Effects of remote ischaemic preconditioning on peri-operative myocardial injury and clinical outcomes in patients undergoing elective cardiac bypass surgery

Ischaemic heart disease (IHD) is a major cause of morbidity and mortality in the world. Coronary artery bypass graft (CABG) surgery is the revascularisation strategy of choice in a significant number of patients, particularly those with diabetes mellitus and complex coronary disease. During cardiac surgery, the myocardium is subjected to peri-operative myocardial injury (PMI), which has been associated with worse short and long-term clinical outcomes. Higher-risks patients are currently being operated on with subsequent higher risk of PMI and worse prognosis: therefore new strategies are required to potentiate the innate mechanisms of cardioprotection. In this regard, remote ischaemic preconditioning (RIPC) is a promising non-invasive intervention able to reduce PMI in these patients: however, not all the studies have shown significant cardioprotection with RIPC for a number of factors, amongst which the intensity of the preconditioning stimulus may play a significant role. We therefore investigated whether an enhanced RIPC stimulus, given with transient simultaneous multi-limb ischaemia/reperfusion, was able to reduce PMI and improve short-term clinical outcomes in patients undergoing elective cardiac surgery: we demonstrated that our preconditioning stimulus can significantly reduce PMI, length of intensive care unit (ICU) stay and incidence of atrial fibrillation (AF) in these patients. In addition, further retrospective analyses showed improved myocardial protection in preconditioned diabetic patients undergoing CABG surgery and in control CABG subjects receiving combined antegrade and retrograde cardioplegia compared to control CABG patients having antegrade cardioplegia or intermittent cross-clamp-fibrillation. We also conducted a multi-centre, double-blinded randomised control clinical trial, in which we investigated the effects of RIPC on clinical outcomes at 1 year in high-risk patients undergoing elective CABG surgery with or without valve surgery (the ERICCA trial). The results of this study are due to be presented in March 2015 and have the potential to significantly impact on clinical practice in cardiac surgery

Is there a role for ischaemic conditioning in cardiac surgery?

Coronary artery disease (CAD) is a major cause of morbidity and mortality worldwide. Coronary artery bypass graft (CABG) surgery is the revascularisation strategy of choice in patients with diabetes mellitus and complex CAD. Owing to a number of factors, including the ageing population, the increased complexity of CAD being treated, concomitant valve and aortic surgery, and multiple comorbidities, higher-risk patients are being operated on, the result of which is an increased risk of sustaining perioperative myocardial injury (PMI) and poorer clinical outcomes. As such, new treatment strategies are required to protect the heart against PMI and improve clinical outcomes following cardiac surgery. In this regard, the heart can be endogenously protected from PMI by subjecting the myocardium to one or more brief cycles of ischaemia and reperfusion, a strategy called "ischaemic conditioning". However, this requires an intervention applied directly to the heart, which may be challenging to apply in the clinical setting. In this regard, the strategy of remote ischaemic conditioning (RIC) may be more attractive, as it allows the endogenous cardioprotective strategy to be applied away from the heart to the arm or leg by simply inflating and deflating a cuff on the upper arm or thigh to induce one or more brief cycles of ischaemia and reperfusion (termed "limb RIC"). Although a number of small clinical studies have demonstrated less PMI with limb RIC following cardiac surgery, three recently published large multicentre randomised clinical trials found no beneficial effects on short-term or long-term clinical outcomes, questioning the role of limb RIC in the setting of cardiac surgery. In this article, we review ischaemic conditioning as a therapeutic strategy for endogenous cardioprotection in patients undergoing cardiac surgery and discuss the potential reasons for the failure of limb RIC to improve clinical outcomes in this setting. Crucially, limb RIC still has the therapeutic potential to protect the heart in other clinical settings, such as acute myocardial infarction, and it may also protect other organs against acute ischaemia/reperfusion injury (such as the brain, kidney, and liver)

Social Networking in Second Language Learning

Aquesta tesi se centra en l'aprenentatge informal d'una segona llengua en comunitats en línia com Livemocha i Busuu. Els objectius són: (1) analitzar el potencial de les comunitats en línia per a aconseguir resultats d'aprenentatge a llarg termini; (2) examinar les accions dels estudiants mentre construeixen oportunitats d'ús de la segona llengua en aquests entorns, i (3) explorar les potencialitats i les limitacions de les eines de les comunitats en línia. Amb la finalitat d'assolir aquests objectius, l'estudi, que s'inscriu en el marc teòric de la perspectiva sociocultural i de la teoria de l'activitat, ha utilitzat una metodologia de recerca principalment qualitativa i centrada en el mètode etnogràfic. La recerca conclou amb una reflexió crítica sobre la importància de l'autonomia de l'estudiant. S'ha destacat que l'autonomia de l'estudiant és un requisit important perquè l'experiència d'aprenentatge informal en aquests entorns sigui eficaç. A més, aquest estudi tradueix els resultats obtinguts en un conjunt de recomanacions pedagògiques dirigides a experts d'entorns d'aprenentatge, a estudiants i a professors d'idiomes, per tal de fomentar una experiència d'aprenentatge en les comunitats en línia més positiva tenint en compte, també, la seva possible aplicació en un context d'aprenentatge formal.Esta tesis está centrada en el aprendizaje informal de una segunda lengua en comunidades en línea como Livemocha y Busuu. Los objetivos son: (1) analizar el potencial de las comunidades en línea para lograr resultados de aprendizaje a largo plazo; (2) examinar las acciones de los estudiantes mientras construyen oportunidades de uso de la segunda lengua en estos entornos, y (3) explorar las potencialidades y las limitaciones de las herramientas de las comunidades en línea. Con la finalidad de alcanzar estos objetivos, el estudio, que se inscribe en el marco teórico de la perspectiva sociocultural y de la teoría de la actividad, ha utilizado una metodología de investigación principalmente cualitativa y centrada en el método etnográfico. La investigación concluye con una reflexión crítica sobre la importancia de la autonomía del estudiante. Se ha destacado que la autonomía del estudiante es un requisito importante para que la experiencia de aprendizaje informal en estos entornos sea eficaz. Además, este estudio traduce los resultados obtenidos en una serie de recomendaciones pedagógicas dirigidas a expertos de entornos de aprendizaje, a estudiantes y a profesores de idiomas, con el fin de fomentar una mejor experiencia de aprendizaje en las comunidades en línea tomando en consideración también su posible aplicación en un contexto de aprendizaje formal.This thesis deals with informal second language learning in online communities such as Livemocha and Busuu. The thesis' objectives are: (1) analyse the potential effectiveness of these communities for long-term learning outcomes; (2) examine learners' construction of opportunities for L2 use in these environments; (3) explore affordances and constraints of online communities. To this end, a longitudinal multiple ethnographic case study approach was used under the theoretical framework of Socio-Cultural Theory and Activity Theory (AT). The research concludes with a critical reflection on the role of learner autonomy as a prerequisite for the creation of effective learning experiences in these environments, as this study clearly demonstrates. Moreover, the study translates its findings into a set of pedagogical recommendations for platform developers, learners and teachers to maximize the advantages of L2 learning in online communities as well as establish possible applications in formal learning settings

Protection of organs other than the heart by remote ischemic conditioning

Organ or tissue dysfunction due to acute ischemia–reperfusion injury (IRI) is the leading cause of death and disability worldwide. Acute IRI induces cell injury and death in a wide variety of organs and tissues in a large number of different clinical settings. One novel therapeutic noninvasive intervention, capable of conferring multiorgan protection against acute IRI, is ‘remote ischemic conditioning’ (RIC). This describes an endogenous protective response to acute IRI, which is triggered by the application of one or more brief cycles of nonlethal ischemia and reperfusion to one particular organ or tissue. Originally discovered as a therapeutic strategy for protecting the myocardium against acute IRI, it has been subsequently demonstrated that RIC may confer protection against acute IRI in a number of different noncardiac organs and tissues including the kidneys, lungs, liver, skin flaps, ovaries, intestine, stomach and pancreas. The discovery that RIC can be induced noninvasively by applying the RIC stimulus to the skeletal tissue of the upper or lower limb has facilitated its application to a number of clinical settings in which organs and tissues are at high risk of acute IRI. In this article, we review the experimental studies that have investigated RIC in organs and tissues other than the heart, and we explore the therapeutic potential of RIC in preventing organ and tissue dysfunction induced by acute IRI

SARS-CoV-2 and Pre-existing Vascular Diseases: Guilt by Association?

Severe Acute Respiratory Syndrome coronavirus-2 has rapidly spread and emerged as a pandemic. Although evidence on its pathophysiology is growing, there are still issues that should be taken into consideration, including its effects on pre-existing peripheral vascular disease. The aim of this review is to describe the thrombotic and endothelial dysfunctions caused by SARS-CoV-2, assess if cardiovascular comorbidities render an individual susceptible to the infection and determine the course of pre-existing vascular diseases in infected individuals. A search through MEDLINE, PubMed and EMBASE was conducted and more than 260 articles were identified and 97 of them were reviewed; the rest were excluded because they were not related to the aim of this study. Hypertension, cardiovascular disease, diabetes mellitus and cerebrovascular diseases comprised 24.30% ± 16.23%, 13.29% ± 12.88%, 14.82% ± 7.57% and 10.82% ± 11.64% of the cohorts reviewed, respectively. Arterial and venous thrombotic complications rocketed up to 31% in severely infected individuals in some studies. We suggest that hypertension, cardiovascular diseases, diabetes and cerebrovascular diseases may render an individual susceptible to severe COVID-19 infection. Pre-existing vascular diseases are expected to deteriorate with SARS-CoV-2 infection as a consequence of its increased thrombotic burden and the development of endothelial dysfunction. COVID-19 has emerged only a few months ago and it is premature to predict the long-term effects to the vascular system. Its disturbances of the coagulation mechanisms and effects on vascular endothelium will likely provoke a surge of vascular complications in the coming months

I resti umani del sito epipaleolitico SHM-1 (Hergla – Tunisia)

Analisi antropologica dei resti ossei provenienti dal sito Epipaleolitico di SHM-1 (Hergla, Tunisia

Remote Ischemic Preconditioning: Would You Give Your Right Arm to Protect Your Kidneys?

Commentary on Zarbock A, Schmidt C, Van Aken H, et al. Effect of remote ischemic preconditioning on kidney injury among high-risk patients undergoing cardiac surgery: a randomized clinical trial. JAMA. 2015;313(21):2133-2141

Defining Peri-Operative Myocardial Injury during Cardiac Surgery Using High-Sensitivity Troponin T

Objective: Cut-offs for high-sensitivity troponin (hs-Tn) elevations to define prognostically significant peri-operative myocardial injury (PMI) in cardiac surgery is not well-established. We evaluated the associations between peri-operative high-sensitivity troponin T (hs-TnT) elevations and 1-year all-cause mortality in patients undergoing cardiac surgery. Methods: The prognostic significance of baseline hs-TnT and various thresholds for post-operative hs-TnT elevation at different time-points on 1-year all-cause mortality following cardiac surgery were assessed after adjusting for baseline hs-TnT and EuroSCORE in a post-hoc analysis of the ERICCA trial. Results: 1206 patients met the inclusion criteria. Baseline elevation in hs-TnT >x1 99th percentile upper reference limit (URL) was significantly associated with 1-year all-cause mortality (adjusted hazard ratio 1.90, 95% confidence interval 1.15–3.13). In the subgroup with normal baseline hs-TnT (n = 517), elevation in hs-TnT at all post-operative time points was associated with higher 1-year mortality, reaching statistical significance for elevations above: ≥100 × URL at 6 h; ≥50 × URL at 12 and 24 h; ≥35 × URL at 48 h; and ≥30 × URL at 72 h post-surgery. Elevation in hs-TnT at 24 h ≥ 50 × URL had the optimal sensitivity and specificity (73% and 75% respectively). When the whole cohort of patients was analysed, including those with abnormal baseline hs-TnT (up to 10 × URL), the same threshold had optimal sensitivity and specificity (66% and 70%). Conclusions: Both baseline and post-operative hs-TnT elevations are independently associated with 1-year all-cause mortality in patients undergoing cardiac surgery. The optimal threshold to define a prognostically significant PMI in our study was ≥50 × URL elevation in hs-TnT at 24 h