) in real-world practice. Materials and Methods: A total of 296 patients with nonischemic DCM who were treated with ARB or ACEI continuously (group A, n = 150) or had their medication switched to sacubitril/valsartan (group S, n = 146) were included. The sacubitril/valsartan group was divided into early change (within 60 days, group S/E, n = 59) and late change (group S/L, n = 87) groups. Changes in echocardiographic parameters from the time of initial diagnosis to the last follow-up were analyzed. Results: Patients in group S showed greater left ventricular (LV) end-diastolic dimension (EDD) (group A vs. S, 61.7 ± 7.4 vs. 66.5 ± 8.0, p < 0.001) and lower LV ejection fraction (LVEF) (28.9 ± 8.2% vs. 23.9 ± 7.5%, p < 0.001) than those in group A at initial diagnosis. During a median follow-up of 76 months, patients in group S/E, ∆ LVEF (%) and ∆ LVESD (mm) were significantly improved compared with those in patients in group A (group A vs. S/E, ∆ LVEF, p = 0.036; ∆ LVESD, p = 0.023) or S/L (group S/E vs. S/L, ∆ LVEF, p = 0.05; ∆ LVESD, p = 0.005). Among patients whose medications were switched to sacubitril/valsartan, those with an earlier change showed a significant correlation with greater LVEF improvement (r = -0.367, p < 0.001) and LV reverse remodeling (r = 0.277, p < 0.001). Conclusions: in patients with nonischemic DCM, an early switch to sacubitril/valsartan was associated with greater improvement in LV function. Patients might benefit in terms of LV function by early switching to sacubitril/valsartan.

Identification of Nontuberculous Mycobacteria in Patients with Pulmonary Diseases in Gyeongnam, Korea, Using Multiplex PCR and Multigene Sequence-Based Analysis.

BACKGROUND: Nontuberculous mycobacteria (NTM) are widely present in environments, such as soil and water, and have recently been recognized as important pathogenic bacteria. The incidence of NTM-related infections is steadily increasing. As the diagnosis and treatment of NTM infection should be distinguished from tuberculosis, and the treatment should be specific to the species of NTM acquired, accurate species identification is required. METHODS: In this study, two-step multiplex PCR (mPCR) and multigene sequence-based analysis were used to accurately identify NTM species in 320 clinical isolates from Gyeongsang National University Hospital (GNUH). In particular, major mycobacterial strains with a high isolation frequency as well as coinfections with multiple species were diagnosed through two-step mPCR. Multigene sequencing was performed to accurately identify other NTM species not detected by mPCR. Variable regions of the genes 16S rRNA, rpoB, hsp65, and 16S-23S rRNA internal transcribed spacer were included in the analysis. RESULTS: Two-step mPCR identified 234 (73.1%) cases of M. intracellulare, 26 (8.1%) cases of M. avium subsp. avium, and 13 (4.1%) cases of M. avium subsp. hominissuis infection. Additionally, 9 (2.8%) M. fortuitum, 9 (2.8%) M. massiliense, 2 (0.6%) M. abscessus, and 4 (1.2%) M. kansasii isolates were identified. Coinfection was identified in 7 (2.2%) samples. The sixteen samples not classified by two-step mPCR included 6 (1.9%) cases of M. chimaera, 4 (1.3%) M. gordonae, 1 (0.3%) M. colombiense, 1 (0.3%) M. mageritense, and 1 (0.3%) M. persicum identified by sequence analysis. CONCLUSIONS: The results of this study suggest a strategy for rapid detection and accurate identification of species using two-step mPCR and multigene sequence-based analysis. To the best of our knowledge, this study is the first to report the identification of NTM species isolated from patients in Gyeongnam/Korea.

Helicobacter pylori Antigens Inducing Early Immune Response in Infants.

To identify the Helicobacter pylori antigens operating during early infection in sera from infected infants using proteomics and immunoblot analysis. Two-dimensional (2D) large and small gel electrophoresis was performed using H. pylori strain 51. We performed 2D immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM) antibody immunoblotting using small gels on sera collected at the Gyeongsang National University Hospital from 4-11-month-old infants confirmed with H. pylori infection by pre-embedding immunoelectron microscopy. Immunoblot spots appearing to represent early infection markers in infant sera were compared to those of the large 2D gel for H. pylori strain 51. Corresponding spots were analyzed by matrix-assisted laser desorption/ionization time of flight-mass spectrometry (MALDI-TOF-MS). The peptide fingerprints obtained were searched in the National Center for Biotechnology Information (NCBI) database. Eight infant patients were confirmed with H. pylori infection based on urease tests, histopathologic examinations, and pre-embedding immunoelectron microscopy. One infant showed a 2D IgM immunoblot pattern that seemed to represent early infection. Immunoblot spots were compared with those from whole-cell extracts of H. pylori strain 51 and 18 spots were excised, digested in gel, and analyzed by MALDI-TOF-MS. Of the 10 peptide fingerprints obtained, the H. pylori proteins flagellin A (FlaA), urease ß subunit (UreB), pyruvate ferredoxin oxidoreductase (POR), and translation elongation factor Ts (EF-Ts) were identified and appeared to be active during the early infection periods. These results might aid identification of serological markers for the serodiagnosis of early H. pylori infection in infants.

Surgical Trends of Shoulder Arthroplasty: Nationwide Epidemiologic Study in South Korea.

Background: The aim of this study was to determine the nationwide shoulder arthroplasty trends in South Korea based on an analysis of nationwide data acquired from the Korean Health Insurance Review and Assessment Service (HIRA). Methods: We analyzed a nationwide database acquired from the HIRA that covered 2008 to 2017. International Classification of Diseases, 10th Revision (ICD-10) codes and procedure codes were used to identify patients who underwent shoulder arthroplasty, including total shoulder arthroplasty (TSA), hemiarthroplasty (HA), and revision shoulder arthroplasty. Results: From 2008 to 2017, a total of 19,831 shoulder arthroplasties were performed; there were 16,162 TSAs and 3,669 hemiarthroplasties. During the 10-year study period, there was an exponential increase in the incidence of TSA (from 513 cases in 2008 to 3,583 cases in 2017), while the number of hemiarthroplasties remained steady. The most common diagnoses for TSA were rotator cuff tears (6,304 cases, 39.0%) and osteoarthritis (6,589 cases, 40.8%) for all 9 years. Osteoarthritis was the most common reason for TSA during the first 3 years (2008-2010), but rotator cuff tears ultimately surpassed osteoarthritis during the last 3 years (2015-2017). HA was performed to treat proximal humerus fracture (1,770 cases, 48.2%) and osteoarthritis (774 cases, 21.1%). In terms of hospital types, the rate of TSA in hospitals with 30-100 inpatient beds increased from 21.83% to 46.27%, while the rates of the other types of surgery decreased. A total of 430 revision surgeries were performed during the study period, and infection (152 cases, 35.3%) was the most common reason for revision surgery. Conclusions: Overall, the total count and incidence of TSA, unlike HA, increased rapidly between 2008 and 2017 in South Korea. Moreover, at the end of the study period, nearly half of the TSAs were performed in small hospitals (30 to 100 beds). Rotator cuff tears were the leading cause of TSA at the end of the study period. These findings revealed an explosive increase in reverse TSA surgery.

A novel repeat sequence-based PCR (rep-PCR) using specific repeat sequences of Mycobacterium intracellulare as a DNA fingerprinting.

Repetitive sequence-based PCR (rep-PCR) is a potential epidemiological technique that can provide high-throughput genotype fingerprints of heterogeneous Mycobacterium strains rapidly. Previously published rep-PCR primers, which are based on nucleotide sequences of Gram-negative bacteria may have low specificity for mycobacteria. Moreover, it was difficult to ensure the continuity of the study after the commercial rep-PCR kit was discontinued. Here, we designed a novel rep-PCR for Mycobacterium intracellulare, a major cause of nontuberculous mycobacterial pulmonary disease with frequent recurrence. We screened the 7,645 repeat sequences for 200 fragments from the genome of M. intracellulare ATCC 13950 in silico, finally generating five primers with more than 90% identity for a total of 226 loci in the genome. The five primers could make different band patterns depending on the genome of three different M. intracellulare strains using an in silico test. The novel rep-PCR with the five primers was conducted using 34 bacterial samples of 7 species containing 25 M. intracellulare clinical isolates, compared with previous published rep-PCRs. This shows distinguished patterns depending on species and blotting assay for 6 species implied the sequence specificity of the five primers. The Designed rep-PCR had a 95-98% of similarity value in the reproducibility test and showed 7 groups of fingerprints in M. intracellulare strains. Designed rep-PCR had a correlation value of 0.814 with VNTR, reference epidemiological method. This study provides a promising genotype fingerprinting method for tracing the recurrence of heterogeneous M. intracellulare.

Antigenic Determinant of Helicobacter pylori FlaA for Developing Serological Diagnostic Methods in Children.

The early diagnosis of Helicobacter pylori infection is important for gastric cancer prevention and treatment. Although endoscopic biopsy is widely used for H. pylori diagnosis, an accurate biopsy cannot be performed until a lesion becomes clear, especially in pediatric patients. Therefore, it is necessary to develop convenient and accurate methods for early diagnosis. FlaA, an essential factor for H. pylori survival, shows high antigenicity and can be used as a diagnostic marker. We attempted to identify effective antigens containing epitopes of high diagnostic value in FlaA. Full-sized FlaA was divided into several fragments and cloned, and its antigenicity was investigated using Western blotting. The FlaA fragment of 1345-1395 bp had strong immunogenicity. ELISA was performed with serum samples from children by using the 1345-1395 bp recombinant antigen fragment. IgG reactivity showed 90.0% sensitivity and 90.5% specificity, and IgM reactivity showed 100% sensitivity and specificity. The FlaA fragment of 1345-1395 bp discovered in the present study has antigenicity and is of high value as a candidate antigen for serological diagnosis. The FlaA 1345-1395 bp epitope can be used as a diagnostic marker for H. pylori infection, thereby controlling various gastric diseases such as gastric cancer and peptic ulcers caused by H. pylori.

Alpha-2-Macroglobulin as a New Promising Biomarker Improving the Diagnostic Sensitivity of Bovine Paratuberculosis.

Johne's disease (JD) is a chronic granulomatous enteritis of ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP), which induces persistent diarrhea and cachexia. JD causes huge economic losses to the dairy industry due to reduced milk production and premature culling. Infected animals excrete MAP via feces during the prolonged subclinical stage without exhibiting any clinical signs. Therefore, accurate detection of subclinical stage animals is crucial for successful eradication of JD in the herd. In the current study, we analyzed serum samples of MAP-infected and non-infected cattle to identify potential biomarker candidates. First, we identified 12 differentially expressed serum proteins in subclinical and clinical shedder groups compared to the healthy control group. Second, we conducted ELISA for three selected biomarkers (alpha-2-macroglobulin (A2M), alpha-1-beta glycoprotein, and transthyretin) and compared their diagnostic performance with that of two commercial ELISA diagnostic kits. Serum A2M levels were significantly higher in the MAP-exposed, subclinical shedder, subclinical non-shedder, and clinical shedder groups than in the healthy control group, suggesting its possible use as a diagnostic biomarker for MAP infection. Furthermore, A2M demonstrated a sensitivity of 90.4%, and a specificity of 100% while the two commercial ELISA kits demonstrated a sensitivity of 67.83 and 73.04% and a specificity of 100%, respectively. In conclusion, our results suggest that measuring A2M by ELISA can be used as a diagnostic tool to detect MAP infection, considerably improving the detection rate of subclinical shedders and MAP-exposed animals that are undetectable using current diagnostic tools.

Increased Risk of Severe Gastric Symptoms by Virulence Factors vacAs1c, alpA, babA2, and hopZ in Helicobacter pylori Infection.

Two virulence factors of Helicobacter pylori, cagA and vacA, have been known to play a role in the development of severe gastric symptoms. However, they are not always associated with peptic ulcer or gastric cancer. To predict the disease outcome more accurately, it is necessary to understand the risk of severe symptoms linked to other virulence factors. Several other virulence factors of H. pylori have also been reported to be associated with disease outcomes, although there are many controversial descriptions. H. pylori isolates from Koreans may be useful in evaluating the relevance of other virulence factors to clinical symptoms of gastric diseases because the majority of Koreans are infected by toxigenic strains of H. pylori bearing cagA and vacA. In this study, a total of 116 H. pylori strains from Korean patients with chronic gastritis, peptic ulcers, and gastric cancers were genotyped. The presence of virulence factors vacAs1c, alpA, babA2, hopZ, and the extremely strong vacuolating toxin was found to contribute significantly to the development of severe gastric symptoms. The genotype combination vacAs1c/alpA/babA2 was the most predictable determinant for the development of severe symptoms, and the presence of babA2 was found to be the most critical factor. This study provides important information on the virulence factors that contribute to the development of severe gastric symptoms and will assist in predicting clinical disease outcomes due to H. pylori infection.

Differential clinical impact of chronic total occlusion revascularization based on left ventricular systolic function.

BACKGROUND: The effect of chronic total occlusion (CTO) revascularization on survival remains controversial. Furthermore, data regarding outcome differences for CTO revascularization based on left ventricular systolic function (LVSF) are limited. The differential outcomes from CTO revascularization in patients with preserved LVSF (PLVSF) versus reduced LVSF (RLVSF) were assessed. METHODS: A total of 2,173 CTO patients were divided into either a PLVSF (n = 1661, Ejection fraction ≥ 50%) or RLVSF (n = 512, < 50%) group. Clinical outcomes were compared between successful CTO revascularization (SCR) versus optimal medical therapy (OMT) within each group. The primary endpoint was a composite of all-cause death or non-fatal myocardial infarction. Inverse probability of treatment weighting for endpoint analysis and a contrast test for comparison of survival probability differences according to LVSF were used. RESULTS: Patients with RLVSF had a mean 37% ejection fraction (EF) and 19% had EF < 30%. The median follow-up duration was 1,138 days. Regardless of LVSF, the primary endpoint incidence was significantly lower in patients treated with SCR [RLVSF: 29.7% vs. 49.7%, hazard ratio (HR) = 0.46, 95% confidence interval (CI): 0.36-0.62, p < 0.0001; PLVSF 7.3% vs. 16.9%, HR = 0.68, 95% CI: 0.54-0.93, p = 0.0019], which was mainly driven by a reduction in cardiac death. The difference in survival probability was greater and became more pronounced over time in patients with RLVSF than with PLVSF (1-year, p = 0.197; 3-years, p = 0.048; 5-years, p = 0.036). CONCLUSIONS: SCR was associated with better survival benefit than OMT regardless of LVSF. The benefit was greater and became more significant over time in patients with RLVSF versus PLVSF.

Periodic variation and its effect on management and prognosis of Korean patients with acute myocardial infarction.

BACKGROUND: The characteristics of the periodic variation in acute myocardial infarction (AMI) and the subsequent effect on management and prognosis have not been fully investigated in a large number of Asian populations. METHODS AND RESULTS: From a prospective, observational multicenter online registry, 4,573 patients diagnosed as AMI in Korea from January to December 2006 were included. The highest incidence of AMI was between 8 a.m. and noon. The number of cases was highest in the winter and lowest in the autumn (13.6 vs 11.4 patients per day, P<0.001). Patients with symptom onset during working hours had a shorter time to first medical contact (203+/-288 min) compared with out-of-hours onset (230+/-288 min, P=0.003). In patients who underwent primary angioplasty, out-of hours symptom onset was associated with a greater time delay in both the patient's and the medical facility's response (door-to-balloon time out-of hours vs working hours: 101+/-54 min vs 84+/-44 min, P<0.001). In patients with ST-segment elevation myocardial infarction, symptoms to first medical contact showed a significant relationship to in-hospital mortality (for every 10 min of symptoms to first medical contact, odds ratio 1.006, 95% confidence interval 1.001-1.012, P=0.018) CONCLUSIONS: Circadian and periodic variation in AMI exists in Korean patients, which resulted in different patient behavior, hospital management and outcomes.

Complications of veno-arterial extracorporeal membrane oxygenation for refractory cardiogenic shock or cardiac arrest.

BACKGROUND: The frequency of using veno-arterial extracorporeal membrane oxygenation increased, especially in patients with refractory cardiogenic shock or cardiac arrest. However, data of complications of veno-arterial extracorporeal membrane oxygenation are lacking. This study sought to investigate the incidence of veno-arterial extracorporeal membrane oxygenation complications for acute myocardial infarction patients with refractory cardiogenic shock or cardiac arrest and its relationship with patient survival. METHODS: This study included 151 consecutive patients who underwent veno-arterial extracorporeal membrane oxygenation between 2006 and 2018 at a single referral center. We divided the patients into those who survived for 30 days after veno-arterial extracorporeal membrane oxygenation (n = 57, 38%; group 1) and those who died within 30 days after veno-arterial extracorporeal membrane oxygenation support (n = 94, 62%; group 2). The major adverse clinical events associated with veno-arterial extracorporeal membrane oxygenation were defined as first occurrence of infection, major bleeding, and stroke. RESULTS: Adverse clinical events associated with veno-arterial extracorporeal membrane oxygenation occurred in 34 (59.6%) and 56 (59.6%) patients in groups 1 and 2, respectively. Group 2 had more patients who underwent new renal replacement therapy (21.1% vs 37.2%, p = 0.037). After multivariable analysis, cardiac arrest was independently associated with 30-day mortality (odds ratio = 3.6; 95% confidence interval = 1.7-7.63; p = 0.001). After excluding patients who died within 48 h after undergoing veno-arterial extracorporeal membrane oxygenation, new renal replacement therapy (odds ratio = 4.47; 95% confidence interval = 1.58-12.61; p = 0.005) and major adverse clinical events (odds ratio = 2.66; 95% confidence interval = 1.01-7.03; p = 0.049) were independently associated with 30-day mortality. CONCLUSION: Although veno-arterial extracorporeal membrane oxygenation can improve the survival, it is associated with morbidity. Therefore, risk-benefit analysis for veno-arterial extracorporeal membrane oxygenation and prevention of complications are important to improve prognosis.

Efficacy and tolerability of two formulations of ramipril in Korean adults with mild to moderate essential hypertension: an 8-week, multicenter, prospective, randomized, open-label, parallel-group noninferiority trial.

OBJECTIVE: This study was designed to compare the efficacy and tolerability of a new generic formulation of ramipril (test) and the branded formulation of ramipril (reference) to satisfy regulatory requirements for marketing of the generic product for use in Korean patients with mild to moderate hypertension. METHODS: This was an 8-week, multicenter, prospective, randomized, open-label, parallel-group non-inferiority trial in adult patients (age > 18 years) with mild to moderate essential hypertension (sitting dia-stolic blood pressure [SiDBP] 90-109 mm Hg). After a 2-week washout of previous antihypertensive medications, eligible patients were randomized to receive either ramipril 5 mg/d in the morning (low-dose group: baseline SiDBP 90-99 mm Hg) or ramipril 10 mg/d (high-dose group: baseline SiDBP 100-109 mm Hg) for the first 4 weeks. If SiDBP was > or = 90 mm Hg after 4 weeks of treatment, the dose was increased to 10 mg/d for the remaining 4 weeks in the low-dose group, and hydrochlorothiazide 12.5 mg was added to the regimen for the remaining 4 weeks in the high-dose group. The primary end point was the change in SiDBP from baseline to week 8. Secondary end points included a noninferiority analysis of the test and reference formulations with respect to the change in mean sitting systolic blood pressure (SiSBP) from baseline to week 8; SiDBP and SiSBP response rates (proportion of patients achieving an SiDBP < 90 mm Hg and SiSBP < 140 mm Hg, respectively) at 8 weeks; and changes from baseline in SiSBP, pulse wave velocity (PWV), exercise capacity, left-ventricular diastolic function (LVDF), and levels of brain natriuretic peptide (BNP) and high-sensitivity C-reactive protein (hs-CRP). Laboratory and clinical adverse events (AEs) were monitored at each study visit (4 and 8 weeks). RESULTS: The modified intent-to-treat population consisted of 89 patients (45 test, 44 reference; 60 men, 29 women; mean age, 49.7 years; mean weight, 69.9 kg). At week 8, mean (SD) SiSBP and SiDBP were significantly decreased from baseline in both groups (test: from 145.0 [9.7]/98.1 [5.3] mm Hg to 132.2 [11.1]/ 91.8 [7.1] mm Hg [P < 0.001]; reference: from 145.1 [11.4]/98.0 [5.7] mm Hg to 134.0 [14.6]/92.5 [7.9] mm Hg [P < 0.001]). The changes in blood pressure at week 8 did not differ significantly between the test and reference groups or between the low- and highdose groups in a subgroup analysis. Blood pressure response rates at 8 weeks did not differ significantly between the groups receiving the test and reference formulations (SiDBP: 26.7% and 31.8%, respectively; SiSBP: 37.8% and 40.9%). In addition, there were no significant between-group differences in the change in PWV (-63.8 and -38.7 cm/sec), LVDF at rest or after exercise, or levels of BNP or hs-CRP. The incidence of AEs was 64.4% in the test formulation group and 68.2% in the reference group formulation (P = NS). The most common AE in both groups was cough (10/45 [22.2%] and 10/44 [22.7%]). CONCLUSIONS: There were no significant differences in the efficacy and tolerability of the test and reference formulations of ramipril in these Korean adults with mild to moderate hypertension. The new generic formulation was noninferior to the reference formulation in terms of the change in SiDBP at week 8.

Differential Transcriptome Profile and Exercise Capacity in Cardiac Remodeling by Pressure Overload versus Volume Overload.

BACKGROUND: We compared the gene expression profiles in the hypertrophied myocardium of rats subjected to pressure overload (PO) and volume overload (VO) using DNA chip technology, and compared the effects on exercise capacity with a treadmill test. METHODS: Constriction of the abdominal aorta or mitral regurgitation induced by a hole in the mitral leaflet were used to induce PO (n = 19), VO (n = 16) or PO + VO (n = 20) in rats. Serial echocardiographic studies and exercise were performed at 2-week intervals, and invasive hemodynamic examination by a pressure-volume catheter system was performed 12 weeks after the procedure. The gene expression profiles of the left ventricle (LV) 12 weeks after the procedure were analyzed by DNA chip technology. RESULTS: In hemodynamic analyses, the LV end-diastolic pressure and the end-diastolic pressure-volume relationship slope were greater in the PO group than in the VO group. When we compared LV remodeling and exercise capacity, cardiac fibrosis and exercise intolerance developed in the PO group but not in the VO group (exercise duration, 434.0 ± 80.3 vs. 497.8 ± 49.0 seconds, p < 0.05, respectively). Transcriptional profiling of cardiac apical tissues revealed that gene expression related to the inflammatory response and cellular signaling pathways were significantly enriched in the VO group, whereas cardiac fibrosis, cytoskeletal pathway and G-protein signaling genes were enriched in the PO group. CONCLUSIONS: We found that many genes were regulated in PO, VO or both, and that there were different regulation patterns by cardiac remodeling. Cardiac fibrosis and cytoskeletal pathway were important pathways in the PO group and influenced exercise capacity. Cardiac fibrosis influences exercise capacity before LV function is reduced.

Efficacy of postprocedural anticoagulation after primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: A post-hoc analysis of the randomized INNOVATION trial.

There exists controversy on whether and for how long anticoagulation is necessary after primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI).We aimed to study the impact of prolonged (>24 h) or brief (<24 h) postprocedural anticoagulation on infarct size assessed by cardiac magnetic resonance (CMR) after 30 days as well as on left ventricular ejection fraction (LVEF) and left ventricular (LV) remodeling evaluated by 2D-echocardiography after 9 months from the INNOVATION trial (Clinical Trial Registration: NCT02324348).Of the 114 patients (mean age: 59.5 years) enrolled, 76 (66.7%) received prolonged anticoagulation therapy (median duration: 72.6 h) and 38 (33.3%) patients received brief anticoagulation therapy (median duration: 5 h) after primary PCI. There was no significant difference in infarct size (mean size: 15.6% after prolonged anticoagulation versus 19.8% after brief anticoagulation, P = .100) and the incidence of microvascular obstruction (50.7% versus 52.9%, P = .830) between the groups. Even after adjusting, prolonged anticoagulation therapy could not reduce larger infarct (defined as >75 percentile of infarct size; 19.7% versus 35.3%; adjusted odd ratio [OR]: 0.435; 95% confidence interval [CI]: 0.120-1.57; P = .204). Similar results were observed in subanalyses of major high-risk subgroups. Moreover, follow-up LVEF <35% (3.2% versus 7.4%; adjusted OR: 0.383; 95% CI: 0.051-2.884; P = .352) and LV remodeling (defined as >20% increase in LV end-diastolic volume; 37.1% versus 18.5%; adjusted OR: 2.249; 95% CI: 0.593-8.535; P = .234) were similar between groups.These data suggest that prolonged postprocedural anticoagulation may not provide much benefit after successful primary PCI in patients with STEMI. However, further studies are needed.

Development of bone regeneration strategies using human periosteum-derived osteoblasts and oxygen-releasing microparticles in mandibular osteomyelitis model of miniature pig.

Hypoxia and limited vascularization inhibit bone growth and recovery after surgical debridement to treat osteomyelitis. Similarly, despite significant efforts to create functional tissue-engineered organs, clinical success is often hindered by insufficient oxygen diffusion and poor vascularization. To overcome these shortcomings, we previously used the oxygen carrier perfluorooctane (PFO) to develop PFO emulsion-loaded hollow microparticles (PFO-HPs). PFO-HPs act as a local oxygen source that increase cell viability and maintains the osteogenic differentiation potency of human periosteum-derived cells (hPDCs) under hypoxic conditions. In the present study, we used a miniature pig model of mandibular osteomyelitis to investigate bone regeneration using hPDCs seeded on PFO-HPs (hPDCs/PFO-HP) or hPDCs seeded on phosphate-buffered saline (PBS)-HPs (hPDCs/PBS-HP). Osteomyelitis is characterized by a series of microbial invasion, vascular disruption, bony necrosis, and sequestrum formation due to impaired host defense response. Sequential plain radiography, computed tomography (CT), and 3D reconstructed CT images revealed new bone formation was more advanced in defects that had been implanted with the hPDCs/PFO-HPs than in defects implanted with the hPDCs/PBS-HP. Thus, PFO-HPs are a promising tissue engineering approach to repair challenging bone defects and regenerate structurally organized bone tissue with 3D architecture.

Safety and Efficacy of Biodegradable Polymer-biolimus-eluting Stents (BP-BES) Compared with Durable Polymer-everolimus-eluting Stents (DP-EES) in Patients Undergoing Complex Percutaneous Coronary Intervention.

BACKGROUND AND OBJECTIVES: There are no data comparing clinical outcomes of complex percutaneous coronary intervention (PCI) between biodegradable polymer-biolimus-eluting stents (BP-BES) and durable polymer-everolimus-eluting stents (DP-EES). We sought to evaluate the safety and efficacy of BP-BES compared with DP-EES in patients undergoing complex PCI. METHODS: Patients enrolled in the SMART-DESK registry were stratified into 2 categories based on the complexity of PCI. Complex PCI was defined as having at least one of the following features: unprotected left main lesion, ≥2 lesions treated, total stent length >40 mm, minimal stent diameter ≤2.5 mm, or bifurcation as target lesion. The primary outcome was target lesion failure (TLF), defined as a composite of cardiac death, target vessel-related myocardial infarction (TV-MI), or target lesion revascularization (TLR) at 2 years of follow-up. RESULTS: Of 1,999 patients, 1,145 (57.3%) underwent complex PCI: 521 patients were treated with BP-BES and 624 with DP-EES. In propensity-score matching analysis (481 pairs), the risks of TLF (3.8% vs. 5.2%, adjusted hazard ratio [HR], 0.578; 95% confidence interval [CI], 0.246-1.359; p=0.209), cardiac death (2.5% vs. 2.5%, adjusted HR, 0.787; 95% CI, 0.244-2.539; p=0.689), TV-MI (0.5% vs. 0.4%, adjusted HR, 1.128; 95% CI, 0.157-8.093; p=0.905), and TLR (1.1% vs. 2.9%, adjusted HR, 0.390; 95% CI, 0.139-1.095; p=0.074) did not differ between 2 stent groups after complex PCI. CONCLUSIONS: Clinical outcomes of BP-BES were comparable to those of DP-EES at 2 years after complex PCI. Our data suggest that use of BP-BES is acceptable, even for complex PCI.

Risk Scoring System to Assess Outcomes in Patients Treated with Contemporary Guideline-Adherent Optimal Therapies after Acute Myocardial Infarction.

BACKGROUND AND OBJECTIVES: A risk prediction is needed even in the contemporary era of acute myocardial infarction (AMI). We sought to develop a risk scoring specific for patients with AMI being treated with guideline-adherent optimal therapies, including percutaneous coronary intervention and all 5 medications (aspirin, thienopyridine, ß-blocker, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, and statin). METHODS: From registries, 12,174 AMI patients were evaluated. The primary outcome was 1-year all-cause death or AMI. The Korea Working Group in Myocardial Infarction (KorMI) system was compared with the Assessment of Pexelizumab in Acute Myocardial Infarction (APEX AMI), Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC), and Global Registry of Acute Coronary Events scores (GRACE) models. RESULTS: Ten predictors were identified: left ventricular dysfunction (hazard ratio [HR], 2.3), bare-metal stent (HR, 2.0), Killip class ≥II (HR, 1.9), renal insufficiency (HR, 1.8), previous stroke (HR, 1.6), regional wall-motion- score >20 on echocardiography (HR, 1.5), body mass index ≤24 kg/m² (HR, 1.4), age ≥70 years (HR, 1.4), prior coronary heart disease (HR, 1.4), and diabetes (HR, 1.4). Compared with the previous models, the KorMI system had good discrimination (time-dependent C statistic, 0.759) and showed reasonable goodness-of-fit by Hosmer-Lemeshow test (p=0.84). Moreover, the continuous-net reclassification improvement varied from -27.3% to -19.1%, the integrated discrimination index varied from -2.1% to -0.9%, and the median improvement in risk score was from -1.0% to -0.4%. CONCLUSIONS: The KorMI system would be a useful tool for predicting outcomes in survivors treated with guideline-adherent optimal therapies after AMI.

Role of Quantitative Wall Motion Analysis in Patients with Acute Chest Pain at Emergency Department.

BACKGROUND: Evaluation of acute chest pain in emergency department (ED), using limited resource and time, is still very difficult despite recent development of many diagnostic tools. In this study, we tried to determine the applicability of new semi-automated cardiac function analysis tool, velocity vector imaging (VVI), in the evaluation of the patients with acute chest pain in ED. METHODS: We prospectively enrolled 48 patients, who visited ED with acute chest pain, and store images to analyze VVI from July 2005 to July 2007. RESULTS: In 677 of 768 segments (88%), the analysis by VVI was feasible among 48 patients. Peak systolic radial velocity (Vpeak) and strain significantly decreased according to visual regional wall motion abnormality (Vpeak, 3.50 ± 1.34 cm/s for normal vs. 3.46 ± 1.52 cm/s for hypokinesia, 2.51 ± 1.26 for akinesia, p < 0.01; peak systolic radial strain -31.74 ± 9.15% fornormal, -24.33 ± 6.28% for hypokinesia, -20.30 ± 7.78% for akinesia, p < 0.01). However, the velocity vectors at the time of mitral valve opening (MVO) were directed outward in the visually normal myocardium, inward velocity vectors were revealed in the visually akinetic area (VMVO, -0.85 ± 1.65 cm/s for normal vs. 0.10 ± 1.46 cm/s for akinesia, p < 0.001). At coronary angiography, VMVO clearly increased in the ischemic area (VMVO, -0.88+1.56 cm/s for normal vs. 0.70 + 2.04 cm/s for ischemic area, p < 0.01). CONCLUSION: Regional wall motion assessment using VVI showed could be used to detect significant ischemia in the patient with acute chest pain at ED.