Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting in Patients with Coronary Artery Disease and Diabetic Nephropathy: A Single Center Experience

Background Patients with diabetic nephropathy (DN) and coronary artery disease (CAD) represent a subset of patients with high cardiovascular morbidity and mortality. The optimal revascularization strategy using either percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) remains controversial. The purpose of this study was to compare the clinical outcomes of PCI to CABG in DN patients with CAD. Methods The clinical and angiographic records of DN patients with CAD who underwent either CABG (n=52) or PCI (n=48) were retrospectively analyzed. Results The baseline characteristics were similar in the two groups except for the severity of the CAD. At 30 days, the death rate (PCI: 2.1% vs. CABG: 9.6%, p=0.21) and major adverse cardiac events (MACE) rate (PCI: 2.1% vs. CABG: 9.6%, p=0.21) were similar in comparisons between the PCI and CABG groups. At three years, the death rate (PCI: 18.8% vs. CABG: 19.2%, p=0.94) was similar between the PCI and CABG groups but the MACE rate (PCI: 47.9% vs. CABG: 21.2%, p=0.006) was higher in the PCI group compared to the CABG group. In addition, the repeat revascularization rate was higher in the PCI group compared to the CABG group (PCI: 12.5% vs. CABG: 1.9%, p=0.046). Conclusions The CABG procedure was associated with a lower incidence of MACE and repeat revascularization for up to three years of follow-up in DN patients with CAD. However, the overall survival rate was similar in the CABG and PCI groups. Therefore, CABG may be superior to PCI with regard to MACE and repeat revascularization.ope

A reduced dose of ribavirin does not influence the virologic response during pegylated interferon alpha-2b and ribavirin combination therapy in patients with genotype 1 chronic hepatitis C

Background/AimsWhen combined with pegylated interferon alpha-2b (Peg-IFN α-2b) for the treatment of genotype 1 chronic hepatitis C (CHC) in Korea, the current guideline for the initial ribavirin (RBV) dose is based on body weight. However, since the mean body weight is lower for Korean patients than for patients in Western countries, current guidelines might result in Korean patients being overdosed with RBV.MethodsWe retrospectively reviewed the medical records of patients with genotype 1 CHC who were treated with Peg-IFN α-2b and RBV combination therapy. We divided the patients into groups A (≥15 mg/kg/day, n=23) and B (<15 mg/kg/day, n=26), given that the standard dose is 15 mg/kg/day. The clinical course in terms of the virologic response, adverse events, and dose modification rate was compared between the two groups after therapy completion.ResultsThe early response rates (92.0% vs. 83.3%, P=0.634) and sustained virologic response rates (82.6% vs. 73.1%, P=0.506) did not differ significantly between the two groups. During the treatment period, the RBV dose reduction rate was significantly higher in group A than in group B (60.9% vs. 23.1%, P=0.01).ConclusionsRBV dose reduction is performed frequently when patients are treated according to the current Korean guidelines. Given that lowering the RBV dose did not appear to decrease the virologic response during therapy, reducing RBV doses below the current Korean guideline may be effective for treatment, especially in low-weight patients

Gene Expression Pattern in Transmitochondrial Cytoplasmic Hybrid Cells Harboring Type 2 Diabetes-Associated Mitochondrial DNA Haplogroups

Decreased mitochondrial function plays a pivotal role in the pathogenesis of type 2 diabetes mellitus (T2DM). Recently, it was reported that mitochondrial DNA (mtDNA) haplogroups confer genetic susceptibility to T2DM in Koreans and Japanese. Particularly, mtDNA haplogroup N9a is associated with a decreased risk of T2DM, whereas haplogroups D5 and F are associated with an increased risk. To examine functional consequences of these haplogroups without being confounded by the heterogeneous nuclear genomic backgrounds of different subjects, we constructed transmitochondrial cytoplasmic hybrid (cybrid) cells harboring each of the three haplogroups (N9a, D5, and F) in a background of a shared nuclear genome. We compared the functional consequences of the three haplogroups using cell-based assays and gene expression microarrays. Cell-based assays did not detect differences in mitochondrial functions among the haplogroups in terms of ATP generation, reactive oxygen species production, mitochondrial membrane potential, and cellular dehydrogenase activity. However, differential expression and clustering analyses of microarray data revealed that the three haplogroups exhibit a distinctive nuclear gene expression pattern that correlates with their susceptibility to T2DM. Pathway analysis of microarray data identified several differentially regulated metabolic pathways. Notably, compared to the T2DM-resistant haplogroup N9a, the T2DM-susceptible haplogroup F showed down-regulation of oxidative phosphorylation and up-regulation of glycolysis. These results suggest that variations in mtDNA can affect the expression of nuclear genes regulating mitochondrial functions or cellular energetics. Given that impaired mitochondrial function caused by T2DM-associated mtDNA haplogroups is compensated by the nuclear genome, we speculate that defective nuclear compensation, under certain circumstances, might lead to the development of T2DM

Differences in the Properties and Mirna Expression Profiles between Side Populations from Hepatic Cancer Cells and Normal Liver Cells

AIMS: Because hepatic cancer stem cells (HCSCs) are believed to derive from the conversion of hepatic normal stem cells (HNSCs), the identification of the differences that distinguish HCSCs from HNSCs is important. METHODS: The HCC model was established in F344 rats by DEN induction. Using FACS analysis, side population cells from HCC (SP-HCCs) were isolated from the epithelial-like cells of HCC tissues, and the side population cells from normal liver (SP-NLCs) were isolated from syngeneic normal liver cells. The expression of stem cell markers was detected in both freshly isolated and amplified subpopulations. After induction with HGF, the differentiation of each subpopulation was analyzed by detection of early and late liver markers. In vivo, the biological characteristics of SP-HCCs and SP-NLCs were analyzed by repairing injured livers or forming tumors in nude mice. In addition, the expression of miRNAs was examined in both populations by miRNA array and QRT-PCR. RESULTS: SP-NLCs and SP-HCCs were 4.30±0.011% and 2.100±0.010% of the whole population, respectively. Both SP-NLCs and SP-HCCs displayed greater expression of stem cell markers (CD133 and EpCAM) than NSP-NLCs and NSP-HCCs, respectively (P<0.01), both after fresh isolation and amplification. Upon HGF induction, SP-NLCs generated many ALB positive cells and few CK-7 positive cells, but NSP-NLCs could generate only ALB positive cells. In contrast, SP-HCCs gave rise to only AFP positive cells. As few as 5 × 10⁵ SP-NLCs were capable of repairing liver injury, while the same number of NSP-NLCs could not repair the liver. Furthermore, only 1 × 10⁴ SP-HCCs were necessary to initiate a tumor, while NSP-HCCs could not form a tumor. Compared to SP-NLCs, 68 up-regulated and 10 down-regulated miRNAs were present in SP-HCCs (P<0.01). CONCLUSION: Based on the decisive roles of some miRNAs in the genesis of HCSCs, miRNAs may contribute to the different characteristics that distinguish SP-HCCs from SP-NLCs

Oncologic impact of delay between diagnosis and radical nephroureterectomy

PurposeThis study aimed to evaluate the oncological outcome of delayed surgical wait time from the diagnosis of upper tract urothelial carcinoma (UTUC) to radical nephroureterectomy (RNU).MethodsIn this multicenter retrospective study, medical records were collected between 1988 and 2021 from 18 participating Taiwanese hospitals under the Taiwan UTUC Collaboration Group. Patients were dichotomized into the early (≤90 days) and late (&gt;90 days) surgical wait-time groups. Overall survival, disease-free survival, and bladder recurrence-free survival were calculated using the Kaplan–Meier method and multivariate Cox regression analysis. Multivariate analysis was performed using stepwise linear regression.ResultsOf the 1251 patients, 1181 (94.4%) were classifed into the early surgical wait-time group and 70 (5.6%) into the late surgical wait-time group. The median surgical wait time was 21 days, and the median follow-up was 59.5 months. Our study showed delay-time more than 90 days appeared to be associated with worse overall survival (hazard ratio [HR] 1.974, 95% confidence interval [CI] 1.166−3.343, p = 0.011), and disease-free survival (HR 1.997, 95% CI 1.137−3.507, p = 0.016). This remained as an independent prognostic factor after other confounding factors were adjusted. Age, ECOG performance status, Charlson Comorbidity Index (CCI), surgical margin, tumor location and adjuvant systemic therapy were independent prognostic factors for overall survival. Tumor location and adjuvant systemic therapy were also independent prognostic factors for disease-free survival.ConclusionsFor patients with UTUC undergoing RNU, the surgical wait time should be minimized to less than 90 days. Prolonged delay times may be associated with poor overall and disease-free survival

Search for dark matter produced in association with a single top quark or a top quark pair in proton-proton collisions at s=13 TeV

A search has been performed for heavy resonances decaying to ZZ or ZW in 2l2q final states, with two charged leptons (l = e, mu) produced by the decay of a Z boson, and two quarks produced by the decay of a W or Z boson. The analysis is sensitive to resonances with masses in the range from 400 to 4500 GeV. Two categories are defined based on the merged or resolved reconstruction of the hadronically decaying vector boson, optimized for high- and low-mass resonances, respectively. The search is based on data collected during 2016 by the CMS experiment at the LHC in proton-proton collisions with a center-of-mass energy of root s = 13 TeV, corresponding to an integrated luminosity of 35.9 fb(-1). No excess is observed in the data above the standard model background expectation. Upper limits on the production cross section of heavy, narrow spin-1 and spin-2 resonances are derived as a function of the resonance mass, and exclusion limits on the production of W' bosons and bulk graviton particles are calculated in the framework of the heavy vector triplet model and warped extra dimensions, respectively.A search has been performed for heavy resonances decaying to ZZ or ZW in 2l2q final states, with two charged leptons (l = e, mu) produced by the decay of a Z boson, and two quarks produced by the decay of a W or Z boson. The analysis is sensitive to resonances with masses in the range from 400 to 4500 GeV. Two categories are defined based on the merged or resolved reconstruction of the hadronically decaying vector boson, optimized for high- and low-mass resonances, respectively. The search is based on data collected during 2016 by the CMS experiment at the LHC in proton-proton collisions with a center-of-mass energy of root s = 13 TeV, corresponding to an integrated luminosity of 35.9 fb(-1). No excess is observed in the data above the standard model background expectation. Upper limits on the production cross section of heavy, narrow spin-1 and spin-2 resonances are derived as a function of the resonance mass, and exclusion limits on the production of W' bosons and bulk graviton particles are calculated in the framework of the heavy vector triplet model and warped extra dimensions, respectively.A search for dark matter produced in association with top quarks in proton-proton collisions at a center-of-mass energy of 13 TeV is presented. The data set used corresponds to an integrated luminosity of 35.9 fb(-1) recorded with the CMS detector at the LHC. Whereas previous searches for neutral scalar or pseudoscalar mediators considered dark matter production in association with a top quark pair only, this analysis also includes production modes with a single top quark. The results are derived from the combination of multiple selection categories that are defined to target either the single top quark or the top quark pair signature. No significant deviations with respect to the standard model predictions are observed. The results are interpreted in the context of a simplified model in which a scalar or pseudoscalar mediator particle couples to a top quark and subsequently decays into dark matter particles. Scalar and pseudoscalar mediator particles with masses below 290 and 300 GeV, respectively, are excluded at 95% confidence level, assuming a dark matter particle mass of 1 GeV and mediator couplings to fermions and dark matter particles equal to unity.Peer reviewe

Search for the pair production of light top squarks in the e(+/-)mu(-/+) final state in proton-proton collisions at root s=13 TeV

A search for the production of a pair of top squarks at the LHC is presented. This search targets a region of parameter space where the kinematics of top squark pair production and top quark pair production are very similar, because of the mass difference between the top squark and the neutralino being close to the top quark mass. The search is performed with 35.9 fb(-1) of proton-proton collisions at a centre-of-mass energy of root s = 13 TeV, collected by the CMS detector in 2016, using events containing one electron-muon pair with opposite charge. The search is based on a precise estimate of the top quark pair background, and the use of the M-T2 variable, which combines the transverse mass of each lepton and the missing transverse momentum. No excess of events is found over the standard model predictions. Exclusion limits are placed at 95% confidence level on the production of top squarks up to masses of 208 GeV for models with a mass difference between the top squark and the lightest neutralino close to that of the top quark.Peer reviewe

Search for Higgs boson pair production in the gamma gamma b(b)over-bar final state in pp collisions at root s=13 TeV

A search is presented for the production of a pair of Higgs bosons, where one decays into two photons and the other one into a bottom quark-antiquark pair. The analysis is performed using proton-proton collision data at root s = 13 TeV recorded in 2016 by the CMS detector at the LHC, corresponding to an integrated luminosity of 35.9 fb(-1) . The results are in agreement with standard model (SM) predictions. In a search for resonant production, upper limits are set on the cross section for new spin-0 or spin-2 particles. For the SM-like nonresonant production hypothesis, the data exclude a product of cross section and branching fraction larger than 2.0 fb at 95% confidence level (CL), corresponding to about 24 times the SM prediction. Values of the effective Higgs boson self-coupling K X are constrained to be within the range -11 < K-lambda < 17 at 95% CL, assuming all other Higgs boson couplings are at their SM value. The constraints on K-lambda, are the most restrictive to date. (C) 2018 The Author(s). Published by Elsevier B.V.Peer reviewe

Search for an exotic decay of the Higgs boson to a pair of light pseudoscalars in the final state with two bquarks and two tau leptons in proton-proton collisions at root s=13 TeV The CMS Collaboration

A search for an exotic decay of the Higgs boson to a pair of light pseudoscalar bosons is performed for the first time in the final state with two b quarks and two tau leptons. The search is motivated in the context of models of physics beyond the standard model (SM), such as two Higgs doublet models extended with a complex scalar singlet (2HDM + S), which include the next-to-minimal supersymmetric SM (NMSSM). The results are based on a data set of proton-proton collisions corresponding to an integrated luminosity of 35.9 fb(-1), accumulated by the CMS experiment at the LHC in 2016 at a center-of-mass energy of 13 TeV. Masses of the pseudoscalar boson between 15 and 60 GeVare probed, and no excess of events above the SM expectation is observed. Upper limits between 3 and 12% are set on the branching fraction B(h -> aa -> 2 tau 2b) assuming the SM production of the Higgs boson. Upper limits are also set on the branching fraction of the Higgs boson to two light pseudoscalar bosons in different 2HDM + S scenarios. Assuming the SM production cross section for the Higgs boson, the upper limit on this quantity is as low as 20% for a mass of the pseudoscalar of 40 GeV in the NMSSM. (C) 2018 The Author(s). Published by Elsevier B.V.Peer reviewe

Search for contact interactions and large extra dimensions in the dilepton mass spectra from proton-proton collisions at \sqrt{s} = 13 TeV

A search for nonresonant excesses in the invariant mass spectra of electron and muon pairs is presented. The analysis is based on data from proton-proton collisions at a center-of-mass energy of 13 TeV recorded by the CMS experiment in 2016, corresponding to a total integrated luminosity of 36 fb^{-1}. No significant deviation from the standard model is observed. Limits are set at 95% confidence level on energy scales for two general classes of nonresonant models. For a class of fermion contact interaction models, lower limits ranging from 20 to 32 TeV are set on the characteristic compositeness scale Λ. For the Arkani-Hamed, Dimopoulos, and Dvali model of large extra dimensions, the first results in the dilepton final state at 13 TeV are reported, and values of the ultraviolet cutoff parameter Λ_{T} below 6.9 TeV are excluded. A combination with recent CMS diphoton results improves this exclusion to Λ_{T} below 7.7 TeV, providing the most sensitive limits to date in nonhadronic final states