Clinical efficacy of angiotensin receptor-neprilysin inhibitor in de novo heart failure with reduced ejection fraction

Background/Aims@#We aimed to analyze the efficacy of angiotensin receptor-neprilysin inhibitor (ARNI) by the disease course of heart failure (HF). @*Methods@#We evaluated 227 patients with HF in a multi-center retrospective cohort that included those with left ventricular ejection fraction (LVEF) ≤ 40% undergoing ARNI treatment. The patients were divided into patients with newly diagnosed HF with ARNI treatment initiated within 6 months of diagnosis (de novo HF group) and those who were diagnosed or admitted for HF exacerbation for more than 6 months prior to initiation of ARNI treatment (prior HF group). The primary outcome was a composite of cardiovascular death and worsening HF, including hospitalization or an emergency visit for HF aggravation within 12 months. @*Results@#No significant differences in baseline characteristics were reported between the de novo and prior HF groups. The prior HF group was significantly associated with a higher primary outcome (23.9 vs. 9.4%) than the de novo HF group (adjusted hazard ratio 2.52, 95% confidence interval 1.06–5.96, p = 0.036), although on a higher initial dose. The de novo HF group showed better LVEF improvement after 1 year (12.0% vs 7.4%, p = 0.010). Further, the discontinuation rate of diuretics after 1 year was numerically higher in the de novo group than the prior HF group (34.4 vs 18.5%, p = 0.064). @*Conclusions@#The de novo HF group had a lower risk of the primary composite outcome than the prior HF group in patients with reduced ejection fraction who were treated with ARNI.

Niclosamide Inhibits Aortic Valve Interstitial Cell Calcification by Interfering with the GSK-3β/β-Catenin Signaling Pathway

The most common heart valve disorder is calcific aortic valve stenosis (CAVS), which is characterized by a narrowing of the aortic valve. Treatment with the drug molecule, in addition to surgical and transcatheter valve replacement, is the primary focus of researchers in this field. The purpose of this study is to determine whether niclosamide can reduce calcification in aortic valve interstitial cells (VICs). To induce calcification, cells were treated with a pro-calcifying medium (PCM). Different concentrations of niclosamide were added to the PCM-treated cells, and the level of calcification, mRNA, and protein expression of calcification markers was measured. Niclosamide inhibited aortic valve calcification as observed from reduced alizarin red s staining in niclosamide treated VICs and also decreased the mRNA and protein expressions of calcification-specific markers: runt-related transcription factor 2 and osteopontin. Niclosamide also reduced the formation of reactive oxygen species, NADPH oxidase activity and the expression of Nox2 and p22 phox . Furthermore, in calcified VICs, niclosamide inhibited the expression of β-catenin and phosphorylated glycogen synthase kinase (GSK-3β), as well as the phosphorylation of AKT and ERK. Taken together, our findings suggest that niclosamide may alleviate PCM-induced calcification, at least in part, by targeting oxidative stress mediated GSK-3β/β-catenin signaling pathway via inhibiting activation of AKT and ERK, and may be a potential treatment for CAVS.

Effects of Smoking on Long-Term Clinical Outcomes and Lung Cancer in Patients with Acute Myocardial Infarction

Background and Objectives@#Smoking is well-established as a risk factor for coronary artery disease. However, recent studies demonstrated favorable results, including reduced mortality, among smokers, which are referred to as the “smoker's paradox”. This study examined the impact of smoking on clinical outcomes in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI). @*Methods@#Patients with AMI undergoing PCI between 2004 and 2014 were enrolled and classified according to smoking status. The primary endpoint was a composite of major adverse cardiovascular events (MACE) including cardiac death, myocardial infarction, stroke, and revascularization. @*Results@#Among the 10,683 patients, 4,352 (40.7%) were current smokers. Smokers were 10.7 years younger and less likely to have comorbidities such as hypertension, diabetes mellitus, chronic kidney disease, stroke, and prior PCI. Smokers had less MACE (hazard ratio [HR], 0.644; 95% confidence interval [CI], 0.594–0.698; p<0.001) and cardiac death (HR, 0.494; 95% CI, 0.443–0.551; p<0.001) compared to nonsmokers during the 5 years in an unadjusted model. However, after propensity-score matching, smokers showed higher risk of MACE (HR, 1.125; 95% CI, 1.009–1.254; p=0.034) and cardiac death (HR, 1.190; 95% CI, 1.026–1.381; p=0.022). Smoking was a strong independent predictor of lung cancer (propensityscore matched HR, 2.749; 95% CI, 1.416–5.338; p=0.003). @*Conclusions@#In contrast to the unadjusted model, smoking is associated with worse cardiovascular outcome and higher incidence of lung cancer after adjustment of various confounding factors. This result can be explained by the characteristics of smokers, which were young and had fewer comorbidities.

Effects of Smoking on Long-Term Clinical Outcomes and Lung Cancer in Patients with Acute Myocardial Infarction

Background and Objectives@#Smoking is well-established as a risk factor for coronary artery disease. However, recent studies demonstrated favorable results, including reduced mortality, among smokers, which are referred to as the “smoker's paradox”. This study examined the impact of smoking on clinical outcomes in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI). @*Methods@#Patients with AMI undergoing PCI between 2004 and 2014 were enrolled and classified according to smoking status. The primary endpoint was a composite of major adverse cardiovascular events (MACE) including cardiac death, myocardial infarction, stroke, and revascularization. @*Results@#Among the 10,683 patients, 4,352 (40.7%) were current smokers. Smokers were 10.7 years younger and less likely to have comorbidities such as hypertension, diabetes mellitus, chronic kidney disease, stroke, and prior PCI. Smokers had less MACE (hazard ratio [HR], 0.644; 95% confidence interval [CI], 0.594–0.698; p<0.001) and cardiac death (HR, 0.494; 95% CI, 0.443–0.551; p<0.001) compared to nonsmokers during the 5 years in an unadjusted model. However, after propensity-score matching, smokers showed higher risk of MACE (HR, 1.125; 95% CI, 1.009–1.254; p=0.034) and cardiac death (HR, 1.190; 95% CI, 1.026–1.381; p=0.022). Smoking was a strong independent predictor of lung cancer (propensityscore matched HR, 2.749; 95% CI, 1.416–5.338; p=0.003). @*Conclusions@#In contrast to the unadjusted model, smoking is associated with worse cardiovascular outcome and higher incidence of lung cancer after adjustment of various confounding factors. This result can be explained by the characteristics of smokers, which were young and had fewer comorbidities.

Angiotensin Receptor Blockers as an Alternative to Angiotensin-Converting Enzyme Inhibitors in Patients with Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs) are the first choice for the treatment of acute myocardial infarction (AMI), and angiotensin receptor blockers (ARBs) should be considered in patients intolerant to ACEIs. Although previous studies support the use of ARBs as an alternative to ACEIs, these studies showed inconsistent results. The objective of this study was to demonstrate the clinical impact of ARBs as an alternative to ACEIs in patients with AMI undergoing percutaneous coronary intervention (PCI). METHODS: The CardiOvascular Risk and idEntificAtion of potential high-risk population in AMI (COREA-AMI) registry enrolled all consecutive patients with AMI undergoing PCI. The primary endpoint was the composite of cardiovascular death, myocardial infarction, stroke, or hospitalization due to heart failure. RESULTS: Of the 3,328 eligible patients, ARBs replaced ACEIs in 816 patients, while 824 patients continued to use ACEIs and 826 patients continued to use ARBs. The remaining 862 patients did not receive ACEIs/ARBs. After the adjustment with inverse probability weighting, the primary endpoints in the first groups were similar (7.5% vs. 8.0%, hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.75–1.05; P = 0.164). Composite events were less frequent in the ACEI to ARB group than no ACEI/ARB group (7.5% vs. 11.8%, HR, 0.76; 95% CI, 0.64–0.90; P = 0.002). CONCLUSION: The alternative use of ARBs following initial treatment with ACEIs demonstrates comparable clinical outcomes to those with continued use of ACEIs and is associated with an improved rate of composite events compared to no ACEI/ARB use in patients with AMI undergoing PCI. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02385682

Association between the Red Cell Distribution Width and Vasospastic Angina in Korean Patients

PURPOSE: The association between the red cell distribution width (RDW) and vasospastic angina (VSA) has not been elucidated. We investigated the association of the RDW with the incidence and angiographic subtypes of VSA in Korean patients. MATERIALS AND METHODS: A total of 460 patients who underwent intracoronary ergonovine provocation tests were consecutively enrolled and classified into two groups: the VSA group (n=147, 32.0%) and non-VSA group (n=313, 68.0%). The subjects were classified into 3 subgroups (tertiles) according to the baseline level of RDW assessed before the angiographic provocation test. RESULTS: The VSA group had a higher RDW than the non-VSA group (12.9±0.8% vs. 12.5±0.7%, p=0.013). The high RDW level demonstrated an independent association with the high incidence of VSA [second tertile: hazard ratio (HR) 1.96 (1.13-2.83), third tertile: HR 2.33 (1.22-3.47), all p<0.001]. Moreover, the highest RDW tertile level had a significant association with the prevalence of the mixed-type coronary spasm [HR 1.29 (1.03-1.59), p=0.037]. CONCLUSION: The high level of RDW was significantly associated with the prevalence of VSA and the high-risk angiographic subtype of coronary spasm, suggesting that a proactive clinical investigation for VSA could be valuable in Korean patients with an elevated RDW.

Three Cases of Cervical Rib / 대한이비인후과학회지

Cervical rib is a normal asymptomatic congenital bone abnormality that occurs in 0.4% of the population; 70% of these cases are bilateral. Cervical ribs are found incidentally on routine radiographs, though sometimes patients complain of a hard or pulsatile neck mass in the supraclavicular area. Although most of these ribs produce no symptoms and need no therapy, a few cases are symptomatic and require treatment. Furthermore, a cervical rib can displace the great vessels superiorly and may cause iatrogenic hemorrhage during neck surgery. Thus, otorhinolaryngologists should be aware of the diagnosis and management of this condition in patients with a neck mass. Here, we report three cases of cervical rib and include a review of literature.

Follicular Variant of Papillary Thyroid Carcinoma: Clinical Manifestation and Prognosis / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Despite relatively high incidences of follicular variant of papillary thyroid carcinoma (FV-PTC), there is a continuous debate regarding the clinical behavior, treatment outcome, prognostic variables and survival of this disease. We performed this study for the purpose of getting further understanding and more supporting ideas for the treatment of FV-PTC. SUBJECTS AND METHOD: A clinicopathologic analysis of 116 patients who underwent a thyroidectomy with a final diagnosis of FV-PTC divided the patients into three groups: the FV-PTC only group (group A, n=78), the FV-PTC group who developed classical papillary thyroid carcinoma (C-PTC) (group B, n=38) and the C-PTC only (group C, n=320, 2003, Korea Cancer Center Hospital). The three groups were compared with respect to the following various clinicopathological characteristics: age at diagnosis, tumor size, stage of tumor, capsular invasion, age, metastasis, extent, size score, multifocality of tumor, LN metastasis, treatment, and recurrence. RESULTS: The mean tumor sizes, disease stage, and type of initial surgery were similar in three groups. However, the prevalence of nodal disease and capsular invasion were significantly higher in the groups B and C compared to the patients of group A. The 8-year disease-free survival rate was 93.7% in the patients with FV-PTC only, 90.4% in the patients with C-PTC only and 88.2% in the patients with FV-PTC group, who developed C-PTC (p>0.05). CONCLUSION: The clinical behavior and prognosis of PTC and FV-PTC groups did not differ significantly. In treating FV-PTC, we find that it is desirable to choose a similar strategy as that used to treat C-PTC.

Effect of Decursin on the Expression of beta-Catenin and Matrix Metalloproteinase-7 in Prostate Cancer Cell Lines / 대한비뇨기과학회지

PURPOSE: Alterations in the Wnt/beta-catenin pathway are associated with the development and progression of human prostate cancer. Decursin can attenuate the Wnt/beta-catenin pathway. We investigated the relationship between the Wnt/beta-catenin pathway and decursin in prostate cancer cells. MATERIALS AND METHODS: PC-3 and LNCaP cell lines were used. Cell viability was measured with methyl-thiazole tetrazolium bromide (MTT) assays, and cell apoptosis analysis was performed by FACScan. The amount of beta-catenin protein after treatment with decursin was measured by Western blot analysis. Expression of MMP-7 mRNA was detected by real-time polymerase chain reaction (RT-PCR). RESULTS: Death and apoptosis were increased after treatment with decursin 0.5-100 micrometer in PC-3 and LNCaP cells. This was revealed dose and time-dependent increase of cancer cell death on 24, 48 and 72 hours. FACScan showed an increment of apoptosis on 24, 48 hours. Expression of intracellular beta-catenin protein was decreased dose-dependently in both of prostate cancer cell lines. Decursin reduced MMP-7 mRNA expression on 6, 12, 24, 48 hours dose-dependently. CONCLUSIONS: Decursin affects the viability of prostate cancer cells. Increased cancer cell death was associated with increased apoptosis. This study suggests that decursin may play a role in the treatment of prostate cancer.

Cryptosporidiosis in a Small Bowel Transplant Recipient / 대한이식학회지

No abstract available.

Effect of the G-CSF schedule for harvesting peripheral blood progenitor cells from healthy donors / 대한내과학회지

BACKGROUND/AIMS: Peripheral blood progenitor cells (PBSC) have been used instead of bone marrow cells for allogeneic transplantation. Progenitor cells are mobilized using granulocyte colony stimulating factor (G-CSF). Kinetic studies of G-CSF have shown that the CD34+ cells peak on day 5, although the optimal time for harvesting has not been established. METHODS: We compared two mobilization schedules using G-CSF. In groups I and II, G-CSF 10 microgram/kg/day was administered subcutaneously for 3 or 4 days, respectively, and leukapheresis was performed the next day. RESULTS: In groups I and II, a respective mean number of 5.84 x 106 and 10.76 x 106 circulating CD34+ cells per kilogram of the recipient's weight was collected by leukapheresis. The yield of the two collections did not differ significantly (p=0.386). CONCLUSION: This study suggested that the two mobilization schedules are equally effective. To avoid prolonged exposure to G-CSF, the day 4 collection schedule is the preferred mobilization strategy.

A Case of Rectal Anisakiasis / 대한소화기내시경학회지

Anisakiasis refers to the infestation of humans by a species of marine nematode larvae belonging to the subfamily Anisakidae, and this condition is seen in people who eat inadequately prepared or raw salt-water fish and squid. Because Koreans like to eat raw fish, anisakiasis of the stomach has been reported occasionally, but involvement of the small bowel or colon is relatively rare. In the case of the colon, anisakiasis of the ascending colon or the transverse colon has been only infrequently reported, and the incidence of rectal anisakiasis is very rare. The present case is a 58-year-old man with no definite abdominal symptoms who visited our hospital for a medical checkup. A 2 cm sized whitish linear live larva was revealed in the rectum and it was removed by colonoscopy.

The Protective Mechanism of Zinc in Fungal Metabolte Gliotoxin - induced Apoptosis

Gliotoxin, a fungal metabolite, is one of the epipolythiodioxopiperazine classes and has a variety of effects including imrnunomodulatory and apoptotic agents. This study is designed to evaluate the effect of zinc on gliotoxin-induced death of HL-60 cells. Here, we demonstrated that treatment of gliotoxin decreased cell viability in a dose and time-dependent manner. Gliotoxin-induced cell death was confirtned as apoptosis characterized by chromatin marginafion, fragmentation and ladder-pattern digestion of genomic DNA. Gliotoxin increased the proteolytic activities of caspase 3, 6, 8, and 9. Caspase-3 activation was further confirmed by the degradation of procaspase-3 and PARP in gliotoxin-treated HL-60 cells. Zinc compounds including ZnC12 and ZnSO4 markedly inhibited gliotoxin-induced apoptosis in HL-60 cells (from 30% to 90%). Consistent with anti- apoptotic effects, zinc also suppressed the enzymatic activities of caspase-3 and -9 proteases. In addition, cleavage of both PARP and procaspase 3 in gliotoxin-treated HL-60 cells was inhibited by the addition of zinc compounds. We further demonstrated that expression of Fas ligand by gliotoxin was suppressed by zinc compounds. These data suggest that zinc may prevent gliotoxin- induced apoptosis via inhibition of Fas ligand expression as well as suppression of caspase family cysteine proteases-3 and -9 in HL-60 cells.