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Background The European impact of the clinical high risk for psychosis (CHR-P) paradigm is constrained by the lack of critical mass (detection) to power prognostic and preventive interventions. Methods An ITAlian partnership for psychosis prevention (ITAPP) was created across CHR-P centers, which were surveyed to describe: (a) service, catchment area, and outreach; (b) service users; and (c) interventions and outcomes. Descriptive statistics and Kaplan-Meier failure function complemented the analyses. Results The ITAPP included five CHR-P clinical academic centers established from 2007 to 2018, serving about 13 million inhabitants, with a recruitment capacity of 277 CHR-P individuals (mean age: 18.7 years, SD: 4.8, range: 12-39 years; 53.1% females; 85.7% meeting attenuated psychotic symptoms; 85.8% without any substance abuse). All centers were multidisciplinary and included adolescents and young adults (transitional) primarily recruited through healthcare services. The comprehensive assessment of at-risk mental state was the most widely used instrument, while the duration of follow-up, type of outreach, and preventive interventions were heterogeneous. Across 205 CHR-P individuals with follow up (663.7 days ± 551.7), the cumulative risk of psychosis increased from 8.7% (95% CI 5.3-14.1) at 1 year to 15.9% (95% CI 10.6-23.3) at 2 years, 21.8% (95% CI 14.9-31.3) at 3 years, 34.8% (95% CI 24.5-47.9) at 4 years, and 51.9% (95% CI 36.3-69.6) at 5 years. Conclusions The ITAPP is one of the few CHR-P clinical research partnerships in Europe for fostering detection, prognosis, and preventive care, as well as for translating research innovations into practice.

Individuals with psychoses have brain alterations, particularly in frontal and temporal cortices, that may be particularly prominent, already at illness onset, in those more likely to have poorer symptom remission following treatment with the first antipsychotic. The identification of strong neuroanatomical markers of symptom remission could thus facilitate stratification and individualized treatment of patients with schizophrenia. We used magnetic resonance imaging at baseline to examine brain regional and network correlates of subsequent symptomatic remission in 167 medication-naïve or minimally treated patients with first-episode schizophrenia, schizophreniform disorder, or schizoaffective disorder entering a three-phase trial, at seven sites. Patients in remission at the end of each phase were randomized to treatment as usual, with or without an adjunctive psycho-social intervention for medication adherence. The final follow-up visit was at 74 weeks. A total of 108 patients (70%) were in remission at Week 4, 85 (55%) at Week 22, and 97 (63%) at Week 74. We found no baseline regional differences in volumes, cortical thickness, surface area, or local gyrification between patients who did or did not achieved remission at any time point. However, patients not in remission at Week 74, at baseline showed reduced structural connectivity across frontal, anterior cingulate, and insular cortices. A similar pattern was evident in patients not in remission at Week 4 and Week 22, although not significantly. Lack of symptom remission in first-episode psychosis is not associated with regional brain alterations at illness onset. Instead, when the illness becomes a stable entity, its association with the altered organization of cortical gyrification becomes more defined.

The current management of patients with primary psychosis worldwide is often remarkably stereotyped. In almost all cases an antipsychotic medica­tion is prescribed, with second-generation antipsychotics usually preferred to first-generation ones. Cognitive behavioral therapy is rarely used in the vast majority of countries, although there is evidence to support its efficacy. Psychosocial interventions are often provided, especially in chronic cases, but those applied are frequently not validated by research. Evidence-based family interventions and supported employment programs are seldom implemented in ordinary practice. Although the notion that patients with primary psychosis are at increased risk for cardiovascular diseases and diabetes mellitus is widely shared, it is not frequent that appropriate measures be implemented to address this problem. The view that the management of the patient with primary psychosis should be personalized is endorsed by the vast majority of clinicians, but this personalization is lacking or inadequate in most clinical contexts. Although many mental health services would declare themselves “recovery-oriented”, it is not common that a focus on empowerment, identity, meaning and resilience is ensured in ordinary practice. The present paper aims to address this situation. It describes systematically the salient domains that should be considered in the characterization of the individual patient with primary psychosis aimed at personalization of management. These include positive and negative symptom dimensions, other psychopathological components, onset and course, neurocognition and social cognition, neurodevelopmental indicators; social functioning, quality of life and unmet needs; clinical staging, antecedent and concomitant psychiatric conditions, physical comorbidities, family history, history of obstetric complications, early and recent environmental exposures, protective factors and resilience, and internalized stigma. For each domain, simple assessment instruments are identified that could be considered for use in clinical practice and included in standardized decision tools. A management of primary psychosis is encouraged which takes into account all the available treatment modalities whose efficacy is supported by research evidence, selects and modulates them in the individual patient on the basis of the clinical characterization, addresses the patient’s needs in terms of employment, housing, self-care, social relationships and education, and offers a focus on identity, meaning and resilience.

Nearly half of all patients with heart failure (HF) have a normal left ventricular (LV) ejection fraction (EF) and the condition is termed heart failure with preserved ejection fraction (HFpEF). It is assumed that in these patients HF is due primarily to LV diastolic dysfunction. The prognosis in HFpEF is almost as severe as in HF with reduced EF (HFrEF). In contrast to HFrEF where drugs and devices are proven to reduce mortality, in HFpEF there has been limited therapy available with documented effects on prognosis. This may reflect that HFpEF encompasses a wide range of different pathological processes, which multimodality imaging is well placed to differentiate. Progress in developing therapies for HFpEF has been hampered by a lack of uniform diagnostic criteria. The present expert consensus document from the European Association of Cardiovascular Imaging (EACVI) provides recommendations regarding how to determine elevated LV filling pressure in the setting of suspected HFpEF and how to use multimodality imaging to determine specific aetiologies in patients with HFpEF.

Cor pulmonale is the condition in which the right ventricle undergoes morphological and/or functional changes due to diseases that affect the lungs, the pulmonary circulation, or the breathing process. Depending on the speed of onset of the pathological condition and subsequent effects on the right ventricle, it is possible to distinguish the acute cor pulmonale from the chronic type of disease. Echocardiography plays a central role in the diagnostic and therapeutic work-up of these patients, because of its non-invasive nature and wide accessibility, providing its greatest usefulness in the acute setting. It also represents a valuable tool for tracking right ventricular function in patients with cor pulmonale, assessing its stability, deterioration, or improvement during follow-up. In fact, not only it provides parameters with prognostic value, but also it can be used to assess the efficacy of treatment. This review attempts to provide the current standards of an echocardiographic evaluation in both acute and chronic cor pulmonale, focusing also on the findings present in the most common pathologies causing this condition.

Negative symptoms are associated with poor clinical and psychosocial outcome in schizophrenia. Their prevalence and identification in first-episode patients remains controversial. In a large cohort of patients in the early stage of schizophrenia, schizophreniform or schizoaffective disorder, we investigated, over the different phases of the OPTiMiSE trial (baseline, 4, 10 and 22 weeks of treatment), the prevalence of negative symptoms of moderate severity, unconfounded by depression and extrapyramidal symptoms at baseline. Moreover, we assessed symptomatic remission, attrition rate and psychosocial functioning in subjects with short-term (4 weeks) persistent unconfounded negative symptoms (PNS) and in those with negative symptoms that did not persist at follow-up and/or were confounded at baseline (N-PNS). Negative symptoms of moderate severity were observed in 59% of subjects at baseline. They were associated with worse psychosocial functioning and longer duration of psychosis at intake in the study. Eleven percent of subjects had PNS unconfounded at baseline and 7.9% had PNS unconfounded at both baseline and end of 4-week treatment. Psychosocial functioning was comparable in PNS and N-PNS subjects at baseline but it was significantly worse in the former group after 4-weeks. PNS subjects showed lower remission and higher attrition rates at the end of all treatment phases. Fifty-six percent of subjects completing phase 3 (clozapine treatment) had PNS, and 60% of them were non-remitters at the end of this phase. The presence of short-term PNS during the first phases of psychosis was associated with poor clinical outcome and resistance to antipsychotic treatment, including clozapine.

Left ventricular (LV) global longitudinal strain (GLS) can detect an early dysfunction in arterial hypertension. We investigated regional LV patterns of longitudinal strain (LS) and base-to-apex behaviour in newly diagnosed, never-treated hypertensive patients (HTN) without LV hypertrophy.180 HTN and 115 healthy controls underwent standard echocardiography, including regional LS and GLS assessment (in absolute values). The average LS of six basal (BLS), six middle (MLS), and six apical (ALS) segments and relative regional strain ratio = [ALS/(BLS + MLS)] were also computed.The two groups were comparable for sex, age and heart rate. Body mass index (BMI), systolic, diastolic and mean blood pressure (BP) (all p 0.0001) were higher in HTN. Despite LV ejection fraction (EF) was comparable, GLS, BLS and MLS resulted lower in HTN (all p 0.0001), without difference in ALS. Relative regional strain ratio resulted higher in HTN (p 0.001). Dividing HTN group according to lower normal values derived from the controls, BLS was able to identify a higher rate of LV dysfunction than GLS. By a multiple linear regression analysis performed in the pooled population after adjusting for age, sex, BMI, end-systolic stress, relative wall thickness and LV mass index, the association between BLS and mean BP remained significant (β coefficient = -0.42, p 0.0001), despite the significant impact of male sex. In a similar model, MLS and mean BP resulted also independently associated (β = -0.21, p 0.002).Despite normal LV EF, LS dysfunction is detectable in HTN, mainly involving basal and middle segments, resulting in higher relative regional strain ratio.

Systemic lupus erythematosus (SLE), is characterized by a systemic involvement including myocardial dysfunction. Being standard echocardiography not able at fully detecting subclinical alterations, speckle tracking echocardiography (STE) has recently emerged as a quantitative ultrasound technique to accurately estimate myocardial function.We conducted a systematic review with meta-analysis of studies reporting STE parameters in patients with SLE.A total of 9 studies were included in the analysis. Left ventricle global longitudinal strain (GLS) was significantly lower in SLE patients than in non-SLE controls (MD: -2.331, 95% CI: -3.083, -1.580, p 0.001). In addition, we found significant differences between SLE patients and non-SLE controls in left ventricle GLS rate (MD: -0.115, 95% CI: -0.177 to 0.063, p 0.001), left ventricle circumferential strain(MD: -1.841, 95% CI: -3.160 to 0.521, p = 0.006) and left ventricle radial strain(MD: -11.03, 95% CI: -13.819 to 8.241, p 0.001). Right ventricle strain was significantly lower in SLE patients than in non-SLE controls (MD: -5.814, 95% CI: -7.347, -4.281, p 0.001). Meta-regression models showed a lower difference in left ventricle GLS between SLE cases and controls for studies with a higher prevalence of female gender and higher prevalence of hypertension.SLE patients have lower STE parameters than controls, thus suggesting the presence of an impaired myocardial function involving both left and right ventricle.

BACKGROUND In hypertensive patients, an impairment of midwall myocardial mechanics was described in presence of left ventricular (LV) concentric geometry. Under these circumstances, also LV longitudinal dysfunction was found. PURPOSE Our aim was to evaluate longitudinal and circumferential systolic function and correlations between these two functional components in newly diagnosed hypertensive patients without clinically defined LV hypertrophy (LVH). One hundred and thirty-eight newly diagnosed, never-treated hypertensive patients without LVH and a control group of 105 healthy normotensive individuals underwent two-dimensional and speckle tracking echocardiography. Global longitudinal strain (GLS) was derived (in absolute value) and midwall fractional shortening (MFS) computed. In addition, the hypertensive population was divided into two groups according to GLS: normal GLS (≥20%, n = 94) and reduced GLS (

In 2016, an update of the 2009 recommendations for the evaluation of left ventricular (LV) diastolic function (DF) was released by the American Society of Echocardiography and the European Association of Cardiovascular Imaging. The aims of this study were to assess the concordance between the 2016 and 2009 recommendations and to test the impact of the consideration of "myocardial disease" recommended in the 2016 update on the evaluation of diastolic dysfunction (DD) and LV filling pressures in patients with normal and reduced LV ejection fractions referred to a general echocardiography laboratory.A total of 1,508 outpatients referred to an echocardiography laboratory during a predefined 5-month period were prospectively enrolled. All patients underwent targeted clinical history and Doppler echocardiographic examination. DD and LV filling pressures were assessed according to 2009 and 2016 recommendations. Concordance was calculated using the κ coefficient and overall proportion of agreement.Overall proportion of agreement between the two recommendations was 64.7% (κ = 0.43). Comparing the 2009 and 2016 recommendations, 47.5% and 36.1% patients, respectively, had DD (P .0001), and 22.7% and 12.6% had elevated LV filling pressures (P .0001). This difference remained significant in the setting of patients with normal LV ejection fractions (21.6% vs 10.7%, P .0001). In the application of the 2016 recommendations, whether or not the presence of "myocardial disease" was considered, the prevalence of indeterminate diastolic function was, respectively, 7.3% versus 13.7%, while patients in whom the DD grade could not be determined were 8.1% versus 14.4% (P .0001 for all).Considering the presence of myocardial disease when applying the 2016 recommendations resulted in a lower prevalence of inconclusive diagnosis.

Background The search for reliable cardiac functional parameters is crucial in patients with mitral regurgitation (MR). In the Italian arm of the European Registry of MR, we compared the ability of global longitudinal strain (GLS) and left ventricular (LV) ejection fraction (LVEF) to detect cardiac damage in MR. Methods Five hundred four consecutive patients with MR underwent a complete echo-Doppler exam. A total of 431, 53 and 20 patients had degenerative, secondary and mixed MR, respectively. The main echocardiographic parameters, including LV and left atrial (LA) size measurements, pulmonary artery systolic pressure (PASP) and GLS were compared between patients with mild MR (n = 392) vs. moderate to severe MR (n = 112). Results LVEF and GLS were related one another in the pooled population, and separately in patients with mild and moderate/severe MR (all p Conclusions Both LVEF and GLS are independently associated with LV and LA size, but only GLS is related to pulmonary arterial pressure. GLS is a powerful hallmark of cardiac damage in MR.

BACKGROUND In hypertensive patients, high left ventricular (LV) mass/end-diastolic volume ratio (LVM/EDV) is related to LV dysfunction and myocardial fibrosis. PURPOSE We examined the ability of 3D-echo-derived LVM/EDV ratio in identifying early systolic and diastolic dysfunction in relation with LV concentric geometry in native hypertensive patients. METHODS One-hundred and forty-four newly diagnosed, never treated hypertensive patients underwent 2D-echo, including computation of 2D-derived global longitudinal strain (GLS), and 3D-echo. The study population was divided into two groups: elevated 3D-LVM/EDV (≥1.23 in women and ≥1.22 in men), corresponding to LV concentric geometry (n = 50), and normal ratio (

Importance: The goal of schizophrenia treatment has shifted from symptom reduction and relapse prevention to functional recovery; however, recovery rates remain low. Prospective identification of variables associated with real-life functioning domains is essential for personalized and integrated treatment programs. Objective: To assess whether baseline illness-related variables, personal resources, and context-related factors are associated with work skills, interpersonal relationships, and everyday life skills at 4-year follow-up. Design, Setting, and Participants: This multicenter prospective cohort study was conducted across 24 Italian university psychiatric clinics or mental health departments in which 921 patients enrolled in a cross-sectional study were contacted after 4 years for reassessment. Recruitment of community-dwelling, clinically stable persons with schizophrenia was conducted from March 2016 to December 2017, and data were analyzed from January to May 2020. Main Outcomes and Measures: Psychopathology, social and nonsocial cognition, functional capacity, personal resources, and context-related factors were assessed, with real-life functioning as the main outcome. Structural equation modeling, multiple regression analyses, and latent change score modeling were used to identify variables that were associated with real-life functioning domains at follow-up and with changes from baseline in these domains. Results: In total, 618 participants (427 male [69.1%]; mean [SD] age, 45.1 [10.5] years) were included. Five baseline variables were directly associated with real-life functioning at follow-up: neurocognition with everyday life (β, 0.274; 95% CI, 0.207-0.341; P

This chapter aims at providing hints to improve existing frameworks for disaster risk management based on a review of the main documents framing disaster management within the last two and a half decades and with reference to the potential contribution of resilience thinking. The evolution path of disaster risk management shows that, although some progresses have been made, there are still numerous gaps to be filled. On the opposite, focusing on the increasing convergence of resilience and disaster studies, it emerges that a resilience-based approach could still provide significant theoretical and operational inputs towards an improved disaster risk management. In particular, this chapter emphasizes the potential contribution of resilience thinking in developing a new framework for guiding disaster risk management capable of (1) taking into consideration the rapidly changing risk landscapes due to the interplay between climate change and the consequent increase of hazardous events, urbanization patterns and the complex interrelationships among them; (2) shifting from sectoral approaches to disaster risk reduction (DRR) towards integrated approaches and cross-sectoral strategies and tools; (3) embracing transformational perspectives to significantly reduce disaster losses and achieve sustainability goals; (4) improving learning capacity through the setting up of continual learning processes; (5) emphasizing the role of spatial and land use planning for DRR; and (6) developing more innovative governance models based on collaboration, shared responsibility and active engagement of the stakeholders.

Although the increase in the frequency and intensity of disasters assigns a key role to disaster risk management in current debate on sustainable development, the efforts of national and local authorities to develop risk-informed planning strategies and increase disaster preparedness are still limited. In multi-hazard urban environments, the main criticality to support risk-informed planning strategies is the persisting lack of effective knowledge bases focused on the vulnerability of exposed assets to different hazards. Hence, this contribution, according to the first priority of the Sendai Framework for Disaster Risk Reduction—understanding disaster risk—and by tidying up methods and indicators developed in both EU research projects and scientific studies devoted to multi-risk and vulnerability assessment, aims at better using available knowledge to guide risk-informed spatial planning. In detail, an indicator-based method to carry out a comprehensive exposure and vulnerability analysis has been outlined and tested on a case study area, the multi-hazard urban area of Campi Flegrei, located in the western part of the metropolitan city of Naples in the South of Italy. The proposed method may contribute to the building up of an effective risk knowledge base, enabling planners to easily access information on exposure and vulnerabilities to different hazards, and to differently combine them into output maps capable of supporting risk- informed planning strategies.

Progress in the treatment of cancer has significantly improved survival of oncologic patients in recent decades. However, anticancer therapies, particularly some new, more potent and targeted agents, are potentially cardiotoxic. As a consequence, cardiovascular complications, including heart failure, arterial hypertension, coronary artery disease, venous thromboembolism, peripheral vascular disease, arrhythmias, pericardial disease, and pulmonary hypertension, as related to cancer itself or to anticancer treatments, are increasingly observed and may adversely affect prognosis in oncologic patients. Cardiovascular oncology is an emerging field in cardiology and internal medicine, which is rapidly growing, dealing with the prevention, the early detection, and the management of cardiovascular disease, in all stages of anticancer therapy and during the survivorship period, now crucial for reducing cardiovascular morbidity and mortality in cancer patients. In this narrative review, the existing literature regarding the epidemiology of cardiovascular oncology, the mechanisms of cardiovascular complications in cancer, and the pathophysiology of cardiotoxicity related to chemotherapeutic agents, targeted therapies, immunotherapies, and radiotherapy will be analyzed and summarized.

Background This double-blind (DB), randomized, parallel-group study was designed to evaluate efficacy and safety of paliperidone palmitate 6-month (PP6M) formulation relative to paliperidone palmitate 3-month (PP3M) formulation in patients with schizophrenia. Methods Following screening, patients entered an open-label (OL) maintenance phase and received 1 injection cycle of paliperidone palmitate 1-month (PP1M; 100 or 150 mg eq.) or PP3M (350 or 525 mg eq.). Clinically stable patients were randomized (2:1) to receive PP6M (700 or 1000 mg eq., gluteal injections) or PP3M (350 or 525 mg eq.) in a 12-month DB phase; 2 doses of PP6M (corresponding to doses of PP1M and PP3M) were chosen. Results Overall, 1036 patients were screened, 838 entered the OL phase, and 702 (mean age: 40.8 years) were randomized (PP6M: 478; PP3M: 224); 618 (88.0%) patients completed the DB phase (PP6M: 416 [87.0%]; PP3M: 202 [90.2%]). Relapse rates were PP6M, 7.5% (n = 36) and PP3M, 4.9% (n = 11). The Kaplan-Meier estimate of the difference (95% CI) between treatment groups (PP6M − PP3M) in the percentages of patients who remained relapse free was −2.9% (−6.8%, 1.1%), thus meeting noninferiority criteria (95% CI lower bound is larger than the pre-specified noninferiority margin of −10%). Secondary efficacy endpoints corroborated the primary analysis. Incidences of treatment-emergent adverse events were similar between PP6M (62.1%) and PP3M (58.5%). No new safety concerns emerged. Conclusions The efficacy of a twice-yearly dosing regimen of PP6M was noninferior to that of PP3M in preventing relapse in patients with schizophrenia adequately treated with PP1M or PP3M. Trial Registration Clinical Trials.gov identifier: NCT03345342

Heart failure (HF) is among the most important and frequent complications of diabetes mellitus (DM). The detection of subclinical dysfunction is a marker of HF risk and presents a potential target for reducing incident HF in DM. Left ventricular (LV) dysfunction secondary to DM is heterogeneous, with phenotypes including predominantly systolic, predominantly diastolic, and mixed dysfunction. Indeed, the pathogenesis of HF in this setting is heterogeneous. Effective management of this problem will require detailed phenotyping of the contributions of fibrosis, microcirculatory disturbance, abnormal metabolism, and sympathetic innervation, among other mechanisms. For this reason, an imaging strategy for the detection of HF risk needs to not only detect subclinical LV dysfunction (LVD) but also characterize its pathogenesis. At present, it is possible to identify individuals with DM at increased risk HF, and there is evidence that cardioprotection may be of benefit. However, there is insufficient justification for HF screening, because we need stronger evidence of the links between the detection of LVD, treatment, and improved outcome. This review discusses the options for screening for LVD, the potential means of identifying the underlying mechanisms, and the pathways to treatment.

The growing exposure and vulnerability of cities to hazardous events and the ineffectiveness of urban planning in providing adequate responses to the need of risk reduction exacerbate the impacts of natural hazards, leading more and more often to disasters. The most recent international documents on disaster risk reduction (DRR) largely emphasize the urgency to review current approaches to risk knowledge, by overcoming the widespread frag-mentation and segmentation of data, information and competencies, to bet-ter support a risk-informed urban development and to provide more ade-quate information on risks to different users, including citizens. Thus, start-ing from a brief analysis of the most critical issues that affect risk knowledge in Italy and according to the objectives of the first priority area of the Sendai Framework 2015-2030, this contribution outlines a methodo-logical frame for building up an integrated risk knowledge base, specifically tailored to planning purposes. Furthermore, based on the outlined methodo-logical frame, three main research questions will be specifically addressed: how to identify the main gaps in existing knowledge; how to shift from a single hazard/risk perspective to a multi-risk perspective, capable of taking into account the potential interactions among different hazard sources; how to improve current knowledge on vulnerability of exposed assets.

Aims The present study sought to evaluate the correlation between indices of non-invasive myocardial work (MW) and left ventricle (LV) size, traditional and advanced parameters of LV systolic and diastolic function by 2D echocardiography (2DE). Methods and results A total of 226 (85 men, mean age: 45 ± 13 years) healthy subjects were enrolled at 22 collaborating institutions of the Normal Reference Ranges for Echocardiography (NORRE) study. Global work index (GWI), global constructive work (GCW), global work waste (GWW), and global work efficiency (GWE) were estimated from LV pressure-strain loops using custom software. Peak LV pressure was estimated non-invasively from brachial artery cuff pressure. LV size, parameters of systolic and diastolic function and ventricular-arterial coupling were measured by echocardiography. As advanced indices of myocardial performance, global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) were obtained. On multivariable analysis, GWI was significantly correlated with GLS (standardized beta-coefficient = −0.23, P Conclusion The non-invasive MW indices show a good correlation with traditional 2DE parameters of myocardial systolic function and myocardial strain.

Objectives: To analyze left ventricular (LV) myocardial deformation and contractile reserve (CR) in asymptomatic patients with severe aortic regurgitation (AR) at rest and during exercise, and their correlation with functional capacity. Background: The natural history of chronic AR is characterized by a prolonged silent phase before onset of symptoms and overt LV dysfunction. Assessment of LV systolic function and contractile reserve has an important role in the decision-making of AR asymptomatic patients. Methods: Standard echo, lung ultrasound, and LV 2D speckle tracking strain were performed at rest and during exercise in asymptomatic patients with severe AR and in age- and sex-comparable healthy controls. Results: 115 AR patients (male sex 58.2%; 52.3±18.3years) and 55 controls were enrolled. Baseline LV ejection fraction was comparable between the groups. Resting LV global longitudinal strain (GLS) and myocardial work efficiency (MWE) were significantly reduced in AR (GLS-15.8±2.8 vs −21.4±4.4; P&nbsp

In recent years, the survival of patients with cancer has improved thanks to advances in antineoplastic therapeutic protocols. This has led to an increasing burden of cardiovascular complications related to cancer treatment. Therefore, a new branch of cardiology has been created, ``cardio-oncology,'' with the aims of preventing cardiovascular complications related to antineoplastic treatment, achieving early diagnosis and treatment of any complications, and allowing completion of the expected antineoplastic treatment. Stress echocardiography has a pivotal role in achieving a timely diagnosis of coronary artery disease and thus is the best management approach in this clinical setting. Atherosclerotic processes can be exacerbated by both chemotherapy and chest irradiation in patients with cancer, even several years after anticancer treatment completion. Moreover, stress echocardiography has many other potential applications, such as in the evaluation of subclinical left ventricular dysfunction and contractile reserve in patients treated with anticancer drugs that have the potential to induce myocardial damage, as well as evaluating valve disease. The objective of this review is to delineate the role of stress echocardiography in cardio-oncology.

BackgroundHypoxia affects myocardial oxygen supply resulting in subclinical cardiac dysfunction in obstructive sleep apnea (OSA) patients, with cardiovascular complications being associated with increased oxidative burst (OB). The aims of our study were to assess left ventricular (LV) dynamic myocardial deformation and diastolic reserve at rest and upon exercise, along with OB determination in this patients subset.MethodsConventional echocardiography, Doppler myocardial imaging and LV 2D speckle tracking echocardiography were performed in 55 OSA patients with preserved LV ejection fraction (EF) and 35 age and sex-comparable healthy controls. Peripheral OB levels were evaluated by flow cytometry.ResultsDespite comparable LVEF, LV global longitudinal strain (GLS) was significantly reduced in OSA at rest (− 13.4 ± 3.8 vs − 18.4 ± 3.3 in controls,P P P P r = − 0.50,P P = 0.001) but, unlike OSA severity, was not associated with LV diastolic dysfunction.ConclusionsEvaluation of diastolic function and myocardial deformation during exercise is feasible through stress echocardiography. OSA patients with preserved LVEF show subclinical LV systolic dysfunction, impaired LV systolic and diastolic reserve, reduced exercise tolerance, and increased peripheral levels of OB. Therapy aimed at increasing LV diastolic function reserve might improve the quality of life and exercise tolerability in OSA patients.

Heart failure (HF) is a highly prevalent clinical syndrome characterized by considerable phenotypic heterogeneity. The traditional classification based on left ventricular ejection fraction (LVEF) is widely accepted by the guidelines and represents the grounds for patient enrollment in clinical trials, even though it shows several limitations. Ejection fraction (EF) is affected by preload, afterload, and contractility, it being problematic to express LV function in several conditions, such as HF with preserved EF (HFpEF), valvular heart disease, and subclinical HF, and in athletes. Over the last two decades, developments in diagnostic techniques have provided useful tools to overcome EF limitations. Strain imaging analysis (particularly global longitudinal strain (GLS)) has emerged as a useful echocardiographic technique in patients with HF, as it is able to simultaneously supply information on both systolic and diastolic functions, depending on cardiac anatomy and physiology/pathophysiology. The use of GLS has proved helpful in terms of diagnostic performance and prognostic value in several HF studies. Universally accepted cutoff values and variability across vendors remain an area to be fully explored, hence limiting routine application of this technique in clinical practice. In the present review, the current role of GLS in the diagnosis and management of patients with HF will be discussed. We describe, by critical analysis of the pros and cons, various clinical settings in HF, and how the appropriate use and interpretation of GLS can provide important clues.

Human umbilical cord endothelial cells (HUVECs) obtained from women affected by gestational diabetes (GD-HUVECs) display durable pro-atherogenic modifications and might be considered a valid in vitro model for studying chronic hyperglycemia effects on early endothelial senescence. Here, we demonstrated that GD- compared to C-HUVECs (controls) exhibited oxidative stress, altered both mitochondrial membrane potential and antioxidant response, significant increase of senescent cells characterized by a reduced NAD-dependent deacetylase sirtuin-1 (SIRT1) activity together with an increase in cyclin-dependent kinase inhibitor-2A (P16), cyclin-dependent kinase inhibitor-1 (P21), and tumor protein p53 (P53) acetylation. This was associated with the p300 activation, and its silencing significantly reduced the GD-HUVECs increased protein levels of P300 and Ac-P53 thus indicating a persistent endothelial senescence via SIRT1/P300/P53/P21 pathway. Overall, our data suggest that GD-HUVECs can represent an "endothelial hyperglycemic memory" model to investigate in vitro the early endothelium senescence in cells chronically exposed to hyperglycemia in vivo.

International audience; Two methods are currently available for left atrial (LA) strain measurement by speckle tracking echocardiography, with two different reference timings for starting the analysis: QRS (QRS-LASr) and P wave (P-LASr). The aim of MASCOT HIT study was to define which of the two was more reproducible, more feasible, and less time consuming. In 26 expert centers, LA strain was analyzed by two different echocardiographers (young vs senior) in a blinded fashion. The study population included: healthy subjects, patients with arterial hypertension or aortic stenosis (LA pressure overload, group 2) and patients with mitral regurgitation or heart failure (LA volume–pressure overload, group 3). Difference between the inter-correlation coefficient (ICC) by the two echocardiographers using the two techniques, feasibility and analysis time of both methods were analyzed. A total of 938 subjects were included: 309 controls, 333 patients in group 2, and 296 patients in group 3. The ICC was comparable between QRS-LASr (0.93) and P-LASr (0.90). The young echocardiographers calculated QRS-LASr in 90% of cases, the expert ones in 95%. The feasibility of P-LASr was 85% by young echocardiographers and 88% by senior ones. QRS-LASr young median time was 110 s (interquartile range, IR, 78-149) vs senior 110 s (IR 78-155); for P-LASr, 120 s (IR 80-165) and 120 s (IR 90-161), respectively. LA strain was feasible in the majority of patients with similar reproducibility for both methods. QRS complex guaranteed a slightly higher feasibility and a lower time wasting compared to the use of P wave as the reference.

Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by neoplastic transformation of pluripotent cells due to a typical cytogenetic and molecular mutation known as Philadelphia (Ph) chromosome. In 2001, the introduction of the tyrosine kinasis inhibitor (TKI) imatinib as a therapeutic strategy for CML with PH chromosome mutation represented an important step towards treatment of these patients, and nowadays, this drug represents the gold therapeutic standard in this clinical setting. A second generation of TKIs (dasatinib, nilotinib, and bosutinib) showed an effective action in all patients with mutations resistant to imatinib. Ponatinib is a third-generation TKI and is the only inhibitor with activity against T3151 mutation. The impact of ponatinib on cardiovascular events was first evaluated in the PACE trial. We therefore report and discuss most relevant evidence currently available on cardiovascular events associated with the use of ponatinib. Though many exams can be used for diagnosis and follow-up of this kind of cardiotoxicity, echocardiography seems to have a pivotal role thanks to its feasibility, availability, and low cost.

Aims To obtain the normal range for 2D echocardiographic (2DE) measurements of left ventricular (LV) layer-specific strain from a large group of healthy volunteers of both genders over a wide range of ages. Methods and results A total of 287 (109 men, mean age: 46 ± 14 years) healthy subjects were enrolled at 22 collaborating institutions of the EACVI Normal Reference Ranges for Echocardiography (NORRE) study. Layer-specific strain was analysed from the apical two-, three-, and four-chamber views using 2DE software. The lowest values of layer-specific strain calculated as ±1.96 standard deviations from the mean were −15.0% in men and −15.6% in women for epicardial strain, −16.8% and −17.7% for mid-myocardial strain, and −18.7% and −19.9% for endocardial strain, respectively. Basal-epicardial and mid-myocardial strain decreased with age in women (epicardial; P = 0.008, mid-myocardial; P = 0.003) and correlated with age (epicardial; r = −0.20, P = 0.007, mid-myocardial; r = −0.21, P = 0.006, endocardial; r = −0.23, P = 0.002), whereas apical-epicardial, mid-myocardial strain increased with the age in women (epicardial; P = 0.006, mid-myocardial; P = 0.03) and correlated with age (epicardial; r = 0.16, P = 0.04). End/Epi ratio at the apex was higher than at the middle and basal levels of LV in men (apex; 1.6 ± 0.2, middle; 1.2 ± 0.1, base 1.1 ± 0.1) and women (apex; 1.6 ± 0.1, middle; 1.1 ± 0.1, base 1.2 ± 0.1). Conclusion The NORRE study provides useful 2DE reference ranges for novel indices of layer-specific strain.

Background: Primary prevention has the potential to modify the course of depression, but the consistency and magnitude of this effect are currently undetermined. Methods: PRISMA and RIGHT compliant (PROSPERO:CRD42020179659) systematic meta-review, PubMed/Web of Science, up to June 2020. Meta-analyses of controlled interventions for the primary prevention of depressive symptoms [effect measures: standardized mean difference (SMD)] or depressive disorders [effect measure: relative risk (RR)] were carried out. Results were stratified by: (i) age range; (ii) target population (general and/or at-risk); (iii) intervention type. Quality (assessed with AMSTAR/AMSTAR-PLUS content) and credibility (graded as high/moderate/low) were assessed. USPSTF grading system was used for recommendations. Results: Forty-six meta-analyses (k=928 individual studies, n=286,429 individuals, mean age=22.4 years, 81.1% female) were included. Effect sizes were: SMD=0.08-0.53; for depressive symptoms; RR=0.90-0.28 for depressive disorders. Sensitivity analyses including only RCTs did not impact the findings. AMSTAR median=9 (IQR=8-9); AMSTAR-PLUS content median=4.25 (IQR=4-5). Credibility of the evidence was insufficient/low in 43 (93.5%) meta-analyses, moderate in two (4.3%), and high in one (2.2%): reduction of depressive symptoms using psychosocial interventions for young adults only, and a combination of psychological and educational interventions in primary care had moderate credibility; preventive administration of selective serotonin reuptake inhibitors (SSRIs) for depressive disorders in individuals with a stroke had high credibility. Limitations: Intervention heterogeneity and lack of long-term efficacy evaluation. Conclusions: Primary preventive interventions for depression might be effective. Among them, clinicians may offer SSRIs post-stroke to prevent depressive disorders, and psychosocial interventions for children/adolescents/young adults with risk factors or during the prenatal/perinatal period.

Dilated cardiomyopathy (DCM) is defined by the presence of left ventricular or biventricular dilatation and systolic dysfunction in the absence of abnormal loading conditions or coronary artery disease sufficient to explain these changes. This is a heterogeneous disease frequently having a genetic background. Imaging is important for the diagnosis, the prognostic assessment and for guiding therapy. A multimodality imaging approach provides a comprehensive evaluation of all the issues related to this disease. The present document aims to provide recommendations for the use of multimodality imaging according to the clinical question. Selection of one or another imaging technique should be based on the clinical condition and context. Techniques are presented with the aim to underscore what is 'clinically relevant' and what are the tools that 'can be used'. There remain some gaps in evidence on the impact of multimodality imaging on the management and the treatment of DCM patients where ongoing research is important. ispartof: EUROPEAN HEART JOURNAL-CARDIOVASCULAR IMAGING vol:20 issue:10 pages:1075-1093 ispartof: location:England status: published

Aims This study assessed the impact of the strain-guided therapeutic approach on cancer therapy-related cardiac dysfunction (CTRCD) and rate of cancer therapy (CT) interruption in breast cancer. Methods and results We enrolled 116 consecutive female patients with HER2-positive breast cancer undergoing a standard protocol by EC (epirubicine + cyclophosphamide) followed by paclitaxel + trastuzumab (TRZ). Coronary artery, valvular and congenital heart disease, heart failure, primary cardiomyopathies, permanent or persistent atrial fibrillation, and inadequate echo-imaging were exclusion criteria. Patients underwent an echo-Doppler exam with determination of ejection fraction (EF) and global longitudinal strain (GLS) at baseline and every 3 months during CT. All patients developing subclinical (GLS drop >15%) or overt CTRCD (EF reduction Conclusion These findings highlight the usefulness of ‘strain oriented’ approach in reducing the rate of overt CTRCD and CT interruption by a timely cardioprotective treatment initiation.

In the last few years, multiple echocardiographic nomograms have been published. However, normal values calculated in the general population are not applicable to athletes, whose hearts may be enlarged and hypercontractile. Accordingly, athletes require specific nomograms. Our aim is to provide a critical review of echocardiographic nomograms on two-dimensional (2D) measures for athletes. We performed a systematic search in the National Library of Medicine for Medical Subject Headings and free text terms including echocardiography, athletes, normal values and nomograms. The search was refined by adding the keywords heart, sport, elite, master, children and young. Twenty-eight studies were selected for the final analysis. Our research revealed that currently available ranges of normality for athletes reported by different authors are quite consistent, with limited exceptions (e.g. atria, aorta). Numerical and methodological limitations, however, emerged. Numerical limitations included a limited sample size (e.g.

Background: Speckle tracking advancements make now available the analysis of layer-specific myocardial deformation. This study investigated multilayer longitudinal strain in Anderson-Fabry disease (AFD) patients at diagnosis. Methods: In a case-control study, 33 newly diagnosed, untreated AFD patients and 33 healthy age- and sex-matched healthy controls underwent a complete echocardiogram, including assessment of left ventricular (LV) transmural global longitudinal strain (GLS), subendocardial longitudinal strain (LSsubendo), subepicardial longitudinal strain (LSsubepi), and strain gradient (LSsubendo-LSsubpepi). Results: Anderson-Fabry disease patients had similar blood pressure, heart rate, and ejection fraction but higher body mass index in comparison with controls. LV mass index, maximal, and relative wall thickness were significantly greater in AFD patients. LSsubendo was significantly higher than LSsubepi in both groups, but GLS (P

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the presence of antiphospholipid antibodies, vascular thrombosis (venous, arterial, or small vessels), and/or pregnancy morbidity. Diagnosis of APS is based on the presence of at least one clinical criterion (thrombotic events or pregnancy morbidity) and at least one of the laboratory criteria (persistently medium/high titer immunoglobulin G [IgG]/immunoglobulin M [IgM] anticardiolipin antibodies, and/or medium/high titer IgG/IgM anti-β2-glycoprotein I antibodies, and/or a positive lupus anticoagulant test), confirmed after repetition at least 12 weeks apart. The clinical spectrum of APS encompasses additional (extracriteria) clinical manifestations, including cardiac diseases. Heart involvement may become evident as a consequence of direct (autoimmune-mediated) or indirect (thrombosis) mechanisms, and include valve heart disease (vegetations and/or thickening associated with functional abnormalities) and intracardiac thrombosis, coronary, and vascular accelerated atherosclerosis, along with ischemic heart disease. APS can also cause pulmonary arterial hypertension, left ventricular dysfunction, and heart failure. This review describes the major cardiac manifestations of APS and illustrates the role of cardiac imaging for diagnosing subclinical and overt heart involvement and addressing management of these patients. The possible role of therapeutic strategies in cardiac manifestations of APS is also discussed.

Background: Transcatheter aortic valve replacement (TAVR) is an alternative treatment in surgically intermediate- or high-risk patients with classical low-flow, low-gradient (LFLG) aortic stenosis (AS). The objective of this study was to investigate whether two-dimensional (2D) speckle-tracking echocardiography (STE) can predict left ventricular (LV) flow reserve during dobutamine stress echocardiography (DSE) and remodeling after TAVR in patients with LFLG AS.Methods: Seventy-five symptomatic patients with severe LFLG AS were recruited (mean age, 77.6 +/- 8.4 years). Patients underwent a complete clinical evaluation, standard echocardiography, 2D STE, and DSE. Echocardiographic analysis was performed before and 6 months after TAVR using global longitudinal strain (GLS) measured on 2D STE.Results: All patients received self-expanding transcatheter prosthetic valves. Six months after TAVR, LV GLS (12.8 +/- 3.2% vs 16.3 +/- 4.2%, P < .0001) significantly increased. In a multivariate analysis, LV GLS before TAVR (P < .0001) was an independent predictor of LV flow reserve during DSE. By receiver operating characteristic curve analysis, a cutoff value for LV GLS of

Objective: In the present study we aim to evaluate whether some of the proteins previously identified in the secretome of senescent bone marrow (BM)- and adipose (A)-mesenchymal stromal cells (MSCs) could be involved in regulation of senescence phenomena. Materials and Methods: Among the identified proteins, we selected Filamin B (FLNB) and Aminopeptidase N (CD13) that were exclusively found in the secretome of senescent cells. We silenced their mRNA expression in BM-MSCs by means of RNA interference technology and induced acute senescence by hydrogen peroxide treatment. Our goal was to evaluate if FLNB or CD13 silencing may affect onset of senescence. Results: Our preliminary data showed that CD13 protein could be a key factor involved in the regulation and determination of both primary and paracrine induced senescence in human BM-MSCs. On the other hand, Filamin B seems not to be involved in the determination of primary senescence whereas its presence could be part of the mechanism that regulates the senescence induction in human BM-MSCs by paracrine signaling. Conclusion: Our study provides a useful base for identifying the complex extracellular protein networks involved in the regulation of MSC cellular senescence.

Our aim was to identify subclinical right ventricular (RV) alterations in systemic lupus erythematosus (SLE) by combining standard and three-dimensional echocardiography (3DE). Fifty SLE patients without concomitant cardiac disease and 50 healthy controls, matched for age and gender, were enrolled. Disease damage was evaluated by inflammatory markers and SLE damage index. All patients underwent an echo-Doppler examination with 3DE assessment of RV function, RV septal and lateral longitudinal strain. The two groups had comparable body mass index and blood pressure. RV transversal middle diameter and pulmonary arterial pressure were significantly higher in SLE compared to controls. By 3DE, RV end-systolic volume ( p = 0.037) was greater, whereas stroke volume ( p = 0.023), ejection fraction ( p

BACKGROUND: No established treatment algorithm exists for patients with schizophrenia. Whether switching antipsychotics or early use of clozapine improves outcome in (first-episode) schizophrenia is unknown.METHODS: This three-phase study was done in 27 centres, consisting of general hospitals and psychiatric specialty clinics, in 14 European countries and Israel. Patients aged 18-40 years who met criteria of the DSM-IV for schizophrenia, schizophreniform disorder, or schizoaffective disorder were treated for 4 weeks with up to 800 mg/day amisulpride orally in an open-label design (phase 1). Patients who did not meet symptomatic remission criteria at 4 weeks were randomly assigned to continue amisulpride or switch to olanzapine (≤20 mg/day) during a 6-week double-blind phase, with patients and staff masked to treatment allocation (phase 2). Randomisation was done online by a randomisation website; the application implemented stratification by site and sex, and applied the minimisation method for randomisation. Patients who were not in remission at 10 weeks were given clozapine (≤900 mg/day) for an additional 12 weeks in an open-label design (phase 3). The primary outcome was the number of patients who achieved symptomatic remission at the final visits of phases 1, 2, and 3, measured by intention-to-treat analysis. Data were analysed with a generalised linear mixed model, with a logistic link and binomial error distribution. This trial is registered with ClinicalTrials.gov, number NCT01248195, and closed to accrual.FINDINGS: Between May 26, 2011, and May 15, 2016, we recruited 481 participants who signed informed consent. Of the 446 patients in the intention-to-treat sample, 371 (83%) completed open-label amisulpride treatment, and 250 (56%) achieved remission after phase 1. 93 patients who were not in remission continued to the 6-week double-blind switching trial, with 72 (77%) patients completing the trial (39 on olanzapine and 33 on amisulpride); 15 (45%) patients on amisulpride versus 17 (44%) on olanzapine achieved remission (p=0·87). Of the 40 patients who were not in remission after 10 weeks of treatment, 28 (70%) started on clozapine; 18 (64%) patients completed the 12-week treatment, and five (28%) achieved remission. The number of serious adverse events did not differ between the treatment arms in phase 2: one patient on olanzapine was admitted to hospital because of an epileptic seizure, and one patient on amisulpride was admitted to hospital twice because of exacerbations of psychotic symptoms. Over the course of the trial, two serious suicide attempts were reported.INTERPRETATION: For most patients in the early stages of schizophrenia, symptomatic remission can be achieved using a simple treatment algorithm comprising the sequential administration of amisulpride and clozapine. Since switching to olanzapine did not improve outcome, clozapine should be used after patients fail a single antipsychotic trial-not until two antipsychotics have been tried, as is the current recommendation.FUNDING: European Commission Seventh Framework Program.

Cardiovascular (CV) imaging is an important tool in baseline risk assessment and detection of CV disease in oncology patients receiving cardiotoxic cancer therapies. This position statement examines the role of echocardiography, cardiac magnetic resonance, nuclear cardiac imaging and computed tomography in the management of cancer patients. The Imaging and Cardio-Oncology Study Groups of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) in collaboration with the European Association of Cardiovascular Imaging (EACVI) and the Cardio-Oncology Council of the ESC have evaluated the current evidence for the value of modern CV imaging in the cardio-oncology field. The most relevant echocardiographic parameters, including global longitudinal strain and three-dimensional ejection fraction, are proposed. The protocol for baseline pre-treatment evaluation and specific surveillance algorithms or pathways for anthracycline chemotherapy, HER2-targeted therapies such as trastuzumab, vascular endothelial growth factor tyrosine kinase inhibitors, BCr-Abl tyrosine kinase inhibitors, proteasome inhibitors and immune checkpoint inhibitors are presented. The indications for CV imaging after completion of oncology treatment are considered. The typical consequences of radiation therapy and the possibility of their identification in the long term are also summarized. Special populations are discussed including female survivors planning pregnancy, patients with carcinoid disease, patients with cardiac tumours and patients with right heart failure. Future directions and ongoing CV imaging research in cardio-oncology are discussed.

OBJECTIVE The risk genotype for the common variant rs7903146 of the transcription factor 7-like-2 (TCF7L2) gene has been found to affect the incretin response in healthy and obese adults; however, whether a similar functional defect is also present in obese adolescents remains unexplored. Herein, we examined the functional effect of the rs7903146 variant in the TCF7L2 gene on the incretin effect and determined its translational metabolic manifestation by performing deep phenotyping of the incretin system, β-cell function relative to insulin sensitivity, the gastrointestinal-induced glucose disposal (GIGD) in obese youth with normal and impaired glucose tolerance. RESEARCH DESIGN AND METHODS Thirty-nine obese adolescents without diabetes (median age 15 [25th, 75th percentile 14, 18] years; BMI 37 [33, 43] kg/m2) were genotyped for the rs7903146 variant of TCF7L2 and underwent a 3-h oral glucose tolerance test (OGTT) followed by an isoglycemic intravenous glucose infusion (iso-intravenous glucose tolerance test [IVGTT]) to match the plasma glucose concentrations during the OGTT and a hyperglycemic clamp with arginine stimulation. The incretin effect was measured as 100 * (AUC-SROGTT − AUC-SRiso-IVGTT) / AUC-SROGTT, where AUC-SR = area under the curve of C-peptide secretion rate. Participants were grouped into tertiles according to the percentage incretin effect (high, moderate, and low) to describe their metabolic phenotype. RESULTS The presence of T risk allele for TCF7L2 was associated with a markedly reduced incretin effect compared with the wild-type genotype (0.3% [−7.2, 14] vs. 37.8% [12.5, 52.4], P < 0.002). When the cohort was stratified by incretin effect, the high, moderate, and low incretin effect groups did not differ with respect to anthropometric features, while the low incretin effect group exhibited higher 1-h glucose (P = 0.015) and a reduced disposition index, insulin sensitivity, and insulin clearance compared with the high incretin effect group. GIGD was reduced in the low incretin effect group (P = 0.001). The three groups did not differ with respect to intravenous glucose-induced insulin secretion and arginine response during the hyperglycemic clamp. CONCLUSIONS A reduced incretin effect and its association with the TCF7L2 variant rs7903146 identify an early metabolic phenotype in obese youth without diabetes, featuring a higher plasma glucose peak at 1 h; lower insulin secretion, sensitivity, and clearance; and GIGD.

The annual meeting of the European Association of Cardiovascular Imaging, EuroEcho 2019, was held in Vienna, Austria, in December 2019. In this article, we present a summary of the ‘Highlights’ session.

Background: The objective of this study was to assess the safety and performance of the Omnipod® personalized model predictive control (MPC) algorithm in adults, adolescents, and children aged ≥6 years with type 1 diabetes (T1D) under free-living conditions using an investigational device. Materials and Methods: A 96-h hybrid closed-loop (HCL) study was conducted in a supervised hotel/rental home setting following a 7-day outpatient standard therapy (ST) phase. Eligible participants were aged 6–65 years with A1C

The bioactive form of vitamin D, 1,25-dihydroxyvitamin D (1,25D3), exerts immunomodulatory actions resulting in neuroprotective effects potentially useful against neurodegenerative and autoimmune diseases. In fact, vitamin D deficiency status has been correlated with painful manifestations associated with different pathological conditions. In this study, we have investigated the effects of vitamin D deficiency on microglia cells, as they represent the main immune cells responsible for early defense at central nervous system (CNS), including chronic pain states. For this purpose, we have employed a model of low vitamin D intake during gestation to evaluate possible changes in primary microglia cells obtained from postnatal day(P)2-3 pups. Afterwards, pain measurement and microglia morphological analysis in the spinal cord level and in brain regions involved in the integration of pain perception were performed in the parents subjected to vitamin D restriction. In cultured microglia, we detected a reactive—activated and proliferative—phenotype associated with intracellular reactive oxygen species (ROS) generation. Oxidative stress was closely correlated with the extent of DNA damage and increased β-galactosidase (B-gal) activity. Interestingly, the incubation with 25D3 or 1,25D3 or palmitoylethanolamide, an endogenous ligand of peroxisome proliferator-activated-receptor-alpha (PPAR-α), reduced most of these effects. Morphological analysis of ex-vivo microglia obtained from vitamin-D-deficient adult mice revealed an increased number of activated microglia in the spinal cord, while in the brain microglia appeared in a dystrophic phenotype. Remarkably, activated (spinal) or dystrophic (brain) microglia were detected in a prominent manner in females. Our data indicate that vitamin D deficiency produces profound modifications in microglia, suggesting a possible role of these cells in the sensorial dysfunctions associated with hypovitaminosis D.

Background During the last decades, a renewed interest for negative symptoms (NS) was brought about by the increased awareness that they interfere severely with real-life functioning, particularly when they are primary and persistent. Methods In this guidance paper, we provide a systematic review of the evidence and elaborate several recommendations for the conceptualization and assessment of NS in clinical trials and practice. Results Expert consensus and systematic reviews have provided guidance for the optimal assessment of primary and persistent negative symptoms; second-generation rating scales, which provide a better assessment of the experiential domains, are available; however, NS are still poorly assessed both in research and clinical settings. This European Psychiatric Association (EPA) guidance recommends the use of persistent negative symptoms (PNS) construct in the context of clinical trials and highlights the need for further efforts to make the definition of PNS consistent across studies in order to exclude as much as possible secondary negative symptoms. We also encourage clinicians to use second-generation scales, at least to complement first-generation ones. The EPA guidance further recommends the evidence-based exclusion of several items included in first-generation scales from any NS summary or factor score to improve NS measurement in research and clinical settings. Self-rated instruments are suggested to further complement observer-rated scales in NS assessment. Several recommendations are provided for the identification of secondary negative symptoms in clinical settings. Conclusions The dissemination of this guidance paper may promote the development of national guidelines on negative symptom assessment and ultimately improve the care of people with schizophrenia.

Background Mental disorders in comorbidity with chronic skin diseases may worsen disease outcome and patients’ quality of life. We hypothesized the comorbidity of depression, anxiety syndromes, or symptoms as attributable to biological mechanisms that the combined diseases share. Methods We conducted a systematic review based on the Preferred Reporting Items for Systematic Review and Meta-Analysis statement searching into PubMed, PsycInfo, and Scopus databases. We examined the literature regarding the comorbidity of psoriasis (Ps), atopic dermatitis (AD), or hidradenitis suppurativa with depression and/or anxiety in adults ≥18 years and the hypothetical shared underlying biological mechanisms. Results Sixteen studies were analyzed, mostly regarding Ps and AD. Brain-derived neurotrophic factor/tropomyosin receptor kinase B signaling and nuclear factor kappa-light-chain-enhancer of activated B cells/p38 mitogen-activated protein kinase pathways arose as shared mechanisms in Ps animal models with depression- and/or anxiety-like behaviors. Activated microglia and neuroinflammatory responses emerged in AD depressive models. As to genetic studies, atopic-dermatitis patients with comorbid anxiety traits carried the short variant of serotonin transporter and a polymorphism of the human translocator protein gene. A GA genotype of catechol-O-methyltransferase gene was instead associated with Ps. Reduced natural killer cell activity, IL-4, serotonin serum levels, and increased plasma cortisol and IgE levels were hypothesized in comorbid depressive AD patients. In Ps patients with comorbid depression, high serum concentrations of IL-6 and IL-18, as well as IL-17A, were presumed to act as shared inflammatory mechanisms. Conclusions Further studies should investigate mental disorders and chronic skin diseases concurrently across patients’ life course and identify their temporal relation and biological correlates. Future research should also identify biological characteristics of individuals at high risk of the comorbid disorders and associated complications.

Aims Pre-participation evaluation (PPE) is recommended to prevent sudden cardiac death in athletes. Although imaging is not advocated as a first-line screening tool, there is a growing interest in the use of echocardiography in PPE of athletes. This survey aimed to map the use of imaging in the setting of PPE and explore physician beliefs and potential barriers that may influence individual practices. Methods An international survey of healthcare professionals was performed across ESC Member Countries. Percentages were reported based on the number of respondents per question. Results In total, 603 individuals from 97 countries participated in the survey. Two-thirds (65%) of respondents use echocardiography always or often as part of PPE of competitive athletes and this practice is not influenced by the professional or amateur status of the athlete. The majority (81%) of respondents who use echocardiography as a first-line screening tool perform the first echocardiogram during adolescence or at the first clinical evaluation, and 72% repeat it at least once in the athletes’ career, at 1–5 yearly intervals. In contrast, cardiac magnetic resonance is reserved as a second-line investigation of symptomatic athletes. The majority of the respondents did not report any barriers to echocardiography, while several barriers were identified for cardiac magnetic resonance. Conclusions Echocardiography is frequently used as a first-line screening tool of athletes. In the absence of scientific evidence, before such practice is recommended, large studies using echocardiography in the PPE setting are necessary.

Background Patients with schizophrenia spectrum disorders (SSD) have worse physical health and reduced life expectancy compared to the general population. In 2009, the European Psychiatric Association, the European Society of Cardiology and the European Association for the Study of Diabetes published a position paper aimed to improve cardiovascular and diabetes care in patients with severe mental illnesses. However, the initiative did not produce the expected results. Experts in SSD or in cardiovascular and metabolic diseases convened to identify main issues relevant to management of cardiometabolic risk factors in schizophrenia patients and to seek consensus through the Delphi method. Methods The steering committee identified four topics: 1) cardiometabolic risk factors in schizophrenia patients; 2) cardiometabolic risk factors related to antipsychotic treatment; 3) differences in antipsychotic cardiometabolic profiles; 4) management of cardiometabolic risk. Twelve key statements were included in a Delphi questionnaire delivered to a panel of expert European psychiatrists. Results Consensus was reached for all statements with positive agreement higher than 85% in the first round. European psychiatrists agreed on: 1) high cardiometabolic risk in patients with SSD, 2) importance of correct risk management of cardiometabolic diseases, from lifestyle modification to treatment of risk factors, including the choice of antipsychotic drugs with a favourable cardiometabolic profile. The expert panel identified the psychiatrist as the central coordinating figure of management, possibly assisted by other specialists and general practitioners. Conclusions This study demonstrates high level of agreement among European psychiatrists regarding the importance of cardiovascular risk assessment and management in subjects with SSD.

First generation antipsychotics (FGAs) are more likely to induce extrapyramidal side-effects (EPS) than second generation antipsychotics (SGAs), and EPS have been shown associated to cognitive deficits in schizophrenia. So far, no study has explored the relationships between EPS and social cognition (SC) in people with schizophrenia. Therefore, we assessed the prevalence of EPS in a large sample of drug-treated community-dwelling persons with schizophrenia and explored their relationships with patients' neurocognitive and SC abilities. 875 patients underwent EPS, psychopathological, neurocognitive and SC assessments by means of standardized measures. Relationships between EPS, psychopathology and neurocognitive and SC measures were investigated by correlation tests. Moreover, a partial correlation network was computed by means of a network analysis. 256 patients were treated with FGAs alone or in combination with SGA and 619 with SGAs. EPS were significantly more frequent in FGA-treated group than in the SGA-treated one. Patients with EPS disclosed a more severe psychopathology and were more impaired in neurocognitive and SC measures compared to those without EPS. Disorganization, expressive deficit, and duration of illness were significantly associated to both neurocognitive and SC measures while EPS were associated to neurocognitive measures only. The network analysis showed that parkinsonism was the sole EPS directly connected to both psychopathological and neurocognitive indices whereas no direct connection emerged between EPS and SC measures. Present findings confirm that EPS are still present in the era of SGAs and contribute, together with other clinical variables, to the neurocognitive but not to the SC impairment of patients with schizophrenia.

Negative symptoms of schizophrenia remain a major therapeutic challenge. The progress in the conceptualization and assessment is not yet fully reflected by treatment research. Nevertheless, there is a growing evidence base regarding the effects of biological and psychosocial interventions on negative symptoms. The importance of the distinction between primary and secondary negative symptoms for treatment selection might seem evident, but the currently available evidence remains limited. Good clinical practice is recommended for the treatment of secondary negative symptoms. Antipsychotic treatment should be optimized to avoid secondary negative symptoms due to side effects and due to positive symptoms. For most available interventions, further evidence is needed to formulate sound recommendations for primary, persistent, or predominant negative symptoms. However, based on currently available evidence recommendations for the treatment of undifferentiated negative symptoms (including both primary and secondary negative symptoms) are provided. Although it has proven difficult to formulate an evidence-based recommendation for the choice of an antipsychotic, a switch to a second-generation antipsychotic should be considered for patients who are treated with a first-generation antipsychotic. Antidepressant add-on to antipsychotic treatment is an option. Social skills training is recommended as well as cognitive remediation for patients who also show cognitive impairment. Exercise interventions also have shown promise. Finally, access to treatment and to psychosocial rehabilitation should be ensured for patients with negative symptoms. Overall, there is definitive progress in the field, but further research is clearly needed to develop specific treatments for negative symptoms.

Given their beneficial potential on human health, plant food bioactive molecules are important components influencing nutrition. Polyphenols have been widely acknowledged for their potentially protective role against several complex diseases. In particular, the polyphenols of olive oil (OOPs) emerge as the key components of many healthy diets and have been widely studied for their beneficial properties. The qualitative and quantitative profile defining the composition of olive oil phenolic molecules as well as their absorbance and metabolism once ingested are key aspects that need to be considered to fully understand the health potential of these molecules. In this review, we provide an overview of the key aspects influencing these variations by focusing on the factors influencing the biosynthesis of OOPs and the findings about their absorption and metabolism. Despite the encouraging evidence, the health potential of OOPs is still debated due to limitations in current studies. Clinical trials are necessary to fully understand and validate the beneficial effects of olive oil and OOPs on human health. We provide an update of the clinical trials based on olive oil and/or OOPs that aim to understand their beneficial effects. Tailored studies are needed to standardize the polyphenolic distribution and understand the variables associated with phenol-enriched OO. An in-depth knowledge of the steps that occur following polyphenol ingestion may reveal useful insights to be used in clinical settings for the prevention and treatment of many diseases.