Objective: : Osteoporosis result from age-related decline in the number of osteoblast progenitors in the bone marrow. Probiotics have beneficial effects on the host, when administered in appropriate amounts. This study investigated the effects of probiotics expressing specific genes, especially the effects of genetically modified bone morphogenetic protein (BMP)-2-expressing Lactobacillus plantarum CJNU 3003 (LP) on ovariectomized rats. Methods: : Twenty-eight female Wistar rats (250–300 g, 12 weeks old) were divided into four groups : the sham (control), the ovariectomy (OVX)-induced osteoporosis group (OVX), the OVX and LP (OVX/LP), OVX and genetically modified BMP-2-expressing LP (OVX/LP with BMP) groups. The three groups underwent bilateral OVX and two of these groups were administered two different types of LP via oral gavage daily. At 16 weeks post-OVX, blood was collected from the heart and the bilateral tibiae were extracted and were scanned by ex-vivo micro-computed tomography and stained with hematoxylin-and-eosin (H&E) and Masson’s trichrome stain for pathological assessment. The serum levels of osteocalcin (OC), rat C-telopeptide of type I collagen (CTX-I), BMP-2, and receptor activator of nuclear factor-ĸB ligand (RANKL) were measured. Results: : The 3D-micro-computed tomography images showed that the trabecular structure in the OVX/LP with BMP group was maintained compared with OVX and OVX/LP groups. No significant differences were detected in trabecular thickness (Tb.Th) between control and OVX/LP with BMP groups (p>0.05). Furthermore, a tendency toward increased BMD, trabecular bone volume, Tb.Th, and trabecular number and decreased trabecular separation was found in rats in the OVX/LP with BMP groups when compared with the OVX and OVX/LP groups (p>0.05). The H&E and Masson’s trichrome stained sections showed a thicker trabecular bone in the OVX/LP with BMP group compared with the OVX and OVX/LP groups. There was no difference in serum levels of OC, CTX and RANKL control and OVX/LP with BMP groups (p>0.05). In contrast, significant differences were found in OC and CTX-1 levels between the OVX and OVX/LP with BMP groups (p<0.05). Conclusion : Our results showed that the expression of genetically modified BMP-2 showed inhibition effect for bone loss in a rat model of osteoporosis.

Background: Nilotinib is a tyrosine kinase inhibitor approved by the Ministry of Food and Drug Safety for frontline and 2nd line treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML). This study aimed to confirm the safety and efficacy of nilotinib in routine clinical practice within South Korea. Methods: An open-label, multicenter, single-arm, 12-week observational post-marketing surveillance (PMS) study was conducted on 669 Korean adult patients with Ph + CML from December 24, 2010, to December 23, 2016. The patients received nilotinib treatment in routine clinical practice settings. Safety was evaluated by all types of adverse events (AEs) during the study period, and efficacy was evaluated by the complete hematological response (CHR) and cytogenetic response. Results: During the study period, AEs occurred in 61.3% (410 patients, 973 events), adverse drug reactions (ADRs) in 40.5% (271/669 patients, 559 events), serious AEs in 4.5% (30 patients, 37 events), and serious ADRs in 0.7% (5 patients, 8 events). Furthermore, unexpected AEs occurred at a rate of 6.9% (46 patients, 55 events) and unexpected ADRs at 1.2% (8 patients, 8 events). As for the efficacy results, CHR was achieved in 89.5% (442/494 patients), and minor cytogenetic response or major cytogenetic response was achieved in 85.8% (139/162 patients). Conclusion This PMS study shows consistent results in terms of safety and efficacy compared with previous studies. Nilotinib was well tolerated and efficacious in adult Korean patients with Ph + CML in routine clinical practice settings.

BACKGROUND AND OBJECTIVES: Microvascular damage due to distal embolization during percutaneous coronary intervention (PCI) is an important cause of periprocedural myocardial infarction. We assessed the lipid-core plaque using near-infrared spectroscopy (NIRS) and microvascular dysfunction invasively with the index of microcirculatory resistance (IMR) and evaluated their relationship. METHODS: This study is pilot retrospective observational study. We analyzed 39 patients who performed NIRS before and after PCI, while fractional flow reserve, thermo-dilution coronary flow reserve (CFR) and IMR were measured after PCI. The maximum value of lipid core burden index (LCBI) for any of the 4-mm segments at the culprit lesion (culprit LCBI(4mm)) was calculated at the culprit lesion. We divided the patients into 2 groups using a cutoff of culprit LCBI(4mm) ≥500. RESULTS: Mean pre-PCI LCBI was 333±196 and mean post-PCI IMR was 20±14 U. Post-PCI IMR was higher (15.6±7.3 vs. 42.6±17.6 U, p<0.001) and post-PCI CFR was lower (3.7±2.2 vs. 2.1±1.0, p=0.029) in the high LCBI group. Pre-PCI LCBI was positively correlated with post-PCI IMR (ρ=0.358, p=0.025) and negatively correlated with post-PCI CFR (ρ=−0.494, p=0.001). The incidence of microvascular dysfunction (IMR ≥25 U) was higher in the high LCBI group (9.4% vs. 85.7%, p<0.001). However, there were no significant differences in the incidences of creatine Kinase-MB (9.4% vs. 14.3%, p=0.563) and troponin-I elevation (12.5% vs. 14.3%, p=1.000). CONCLUSIONS: A large lipid-core plaque at the ‘culprit’ lesion is observed higher incidence of post-PCI microvascular dysfunction after PCI. Prospective study with adequate subject numbers will be needed.
Coronary Artery Disease ; Creatine ; Humans ; Incidence ; Microvessels ; Myocardial Infarction ; Observational Study ; Percutaneous Coronary Intervention ; Prospective Studies ; Retrospective Studies ; Spectroscopy, Near-Infrared ; Troponin I

BACKGROUND AND OBJECTIVES: Microvascular damage due to distal embolization during percutaneous coronary intervention (PCI) is an important cause of periprocedural myocardial infarction. We assessed the lipid-core plaque using near-infrared spectroscopy (NIRS) and microvascular dysfunction invasively with the index of microcirculatory resistance (IMR) and evaluated their relationship. METHODS: This study is pilot retrospective observational study. We analyzed 39 patients who performed NIRS before and after PCI, while fractional flow reserve, thermo-dilution coronary flow reserve (CFR) and IMR were measured after PCI. The maximum value of lipid core burden index (LCBI) for any of the 4-mm segments at the culprit lesion (culprit LCBI(4mm)) was calculated at the culprit lesion. We divided the patients into 2 groups using a cutoff of culprit LCBI(4mm) ≥500. RESULTS: Mean pre-PCI LCBI was 333±196 and mean post-PCI IMR was 20±14 U. Post-PCI IMR was higher (15.6±7.3 vs. 42.6±17.6 U, p<0.001) and post-PCI CFR was lower (3.7±2.2 vs. 2.1±1.0, p=0.029) in the high LCBI group. Pre-PCI LCBI was positively correlated with post-PCI IMR (ρ=0.358, p=0.025) and negatively correlated with post-PCI CFR (ρ=−0.494, p=0.001). The incidence of microvascular dysfunction (IMR ≥25 U) was higher in the high LCBI group (9.4% vs. 85.7%, p<0.001). However, there were no significant differences in the incidences of creatine Kinase-MB (9.4% vs. 14.3%, p=0.563) and troponin-I elevation (12.5% vs. 14.3%, p=1.000). CONCLUSIONS A large lipid-core plaque at the ‘culprit’ lesion is observed higher incidence of post-PCI microvascular dysfunction after PCI. Prospective study with adequate subject numbers will be needed.

With recent advances in molecular diagnostic methods and targeted cancer therapies, several molecular tests have been recommended for gastric cancer (GC) and colorectal cancer (CRC). Microsatellite instability analysis of gastrointestinal cancers is performed to screen for Lynch syndrome, predict favorable prognosis, and screen patients for immunotherapy. The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor has been approved in metastatic CRCs with wildtype RAS (KRAS and NRAS exon 2–4). A BRAF mutation is required for predicting poor prognosis. Additionally, amplification of human epidermal growth factor receptor 2 (HER2) and MET is also associated with resistance to EGFR inhibitor in metastatic CRC patients. The BRAF V600E mutation is found in sporadic microsatellite unstable CRCs, and thus is helpful for ruling out Lynch syndrome. In addition, the KRAS mutation is a prognostic biomarker and the PIK3CA mutation is a molecular biomarker predicting response to phosphoinositide 3-kinase/AKT/mammalian target of rapamycin inhibitors and response to aspirin therapy in CRC patients. Additionally, HER2 testing should be performed in all recurrent or metastatic GCs. If the results of HER2 immunohistochemistry are equivocal, HER2 silver or fluorescence in situ hybridization testing are essential for confirmative determination of HER2 status. Epstein-Barr virus–positive GCs have distinct characteristics, including heavy lymphoid stroma, hypermethylation phenotype, and high expression of immune modulators. Recent advances in next-generation sequencing technologies enable us to examine various genetic alterations using a single test. Pathologists play a crucial role in ensuring reliable molecular testing and they should also take an integral role between molecular laboratories and clinicians.

BACKGROUND AND OBJECTIVES: This trial evaluated the safety and efficacy of the Genoss drug-eluting coronary stent. METHODS: This study was a prospective, multicenter, randomized trial with a 1:1 ratio of Genoss drug-eluting stent (DES)™ and Promus Element™. Inclusion criteria were the presence of stable angina, unstable angina, or silent ischemia. Angiographic inclusion criteria were de novo coronary stenotic lesion with diameter stenosis >50%, reference vessel diameter of 2.5–4.0 mm, and lesion length ≤40 mm. The primary endpoint was in-stent late lumen loss at 9-month quantitative coronary angiography follow-up. Secondary endpoints were in-segment late lumen loss, binary restenosis rate, death, myocardial infarction (MI), target lesion revascularization (TLR), target vessel revascularization (TVR), and stent thrombosis during 9 months of follow-up. RESULTS: We enrolled 38 patients for the Genoss DES™ group and 39 patients for the Promus Element™ group. In-stent late lumen loss at 9 months was not significantly different between the 2 groups (0.11±0.25 vs. 0.16±0.43 mm, p=0.567). There was no MI or stent thrombosis in either group. The rates of death (2.6% vs. 0%, p=0.494), TLR (2.6% vs. 2.6%, p=1.000), and TVR (7.9% vs. 2.6%, p=0.358) at 9 months were not significantly different. CONCLUSION: This first-in-patient study of the Genoss DES™ stent showed excellent angiographic outcomes for in-stent late lumen loss and major adverse cardiac events over a 9-month follow-up.
Angina, Stable ; Angina, Unstable ; Constriction, Pathologic ; Coronary Angiography ; Coronary Artery Disease ; Drug-Eluting Stents ; Follow-Up Studies ; Humans ; Ischemia ; Mortality ; Myocardial Infarction ; Polymers* ; Prospective Studies ; Sirolimus ; Stents* ; Thrombosis

Remission is a primary end point of in clinical practice and trials of treatments for rheumatoid arthritis (RA). The 2011 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) remission criteria were developed to provide a consensus definition of remission. This study aimed to assess the concordance between the new remission criteria and the physician’s clinical judgment of remission and also to identify factors that affect the discordance between these two approaches. A total of 3,209 patients with RA were included from the KORean Observational Study Network for Arthritis (KORONA) database. The frequency of remission was evaluated based on each approach. The agreement between the results was estimated by Cohen's kappa (κ). Patients with remission according to the 2011 ACR/EULAR criteria (i.e. the Boolean criteria) and/or physician judgment (n = 855) were divided into three groups: concordant remission, the Boolean criteria only, and physician judgment only. Multinomial logistic regression analysis was used to identify factors responsible for the assignment of patients with remission to one of the discordant groups rather than the concordant group. The remission rates using the Boolean criteria and physician judgment were 10.5% and 19.9%, respectively. The agreement between two approaches for remission was low (κ = 0.226) and the concordant remission rate was only 5.5% (n = 177). Pain affected classification in both discordant groups, whereas fatigue was associated with remission only by physician clinical judgment. The Boolean criteria were more stringent than clinical judgment. Patient subjective symptoms such as pain and fatigue were associated with discordance between the two approaches.
Arthritis ; Arthritis, Rheumatoid* ; Classification ; Consensus ; Fatigue ; Humans ; Judgment* ; Logistic Models ; Observational Study ; Rheumatic Diseases

BACKGROUND AND OBJECTIVES: Intracardiac electrocardiograms (ECGs) from the coronary sinus (CS) provide important information for identifying a left-sided bypass tract. However, a previous study revealed an anatomical discrepancy between the CS and mitral annulus (MA) in cadaver hearts. The purpose of this study was to evaluate the anatomical relationship between the CS and MA in the living body by using fluoroscopy. SUBJECTS AND METHODS: We analyzed patients who had an ablation for 42 left-sided bypass tracts and one paroxysmal atrial fibrillation. A left atriogram was performed during the ablation by using a pigtail catheter via the transseptal approach. The distances between the CS and MA were measured at 30° right anterior oblique (RAO) and 60° left anterior oblique (LAO) projections at the end of ventricular systole and diastole. RESULTS: The distances between the CS and MA at the RAO projection were 9.74±3.50, 3.86±2.58, and 9.02±6.04 mm during systole and 12.89±5.59, 3.97±3.24, and 10.71±4.12 mm during diastole at the proximal, middle, and distal CS, respectively. The distances between the CS and MA at the LAO projection were 6.84±2.77, 1.80±1.51, and 4.57±3.24 mm during systole and 9.91±3.25, 4.21±3.59, and 7.02±3.12 mm during diastole at the proximal, middle, and distal CS, respectively. CONCLUSION: An anatomical discrepancy was detected between the CS and MA in most cases. Therefore, intracardiac ECGs of the CS cannot exactly localize left-sided bypass tracts.
Atrial Fibrillation ; Cadaver ; Catheters ; Coronary Sinus* ; Diastole ; Electrocardiography ; Fluoroscopy* ; Heart ; Humans ; Systole

BACKGROUND AND OBJECTIVES: Microvascular function is a useful predictor of left ventricular functional changes in patients with ST-segment elevation myocardial infarction (STEMI). We evaluated the usefulness of the hyperemic microvascular resistance index (hMVRI) for predicting long-term major adverse cardiovascular events (MACEs) in patients with STEMI assessed immediately after primary percutaneous coronary intervention (PCI). SUBJECTS AND METHODS: hMVRI were evaluated in 145 patients with first acute STEMI treated with primary PCI using an intracoronary Doppler wire. hMVRI was defined as the ratio of mean aortic pressure over hyperemic averaged peak velocity of infarct-related artery. Major adverse cardiovascular events (MACEs) included cardiac death and re-hospitalization for congestive heart failure. RESULTS: During the mean follow-up of 85+/-43 months, MACEs occurred in 17.2% of patients. Using a receiver-operating characteristics analysis, hMVRI >2.82 mm Hg.cm-1.sec (sensitivity: 87%; specificity: 69%; and area under curve: 0.818) was the best cut-off values for predicting future cardiac events. The Cox proportional hazard analysis showed that hMVRI was an independent predictor for long-term MACEs (hazard ratio 1.741, 95% confidence interval 1.348-2.264, p<0.001). The Kaplan-Meier survival analysis showed a higher incidence of MACEs in patients with hMVRI >2.82 mm Hg.cm-1.sec (p<0.001). CONCLUSION: hMVRI was a strong predictor of long-term MACEs in patients with STEMI treated with primary PCI.
Area Under Curve ; Arterial Pressure ; Arteries ; Death ; Follow-Up Studies ; Heart Failure ; Humans ; Incidence ; Microcirculation ; Myocardial Infarction* ; Percutaneous Coronary Intervention ; Sensitivity and Specificity

We assessed the success rate of empirical antifungal therapy with itraconazole and evaluated risk factors for predicting the failure of empirical antifungal therapy. A multicenter, prospective, observational study was performed in patients with hematological malignancies who had neutropenic fever and received empirical antifungal therapy with itraconazole at 22 centers. A total of 391 patients who had abnormal findings on chest imaging tests (31.0%) or a positive result of enzyme immunoassay for serum galactomannan (17.6%) showed a 56.5% overall success rate. Positive galactomannan tests before the initiation of the empirical antifungal therapy (P=0.026, hazard ratio [HR], 2.28; 95% confidence interval [CI], 1.10-4.69) and abnormal findings on the chest imaging tests before initiation of the empirical antifungal therapy (P=0.022, HR, 2.03; 95% CI, 1.11-3.71) were significantly associated with poor outcomes for the empirical antifungal therapy. Eight patients (2.0%) had premature discontinuation of itraconazole therapy due to toxicity. It is suggested that positive galactomannan tests and abnormal findings on the chest imaging tests at the time of initiation of the empirical antifungal therapy are risk factors for predicting the failure of the empirical antifungal therapy with itraconazole. (Clinical Trial Registration on National Cancer Institute website, NCT01060462)
14-alpha Demethylase Inhibitors/adverse effects/therapeutic use ; Adolescent ; Adult ; Aged ; Antifungal Agents/adverse effects/*therapeutic use ; Aspergillosis/complications/*drug therapy ; Candidiasis/complications/*drug therapy ; Coccidioidomycosis/complications/drug therapy ; Febrile Neutropenia/complications/drug therapy ; Female ; Hematologic Neoplasms/complications/drug therapy/*microbiology ; Humans ; Itraconazole/adverse effects/*therapeutic use ; Male ; Mannans/blood ; Middle Aged ; Prospective Studies ; Treatment Outcome ; Young Adult