Precision medicine in heart failure no longer a visual theory but a realistic opportunity

Over the last decades, major advances in the understanding of pathophysiology in a wide spectrum of cardiovascular diseases provided several effective pharmacological and non-pharmacological therapies [1]. Along with novel rehabilitation and follow up strategies, these advances have improved the survival rate of cardiac diseases, globally, and contributed generally to a significant increase in life expectancy [2]. As a consequence, there is a parallel increase of patients suffering from challenging and multifaceted syndromes such as heart failure (HF). HF is a recognised pandemic disease, with a progressively increasing prevalence in the aging population [3]. It is a major public health issue, considering both its social and economic implications. HF patients are characterised by a high level of complexity because of the advanced age and the presence of multiple relevant comorbidities requiring dedicated polytherapy [1]. Therefore, overall mortality of HF patients is still unacceptably high, exceeding that of several neoplasms, carrying a risk of approximately 10% at 12 months from clinical onset [4]

Iperpotassiemia nello scompenso cardiaco: nuove soluzioni per un vecchio problema

Il potassio \ue8 il principale ione intracellulare e la sua omeostasi \ue8 finemente regolata dall\u2019apparato renale e gastrointestinale. L\u2019insufficienza renale e l\u2019iperpotassiemia sono condizioni di comune riscontro nei pazienti con scompenso cardiaco, risultato di una complessa interazione tra cuore e rene (es. sindrome cardio-renale) e degli effetti collaterali dei farmaci comunemente impiegati per il trattamento della malattia cardiaca (es. inibitori del sistema renina-angiotensina-aldosterone). Sebbene l\u2019iperpotassiemia incrementi il rischio di disturbi di conduzione ed aritmie minacciose per la vita, il suo significato prognostico nello scompenso cardiaco \ue8 incerto. L\u2019iperpotassiemia e la progressione del danno renale costituiscono i principali limiti all\u2019introduzione e alla titolazione delle terapie eziologiche dello scompenso cardiaco. L\u2019ingresso in commercio di nuovi farmaci per la prevenzione e il trattamento cronico dell\u2019iperpotassiemia permette di introdurre e modulare la terapia anti-neurormonale in pazienti con scompenso cardiaco altrimenti esclusi per i livelli di potassio sierico eccessivamente elevati. Questa rassegna tratta gli aspetti fisiopatologici ed epidemiologico-prognostici dell\u2019iperpotassiemia, offrendo, inoltre, un\u2019analisi sulle possibili strategie di trattamento della disionia nello scompenso cardiaco

Validation and Performance Comparison of Two Scoring Systems Created Specifically to Predict the Risk of Deep Sternal Wound Infection after Bilateral Internal Thoracic Artery Grafting

Background: The Gatti and the bilateral internal mammary artery (BIMA) scores were created to predict the risk of deep sternal wound infection (DSWI) after bilateral internal thoracic artery (BITA) grafting. Methods: Both scores were evaluated retrospectively in two consecutive series of patients undergoing isolated multi-vessel coronary surgical procedures - i.e., the Trieste (n = 1,122; BITA use, 52.1%; rate of DSWI, 5.7%) and the Besan\ue7on cohort (n = 721; BITA use, 100%; rate of DSWI, 2.5%). Baseline patient characteristics were compared between the two validation samples. For each score, the accuracy of prediction and predictive power were assessed by the area under the receiver-operating characteristic curve (AUC) and the Goodman-Kruskal gamma coefficient, respectively. Results: There were significant differences between the two series in terms of age, gender, New York Heart Association functional class, chronic lung disease, left ventricular function, surgical priority, and the surgical techniques used. In the Trieste series, accuracy of prediction of the Gatti score for DSWI was higher than that of the BIMA score (AUC, 0.729 vs. 0.620, p = 0.0033). The difference was not significant, however, in the Besan\ue7on series (AUC, 0.845 vs. 0.853, p = 0.880) and when only BITA patients of the Trieste series were considered for analysis (AUC, 0.738 vs. 0.665, p = 0.157). In both series, predictive power was at least moderate for the Gatti score and low for the BIMA score. Conclusions: The Gatti and the BIMA scores seem to be useful for pre-operative evaluation of the risk of DSWI after BITA grafting. Further validation studies should be performed

L-DOPA preloading increases the uptake of borophenylalanine in C6 glioma rat model: a new strategy to improve BNCT efficacy.

Purpose: Boron neutron capture therapy (BNCT) is a radiotherapeutic modality based on 10B(n,a)7Li reaction, for the treatment of malignant gliomas. One of the main limitations for BNCT effectiveness is the insufficient intake of 10B nuclei in the tumor cells. This work was aimed at investigating the use of L-DOPA as a putative enhancer for 10B-drug 4-dihydroxy-borylphenylalanine (BPA) uptake in the C6-glioma model. The investigation was first per- formed in vitro and then extended to the animal model. Methods and Materials: BPA accumulation in C6-glioma cells was assessed using radiowave dielectric spectros- copy, with and without L-DOPA preloading. Two L-DOPA incubation times (2 and 4 hours) were investigated, and the corresponding effects on BPA accumulation were quantified. C6-glioma cells were also implanted in the brain of 32 rats, and tumor growth was monitored by magnetic resonance imaging. Rats were assigned to two experimental branches: (1) BPA administration; (2) BPA administration after pretreatment with L-DOPA. All an- imals were sacrificed, and assessments of BPA concentrations in tumor tissue, normal brain, and blood samples were performed using high-performance liquid chromatography. Results: L-DOPA preloading induced a massive increase of BPA concentration in C6-glioma cells only after a 4-hour incubation. In the animal model, L-DOPA pretreatment produced a significantly higher accumulation of BPA in tumor tissue but not in normal brain and blood samples. Conclusions: This study suggests the potential use of L-DOPA as enhancer for BPA accumulation in malig- nant gliomas eligible for BNCT. L-DOPA preloading effect is discussed in terms of membrane transport mechanisms

Influence of thermal conductivity on the dynamic response of magnetocaloric materials

We compare the magnetocaloric effect of samples prepared with different thermal conductivities to investigate the potential of composite materials. By applying the magnetic field under operating conditions we test the material’s response and compare this to heat transfer simulations in order to check the reliability of the adiabatic temperature change probe used. As a result of this study we highlight how the material’s thermal conductivity influences τ , the time constant of temperature change. This parameter ultimately limits the maximum frequency of a refrigerant cycle and offers fundamental information about the correlation between thermal conductivity and the magnetocaloric effect

Persistent modification of forebrain networks and metabolism in rats following adolescent exposure to a 5-HT7 receptor agonist

RATIONALE: The serotonin 7 receptor (5-HT7-R) is part of a neuro-transmission system with a proposed role in neural plasticity and in mood, cognitive or sleep regulation. OBJECTIVES: We investigated long-term consequences of sub-chronic treatment, during adolescence (43-45 to 47-49 days old) in rats, with a novel 5-HT7-R agonist (LP-211, 0 or 0.250 mg/kg/day). METHODS: We evaluated behavioural changes as well as forebrain structural/functional modifications by in vivo magnetic resonance (MR) in a 4.7 T system, followed by ex vivo histology. RESULTS: Adult rats pre-treated during adolescence showed reduced anxiety-related behaviour, in terms of reduced avoidance in the light/dark test and a less fragmented pattern of exploration in the novel object recognition test. Diffusion tensor imaging (DTI) revealed decreased mean diffusivity (MD) in the amygdala, increased fractional anisotropy (FA) in the hippocampus (Hip) and reduced axial (D||) together with increased radial (D⊥) diffusivity in the nucleus accumbens (NAcc). An increased neural dendritic arborization was confirmed in the NAcc by ex vivo histology. Seed-based functional MR imaging (fMRI) identified increased strength of connectivity within and between "limbic" and "cortical" loops, with affected cross-correlations between amygdala, NAcc and Hip. The latter displayed enhanced connections through the dorsal striatum (dStr) to dorso-lateral prefrontal cortex (dl-PFC) and cerebellum. Functional connection also increased between amygdala and limbic elements such as NAcc, orbito-frontal cortex (OFC) and hypothalamus. MR spectroscopy (1H-MRS) indicated that adolescent LP-211 exposure increased glutamate and total creatine in the adult Hip. CONCLUSIONS: Persistent MR-detectable modifications indicate a rearrangement within forebrain networks, accounting for long-lasting behavioural changes as a function of developmental 5-HT7-R stimulatio

Pericardiectomy for constrictive pericarditis: a risk factor analysis for early and late failure

Predictors of early and late failure of pericardiectomy for constrictive pericarditis (CP) have not been established. Early and late outcomes of a cumulative series of 81 (mean age 60\ua0years; mean EuroSCORE II, 3.3%) consecutive patients from three European cardiac surgery centers were reviewed. Predictors of a combined endpoint comprising in-hospital death or major complications (including multiple transfusion) were identified with binary logistic regression. Non-parametric estimates of survival were obtained with the Kaplan\u2013Meier method. Predictors of poor late outcomes were established using Cox proportional hazard regression. There were 4 (4.9%) in-hospital deaths. Preoperative central venous pressure > 15\ua0mmHg (p = 0.005) and the use of cardiopulmonary bypass (p = 0.016) were independent predictors of complicated in-hospital course, which occurred in 29 (35.8%) patients. During follow-up (median, 5.4\ua0years), preoperative renal impairment was a predictor of all-cause death (p = 0.0041), cardiac death (p = 0.0008), as well as hospital readmission due to congestive heart failure (p = 0.0037); while partial pericardiectomy predicted all-cause death (p = 0.028) and concomitant cardiac operation predicted cardiac death (p = 0.026), postoperative central venous pressure < 10\ua0mmHg was associated with a low risk both of all-cause and cardiac death (p < 0.0001 for both). Ten-year adjusted survival free of all-cause death, cardiac death, and hospital readmission were 76.9%, 94.7%, and 90.6%, respectively. In high-risk patients with CP, performing pericardiectomy before severe constriction develops and avoiding cardiopulmonary bypass (when possible) could contribute to improving immediate outcomes post-surgery. Complete removal of cardiac constriction could enhance long-term outcomes

Generalized approach to translating exercise tests and prescribing exercise

Although there is evidence supporting the benefit of regular exercise, and recommendations about exercise and physical activity, the process of individually prescribing exercise following exercise testing is more difficult. Guidelines like % heart rate (HR) reserve (HRR) require an anchoring maximal test and do not always provide a homogenous training experience. When prescribing HR on the basis of % HRR, rating of perceived exertion or Talk Test, cardiovascular/perceptual drift during sustained exercise makes prescription of the actual workload difficult. To overcome this issue, we have demonstrated a strategy for "translating" exercise test responses to steady state exercise training on the basis of % HRR or the Talk Test that appeared adequate for individuals ranging from cardiac patients to athletes. However, these methods depended on the nature of the exercise test details. In this viewpoint, we combine these data with workload expressed as Metabolic Equivalent Task (METs). We demonstrate that there is a regular stepdown between the METs during training to achieve the same degree of homeostatic disturbance during testing. The relationship was linear, was highly-correlated (r = 0.89), and averaged 71.8% (Training METs/Test METs). We conclude that it appears possible to generate a generalized approach to correctly translate exercise test responses to exercise training