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Background and aimsA prothrombotic state was demonstrated in patients with Cushing’s syndrome and is involved in the development and progression of cardiovascular and renal damage in hypertensive patients. This study was designed to examine the relationships between cortisol secretion and the hemostatic and fibrinolytic systems in hypertension.MethodsIn 149 middle-aged, nondiabetic, essential hypertensive patients free of cardiovascular and renal complications, we measured hemostatic markers that express the spontaneous activation of the coagulation and fibrinolytic systems and assessed daily cortisol levels (8 AM, 3 PM, 12 AM; area under the curve, AUC-cortisol) together with the cortisol response to dexamethasone overnight suppression (DST-cortisol).ResultsPlasma levels of D-dimer (D-dim), prothrombin fragment 1 + 2 (F1 + 2), and von Willebrand factor (vWF) were progressively and significantly higher across tertiles of AUC-cortisol and DST-cortisol, whereas no differences were observed in fibrinogen, tissue plasminogen activator, plasminogen activator inhibitor-1, antithrombin III, protein C, and protein S. D-dim, F1 + 2, and vWF were significantly and directly correlated with age and both AUC-cortisol and DST-cortisol. Multivariate regression analysis showed that both AUC-cortisol and DST-cortisol were related to plasma D-dim, F1 + 2, and vWF independently of age, body mass index, blood pressure, and renal function.ConclusionGreater daily cortisol profile and cortisol response to overnight suppression are independently associated with a prothrombotic state in hypertensive patients and might contribute to the development of organ damage and higher risk of cardiovascular complications.

Abstract Background Pulmonary embolism (PE) without overt deep vein thrombosis (DVT) was common in hospitalized coronavirus-induced disease (COVID)-19 patients and represented a diagnostic, prognostic, and therapeutic challenge. The aim of this study was to analyze the prognostic role of PE on mortality and the preventive effect of heparin on PE and mortality in unvaccinated COVID-19 patients without overt DVT. Methods Data from 401 unvaccinated patients (age 68 ± 13 years, 33% females) consecutively admitted to the intensive care unit or the medical ward were included in a retrospective longitudinal study. PE was documented by computed tomography scan and DVT by compressive venous ultrasound. The effect of PE diagnosis and any heparin use on in-hospital death (primary outcome) was analyzed by a classical survival model. The preventive effect of heparin on either PE diagnosis or in-hospital death (secondary outcome) was analyzed by a multi-state model after having reclassified patients who started heparin after PE diagnosis as not treated. Results Median follow-up time was 8 days (range 1–40 days). PE cumulative incidence and in-hospital mortality were 27% and 20%, respectively. PE was predicted by increased D-dimer levels and COVID-19 severity. Independent predictors of in-hospital death were age (hazards ratio (HR) 1.05, 95% confidence interval (CI) 1.03–1.08, p

Subclinical carotid artery disease anticipates major cardiovascular events, and previous studies show that low vitamin D levels are associated with arterial stiffening in hypertension. The aim of the study was to examine the relationship of 25-hydroxyvitamin D [25(OH)D] levels with subclinical carotid disease in hypertensive patients. In 223 middle-aged, nondiabetic, primary hypertensive patients free of major cardiovascular and renal complications, we measured 25(OH)D and parathyroid hormone (PTH) and assessed subclinical carotid arteries changes by B-mode ultrasonography. The carotid intima-media thickness (IMT) and presence of plaques were assessed together with measurements of indexes of carotid artery distensibility (coefficient of distensibility) or stiffening (Young's elastic modulus; β-stiffness). Lower 25(OH)D levels were associated with older age (p < 0.001), longer duration of hypertension (p = 0.019), higher fasting plasma glucose (p = 0.037), and insulin (p = 0.044), Homeostatic Model Assessment (HOMA) index (p = 0.044), and PTH (p < 0.001). Insufficient and deficient 25(OH)D were associated with progressively greater carotid IMT (p < 0.001), frequency of carotid plaques (p = 0.026), Young's elastic modulus (p = 0.002), and β-stiffness (p < 0.001), and progressively lower carotid coefficient of distensibility (p < 0.001). Serum levels of 25(OH)D were negatively correlated with age (p < 0.001), duration of hypertension (p = 0.006), fasting glucose (p < 0.001), HOMA index (p = 0.032), PTH (p < 0.001), carotid IMT (p < 0.001), Young's elastic modulus (p = 0.025), and β-stiffness (p < 0.001), and positively related with carotid coefficient of distensibility (p < 0.001). Multivariate regression analysis showed that both higher carotid IMT (p = 0.004) and lower coefficient of distensibility (p = 0.002) were related to lower 25(OH)D independent of age, severity, and duration of hypertension and metabolic variables. In conclusion, deficiency/insufficiency of 25(OH)D independently predicts subclinical carotid disease in uncomplicated, middle-aged, hypertensive patients and might predispose these patients to major cardiovascular complications. [ABSTRACT FROM AUTHOR]

Abstract Background Sequential Organ Failure Assessment (SOFA) and other illness prognostic scores predict adverse outcomes in critical patients. Their validation as a decision-making tool in the emergency department (ED) of secondary hospitals is not well established. The aim of this study was to compare SOFA, NEWS2, APACHE II, and SAPS II scores as predictors of adverse outcomes and decision-making tool in ED. Methods Data of 121 patients (age 73 ± 10 years, 58% males, Charlson Comorbidity Index 5.7 ± 2.1) with a confirmed sepsis were included in a retrospective study between January 2017 and February 2020. Scores were computed within the first 24 h after admission. Primary outcome was the occurrence of either in-hospital death or mechanical ventilation within 7 days. Secondary outcome was 30-day all-cause mortality. Results Patients older than 64 years (elderly) represent 82% of sample. Primary and secondary outcomes occurred in 40 and 44%, respectively. Median 30-day survival time of dead patients was 4 days (interquartile range 1–11). The best predictive score based on the area under the receiver operating curve (AUROC) was SAPS II (0.823, 95% confidence interval, CI, 0.744–0.902), followed by APACHE II (0.762, 95% CI 0.673–0.850), NEWS2 (0.708, 95% CI 0.616–0.800), and SOFA (0.650, 95% CI 0.548–0.751). SAPS II cut-off of 49 showed the lowest false-positive rate (12, 95% CI 5–20) and the highest positive predictive value (80, 95% CI 68–92), whereas NEWS2 cut-off of 7 showed the lowest false-negative rate (10, 95% CI 2–19) and the highest negative predictive value (86, 95% CI 74–97). By combining NEWS2 and SAPS II cut-offs, we accurately classified 64% of patients. In survival analysis, SAPS II cut-off showed the highest difference in 30-day mortality (Hazards Ratio, HR, 5.24, 95% CI 2.99–9.21, P

Background and aimsPast studies reported a significant contribution of a prothrombotic state to the development and progression of target organ damage in hypertensive patients. Stiffening of arterial vessels is associated with aging and hypertension, and additional factors could contribute to this process. This study was designed to examine the relationships between arterial stiffening and the hemostatic and fibrinolytic system.MethodsIn 128 middle-aged, nondiabetic, essential hypertensive patients without major cardiovascular and renal complications, we measured coagulation markers that express the spontaneous activation of the hemostatic and fibrinolytic system and assessed stiffness of the arterial tree by measurement of the carotid/femoral pulse wave velocity (cfPWV) and pulse wave analysis with calculation of the brachial augmentation index (AIx).ResultsLevels of fibrinogen (FBG), D-dimer (D-d), and plasminogen activator-inhibitor 1 (PAI-1) were significantly higher in patients with PWV and AIx above the median of the distribution. FBG, D-d, and PAI-1 were significantly and directly related with both cfPWV and AIx, and multivariate regression analysis indicated that the relationships of D-d and PAI-1 with both cfPWV and AIx and of FBG with AIx, were independent of age, body mass index, severity and duration of hypertension, use of antihypertensive drugs, blood glucose, and plasma lipids.ConclusionIn middle-aged, uncomplicated, nondiabetic patients with essential hypertension, spontaneous activation of plasma hemostatic cascade and impaired fibrinolysis is significantly and independently associated with stiffening of the arterial tree.

Seismic events that have occurred in Italy in recent decades have shown the significant vulnerability of the Italian building stock. In particular, residential masonry buildings have suffered serious damage, highlighting the need to plan effective mitigation strategies as soon as possible. In this context, this study aims to evaluate the effectiveness of possible retrofit interventions for masonry buildings. Fragility curves of macro-classes of residential masonry buildings have been developed in both as-built and retrofitted conditions within the DPC-ReLUIS agreement (Department of Civil Protection—Network of University Laboratories for Earthquake Engineering). In particular, three sets of fragility curves, developed by the University of Padova (UniPD) and the University of Genova (UniGEa and UniGEb) are discussed and compared herein. The three models show similar estimates of the expected structural improvements for the examined retrofit interventions when applied to the building macro-classes, although some differences, due to the different analysis approaches, can be observed.

Background and aimsCardiac structural and functional changes have been demonstrated in patients with non-alcoholic fatty liver disease (NAFLD). Because of the frequent association of NAFLD with hypertension, we aimed to examine the relationship of liver steatosis with left ventricular (LV) changes in patients with hypertension.Materials and methodsIn a cross-sectional study, we included 360 untreated, essential hypertensive patients who were free of major cardiovascular and renal complications. Liver steatosis was assessed by three different biochemical scores (NAFLD Liver Fat Score, LFS; Fatty Liver Index, FLI; Hepatic Steatosis Index, HSI). Echocardiography was performed with standard B-mode and tissue-Doppler imaging.ResultsLV hypertrophy was present in 19.4% and LV diastolic dysfunction in 49.2% of patients who had significantly higher body mass index (BMI), blood pressure (BP), and homeostatic model assessment (HOMA) index and higher frequency of the metabolic syndrome and liver steatosis that was defined by presence of 2 or more positive scores. LV mass index increased progressively across patients who had none, 1, or 2 or more liver steatosis scores, with associated progressive worsening of LV diastolic function. LV mass index was significantly and positively correlated with age, BMI, BP, HOMA-index, LFS, and HSI. Logistic regression analysis showed that age, BP, and liver steatosis scores independently predicted LV hypertrophy and diastolic dysfunction. Liver steatosis independently predicted LV dysfunction but not LV hypertrophy even after inclusion in analysis of the HOMA-index.ConclusionNAFLD is associated with LV hypertrophy and diastolic dysfunction in untreated patients with hypertension. In hypertension, NAFLD could contribute to LV diastolic dysfunction with mechanisms unrelated to insulin resistance.

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Aims: The revolution in the therapeutic approach to type 2 diabetes (T2D) requires a rethinking of the positioning of basal insulin (BI) therapy. Given the considerable number of open questions, a group of experts was convened with the aim of providing, through a Delphi consensus method, practical guidance for doctors. Methods: A group of 6 experts developed a series of 29 statements on: the role of metabolic control in light of the most recent guidelines; BI intensification strategies: (1) add-on versus switch; (2) inertia in starting and titrating; (3) free versus fixed ratio combination; basal-bolus intensification and de-intensification strategies; second generation analogues of BI (2BI). A panel of 31 diabetologists, by accessing a dedicated website, assigned each statement a relevance score on a 9-point scale. The RAND/UCLA Appropriateness Method was adopted to assess the existence of disagreement among participants. Results: Panelists showed agreement for all 29 statements, of which 26 were considered relevant, one was considered not relevant and two were of uncertain relevance. Panelists agreed that the availability of new classes of drugs often allows the postponement of BI and the simplification of therapy. It remains essential to promptly initiate and titrate BI when required. BI should always, unless contraindicated, be started in addition to, and not as a replacement, for ongoing treatments with cardiorenal benefits. 2BIs should be preferred for their pharmacological profile, greater ease of self-titration and flexibility of administration. Conclusion: In a continuously evolving scenario, BI therapy still represents an important option in the management of T2D patients. [ABSTRACT FROM AUTHOR]

Recent Italian earthquakes have shown the high seismic vulnerability of pallet racking systems. In the down-aisle direction and in the absence of bracing systems, these structures are very flexible moment-resisting frames. Instead, in the cross-aisle direction they consist of slender trusses, stiffened by various bracing systems; the latter, although necessary for lateral stability, attract significant seismic accelerations, which can cause the stored goods to fall, posing a threat to human safety. To reduce this risk while increasing the rack structural performance, some mitigation systems were proposed, based on specific base-isolation or dissipation devices. In this paper, an innovative passive control system is investigated, i.e., the Load-Level Isolation System (LLIS), which consists of applying isolators to the load level to control the movement of pallets in the cross-aisle direction. The LLIS is based on the Tuned Mass Damper (TMD) strategy and exploits the high payload of these structures. Among the major uncertainties of this system are the amount of isolated mass and its position within the structure. Therefore, for a case study rack, the LLIS parameters (isolation stiffness and damping ratio) are optimized for various arrangements of this system, considering cases with one or two isolated levels. The applied optimization procedure is an extension of the classical TMD approaches. The effectiveness of the optimized LLISs is then investigated through bidirectional Time-History analyses on 3D Finite Element rack models. The results show that using the LLIS, even on a single load-level, can greatly reduce the upright stresses and the cross-aisle displacements and accelerations, and that the optimal position of the LLIS is in the upper part of the rack.

IntroductionStress hyperglycemia is a frequent finding in patients with COVID-19 infection and could affect the outcome of disease. Cytokines released in response to infection could have adverse effects on insulin sensitivity and pancreatic beta-cell function. The aim of the study was to examine the relationships of stress hyperglycemia with cytokines and clinical outcomes in hospitalized patients with COVID-19.MethodsIn a cross-sectional analysis of 150 patients hospitalized for COVID-19 infection who were included in the GIRA-COVID database, we identified patients with stress hyperglycemia by calculation of the Stress Hyperglycemia Ratio (SHR) and use of a cut-off of 1.14. Plasma levels of cytokines principally involved in COVID-19 infection-related cytokine storm were measured. Outcome variables were use of mechanical ventilation and death within 60 days from hospital admission.ResultsPatients with SHR > 1.14 had significantly higher plasma insulin, HOMA-index, and levels of interleukin-10 (IL-10), interleukin-10/tumor necrosis factor-a ratio (IL-10/TNF-α), and CXC motif chemokine ligand 10 (CXCL10) than patients with SHR ≤ 1.14. IL-10, IL-10/TNF-α ratio, CXCL10, and IFN-γ were significantly and directly related with SHR in univariate analysis and multivariate logistic regression models showed that IL-10, IL-10/TNF-α ratio, and CXCL10 were independently associated with SHR>1.14. In a multivariate logistic model, stress hyperglycemia predicted use of mechanical ventilation (OR 2.453; CI 1.078–6.012) and death (OR 2.281; CI 1.049–7.369) independently of diabetes and other major confounders.ConclusionsIn patients hospitalized for COVID-19 infection, stress hyperglycemia is associated with worse clinical outcomes and is independently related to levels of cytokines that might impair glucose homeostasis.