Despite advances in treatment, mortality in acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) remains high. Short-term mechanical circulatory support devices acutely improve ...hemodynamic conditions.
The aim of this study was to determine whether a new percutaneous mechanical circulatory support (pMCS) device (Impella CP, Abiomed, Danvers, Massachusetts) decreases 30-day mortality when compared with an intra-aortic balloon pump (IABP) in patients with severe shock complicating AMI.
In a randomized, prospective, open-label, multicenter trial, 48 patients with severe CS complicating AMI were assigned to pMCS (n = 24) or IABP (n = 24). Severe CS was defined as systolic blood pressure <90 mm Hg or the need for inotropic or vasoactive medication and the requirement for mechanical ventilation. The primary endpoint was 30-day all-cause mortality.
At 30 days, mortality in patients treated with either IABP or pMCS was similar (50% and 46%, respectively; hazard ratio with pMCS: 0.96; 95% confidence interval: 0.42 to 2.18; p = 0.92). At 6 months, mortality rates for both pMCS and IABP were 50% (hazard ratio: 1.04; 95% confidence interval: 0.47 to 2.32; p = 0.923).
In this explorative randomized controlled trial involving mechanically ventilated patients with CS after AMI, routine treatment with pMCS was not associated with reduced 30-day mortality compared with IABP. (IMPRESS in Severe Shock; NTR3450)
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The first day of the Cenozoic Gulick, Sean P. S.; Bralower, Timothy J.; Ormö, Jens ...
Proceedings of the National Academy of Sciences - PNAS,
09/2019, Letnik:
116, Številka:
39
Journal Article
Recenzirano
Odprti dostop
Highly expanded Cretaceous-Paleogene (K-Pg) boundary section from the Chicxulub peak ring, recovered by International Ocean Discovery Program (IODP)-International Continental Scientific Drilling ...Program (ICDP) Expedition 364, provides an unprecedented window into the immediate aftermath of the impact. Site M0077 includes ∼130 m of impact melt rock and suevite deposited the first day of the Cenozoic covered by <1 m of micrite-rich carbonate deposited over subsequent weeks to years. We present an interpreted series of events based on analyses of these drill cores. Within minutes of the impact, centrally uplifted basement rock collapsed outward to forma peak ring capped in melt rock. Within tens of minutes, the peak ring was covered in ∼40 m of brecciated impact melt rock and coarsegrained suevite, including clasts possibly generated by melt-water interactions during ocean resurge. Within an hour, resurge crested the peak ring, depositing a 10-m-thick layer of suevite with increased particle roundness and sorting.Within hours, the full resurge deposit formed through settling and seiches, resulting in an 80-m-thick fining-upward, sorted suevite in the flooded crater. Within a day, the reflected rim-wave tsunami reached the crater, depositing a cross-bedded sand-to-fine gravel layer enriched in polycyclic aromatic hydrocarbons overlain by charcoal fragments. Generation of a deep crater open to the ocean allowed rapid flooding and sediment accumulation rates among the highest known in the geologic record. The high-resolution section provides insight into the impact environmental effects, including charcoal as evidence for impactinduced wildfires and a paucity of sulfur-rich evaporites from the target supporting rapid global cooling and darkness as extinction mechanisms.
Bioresorbable vascular scaffolds were developed to overcome the shortcomings of drug-eluting stents in percutaneous coronary intervention (PCI). We performed an investigator-initiated, randomized ...trial to compare an everolimus-eluting bioresorbable scaffold with an everolimus-eluting metallic stent in the context of routine clinical practice.
We randomly assigned 1845 patients undergoing PCI to receive either a bioresorbable vascular scaffold (924 patients) or a metallic stent (921 patients). The primary end point was target-vessel failure (a composite of cardiac death, target-vessel myocardial infarction, or target-vessel revascularization). The data and safety monitoring board recommended early reporting of the study results because of safety concerns. This report provides descriptive information on end-point events.
The median follow-up was 707 days. Target-vessel failure occurred in 105 patients in the scaffold group and in 94 patients in the stent group (2-year cumulative event rates, 11.7% and 10.7%, respectively; hazard ratio, 1.12; 95% confidence interval CI, 0.85 to 1.48; P=0.43); event rates were based on Kaplan-Meier estimates in time-to-event analyses. Cardiac death occurred in 18 patients in the scaffold group and in 23 patients in the stent group (2-year cumulative event rates, 2.0% and 2.7%, respectively), target-vessel myocardial infarction occurred in 48 patients in the scaffold group and in 30 patients in the stent group (2-year cumulative event rates, 5.5% and 3.2%), and target-vessel revascularization occurred in 76 patients in the scaffold group and in 65 patients in the stent group (2-year cumulative event rates, 8.7% and 7.5%). Definite or probable device thrombosis occurred in 31 patients in the scaffold group as compared with 8 patients in the stent group (2-year cumulative event rates, 3.5% vs. 0.9%; hazard ratio, 3.87; 95% CI, 1.78 to 8.42; P<0.001).
In this preliminary report of a trial involving patients undergoing PCI, there was no significant difference in the rate of target-vessel failure between the patients who received a bioresorbable scaffold and the patients who received a metallic stent. The bioresorbable scaffold was associated with a higher incidence of device thrombosis than the metallic stent through 2 years of follow-up. (Funded by Abbott Vascular; AIDA ClinicalTrials.gov number, NCT01858077 .).
Abstract
The manufacturing process of cement emits one metric ton of carbon dioxide greenhouse gas. Considering the situation reducing the gas emission without affecting cement production, industrial ...wastes like metakaolin (MK) can be partially replaced with cement due to high pozzolanic reactivity to arrive the high-strength concrete. This present examination attentions on the obtaining optimum percentage of metakaolin to be substituted for cement proportion and aims to determine the concrete sample’s mechanical characteristics, equivalent CO
2
emissions, and energy factor for environmental advantages through comparison with metakaolin varied from 0% to 20% at 5% incremental rate was determined and compared with the conventional control mix. Concrete samples are tested at the periodical interval of 7, 14, and 28 days in addition results, 5% of metakaolin is the optimum percentage to be replaced for cement in concrete. The negative sign implies that replacing binder with MK gradually decreases energy requirements (−2.16% to −7.74%) as well as carbon dioxide emissions (−4.17% to −15.41%). The use of mineral admixture like high reactive metakaolin additional cementitious elements has a considerable effect and may have an impact on the creation of environmentally friendly, sustainable concrete. In conclusion, effective utilization of high reactive metakaolin in high-strength concrete leads to substantial cost, and reducing global gas emissions eventually reduces energy consumption and a notable decrease in environmental pollution.
Yes-associated protein 1 (YAP1) is a multifunctional protein that can interact with different transcription factors to activate gene expression. The role of YAP1 in tumorigenesis is unclear. We aimed ...to investigate the functional role of YAP1 in tumorigenesis of gastric cancer.
YAP1 expression in gastric adenocarcinoma was evaluated. The biological function was determined by proliferation assay, colony formation, cell invasion, and flow cytometric analysis through knocking down or ectopic expressing YAP1 in gastric cancer cell lines coupled with in vivo study. The possible downstream effectors of YAP1 were investigated by expression microarray.
YAP1 protein expression was upregulated in gastric cancer. Nuclear accumulation of YAP1 was associated with poor disease-specific survival (P = 0.021), especially in patients with early-stage diseases (P < 0.001). Knockdown YAP1 resulted in a significant reduction in proliferation, anchorage-dependent colony formation, cell invasion, and cell motility. Ectopic YAP1 expression promoted anchorage-independent colony formation, induced a more invasive phenotype, and accelerated cell growth both in vitro and in vivo. Microarray analysis highlighted the alteration of MAPK (mitogen-activated protein kinase) pathway by YAP1. We confirmed a constitutive activation of RAF/MEK/ERK (extracellular signal-regulated kinase) in YAP1-expressing MKN45 cells and further showed that YAP1 enhanced serum/epidermal growth factor-induced c-Fos expression in gastric cancer cells.
Our findings supported that YAP1 exhibits oncogenic property in gastric cancer. We provided the first evidence that YAP1 exerted the oncogenic function by enhancing the capacity to activate the early-response gene pathway. YAP1 could be a prognostic biomarker and potential therapeutic target for gastric cancer.
The formation of peak rings in large impact craters Morgan, Joanna V.; Gulick, Sean P. S.; Bralower, Timothy ...
Science (American Association for the Advancement of Science),
11/2016, Letnik:
354, Številka:
6314
Journal Article
Recenzirano
Odprti dostop
Large impacts provide a mechanism for resurfacing planets through mixing near-surface rocks with deeper material. Central peaks are formed from the dynamic uplift of rocks during crater formation. As ...crater size increases, central peaks transition to peak rings. Without samples, debate surrounds the mechanics of peak-ring formation and their depth of origin. Chicxulub is the only known impact structure on Earth with an unequivocal peak ring, but it is buried and only accessible through drilling. Expedition 364 sampled the Chicxulub peak ring, which we found was formed from uplifted, fractured, shocked, felsic basement rocks. The peak-ring rocks are cross-cut by dikes and shear zones and have an unusually low density and seismic velocity. Large impacts therefore generate vertical fluxes and increase porosity in planetary crust.
In selected patients with an acute myocardial infarction (AMI) complicated by Cardiogenic shock (CS), mechanical circulatory support with Impella may be beneficial, although conclusive evidence is ...still lacking. Nevertheless, it has been suggested that Impella initiation prior to primary PCI might improve survival. To investigate the effect pre-PCI versus immediate post-PCI Impella initiation on short term mortality. A prospective, single center, observational study, was performed including all patients with STEMI complicated by CS, treated with primary PCI and Impella. Thirty day mortality was compared between patients with Impella initiation pre-PCI and immediately post-PCI. A total of 88 patients were included. In the pre-PCI group (n = 21), admission heart rate was lower (84 versus 94 bpm, p = 0.04) and no IABP was implanted before Impella initiation, versus 17.9% in post-PCI group (n = 67), p = 0.04. Total 30-day all-cause mortality was 58%, and was lower in pre-PCI group, 47.6% versus 61.2% in the post-PCI group, however not statistically significant (HR 0.7, 95% CI 0.3-1.3, p = 0.21). Thirty-day cardiac mortality was significantly lower in the pre-PCI group, 19% versus 44.7% in the post-PCI group (HR 0.3, 95% CI 0.09-0.96, p = 0.042). Pre-PCI Impella initiation in AMICS patients was not associated with a statistically significant difference in 30-day all-cause mortality, compared to post-PCI Impella initiation.
In 10% to 15% of patients with ST-segment elevation myocardial infarction (STEMI), concurrent coronary chronic total occlusion (CTO) in a non-infarct-related artery is present and is associated with ...increased morbidity and mortality.
The EXPLORE (Evaluating Xience and Left Ventricular Function in Percutaneous Coronary Intervention on Occlusions After ST-Elevation Myocardial Infarction) trial evaluated whether patients with STEMI and concurrent CTO in a non-infarct-related artery benefit from additional percutaneous coronary intervention (PCI) of CTO shortly after primary PCI.
From November 2007 through April 2015, we enrolled 304 patients with acute STEMI who underwent primary PCI and had concurrent CTO in 14 centers in Europe and Canada. A total of 150 patients were randomly assigned to early PCI of the CTO (CTO PCI), and 154 patients were assigned to conservative treatment without PCI of the CTO (no CTO PCI). Primary outcomes were left ventricular ejection fraction (LVEF) and left ventricular end diastolic volume (LVEDV) on cardiac magnetic resonance imaging after 4 months.
The investigator-reported procedural success rate in the CTO PCI arm of the trial was 77%, and the adjudicated success rate was 73%. At 4 months, mean LVEF did not differ between the 2 groups (44.1 ± 12.2% vs. 44.8 ± 11.9%, respectively; p = 0.60). Mean LVEDV at 4 months was 215.6 ± 62.5 ml in the CTO PCI arm versus 212.8 ± 60.3 ml in the no-CTO PCI arm (p = 0.70). Subgroup analysis revealed that patients with CTO located in the left anterior descending coronary artery who were randomized to the CTO PCI strategy had significantly higher LVEF compared with patients randomized to the no-CTO PCI strategy (47.2 ± 12.3% vs. 40.4 ± 11.9%; p = 0.02). There were no differences in terms of 4-month major adverse coronary events (5.4% vs. 2.6%; p = 0.25).
Additional CTO PCI within 1 week after primary PCI for STEMI was feasible and safe. In patients with STEMI and concurrent CTO, we did not find an overall benefit for CTO PCI in terms of LVEF or LVEDV. The finding that early CTO PCI in the left anterior descending coronary artery subgroup was beneficial warrants further investigation. (Evaluating Xience and Left Ventricular Function in Percutaneous Coronary Intervention on Occlusions After ST-Segment Elevation Myocardial Infarction; NTR1108).
Early relapse after platinum chemotherapy in epithelial ovarian cancer (EOC) portends poor survival. A‐priori identification of platinum resistance is therefore crucial to improve on standard ...first‐line carboplatin–paclitaxel treatment. The DNA repair pathway homologous recombination (HR) repairs platinum‐induced damage, and the HR recombinase RAD51 is overexpressed in cancer. We therefore designed a REMARK‐compliant study of pre‐treatment RAD51 expression in EOC, using fluorescent quantitative immunohistochemistry (qIHC) to overcome challenges in quantitation of protein expression in situ. In a discovery cohort (n = 284), RAD51‐High tumours had shorter progression‐free and overall survival compared to RAD51‐Low cases in univariate and multivariate analyses. The association of RAD51 with relapse/survival was validated in a carboplatin monotherapy SCOTROC4 clinical trial cohort (n = 264) and was predominantly noted in HR‐proficient cancers (Myriad HRDscore < 42). Interestingly, overexpression of RAD51 modified expression of immune‐regulatory pathways in vitro, while RAD51‐High tumours showed exclusion of cytotoxic T cells in situ. Our findings highlight RAD51 expression as a determinant of platinum resistance and suggest possible roles for therapy to overcome immune exclusion in RAD51‐High EOC. The qIHC approach is generalizable to other proteins with a continuum instead of discrete/bimodal expression.
Synopsis
Quantitative immunohistochemistry (qIHC) reveals that high expression of the DNA repair protein RAD51 in epithelial ovarian cancer is associated with early relapse after platinum chemotherapy, and also with decreased cytotoxic T‐cell infiltration into tumors.
High nuclear expression score for RAD51 (RAD51NES) was correlated with early relapse and shorter survival in two independent EOC patient cohorts (n = 264 + 284).
RAD51NES was prognostically relevant primarily for EOCs that did not have homologous recombination deficiency (HRD).
RAD51 expression was correlated with a unique immune phenotype in cancer, with increased chemokines but reduced cytotoxic T‐cell infiltration.
Quantitative immunohistochemistry (qIHC) reveals that high expression of the DNA repair protein RAD51 in epithelial ovarian cancer (EOC) is associated with early relapse after platinum chemotherapy, and also with decreased cytotoxic T‐cell infiltration into tumors.
Accessory mineral geochronometers such as apatite, baddeleyite, monazite, xenotime and zircon are increasingly being recognized for their ability to preserve diagnostic microstructural evidence of ...hypervelocity-impact processes. To date, little is known about the response of titanite to shock metamorphism, even though it is a widespread accessory phase and a U–Pb geochronometer. Here we report two new mechanical twin modes in titanite within shocked granitoid from the Chicxulub impact structure, Mexico. Titanite grains in the newly acquired core from the International Ocean Discovery Program Hole M0077A preserve multiple sets of polysynthetic twins, most commonly with composition planes (
K
1
) = ~
{
1
¯
11
}
, and shear direction (
η
1
) = < 110 > , and less commonly with the mode
K
1
= {130},
η
1
= ~ <522 > . In some grains, {130} deformation bands have formed concurrently with the deformation twins, indicating dislocation slip with Burgers vector
b
= < 341 > can be active during impact metamorphism. Titanite twins in the modes described here have not been reported from endogenically deformed rocks; we, therefore, propose this newly identified twin form as a result of shock deformation. Formation conditions of the twins have not been experimentally calibrated, and are here empirically constrained by the presence of planar deformation features in quartz (12 ± 5 and ~ 17 ± 5 GPa) and the absence of shock twins in zircon (< 20 GPa). While the lower threshold of titanite twin formation remains poorly constrained, identification of these twins highlight the utility of titanite as a shock indicator over the pressure range between 12 and 17 GPa. Given the challenges to find diagnostic indicators of shock metamorphism to identify both ancient and recent impact evidence on Earth, microstructural analysis of titanite is here demonstrated to provide a new tool for recognizing impact deformation in rocks where other impact evidence may be erased, altered, or did not manifest due to generally low (< 20 GPa) shock pressure.
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