Tumor microenvironment in thyroid cancer: Immune cells, patterns, and novel treatments.

The tumor immune microenvironment of thyroid cancer is the heterogeneous histological space in which tumor cells coexist with host cells. Published data from this review were identified by search and selection database of Pubmed, Elsevier, and Science Direct. Searching was made in two steps using different keywords. In thyroid pathology, the inflammatory response is very important, and might have a key role finding new diagnostic and therapeutic methods, particularly in thyroid cancer. Different immune cells may be more or less present in different types of thyroid cancer and may even have different functions, hence the importance of knowing their presence in different thyroid tumor pathologies. Cancer-related inflammation could be a useful target for new diagnostic and therapeutic strategies by analyzing peritumoral and intratumoral immune cells in different types of thyroid tumors. Moreover, novel strategies for thyroid cancer treatments, such as monoclonal antibodies targeting checkpoint inhibitors, are emerging as promising alternatives.

Subjective well-being, happiness, and environmental health factors related to women planning a pregnancy or pregnant, using mobile health intervention.

Objectives: To compare the environmental health results in women trying to get pregnant or pregnant using a mobile health application (Green Page) through healthcare professionals or self-completed by women, and to explore the relationship between the subjective well-being of these women with their lifestyles and environmental factors. Methods: A descriptive study with mixed methods was conducted in 2018. A mobile health survey was used in two phases. Phase 1 was a cross-sectional study through professionals (n = 1100) followed by phase 2, a convenience sampling through women's self-reporting (n = 3425). A personalized report was downloadable with health recommendations for the well-being of the mother and child. Results: Of the 3205 participants (mean age = 33 years, SD = 0.2 years), 1840 were planning a pregnancy and 1365 were pregnant. One in five pregnant women had a low level of happiness. Globally, subjective well-being and happiness were found to be negatively associated with lack of contact with nature, sedentary lifestyle, excess weight, environmental exposure, and older age in pregnancy. Precisely 45%, 60%, and 14% of women were exposed to tobacco, alcohol, and illegal drugs, respectively. The women self-reported levels of risk factors higher than when the tool was used by or through professionals. Conclusions: The use of mobile health interventions focused on environmental health during planning or pregnancy periods could help improve the quality of healthcare and foster greater involvement of women in their self-care process, thus promoting empowerment, healthier environments, and lifestyles. Ensuring equity of access and data protection are global challenges to be addressed.

High medium-term incidence of major cardiovascular events in discharged patients with unstable angina.

The introduction of high-sensitivity troponin (hsTn) assays has reduced the diagnosis of unstable angina (UA) in favor of non-ST elevation myocardial infarction (NSTEMI) in the context of non-ST elevation acute coronary syndrome (NSTEACS). It is unclear whether the detection of these hsTn levels affects the prognosis and therefore whether a different therapeutic approach is warranted. This study aims to determine whether using hsTn results in medium-term prognostic differences in patients with UA and NSTEMI. Methods: This multicenter, prospective registry study included consecutive patients who underwent hsTn assays and were discharged with a diagnosis of NSTEACS. Patients were followed for two years. Outcomes were the occurrence of major adverse cardiovascular events (MACE: cardiovascular death, non-fatal myocardial infarction, and non-fatal ischemic stroke), major bleeding, and all-cause mortality. Results: Patients with UA and NSTEMI did not show differences in terms of the invasive interventions received, the coronary artery disease diagnosed, the type of revascularization performed, or the proportion presenting MACE (UA 18.1% vs. NSTEMI 18.9%; p = 0.79). However, patients with NSTEMI had higher cardiovascular mortality at two years (UA 4% vs. NSTEMI 9.2%; p = 0.012), as well as, all-cause mortality (UA vs. 7.9% vs. NSTEMI 16.4%; p = 0.002). Conclusions: Medium-term incidence of MACE was similar in patients with UA and NSTEMI, but cardiovascular and all-cause mortality in NSTEMI patients was over twice that of patients with UA.

Evidence for a lack of inotropic and chronotropic effects of glucagon and glucagon receptors in the human heart.

BACKGROUND: Glucagon is thought to increase heart rate and contractility by stimulating glucagon receptors and increasing 3',5'-cyclic adenosine monophosphate (cAMP) production in the myocardium. This has been confirmed in animal studies but not in the human heart. The cardiostimulatory effects of glucagon have been correlated with the degree of cardiac dysfunction, as well as with the enzymatic activity of phosphodiesterase (PDE), which hydrolyses cAMP. In this study, the presence of glucagon receptors in the human heart and the inotropic and chronotropic effects of glucagon in samples of failing and nonfailing (NF) human hearts were investigated. METHODS: Concentration‒response curves for glucagon in the absence and presence of the PDE inhibitor IBMX were performed on samples obtained from the right (RA) and left atria (LA), the right (RV) and left ventricles (LV), and the sinoatrial nodes (SNs) of failing and NF human hearts. The expression of glucagon receptors was also investigated. Furthermore, the inotropic and chronotropic effects of glucagon were examined in rat hearts. RESULTS: In tissues obtained from failing and NF human hearts, glucagon did not exert inotropic or chronotropic effects in the absence or presence of IBMX. IBMX (30 µM) induced a marked increase in contractility in NF hearts (RA: 83 ± 28% (n = 5), LA: 80 ± 20% (n = 5), RV: 75 ± 12% (n = 5), and LV: 40 ± 8% (n = 5), weaker inotropic responses in the ventricular myocardium of failing hearts (RV: 25 ± 10% (n = 5) and LV: 10 ± 5% (n = 5) and no inotropic responses in the atrial myocardium of failing hearts. IBMX (30 µM) increased the SN rate in failing and NF human hearts (27.4 ± 3.0 beats min-1, n = 10). In rat hearts, glucagon induced contractile and chronotropic responses, but only contractility was enhanced by 30 µM IBMX (maximal inotropic effect of glucagon 40 ± 8% vs. 75 ± 10%, in the absence or presence of IBMX, n = 5, P < 0.05; maximal chronotropic response 77.7 ± 6.4 beats min-1 vs. 73 ± 11 beats min-1, in the absence or presence of IBMX, n = 5, P > 0.05). Glucagon receptors were not detected in the human heart samples. CONCLUSIONS: Our results conflict with the view that glucagon induces inotropic and chronotropic effects and that glucagon receptors are expressed in the human heart.

Molecular mechanisms of postoperative atrial fibrillation in patients with obstructive sleep apnea.

Obstructive sleep apnea (OSA) promotes atrial remodeling and fibrosis, providing a substrate for atrial fibrillation (AF). Herein, we investigate the pathophysiological mechanisms of AF in association with OSA in a cohort of cardiac surgery patients. A prospective study including patients undergoing cardiac surgery. Biomarkers reflective of AF pathophysiology (interleukin [IL-6], C-reactive protein [CRP], von Willebrand factor [vWF], N-terminal pro-brain natriuretic peptide [NT-proBNP], high-sensitivity Troponin T [hs-TnT], and Galectin-3 [Gal-3]) was assessed by functional or immunological assays. miRNAs involved in AF were analyzed by reverse transcription-polymerase chain reaction (RT-PCR). Using atrial tissue samples, fibrosis was assessed by Masson's trichrome. Connexin 40 and 43 (Cx40; Cx43) were evaluated by immunolabeling. Fifty-six patients (15 with OSA and 41 non-OSA) were included in this hypothesis-generating pilot study. OSA group had a higher incidence of postoperative AF (POAF) (46.7% vs. 19.5%; p = .042), presented an increased risk of POAF (OR 3.61, 95% CI 1.01-12.92), and had significantly higher baseline levels of NT-proBNP (p = .044), vWF (p = .049), Gal-3 (p = .009), IL-6 (p = .002), and CRP (p = .003). This group presented lower levels of miR-21 and miR-208 (both p < .05). Also, lower Cx40 levels in POAF and/or OSA patients (50.0% vs. 81.8%, p = .033) were found. The presence of interstitial fibrosis (according to myocardial collagen by Masson's trichrome) was raised in OSA patients (86.7% vs. 53.7%, p = .024). Several biomarkers and miRNAs involved in inflammation and fibrosis were dysregulated in OSA patients, which together with a higher degree of interstitial fibrosis, altered miRNA, and Cxs expression predisposes to the development of a substrate that increases the AF risk.

Hydroxytyrosol: Its role in the prevention of cardiovascular diseases.

In recent years, non-pharmacology treatments and their effectiveness have gained popularity due to their beneficial properties in the prevention of cardiovascular diseases. Phenolic compounds intake provides a natural means of improving in vivo antioxidant status. Thus, the purpose of this review is to discuss the potential benefits of hydroxytyrosol (HT), a phenolic compound with powerful antioxidant and anti-inflammatory properties, in preventing and reducing cardiovascular risk factors, concretely atherosclerosis. Closer inspection of the studies showed a significant improvement of lipid profile, antioxidant capacity and inflammatory state. A note of caution is due in vitro studies because the lack of validated approaches difficult the goodness of fit with the in vivo and clinical research. However, animal and clinical studies were very encouraging, determining HT supplementation useful on inflammation, oxidative stress, endothelial function and cardiovascular diseases in general.

Imaging in atrial fibrillation: A way to assess atrial fibrosis and remodeling to assist decision-making.

The 2020 ESC atrial fibrillation (AF) guidelines suggest the novel 4S-AF scheme for the characterization of AF. Imaging techniques could be helpful for this objective in everyday clinical practice, and information derived from these techniques reflects basic aspects of the pathophysiology of AF, which may facilitate treatment decision-making, and optimal management of AF patients. The aim of this review is to provide an overview of the mechanisms associated with atrial fibrosis and to describe imaging techniques that may help the management of AF patients in clinical practice. Transthoracic echocardiography is the most common procedure given its versatility, safety, and simplicity. Transesophageal echocardiography provides higher resolution exploration, and speckle tracking echocardiography can provide incremental functional and prognostic information over conventional echocardiographic parameters. In addition, LA deformation imaging, including LA strain and strain rate, are related to the extent of fibrosis. On the other hand, multidetector-row computed tomography and cardiac magnetic resonance provide higher resolution data and more accurate assessment of the dimensions, structure, and spatial relationships of the LA. Imaging is central when deciding on catheter ablation or cardioversion, and helps in selecting those patients who will really benefit from these procedures. Moreover, imaging enhances the understanding of the underlying mechanisms of atrial remodeling and might assists in refining the risk of stroke, which help to select the best medical therapies/interventions. In summary, evaluation of LA enlargement, LA remodeling and fibrosis with imaging techniques adds clinical and prognostic information and should be assessed as a part of routine comprehensive AF evaluation.

Confirmation of radiant catalytic ionization efficacy for airborne SARS-CoV-2 elimination indoors using "COVID19 traps".

Radiant catalytic ionization (RCI) is a novel technology that uses the appropriate wavelength (240-260 nm) and the phenomenon of photo-oxidation leading to permanent removal of viruses, bacteria, and fungi. Here, two analyses were performed. The first of them was a complete analysis of environmental biosecurity in a hospital environment. The second one was a longitudinal study with 40 patients with confirmed COVID19 and high viral load to assess the efficacy of RCI technology eliminating airborne SARS-CoV-2 indoors. A significant decrease in the number of bacteria and fungi colony-forming units (CFUs) was found in rooms with RCI when compared with rooms without it (p=0.03 for both of them). In the second part of the study, 16 samples out of 40 (40%) were positives when RCI technology was absent; whereas, these samples were negative when the equipment was on. Incidence rates (IR) with their Poisson 95% Confidence Intervals (CI) were calculated as the number of positive tests with the purifier or without it, showing an IR difference of 48.5% [CI(15.9-81), p=0.004]. Furthermore, the IR ratio was calculated obtaining a value of 3.3, confirming that RCI diminished more than 3-fold the presence of the SARS-CoV-2 in the air of the patients' rooms, thus laying the first stone in the fight for prevention of SARS-CoV-2 dissemination indoors.

MiR-146a Contributes to Thromboinflammation and Recurrence in Young Patients with Acute Myocardial Infarction.

Studies on older patients have established notable conceptual changes in the etiopathogenesis of acute coronary syndrome (ACS), but little is known about this disease in young patients (<45 years). Of special interest is thromboinflammation, key at onset, evolution and therapy of cardiovascular pathology. Therefore, we explored whether ACS at an early age is a thromboinflammatory disease by analyzing NETs and rs2431697 of miR-146a (a miRNA considered as a brake of TLR/NF-kB pathway), elements previously related to higher rates of recurrence in atrial fibrillation and sepsis. We included 359 ACS patients (<45 years) and classified them for specific analysis into G1 (collected during the hospitalization of the first event), G2 and G3 (retrospectively collected from patients with or without ACS recurrence, respectively). cfDNA and citH3−DNA were quantified, and rs2431697 was genotyped. Analysis in the overall cohort showed a moderate but significant correlation between cfDNA and citH3−DNA and Killip−Kimball score. In addition, patients with citH3−DNA > Q4 more frequently had a history of previous stroke (6.1% vs. 1.6%). In turn, rs2431697 did not confer increased risk for the onset of ACS, but T carriers had significantly higher levels of NET markers. By groups, we found that cfDNA levels were similarly higher in all patients, but citH3−DNA was especially higher in G1, suggesting that in plasma, this marker may be attenuated over time. Finally, patients from G2 with the worst markers (cfDNA and citH3−DNA > Q2 and T allele) had a two-fold increased risk of a new ischemic event at 2-year follow-up. In conclusion, our data confirm that ACS is younger onset with thromboinflammatory disease. In addition, these data consolidate rs2431697 as a silent proinflammatory factor predisposing to NETosis, and to a higher rate of adverse events in different cardiovascular diseases.

Dual Effect of Immune Cells within Tumour Microenvironment: Pro- and Anti-Tumour Effects and Their Triggers.

Our body is constantly exposed to pathogens or external threats, but with the immune response that our body can develop, we can fight off and defeat possible attacks or infections. Nevertheless, sometimes this threat comes from an internal factor. Situations such as the existence of a tumour also cause our immune system (IS) to be put on alert. Indeed, the link between immunology and cancer is evident these days, with IS being used as one of the important targets for treating cancer. Our IS is able to eliminate those abnormal or damaged cells found in our body, preventing the uncontrolled proliferation of tumour cells that can lead to cancer. However, in several cases, tumour cells can escape from the IS. It has been observed that immune cells, the extracellular matrix, blood vessels, fat cells and various molecules could support tumour growth and development. Thus, the developing tumour receives structural support, irrigation and energy, among other resources, making its survival and progression possible. All these components that accompany and help the tumour to survive and to grow are called the tumour microenvironment (TME). Given the importance of its presence in the tumour development process, this review will focus on one of the components of the TME: immune cells. Immune cells can support anti-tumour immune response protecting us against tumour cells; nevertheless, they can also behave as pro-tumoural cells, thus promoting tumour progression and survival. In this review, the anti-tumour and pro-tumour immunity of several immune cells will be discussed. In addition, the TME influence on this dual effect will be also analysed.

Clinical implications of diabetes mellitus in patients with acute coronary syndrome: Prognostic role and use of new P2Y12 receptor inhibitors.

AIMS: We investigated the impact of diabetes mellitus (DM) in acute coronary syndrome (ACS) patients, and the 2-year prognosis based on antiplatelet therapy. METHODS: This is a prospective and multicenter registry including hospitalized ACS patients. Clinical management and antiplatelet therapy at discharge were recorded. Bleeding events, all-cause mortality and major adverse cardiovascular events (MACEs) were recorded during 2-years and compared according to DM and the P2Y12 receptor inhibitor. RESULTS: From 1717 ACS patients, 653 (38%) had DM. Diabetic patients were older, more commonly females, with higher prevalence of comorbidities and more conservative management. After excluding antiplatelet monotherapy or oral anticoagulation, clopidogrel was prescribed in 59.6% of DM patients. Cox regression analysis showed that DM was an independent risk factor for MACE (aHR 1.39, 95% CI 1.05-1.83). The use of clopidogrel instead of ticagrelor/prasugrel was also independently associated with MACE (aHR 1.71, 95% CI 1.11-2.63), and all-cause mortality (aHR 2.47, 95% CI 1.23-4.96) in diabetic patients (log-rank p-values < 0.001). CONCLUSIONS: In ACS patients, DM was associated with higher risk of MACE. In such patients, the use of ticagrelor/prasugrel reduced MACE and mortality compared to clopidogrel. Novel P2Y12 receptor inhibitors might be used as the first therapeutic choice in these high-risk patients.

Novel insights in the relationship of gut microbiota and coronary artery diseases.

Atherosclerosis is a chronic, progressive, inflammatory disease in the vasculature and is common in both coronary and peripheral arteries. Human beings harbor a complex and dynamic population of microorganisms defined as the microbiota. Importantly, alterations in the bacterial composition (dysbiosis) and the metabolic compounds produced by these bacteria have been associated with the pathogenesis of many inflammatory diseases and infections. There is also a close relationship between intestinal microbiota and cardiovascular diseases. The aim of this review was to analyze how changes in the gut microbiota and their metabolites might affect coronary artery diseases. The most representative groups of bacteria that make up the intestinal microbiota are altered in coronary artery disease patients, resulting in a decrease in Bacteroidetes and an increase in Firmicutes. In relation to metabolites, trimethylamine-N-oxide plays an important role in atherosclerosis and may act as a cardiovascular risk predictor. In addition, the use of probiotics, prebiotics, diet modulation, and fecal transplantation, which may represent alternative treatments for these diseases, is thoroughly discussed. Finally, the role of lipid-lowering treatments is also analyzed as they may affect and alter the gut microbiota and, conversely, gut microbiota diversity could be associated with resistance or sensitivity to these treatments.

Antithrombotic Therapy in Patients with Peripheral Artery Disease: A Focused Review on Oral Anticoagulation.

Peripheral artery disease (PAD) is a major cause of morbidity and mortality but it is usually underdiagnosed and undertreated. Patients with PAD present dysregulated procoagulant, anticoagulant, and fibrinolytic pathways leading to arterial and venous thrombosis. The risk of several ischemic-related complications could be mitigated with appropriate antithrombotic therapy, which plays a central role in all types of PAD. For years, antiplatelets have been indicated in patients with symptomatic PAD or those who have undergone revascularization. Unfortunately, a non-negligible proportion of patients with PAD will suffer from adverse events during the follow-up, even despite proper medical therapies for the prevention of PAD complications. Thus, there is room for improving clinical outcomes in these patients. Given the implication of both, primary and secondary hemostasis in arterial thrombosis and the pathophysiology of PAD, the combination of antiplatelets and anticoagulants has emerged as a potential antithrombotic alternative to antiplatelets alone. In this narrative review article, we have highlighted the most recent evidence about antithrombotic therapy in PAD patients, with a special focus on oral anticoagulation. Certainly, COMPASS and VOYAGER PAD trials have shown promising results. Thus, rivaroxaban in combination with aspirin seem to reduce cardiovascular outcomes with a similar bleeding risk compared to aspirin alone. Nevertheless, results from real-world studies are needed to confirm these observations, and other trials will provide novel evidence about the safety and efficacy of emerging anticoagulant agents.

Gut Microbiota and the Quality of Oral Anticoagulation in Vitamin K Antagonists Users: A Review of Potential Implications.

The efficacy and safety of vitamin K antagonists (VKAs) as oral anticoagulants (OACs) depend on the quality of anticoagulation control, as reflected by the mean time in therapeutic range (TTR). Several factors may be involved in poor TTR such as comorbidities, high inter-individual variability, interacting drugs, and non-adherence. Recent studies suggest that gut microbiota (GM) plays an important role in the pathogenesis of cardiovascular diseases, but the effect of the GM on anticoagulation control with VKAs is unknown. In the present review article, we propose different mechanisms by which the GM could have an impact on the quality of anticoagulation control in patients taking VKA therapy. We suggest that the potential effects of GM may be mediated first, by an indirect effect of metabolites produced by GM in the availability of VKAs drugs; second, by an effect of vitamin K-producing bacteria; and finally, by the structural modification of the molecules of VKAs. Future research will help confirm these hypotheses and may suggest profiles of bacterial signatures or microbial metabolites, to be used as biomarkers to predict the quality of anticoagulation. This could lead to the design of intervention strategies modulating gut microbiota, for example, by using probiotics.

Intestinal microbiota alterations in chronic kidney disease and the influence of dietary components.

In chronic kidney disease, as in many other diseases, dysbiosis of intestinal microbiota has been reported as a disturbance or imbalance of the normal microbiome content that could disrupt the symbiotic relationship between the host and associated microbes, a disruption that can result in diseases. The disruption of gut barrier function allows the translocation of endotoxins and bacterial metabolites to the organism, thus contributing to uremic toxicity, inflammation and progression of chronic kidney disease. Increased intake of some nutrients and different nutritional strategies have been proposed to modulate gut microbiota, thus offering the opportunity for therapeutic interventions modifying the diet, decreasing uremic toxins production, increasing toxin excretion and finally modifying the normal microbiome content. The use of probiotics, prebiotics and low protein diets, among other approaches, could also improve this imbalance and/or decrease permeability of the intestinal barrier. In this review, the link between nutrients, microbiota and uremic toxins with chronic kidney disease progression has been studied thoroughly. Furthermore, this review outlines potential mechanisms of action and efficacy of probiotics, prebiotics and low protein diets as a new chronic kidney disease management tool.

Novel biomarkers in Alzheimer's disease using high resolution proteomics and metabolomics: miRNAS, proteins and metabolites.

Alzheimer's disease (AD) is the most common form of dementia. It affects approximately 6% of people over the age of 65 years. It is a clinicopathological, degenerative, chronical and progressive disease that exhibits a deterioration of memory, orientation, speech and other functions. Factors contributing to the pathogenesis of the disease are the presence of extracellular amyloid deposits, called neuritic senile plaques, and fibrillary protein deposits inside neurons, known as neurofibrillary bundles, that appear mainly in the frontal and temporal lobes. AD has a long preclinical latency and is difficult to diagnose and prevent at early stages. Despite the advent of novel high-throughput technologies, it is a great challenge to identify precise biomarkers to understand the progression of the disease and the development of new treatments. In this sense, important knowledge is emerging regarding novel molecular and biological candidates with diagnostic potential, including microRNAs that have a key role in gene repression. On the other hand, proteomic approaches offer a platform for the comprehensive analysis of the whole proteome in a certain physiological time. Proteomic technology investigates protein expression directly and reveals post-translational modifications known to be determinant for many human diseases. Clinically, there is growing evidence for the role of proteomic and metabolomic technologies in AD biomarker discovery. This review discusses the role of several miRNAs identified using genomic technologies, and the importance of novel proteomic and metabolomic approaches to identify new proteins and metabolites that may be useful as biomarkers for monitoring the progression and treatment of AD.

Evidences of SARS-CoV-2 virus air transmission indoors using several untouched surfaces: A pilot study.

Nowadays, there is an important controversy about coronavirus air transmission. The aim of this study was to determine aerosol transmission from patients with coronavirus infection using "COVID-19 traps" that included different untouched surfaces within them. 42 swab samples of 6 different surfaces placed in the rooms of 6 patients with a positive diagnostic of COVID-19 were analyzed with RT-PCR technique to evaluate the presence of the virus and its stability. Samples were collected at 24, 48 and 72 h. Patients were in an intensive care unit (ICU) and in a COVID-19 ward unit (CWU) at a Spanish referral hospital. None of the samples placed in the ICU unit were positive for COVID-19. However, two surfaces, placed in a CWU room with a patient that required the use of respiratory assistance were positive for coronavirus at 72 h. Surfaces could not be touched by patients or health workers, so viral spreading was unequivocally produced by air transmission. Thus, fomites should be considered as a possible mode of transmission of coronavirus and frequent disinfection of surfaces should be taken into account. Our results, although preliminary, point the importance of SARS-CoV-2 virus air transmission indoors and may shed some light in this debate.

Immunoscore: a novel prognostic tool. Association with clinical outcome, response to treatment and survival in several malignancies.

The predictive accuracy of the traditional staging system for cancer, the American Joint Committee on Cancer/Union Internationale Centre le Cancer (AJCC/UICC) classification of malignant tumors, is based on disease progression as a tumor cell-autonomous process, regardless the effects of the host immune response. The natural history of a tumor includes different phases of growth, migration and invasion. During these phases, tumor cells interact with their microenvironment and are influenced by signals from stromal, endothelial, inflammatory and immune cells. Indeed, tumors are often infiltrated by defensive cells such as lymphocytes, macrophages or mast cells and it has been shown extensively that lymphocytes may control cancer outcome, as evidenced in several human malignancies. Increasing evidence suggests that cancer progression is strongly influenced by host immune response, which is represented by immune cell infiltrates. The T-lymphocyte-based immunoscore (IS) has proved to be a prognostic factor in human malignancies such as colon, pancreas and lung cancer, hepatocellular carcinoma, melanoma and even brain metastases. Although the IS was initially established to evaluate the prognosis of stage I/II/III colon cancer patients, its association with clinical outcomes and survival has been shown in other malignancies. The aim of this review is to analyze the association of IS with prognosis, survival and response to therapy in different tumor types.

One-year efficacy and safety of prasugrel and ticagrelor in patients with acute coronary syndromes: Results from a prospective and multicentre ACHILLES registry.

BACKGROUND: Prasugrel and ticagrelor have demonstrated higher efficacy than clopidogrel in their main clinical trials for patients with acute coronary syndrome (ACS). However, the long-term prognosis and different clinical characteristics related to the type of antiplatelet prescription in current clinical practice ACS patients have not been analysed in depth. The objective of this study was to analyse the clinical profile of ACS and the efficacy and safety of novel oral P2Y12 inhibitors in current clinical practice patients discharged afterACS. METHODS: We collected data from the ACHILLES registry, and an observational, prospective and multicentre registry of patients discharged after ACS. We analysed baseline characteristics, clinical profile and therapy during ACS admission and compared with the different treatments at discharge. After 1 year of follow-up, ischaemic and major bleeding events were analysed. Multivariate Cox regression analysis and Kaplan Meier curves were also plotted. RESULTS: Of 1717 consecutive patients, 1294 (75.4%) were discharged with a P2Y12 inhibitor without oral anticoagulation. Novel oral P2Y12 inhibitors were indicated in 47%. Patients treated with clopidogrel were elderly (69.1 ± 13.4 vs 60.4 ± 11.5 years; P < .001) and had a higher prevalence of cardiovascular risk factors. GRACE and CRUSADE scores were higher in the clopidogrel than in novel oral P2Y12 inhibitors group (P < .001). After 1 year of follow-up, 64(5.0%/year) patients had a new myocardial infarction, 127(10.0%/year) had a major adverse cardiovascular event (MACE) and 78(6.1%/year) died. Patients treated with clopidogrel had a significantly higher annual rate of cardiovascular mortality, MACE and all-cause mortality (allP < .001) without differences in major bleeding (P = .587) compared with novel oral P2Y12 inhibitors. After multivariate adjustment for the main clinical variables related to adverse prognosis in ACS patients, the discharge with novel oral P2Y12 inhibitors therapy was independently associated with lower risk of all-cause mortality (HR0.49, 95% CI [0.24-0.98], P = .044) and lower risk of MACE (HR0.64, 95% CI [0.41-0.98], P = .044). CONCLUSIONS: In this prospective, observational and current clinical practice ACS registry, the use of novel oral P2Y12 inhibitors was associated with a reduction in adverse events compared with clopidogrel in patients with ACS. Novel oral P2Y12 inhibitors prescription at discharge was independently associated with lower all-cause mortality and MACE without differences in bleeding events. However, clopidogrel remained the most common P2Y12 inhibitor employed for ACS, especially in older and high-risk patients.