Isolation and characterization of extracellular vesicles secreted by pre-pubertal Sertoli cells

Recent studies have shown that extracellular vesicles (Ev) are an important mechanism of intercellular communication. In fact, Ev may contain proteins, DNA and mRNA. In particular, the latter play an important role in various biological processes including regulation and cell differentiation [1]. Sertoli cells (SC), previously considered as a mere “sustentacular cell”, were re-evalued in their functions and elevated to the rank of a “sentinel” in spermatogenesis due to production of trophic, differentiation and immune-modulators factors. Porcine pre-pubertal SC, isolated by our method [2], upon 48 hours culture, SC were stimulated with recombinant a-follitropin (rFSH) or FSH + testosterone (T) to evaluate both the presence in the medium of SC-derived Ev (SC-Ev) and SC-Ev content, in terms of mRNA for Anti-Müllerian hormone (AMH), inhibin B, Androgen Binding Protein (ABP) and FSH-receptor (FSH-r), by RT-PCR. SEM analysis highlighted the presence of SC-Nv in culture medium with mean diameters < 149 nm. We have also demonstrated, within the SC-Ev, significant increase in mRNA for AMH, ABP and FSH-r after both FSH and FSH+T stimulation, as compared to unstimulated SC-Ev. Differently from unstimulated SC-Ev, mRNA inhibin B levels were unchanged in FSH-stimulated SC-Ev, and increased after FSH+T stimulation. Interestingly, an opposite trend was shown in mRNA secretion, in control SC monolayer where, we demonstrated a decrease of AMH and FSH-r mRNA (after both stimulations with FSH or FSH + T) and an increase of inhibin B mRNA. On the contrary, mRNA ABP levels, in SC monolayer, decreased after stimulation with FSH but were unchanged in the presence of FSH+T. For the first time in the Literature, our work has shown the presence of SC-Nv containing AMH, inhibin B, ABP and FSH-r mRNA regulated by FSH with or without T. This result may suggest that other testicular cells could produce factors that, until now, were considered an exclusive SC secretory product.This work was supported by Mr.Gary Harlem (Altucell Inc. 3 Astor Court, Dix Hills, New York, NY) and Merck-Serono (London, UK)

The cold facts of long-term ECG monitoring

Two recently published trials have provided evidence in favor of longer ECG monitoring among patients with cryptogenic stroke (CS). In the CRYSTAL-AF trial, new atrial fibrillation (AF) was detected in 12.4% of patients with implantable monitor when compared with 2% among those receiving standard follow-up. A similar result was observed in the EMBRACE trial in which AF was detected in 16.1% of patients who received 30-day event recorder (3.2% in controls). These data are compelling in convincing us that long-term ECG technologies have superior sensitivity for the detection of AF in CS; however, clinical specificity for the definition of CS etiology of such findings cannot be established and can be lower than expected, leaving open questions about the etiologic weight of AF in CS. The causative role of AF in this subpopulation remains to be proven, and diagnostic routes cannot be solely unbalanced toward the research of AF

Thromboembolic risk and effect of oral anticoagulation according to atrial fibrillation patterns: A systematic review and meta‐analysis

Oral anticoagulation (OAC) is recommended in both paroxysmal atrial fibrillation (pxAF) and nonparoxysmal AF (non-pxAF), but disagreement exists in classes of recommendation. Data on incidence/rate of stroke in pxAF are conflicting, and OAC is often underused in this population. The objectives of the meta-analysis were to investigate different impact on outcomes of pxAF and non-pxAF, with and without OAC. Two reviewers searched for prospective studies on risk of stroke and systemic embolism (SE) in pxAF and non-pxAF, with and without OAC. Quality of evidence was assessed according to GRADE approach. Stroke combined with SE was the main outcome. Meta-regression was performed to evaluate OAC effect on stroke and SE incidence rate. We identified 18 studies. For a total of 239 528 patient-years of follow-up. The incidence rate of stroke/SE was 1.6% (95% confidence interval [CI]: 1.3%-2.0%) in pxAF and 2.3% (95% CI: 2.0%-2.7%) in non-pxAF. Paroxysmal AF was associated with a lower risk of overall thromboembolic (TE) events (risk ratio: 0.72, 95% CI: 0.65-0.80, P &lt; 0.00001) compared with non-pxAF. In both groups, the annual rate of TE events decreased as proportion of patients treated with OAC increased. Non-pxAF showed a reduction from 3.7% to 1.7% and pxAF from 2.5% to 1.2%. Major bleeding rates did not differ among groups. Stroke/SE risk is significantly lower, although clinically meaningful, in pxAF. OAC consistently reduces TE event rates across any AF pattern. As a whole, these data provide the evidence to warrant OAC irrespective of the AF pattern in most (virtually all) patients

Nutrizione e malnutrizione in terapia intensiva cardiologica. Nozioni di base per il cardiologo clinico

Patients admitted to coronary care units (CCU) have largely changed in the last decades. As observed in national and international registries, they are older, with different degrees of disability and several comorbidities. Moreover, they often undergo complex procedures. In this scenario, the cardiologist of the CCU has to deal with multidisciplinarity that should involve physiology and pathophysiology of nutrition. Despite the lack of specific data about our CCUs, hospital malnutrition is indeed a common entity that can reach a prevalence of 50% in elderly patients aged more than 75 years old. Malnutrition has several consequences in CCU patients since it involves respiratory drive, immune system and, clinically, patients have longer CCU stay and more complications. Briefly, malnutrition has a significant impact on their final outcome. In the clinical arena, the main issues for CCU physicians are the nutritional screening tools to promote an early recognition of patients with malnutrition, the pathophysiological knowledge of nutrition for a correct interaction with nutritionists, and the way of administration with its major complications. The changes in the population within CCUs are relatively recent and, although specific data in the cardiology setting are still scarce, nutrition science has reached a high level of knowledge to understand and plan tailored nutritional schemes based on the clinical and demographic features of our sick patients. Key words. Coronary care unit; Critically ill; Malnutrition; Nutrition

Role of cardiac electronic implantable device in the stratification and management of embolic risk of silent atrial fibrillation: are all atrial fibrillations created equal?

Introduction: Ischemic strokes may be associated with atrial fibrillation (AF). AF detection is critical in ischemic stroke survivors, often recommending a switch from antiplatelet therapy to oral anticoagulants for secondary prevention.Areas covered: Cardiac implantable electronic devices (CIED) with their long-term recording capability allows to document AF and to quantify the arrhythmia burden. Recent series in pacemaker and implantable cardioverter-defibrillator (ICD) recipients with no prior stroke showed that short episodes of AF increased stroke risk compared with those without AF recorded. Detection of AF by CIEDs represent a unique opportunity for promp prevention of embolic risk in silent AF. It will be attractive to identify AF before a stroke occurs.Expert commentary: The purpose of this article is to review the role of CIED to detect AF, to quantify the role of AF burden, and to guide primary and secondary stroke prevention

Simultaneous strain–volume analysis by three-dimensional echocardiography

International audienceObjective: The aim of this study is to compare three-dimensional echocardiography strain–volume analysis with tagging cardiac magnetic resonance (cMR) measurements.Background and methods: Strain–volume analysis represents a noninvasive method to assess myocardial function and volumes simultaneously. It can be derived from echocardiography and speckle-tracking; however, it shows some variability that can limit clinical utilization. A three-dimensional approach partially overcomes these limitations since full-volume acquisition avoids images being foreshortened and geometrical reconstruction. In the study presented here, 23 healthy subjects were studied by three-dimensional echocardiography and cMR during the same session. Images were stored and the better cardiac cycle was chosen for simultaneous analysis of volumes and longitudinal (Long) and circumferential (Circ) strain. By means of full-volume acquisition all parameters can be calculated for each frame of the cardiac cycle using the speckle-tracking method. With cMR, left ventricle volumes were calculated as recommended; myocardial strains were computed in short-axis and long-axis views using the tagging technique. For each patient, volumes and strain values were plotted in a Cartesian system for strain–volume analysis. Data were compared between the two methods using Bland–Altman analysis based on mean difference and 95% limits of agreement (LoA).Results: The volume as measured by three-dimensional echocardiography and cMR was comparable with the slightly higher end-diastolic volumes measured by cMR (mean difference 15.24 ml; LoA −53.6 to 26.5 ml, end-systolic volume 0.3 ml; LoA −19.9 to 20.5 ml). Long shortening was very similar in the two methods (1.5%; LoA −3.9 to 7%), whereas Circ strain was systematically lower with cMR (−8.5%; LoA −15.5 to −1.5%). Very similar values between three-dimensional echo and cMR both for Slope of strain–volume curves (−0.015; LoA −0.08 to 0.05) and ratio (−0.001; LoA −0.04 to 0.04) were observed in the longitudinal plane. Analysis of strain–volume per patient showed a significant correlation coefficient between techniques for both Long Slope (r = 0.65; P = 0.001) and Long Ratio (r = 0.70; P = 0.001).Conclusion: Longitudinal strain–volume analysis performed with three-dimensional speckle-tracking echocardiography is closely comparable with cMR, which is usually considered the gold standard for volume and function assessment

T1 and T2 mapping in the identification of acute myocardial injury in patients with NSTEMI

Aims: To test T1 and T2 mapping in the assessment of acute myocardial injury in patients with non-ST-segment elevation myocardial infarction (NSTEMI), evaluated before revascularization. Methods: Forty-seven patients with acute NSTEMI underwent cardiac magnetic resonance (CMR) at 1.5 T, including T1 and T2 mapping. Results: Coronary angiography (CA) evidenced an obstructive coronary artery disease (CAD) in 36 patients (80%) and a non-obstructive CAD in 11 patients (20%). Edema was detected in 51.1/65.9% of patients in T1/T2 maps, respectively. This difference was due to artifacts in T1 maps. T1/T2 values were significantly higher in the infarcted myocardium (IM) compared with the remote myocardium (RM) (in T1: 1151.6 ± 53.5 ms vs. 958.2 ± 38.6 ms, respectively; in T2: 69 ± 6 ms vs. 51.9 ± 2.9 ms, respectively; p < 0.0001 for both). We found both an obstructive CAD at CA and myocardial edema at CMR in 53.2% of patients, while 8.5% of patients had a non-obstructive CAD and no edema. However, 25.5% of patients had an obstructive CAD without edema, while 12.8% of patients showed edema despite a non-obstructive CAD. Furthermore, in 6 of the edema-positive patients with multi-vessels obstructive CAD, CMR identified myocardial edema in a vascular territory different from that of the lesion supposed to be the culprit at CA. Conclusions: In a non-negligible percentage of NSTEMI patients, T1 and T2 mapping detect myocardial edema without significant stenosis at CA and vice versa. Therefore, CA and CMR edema imaging might provide complementary information in the evaluation of NSTEMI

Myocardial T1 and T2 mapping in diastolic and systolic phase

The aim of this study was to evaluate the regional (i.e. myocardial segments) variability as well as the overall image quality of cardiac T1 and T2 maps obtained in diastole and in systole. In 22 healthy subjects (group-1), diastolic T1 and T2 maps were obtained at 1.5 T in short-axis view at basal, mid-ventricular and apical level, as well as in 4-chamber (4 ch) and in 2-chamber (2 ch) views. In another group of 25 patients (group-2), the maps were obtained in both diastole and systole. In the group-1, 15.4% of myocardial segments in T1 maps and 0.8% of myocardial segments in T2 maps, mainly located at apical level, showed relevant artifacts and/or partial-volume effect and had to be discarded. We found no significant difference in T1 values among basal, mid-ventricular and apical segments. T2 values at apical level were significantly higher than at basal and mid-ventricular level (short-axis, p < 0.0001; 4 ch, p < 0.009; 2 ch, p = 0.0002 at ANOVA tests). In the group-2, 21.1%/5.3% and 4.0%/0.8% of segments showed relevant artifacts in diastolic/systolic T1 and T2 maps, respectively. Apical T2 values were significantly lower in systole than in diastole. In systole, there were no significant differences in T1/T2 among basal, mid-ventricular and apical segments. The overall quality of T1 and T2 maps drops in apical segments. This could be problematic when evaluating focal myocardial changes. The acquisition in systole increases the number of evaluable segments