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Supplementary Figure from PIM2 Expression Induced by Proinflammatory Macrophages Suppresses Immunotherapy Efficacy in Hepatocellular Carcinoma

Cancer immunotherapy restores or enhances the effector function of T cells in the tumor microenvironment, but the efficacy of immunotherapy has been hindered by therapeutic resistance. Here, we identify the proto-oncogene serine/threonine protein kinase PIM2 as a novel negative feedback regulator of IFNγ-elicited tumor inflammation, thus endowing cancer cells with aggressive features. Mechanistically, IL1β derived from IFNγ-polarized tumor macrophages triggered PIM2 expression in cancer cells via the p38 MAPK/Erk and NF-κB signaling pathways. PIM2+ cancer cells generated by proinflammatory macrophages acquired the capability to survive, metastasize, and resist T-cell cytotoxicity and immunotherapy. A therapeutic strategy combining immune checkpoint blockade (ICB) with IL1β blockade or PIM2 kinase inhibition in vivo effectively and successfully elicited tumor regression. These results provide insight into the regulatory and functional features of PIM2+ tumors and suggest that strategies to influence the functional activities of inflammatory cells or PIM2 kinase may improve the efficacy of immunotherapy.Significance:Cross-talk between T cells and macrophages regulates cancer cell PIM2 expression to promote cancer aggressiveness, revealing translational approaches to improve response to ICB in hepatocellular carcinoma.

Supplementary Data from PIM2 Expression Induced by Proinflammatory Macrophages Suppresses Immunotherapy Efficacy in Hepatocellular Carcinoma

To develop a new way of renewable utilization of ground granular blast furnace slag (GGBFS), a novel ZnO-loaded graphene-reinforced alkali-activated slag-based geopolymer (ZnO/GASG) nanocomposite was originally prepared. The photocatalytic performance of ZnO/GASG was evaluated by solar hydrogen production and wastewater treatment of dyeing pollutant. The mechanical strength results indicated that the lamellate graphene inserted in the substrate of alkali-activated slag-based geopolymer (ASG) has played a critical role in crack-arresting extension so as to lead the significant increases of compressive and flexural strengthens of GASG test block. The XRD, FESEM and XPS results revealed that ZnO in the form of amorphous state dispersed on the surface of GASG when the loading approached to 2 wt%, and ZnO existed in the form of zincite when the loading was greater than 10 wt%. UV–vis diffuse reflectance spectra demonstrated that the absorption edge all of ZnO/GASG nanocomposites were blue-shifted due to the quantum size effect. The highest photocatalytic activities for H2 production (2281.3 μmol/g) and wastewater degradation (95.7%, solar light) over 15ZnO/GASG composite were ascribed to the efficient separation of photoinduced electron-hole pairs. The hole and hydroxyl radical play significant role in photocatalytic degradation of dyeing pollutant.

Aims Facial features were associated with increased risk of coronary artery disease (CAD). We developed and validated a deep learning algorithm for detecting CAD based on facial photos. Methods and results We conducted a multicentre cross-sectional study of patients undergoing coronary angiography or computed tomography angiography at nine Chinese sites to train and validate a deep convolutional neural network for the detection of CAD (at least one ≥50% stenosis) from patient facial photos. Between July 2017 and March 2019, 5796 patients from eight sites were consecutively enrolled and randomly divided into training (90%, n = 5216) and validation (10%, n = 580) groups for algorithm development. Between April 2019 and July 2019, 1013 patients from nine sites were enrolled in test group for algorithm test. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were calculated using radiologist diagnosis as the reference standard. Using an operating cut point with high sensitivity, the CAD detection algorithm had sensitivity of 0.80 and specificity of 0.54 in the test group; the AUC was 0.730 (95% confidence interval, 0.699–0.761). The AUC for the algorithm was higher than that for the Diamond–Forrester model (0.730 vs. 0.623, P Conclusion Our results suggested that a deep learning algorithm based on facial photos can assist in CAD detection in this Chinese cohort. This technique may hold promise for pre-test CAD probability assessment in outpatient clinics or CAD screening in community. Further studies to develop a clinical available tool are warranted.

Cancer immunotherapy restores or enhances the effector function of T cells in the tumor microenvironment, but the efficacy of immunotherapy has been hindered by therapeutic resistance. Here, we identify the proto-oncogene serine/threonine protein kinase PIM2 as a novel negative feedback regulator of IFNγ-elicited tumor inflammation, thus endowing cancer cells with aggressive features. Mechanistically, IL1β derived from IFNγ-polarized tumor macrophages triggered PIM2 expression in cancer cells via the p38 MAPK/Erk and NF-κB signaling pathways. PIM2+ cancer cells generated by proinflammatory macrophages acquired the capability to survive, metastasize, and resist T-cell cytotoxicity and immunotherapy. A therapeutic strategy combining immune checkpoint blockade (ICB) with IL1β blockade or PIM2 kinase inhibition in vivo effectively and successfully elicited tumor regression. These results provide insight into the regulatory and functional features of PIM2+ tumors and suggest that strategies to influence the functional activities of inflammatory cells or PIM2 kinase may improve the efficacy of immunotherapy. Significance: Cross-talk between T cells and macrophages regulates cancer cell PIM2 expression to promote cancer aggressiveness, revealing translational approaches to improve response to ICB in hepatocellular carcinoma.

Objectives To evaluate the 3-year clinical outcomes of a polymer-free sirolimus-eluting, Nano plus stent for the treatment of coronary artery disease in the NANO multicenter Registry. Background The long-term clinical data evaluating the safety and efficacy of the novel polymer-free sirolimus-eluting Nano plus stent (Lepu Medical, Beijing, China) is limited. Methods The NANO all-comers Registry trial was a prospective, multicenter clinical registry conducted in 26 centers in China between August 2016 and January 2017. A total of 2481 consecutive patients were exclusively treated with the Nano plus stent. The primary clinical endpoint, target lesion failure (TLF, defined as cardiac death, target vessel nonfatal myocardial infarction, and clinically driven target lesion revascularization [CD-TLR]), was analyzed at 3 years. Results At 3 years, 2295 patients (92.5%) were followed. The incidence of TLF was 6.8% (168/2481). The rate of cardiac death was 3.8% (94/2481), target vessel nonfatal myocardial infarction 0.7% (18/2481), and CD-TLR 2.9% (68/2481). The rate of definite/probable stent thrombosis was 0.5% (13/2481). The risk factors of diabetes mellitus, acute myocardial infarction, age, chronic renal failure, in-stent restenosis, chronic total occlusion, and left ventricular ejection fraction Conclusions At three years, the rate of TLF was relatively low in patients treated with the polymer-free Nano plus stent. The polymer-free Nano plus stent showed a favorable safety and efficacy profile in real-world patients. Clinical trial registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT02929030.

A novel and eco-efficient CaMoO4/electroconductive geopolymer composite (CaMoO4/EGC) was synthesized for the first time to realize double goals of high-value recycling of silicomanganese slag (SS) and effective treatment of dye wastewater by photocatalytic degradation. The XRD and XPS results demonstrated that the CaMoO4 active phase was formed by the reaction between silicomanganese slag-based geopolymer and (NH4)6Mo7O24⋅4H2O. The BET specific surface areas of CaMoO4/EGC samples increased with increasing content of CaMoO4. The FESEM results indicated that the elements of S, Mn, Mo and Ca evenly distributed in the matrix of 4CaMoO4/EGC. The photoluminescence (PL) spectrum showed that 4CaMoO4/EGC possessed the lowest PL peak at 469 nm and could have the highest photocatalytic activity. The response surface methodology (RSM) was employed to evaluate the main influence factors on the degradation rate of Basic Violet 5BN (BV5) dye and to predict the optimal condition of photocatalytic degradation. The variance analysis results of F-value (75.33), p-value (

Background: Both stereotactic body radiotherapy (SBRT) and radiofrequency ablation (RFA) are effective local treatments for hepatocellular carcinoma (HCC), but whether RFA is superior to SBRT is still controversial. Therefore, we performed a meta-analysis to compare the treatment outcomes of SBRT with RFA as curable or bridge intention. Methods: We searched online databases for studies that compared treatment outcomes for SBRT and RFA. Eligibility criteria included evaluation of local control, overall survival (OS), transplant rate, and post-transplant pathological necrosis. Results: As no randomized clinical trials met the criteria, 10 retrospective studies with a total of 2,732 patients were included. Two studies were in favor of SBRT in local control, two studies preferred RFA in OS, and others reported comparable outcomes for both. SBRT demonstrated significantly higher 1- and 3-year local control than RFA [odds ratio (OR) 0.42, 95% CI 0.24-0.74, P = 0.003; and OR 0.54, 95% CI 0.37-0.80, P = 0.002, respectively]. However, SBRT reported significantly shorter 1- and 2-year OS (OR 1.52, 95% CI 1.21-1.90, P = 0.0003; and OR 1.66, 95% CI 1.38-2.01, P < 0.00001, respectively). As bridge treatment, no significant difference was shown in transplant rate and post-transplant pathological necrosis rate (OR 0.57, 95% CI 0.32-1.03, P = 0.060; and OR 0.49, 95% CI 0.13-1.82, P = 0.290, respectively). Conclusions: This study demonstrates SBRT is able to complete a better local control for HCC than RFA, though the OS is inferior to RFA because of tumor burden or liver profiles of the enrolled studies. Well-designed, randomized, multicenter trials will be required to further investigate the conclusion.

Amine functionalized solid sorbents exhibit promising prospects for post-combustion CO2 capture. One of the most significant challenges at present is the development of cost-effective supports with excellent pore structure and surface texture for amine loading. In this study, geopolymer was treated with nitric acid to suitable degrees. Changes in the porosity, surface silanol density, and degree of polymerization of the geopolymer matrix were systematically evaluated using various spectroscopic techniques, and a mechanism for such regulation was proposed. Moreover, these changes were compared with the variation in the amine grafting amounts and CO2 capture capabilities. Geopolymers treated under an appropriate acid condition exhibits an unexpectedly large specifical surface area of 412 m2/g with a superior silanol density of 4.25 mmol/g being achieved, which facilitate a high (3-Aminopropyl)triethoxysilane (APTES) grafting amount of 3.5 mmol N/g. The as-prepared amine functionalized solid sorbent showed a CO2 adsorption capacity of 1.82 mmol/g at 1 atm and 60 ℃, with fast adsorption kinetics and low energy requirement for regeneration, which are competitive with sorbents prepared using traditional silica supports, despite its simple and robust fabrication route. The superior amine grafting capability of the support and CO2 capture performance of the resultant sorbent are related to the special Si-O(Na)-Al network parent structure of the geopolymer matrix, which allows the formation of abundant pore structures and reserved Si-OH groups that are conveniently achieved via the release of Na and Al during acid regulation. Beyond the confines of this study, the present work would provide new opportunities for cost-effective and efficient preparation of materials that require matrices of high porosity and silanol density.

Background Tremendous efforts have been made to establish the concept of vascular restoration therapy with a fully bioresorbable scaffold for coronary artery disease. With an improved scaffold design and technologies, the novel NeoVas scaffold has shown promising clinical performance at 6 months follow-up. Objective The aim of this study was to investigate the 1 year clinical outcomes and multislice computed tomography (MSCT) angiographic results after implantation of the NeoVas scaffold in patients with single de novo coronary artery lesions. Methods The NeoVas first-in-man study was a prospective, two-center, single-arm study enrolling 31 patients who were eligible for the treatment. The composite endpoint of target lesion failure (TLF)-defined as cardiac death, target vessel myocardial infarction, and clinically indicated target lesion revascularization (TLR)-was assessed. Of the 31 patients scheduled for 1 year clinical follow-up, 29 patients received MSCT examinations. Results At 1 year follow-up, there was only 1 (3.2%) TLF, attributed to 1 patient who suffered ischemia-driven TLR at 181 days postprocedure. No cardiac deaths or scaffold thrombosis were observed. MSCT analysis demonstrated excellent vessel patency, with a median in-scaffold lumen area of 10.6 mm2 (interquartile range [IQR]: 8.2-11.7 mm2 ) and a minimal lumen diameter of 2.7 mm (IQR: 2.4-3.0 mm). Conclusions This study demonstrated the safety and efficacy of the NeoVas scaffold for patients with single de novo coronary artery lesions at 1 year of follow-up. Noninvasive MSCT data confirmed vessel patency and the maintenance of vessel dimensions following implantation of the NeoVas bioresorbable sirolimus-eluting scaffold.

Fly ash-based geopolymer (FAG) possesses extremely low electroconductivity (0.00086 S/m). A new study indicates that graphene could be used as an electron acceptor to improve electroconductivity of geopolymer. In this paper, an electroconductive graphene (GR)/fly ash-based geopolymer (GR/FAG) composite was synthesized by assembly of graphene into the matrix of alkali-activated fly ash-based geopolymer for first time. The results showed that the electroconductivity increased by 348.8 times when adding 1 wt% GR in FAG. The electrochemical impedance of 1.0GR/FAG was much smaller than that of the pure FAG. The N2 adsorption-desorption isotherms indicated that the graphene could effectively improve the microstructure and pore parameters of FAG. The SEM and EDS results displayed the flake graphene was covered by amorphous fly ash-based geopolymer gels. The XPS results demonstrated that the C C/C C binding energy was predominant surface state. The results of UV–Vis-DRS and PL spectra revealed that the absorption onsets of GR/FAG composites were red-shifted and the photoluminescence intensities progressively decreased with increasing graphene content. The photocatalytic degradation of indigo carmine dye was positive correlation with the electroconductivity of GR/FAG composite, and underwent a degradation mechanism of hydroxyl radical.

Surface modification of activated carbon is an effective strategy to enhance its adsorption performance. However, most studies have focused on the use of chemical modifiers, and the products are usually in a powder form. Herein, we report the effective surface modification of activated carbon through geopolymer chemistry via simultaneous alkali-activated functionalization and polycondensation, thus yielding a monolithic adsorbent. The CO2 adsorption capacity of the optimized adsorbent was 2.25 times higher than that of the average of the constituents. Moreover, geopolymers can also function as efficient binders to supply a sufficient compressive strength of 22.3 MPa for the resultant adsorbent. Under different conditions, significant surface texture reconstruction of activated carbon was observed and confirmed via systematic XRD, FESEM, BET, XPS, and Raman spectrum characterisations combined with density functional theory (DFT) calculations. The effective surface modification was associated with the high alkaline environment during the geopolymerization reaction, which intercalates –C O, -OK, and -COOK functional groups on the activated carbon surface. These groups exhibited stronger CO2 affinity than that of pure activated carbon and thus endowed the high-strength adsorbent with enhanced CO2 adsorption capacity.

The transformation of geopolymers into zeolite materials for use as bulk-type adsorbents is an outstanding strategy for water pollution control. However, only sodium ion (Na+)-type zeolites can be typically obtained from geopolymers, which limits their variety. In this study, Li-ABW zeolite (Li-ABW), K–F zeolite (K–F), and phillipsite, were obtained via the hydrothermal transformation of a circulating fluidized bed fly ash (CFBFA)-based geopolymer using single alkali metal cations of either lithium (Li+) or potassium (K+), as well as coexisting Na+ and K+ as structure-directing agents. X-ray diffractometry and field emission scanning electron microscopy indicate that the amorphous CFBFA-based geopolymer was converted into well-defined Li-ABW zeolite, K–F zeolite, and phillipsite. The obtained zeolite products were subsequently employed as adsorbents to remove lead ions (Pb2+) from the aqueous solution, leading to adsorption capacities of 160.70, 239.50 and 252.70 mg/g for Li-ABW, K–F, and phillipsite, respectively. The kinetics of Pb2+ adsorption on the three zeolite samples fit the pseudo-second order model well, suggesting that Pb2+ adsorption on the zeolite samples occurs via chemical adsorption. The adsorption isotherms followed the Langmuir model, thereby confirming monolayer adsorption of Pb2+ on the as-synthesized zeolites. The combined results indicate that the zeolites derived from the CFBFA-based geopolymers are appropriate for Pb2+ removal from wastewater. This work provides new insights for the use of CFBFA industrial waste and the development of geopolymer-based adsorbents for the sustainable development of wastewater treatment methods.

Advances in our understanding about atherosclerotic evolution have enabled us to identify specific plaque characteristics that are associated with coronary plaque vulnerability and cardiovascular events. With constant improvements in signal and image processing an arsenal of invasive and non-invasive imaging modalities have been developed that are capable of identifying these features allowing in vivo assessment of plaque vulnerability. Areas covered: This review article presents the available and emerging imaging modalities introduced to assess plaque morphology and biology, describes the evidence from the first large scale studies that evaluated the efficacy of invasive and non-invasive imaging in detecting lesions that are likely to progress and cause cardiovascular events and discusses the potential implications of the in vivo assessment of coronary artery pathology in the clinical setting. Expert commentary: Invasive imaging, with its high resolution, and in particular hybrid intravascular imaging appears as the ideal approach to study the mechanisms regulating atherosclerotic disease progression; whereas non-invasive imaging is expected to enable complete assessment of coronary tree pathology, detection of high-risk lesions, more accurate risk stratification and thus to allow a personalized treatment of vulnerable patients.

Purpose: Immunotherapy combined with chemotherapy have synergistic effects in multiple malignancies. We aimed to compare the efficacy and safety of toripalimab plus hepatic arterial infusion chemotherapy (HAIC) of oxaliplatin, fluorouracil, and leucovorin versus lenvatinib in advanced hepatocellular carcinoma (HCC). Materials and Methods: We conducted this retrospective study at 3 hospitals in China and eligible patients were 18 years or older and had a primary diagnosis of unresectable HCC with macroscopic vascular invasion and/or extrahepatic spread. These patients were treated with toripalimab plus HAIC or lenvatinib monotherapy. The primary endpoint was progression-free survival (PFS) and the secondary endpoints were overall survival (OS), disease control rate per response evaluation criteria in solid tumors (RECIST) 1.1, and objective response rate (ORR) per RECIST 1.1. The results were compared by Student's test or the chi-square test, and the survival curves were calculated by the Kaplan–Meier method, and propensity-score matching (PSM) was used to reduce bias. Results: A total of 118 patients were recruited for this study: 53 in the TorHAIC group and 65 in the lenvatinib group. We found that the TorHAIC group showed a longer PFS (9.3 [95% CI, 7.81-10.8] vs 4.8 months [95% CI, 3.31−6.29]; hazard ratio [HR] = 0.57, 95% CI, 0.38-0.85; p = .006), a longer OS (17.13 [95% CI, 13.99−20.27] vs 10.1 months [95% CI, 8.14−12.06]; HR = 0.5, 95% CI, 0.31 − 0.81; p = .005), a higher disease control rate (86.8% vs 69.2%, p = .002) and a higher ORR (47.2% vs 9.2%, p

Quench-back from the mandrel has been widely used in quench protection of superconducting magnets. The rational use of quench-back requires detailed understanding of the heat transfer and electromagnetic process in the magnet during a quench process. A coupled transient thermal-electromagnetic-circuit finite-element model was developed to study the quench process with quench-back. This model sequentially solves two different physics models: one is the thermal physics model, which is used to solve the 3-D temperature field, and the other one is the coupled electromagnetic-circuit physics model, which is used to solve the 2-D axisymmetric electromagnetic field and lumped circuit model. The two models are coupled by applying results from one model as inputs into the other model. The quench process of two solenoid magnets in practical engineering is calculated using this model. Results, such as current, hot-spot temperature, and overvoltage during the quench process, were presented. The effect of quench-back on speeding up the quench process is presented. This can provide a theoretical guidance for application of quench-back in quench protection.

A hetero-structure activated carbon/geopolymer composite catalyst enhanced with iron was fabricated via facile activated carbon embedded polymerization and controlled impregnation. Over the temperature window of 350-500 ℃, the as-synthesized catalyst exhibited NO conversion greater than 96.5%, N2 selectivity above 94% with stable durability, excellent SO2 and H2O resistance. The high NO conversion and N2 selectivity may be associated with synergistic effects of extra-framework iron species in the geopolymer rings and excessive iron species agglomerated to form FeOx clusters on the activated carbon surface with enhanced redox capability. These are attached to the composite catalyst’s unique hetero-structure, where the former provides active sites for lower temperature SCR while the latter provides reactivity at higher temperatures. The complex iron species in the catalyst are facile controllable through impregnation. This composite catalyst demonstrated a new approach for developing cost-effective NH3-SCR catalysts for practical implications.

Maf1 is a transcriptional repressor downstream of mTORC1by inhibiting transcription of lipogenic genes by RNA Pol II and ribosomal/transfer RNA genes by RNA Pol III. We recently showed that Maf1 suppresses the growth of cultured liver cancer cells and xenograft tumors by blocking Akt-mTOR signaling through the tumor suppressor PTEN. However, whether Maf1 has tumor suppressor activity has never been demonstrated in physiologically relevant tumor models. Here, we investigated the role of Maf1 in hepatocarcinogenesis in NRas/Akt- and c-Myc-driven mouse liver cancer models generated by hydrodynamic transfection (HDT). We found that Maf1 or Maf1-4A, a non-phosphorylatable and active form of Maf1, significantly attenuated the development of NRas/Akt-driven liver tumors. On the other hand, while knockdown of Maf1 alone did not cause any discernible abnormality in the mouse liver, down-regulation of Maf1 markedly accelerated c-Myc-induced liver tumor development. At the molecular level, Maf1 strongly suppressed phosphorylation of Akt-mTOR pathway components, including Akt and S6. Conclusions: Maf1 suppresses hepatocarcinogenesis through restraining Akt/mTOR signaling. These new findings provide first in vivo evidence that Maf1 is a liver tumor suppressor. Citation Format: Di Cao, Xiaoxing Li, Yang Yang, Yu-Feng Zhou, Mei-Yin Zhang, Shan-Shan Zhang, Qian-Nan Ren, Hui-Zhong Zhang, Yao-Jun Zhang, Shi-Juan Mai, Hui-Yun Wang. Maf1 suppresses hepatocarcinogenesis in mice through inhibition of Akt-mTOR signaling [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5977.

Geopolymer is a new type of inorganic polymer materials synthesized by reaction of natural mineral or industrial aluminosilicate solid wastes with aqueous solution of alkali-activator under the curing condition of room temperature or below 100 °C. Many research results demonstrated that the chemical structure and physical properties strongly depended on the raw material chemical composition and preparation conditions. Even though geopolymer as new construction material has been extensively investigated in recent years, the essential brittleness still limits it as commercial building material for the application in the field of municipal engineering. Hence, it was urgent for researchers to explore some alternative approaches. Recently, a number of studies reported that the geopolymers were used as various catalysts for environmental governance. The present review described the latest progresses on the synthesis techniques of the geopolymer-based catalysts in detail, and then focused on the current applications in the environmental governance from the view of source control and end-of-pipe treatment, in which the source control included hydrogen generation, biodiesel production and other heterogeneous catalysis, and the end-of-pipe treatment contained photocatalytic degradation of dye wastewater and gas purification. It is considered that the geopolymer is a promising candidate for recycling of industrial solid waste and developing cost-effective heterogeneous catalysts for environmental governance.

Silicomanganese slag is a solid waste in metallurgical industry and can be transformed into an alkali-activated silicomanganese slag-based cementitious-material (ASSC) for the first time. The ASSC shows quite low electro-conductivity and can be raised dramatically by incorporated carbon black (CB) in the matrix of ASSC to create an electro-conductive alkali-activated silicomanganese slag-based cementitious-composite (EASSC), served as a low cost and environmentally-friendly photocatalyst for the removal of dye pollutant in the paper. The interrelationships of mechanical, optical, electroconductive, microstructural, and photocatalytic properties are evaluated. The network of CB plays a critical role in the electron transfers. The electrical conductivity of EASSC doped 4.5% CB drastically increases by 594.2 times compared to that of ASSC. The FESEM, XRD, and XPS results indicated that the EASSC with mean grain size about 50 nm is composed of amorphous calcium silicate hydrate (CSH), alabandite (&alpha, MnS) and CB. The UV&ndash, vis DRS and PL exhibit that the absorption edges of electro-conductive alkali-activated silicomanganese slag-based cementitious-composite EASSC samples are gradually blue-shifted and the photoluminescence intensities progressively decrease with increasing CB content. The activities of photocatalytic degradation of basic violet 5BN dye are positive correlated to the electro-conductivities. The separation efficiency of photo-generated electron-hole pairs is enhanced due to the electron transfers from &alpha, MnS to the network of CB. The photocatalytic degradation of dye pollutant belongs to the second order kinetics via a reaction mechanism of superoxide radical (&bull, O2&minus, ) intermediate.

ObjectiveThe study sought to compare angiographic and clinical outcomes of new-generation drug-eluting stents (DES) versus drug-coated balloon (DCB) in patients with coronary in-stent restenosis (ISR).DesignMeta-analysis using data from randomised trial found by searches on PubMed, the Cochrane Library, ClinicalTrials.gov and websites of major cardiovascular congresses.SettingOnly randomised trials comparing DES with DCB were included.ParticipantsPatients with ISR in the included trials.InterventionsNew-generation DES versus DCB.OutcomesThe angiographic and clinical outcomes including cardiac death, all-cause death, myocardial infarction, target lesion revascularisation (TLR), target vessel revascularisation (TVR), major adverse cardiac events (MACE) and stent thrombosis were investigated.ResultsFive trials including 913 patients were eligible and included. Pooled analysis in angiographic results identified that new-generation DES were associated with higher acute luminal gain (−0.31 mm, 95% CI −0.42 to −0.20, PConclusionsInterventions with new-generation DES appear to be associated with significant reduction in per cent diameter stenosis and TLR at short-term follow-up, but had similar MACE, myocardial infarction and cardiac death for patients with coronary ISR compared with DCB. Appropriately powered studies with longer term follow-up are warranted to confirm these findings.

To examine the implications of endothelial shear stress (ESS) distribution in the formation of neoatherosclerotic lesions.Thirty six patients with neoatherosclerotic lesions on optical coherence tomography (OCT) were included in this study. The OCT data were used to reconstruct coronary anatomy. Blood flow simulation was performed in the models reconstructed from the stent borders which it was assumed that represented the lumen surface at baseline, immediate after stent implantation, and the estimated ESS was associated with the neointima burden, neoatherosclerotic burden and neointima characteristics. In segments with neointima rupture blood flow simulation was also performed in the model representing the lumen surface before rupture and the ESS was estimated at the ruptured site.An inverse association was noted between baseline ESS and the incidence and the burden of neoatherosclerotic (β = -0.60, P 0.001, and β = -4.05, P 0.001, respectively) and lipid-rich neoatherosclerotic tissue (β = -0.54, P 0.001, and β = -3.60, P 0.001, respectively). Segments exposed to low ESS (1 Pa) were more likely to exhibit macrophages accumulation (28.2% vs 10.9%, P 0.001), thrombus (11.0% vs 2.6%, P 0.001) and evidence of neointima discontinuities (8.1% vs 0.9%, P 0.001) compared to those exposed to normal or high ESS. In segments with neointima rupture the ESS was high at the rupture site compared to the average ESS over the culprit lesion (4.00 ± 3.65 Pa vs 3.14 ± 2.90 Pa, P 0.001).Local EES is associated with neoatherosclerotic lesion characteristics, which suggests involvement of ESS in the formation of vulnerable plaques in stented segments.

Spatially and temporally continuous estimation of plant photosynthetic carbon fixation (or gross primary production, GPP) is crucial to our understanding of the global carbon cycle and the impact of climate change. Besides spatial, seasonal and interannual variations, GPP also exhibits strong diurnal variations. Satellite retrieved solar-induced chlorophyll fluorescence (SIF) provides a spatially continuous, but temporally discrete measurement of plant photosynthesis, and has the potential to be used to estimate GPP at global scale. However, it remains unclear whether the seasonal time series of SIF snapshots taken at a fixed time of the day can be used to infer daily total GPP variation at spatial and seasonal scales. In this study, we first used GPP estimates from 135 eddy covariance flux sites, covering a wide range of geographic locations and biome types, to investigate the relationship between the instantaneous GPP (GPPinst) and daily GPP (GPPdaily) on the seasonal course for different times of the day. Latitudinal and diurnal patterns were found to correspond to variations in photosynthetically active radiation (PAR) and light use efficiency (LUE), respectively. We then used the Soil-Canopy Observation Photosynthesis and Energy Balance (SCOPE) model and the FluxCom GPP product to investigate the instantaneous and daily SIF-GPP relationships at five flux tower sites along a latitudinal gradient and at a global scale for different biome types. The results showed that daily SIF had a stronger linear correlation with daily GPP than instantaneous SIF at the seasonal scale, with an instantaneous to daily SIF conversion factor following the latitudinal and seasonal pattern driven by PAR. Our study highlights the necessity to take the latitudinal and diurnal factors into consideration for SIF-GPP relationship analyses or for physiological phenology analyses based on SIF.

Background— There is a paucity of data on the use of optimal medical therapy (OMT) in patients with complex coronary artery disease undergoing revascularization with percutaneous coronary intervention or coronary artery bypass grafting (CABG) and its long-term prognostic significance. Methods and Results— The Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) trial is a multicenter, randomized, clinical trial of patients (n=1800) with complex coronary disease randomized to revascularization with percutaneous coronary intervention or CABG. Detailed drug history was collected for all patients at discharge and at the 1-month, 6-month, 1-year, 3-year, and 5-year follow-ups. OMT was defined as the combination of at least 1 antiplatelet drug, statin, β-blocker, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker. Five-year clinical outcomes were stratified by OMT and non-OMT. OMT was underused in patients treated with coronary revascularization, especially CABG. OMT was an independent predictor of survival. OMT was associated with a significant reduction in mortality (hazard ratio, 0.64; 95% confidence interval, 0.48–0.85; P =0.002) and composite end point of death/myocardial infarction/stroke (hazard ratio, 0.73; 95% confidence interval, 0.58–0.92; P =0.007) at the 5-year follow-up. The treatment effect with OMT (36% relative reduction in mortality over 5 years) was greater than the treatment effect of revascularization strategy (26% relative reduction in mortality with CABG versus percutaneous coronary intervention over 5 years). On stratified analysis, all the components of OMT were important for reducing adverse outcomes regardless of revascularization strategy. Conclusions— The use of OMT remains low in patients with complex coronary disease requiring coronary intervention with percutaneous coronary intervention and even lower in patients treated with CABG. Lack of OMT is associated with adverse clinical outcomes. Targeted strategies to improve OMT use in postrevascularization patients are warranted. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00114972.

Background: Studies have suggested that use of prolonged dual antiplatelet therapy (DAPT) following new generation drug-eluting stent implantation may increase costs and potential bleeding events. This study aimed to investigate the association of DAPT status with clinical safety in patients undergoing everolimus-eluting stent (EES) implantation in the SEEDS study (A Registry to Evaluate Safety and Effectiveness of Everolimus Drug-eluting Stent for Coronary Revascularization) at 2-year follow-up. Methods: The SEEDS study is a prospective, multicenter study, where patients ( n = 1900) with small vessel, long lesion, or multi-vessel diseases underwent EES implantation. Detailed DAPT status was collected at baseline, 6-month, 1- and 2-year. DAPT interruption was defined as any interruption of aspirin and/or clopidogrel more than 14 days. The net adverse clinical events (NACE, a composite endpoint of all-cause death, all myocardial infarction (MI), stroke, definite/probable stent thrombosis (ST), and major bleeding (Bleeding Academic Research Consortium II-V)) were investigated according to the DAPT status at 2-year follow-up. Results: DAPT was used in 97.8% of patients at 6 months, 69.5% at 12 months and 35.4% at 2 years. It was observed that the incidence of NACE was low (8.1%) at 2 years follow-up, especially its components of all-cause death (0.9%), stroke (1.1%), and definite/probable ST (0.7%). DAPT was not an independent predictor of composite endpoint of all-cause death/MI/stroke (hazard ratio [ HR ]: 0.693, 95% confidence interval [ CI ]: 0.096-4.980, P = 0.715) and NACE ( HR : 1.041, 95% CI : 0.145-7.454, P = 0.968). Of 73 patients who had DAPT interruption, no patient had ST at 12-month, and only 1 patient experienced ST between 1- and 2-year (1.4%). There was a high frequency of major bleeding events (53/65, 82.5%) occurred in patients receiving DAPT treatment. Conclusions: Prolonged DAPT use was not associated with improved clinical safety. The study emphasized that duration of DAPT needs to be shortened in Chinese patients following EES implantation (ClinicalTrials.gov identifier: NCT 01157455).

Background Cigarette smoking is a well-known risk factor for development of coronary artery disease (CAD). However, some studies have suggested a "smoker's paradox," meaning neutral or favorable outcomes in smokers who have developed CAD, especially myocardial infarction (MI). Objectives The study aimed to examine the association of smoking status with clinical outcomes in the randomized controlled SYNTAX (SYNergy Between PCI With TAXUS and Cardiac Surgery) trial at 5-year follow-up. Methods Detailed smoking history was collected at baseline, 6-month, 1-year, 3-year, and 5-year follow-up. The composite endpoints included death/MI/stroke (primary endpoint) plus major adverse cardiac and cerebrovascular events (MACCE) (combination of death/MI/stroke and target lesion revascularization) according to patient smoking status. The comparison of 5-year clinical outcomes between the groups according to smoking status was performed with Cox regression using smoking status at baseline or smoking as a time-dependent covariate. Results A sizeable proportion (n = 322, 17.9%) of patients had changing smoking status during 5-year follow-up. One in 5 patients with complex CAD was smoking at baseline. However, 60% stopped after revascularization while others continued to smoke. Smokers had worse clinical outcomes due to a higher incidence of recurrent MI in both revascularization arms. Smoking was an independent predictor of the composite endpoint of death/MI/stroke (hazard ratio [HR]: 1.8; 95% confidence interval [CI]: 1.3 to 2.5; p = 0.001) and MACCE (HR: 1.4; 95% CI: 1.1 to 1.7; p = 0.02). Conclusions Smoking is associated with poor clinical outcomes after revascularization in patients with complex CAD. This places further emphasis on efforts at smoking cessation to improve revascularization benefits. (SYNTAX Study: TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries; NCT00114972)

Objective To investigate clinical outcomes of coronary intervention using a biolimus-eluting stent (BES) compared with a sirolimus-eluting stent (SES) in patients with acute myocardial infarction (AMI) in the L imus E luted from A D urable versus ER odable Stent (LEADERS) coating trial at the final 5-year follow-up. Methods The LEADERS trial is a multicentre all-comer study, where patients (n=1707) were randomised to percutaneous intervention with either BES containing biodegradable polymer or SES containing durable polymer. Out of 1707 patients enrolled in this trial, 573 patients had percutaneous coronary intervention for AMI (BES=280, SES=293) and were included in the current analysis. Patient-oriented composite endpoint (POCE, including all death, all myocardial infarction (MI) and all revascularisations), major adverse cardiac events (MACE, including cardiac death, MI and clinically indicated target vessel revascularisation) and stent thrombosis were assessed at 5-year follow-up. Results The baseline clinical, angiographic and procedural characteristics were well matched between BES and SES groups. In all patients with AMI, coronary intervention with a BES, compared with SES, significantly reduced POCE (28.9% vs 42.3%; relative risk (RR) 0.61, 95% CI 0.47 to 0.82, p=0.001) at 5-year follow-up. There was also a reduction in MACE rate in the BES group (18.2% vs 25.9%; RR 0.67, 95% CI 0.47 to 0.95, p=0.025); however, there was no difference in cardiac death and stent thrombosis. In patients with ST-elevation MI (STEMI), coronary intervention with BES significantly reduced POCE (24.4% vs 39.3%; RR 0.55, 95% CI 0.36 to 0.85, p=0.006), MACE (12.6% vs 25.0%; RR 0.47, 95% CI 0.26 to 0.83, p=0.008) and cardiac death (3.0% vs 11.4%; RR 0.25, 95% CI 0.08 to 0.75, p=0.007), along with a trend towards reduction in definite stent thrombosis (3.7% vs 8.6%; RR 0.41, 95% CI 0.15 to 1.18, p=0.088), compared with SES. Conclusions BES, compared with SES, significantly improved safety and efficacy outcomes in patients with AMI, especially those with STEMI, at 5-year follow-up. Trial registration number NCT 00389220.

Objectives This study sought to investigate the in-scaffold vascular response (SVR) and edge vascular response (EVR) after implantation of an everolimus-eluting bioresorbable scaffold (BRS) using serial optical coherence tomography (OCT) imaging. Background Although studies using intravascular ultrasound have evaluated the EVR in metal stents and BRSs, there is a lack of OCT-based SVR and EVR assessment after BRS implantation. Methods In the ABSORB Cohort B (ABSORB Clinical Investigation, Cohort B) study, 23 patients (23 lesions) in Cohort B1 and 17 patients (18 lesions) in Cohort B2 underwent truly serial OCT examinations at 3 different time points (Cohort B1: post-procedure, 6 months, and 2 years; B2: post-procedure, 1 year, and 3 years) after implantation of an 18-mm scaffold. A frame-by-frame OCT analysis was performed at the 5-mm proximal, 5-mm distal edge, and 2-mm in-scaffold margins, whereas the middle 14-mm in-scaffold segment was analyzed at 1-mm intervals. Results The in-scaffold mean luminal area significantly decreased from baseline to 6 months or 1 year (7.22 ± 1.24 mm 2 vs. 6.05 ± 1.38 mm 2 and 7.64 ± 1.19 mm 2 vs. 5.72 ± 0.89 mm 2 , respectively; both p 2 vs. 5.58 ± 1.53 mm 2 ; p Conclusions This OCT-based serial EVR and SVR evaluation of the Absorb Bioresorbable Vascular Scaffold (Abbott Vascular, Santa Clara, California) showed less luminal loss at the edges than luminal loss within the scaffold. The luminal reduction of both edges is not a nosologic entity, but an EVR in continuity with the SVR, extending from the in-scaffold margin to both edges. (ABSORB Clinical Investigation, Cohort B [ABSORB B]; NCT00856856 )

Intravascular imaging-based natural history studies of atherosclerosis have provided insight into atherosclerotic evolution and demonstrated that local hemodynamic factors, plaque burden, and the composition of the atheroma regulate plaque growth and determine vulnerable plaque formation [(1,2)][1

Bioresorbable vascular scaffolds (BRS) represent a novel approach to provide transient vessel support to drug-delivery capability without the long-term limitations of metallic drug-eluting stents (DES). The technology has the potential to overcome many of the safety concerns associated with metallic DES and possibly even convey further clinical benefit. In particular, the BRS are designed to provide short-term lumen support, and after being completely bioresorbed, eliminate the permanent caging typical of metallic DES. However, this technology has required new imaging modalities and methodologies for its assessment because the design, degradation rate, loss of mechanical property, and drug deliverability may affect its safety and efficacy. We provide an overview of all existing methods for assessing bioresorbable devices, from noninvasive to invasive, from light to sound based, and from morphological to functional parameters.

Objectives The present study established criteria to differentiate simple from complex bifurcation lesions and compared 1-year outcomes stratified by lesion complexity after provisional stenting (PS) and 2-stent techniques using drug-eluting stents. Background Currently, no criterion can distinguish between simple and complex coronary bifurcation lesions. Comparisons of PS and 2-stent strategies stratified by lesion complexity have also not been reported previously. Methods Criteria of bifurcation complexity in 1,500 patients were externally tested in another 3,660 true bifurcation lesions after placement of drug-eluting stents. The primary endpoint was the occurrence of a major adverse cardiac event (MACE) at 12 months. The secondary endpoint was the rate of stent thrombosis (ST). Results Complex (n = 1,108) bifurcation lesions were associated with a higher 1-year rate of MACE (16.8%) compared with simple (n = 2,552) bifurcation lesions (8.9%) (p Conclusions Complex bifurcation lesions had higher rates of 1-year MACE and ST. The 2-stent and PS techniques were overall equivalent in 1-year MACE. However, 2-stent techniques for complex lesions elicited a lower rate of cardiac death and in-hospital MACE but higher rates of in-hospital ST and revascularization at 1 year for simple lesions.