Low HDL cholesterol and the eNOS Glu298Asp polymorphism are associated with inducible myocardial ischemia in patients with suspected stable coronary artery disease.

BACKGROUND: The endothelial nitric oxide synthase (eNOS) gene deficiency is known to cause impaired coronary vasodilating capability in animal models. In the general clinical population, the eNOS gene polymorphisms, able to affect eNOS activity, were associated with cardiometabolic risk features and prevalence of coronary artery disease (CAD). AIM: To investigate the association of eNOS Glu298Asp gene polymorphism, cardiometabolic profile, obstructive CAD and inducible myocardial ischemia in patients with suspected stable CAD. METHODS: A total of 506 patients (314 males; mean age 62 ± 9 years) referred for suspected CAD was enrolled. Among these, 325 patients underwent stress ECG or cardiac imaging to assess the presence of inducible myocardial ischemia and 436 patients underwent non-invasive computerized tomography or invasive coronary angiography to assess the presence of obstructive CAD. Clinical characteristics and blood samples were collected for each patient. RESULTS: In the whole population, 49.6% of patients were homozygous for the Glu298 genotype (Glu/Glu), 40.9% heterozygotes (Glu/Asp) and 9.5% homozygous for the 298Asp genotype (Asp/Asp). Obstructive CAD was documented in 178/436 (40.8%) patients undergoing coronary angiography while myocardial ischemia in 160/325 (49.2%) patients undergoing stress testing. Patients with eNOS Asp genotype (Glu/Asp + Asp/Asp) had no significant differences in clinical risk factors and in circulating markers. Independent predictors of obstructive CAD were age, gender, obesity, and low HDL-C. Independent predictors of myocardial ischemia were gender, obesity, low HDL-C and Asp genotype. In the subpopulation in which both stress tests and coronary angiography were performed, the Asp genotype remained associated with increased myocardial ischemia risk after adjustment for obstructive CAD. CONCLUSION: In this population, low-HDL cholesterol was the only cardiometabolic risk determinant of obstructive CAD. The eNOS Glu298Asp gene polymorphism was significantly associated with inducible myocardial ischemia independently of other risk factors and presence of obstructive CAD.

Acute-phase response following one-stage full-mouth versus quadrant non-surgical periodontal treatment in subjects with comorbid type 2 diabetes: A randomized clinical trial.

AIM: To compare the level of inflammatory markers and endothelial function 24 h (Day 1) and 90 days (Day 90) after conventional quadrant-wise scaling and root planing (Q-SRP) versus one-stage full-mouth SRP (FM-SRP) in patients affected by type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: Patients affected by periodontitis and T2DM were randomly allocated to receive FM-SRP or Q-SRP and followed up at Day 1 and Day 90. Serum samples, vital signs, and flow-mediated dilation (FMD) parameters were collected at baseline, Day 1, and Day 90. Periodontal variables were collected at baseline and Day 90. The primary outcome was the C-reactive protein (CRP) concentration at Day 1 after periodontal treatment. Student's t-test for independent samples was used for between-group comparisons (Mann-Whitney U test for non-normal data), while analysis of variance with post hoc Tukey tests (Kruskal-Wallis and Dunn tests for non-normal data) were used for intra-group comparisons. RESULTS: Forty subjects were included in the study. FM-SRP produced a significant increase in CRP and a significant reduction in FMD at Day 1 compared to Q-SRP (p < .05). The absolute change in HbA1c (mmol/mol) from baseline to Day 90 was significantly improved in the Q-SRP (ΔHbA1c = -1.59 [SD = 1.20]) compared to the FM-SRP group (ΔHbA1c = -0.8 [SD = 0.95]) (p = .04). CONCLUSIONS: FM-SRP triggers a robust acute-phase response at 24 h after treatment compared to Q-SRP. Such systemic acute perturbations may offset the beneficial systemic effects of periodontal treatment in terms of HbA1c reduction and improvement in endothelial function in T2DM subjects.

Multi-centric study for development and validation of a CT head rule for mild traumatic brain injury in direct oral anticoagulants: the HERO-M nomogram.

BACKGROUND: Nomograms are easy-to-handle clinical tools which can help in estimating the risk of adverse outcome in certain population. This multi-center study aims to create and validate a simple and usable clinical prediction nomogram for individual risk of post-traumatic Intracranial Hemorrhage (ICH) after Mild Traumatic Brain Injury (MTBI) in patients treated with Direct Oral Anticoagulants (DOACs). METHODS: From January 1, 2016 to December 31, 2019, all patients on DOACs evaluated for an MTBI in five Italian Emergency Departments were enrolled. A training set to develop the nomogram and a test set for validation were identified. The predictive ability of the nomogram was assessed using AUROC, calibration plot, and decision curve analysis. RESULTS: Of the 1425 patients in DOACs in the study cohort, 934 (65.5%) were included in the training set and 491 (34.5%) in the test set. Overall, the rate of post-traumatic ICH was 6.9% (7.0% training and 6.9% test set). In a multivariate analysis, major trauma dynamic (OR: 2.73, p = 0.016), post-traumatic loss of consciousness (OR: 3.78, p = 0.001), post-traumatic amnesia (OR: 4.15, p < 0.001), GCS < 15 (OR: 3.00, p < 0.001), visible trauma above the clavicles (OR: 3. 44, p < 0.001), a post-traumatic headache (OR: 2.71, p = 0.032), a previous history of neurosurgery (OR: 7.40, p < 0.001), and post-traumatic vomiting (OR: 3.94, p = 0.008) were independent risk factors for ICH. The nomogram demonstrated a good ability to predict the risk of ICH (AUROC: 0.803; CI95% 0.721-0.884), and its clinical application showed a net clinical benefit always superior to performing CT on all patients. CONCLUSION: The Hemorrhage Estimate Risk in Oral anticoagulation for Mild head trauma (HERO-M) nomogram was able to predict post-traumatic ICH and can be easily applied in the Emergency Department (ED).

Speckle tracking echocardiography in heart failure development and progression in patients with apneas.

Obstructive (OA) and central apneas (CA) are highly prevalent breathing disorders that have a negative impact on cardiac structure and function; while OA promote the development of progressive cardiac alterations that can eventually lead to heart failure (HF), CA are more prevalent once HF ensues. Therefore, the early identification of the deleterious effects of apneas on cardiac function, and the possibility to detect an initial cardiac dysfunction in patients with apneas become relevant. Speckle tracking echocardiography (STE) imaging has become increasingly recognized as a method for the early detection of diastolic and systolic dysfunction, by the evaluation of left atrial and left and right ventricular global longitudinal strain, respectively. A growing body of evidence is available on the alterations of STE in OA, while very little is known with regard to CA. In this review, we discuss the current knowledge and gap of evidence concerning apnea-related STE alterations in the development and progression of HF.

Risk of delayed intracranial haemorrhage after an initial negative CT in patients on DOACs with mild traumatic brain injury.

BACKGROUND: Repeat head CT in patients on direct oral anticoagulant therapy (DOACs) with minor traumatic brain injury (MTBI) after an initial CT scan without injury on arrival in the Emergency Department (ED) is a common clinical practice but is not based on clear evidence. AIM: To assess the incidence of delayed intracranial haemorrhage (ICH) in patients taking DOACs after an initial negative CT and the association of clinical and risk factors presented on patient arrival in the ED. METHODS: This retrospective multicentre observational study considered patients taking DOACs undergoing repeat CT after a first CT free of injury for the exclusion of delayed ICH after MTBI. Timing between trauma and first CT in the ED and pre- or post-trauma risk factors were analysed to assess a possible association with the risk of delayed ICH. RESULTS: A total of 1426 patients taking DOACs were evaluated in the ED for an MTBI. Of these, 68.3% (916/1426) underwent a repeat CT after an initial negative CT and 24 h of observation, with a rate of delayed ICH of 1.5% (14/916). Risk factors associated with the presence of a delayed ICH were post-traumatic loss of consciousness, post-traumatic amnesia and the presence of a risk factor when the patient presented to the ED within 8 h of the trauma. None of the patients with delayed ICH at 24-h repeat CT required neurosurgery or died within 30 days. CONCLUSIONS: Delayed ICH is an uncommon event at the 24-h control CT and does not affect patient outcome. Studying the timing and characteristics of the trauma may indicate patients who may benefit from more in-depth management.

"Decision tree analysis for assessing the risk of post-traumatic haemorrhage after mild traumatic brain injury in patients on oral anticoagulant therapy".

BACKGROUND: The presence of oral anticoagulant therapy (OAT) alone, regardless of patient condition, is an indication for CT imaging in patients with mild traumatic brain injury (MTBI). Currently, no specific clinical decision rules are available for OAT patients. The aim of the study was to identify which clinical risk factors easily identifiable at first ED evaluation may be associated with an increased risk of post-traumatic intracranial haemorrhage (ICH) in OAT patients who suffered an MTBI. METHODS: Three thousand fifty-four patients in OAT with MTBI from four Italian centers were retrospectively considered. A decision tree analysis using the classification and regression tree (CART) method was conducted to evaluate both the pre- and post-traumatic clinical risk factors most associated with the presence of post-traumatic ICH after MTBI and their possible role in determining the patient's risk. The decision tree analysis used all clinical risk factors identified at the first ED evaluation as input predictor variables. RESULTS: ICH following MTBI was present in 9.5% of patients (290/3054). The CART model created a decision tree using 5 risk factors, post-traumatic amnesia, post-traumatic transitory loss of consciousness, greater trauma dynamic, GCS less than 15, evidence of trauma above the clavicles, capable of stratifying patients into different increasing levels of ICH risk (from 2.5 to 61.4%). The absence of concussion and neurological alteration at admission appears to significantly reduce the possible presence of ICH. CONCLUSIONS: The machine-learning-based CART model identified distinct prognostic groups of patients with distinct outcomes according to on clinical risk factors. Decision trees can be useful as guidance in patient selection and risk stratification of patients in OAT with MTBI.

Efficacy of Ceftazidime-avibactam Plus Aztreonam in Patients With Bloodstream Infections Caused by Metallo-ß-lactamase-Producing Enterobacterales.

BACKGROUND: In vitro data support the use of combination of aztreonam (ATM) with ceftazidime-avibactam (CAZ-AVI), but clinical studies are lacking. The aim of our study was to compare the outcome of patients with bloodstream infections (BSIs) due to metallo-ß-lactamase (MBL)-producing Enterobacterales treated either with CAZ-AVI plus ATM or other active antibiotics (OAAs). METHODS: This was a prospective observational study including patients admitted to 3 hospitals in Italy and Greece. The primary outcome measure was 30-day all-cause mortality. Secondary outcomes were clinical failure at day 14 and length of stay after BSI diagnosis. Cox regression analysis including a propensity score (PS) for receiving CAZ-AVI + ATM was performed to evaluate primary and secondary outcomes. A PS-based matched analysis was also performed. RESULTS: We enrolled 102 patients with BSI; 82 had infections caused by NDM-producing (79 Klebsiella pneumoniae and 3 Escherichia coli) and 20 by VIM-producing (14 K. pneumoniae, 5 Enterobacter species, 1 Morganella morganii) strains. The 30-day mortality rate was 19.2% in the CAZ-AVI + ATM group vs 44% in the OAA group (P = .007). The PS-adjusted analysis showed that the use of CAZ-AVI + ATM was associated with lower 30-day mortality (hazard ratio [HR], 0.37 [95% confidence interval {CI}, .13-.74]; P = .01), lower clinical failure at day 14 (HR, 0.30 [95% CI, .14-.65]; P = .002), and shorter length of stay (subdistributional HR, 0.49 [95% CI, .30-.82]; P = .007). The PS-matched analysis confirmed these findings. CONCLUSIONS: The CAZ-AVI + ATM combination offers a therapeutic advantage compared to OAAs for patients with BSI due to MBL-producing Enterobacterales. Further studies are warranted.

Predictors of hospital-acquired bacterial and fungal superinfections in COVID-19: a prospective observational study.

BACKGROUND: Bacterial and fungal superinfections may complicate the course of hospitalized patients with COVID-19. OBJECTIVES: To identify predictors of superinfections in COVID-19. METHODS: Prospective, observational study including patients with COVID-19 consecutively admitted to the University Hospital of Pisa, Italy, between 4 March and 30 April 2020. Clinical data and outcomes were registered. Superinfection was defined as a bacterial or fungal infection that occurred ≥48 h after hospital admission. A multivariate analysis was performed to identify factors independently associated with superinfections. RESULTS: Overall, 315 patients with COVID-19 were hospitalized and 109 episodes of superinfections were documented in 69 (21.9%) patients. The median time from admission to superinfection was 19 days (range 11-29.75). Superinfections were caused by Enterobacterales (44.9%), non-fermenting Gram-negative bacilli (15.6%), Gram-positive bacteria (15.6%) and fungi (5.5%). Polymicrobial infections accounted for 18.3%. Predictors of superinfections were: intestinal colonization by carbapenem-resistant Enterobacterales (OR 16.03, 95% CI 6.5-39.5, P < 0.001); invasive mechanical ventilation (OR 5.6, 95% CI 2.4-13.1, P < 0.001); immunomodulatory agents (tocilizumab/baricitinib) (OR 5.09, 95% CI 2.2-11.8, P < 0.001); C-reactive protein on admission >7 mg/dl (OR 3.59, 95% CI 1.7-7.7, P = 0.001); and previous treatment with piperacillin/tazobactam (OR 2.85, 95% CI 1.1-7.2, P = 0.028). Length of hospital stay was longer in patients who developed superinfections ompared with those who did not (30 versus 11 days, P < 0.001), while mortality rates were similar (18.8% versus 23.2%, P = 0.445). CONCLUSIONS: The risk of bacterial and fungal superinfections in COVID-19 is consistent. Patients who need empiric broad-spectrum antibiotics and immunomodulant drugs should be carefully selected. Infection control rules must be reinforced.

Recognition in Emergency Department of Septic Patients at Higher Risk of Death: Beware of Patients without Fever.

Background and Objectives: Chances of surviving sepsis increase markedly upon prompt diagnosis and treatment. As most sepsis cases initially show-up in the Emergency Department (ED), early recognition of a septic patient has a pivotal role in sepsis management, despite the lack of precise guidelines. The aim of this study was to identify the most accurate predictors of in-hospital mortality outcome in septic patients admitted to the ED. Materials and Methods: We compared 651 patients admitted to ED for sepsis (cases) with 363 controls (non-septic patients). A Bayesian mean multivariate logistic regression model was performed in order to identify the most accurate predictors of in-hospital mortality outcomes in septic patients. Results: Septic shock and positive qSOFA were identified as risk factors for in-hospital mortality among septic patients admitted to the ED. Hyperthermia was a protective factor for in-hospital mortality. Conclusions: Physicians should bear in mind that fever is not a criterium for defining sepsis; according to our results, absence of fever upon presentation might be indicative of greater severity and diagnosis of sepsis should not be delayed.

May Measurement Month 2018: an analysis of blood pressure screening results from Italy.

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.

Expert consensus and evidence-based recommendations for the assessment of flow-mediated dilation in humans.

Endothelial dysfunction is involved in the development of atherosclerosis, which precedes asymptomatic structural vascular alterations as well as clinical manifestations of cardiovascular disease (CVD). Endothelial function can be assessed non-invasively using the flow-mediated dilation (FMD) technique. Flow-mediated dilation represents an endothelium-dependent, largely nitric oxide (NO)-mediated dilatation of conduit arteries in response to an imposed increase in blood flow and shear stress. Flow-mediated dilation is affected by cardiovascular (CV) risk factors, relates to coronary artery endothelial function, and independently predicts CVD outcome. Accordingly, FMD is a tool for examining the pathophysiology of CVD and possibly identifying subjects at increased risk for future CV events. Moreover, it has merit in examining the acute and long-term impact of physiological and pharmacological interventions in humans. Despite concerns about its reproducibility, the available evidence shows that highly reliable FMD measurements can be achieved when specialized laboratories follow standardized protocols. For this purpose, updated expert consensus guidelines for the performance of FMD are presented, which are based on critical appraisal of novel technical approaches, development of analysis software, and studies exploring the physiological principles underlying the technique. Uniformity in FMD performance will (i) improve comparability between studies, (ii) contribute to construction of reference values, and (iii) offer an easy accessible and early marker of atherosclerosis that could complement clinical symptoms of structural arterial disease and facilitate early diagnosis and prediction of CVD outcomes.

Olfactory evaluation in Mild Cognitive Impairment: correlation with neurocognitive performance and endothelial function.

Mild Cognitive Impairment (MCI) is an intermediate condition between normal aging and dementia, associated with an increased risk of progression into the latter within months or years. Olfactory impairment, a well-known biomarker for neurodegeneration, might be present in the condition early, possibly representing a signal for future pathological onset. Our study aimed at evaluating olfactory function in MCI and healthy controls in relation to neurocognitive performance and endothelial function. A total of 85 individuals with MCI and 41 healthy controls, matched for age and gender, were recruited. Olfactory function was assessed by Sniffin' Sticks Extended Test (Burghart, Medizintechnik, GmbH, Wedel, Germany). A comprehensive neurocognitive assessment was performed. Endothelial function was assessed by flow-mediated dilation (FMD) of the brachial artery by ultrasound. MCI individuals showed an impaired olfactory function compared to controls. The overall olfactory score is able to predict MCI with a good sensitivity and specificity (70.3 and 77.4% respectively). In MCI, olfactory identification score is correlated with a number of neurocognitive abilities, including overall cognitive status, dementia rating, immediate and delayed memory, visuospatial ability and verbal fluency. FMD was reduced in MCI (2.90 ± 2.15 vs. 3.66 ± 1.96%, P = 0.016) and was positively associated with olfactory identification score (ρs =0.219, P = 0.025). The association remained significant after controlling for age, gender, and smoking. In conclusion, olfactory evaluation is able to discriminate between MCI and healthy individuals. Systemic vascular dysfunction might be involved, at least indirectly, in olfactory dysfunction in MCI.

Dapagliflozin acutely improves endothelial dysfunction, reduces aortic stiffness and renal resistive index in type 2 diabetic patients: a pilot study.

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors reduce blood pressure (BP) and renal and cardiovascular events in patients with type 2 diabetes through not fully elucidated mechanisms. Aim of this study was to investigate whether dapagliflozin is able to acutely modify systemic and renal vascular function, as well as putative mechanisms. METHODS: Neuro-hormonal and vascular variables, together with 24 h diuresis, urinary sodium, glucose, isoprostanes and free-water clearance were assessed before and after a 2-day treatment with dapagliflozin 10 mg QD in sixteen type 2 diabetic patients; data were compared with those obtained in ten patients treated with hydrochlorothiazide 12.5 mg QD. Brachial artery endothelium-dependent and independent vasodilation (by flow-mediated dilation) and pulse wave velocity were assessed. Renal resistive index was obtained at rest and after glyceryl trinitrate administration. Differences were analysed by repeated measures ANOVA, considering treatment as between factor and time as within factor; Bonferroni post hoc comparison test was also used. RESULTS: Dapagliflozin decreased systolic BP and induced an increase in 24 h diuresis to a similar extent of hydrochlorothiazide; 24 h urinary glucose and serum magnesium were also increased. 24 h urinary sodium and fasting blood glucose were unchanged. Oxidative stress was reduced, as by a decline in urinary isoprostanes. Flow-mediated dilation was significantly increased (2.8 ± 2.2 to 4.0 ± 2.1%, p < 0.05), and pulse-wave-velocity was reduced (10.1 ± 1.6 to 8.9 ± 1.6 m/s, p < 0.05), even after correction for mean BP. Renal resistive index was reduced (0.62 ± 0.04 to 0.59 ± 0.05, p < 0.05). These vascular modifications were not observed in hydrochlorothiazide-treated individuals. CONCLUSIONS: An acute treatment with dapagliflozin significantly improves systemic endothelial function, arterial stiffness and renal resistive index; this effect is independent of changes in BP and occurs in the presence of stable natriuresis, suggesting a fast, direct beneficial effect on the vasculature, possibly mediated by oxidative stress reduction.

Carotid-Ventricular Coupling During Exercise: A Pilot Study.

OBJECTIVES: To evaluate carotid elasticity and left ventricular elastance during a graded bicycle semisupine exercise test in patients with known or suspected coronary artery disease and compare them with a control group of healthy young volunteers. METHODS: Thirty-six elderly patients and 18 young healthy volunteers were recruited. The right carotid diameter was estimated by an automatic system applied to B-mode sonographic sequences, central mean blood and pulse pressures by radial artery tonometry, and cardiac volumes by 2-dimensional transthoracic echocardiography; from these direct measurements, the carotid cross-sectional distensibility coefficient and left ventricular elastance index were obtained. Analyses were performed at rest, at peak stress, and during the recovery phase. RESULTS: The elderly patients included 20 men (mean age ± SD, 61 ± 8 years); the volunteers included 9 men (mean age, 34 ± 3 years). The mean blood pressure (at rest: patients, 97 ± 7 mm Hg; controls, 93 ± 9 mm Hg; not significant) increased similarly in both groups during exercise and decreased during the recovery phase. The diameter was higher in patients than controls (7.5 ± 1.1 versus 6.2 ± 0.5 mm) and increased significantly with exercise only in the latter group (at peak: 6.5 ± 0.6 mm; P < .05). The distensibility coefficient and elastance index were lower in patients than controls during the test phases [at rest: 24.5 ± 10.2 versus 60.8 ± 21.3 × 10(-3)/kPa and 3.6 ± 1.4 versus 1.6 ± 0.8 mm Hg/(mL/m(2))] and mostly changed in the controls, showing a decreased distensibility coefficient (peak: 40.6 ± 15.1 × 10(-3)/kPa) and an increased elastance index [peak: 5.9 ± 2.8 mm Hg/(mL/m(2))]. CONCLUSIONS: In older patients with multiple cardiovascular risk factors or established coronary artery disease, an abnormal carotid-ventricular adaptation to exercise was observed when compared to young healthy individuals.

Birth weight and arterial hypertension.

PURPOSE OF REVIEW: To provide an overview of available evidence of the relationship between birth weight and future hypertension development. RECENT FINDINGS: Fetal programming plays a significant role in future hypertension. Both low and high birth weight are able to influence weight gain during childhood, adult weight and blood pressure values during childhood and adulthood. To date, an increasing amount of evidence is available especially for the relationship between low birth weight and hypertension, supported also by pathophysiological studies. SUMMARY: In the era of personalized medicine, the possibility to reduce cardiovascular risk before or soon after birth and intervene on risk factors during childhood is appealing and promising for the future.

Intima media thickness, pulse wave velocity, and flow mediated dilation.

The identification of vascular alterations at the sub-clinical, asymptomatic stages are potentially useful for screening, prevention and improvement of cardiovascular risk stratification beyond classical risk factors.Increased intima-media thickness of the common carotid artery is a well-known marker of early atherosclerosis, which significantly correlates with the development of cardiovascular diseases. More recently, other vascular parameters evaluating both structural and functional arterial proprieties of peripheral arteries have been introduced, for cardiovascular risk stratification and as surrogate endpoints in clinical trials. Increased arterial stiffness, which can be detected by applanation tonometry as carotid-femoral pulse wave velocity, has been shown to predict future cardiovascular events and to significantly improve risk stratification.Finally, earlier vascular abnormalities such as endothelial dysfunction in the peripheral arteries, detected as reduced flow-mediated dilation of the brachial artery, are useful in the research setting and as surrogate endpoints in clinical trials and have also been suggested for their possible clinical use in the future.This manuscript will briefly review clinical evidence supporting the use of these different vascular markers for cardiovascular risk stratification, focusing on the correct methodology, which is a crucial issue to address in order to promote their use in future for routine clinical practice.

Predictive role of renal resistive index for clinical outcome after revascularization in hypertensive patients with atherosclerotic renal artery stenosis: a monocentric observational study.

BACKGROUND: The present study evaluated the predictive value of renal resistive index (RI) for renal function and blood pressure (BP) outcome in hypertensive patients with unilateral atherosclerotic renal artery stenosis submitted to successful revascularization. METHODS: In 158 hypertensive patients with atherosclerotic renal artery stenosis RI was acquired. Twelve months after revascularization, they were classified on the basis of renal function and BP outcome as benefit (BP < 140/90 mmHg or diastolic BP reduction > 15 mmHg with the same of reduced drugs; decrease in glomerular filtration rate > 20%), or failure. RESULTS: Regarding renal function outcome, RI in the stenotic and in the contralateral kidney were significantly higher in patients with failure (n = 20) than in those with benefit (0.72 ± 0.11 vs 0.61 ± 0.11 and 0.76 ± 0.08 vs 0.66 ± 0.09, p < 0.05). Among different cutpoints generated, RI in the contralateral kidney >0.73 provided the largest area under the curve (0.77), and the highest sensitivity (80%) and specificity (72%). In the multivariate logistic regression analysis, RI in the contralateral kidney >0.73 was an independent predictor of a failure in renal function outcome.Regarding BP outcome, patients with no benefit from revascularization (n = 60) had similar RI in the stenotic and contralateral kidney (p = ns), but presented higher pulse pressure, albuminuria and hypertension duration in comparison to patients with improved BP control. CONCLUSIONS: RI in the contralateral kidney is an independent predictor of renal function outcome after successful revascularization in hypertensive patients with unilateral atherosclerotic renal artery stenosis, whereas it is not able to predict blood pressure outcome.

Non-invasive assessment of carotid PWV via accelerometric sensors: validation of a new device and comparison with established techniques.

PURPOSE: Carotid pulse wave velocity (PWV) is considered as a surrogate marker for carotid stiffness and its assessment is increasingly being used in clinical practice. However, at the moment, its estimation needs specific equipment and a moderate level of technical expertise; moreover, it is based on a mathematical model. The aim of this study was to validate a new system for non-invasive and model-free carotid PWV assessment based on accelerometric sensors by comparison with currently used techniques. METHODS: Accelerometric PWV (accPWV) values were obtained in 97 volunteers free of cardiovascular disease (age 24-85 years) and compared with standard ultrasound-based carotid stiffness parameters, such as carotid PWV (cPWV), relative distension (relD) and distensibility coefficient (DC). Moreover, the comparison between accPWV measurements and carotid-femoral PWV (cfPWV) was performed. RESULTS: Accelerometric PWV evaluations showed a significant correlation with cPWV measurements (R = 0.67), relD values (R = 0.66) and DC assessments (R = 0.64). These values were also significantly correlated with cfPWV evaluations (R = 0.46). In addition, the first attempt success rate was equal to 76.8 %. CONCLUSIONS: The accelerometric system allows a simple and quick local carotid stiffness evaluation and the values obtained with this system are significantly correlated with known carotid stiffness biomarkers. Therefore, the presented device could provide a concrete opportunity for an easy carotid stiffness evaluation even in clinical practice.

Reversal or Repletion Treatment Strategies and Outcomes of Patients With Major Bleeding Events Managed in the Emergency Department: Large Real-Life Investigation in the Northwestern Healthcare District of Tuscany.

OBJECTIVE: To verify the incidence of bleeding events in patients on ongoing anticoagulant treatment in the real world and compare the results of different reversal or repletion strategies currently available for pharmacological treatment. METHODS: Patients managed in the emergency department (ED) with major bleeding events, on ongoing anticoagulation were stratified according to bleeding site and reversal or repletion therapy with andexanet alfa (ADX), idarucizumab (IDA), prothrombin complex concentrate (PCC), and vitamin K (Vit-K). ENDPOINT: Death at 30 days was compared in the subgroups with cerebral hemorrhage (CH) and gastrointestinal (GI) bleeding. RESULTS: Of the 809,397 visits in the years 2022-2023 at 6 EDs in the northwestern health district of Tuscany, 5372 patients with bleeding events were considered; 3740 were excluded due to minor bleeding or propensity score matching. Of the remaining 1632 patients with major bleeding, 548 on ongoing anticoagulation were enrolled; 334 received reversal or repletion agents. Patients with CH (n = 176) and GI bleeding (n = 108) represented the primary analysis cohorts in the study's strategic treatment assessment. Overall, 30-day survival of patients on ongoing aFXa treatment receiving on-label ADX versus off-label PCC showed a relative increase of 71%, while 30-day survival of patients on ongoing aFII receiving on-label IDA versus off-label PCC showed a relative increase of 30%; no substantial difference was found when comparing on-label PCC combined with Vit-K versus off-label Vit-K alone. Indeed, patients undergoing on-label ADX or IDA showed a statistically significant difference over off-label PCC (ADX vs. PCC: n = 15, events = 4, mean ± SD 82.50 ± 18.9, vs. 49, 13, 98.82 ± 27, respectively; analysis of variance [ANOVA] variance 8627; P < 0.001; posthoc test diff 32, 95% confidence interval: 28-35; P < 001; IDA vs. PCC: 20, 5, 32.29 ± 15.0 vs. 2, 1, 28.00 ± 0.0, respectively; ANOVA 1484; P < 0.001; posthoc test -29, -29 -29, respectively; P = n.d.). On-label PCC combined with Vit-K showed overall a slight statistically significant difference versus off-label Vit-K alone (52, 16, 100.58 ± 22.6 vs. 53, 11, 154.62 ± 29.8, respectively; ANOVA 310; P < 0.02; posthoc test 4, 0.7-7.2, respectively; P < 0.02). Data were confirmed in the group of patients with CH (ADX vs. PCC: n = 13, events = 3, mean ± SD 91.55 ± 18.6 vs. 78, 21, 108.91 ± 20.9, respectively; ANOVA variance 10,091, F = 261; P < 0.001; posthoc difference test 36, 95% confidence interval: 30-41; P < 0.001; IDA vs. PCC: 10, 2, 4.50 ± 2.5 vs. 78, 21, 108.91 ± 20.9, respectively; ANOVA 16,876,303, respectively; P < 0.001; posthoc test 41, 34-47, respectively; P < 0.001). On-label PCC combined with Vit-K showed an overall slight statistically significant difference compared with off-label Vit-K alone (P < 0.01 and P < 0.001 in the subgroups of CH and GI bleeding). CONCLUSIONS: Patients undergoing specific reversal therapy with on-label ADX or IDA, when treated with aFXa or aFII anticoagulants, respectively, showed statistically elevated differences in 30-day death compared with off-label repletion therapy with PCC. Overall, 30-day survival of patients on ongoing aFXa or aFII receiving on-label reversal therapy with ADX or IDA compared with off-label PCC repletion agents showed an increase of 71% and 30%, respectively.

Trauma Center model application in the University Hospital of Pisa: a single-center comparative study.

The Trauma Center, Hub, is a highly specialized hospital indicated for complex major trauma management after stabilization at a 1st level hospital, Spoke. Although in the United States this organization demonstrated its effectiveness in mortality, in the Italian context, data available are limited. On 30 September 2018, the University Hospital of Pisa formalized the introduction of the Trauma Center, optimizing Emergency Department (ED) organization to guarantee the highest standard of care. The aim of this study was to demonstrate that the new model led better outcomes. We conducted a comparative retrospective study on 1154 major traumas over 24 months: the first 12 months (576 patients) correspond to the period before Trauma Center introduction, and the following 12 (457 patients) to the subsequent period. Results showed increase in greater dynamics and primary centralization by helicopter (p < 0.001, p 0.006). A systematic assessment with ABCDE algorithm was performed in a higher number of patients in the most recent period, from 38.4% to 80.3% (p < 0.001). Focused Assessment with Sonography for Trauma (FAST) performed by the emergency doctor increased after Trauma Center introduction, p value < 0.001. The data show an increase of ATLS certification among staff from 51.9 to 71.4% and a reduction in early and late mortality after the Trauma Center introduction (p value 0.05 and < 0.01). Fewer patients required intensive and surgical treatments, with a shorter hospital stay. The results demonstrate the advantage in terms of outcomes in the organization of the Trauma Center in the Italian context.