Heart failure with preserved ejection fraction (HFpEF) remains a poorly characterized syndrome with many unknown aspects related to different patient profiles, various associated risk factors and a ...wide range of aetiologies. It comprises several pathophysiological pathways, such as endothelial dysfunction, myocardial fibrosis, extracellular matrix deposition and intense inflammatory system activation. Until now, HFpEF has only been described with regard to clinical features and its most commonly associated risk factors, disregarding all biological mechanisms responsible for cardiovascular deteriorations. Recently, innovations in laboratory and metabolomic findings have shown that HFpEF appears to be strictly related to specific cells and molecular mechanisms' dysregulation. Indeed, some biomarkers are efficient in early identification of these processes, adding new insights into diagnosis and risk stratification. Moreover, recent advances in intermediate metabolites provide relevant information on intrinsic cellular and energetic substrate alterations. Therefore, a systematic combination of clinical imaging and laboratory findings may lead to a 'precision medicine' approach providing prognostic and therapeutic advantages. The current review reports traditional and emerging biomarkers in HFpEF and it purposes a new diagnostic approach based on integrative information achieved from risk factor burden, hemodynamic dysfunction and biomarkers' signature partnership.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Patients with heart failure are conventionally stratified into phenotypic groups based on their ejection fraction. The aim of this stratification is to improve disease management with a more targeted ...therapeutic approach. A further subdivision based on patient gender is justified. It is recognized that women are underrepresented in randomized controlled clinical trials, resulting in limited clinical and molecular differentiation between males and females. However, many observational studies show that the onset, development, and clinical course of the disease may substantially differ between the two sexes. According to the emerging concept of precision medicine, investigators should further explore the mechanisms responsible for the onset of heart failure due to sex differences. Indeed, the synergistic or opposing effects of sex hormones on the cardiovascular system and underlying heart failure mechanisms have not yet been clarified. Sex hormones, risk factors impact, and cardiovascular adaptations may be relevant for a better understanding of the intrinsic pathophysiological mechanisms in the two sexes. Despite the differences, treatment for HF is similar across the whole population, regardless of sex and gender. In our review, we describe the main differences in terms of cardiovascular dysfunction, risk factors, and cellular signaling modifications related to the hormonal pattern.
Background: Advanced heart failure (HF) is a condition often requiring elevated doses of loop diuretics. Therefore, these patients often experience poor diuretic response. Both conditions have a ...detrimental impact on prognosis and hospitalization. Aims: This retrospective, multicenter study evaluates the effect of the addition of oral metolazone on diuretic response (DR), clinical congestion, NTproBNP values, and renal function over hospitalization phase. Follow-up analysis for a 6-month follow-up period was performed. Methods: We enrolled 132 patients with acute decompensated heart failure (ADHF) in advanced NYHA class with reduced ejection fraction (EF < 40%) taking a mean furosemide amount of 250 ± 120 mg/day. Sixty-five patients received traditional loop diuretic treatment plus metolazone (Group M). The mean dose ranged from 7.5 to 15 mg for one week. Sixty-seven patients continued the furosemide (Group F). Congestion score was evaluated according to the ESC recommendations. DR was assessed by the formula diuresis/40 mg of furosemide. Results: Patients in Group M and patients in Group F showed a similar prevalence of baseline clinical congestion (3.1 ± 0.7 in Group F vs. 3 ± 0.8 in Group M) and chronic kidney disease (CKD) (51% in Group M vs. 57% in Group F; p = 0.38). Patients in Group M experienced a better congestion score at discharge compared to patients in Group F (C score: 1 ± 1 in Group M vs. 3 ± 1 in Group F p > 0.05). Clinical congestion resolution was also associated with weight reduction (−6 ± 2 in Group M vs. −3 ± 1 kg in Group F, p < 0.05). Better DR response was observed in Group M compared to F (940 ± 149 mL/40 mgFUROSEMIDE/die vs. 541 ± 314 mL/40 mgFUROSEMIDE/die; p < 0.01), whereas median ΔNTproBNP remained similar between the two groups (−4819 ± 8718 in Group M vs. −3954 ± 5560 pg/mL in Group F NS). These data were associated with better daily diuresis during hospitalization in Group M (2820 ± 900 vs. 2050 ± 1120 mL p < 0.05). No differences were found in terms of WRF development and electrolyte unbalance at discharge, although Group M had a significant saline solution administration during hospitalization. Follow-up analysis did not differ between the group but a reduced trend for recurrent hospitalization was observed in the M group (26% vs. 38%). Conclusions: Metolazone administration could be helpful in patients taking an elevated loop diuretics dose. Use of thiazide therapy is associated with better decongestion and DR. Current findings could suggest positive insights due to the reduced amount of loop diuretics in patients with advanced HF.
SARS-Cov-2 infection, a pandemic disease since March 2020, is associated with a high percentage of cardiovascular complications mainly of a thromboembolic (TE) nature. Although clinical patterns have ...been described for the assessment of patients with increased risk, many TE complications occur in patients with apparently moderate risk. Notably, a recent statement from the European Society of Cardiology (ESC) atherosclerosis and vascular biology working group pointed out the key role of vascular endothelium for the recruitment of inflammatory and thrombotic pathways responsible for both disseminated intravascular coagulation and cardiovascular complications. Therefore, a better understanding of the pathophysiological process linking infection to increased TE risk is needed in order to understand the pathways of this dangerous liaison and possibly interrupt it with appropriate treatment. In this review, we describe the histological lesions and the related blood coagulation mechanisms involved in COVID-19, we define the laboratory parameters and clinical risk factors associated with TE events, and propose a prophylactic anticoagulation treatment in relation to the risk category. Finally, we highlight the concept that a solid risk assessment based on prospective multi-center data would be the challenge for a more precise risk stratification and more appropriate treatment.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The coronavirus 2019 (COVID‐19) infection pandemic has affected the care of patients with heart failure (HF). Several consensus documents describe the appropriate diagnostic algorithm and treatment ...approach for patients with HF and associated COVID‐19 infection. However, few questions about the mechanisms by which COVID can exacerbate HF in patients with high‐risk (Stage B) or symptomatic HF (Stage C) remain unanswered. Therefore, the type of HF occurring during infection is poorly investigated. The diagnostic differentiation and management should be focused on the identification of the HF phenotype, underlying causes, and subsequent tailored therapy. In this framework, the relationship existing between COVID and onset of acute decompensated HF, isolated right HF, and cardiogenic shock is questioned, and the specific management is mainly based on local hospital organization rather than a standardized model. Similarly, some specific populations such as advanced HF, heart transplant, patients with left ventricular assist device (LVAD), or valve disease remain under investigated. In this systematic review, we examine recent advances regarding the relationships between HF and COVID‐19 pandemic with respect to epidemiology, pathogenetic mechanisms, and differential diagnosis. Also, according to the recent HF guidelines definition, we highlight different clinical profile identification, pointing out the main concerns in understudied HF populations.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Pneumocystis jirovecii pneumonia (PJP) is an opportunistic infection typically observed in AIDS patients, for whom it represents a leading cause of death. However, its incidence among HIV-negative ...immunocompromised patients is progressively increasing, with a significantly higher mortality compared to that of AIDS-patients. We performed a retrospective observational study on HIV-negative patients with PJP. We aimed to determine their epidemiological features and their biohumoral and therapeutic variables, searching for a correlation between them and our patients’ outcome. We included all patients admitted to our Internal Medicine ward from January 2010 to June 2015, who were immunocompromised at the time of admission and had microbiologically confirmed PJP (association between compatible clinical-radiological findings and qualitative polymerase chain reaction positivity on bronchoalveolar lavage). Their immune impairment was assessed considering both their medical history and their complete white blood cells (WBC), differential WBC and their CD4 cell count. Transfer to Intensive Care Unit (ICU) or death was considered as an unfavorable clinical outcome, while hospital discharge or transfer to a non-ICU ward was considered as a favorable outcome. We included a total of 18 patients in our statistical analysis. We used Student’s t-test and Fischer’s χ-square test to compare, respectively, normally distributed continuous variables and non-continuous variables. Our patients’ mean age was 65±13.9 years. All of them had cancer, mostly hematological malignancies (13/18), notably non-Hodgkin lymphoma (NHL; 8/13). They were all being or had been recently treated with chemotherapy (10/18) and/or high-dose glucocorticoids, with full dose or during tapering (13/18). Statistical analysis of blood tests results showed a significant difference between mean serum lactate dehydrogenase (LDH) concentration in the group of patients with favorable vs unfavorable outcome. Also, mean serum immunoglobulins G (IgG) concentration and certain arterial blood gas findings (mean arterial paO2/FiO2, mean blood Ph and mean paCO2) at the time of admission were significantly different in the two groups of patients. 12/18 patient’s outcome turned out unfavorable. Trimethoprim + sulfamethoxazole (TMP+SMX) treatment was given to all our patients, with a mean duration of 13.39±9.36 days. Patients with a favorable outcome had received TMP+SMX treatment significantly earlier than those with an unfavorable outcome. Hematological malignancies, according to literature, confer the strongest predisposition to PJP. Both chemotherapy and high-dose Glucocorticoid treatment are well known predisposing factors. A remarkable elevation of serum LDH represents both a typical clinical feature and a well-known negative prognostic factor in PJP. Low IgG levels have never been reported as a negative prognostic factor, but their role in enhancing macrophage killing of pneumocystis may account for the worst observed prognosis in the group of patients with lower mean levels. Therefore, in order to reduce the heavy mortality rate associated with PJP, an early beginning of specific treatment is of utmost importance, and even if this is certainly true for many infectious diseases, the time gap is particularly limited in the setting of this type of pneumonia. Hence, PJP should be ruled out as soon as possible and, in case of a strong clinical- radiological suspicion, therapy should be started immediately, even while waiting for microbiological confirmation (especially in critically-ill patients).
« Qu’est-ce que le langage et à quoi sert-il ? » « Qu’est-ce qu’un signe linguistique et en quoi consiste sa signification ? » « Quels sont les effets que les expressions linguistiques produisent, ...les contraintes qu’il faut respecter et les précautions qu’il convient de prendre lorsqu’on les utilise ? » Ce complexe de questions, dont on peut retracer l’origine dans un certain nombre de textes de l’Antiquité, oriente depuis les enjeux fondamentaux de la réflexion sur la nature et le sens des expressions linguistiques ainsi que sur les conditions effectives de leur utilisation. Au fil des débats philosophiques, littéraires et autres, cette compréhension du langage s’est déclinée en une variété de manières d’entendre ce que, pour une expression linguistique ou une suite d’expressions linguistiques données, « signifier » veut dire. Les contributions de ce numéro thématique se sont concentrées sur les idées linguistiques que les auteurs de langue et culture grecque – confrontés, plus ou moins explicitement, à la question « comment penser le langage ? » – ont développées afin de rendre compte du phénomène complexe de la signification comme propriété des signes linguistiques, corrélat d’un contenu de pensée ou encore comme produit d’une pratique réglée d’échanges. Leone Gazziero “What is language and what is it used for?” “What is a linguistic sign and what does its signification / meaning consist in?” “What are the effects that linguistic expressions produce, the constraints that must be respected in their regard, and the precautions that must be taken when using them?” This complex of questions, whose origin can be traced back to a certain number of texts from Antiquity, has oriented ever since the fundamental issues for reflecting on the nature and meaning of linguistic expressions, and on the actual conditions of their use. In the course of philosophical, literary, and other genres of debate, this understanding of language has developed in a variety of ways of grasping—for a given linguistic expression or sequence of linguistic expressions—what “to signify / to mean” actually means. The contributions in this thematic issue focus on linguistic ideas that authors of Greek language and culture developed (having been confronted, more or less explicitly, with the question “how to think about language?”) in order to account for the complex phenomenon of signification / meaning as a property of linguistic signs, or as a correlate to thought content, or even as the product of a regulated practice of exchanges. Leone Gazziero
Lensing of the CMB is now a well-developed probe of large-scale clustering over a broad range of redshifts. By exploiting the non-Gaussian imprints of lensing in the polarization of the CMB, the CORE ...mission can produce a clean map of the lensing deflections over nearly the full-sky. The number of high-S/N modes in this map will exceed current CMB lensing maps by a factor of 40, and the measurement will be sample-variance limited on all scales where linear theory is valid. Here, we summarise this mission product and discuss the science that it will enable. For example, the summed mass of neutrinos will be determined to an accuracy of 17 meV combining CORE lensing and CMB two-point information with contemporaneous BAO measurements, three times smaller than the minimum total mass allowed by neutrino oscillations. In the search for B-mode polarization from primordial gravitational waves with CORE, lens-induced B-modes will dominate over instrument noise, limiting constraints on the gravitational wave power spectrum amplitude. With lensing reconstructed by CORE, one can "delens" the observed polarization internally, reducing the lensing B-mode power by 60%. This improves to 70% by combining lensing and CIB measurements from CORE, reducing the error on the gravitational wave amplitude by 2.5 compared to no delensing (in the null hypothesis). Lensing measurements from CORE will allow calibration of the halo masses of the 40000 galaxy clusters that it will find, with constraints dominated by the clean polarization-based estimators. CORE can accurately remove Galactic emission from CMB maps with its 19 frequency channels. We present initial findings that show that residual Galactic foreground contamination will not be a significant source of bias for lensing power spectrum measurements with CORE. abridged
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