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Cardiovascular (CV) diseases are burdened by high mortality and morbidity, being responsible for half of the deaths in Europe. Although hypertension is recognized as the most important CV risk factor, hypertension awareness, and blood pressure (BP) control are still unsatisfactory. In 2017 and 2018, respectively >10 000 and >5000 individuals took part in the May Measurement Month (MMM) campaign in Italy, of whom 30.6% and 26.3% were found to have high BP, respectively. To raise public awareness on the importance of hypertension and to collect BP data on a nation-wide scale in Italy. In the frame of the MMM campaign, an opportunistic cross-sectional survey of volunteers aged ≥18 years was carried out in May 2019. BP measurement, the definition of hypertension, and statistical analysis followed the standard MMM protocol. Screening was conducted in multiple sites by health personnel. Among the 10 182 people screened (females: 52.3%, mean age 58 ± 16years) mean BP was 127/78 mmHg, and 3171 (31.1%) participants had arterial hypertension, of whom 62.1% were aware of being hypertensive. Diabetes, body mass index >25 kg/m2 were associated with higher BP and previous myocardial infarction with lower BP. For the third consecutive year we collected a nation-wide snapshot of BP control in a large sample of individuals. The high participation, with some yearly fluctuations likely due to the limitations of the sampling technique, confirms the power of this kind of health campaign in reaching a significant number of people to raise awareness on health topics.

Background: Safety of reconstructive microsurgery in elderly patients is still a topic of debate, because no conclusive evidence exists that provides indications and risk evaluation in elderly patients. The purpose of this study, which the Italian Society for Plastic, Reconstructive, and Aesthetic Surgery (SICPRE) has promoted, is to evaluate the safety and the complication risk of elective reconstructive microsurgery in elderly patients as well as to identify patient- or procedure-related risk factors. The secondary aim is to evaluate the predictive role for complications of the Geriatric 8 score (G8). Methods: A total of 194 consecutive patients from 18 centers, aged 65 or older, who received an elective microsurgical flap between April 2018 and April 2019 were prospectively evaluated. Patient-related, treatment-related, and outcomes data were recorded and statistically analyzed through multiple-adjusted logistic regression models. Results: Our study showed an increased risk of complications and a longer hospitalization in patients aged ≥75 years with the American Society of Anesthesiologists (ASA) score ≥3 (or G8 score ≤11) as compared to patients >65 years of age and

Background The higher cardiovascular variability and the increased prevalence of arrhythmias in patients with obstructive sleep apneas may contribute to their higher rate of fatal events during sleep. In this regard, the use of beta blockers (BB) is debated because they may induce bradyarrhythmias and alter the pattern of heart rate changes induced by apneas. Thus, the aim of our study is to quantify peri‐apneic heart‐rate swings and prevalence of nocturnal bradyarrhythmias in BB‐treated and BB‐naïve patients with obstructive sleep apnea. Methods and Results Our real‐life, retrospective, cohort study analyzed data from patients with obstructive sleep apnea after a basal cardiorespiratory polysomnography. Among 228 eligible participants, we enrolled 78 BB‐treated and 88 BB‐naïve patients excluding those treated with antiarrhythmic drugs or pacemakers, or with uninterpretable ECG traces during polysomnography. In each patient, type and frequency of arrhythmias were identified and peri‐apneic changes of RR intervals were evaluated for each apnea. BB‐treated patients were older and with more comorbidities than BB‐naïve patients, but had similar obstructive sleep apnea severity, similar frequency of arrhythmic episodes, and similar prevalence of bradyarrhythmias. Apnea‐induced heart‐rate swings, unadjusted for age, showed lower RR interval changes in BB‐treated (133.5±63.8 ms) than BB‐naïve patients (171.3±87.7 ms, P =0.01), lower RR interval increases during apneas (58.5±28.5 versus 74.6±40.2 ms, P =0.01), and lower RR interval decreases after apneas (75.0±42.4 versus 96.7±55.5 ms, P Conclusions BB appear to be safe in patients with obstructive sleep apnea because they are not associated with worse episodes of nocturnal bradyarrhythmias and even seem protective in terms of apnea‐induced changes of heart rate.

Introduction: Limited information is available on blood pressure (BP) behavior in workers exposed to chronic intermittent hypoxia (CIH), and even less is known regarding effects of CIH on 24-h ambulatory BP in those affected by arterial hypertension at sea level (SL). The aims of this study were to assess clinic and 24-h ambulatory BP at SL and at high altitude (HA; 3,870 m above SL) in workers exposed to CIH, and to compare BP response to HA exposure between normotensive and hypertensive workers.Methods: Nineteen normotensive and 18 pharmacologically treated hypertensive miners acclimatized to CIH were included, whose work was organized according to a “7 days-on−7 days-off” shift pattern between SL and HA. All measurements were performed on the second and seventh day of their HA shift and after the second day of SL sojourn.Results: Compared to SL, 24-h systolic BP (SBP) and diastolic BP (DBP) increased at HA [+14.7 ± 12.6 mmHg (p < 0.001) and +8.7 ± 7.2 mmHg (p < 0.001), respectively], and SBP nocturnal fall decreased consistently (−4.1 ± 9.8%; p < 0.05) in all participants, with hypertensives showing higher nocturnal DBP than normotensives (p < 0.05) despite the current therapy. Also, heart rate (HR) nocturnal fall tended to be reduced at HA. In addition, the 24-h SBP/DBP hypertension threshold of ≥130/80 mmHg was exceeded by 39% of workers at SL and by 89% at HA. Clinic HR, SBP, and DBP were significantly higher on the second day of work at HA compared with SL, the increase being more pronounced for SBP in hypertensives (p < 0.05) and accompanied by, on average, mild altitude sickness in both groups. These symptoms and the values of all cardiovascular variables decreased on the seventh day at HA (p < 0.05) regardless of CIH exposure duration.Conclusion: Long history of work at HA according to scheduled CIH did not prevent the occurrence of acute cardiovascular changes at HA during the first days of exposure. The BP response to HA tended to be more pronounced in hypertensive than in normotensive workers despite being already treated; the BP changes were more evident for 24-h ambulatory BP. Twenty-four-hour ABP monitoring is a useful tool for an appropriate evaluation of BP in CIH workers.

OBJECTIVE: Mean arterial pressure (MAP) is usually calculated by adding one-third of pulse pressure (PP) to DBP. This formula assumes that the average value of pulse waveform is constant in all individuals and coincides with 33.3% of PP amplitude (MAP = DBP + PP × 0.333). Other formulas were lately proposed to improve the MAP estimation, adding to DBP an established percentage of PP: MAP = DBP + PP × 0.40; MAP = DBP + PP × 0.412; MAP = DBP + PP × 0.333 + 5 mmHg. METHODS: The current study evaluated the integral of brachial pulse waveform recorded by applanation tonometry in 1526 patients belonging to three distinct cohorts: normotensive or hypertensive elderly, hypertensive adults, and normotensive adults. RESULTS: The percentage of PP to be added to DBP to obtain MAP was extremely variable among individuals, ranging from 23 to 58% (mean: 42.2 ± 5.5%), higher in women (42.9 ± 5.6%) than men (41.2 ± 5.1%, P

Cardiovascular (CV) diseases are burdened by high mortality and morbidity, being responsible for half of the deaths in Europe. Although hypertension is recognized as the most important CV risk factor, hypertension awareness and blood pressure (BP) control are still unsatisfactory. In 2017, 30.6% of a >10 000 individual sample who took part in the May Measurement Month (MMM) campaign in Italy was found to have high BP. To raise awareness on the hypertension issue and to report BP data on a nation-wide scale in Italy. In the frame of the MMM campaign, an opportunistic cross-sectional survey of volunteers aged ≥18 was carried out in May 2018. Blood pressure measurement, the definition of hypertension and statistical analysis followed the standard MMM protocol. Screenings were conducted in multiple sites by health care personnel. Among the 5554 people screened (females: 48.3%, mean age 58 ± 17 years) mean BP was 127/77 mmHg, and after imputations, 1462 (26.3%) participants were found to have high BP levels. Body mass index >25 was associated with higher systolic BP and diastolic BP (DBP), while diabetes was associated with high DBP only. Our data provide a nation-wide snapshot of BP control in a sample of individuals participating in a national health care campaign, and confirm the power of this kind of healthcare-related activities in reaching a significant number of people to raise awareness on health topics. The apparent positive trend in BP control compared to available data from other similar campaigns carried out during the past years needs to be confirmed with more methodologically robust studies.

Background Prevalence of HIV infection among people who inject drugs (PWID) has been reported to be higher than that of the general population. The present study aimed to estimate the prevalence of HIV infection and associated risk factors among PWID in Dar es Salaam, Tanzania, following the introduction of a comprehensive HIV intervention package (CHIP) for PWID in the country in 2014. Methods We conducted an integrated bio-behavioral survey (IBBS) among PWID using respondent-driven sampling (RDS) in Dar es Salaam, Tanzania, between October and December 2017. Data on socio-demographic characteristics and risky behaviors were collected through face-to-face interviews. Blood samples were collected and tested for HIV infection. We accounted for weighting in the analyses, and logistic regression was performed to assess risk factors for HIV infection. Results A total of 611 PWID (94.4% males and 5.6% females) with a median age of 34 years (IQR 29–38) were recruited. The overall prevalence of HIV infection was 8.7% (95% CI 6.5–10.9). The prevalence of HIV infections for males and females were 6.8% (95% CI 4.7–8.9%) and 41.2% (95% CI 23.7–58.6%) respectively. Adjusted weighted logistic regression analysis (WLRA) showed that being a female (aOR 19.1; 95% CI 5.9–61.8), injecting drugs for more than 10 years (aOR = 7.32; 95% CI 2.1–25.5) compared to 1 year or less and being 45 years or older (aOR = 34.22; 95% CI 2.4–489.5) compared to being 25 years or younger were associated with increased odds of HIV infection. Use of a sterile needle at last injection decreased odds of HIV infection (aOR = 0.3; 95% CI 0.1–0.8). Conclusions The present study observed a decline in prevalence of HIV infections among PWID in Dar es Salaam (8.7%) compared to a previous estimate of 15.5% from an IBBS conducted in 2013. Despite the decrease, HIV prevalence remains high among PWID compared to the general population, and women are disproportionally affected. The decline may be possibly attributed to the on-going implementation of CHIP for PWID, highlighting the need for strengthening the existing harm reduction interventions by incorporating access to sterile needle/syringe and addressing the layered risks for women.

Survivors from COVID-19 pneumonia can present with persisting multisystem involvement (lung, pulmonary vessels, heart, muscle, red blood cells) that may negatively affect exercise capacity. We sought to determine the extent and the determinants of exercise limitation in patients with COVID-19 at the time of hospital discharge. Eighteen consecutive patients with COVID-19 and 1:1 age-, sex-, and body mass index-matched controls underwent: spirometry, echocardiography, cardiopulmonary exercise test and exercise echocardiography for the study of pulmonary circulation. Arterial blood was sampled at rest and during exercise in patients with COVID-19. Patients with COVID-19 lie roughly on the same oxygen consumption isophlets than controls both at rest and during submaximal exercise, thanks to supernormal cardiac output (P < 0.05). Oxygen consumption at peak exercise was reduced by 30% in COVID-19 (P < 0.001), due to a peripheral extraction limit. In addition, within COVID-19 patients, hemoglobin content was associated with peak oxygen consumption (R2=0.46, P = 0.002). Respiratory reserve was not exhausted (median [IRQ], 0.59 [0.15]) in spite of moderate reduction of forced vital capacity (79 ± 40%). Pulmonary artery pressure increase during exercise was not different between patients and controls. Ventilatory equivalents for carbon dioxide were higher in patients with COVID-19 than in controls (39.5 [8.5] vs. 29.5 [8.8], P < 0.001), and such an increase was mainly explained by increased chemosensitivity. When recovering from COVID-19, patients present with reduced exercise capacity and augmented exercise hyperventilation. Peripheral factors, including anemia and reduced oxygen extraction by peripheral muscles were the major determinants of deranged exercise physiology. Pulmonary vascular function seemed unaffected, despite restrictive lung changes.NEW & NOTEWORTHY At the time of hospital discharge, patients with COVID-19 present with reduced functional capacity and exercise hyperventilation. Peripheral factors, namely reduced oxygen extraction (myopathy) and anemia, which are not fully compensated by a supernormal cardiac output response, account for exercise limitation before exhaustion of the respiratory reserve. Enhanced chemoreflex sensitivity, rather increased dead space, mainly accounts for exercise hyperventilation. The pulmonary vascular response to exercise circulation of survived patients with COVID-19 does not present major pathological changes.

Multiple myeloma (MM) is a hematological disease characterized by the proliferation and accumulation of malignant plasmacells (PCs) in the bone marrow (BM). Despite widespread use of high-dose chemotherapy in combination with autologous stem cell transplantation (ASCT) and the introduction of novel agents (immunomodulatory drugs, IMiDs, and proteasome inhibitors, PIs), the prognosis of MM patients is still poor. CD38 is a multifunctional cell-surface glycoprotein with receptor and ectoenzymatic activities. The very high and homogeneous expression of CD38 on myeloma PCs makes it an attractive target for novel therapeutic strategies. Several anti-CD38 monoclonal antibodies have been, or are being, developed for the treatment of MM, including daratumumab and isatuximab. Here we provide an in-depth look atCD38 biology, the role of CD38 in MM progression and its complex interactions with the BM microenvironment, the importance of anti-CD38 monoclonal antibodies, and the main mechanisms of antibody resistance. We then review a number of multiparametric flow cytometry techniques exploiting CD38 antigen expression on PCs to diagnose and monitor the response to treatment in MM patients.

Background and Purpose: An accurate determination of the cardioembolic risk in patients with atrial fibrillation (AF) is crucial to prevent consequences like stroke. Obstructive sleep apnea (OSA) is a known risk factor for both AF and stroke. We aim to explore a possible association between OSA and an increased cardioembolic risk in patients with AF. Methods: We assessed data from the ESADA (European Sleep Apnea Database) cohort where patients with known AF and OSA were included. Parameters of OSA severity and related hypoxia like lowest Sp o 2 and 4% oxygen desaturation index were analyzed. Patients were stratified according to their cardioembolic risk estimated with the CHA 2 DS 2 -VASc score. Results: From the initial cohort of 14 646 patients, a final set of 363 patients were included in the analysis. Indices of hypoxia during sleep were associated with increased CHA 2 DS 2 -VASc score (4% oxygen desaturation index 17.9 versus 29.6 versus 30.5 events/hour and the lowest Sp o 2 81.2 versus 77.8 versus 77.5% for low, moderate, and high cardioembolic risk, respectively, P Conclusions: These results support the potential role of OSA-related hypoxia in the risk for cardioembolic complications such as stroke in patients with AF.

Aims Interstitial pneumonia due to coronavirus disease 2019 (COVID‐19) is often complicated by severe respiratory failure. In addition to reduced lung compliance and ventilation/perfusion mismatch, a blunted hypoxic pulmonary vasoconstriction has been hypothesized, that could explain part of the peculiar pathophysiology of the COVID‐19 cardiorespiratory syndrome. However, no invasive haemodynamic characterization of COVID‐19 patients has been reported so far. Methods and results Twenty‐one mechanically‐ventilated COVID‐19 patients underwent right heart catheterization. Their data were compared both with those obtained from non‐mechanically ventilated paired control subjects matched for age, sex and body mass index, and with pooled data of 1937 patients with ‘typical’ acute respiratory distress syndrome (ARDS) from a systematic literature review. Cardiac index was higher in COVID‐19 patients than in controls [3.8 (2.7–4.5) vs. 2.4 (2.1–2.8) L/min/m2, P, Vicious circle between the lung and the heart in COVID‐19. Coronavirus‐2 causes an interstitial pneumonia characterized by low lung compliance. The ventilation/perfusion mismatch of non‐ventilated but perfused lung zones is enhanced by specific virus‐related mechanisms, with blunted hypoxic pulmonary vasoconstriction and normal PVR, further promoting the intrapulmonary shunt. High cardiac output due to acute inflammation and hypoxaemia, with low PVR and unimpeded left ventricular preload, predisposes to high filling pressure, which might be favoured by patient characteristics (elderly with cardiovascular comorbidities) and further exacerbated by virus‐related cardiac remodelling. High left ventricular filling pressure promotes lung congestion with further reduction of lung compliance. ACE, angiotensin‐converting enzyme; CSTAT, static lung compliance; LV, left ventricle; PAWP, pulmonary artery wedge pressure; PVR, pulmonary vascular resistance; Qs/Qt, intrapulmonary shunt; SIRS, systemic inflammatory response syndrome.

Objective: Aortic stiffness and central pressure measurements have become increasingly important for the overall estimation of cardiovascular risk. The aim of this study is to verify whether the presence of stenosis in the carotid arteries due to atherosclerotic plaques may induce a bias in the measurement of carotid-femoral pulse wave velocity (PWV) and in the analysis of central pulse waveform variables assessed by carotid tonometry. Methods: Eighty-four patients (age: 67.1 ± 12.4 years) undergoing screening for carotid atherosclerosis were enrolled, divided into three groups according to carotid ultrasound findings (NASCET criteria): 28 patients without significant stenosis, 30 patients with bilateral plaques, and 26 patients with right or left monolateral stenosis. PWV and other variables derived from the central pulse waveform analysis (central blood pressure, augmentation index and forward and backward waves) were measured at both right and left carotid arteries by a validated PulsePen tonometer. A repeatability study was performed in 28 young healthy patients (age: 25.4 ± 2.9 years). Results: A high degree of correlation was found between bilateral measurements in all groups, and particularly in groups with monolateral carotid stenosis, with no significant difference attributable to lateralized stenosis. Right-left differences in asymmetric groups were 0.35 ± 5.12 mmHg (R2 = 0.960) for central blood pressure,-2.12 ± 7.39% (R2 = 0.743) for augmentation index, 0.64 ± 1.56 m/s (R2 = 0.947) for PWV, 0.08 ± 8.48 mmHg for forward wave (R2 = 0.742) and 0.35 ± 2.35 mmHg for backward wave (R2 = 0.907). Conclusion: Measurement of PWV and of variables derived from the central pulse waveform analysis by carotid tonometry is not biased by the presence of local atherosclerotic plaques.

Elevated blood pressure (BP) is a growing burden worldwide, leading to over 10 million deaths each year. May Measurement Month (MMM) is a global initiative organized by the International Society of Hypertension aimed at raising awareness of high BP and to act as a temporary solution to the lack of screening programs worldwide. A similar approach has been used in Italy since 2012, showing inadequate awareness of the consequences of hypertension, a generally increased cardiovascular risk and unsatisfactory BP control in 36% of interviewed individuals. An opportunistic cross-sectional survey of volunteers aged ≥18 was carried out in May 2017, during the joint MMM and World Hypertension Day events. Blood pressure measurement, the definition of hypertension and statistical analysis followed the standard MMM protocol. Screenings were conducted both in cities and villages, indoor and outdoor, by health personnel. Eighty-five sites, involving approximately 300 investigators, took part in MMM17/World Hypertension Day in Italy, screening 10 076 individuals during a month-long period. After multiple imputation, 3099 participants were found (30.8%) to have high BP levels. This was the biggest opportunistic BP screening in a single time-point ever reported in Italy. A significant proportion of individuals had high BP, although it was not possible to differentiate between known treated hypertensive patients with inadequate BP control and as yet undiagnosed hypertensive individuals. Opportunistic screening can reach a significant number of individuals, being a powerful tool for raising awareness and carrying out BP screening.

CD22 is a surface molecule expressed early during the ontogeny of B cells in the bone marrow and spleen, and can be found on B cells isolated from the different lymphoid compartments in humans. CD22 is expressed by most blasts from the majority (60−90%) of B-cell acute lymphoblastic leukemia (B-ALL). Current therapies in adults with newly diagnosed B-ALL are associated with complete remission (CR) rates of 50−90%. However, 30−60% of these patients relapse, and only 25−40% achieve disease-free survival of three years or more. Chemotherapy regimens for patients with refractory/relapsed B-ALL are associated with CR rates ranging from 31% to 44%. Novel immune-targeted therapies, such as blinatumomab and inotuzumab (a humanized anti-CD22 monoclonal antibody conjugated to the cytotoxic antibiotic agent calicheamicin), provide potential means of circumventing chemo-refractory B-ALL cells through novel mechanisms of action. Eighty percent of inotuzumab-treated B-ALL patients may achieve a CR state. This review is focused on the biological and clinical activities of CD22 antibodies in B-ALL, and provides evidence about the potential role played by qualitative and quantitative analysis of the CD22 molecule on individual B-ALL blasts in predicting the depletion of leukemic cells, and, ultimately, leading to better clinical response rates.

Aims Remodelling of the cardiovascular system (including heart and vasculature) is a dynamic process influenced by multiple physiological and pathological factors. We sought to understand whether remodelling in response to a stimulus, exercise training, altered with healthy ageing. Methods A total of 237 untrained healthy male and female subjects volunteering for their first time marathon were recruited. At baseline and after 6 months of unsupervised training, race completers underwent tests including 1.5T cardiac magnetic resonance, brachial and non-invasive central blood pressure assessment. For analysis, runners were divided by age into under or over 35 years (U35, O35). Results Injury and completion rates were similar among the groups; 138 runners (U35: n = 71, women 49%; O35: n = 67, women 51%) completed the race. On average, U35 were faster by 37 minutes (12%). Training induced a small increase in left ventricular mass in both groups (3 g/m2, P Conclusion Medium-term, unsupervised physical training in healthy sedentary individuals induces measurable remodelling of both heart and vasculature. This amount is age dependent, with predominant cardiac remodelling when younger and predominantly vascular remodelling when older.

BACKGROUND: Cryptococcal meningitis accounts for 15% of all AIDS-mortality globally. Most cases in low- and middle-income countries are treated with fluconazole monotherapy, which is associated with a high mortality. New available therapies are needed. Short course amphotericin B has been shown to be a safe and efficient therapeutic option. Sertraline has in vitro fungicidal activity against Cryptococcus and bi-directional synergy with fluconazole. METHODS: We conducted an open label clinical trial to assess the safety and efficacy of sertraline 400 mg/day and fluconazole 1200 mg/day (n=28) vs. sertraline, fluconazole and additional 5-days of amphotericin B deoxycholate 0.7-1 mg/kg (n=18) for cryptococcal meningitis. RESULTS: 2-week survival was 64% (18/28) without amphotericin and 89% (16/18) with amphotericin, and 10-week survival was 21% (6/28) vs. 61% (11/18), respectively (p=0.012). The cerebrospinal fluid (CSF) Cryptococcus clearance rate was 0.264 log(10) colony forming units (CFU)/mL of CSF/day (95%CI: 0.112-0.416) without amphotericin and 0.473 log(10) CFU/mL/day (95%CI: 0.344-0.60) with short-course amphotericin (p=0.03). Sertraline was discontinued in one participant due to side effects. Four participants receiving amphotericin B experienced hypokalemia

This article explores the 1552 posthumous edition of Teofilo Folengo’s Macaronee, which included his masterpiece Baldus, and the preface to the work penned in late 1544/early 1545 by one Vigaso Coc...

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): British Heart Foundation Barts Cardiovascular Biomedical Research Centre onbehalf The Marathon Study Consortium Introduction Cardiovascular function depends on the inter-relation between heart and vasculature. The contribution of aorta and peripheral vessels to the total systolic load of the left ventricle (LV) can be represented respectively by a "pulsatile" and a "resistive" component. We sought to understand their interrelation by exploring how LV remodelling occurred with altered load associated with an external stimulus (training). Methods: 237 untrained healthy male and female subjects volunteering for their first-time marathon were recruited. At baseline and after 6 months of unsupervised training, race completers underwent 1.5T cardiac magnetic resonance, brachial and non-invasive central blood pressure assessment. For analysis, runners were divided into 4 groups according to the variation (positive versus null or negative) in Total Arterial Compliance Index (TACi), representing the pulsatile component of the LV load, and in Systemic Vascular Resistance Index (SVRI), representing the resistive component of the LV load. Results: 138runners (age 21-69 years; F: 51%) completed the race. Data are reported for each variable as Δ mean [95% Confidence Interval]. In the whole cohort, training was associated with a small increase in LV mass index (+3g/m2, [0, 6 g/m2]), indexed LV end-diastolic volume (EDVi) (+3ml/m2, [-2, 5 3ml/m2]), in LV mass/LVEDV ratio (+0.02g/ml, [0.00, 0.04 g/ml]) and in TACi (+0.02ml/m2, [0.02, 0.38 ml/m2]). SVRi mildly fell (-43dyn·s/cm2[-103, 17dyn·s/cm2]). TACi increase was associated with LVEDVi increase and no change in LV mass/EDV (eccentric remodelling). On the other hand, both TACi reduction and SVRi increase were associated with increase in LV mass/EDV and no significant change in LVEDVi (concentric remodelling). A similar increase in LV mass was observed in all groups. See Table. Conclusion: Cardiac remodelling observed after mild, medium term, unsupervised training seems to be related to the modifications of aorta and peripheral vessels. In particular, a reduction in pulsatile load seems associated with eccentric LV remodelling, while an increase in both pulsatile and resistive with concentric LV remodelling. Further research is needed to understand the interaction between TACi and SVRi. Table 1 LV EDVi (ml/m2) LV mass index (g/m2) LV mass/EDV TACi increase (n = 75) +4 [0, 9] +3 [0, 7] 0 [-0.03, 0.03] TACi decrease (n = 62) -1 [-6, 4] +3 [0, 8] 0.04 [0.01, 0.07] SVRi increase (n = 63) 0 [-4,4] +3 [0, 7] +0.03 [0, 0.06] SVRi decrease (n = 73) +3 [-3, 7] +3 [-1, 6] +0.01 [-0.02, 0.04]

Background High number of unintended pregnancies—often leading to induced abortions—are reported among female sex workers (FSWs), highlighting a major unmet need for contraception. To better understand barriers to contraceptive use, we explored FSW’s pregnancy perceptions and experiences of unintended pregnancy. We hypothesized that sex work exacerbates barriers to contraceptive use and that FSW’s pregnancy perceptions and experiences of unintended pregnancy influence future commitment to contraceptive use. Methods We conducted in-depth interviews with 11 FSWs (January–June 2019) in Dar es Salaam, Tanzania. We purposively sampled FSWs with a positive pregnancy test from those participating in a HIV vaccine preparedness cohort. We used open ended questions to explore how FSWs make decisions when facing barriers to contraceptive use, dealing with unintended pregnancy and adhering to contraceptive use after experiencing unintended pregnancy. All interviews were conducted in Kiswahili, audio-recorded, transcribed and translated into English. Grounded theory approach was used to analyse transcripts. Open and selective coding was performed using Nvivo software. Results FSWs reported that sex work impedes good contraceptive behaviour because sex workers felt unable to negotiate consistent condom use, avoided health services due to stigma, missed monthly contraceptive supplies because of inconvenient clinic operating hours or skipped contraceptive pills when intoxicated after taking alcohol. FSWs who perceived pregnancy to be a burden terminated the pregnancy because of fear of loss of income during pregnancy or child rearing expenses in case child support was not assured by their partners. FSWs who perceived pregnancy to be a blessing decided to keep the pregnancy because they desired motherhood and hoped that children would bring prosperity. Family planning counselling and availability of contraceptives during postpartum care influenced the initiation of contraception among FSWs. Financial hardships related to childrearing or painful abortion experiences influenced FSWs’ commitment to good contraceptive practices. Conclusion Our results demonstrate that FSWs face barriers to initiating and adhering to contraceptive use because of sex work stigma, inability to negotiate condoms and failure to access medical services at their convenience. Our findings underscore the need to integrate contraceptive services with HIV programs serving FSWs in their areas of work.

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 ± 16 years) were subdivided into 3 age groups (40–49 y, 50–59 y, 60–69 y) 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 40–49 y (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.

During blood pressure (BP) measurement, the recommended positioning of the cuff bladder center is directly above the brachial artery. We investigated the relevance of incorrect cuff positioning during (1) auscultatory measurement with an appropriate or improperly small cuff and (2) oscillometric measurement with a wide-range cuff designed to guarantee accurate measurements regardless of position. In subjects with wide BP and arm circumference ranges, (1) auscultatory BP was repeatedly measured with a properly positioned cuff (reference) and, simultaneously, with an identical cuff placed on the other arm in either a correct or an incorrect position (test). The measurements were performed with a properly sized (N=57) or an improperly small cuff (N=33). (2) Auscultatory measurements obtained with a properly positioned and sized cuff were compared with oscillometric measurements obtained with a specially designed wide-range cuff (Omron IntelliWrap) placed on the contralateral arm either in a correct or an incorrect position. Auscultatory BP measures were unaffected by incorrect positioning of a properly sized cuff, whereas with undercuffing, BP was overestimated with the cuff displaced by 90° laterally (systolic/diastolic BP differences: 4.9±4.6/4.0±4.6 mm Hg, P

BACKGROUND Aortic pulse wave velocity (PWV) is an indirect index of arterial stiffness and an independent cardiovascular risk factor. Consistency of PWV assessment over time is thus an essential feature for its clinical application. However, studies providing a comparative estimate of the reproducibility of PWV across different noninvasive devices are lacking, especially in the elderly and in individuals at high cardiovascular risk. METHODS Aimed at filling this gap, short-term repeatability of PWV, estimated with 6 different devices (Complior Analyse, PulsePen-ETT, PulsePen-ET, SphygmoCor Px/Vx, BPLab, and Mobil-O-Graph), was evaluated in 102 high cardiovascular risk patients hospitalized for suspected coronary artery disease (72 males, 65 ± 13 years). PWV was measured in a single session twice, at 15-minute interval, and its reproducibility was assessed though coefficient of variation (CV), coefficient of repeatability, and intraclass correlation coefficient. RESULTS The CV of PWV, measured with any of these devices, was CONCLUSIONS Our study shows that the short-term repeatability of PWV measures is good but not homogenous across different devices and at different PWV values. These findings, obtained in patients at high cardiovascular risk, may be relevant when evaluating the prognostic importance of PWV.

OBJECTIVE The timing of mechanical cardiac events is usually evaluated by conventional echocardiography as an index of cardiac systolic function and predictor of cardiovascular outcomes. We aimed to measure the systolic time intervals, namely the isovolumetric contraction time (ICT) and pre-ejection period (PEP), by arterial tonometry. APPROACH Sixty-two healthy volunteers (age 47 ± 17 years) and 42 patients with heart failure and reduced ejection fraction were enrolled (age 66 ± 14 years). Pulse waves were recorded at the carotid artery by arterial tonometry together with simultaneous aortic transvalvular flow by Doppler-echocardiography, synchronized by electrocardiographic gating. The ICT was determined from the time delay between the electrical R wave and the carotid pressure waveform, after adjustment for the pulse transit time from the aortic valve to the carotid artery site, estimated by an algorithm based on the carotid-femoral pulse wave velocity. The PEP was evaluated by adding the electrical QR duration to the ICT. MAIN RESULTS The ICT derived from carotid pulse wave analysis was closely related to that measured by echocardiography (r = 0.90, p

In heart failure (HF) sleep problems and sleep-related breathing disorders are frequently reported and are associated with poor prognosis. However, only few large clinical studies have investigated this issue in heart failure through breathing pattern analysis by polysomnography. Background: In heart failure (HF) sleep problems and sleep-related breathing disorders are frequently reported and are associated with poor prognosis. However, only few large clinical studies have investigated this issue in heart failure through breathing pattern analysis by polysomnography. Methods and results: 370 HF patients, with either moderate-severe reduced ejection fraction or with clinical decompensation, consecutively referred to 10 participating cardiology centers, have been enrolled in the PROMISES Study, an Italian project aimed at generating a large, multidisciplinary database of anthropometric, clinical, echocardiographic and sleep data, the last derived from overnight unattended cardio-respiratory polysomnography in HF patients. Obstructive sleep apnea was the most frequent form of sleep related breathing disorders observed in our cohort (35.4% with an AHI cutoff of 15). The possible determinants of sleep related breathing disorders were analyzed through stepwise logistic regression analysis and two multivariate models showing that a markedly reduced left ventricular ejection fraction was the most important factor associated with central sleep apneas (OR = 7.7 for AHI cutoff = 15 and LVEF ≤ 35%) together with male gender and increasing age. Conventional risk factors for obstructive sleep apnea did not identify HF patients affected by this condition. Conversely, a greater neck circumference was associated with an increased risk for central apneas. Conclusions: Our paper offers a deeper insight into the features of SRBD and its determinants in HF patients, leading in turn to a better clinical management of these comorbid patients.

Body acceleration due to heartbeat-induced reaction forces can be measured as mobile phone accelerometer (m-ACC) signals. Our aim was to test the feasibility of using m-ACC to detect changes induced by stress by ultra-short heart rate variability (USV) indices (standard deviation of normal-to-normal interval&mdash, SDNN and root mean square of successive differences&mdash, RMSSD). Sixteen healthy volunteers were recruited, m-ACC was recorded while in supine position, during spontaneous breathing at rest conditions (REST) and during one minute of mental stress (MS) induced by arithmetic serial subtraction task, simultaneous with conventional electrocardiogram (ECG). Beat occurrences were extracted from both ECG and m-ACC and used to compute USV indices using 60, 30 and 10s durations, both for REST and MS. A feasibility of 93.8% in the beat-to-beat m-ACC heart rate series extraction was reached. In both ECG and m-ACC series, compared to REST, in MS the mean beat duration was reduced by 15% and RMSSD decreased by 38%. These results show that short term recordings (up to 10 s) of cardiac activity using smartphone&rsquo, s accelerometers are able to capture the decrease in parasympathetic tone, in agreement with the induced stimulus.

The Detrended Fluctuation Analysis (DFA) is widely employed to quantify the fractal dynamics of R-R intervals (RRI). This is usually done by estimating a short- and a long-term coefficient, but it is still unclear how much the information provided by such a bi-scale DFA is independent of that of traditional spectral indices. However, more sophisticated DFA approaches have been recently proposed, including the multifractal-multiscale DFA and the DFA for magnitude and sign of RRI changes. The aim of our work is to investigate whether novel DFA approaches allow extracting the information on the nonlinear RRI dynamics that traditional spectral methods cannot retrieve.We selected 4-hour segments of beat-by-beat RRI series from a 24-hour Holter recording, one during daytime (wake), one at night (sleep) in a healthy volunteer. From the wake segment, we generated 100 surrogate series shuffling the phases but preserving the power spectrum, and then from each of the resulting RRI series, we generated the series of the sign and the series of the magnitude of successive RRI changes. We generated similar series from the sleep recording. Thus, we finally obtained 6 original beat-to-beat series to be compared with 600 surrogate series, each of 4-hour duration.The comparison between original and surrogate series showed that for this experimental setting, the traditional monofractal DFA provides the same information retrievable by the power spectrum. However, specific components of the multifractal DFA reveal information not detectable by the power spectrum, particularly in the sleep condition. Furthermore, the DFA of the magnitude of RRI changes reflects important nonlinear components. Therefore, these more sophisticated DFA approaches might effectively improve the clinical value of RRI variability analysis.

Background: Acute exposure to high altitude (>2500 m) is known to induce a rise in blood pressure (BP) and the appearance of sleep related breathing alterations, in particular central sleep apneas and periodic breathing. Little information is available on whether this is the case in humans also for acute exposure to moderate altitude (between 1500 and 2500 m). Aim of this study was to evaluate the effects of acute exposure of healthy volunteers to moderate altitude on conventional and ambulatory BP as well as on the frequency and severity of breathing alterations during sleep. Methods: Forty-four healthy lowlanders underwent 24-hour ambulatory BP monitoring and nocturnal cardio-respiratory sleep study at sea level and during acute (1–2 days after arrival) exposure to moderate altitude (2035 m, Sestriere, Italy). The key variables investigated included average systolic and diastolic BP and heart rate over daytime, night-time and 24 h, the frequency of obstructive and central apneas/hypopnoeas and the behaviour of oxygen saturation during sleep. Results: Compared to sea level, during moderate altitude exposure mean systolic/diastolic BP increased significantly during daytime (respectively from 125.6 ± 10.9 to 130.6 ± 12.3, p = 0.0032 and from 78.8 ± 6.7 to 81.8 ± 7.7 mmHg, p = 0.0048) and during night-time (respectively from 102.4 ± 12.4 to 107.4 ± 12.7, p = 0.0028, and from 62.0 ± 8.2 to 65.8 ± 8.2 mmHg, p = 0.0014), with no change in nocturnal BP dipping. BP increase was more evident in participants aged over 40 years. Apnea-hypopnea index (AHI) increased from 1.60 (0.40–2.90) to 5.4 (2.90–10.60), p < 0.0001), mainly because of increasing frequency of hypopneas and central apneas, in particular in males aged over 40 years. No association was found between size of BP changes and AHI. Conclusion: Our results indicate that in healthy subjects even exposure to moderate altitude may induce significant, although mild, changes in ambulatory BP and in respiratory patterns during sleep with gender and age-related differences. Further studies are needed to explore the clinical relevance of these findings

Closed-loop models of the interactions between blood pressure (BP) and heart rate variations allow for estimation of baroreflex sensitivity (feedback effects of BP changes on heart rate) while also considering the feedforward effects of heart rate on BP. Our study is aimed at comparing modulations of feedback and feedforward couplings over 24 h in normotensive and hypertensive subjects, by assessing closed-loop baroreflex models in ambulatory conditions. Continuous intra-arterial BP recordings were performed for 24 h in eight normotensive and eight hypertensive subjects. Systolic BP (SBP) and pulse interval (PI) beat-by-beat series were analyzed by an autoregressive moving average model over consecutive 6-min running windows, estimating closed-loop feedback and feedforward gains in each window. The open-loop feedback gain was estimated for comparison. Normotensive and hypertensive patients were compared during wake (18:00–22:00) and sleep (23:00–5:00) periods by a mixed-effect linear model at p < 0.05. In both groups feedback (feedforward) gain averaged values were higher (lower) in sleep than in wake. Moreover, the closed-loop feedback gain was higher in normotensive subjects both in wake and sleep, whereas the closed-loop feedforward gain was higher in hypertensive subjects during sleep. By contrast, no significant differences were found between the normotensive and hypertensive groups for the open-loop feedback gain. Therefore, the closed-loop SBP-PI model can detect circadian alterations in the feedforward gain of PI on SBP and derangements of spontaneous baroreflex sensitivity in hypertension not detectable with the open-loop approach. These findings may help to obtain a more comprehensive assessment of the autonomic dysfunction underlying hypertension and for the in-depth evaluation of the benefits of rehabilitation procedures on autonomic cardiovascular modulation.

Background Several devices have been proposed to assess arterial stiffness in clinical daily use over the past few years, by estimating aortic pulse wave velocity (PWV) from a single measurement of brachial oscillometric blood pressure, using patented algorithms. It is uncertain if these systems are able to provide additional elements, beyond the contribution carried by age and blood pressure levels, in the definition of early vascular damage expressed by the stiffening of the arterial wall. Methods and Results The aim of our study was to compare the estimated algorithm‐based PWV values, provided by the Mobil‐O‐Graph system, with the standard noninvasive assessment of aortic PWV in patients with Marfan syndrome (ie, in subjects characterized by premature aortic stiffening and low blood pressure values). Aortic stiffness was simultaneously evaluated by carotid‐femoral PWV with a validated arterial tonometer and estimated with an arm cuff–based ambulatory blood pressure monitoring Mobil‐O‐Graph device on 103 patients with Marfan syndrome (50 men; mean± SD age, 38±15 years). Aortic PWV, estimated by the Mobil‐O‐Graph, was significantly ( P SD, 6.1±1.3 m/s) than carotid‐femoral PWV provided by arterial tonometry (mean± SD , 8.8±3.1 m/s). The average of differences between PWV values provided by the 2 methods (±1.96×SD) was −2.7±5.7 m/s. Conclusions The Mobil‐O‐Graph provides PWV values related to an ideal subject for a given age and blood pressure, but it is not able to evaluate early vascular aging expressed by high PWV in the individual patient. This is well shown in patients with Marfan syndrome.

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 ± 11.3, BMI = 46.7 ± 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

Stays at high altitude induce alterations in cardiovascular control and are a model of specific pathological cardiovascular derangements at sea level. However, high-altitude alterations of the complex cardiovascular dynamics remain an almost unexplored issue. Therefore, our aim is to describe the altered cardiovascular complexity at high altitude with a multiscale entropy (MSE) approach. We recorded the beat-by-beat series of systolic and diastolic blood pressure and heart rate in 20 participants for 15 min twice, at sea level and after arrival at 4554 m a.s.l. We estimated Sample Entropy and MSE at scales of up to 64 beats, deriving average MSE values over the scales corresponding to the high-frequency (MSEHF) and low-frequency (MSELF) bands of heart-rate variability. We found a significant loss of complexity at heart-rate and blood-pressure scales complementary to each other, with the decrease with high altitude being concentrated at Sample Entropy and at MSEHF for heart rate and at MSELF for blood pressure. These changes can be ascribed to the acutely increased chemoreflex sensitivity in hypoxia that causes sympathetic activation and hyperventilation. Considering high altitude as a model of pathological states like heart failure, our results suggest new ways for monitoring treatments and rehabilitation protocols.

Introduction and Aim: Obstructive sleep apnea (OSA) is associated with a higher cardiovascular risk and abnormal autonomic control can play a role in this context. Thus, heart rate variability (HRV) changes induced by sleep may help to understand the autonomic derangement in OSA. Methods: From the ESADA database, we selected 84 polysomnographies with 10-min ECG segments both pre- and post-dormitum in male patients who underwent a diagnostic sleep study at Sleep Disorder Centre of the Antwerp. Patients were classified as moderate, mild or severe OSA based on the Apnea-Hypopnea Index (AHI). We estimated HRV indices of vagal tone (pNN50+ and RMSSD), of sympatho/vagal balance (short term DFA), and vagal/sympatho balance (SampEn), comparing pre- vs post-dormitum (Wilcoxon paired test). Results and Conclusions: From pre- to post-dormitum, the vagal tone increases significantly in moderate and mild OSA only; the sympatho/vagal balance increases similarly in the three groups, see table (data are expressed as median and interquartile range). Our data suggest that in severe OSA we observe a lower increase of vagal indices in post-dormitum associated with a relative sympathetic overactivity, potentially leading, in turn, to a higher risk of cardiovascular events.

IntroductionRisk reduction towards safer behaviour is promoted after enrolment in HIV prevention trials. We evaluated sexual behaviour, changes in sexual behaviour and factors associated with risky behaviour after one-year of follow-up among women enrolled in HIV prevention trials in Northern Tanzania.MethodsSelf-reported information from 1378 HIV-negative women aged 18-44 enrolled in microbicide and vaccine feasibility studies between 2008-2010,was used to assess changes in behaviour during a 12-month follow-up period. Logistic regression with random intercepts was used to estimate odds ratios for trends in each behaviour over time. A behavioural risk score was derived from coefficients of three behavioural variables in a Poisson regression model for HIV incidence and thereafter, dichotomized to risky vs less-risky behaviour. Logistic regression was then used to identify factors associated with risky behaviour at 12 months.ResultsAt baseline, 22% reported multiple partners, 28% were involved in transactional sex and only 22% consistently used condoms with non-regular partners. The proportion of women reporting multiple partners, transactional sex and high-risk sex practices reduced at each 3-monthly visit (33%, 43% and 47% reduction in odds per visit respectively, p for linear trend ConclusionAn overall reduction in risky behaviours over time was observed in HIV prevention cohorts. Risk reduction counselling was associated with decreased risk behaviour but was insufficient to change behaviours of all those at highest risk. Biological HIV prevention interventions such as PrEP for individuals at highest risk, should complement risk reduction counselling so as to minimize HIV acquisition risk.

Detrended Fluctuation Analysis (DFA) is a popular method for assessing the fractal characteristics of biosignals, recently adapted for evaluating the heart-rate multifractal and/or multiscale characteristics. However, the existing methods do not consider the beat-by-beat sampling of heart rate and have relatively low scale resolutions and were not applied to cardiovascular signals other than heart rate. Therefore, aim of this work is to present a DFA-based method for joint multifractal/multiscale analysis designed to address the above critical points and to provide the first description of the multifractal/multiscale structure of interbeat intervals (IBI), systolic blood pressure (SBP), and diastolic blood pressure (DBP) in male and female volunteers separately. The method optimizes data splitting in blocks to reduce the DFA estimation variance and to evaluate scale coefficients with Taylor’s expansion formulas and maps the scales from beat domains to temporal domains. Applied to cardiovascular signals recorded in 42 female and 42 male volunteers, it showed that scale coefficients and degree of multifractality depend on the temporal scale, with marked differences between IBI, SBP, and DBP and with significant sex differences. Results may be interpreted considering the distinct physiological mechanisms regulating heart-rate and blood-pressure dynamics and the different autonomic profile of males and females.

Antibody therapy is a treatment option for several diseases, including multiple myeloma. The logic behind it is relatively simple: A target molecule is selected because of its expression on tumor cells, and the antibody delivers cytotoxic effects. Therapeutic results in multiple myeloma indicate that the anti-CD38 antibodies may have relevant immunotherapeutic properties. See related article by Moreno et al., p. 3176

This study presents the Italian validation of the recently developed Edinburgh Cognitive and Behavioural ALS Screen (ECAS), a short screen for cognitive/behavioural alterations in patients with amyotrophic lateral sclerosis (ALS). We evaluated the psychometric properties of the ECAS Italian version in terms of reliability and convergent validity for both cognitive and behavioural features. Furthermore, we investigated the relationship with affective and clinical variables, in addition to ECAS usability and patients’ insight into cognitive/behaviour changes. Finally, correlations between genetic and cognitive/behavioural data were analysed. We recruited 107 patients with ALS. Normative data were collected on 248 healthy subjects. Participants were administered the ECAS and two standard cognitive screening tools (FAB, MoCA), two psychological questionnaires (BDI, STAI/Y) and an ad hoc usability questionnaire. The FBI was also carried out with caregivers. Results showed that the ECAS Italian version discriminated well between patients and controls. The most prevalent deficit occurred in executive functions and fluency. Correlations were observed between the ECAS and standard cognitive screening tools and between the ECAS carer interview and the FBI, supporting its full convergent validity. In conclusion, the ECAS Italian version provides clinicians with a rapid, feasible and sensitive tool, useful to identify different profiles of cognitive-behavioural impairment in ALS.

Cardiovascular events in hypertensives are associated with elevated average blood pressure (BP) and higher short-term BP variability (V), but little is known on treatment effects on BPV and on how to assess changes in short-term BPV. Aim of our study was to address the methodology of short-term BPV assessment and its reduction by Lercanidipine (L) or Enalapril (E) and their combination, through analysis of 24-hour ambulatory BP recordings from two studies including subjects of different age. Study-1: 64 middle-age hypertensives (52.9 ± 9.5 yrs) received L and E s.i.d. at 10 mg (L10, E10) or 20 mg doses (L20, E20) for 8 weeks. Study-2: 66 elderly hypertensives (65.5 ± 4.7 yrs) received placebo, L10, E20 and L10 + E20 s.i.d. for 4 weeks. In middle-age subjects, both L and E decreased mean BP and, at the highest dose, also short-term BPV. In elderly subjects, L10 alone or in combination with E20 reduced BPV. Treatment-induced reductions in BP levels and BPV were uncorrelated. Different methods for short-term BPV assessment did not always provide superimposable results in the elderly. Our study supports a better reduction of BPV by L in the elderly and by E + L combination at any age, suggesting BPV reduction to be independent from reduction in average BP. Cardiovascular events in hypertensives are associated with elevated average blood pressure (BP) and higher short-term BP variability (V), but little is known on treatment effects on BPV and on how to assess changes in short-term BPV. Aim of our study was to address the methodology of short-term BPV assessment and its reduction by Lercanidipine (L) or Enalapril (E) and their combination, through analysis of 24-hour ambulatory BP recordings from two studies including subjects of different age. Study-1: 64 middle-age hypertensives (52.9 ± 9.5 yrs) received L and E s.i.d. at 10 mg (L10, E10) or 20 mg doses (L20, E20) for 8 weeks. Study-2: 66 elderly hypertensives (65.5 ± 4.7 yrs) received placebo, L10, E20 and L10 + E20 s.i.d. for 4 weeks. In middle-age subjects, both L and E decreased mean BP and, at the highest dose, also short-term BPV. In elderly subjects, L10 alone or in combination with E20 reduced BPV. Treatment-induced reductions in BP levels and BPV were uncorrelated. Different methods for short-term BPV assessment did not always provide superimposable results in the elderly. Our study supports a better reduction of BPV by L in the elderly and by E + L combination at any age, suggesting BPV reduction to be independent from reduction in average BP.

Background and purpose: Both obstructive sleep apnea (OSA) and cardiac organ damage have a crucial role in acute ischemic stroke. Our aim is to explore the relationship between OSA and cardiac organ damage in acute stroke patients. Methods: A total of 130 consecutive patients with acute ischemic stroke were enrolled. Patients underwent full multichannel 24-h polysomnography for evaluation of OSA and echocardiography to evaluate left ventricle (LV) mass index (LV mass/BSA, LV mass/height 2.7), thickness of interventricular septum (IVS) and posterior wall (LVPW), LV ejection fraction and left atrium enlargement. Information on occurrence of arterial hypertension and its treatment before stroke was obtained from patients' history. Results: 61.9% (70) of patients, mostly men (67.1%), with acute stroke had OSA (AHI > 10). Patients with acute stroke and OSA showed a significant increase (P < 0.05) of LV mass index, IVS and LVPW thickness and a significant left atrial enlargement as compared with patients without OSA. LV ejection fraction was not significantly different in stroke patients with and without OSA and was within normal limits. No relationship was found among cardiac alterations, occurrence of OSA and history of hypertension. Conclusion: Acute stroke patients with OSA had higher LV mass and showed greater left atrial enlargement than patients without OSA. This study confirms the high prevalence of OSA in stroke patients, suggesting also an association between OSA and cardiac target organ damage. Our finding of structural LV abnormalities in acute stroke patients with OSA suggests a potential role of OSA as contributing factor in determining both cerebrovascular and cardiac damage, even in absence of clear link with a history of blood pressure elevation.

Background Acute exposure to high‐altitude hypobaric hypoxia induces a blood pressure rise in hypertensive humans, both at rest and during exercise. It is unclear whether this phenomenon reflects specific blood pressure hyperreactivity or rather an upward shift of blood pressure levels. We aimed at evaluating the extent and rate of blood pressure rise during exercise in hypertensive subjects acutely exposed to high altitude, and how these alterations can be counterbalanced by antihypertensive treatment. Methods and Results Fifty‐five subjects with mild hypertension, double‐blindly randomized to placebo or to a fixed‐dose combination of an angiotensin‐receptor blocker (telmisartan 80 mg) and a calcium‐channel blocker (nifedipine slow release 30 mg), performed a cardiopulmonary exercise test at sea level and after the first night's stay at 3260 m altitude. High‐altitude exposure caused both an 8 mm Hg upward shift ( P P P P Conclusions In hypertensive subjects exposed to high altitude, we observed a hypoxia‐driven upward shift and steepening of the blood pressure response to exercise. The effect of the combination of telmisartan/nifedipine slow release outweighed these changes and was associated with better muscle oxygen delivery. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01830530.

In this paper we take the vantage point of the law as a prism through which to observe the new relation that has taken shape between public sector bodies and the citizenry in view of the knowledge enabled by digital technologies. More to the point, we analyse the right to know vis-à-vis the government and its institutions, assessing the way the changes brought about by technology in the digital space are reshaping digital rights, entrusted with striking a new and complex balance between citizens and the government. We will specifically address the right to access government data. To this end we will consider the way the law has evolved in Italy, with a focus on Legislative Decree 97/2016 and the deep changes it has made to Legislative Decree 33/2013, providing tools for greater transparency and knowledge of government activity and administration. We highlight the deep transformation that has resulted from these changes, affecting the legal relationship between public sector bodies and citizens

We assessed language, attention, executive, and social cognition abilities in a sample of patients with Amyotrophic Lateral Sclerosis (ALS) by means of a recently developed cognitive battery based on oculomotor control with eye-tracking (ET) technology. Twenty-one ALS patients and 21 age- and education-matched healthy subjects underwent the ET-based cognitive assessment, together with the standard cognitive screening tools [Frontal Assessment Battery (FAB); Montreal Cognitive Assessment (MoCA); and Digit Sequencing Task]. Psychological measures of anxiety (State-Trait Anxiety Inventory-Y) and depression (Beck Depression Inventory) were also collected, and an ET usability questionnaire was administered. For patients, clinical and respiratory examinations were also performed, together with behavioural assessment (Frontal Behavioural Inventory). The developed battery discriminated among patients and controls with regard to measures of verbal fluency, frontal abilities, and social cognition. Measures of diagnostic utility confirmed a higher diagnostic accuracy of such ET-based tests with respect to FAB; similar diagnostic accuracy emerged when comparing them to the other standard cognitive tools (MoCA, WM). Usability ratings about the ET tests were comparable among the two groups. The ET-based neuropsychological battery demonstrated good levels of diagnostic accuracy and usability in a clinical population of non-demented ALS patients, compared to matched healthy controls. Future studies will be aimed at further investigate validity and usability components by recruiting larger sample of patients, both in moderate-to-severe stages of the disease and affected by more severe cognitive impairment.

Published online: 27 Mar 2017 In his years as Florentine Secretary, Machiavelli repeatedly faced the problem of interpreting the gestures and words of statesmen that were masters of deception. The strategy he developed to uncover these statesmen’s intentions was based on the analysis of human passions, on uncovering the fundamental trait that defined a man’s character. I apply Machiavelli’s strategy of interpretation to Machiavelli himself and uncover the irreconcilable disconnect which shaped his personal tragedy. On one hand, he related to his objects of desire by entirely abandoning himself to them, regardless of how unachievable they were. On the other, to obtain these objects of desire his analytical mind developed strategies which took pride in their adherence to what he called the “effectual truth of the matter.” His incapacity to reconsider his objectives in light of the means at his disposal and his tendency to transfer all of himself into his objectives determined Machiavelli’s successes and failures. He repeatedly failed when he had to set his own goals, or when he approached a problem with empathy. He succeeded when he was given precise and limited objectives and when he understood that he did not share the goals of those he was studying.

Background Marfan syndrome is characterized by aortic root dilation, beginning in childhood. Data about aortic pulsatile hemodynamics and stiffness in pediatric age are currently lacking. Methods and Results In 51 young patients with Marfan syndrome (12.0±3.3 years), carotid tonometry was performed for the measurement of central pulse pressure, pulse pressure amplification, and aortic stiffness (carotid‐femoral pulse wave velocity). Patients underwent an echocardiogram at baseline and at 1 year follow‐up and a genetic evaluation. Pathogenetic fibrillin‐1 mutations were classified between “dominant negative” and “haploinsufficient.” The hemodynamic parameters of patients were compared with those of 80 sex, age, blood pressure, and heart‐rate matched controls. Central pulse pressure was significantly higher (38.3±12.3 versus 33.6±7.8 mm Hg; P =0.009), and pulse pressure amplification was significantly reduced in Marfan than controls (17.9±15.3% versus 32.3±17.4%; P P =0.010; β=−0.271, P =0.026). No significant difference in hemodynamic parameters was found according to fibrillin‐1 genotype. Patients who increased aortic Z‐scores at 1‐year follow‐up presented a higher central pulse pressure than the remaining (42.7±14.2 versus 32.3±5.9 mm Hg; P =0.004). Conclusions Central pulse pressure and pulse pressure amplification were impaired in pediatric Marfan syndrome, and associated with aortic root diameters, whereas aortic pulse wave velocity was similar to that of a general pediatric population. An increased central pulse pressure was present among patients whose aortic dilatation worsened at 1‐year follow‐up.

Background It has been previously shown in patients with heart failure that exercise-based rehabilitation programmes may improve functional capacity and autonomic response. The aim of this study was to investigate this issue further by evaluating whether an association exists between autonomic adaptations and improvements of aerobic capacity in a general population of coronary artery disease patients undergoing cardiac rehabilitation. Methods Ninety consecutive patients (age 60 ± 11 years) attended a rehabilitation programme of moderate continuous training (25 ± 8 sessions, 2-3 sessions/week). Functional capacity expressed as oxygen uptake (peak VO

Background Invasive pressure-flow (P/Q) relationship of the pulmonary circulation can detect the presence of pulmonary hypertension (PH) during exercise and provide information on patients' symptoms and assess disease severity. Doppler-echocardiography was reported to provide accurate but imprecise noninvasive estimates of both resting and exercise pulmonary haemodynamics. However, data on the direct comparison of invasive vs noninvasive approaches to build pressure-flow relationship are scarce. Purpose To compare echocardiographic estimates with invasive measurements of P/Q relationship of the pulmonary circulation during exercise. Methods Patients undergoing a clinically indicated right heart catheterization and echocardiography were studied at rest and during exercise. The ratio between mean pulmonary artery pressure and cardiac output at peak exercise (TPR), as well as P/Q slope throughout exercise were calculated. Both TPR and P/Q slope are abnormal when ≥3 mmHg/L/min. Echocardiographic estimates were compared with invasive measurements. Results Sixty patients were included (mean age 65±14 years, 73% female). PH was present at rest in 38 cases (63%), of precapillary origin in 23 (61%). Heart failure with preserved ejection fraction was diagnosed in 23 patients, of which 17 had no PH at rest. TPR at peak exercise and P/Q slope were abnormal (≥3 mmHg/L/min) in the majority of patients (56 and 45 subjects, respectively). Echocardiographic estimates of P/Q slope and TPR correlated significantly although weakly with invasive measurements (R2=0.38 and 0.56, respectively, p Figure 1 Conclusions Doppler-echocardiography can provide rather accurate and sensitive but imprecise estimates of pressure-flow relationships of the pulmonary circulation during exercise. This intrinsic imprecision may limit its use in clinical practice.