Fabian Sanchis-Gomar

The p38-PGC-1α-irisin-betatrophin axis: Exploring new pathways in insulin resistance.

The discovery of irisin as a novel and promising peptidic hormone has raised hopes regarding the hypothesis that irisin may provide additional benefits, not only for obesity and diabetes, but also for a wide range of pathological conditions since this hormone may prove to be therapeutically and clinically beneficial. In addition, a new hormone, betatrophin, has recently been identified by Yi and coworkers. Both hormones are connected by a new pathway clearly involved in insulin resistance. We hypothesize here how these hormones may be linked and their possible implications in both aged-reduced restricted regenerative capacity and dedifferentiated β cells of diabetic patients.

Benefits of skeletal-muscle exercise training in pulmonary arterial hypertension: The WHOLEi + 12 trial

BACKGROUND Pulmonary arterial hypertension is often associated with skeletal-muscle weakness. The purpose of this randomized controlled trial was to determine the effects of an 8-week intervention combining muscle resistance, aerobic and inspiratory pressure-load exercises on upper/lower-body muscle power and other functional variables in patients with this disease. METHODS Participants were allocated to a control (standard care) or intervention (exercise) group (n=20 each, 45±12 and 46±11years, 60% women and 10% patients with chronic thromboembolic pulmonary hypertension per group). The intervention included five, three and six supervised (inhospital) sessions/week of aerobic, resistance and inspiratory muscle training, respectively. The primary endpoint was peak muscle power during bench/leg press; secondary outcomes included N-terminal pro-brain natriuretic peptide levels, 6-min walking distance, five-repetition sit-to-stand test, maximal inspiratory pressure, cardiopulmonary exercise testing variables (e.g., peak oxygen uptake), health-related quality of life, physical activity levels, and safety. RESULTS Adherence to training sessions averaged 94±0.5% (aerobic), 98±0.3% (resistance) and 91±1% (inspiratory training). Analysis of variance showed a significant interaction (group×time) effect for leg/bench press (P<0.001/P=0.002), with both tests showing an improvement in the exercise group (P<0.001) but not in controls (P>0.1). We found a significant interaction effect (P<0.001) for five-repetition sit-to-stand test, maximal inspiratory pressure and peak oxygen uptake (P<0.001), indicating a training-induced improvement. No major adverse event was noted due to exercise. CONCLUSIONS An 8-week exercise intervention including aerobic, resistance and specific inspiratory muscle training is safe for patients with pulmonary arterial hypertension and yields significant improvements in muscle power and other functional variables.

Early in-hospital variation of red blood cell distribution width predicts mortality in patients with acute heart failure

BACKGROUND Some studies showed that the value of red blood cell distribution width (RDW) at admission may predict clinical outcomes in patients with acutely decompensated heart failure (ADHF). Therefore, this study was planned to investigate whether in-hospital variations of RDW may also predict mortality in this condition. METHODS The final study population consisted of 588 patients admitted to the local Emergency Department (ED), who were hospitalized for ADHF. The RDW was measured at ED admission and after 48h and 96h of hospital stay. In-hospital variations from admission value, expressed as absolute variation (DeltaRDW) or percent variation (Delta%RDW), were then correlated with 30- and 60-day mortality. RESULTS Overall, 87 (14.8%) and 118 (20.1%) patients with ADHF died at 30 or 60days of follow-up. Delta%RDW after 96h of hospital stay independently predicted 30-day mortality (odds ratio, 1.12; 95% CI, 1.07-1.18). An increase >1% of Delta%RDW after 96h of hospital stay independently predicted both 30-day (odds ratio, 2.86; 95% CI, 1.67-4.97) and 60-day (odds ratio, 3.06; 95% CI, 1.89-4.96) mortality. A similar trend was observed for DeltaRDW, since an increase after 96h of hospital stay was associated with a nearly 4-fold higher 30-day mortality (odds ratio, 3.65; 95% CI, 2.02-6.15). CONCLUSION Despite it remains unclear whether RDW is a real risk factor or an epiphenomenon in ADHF, these results suggest that more aggressive management may be advisable in ADHF patients with increasing anisocytosis during the first days of hospitalization.

Influence of middle-distance running on muscular micro RNAs

Abstract A specific subset of micro RNAs (miRs), including miR-133 and miR-206, is specifically expressed in muscle tissue, so that they are currently defined as muscular miRs (myomiRs). To further elucidate the role of myomiRs in muscle biology, we measured miR-133a and miR-206 in plasma of 28 middle-age recreational athletes. The study population consisted of 28 middle aged, recreation athletes (11 women and 17 men; mean age, 46 years) who completed a 21.1 km, half-marathon. The plasma concentration of miR-133a and miR-206, the serum concentration of creatine kinase (CK) and high-sensitivity (HS) cardiac troponin T (cTnT), as well as capillary lactate, were measured before and immediately after the run. The median serum concentration of total CK (257 versus 175 U/L; p < .001), cTnT (17.8 versus 5.6 ng/L; p < .001), and the plasma values of both miR-133a (4.22 versus 0.64 × 10−4; p < .001) and miR-206 (1.36 versus 0.63 × 10−4; p = .001) were considerably increased immediately after the half-marathon run. In multivariate analysis only post-exercise capillary lactate was found to be independently associated with running time. A significant and independent correlation was observed between plasma variations of the two miRs, but not with other physiological or laboratory parameters. The results of this study suggest that the biological significance of miR-133a and 206 variation after middle-distance running parallels but not overlaps the release of biomarkers of nonspecific tissue damage. Enhanced plasma values of these myomiRs may hence reflect a physiological response to high-intensity and/or prolonged exercise rather than tissue injury.

The ‘lottery’ of cardiovascular risk estimation with Internet-based risk calculators

The cardiovascular disease (CVD) is the leading cause of disability and premature death around the world. The ongoing publication of systematic and critical literature reviews has contributed to generate a kaleidoscope of guidelines by different scientific organizations. We investigated the accordance among the most popular web-based CVD risk calculators on the Internet. We carried out a simple study, by estimating the risk of CVD using the most popular Internet-based calculators available on the Internet. A Google search was performed, using the keyword “cardiovascular risk calculator”, to identify the first 10 websites providing free on-line CVD risk calculators. We arbitrarily selected the cardiovascular profile of two subjects of a typical Western family: a 55-year man at a likely intermediate cardiovascular risk and a 45-year woman at a probable low risk. The score calculated according to the two arbitrary CVD risk profiles, one of whom was supposed to be at intermediate risk and the other at lower risk, was extremely variable. More specifically, the 10-year CVD risk of the 55-year old man varied from 3% to over 25% (median value, 12.9%, interquartile range [IQR], 10.7–19.0%), whereas that of the 45-year women varied between 0% and 4% (median value, 1.2%; IQR, 0.4–2.2%), thus displaying a nearly 10-fold variation in both cases. We concluded from our analysis of 11 different Internet-based CVD risk calculators that the final 10-year risk score can be extremely different, especially for the 55-year old man at predictably intermediate risk.

Serum Concentration of Growth Differentiation Factor-15 Is Independently Associated with Global Platelet Function and Higher Fibrinogen Values in Adult Healthy Subjects

&NA; Growth differentiation factor‐15 (GDF‐15) has recently emerged as a strong and independent predictor of cardiovascular events and mortality. However, the pathophysiological mechanisms underlying this important association remain speculative. This study was aimed to investigate the potential associations between the serum concentration of GDF‐15 and clinical or laboratory parameters in a population of ostensibly healthy subjects. The study population consisted of 44 healthy volunteers enrolled from the laboratory staff (14 males and 30 females; mean age, 47 ± 11 years), who had their blood collected for assessing complete blood cell count, GDF‐15, serum creatinine, albumin, cardiac troponin T, galectin‐3, routine coagulation tests, D‐dimer, von Willebrand factor, and platelet function testing using platelet function analyzer‐100. In univariate analysis, serum GDF‐15 was found to be positively associated with age and plasma fibrinogen, and negatively associated with renal function and collagen‐epinephrine (CEPI). In multiple linear regression analysis, serum GDF‐15 remained significantly associated with renal function, CEPI, and plasma fibrinogen. Healthy subjects with GDF‐15 above the median value had a twofold probability of displaying shorter CEPI closure times. Taken together, these results suggest that higher serum values of GDF‐15 may be associated with overall global platelet hyperactivity and increased plasma fibrinogen, so providing another plausible explanation for the association between GDF‐15, cardiovascular events, and mortality.

Increased Cardiovascular Risk Associated With E-Cigarette Use

Increased Cardiovascular Risk Associated With E-Cigarette Use To the Editor Moheimani et al1 suggested that electronic cigarettes (e-cigarettes) are associated with increased cardiovascular risk. To reach this conclusion, the authors measured the heart rate variability, an index of sympathovagal modulation, and 3 parameters of oxidative stress, ie, low-density lipoprotein oxidizability, high-density lipoprotein antioxidant/ anti-inflammatory capacity, and paraoxonase-1 activity, in the plasma of e-cigarettes smokers and nonsmokers.1 Notably, physical activity, or exercise training (both terms are usually used interchangeably), has important effects on sympathovagal activity and oxidative stress, 2 mechanisms analyzed by the authors. Most importantly, the changes induced by shortterm or long-term exercise training on these parameters are substantially different. The reduction of parasympathetic influence after short-term exercise has been demonstrated using heart rate variability, showing a gradual reduction in highfrequency power paralleling increased exercise intensity,2 while long-term exercise–trained individuals have increased heart rate variability as well as improved baroreflex responsiveness.3 On the other hand, short-term exercise bouts considerably increase oxidative stress, wherein trained individuals show an enhanced endogenous antioxidant enzyme capacity and an increased tolerance to exercise-induced oxidative stress.4 Likewise, sedentary lifestyle is also associated with increased oxidative stress5 and negatively affects heart rate variability. In fact, it has been reported that a sedentary lifestyle is as hazardous as smoking in terms of cardiovascular risk. Intriguingly, the authors do not report any observation in reference to exercising habits in both e-cigarette smokers and nonsmokers. This might importantly bias the results of specific parameters evaluated in any single group or even in both groups. It is well known that nonsmoking is associated with increased habitual exercise and vice versa. We absolutely do not advocate smoking, either regular or e-cigarettes, and strongly advise against it. However, the parameters analyzed in this study are probably not the most appropriate for studying the increased cardiovascular risk associated with the use of e-cigarettes unless confounding variables are strictly considered in the analysis.

Prothrombotic State Induced by Middle-Distance Endurance Exercise in Middle-Aged Athletes

Abstract Since the impact of possible prothrombotic factors on blood coagulation resulting from exercise remains elusive, this study investigated the acute effects of middle‐distance endurance running on blood coagulation parameters in middle‐aged athletes. The study population consisted of 33 male endurance runners who were engaged in a 21.1 km run under competitive conditions. Blood samples were collected before the run, immediately after the run, and 3 hours after run completion. Samples were assessed for activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen, D‐dimer, factor VIII (FVIII), von Willebrand factor antigen (VWF:Ag), endogenous thrombin potential (area under the curve of thrombin generation [TGA‐AUC]), and peak thrombin generation (TGA‐PK). Post‐run variations were expressed as delta (&Dgr;). At baseline, APTT was found to be significantly associated with ABO blood group, VWF:Ag, and FVIII; fibrinogen with age; VWF:Ag with BMI, training regimen, and ABO blood group; APTT with FVIII; FVIII with VWF:Ag and ABO blood group; APTT with VWF:Ag; and TGA‐PK with ABO blood group, PT, and TGA‐AUC. Immediately after the run, statistically significant increases were observed for PT, D‐dimer, VWF:Ag, and FVIII, while statistically significant reductions could be observed for APTT, TGA‐AUC, and TGA‐PK. Fibrinogen values remained unchanged. Significant correlations were observed between &Dgr; VWF:Ag and &Dgr; FVIII, &Dgr; APTT and &Dgr; VWF:Ag, &Dgr; APTT and &Dgr; FVIII, &Dgr; TGA‐AUC and &Dgr; TGA‐PK, and between &Dgr; D‐dimer and &Dgr; TGA‐AUC and &Dgr; TGA‐PK. No &Dgr; variation was associated with running time. The results of this study seemingly suggest that middle‐distance competitive running may evoke several prothrombotic changes in blood coagulation.

Sudden Cardiac and Noncardiac Death in Sports: Epidemiology, Causes, Pathogenesis, and Prevention

Abstract Although few doubts remain that physical exercise should be widely promoted for maintenance of health and fitness, the risk of adverse events such as sudden death (especially due to cardiac causes, i.e., sudden cardiac death [SCD]) during exercise remains tangible. The overall risk of sudden death in athletes is relatively low (i.e., usually comprised between 0.1 and 38/100,000 person‐years), and globally comparable to that of the general population. However, up to 20% of all sudden death cases are still recorded while exercising. The most frequent underlying disorders encountered in SCD are hypertrophic cardiomyopathy and coronary artery disease (CAD), representing three quarters of all conditions. The risk related to CAD increases with aging (>35 years old), while that attributable to cardiomyopathies or fatal arrhythmias is especially frequent among young people (<35 years old). Taken together, these findings would lead to the conclusion that physical exercise may be seen as an acute trigger of myocardial ischemia or arrhythmias in some predisposed individuals. Nonetheless, the prevalence of coronary atherosclerosis seems to be higher in athletes than in sedentary subjects with comparable risk profile. On the contrary, coronary plaques in physically active subjects appear more stable, thereby attenuating the risk of rupture and subsequent myocardial ischemia. These findings, along with evidence of a considerable increase of peak coronary blood flow during exercise, make it very likely that an imbalance between oxygen demand and supply may be the most frequent cause of myocardial ischemia in athletes suffering SCD and/or cardiac arrest. Therefore, all subjects who wish to practice moderate‐ to high‐intensity exercise are recommended to undergo preparticipation screening and annual follow‐up.

Epidemiology and clinics of mushroom poisoning in Northern Italy: A 21-year retrospective analysis

Background: Limited information exists about epidemiology and management of mushroom poisoning. We analyzed and described epidemiology, clinical presentation, and clinical course of mushroom-poisoned patients admitted to emergency departments (EDs) of the Province of Parma, Italy. Methods: Data from the database of mycological service were matched with clinical information retrieved from hospitals’ database, from January 1, 1996 to December 31, 2016. Results: Mycologist consultation was obtained in 379/443 identified mushroom poisonings. A remarkable seasonality was found, with significant peak in autumn. Thanks to the collaboration, the implicated species could be identified in 397 cases (89.6%); 108 cases (24.4%) were due to edible mushrooms, Boletus edulis being the most represented (63 cases). Overall, 408 (92%) cases presented with gastrointestinal toxicity. Twenty cases of amatoxin poisoning were recorded (11 Amanita phalloides and 9 Lepiota brunneoincarnata). One liver transplantation was needed. We observed 13 cases of cholinergic toxicity and 2 cases of hallucinogenic toxicity. Finally, 46 cases were due to “mixed” toxicities, and a total of 69 needed hospitalization. Conclusions: Early identification and management of potentially life-threatening cases is challenging in the ED, so that a mycologist service on call is highly advisable, especially during periods characterized by the highest incidence of poisoning.