Rationale and design of the CV-PREVITAL study: an Italian multiple cohort randomised controlled trial investigating innovative digital strategies in primary cardiovascular prevention.

INTRODUCTION: Prevention of cardiovascular disease (CVD) is of key importance in reducing morbidity, disability and mortality worldwide. Observational studies suggest that digital health interventions can be an effective strategy to reduce cardiovascular (CV) risk. However, evidence from large randomised clinical trials is lacking. METHODS AND ANALYSIS: The CV-PREVITAL study is a multicentre, prospective, randomised, controlled, open-label interventional trial designed to compare the effectiveness of an educational and motivational mobile health (mHealth) intervention versus usual care in reducing CV risk. The intervention aims at improving diet, physical activity, sleep quality, psycho-behavioural aspects, as well as promoting smoking cessation and adherence to pharmacological treatment for CV risk factors. The trial aims to enrol approximately 80 000 subjects without overt CVDs referring to general practitioners' offices, community pharmacies or clinics of Scientific Institute for Research, Hospitalization and Health Care (Italian acronym IRCCS) affiliated with the Italian Cardiology Network. All participants are evaluated at baseline and after 12 months to assess the effectiveness of the intervention on short-term endpoints, namely improvement in CV risk score and reduction of major CV risk factors. Beyond the funded life of the study, a long-term (7 years) follow-up is also planned to assess the effectiveness of the intervention on the incidence of major adverse CV events. A series of ancillary studies designed to evaluate the effect of the mHealth intervention on additional risk biomarkers are also performed. ETHICS AND DISSEMINATION: This study received ethics approval from the ethics committee of the coordinating centre (Monzino Cardiology Center; R1256/20-CCM 1319) and from all other relevant IRBs and ethics committees. Findings are disseminated through scientific meetings and peer-reviewed journals and via social media. Partners are informed about the study's course and findings through regular meetings. TRIAL REGISTRATION NUMBER: NCT05339841.

Heart Rate Fractality Disruption as a Footprint of Subthreshold Depressive Symptoms in a Healthy Population.

Objective: Psychopathology (and depression in particular) is a cardiovascular risk factor independent from any co-occurring pathology. This link is traced back to the mind-heart-body connection, whose underlying mechanisms are still not completely known. To study psychopathology in relation to the heart, it is necessary to observe the autonomic nervous system, which mediates among the parts of that connection. Its gold standard of evaluation is the study of heart rate variability (HRV). To investigate whether any association exists between the HRV parameters and sub-threshold depressive symptoms in a sample of healthy subjects. Method: In this cross-sectional study, two short-term HRV recordings (5 min - supine and sitting) have been analyzed in 77 healthy subjects. Here we adopted a three-fold approach to evaluate HRV: a set of scores belonging to the time domain; to the frequency domain (high, low, and very low frequencies) and a set of 'nonlinear' parameters. The PHQ-9 (Patient Health Questionnaire-9) scale was used to detect depressive symptoms. Results: Depressive symptoms were associated only with a parameter from the non-linear approach and specifically the long-term fluctuations of fractal dimensions (DFA-α2). This association remained significant even after controlling for age, gender, BMI (Body-Mass-Index), arterial hypertension, anti-hypertensive drugs, dyslipidemia, and smoking habits. Moreover, the DFA-α2 was not affected by the baroreflex (postural change), unlike other autonomic markers. Conclusions: Fractal analysis of HRV (DFA-α2) allows then to predict depressive symptoms below the diagnostic threshold in healthy subjects regardless of their health status. DFA-α2 may be considered as an imprint of subclinical depression on the heart rhythm.

Intravenous iron therapy improves the hypercapnic ventilatory response and sleep disordered breathing in chronic heart failure.

AIMS: Intravenous iron therapy can improve symptoms in patients with heart failure, anaemia and iron deficiency. The mechanisms underlying such an improvement might involve chemoreflex sensing and nocturnal breathing patterns. METHODS AND RESULTS: Patients with heart failure, reduced left ventricular ejection fraction, anaemia (haemoglobin <13 g/dl in men; <12 g/dl in women) and iron deficiency (ferritin <100 or 100-299 µg/L with transferrin saturation <20%) were 2:1 randomized to patient-tailored intravenous ferric carboxymaltose dose or placebo. Chemoreflex sensitivity cardiorespiratory sleep study, symptom assessment and cardiopulmonary exercise test were performed before and 2 weeks after the last treatment dose. Fifty-eight patients (38 active arm/20 placebo arm) completed the study. Intravenous iron was associated with less severe symptoms, higher haemoglobin (12.5 ± 1.4 vs. 11.7 ± 1.0 mg/dl, p < 0.05) and improved haematinic parameters. Ferric carboxymaltose improved the central hypercapnic ventilatory response (-25.8%, p < 0.05 vs. placebo), without changes in peripheral chemosensitivity. In particular, the central hypercapnic ventilatory responses passed from 4.6 ± 6.5 to 2.9 ± 2.9 L/min/mmHg after ferric carboxymaltose and from 4.4 ± 4.6 to 4.6 ± 3.9 L/min/mmHg after placebo (ptreatment*condition  = 0.046). In patients presenting with sleep-related breathing disorder, apnoea-hypopnoea index was reduced with active treatment as compared to placebo (12 ± 11 vs. 19 ± 13 events/h, p < 0.05). After ferric carboxymaltose, but not after placebo, both peak oxygen uptake (VO2 ) increased (Δ1.1 ± 2.0 ml/kg/min, p < 0.05) and VO2 /workload slope was steeper (Δ0.67 ± 1.7 L/min/W, p < 0.01). CONCLUSIONS: Intravenous ferric carboxymaltose improves the hypercapnic ventilatory response and sleep-related breathing disorders in patients with heart failure, anaemia and iron deficiency. These newly described findings, along with improved oxygen delivery to exercising muscles, likely contribute to the favourable effects of ferric carboxymaltose in anaemic patients with heart failure.

Reduction of 24-h blood pressure variability in extreme obese patients 10 days and 6 months after bariatric surgery depending on pre-existing hypertension.

Bariatric surgery is considered as a first line treatment in extreme obese patients to achieve a reduction in health risks. However, after surgical procedure obese patients with normal blood pressure (BP) levels still present residual risk, which may be partly related to lack of correction of BP profile and variability. AIM: To evaluate short (10 days) and mid-term (6 months) changes of mean values, profile and variability of BP after bariatric surgery in extremely obese patients with and without hypertension. MATERIALS & METHODS: A follow-up of cross-sectional study was conducted in 90 obese patients (aged 41.7 ±â€¯11.3, BMI = 46.7 ±â€¯5.7 kg/m2), who met the eligibility criteria and underwent bariatric surgery. Each patient underwent 24-h ambulatory BP monitoring with profile and variability estimation before, 10 days and 6 months after the intervention. RESULTS: Sixty-seven (74.4%) patients had hypertension. Significant decrease from baseline in mean values of systolic and diastolic BP in 10 days (p < .005) and 6 months (p < .005) follow-up were observed only in patients with hypertension. Moreover, only hypertensive subjects revealed significant reduction (p < 0,05) from baseline in 24-h systolic and diastolic BP weighted standard deviation and average real variability after surgical procedure. No changes were found in dipping status. CONCLUSIONS: Bariatric surgery not only decreased BP levels, but also contributed to reduction in BP variability in early period after intervention mainly in patients with pre-existing hypertension.

Psychological Profile in Coronary Artery By-Pass Graft Patients vs. Valve Replacement Patients Entering Cardiac Rehabilitation after Surgery.

Anxiety and depression are thought to influence the genesis of ischemic diseases and not of valvular diseases, but little is known on the psychological profile of cardiac patients after surgery. Aim of this study was to investigate differences in disease experience and mood between patients undergoing cardiac rehabilitation after coronary artery by-pass graft (CABG) or after valve replacement (VR). We studied 1,179 CABG and 737 VR patients who completed the Illness Behaviour Questionnaire and the Hospital Anxiety and Depression Scale after surgery. We tested the independent effect of the type of surgery by multivariate analysis and between-group differences in prevalence of clinically relevant scores. Relevant scores in the psychosomatic concern scale were more frequent in CABG than in VR patients. After correction by age, sex, education and marital status, scores of disease conviction and psychosomatic concern were higher in CABG patients, scores of denial were higher in VR patients. Unexpectedly, anxiety and depression scores did not differ between groups. Results suggest providing psychological support for anxiety and depression to both VR and CABG patients during cardiac rehabilitation, and planning differentiated interventions of cardiac rehabilitation and secondary prevention tailored to the specific psychological reactions of CABG and VR patients.

Role of T1 mapping as a complementary tool to T2* for non-invasive cardiac iron overload assessment.

BACKGROUND: Iron overload-related heart failure is the principal cause of death in transfusion dependent patients, including those with Thalassemia Major. Linking cardiac siderosis measured by T2* to therapy improves outcomes. T1 mapping can also measure iron; preliminary data suggests it may have higher sensitivity for iron, particularly for early overload (the conventional cut-point for no iron by T2* is 20ms, but this is believed insensitive). We compared T1 mapping to T2* in cardiac iron overload. METHODS: In a prospectively large single centre study of 138 Thalassemia Major patients and 32 healthy controls, we compared T1 mapping to dark blood and bright blood T2* acquired at 1.5T. Linear regression analysis was used to assess the association of T2* and T1. A "moving window" approach was taken to understand the strength of the association at different levels of iron overload. RESULTS: The relationship between T2* (here dark blood) and T1 is described by a log-log linear regression, which can be split in three different slopes: 1) T2* low, <20ms, r2 = 0.92; 2) T2* = 20-30ms, r2 = 0.48; 3) T2*>30ms, weak relationship. All subjects with T2*<20ms had low T1; among those with T2*>20ms, 38% had low T1 with most of the subjects in the T2* range 20-30ms having a low T1. CONCLUSIONS: In established cardiac iron overload, T1 and T2* are concordant. However, in the 20-30ms T2* range, T1 mapping appears to detect iron. These data support previous suggestions that T1 detects missed iron in 1 out of 3 subjects with normal T2*, and that T1 mapping is complementary to T2*. The clinical significance of a low T1 with normal T2* should be further investigated.

Cardiovascular risk and hypertension control in Italy. Data from the 2015 World Hypertension Day.

BACKGROUND: Cardiovascular diseases (CVD) are the first cause of death and disability in western countries. Despite therapeutic advances, their prevalence is constantly increasing. Detailed assessment of modifiable CV risk factors could improve CVD prevention and management. METHODS: to assess CV risk and hypertension control in a sample of the Italian population, individuals participating to the 2015 "World Hypertension Day" were interviewed in 62sites all over Italy. Blood pressure was measured with a validated auscultatory or oscillometric device and information on demography and prevalence of CVD risk factors was collected by an anonymous questionnaire. An ad-hoc modified version of the Systematic COronary Risk Evaluation (SCORE) system was then applied. RESULTS: 8657 recruited individuals (43%women, aged 56.68±16years) were subdivided into 3 age groups (40-49y, 50-59y, 60-69y) for analysis. CV risk was low in 62.4%, 18.0% and 0%; moderate in 26.0%, 66.0% and 62.5%; high/very high in 11.6%, 16% and 37.4%, respectively. Smoking was mainly responsible for increased CV risk among those aged 40-49y (26%smokers), while hypertension was the main factor in the whole sample and in subjects over 50y (36% and 42% respectively). Overall, BP control was unsatisfactory in 36% of individuals (28%, 48% and 31% of those who declared to be normotensive, hypertensive on treatment or unaware of their BP condition, respectively). CONCLUSIONS: In this sample of the Italian population, CV risk was alarmingly high, irrespectively of age, mostly due to presence of modifiable risk factors, including hypertension, which should thus be better addressed, especially in the youngsters.

Arthroscopic management of articular and peri-articular fractures of the upper limb.

The management of articular fractures is always a matter of concern. Each articular fracture is different from the other, whatever the classification system used and the surgical or non-surgical indications employed by the surgeon. The main goals remain anatomical reduction, stable fixation, loose body removal and minimal invasiveness.Open procedures are a compromise. Unfortunately, it is not always possible to meet every treatment goal perfectly, since associated lesions can pass unnoticed or delay treatment, and even in a 'best-case' scenario there can be complications in the long term.In the last few decades, arthroscopic joint surgery has undergone an exponential evolution, expanding its application in the trauma field with the development of arthroscopic and arthroscopically-assisted reduction and internal fixation (ARIF) techniques. The main advantages are an accurate diagnosis of the fracture and associated soft-tissue involvement, the potential for concomitant treatments, anatomical reduction and minimal invasiveness. ARIF techniques have been applied to treat fractures affecting several joints: shoulder, elbow, wrist, hip, knee and ankle.The purpose of this paper is to provide a review of the most recent literature concerning arthroscopic and arthroscopically-assisted reduction and internal fixation for articular and peri-articular fractures of the upper limb, to analyse the results and suggest the best clinical applications.ARIF is an approach with excellent results in treating upper-limb articular and peri-articular fractures; it can be used in every joint and allows treatment of both the bony structure and soft-tissues.Post-operative outcomes are generally good or excellent. While under some circumstances ARIF is better than a conventional approach, the results are still beneficial due to the consistent range of movement recovery and shorter rehabilitation time.The main limitation of this technique is the steep learning curve, but investing in ARIF reduces intra-operative morbidity, surgical errors, operative times and costs. Cite this article: Dei Giudici L, Faini A, Garro L, Tucciarone A, Gigante A. Arthroscopic management of articular and peri-articular fractures of the upper limb. EFORT Open Rev 2016;1:325-331. DOI: 10.1302/2058-5241.1.160016.

Prednisone induces immunophenotypic modulation of CD10 and CD34 in nonapoptotic B-cell precursor acute lymphoblastic leukemia cells.

BACKGROUND: Immunophenotypic modulation is induced by steroids in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients during remission induction therapy. METHODS: We cultured BCP-ALL blasts from diagnostic bone marrow (BM) samples (n = 20) in the presence of prednisone on stroma layer obtained from BM-derived mesenchymal cells to maintain viability. Antigen expression was assessed by multiparametric flow cytometry. RESULTS: Leukemia samples that sustained the treatment in vitro with prednisone, showed significative reduction of CD10 and CD34 expression compared with control, and it was comparable with that observed in residual leukemic cells of the same patients in BM at day 15 of treatment. Modulated cells were viable as determined by Annexin V staining and preserved light scattering properties. Of note, the extent of antigen modulation in vitro correlated with response to prednisone in vivo. CONCLUSIONS: The prednisone-induced immunophenotypic modulation can be reproduced in vitro and this phenomenon may reflect sensitivity to chemotherapy.