Single session cross-frequency bifocal tACS modulates visual motion network activity in young healthy population and stroke patients.

BACKGROUND: Phase synchronization over long distances underlies inter-areal communication and importantly, modulates the flow of information processing to adjust to cognitive demands. OBJECTIVE: This study investigates the impact of single-session, cross-frequency (Alpha-Gamma) bifocal transcranial alternating current stimulation (cf-tACS) to the cortical visual motion network on inter-areal coupling between the primary visual cortex (V1) and the medio-temporal area (MT) and on motion direction discrimination. METHODS: Based on the well-established phase-amplitude coupling (PAC) mechanism driving information processing in the visual system, we designed a novel directionally tuned cf-tACS protocol. Directionality of information flow was inferred from the area receiving low-frequency tACS (e.g., V1) projecting onto the area receiving high-frequency tACS (e.g., MT), in this case, promoting bottom-up information flow (Forward-tACS). The control condition promoted the opposite top-down connection (from MT to V1, called Backward-tACS), both compared to a Sham-tACS condition. Task performance and EEG activity were recorded from 45 young healthy subjects. An additional cohort of 16 stroke patients with occipital lesions and impairing visual processing was measured to assess the influence of a V1 lesion on the modulation of V1-MT coupling. RESULTS: The results indicate that Forward cf-tACS successfully modulated bottom-up PAC (V1 α-phase-MT É£-amplitude) in both cohorts, while producing opposite effects on the reverse MT-to-V1 connection. Backward-tACS did not change V1-MT PAC in either direction in healthy participants but induced a slight decrease in bottom-up PAC in stroke patients. However, these changes in inter-areal coupling did not translate into cf-tACS-specific behavioural improvements. CONCLUSIONS: Single session cf-tACS can alter inter-areal coupling in intact and lesioned brains but is probably not enough to induce longer-lasting behavioural effects in these cohorts. This might suggest that a longer daily visual training protocol paired with tACS is needed to unveil the relationship between externally applied oscillatory activity and behaviourally relevant brain processing.

MEP and TEP features variability: is it just the brain-state?

Objective.The literature investigating the effects of alpha oscillations on corticospinal excitability is divergent. We believe inconsistency in the findings may arise, among others, from the electroencephalography (EEG) processing for brain-state determination. Here, we provide further insights in the effects of the brain-state on cortical and corticospinal excitability and quantify the impact of different EEG processing.Approach.Corticospinal excitability was measured using motor evoked potential (MEP) peak-to-peak amplitudes elicited with transcranial magnetic stimulation (TMS); cortical responses were studied through TMS-evoked potentials' TEPs features. A TMS-EEG-electromyography (EMG) dataset of 18 young healthy subjects who received 180 single-pulse (SP) and 180 paired pulses (PP) to determine short-intracortical inhibition (SICI) was investigated. To study the effect of different EEG processing, we compared the brain-state estimation deriving from three published methods. The influence of presence of neural oscillations was also investigated. To evaluate the effect of the brain-state on MEP and TEP features variability, we defined the brain-state based on specific EEG phase and power combinations, only in trials where neural oscillations were present. The relationship between TEPs and MEPs was further evaluated.Main results.The presence of neural oscillations resulted in more consistent results regardless of the EEG processing approach. Nonetheless, the latter still critically affected the outcomes, making conclusive claims complex. With our approach, the MEP amplitude was positively modulated by the alpha power and phase, with stronger responses during the trough phase and high power. Power and phase also affected TEP features. Importantly, similar effects were observed in both TMS conditions.Significance.These findings support the view that the brain state of alpha oscillations is associated with the variability observed in cortical and corticospinal responses to TMS, with a tight correlation between the two. The results further highlight the importance of closed-loop stimulation approaches while underlining that care is needed in designing experiments and choosing the analytical approaches, which should be based on knowledge from offline studies to control for the heterogeneity originating from different EEG processing strategies.

Bacterial infections as a risk factor for non-neoplastic portal vein thrombosis development in cirrhotic patients.

BACKGROUND: Portal vein thrombosis (PVT) and sepsis are common complications in patients with liver cirrhosis. Factors that lead to PVT are not completely understood. This study aimed to investigate the possible association between bacterial infections and the development of PVT in cirrhotic patients. PATIENTS AND METHODS: 202 consecutive cirrhotic patients without previous infections, followed at the Liver Unit in Verona Hospital, were enrolled from 2017 to 2021 (median follow-up 3.3 years). During the follow-up period, PVT was diagnosed by ultrasound, CT and/or MRI, and episodes of bacterial infections requiring hospitalization were recorded. Malignant PVT was an exclusion criterion. RESULTS: Of the 202 patients enrolled (68.3 % males, mean age 63.8 ± 11 years), 22 (10.8 %) developed PVT during the follow up. In patients with PVT, the prevalence of previous bacterial infections was significantly higher compared to patients without PVT (63.6% vs 31.1 %; p = 0.02). Cox regression analysis revealed that a history of bacterial infection was the only variable that demonstrated a significant association with the risk of de novo PVT occurrence (HR 4.04, 95 % CI: 1.68-9.65). CONCLUSION: in patients with liver cirrhosis bacterial infections are a predisposing factor for the following development of PVT. Further studies are needed to confirm this evidence.

Pathway and directional specificity of Hebbian plasticity in the cortical visual motion processing network.

Cortico-cortical paired associative stimulation (ccPAS), which repeatedly pairs single-pulse transcranial magnetic stimulation (TMS) over two distant brain regions, is thought to modulate synaptic plasticity. We explored its spatial selectivity (pathway and direction specificity) and its nature (oscillatory signature and perceptual consequences) when applied along the ascending (Forward) and descending (Backward) motion discrimination pathway. We found unspecific connectivity increases in bottom-up inputs in the low gamma band, probably reflecting visual task exposure. A clear distinction in information transfer occurred in the re-entrant alpha signals, which were only modulated by Backward-ccPAS, and predictive of visual improvements in healthy participants. These results suggest a causal involvement of the re-entrant MT-to-V1 low-frequency inputs in motion discrimination and integration in healthy participants. Modulating re-entrant input activity could provide single-subject prediction scenarios for visual recovery. Visual recovery might indeed partly rely on these residual inputs projecting to spared V1 neurons.

Interleukin-6: A New Marker of Advanced-Sarcopenic HCC Cirrhotic Patients.

Hepatocellular carcinoma (HCC) is the major cause of liver-related death worldwide. Interleukin 6 (IL-6) promotes the growth of the HCC microenvironment. The correlation between Child-Pugh (CP) and HCC stage and between HCC stage and sarcopenia is still not clear. Our aim was to investigate whether IL-6 is correlated with HCC stage and could represent a diagnostic marker for sarcopenia. Ninety-three HCC cirrhotic patients in different stages, according to BCLC-2022 (stages A, B, and C), were enrolled. Anthropometric and biochemical parameters, comprehensive of IL-6, were collected. The skeletal muscle index (SMI) was measured using dedicated software on computer tomography (CT) images. IL-6 level was higher in advanced (BCLC C) compared to the early-intermediate (BCLC A-B) stages (21.4 vs. 7.7 pg/mL, p < 0.005). On multivariate analysis, IL-6 levels were statistically dependent on the degree of liver disease severity (CP score) and HCC stages (p = 0.001 and p = 0.044, respectively). Sarcopenic patients presented lower BMI (24.7 ± 5.3 vs. 28.5 ± 7.0), higher PMN/lymphocyte ratio (2.9 ± 2.4 vs. 2.3 ± 1.2) and increased values of log (IL-6) (1.3 ± 0.6 vs. 1.1 ± 0.3). Univariate logistic regression between sarcopenia and log (IL-6) showed a significant odds ratio (OR 14.88, p = 0.044) with an AUC of 0.72. IL-6 appears to be an effective biomarker for the diagnosis of advanced cirrhotic HCC. In addition, IL-6 could be considered a marker of cirrhotic HCC-related sarcopenia, suggesting further investigation with BIA- or CT-dedicated software.

Spur cells in liver cirrhosis are predictive of acute-on-chronic liver failure and liver-related mortality regardless of severe anaemia.

Chronic anaemia in advanced liver disease is a frequent finding. The aim was to explore the clinical impact of spur cell anaemia, a rare entity typically associated with end-stage of the disease. One-hundred and nineteen patients (73.9% males) with liver cirrhosis of any etiology were included. Patients with bone marrow diseases, nutrients deficiencies and hepatocellular carcinoma were excluded. In all patients, a blood sample was collected to check for the presence of spur cells on blood smear. A complete blood biochemical panel was recorded together with Child-Pugh (CP) score and Model for End-Stage Liver Disease (MELD) score. For each patients, clinically relevant events, such as acute-on-chronic liver failure (ACLF) and 1 year liver-related mortality, were registered. Patients were then grouped according to the percentage of spur cells at smear (> 5%, 1-5%, < 1%). Severe anaemia was defined as haemoglobin levels lower than 8 g/dL. 9.2% of subjects had > 5% spur cells, only 2 had evidence of haemolysis. In patients with > 5% spur cells, haemoglobin and albumin were lower compared with the other sub-group, while MELD score, CP score, International Normalized Ratio, ferritin, creatinine and unconjugated bilirubin were higher. Patients with more spur cells were more decompensated and developed more frequently ACLF. ACLF and liver-related mortality were significantly and independently associated with the presence of > 5% spur cells but not with baseline severe anaemia. Cirrhotic patients have a fairly high prevalence of spur cells, not always associated with severe haemolytic anaemia. The presence of spur red cells is per se associated with a worse prognosis and, therefore, should be always evaluated to prioritize patients for intensive management and eventually liver transplantation.

Chronic anaemia is a frequent finding in liver cirrhosis and spur cell anaemia has been shown to be an uncommon non-immune haemolytic disease typically related to advanced-liver disease. In our study, spur cell anaemia (spur cells >5%) was found in almost 10% of outpatient cirrhotics and was significantly related to more decompensated disease, higher incidence of ACLF and 1 year liver-related mortality. More importantly, the vast majority of patients with high percentage of spur cells did not have severe anaemia. Therefore, spur cells should be searched for in patients with advanced liver disease by a simple blood smear evaluation, even in the absence of significant anaemia, because of relevant prognostic impact and in order to prioritize patients to intensive management and possibly liver transplantation.

The multi-drug resistant organisms infections decrease during the antimicrobial stewardship era in cirrhotic patients: An Italian cohort study.

BACKGROUND AND PURPOSE: Bacterial infections represent a major cause of morbidity and mortality in cirrhotic patients. Our aim was to assess the incidence of bacterial infections, in particular due to multidrug-resistant organisms (MDROs) before and after the introduction of the antimicrobial stewardship program, "Stewardship Antimicrobial in VErona" (SAVE). In addition, we also analysed the liver complications and the crude mortality during the whole follow up. METHODS: We analysed 229 cirrhotic subjects without previous hospitalization for infections enrolled at the University Verona Hospital from 2017 to 2019 and followed up until December 2021 (mean follow-up 42.7 months). RESULTS: 101 infections were recorded and 31.7% were recurrent. The most frequent were sepsis (24.7%), pneumonia (19.8%), spontaneous bacterial peritonitis (17.8%). 14.9% of infections were sustained by MDROs. Liver complications occurred more frequently in infected patients, and in case of MDROs infections with a significantly higher MELD and Child-Pugh score. In Cox regression analysis, mortality was associated with age, diabetes and bacterial infections episodes (OR 3.30, CI 95%: (1.63-6.70). Despite an increase in total infections over the past three years, a decrease in the incidence rate in MDROs infections was documented concurrently with the introduction of SAVE (IRD 28.6; 95% CI: 4.6-52.5, p = 0.02). CONCLUSIONS: Our study confirms the burden of bacterial infections in cirrhotic patients, especially MDROs, and the strong interconnection with liver complications. The introduction of SAVE decreased MDROs infections. Cirrhotic patients require a closer clinical surveillance to identify colonized patients and avoid the horizontal spread of MDROs in this setting.

Stroke Volume and Arterial Pressure Fluid Responsiveness in Patients With Elevated Stroke Volume Variation Undergoing Major Vascular Surgery: A Prospective Intervention Study.

OBJECTIVES: The identification of potential hemodynamic indicators to increase the predictive power of stroke-volume variation (SVV) for mean arterial pressure (MAP) and stroke volume (SV) fluid responsiveness. DESIGN: A prospective intervention study. SETTING: At a single-center university hospital. PARTICIPANTS: Nineteen patients during major vascular surgery with 125 fluid interventions. INTERVENTIONS: When SVV ≥13% occurred for >30 seconds, 250 mL of Ringer's lactate were given within 2 minutes. MEASUREMENTS AND MAIN RESULTS: Hemodynamic variables, such as pulse-pressure variation (PPV) and dynamic arterial elastance (Edyn), were measured by pulse power-wave analysis. The outcomes were MAP and SV responsiveness, defined as an increase of at least 10% of MAP and SV within 5 minutes of the fluid intervention. Of the fluid interventions, 48% were MAP-responsive, and 66% were SV-responsive. The addition of PPV and Edyn cut-off values to the SVV cut-off decreased sensitivity from 1-to-0.66 to-0.82, and concomitantly increased specificity from 0-to- 0.65-to-0.93 for the prediction of MAP and SV responsiveness in the authors' study setting. The areas under the receiver operating characteristic curves of PPV and Edyn for the prediction of MAP responsiveness were 0.79 and 0.75, respectively. The areas under the receiver operating characteristic curves for PPV and Edyn to predict SV responsiveness were 0.85 and 0.77, respectively. CONCLUSIONS: The PPV and Edyn showed good accuracy for the prediction of MAP and SV responsiveness in patients with elevated SVV during vascular surgery. Either PPV or Edyn may be used in conjunction with SVV to better predict MAP and SV fluid responsiveness in patients undergoing vascular surgery.

Subclinical and clinical atherosclerosis in non-alcoholic fatty liver disease is associated with the presence of hypertension.

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is associated with increased cardiovascular (CV) risk. However, it is unclear whether NAFLD contributes independently to the development of CV disease. Our study aimed at assessing the differences in several indices of atherosclerosis, arterial stiffness and cardiac morphology among patients with isolated NAFLD, isolated hypertension (HT) or a combination of the two conditions. METHODS AND RESULTS: A total of 169 participants (mean age = 50.4 ± 10.2 yrs; males = 73.6%) were divided according to the presence of NAFLD and HT into three groups: only NAFLD (55 patients), only HT (49 patients), and NAFLD + HT (65 patients). Exclusion criteria were a BMI≥35 kg/m2 and a diagnosis of diabetes mellitus. Carotid ultrasonography was performed to measure markers of atherosclerosis and arterial stiffness. Cardiac remodeling was analyzed using echocardiography. The prevalence of subclinical and overt atherosclerosis was significantly higher in the NAFLD + HT patients as compared to the other two groups (atherosclerotic plaques: 43.1%, 10.9%, and 22.4% (p < 0.001) in NAFLD + HT, NAFLD, and HT groups, respectively). No differences were found among indices of arterial stiffening and cardiac remodeling across the three groups. In multivariate regression analysis, the coexistence of NAFLD and HT was an independent risk factor for overt atherosclerosis (OR = 4.88, CI 95% 1.14-20.93), while no association was found when either NAFLD or HT was considered alone. CONCLUSION: Overt atherosclerosis was significantly present only in NAFLD + HT patients, but not in patients with isolated NAFLD. This implies that the impact of NAFLD on vascular structure and function could depend on the coexistence of other major CV risk factors, such as HT.

Effects of direct-acting antiviral agents on lipid and glucose profile in HCV patients with type 2 diabetes: A real-life Italian experience.

OBJECTIVES: Hepatitis C virus (HCV) infection is associated with an increased risk of type 2 diabetes mellitus (T2DM) and cardiovascular diseases. The impact of HCV eradication on the metabolic profile in diabetic patients treated with direct-acting antiviral agents (DAAs) is not well defined. The aim of our study was to evaluate the effects of DAAs on a lipid and glucose profile in a cohort of diabetic patients with different liver fibrotic stages. METHODS: T2DM patients with active HCV infection were consecutively enrolled in this prospective trial. Glycolipidic status was assessed, before starting DAA treatment (T0) and at 12 months after the beginning of treatment (T1). Liver fibrotic stage was assessed by FibroScan. RESULTS: In all, 131 patients were enrolled and all of them achieved a sustained virologic response. At baseline, no significant differences were found in lipid and glucose profiles in subgroup analysis by liver fibrosis, HCV genotype, and cardiovascular risk factors. At T1, total cholesterol and low-density lipoprotein cholesterol, but not triglycerides, significantly increased irrespective of liver fibrotic stage and baseline anthropometric and clinical profiles, while glycated hemoglobin significantly decreased only in F4 patients. CONCLUSIONS: HCV eradication in diabetic patients is associated with a worsening lipid profile that could impact future cardiovascular risk. A careful global monitoring of cardiovascular risk factors in all diabetic patients after HCV eradication is needed.

A Prospective Observational Study on Multiplate®-, ROTEM®- and Thrombin Generation Examinations Before and Early After Implantation of a Left Ventricular Assist Device (LVAD).

Background: Heart failure patients are frequently on coagulation-active medications before LVAD implantation and perioperative bleeding is a frequent complication after left ventricular assist device (LVAD) implantation. The role of point-of-care coagulation tests in assessing bleeding risk for LVAD implantation and the early postoperative time course of these tests is not well established. Methods: We prospectively enrolled 25 patients with terminal heart failure undergoing LVAD implantation. Study related TRAP-, ASPI- and ADP- tests of Multiplate® platelet aggregometry, ROTEM® rotational thromboelastometry (INTEM, EXTEM, FIBTEM), thrombin generation assay and conventional laboratory studies were measured at 11 predefined time-points during the first 21 postoperative days. We examined if preoperative TRAP-, ASPI-, ADP- and ROTEM values are correlated with estimated total blood loss (primary outcome parameter) during the first 21 days after LVAD implantation and compared the baseline values of these measurements between patients with a bleeding event to those without. We performed Spearman's correlation and non-parametric tests for paired and non-paired comparisons. Results: 7 out of 25 (28%) patients experienced a bleeding event of which 4 required surgical revision. Of the preoperatively performed measurements the TRAP test [Spearman's Rho (ρ) = -0.5, p = 0.01], INTEM CFT (ρ = 0.72, p < 0.001), INTEM alpha (-0.7, p < 0.001), EXTEM MCF (ρ = -0.63; p < 0.001), EXTEM alpha (ρ = -0.67; p < 0.001), FIBTEM MCF (ρ = -0.41; p = 0.042), Fibrinogen (Clauss) (ρ = -0.5; p = 0.011), Anti-thrombin activity (ρ = -0.49; p = 0.013) and platelet count (ρ = -0.42; p = 0.034) were significantly correlated to total blood loss. Patients undergoing a surgical bleeding revision had significantly reduced values in TRAP-[31.5 IQR (17.25-43.5U) vs. 69 IQR (52.5-87U); p = 0.004], ASPI-[16.5 IQR (5.5-35.7U) vs. 39 IQR (24.5-62.5U); p = 0.038], ADP-[30 IQR (22-69U) vs. 12.5 IQR (8.7-21.5U); p = 0.01], EXTEM MCF-[63 IQR (57.7-63.7) vs. 67 IQR (65-75.5); p = 0.019] and EXTEM alpha [74 IQR (68.75-74) vs. 79 IQR (78-80.5); p = 0.002] values before LVAD implantation. Conclusion: Multiplate® and ROTEM® measurements before LVAD implantation may identify LVAD candidates with platelet dysfunction and alterations of the primary hemostasis and could guide anesthetists and intensive care practitioners in bleeding risk stratification and in the perioperative clinical management.

Global Longitudinal Strain to Predict Respiratory Failure and Death in Patients Admitted for COVID-19-Related Disease.

Evidence of the involvement of the cardiovascular system in patients with COVID-19 is increasing. The evaluation of the subclinical cardiac involvement is crucial for risk stratification at admission, and left ventricular global longitudinal strain (LVGLS) may be useful for this purpose. A total of 87 consecutive patients admitted to the COVID Center were enrolled from December 2020 to April 2021. A complete echocardiography examination was performed within 72 hours from admission. The main outcome was the need for mechanical ventilation by way of orotracheal intubation (OTI) and mortality, and the secondary outcome was the worsening of the respiratory function during hospitalization, interpreted as a decrease of the ratio between the partial pressure of oxygen and the fraction of inspired oxygen (P/F) <100. Of 87 patients, 14 had severe disease leading to OTI or death, whereas 24 had a P/F <100. LVGLS was significantly impaired in patients with severe disease. After adjustment for risk factors, by considering LVGLS as continuous variable, the latter remained significantly associated with severe acute respiratory distress syndrome (P/F <100) (hazard ratio [HR] 1.48, 95% confidence interval [CI] 1.18 to 1.88, p = 0.001) and OTI/death (HR 1.63, 95% CI 1.13 to 2.38, p = 0.012). When using an LVGLS cutoff of -16.1%, LVGLS ≥ -16.1% was independently associated with a higher risk of severe acute respiratory distress syndrome (HR 4.0, 95% CI 1.4 to 11.1, p= 0.008) and OTI/death (HR 7.3, 95% CI 1.6 to 34.1, p = 0.024). LVGLS can detect high-risk patients at the admission, which can help to guide in starting early treatment of the admitted patients.

Plasma Bile Acid Profile in Patients with and without Type 2 Diabetes.

A paucity of information currently exists on plasma bile acid (BA) profiles in patients with and without type 2 diabetes mellitus (T2DM). We assayed 14 plasma BA species in 224 patients with T2DM and in 102 nondiabetic individuals with metabolic syndrome. Plasma BA levels were measured with ultra-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) technique. Multivariable linear regression analyses were undertaken to assess associations between measured plasma BA species and T2DM status after adjustment for confounding factors. The presence of T2DM was significantly associated with higher plasma concentrations of both primary BAs (adjusted-standardized ß coefficient: 0.279, p = 0.005) and secondary BAs (standardized ß coefficient: 0.508, p < 0.001) after adjustment for age, sex, adiposity measures, serum alanine aminotransferase and use of statins or metformin. More specifically, the presence of T2DM was significantly associated with higher levels of plasma taurochenodeoxycholic acid, taurodeoxycholic acid, glycochenodeoxycholic acid, hyodeoxycholic acid, glycodeoxycholic acid, glycolithocholic acid, deoxycholic acid, taurochenodeoxycholic acid, taurodeoxycholic acid, glycochenodeoxycholic acid and glycodeoxycholic acid (adjusted-standardized ß coefficients ranging from 0.315 to 0.600; p < 0.01 or less), as well as with lower plasma levels of cholic acid (adjusted-standardized ß coefficient: -0.250, p = 0.013) and taurocholic acid (adjusted-standardized ß coefficient: -0.309, p = 0.001). This study shows that there are marked differences in plasma BA profiles between patients with and without T2DM. Further research will be needed to better understand how these differences in plasma BA profiles may interplay with the pathophysiology of T2DM.

Relationship between common carotid distensibility/aortic stiffness and cardiac left ventricular morphology and function in a group of patients affected by chronic rheumatic diseases: an observational study.

OBJECTIVES: Chronic inflammatory arthritis (CIAs), including rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) are characterised by high cardiovascular disease (CVD) risk, partly due to endothelial dysfunction and increased arterial stiffness of the carotid artery and aorta. The aim of the present study is to determine whether ultrasonography measures of carotid and aortic stiffness are correlated with left ventricular mass and function in patients affected by CIAs. METHODS: In this cross-sectional study, we consecutively enrolled outpatients diagnosed with CIAs with no overt CVD. For each participant we assessed disease characteristics, CVD risk factors, medications, including disease-modifying anti-rheumatic drugs (DMARDs), blood pressure, lipids and glucose levels. Carotid ultrasonography was performed in all patients using carotid distensibility (CD) and aortic stiffness index (AoSI) as measures of arterial stiffness. Participants underwent the same day a full echocardiographic study including assessment of left ventricular function and mass (LVM). RESULTS: The study population comprised 208 CIAs patients (mean age 57.4±11.4 y; females 63.9%), including 137 (65.9%) RA, 42 (20.2%) PsA and 29 (13.9%) AS patients. In multiple regression analysis, CD correlated with age (ß=-0.198, p<0.0001), mean arterial pressure (ß=-0.281, p<0.0001) and treatment with DMARDs (ß=-1.976, p=0.021), while AoSI was not associated with any anthropometric, haemodynamic or clinical covariates. CD was inversely related to LVM (r=-0.20, p=0.005), whereas AoSI was directly correlated with diastolic function of the left ventricle (E/E'; r=0.191, p=0.007). CONCLUSIONS: Our results underline the strict correlation between arterial stiffness and left ventricular mass and function in patients with CIAs.

Beneficial effects of DAAs on cardiac function and structure in hepatitis C patients with low-moderate liver fibrosis.

Hepatitis C virus (HCV)-related chronic infection has been associated with a higher incidence of cardiovascular diseases. An altered morphology and function of both left and right heart have been described in HCV patients; however, the causality of the association is still debated. Ninety-eight nonobese and nondiabetic HCV patients (59.5 ± 12.0 years; males 52%) with Fibroscan-Transient Elastography assessed low-moderate liver fibrosis that achieved sustained viral response at 12 and 24 weeks after DAAs (direct-acting antivirals) participated. 56 were matched with 52 control subjects for age, sex and cardiovascular risk factors at baseline. A trans-thoracic echocardiography was performed in each subject at baseline (T0) and repeated in all HCV patients after eradication (6 months later eligibility, T1). TNF-α and IL-10 were measured at baseline and at T1. A concentric remodelling of the left heart in HCV participants was identified, whereas tricuspidal annular plane systolic excursion, right indexed atrial volume, right basal ventricular diameter, inferior vena cava diameter and pulmonary arterial pressure were higher in HCV participants compared to matched controls. After virus eradication, left indexed atrial volume and all right cardiac chambers measures were lower than baseline. A significant reduction of TNF-α was shown at T1, while IL-10 did not change. This study shows a concentric remodelling of the left ventricle and structural modifications in the right sections in HCV patients compared to controls. Virus eradication with DAAs was associated with a reduction of the main right atrioventricular parameters indicating a direct involvement of the HCV in cardiac changes.

Traditional cardiovascular risk factors and residual disease activity are associated with atherosclerosis progression in rheumatoid arthritis patients.

Patients with rheumatoid arthritis (RA) have an increased incidence of cardiovascular events. Ultrasound examination of the carotid arteries can show the presence of plaques and detect the atherosclerotic subclinical process through the evaluation of intima-media thickness (cIMT) and carotid segmental distensibility (cCD). The aim of the present study was to identify which factors could independently influence the evolution of atherosclerosis (plaques, cIMT, and cCD) after 1 year of follow-up in a sample of patients with RA. A total of 137 patients with RA without previous cardiovascular (CV) events were enrolled at baseline, and 105 (M/F: 21/84, age 59.34 ± 11.65 years) were reassessed after one year using ultrasound of carotid arteries to detect atheromatous plaques and to measure cIMT and cCD. After one year, all the indices of subclinical atherosclerosis worsened with respect to baseline (Δ-cIMT = 0.030 ± 0.10 mm, p = 0.005; Δ-cCD = -1.64 ± 4.83, 10-3/KPa, p = 0.005; Δ-plaques = 8.6%, p = 0.035). Traditional CV risk factors (age, mean arterial pressure, and diabetes) and corticosteroid therapy were independently associated with the worsening of subclinical atherosclerosis. Interestingly, when considering RA patients divided according to the degree of disease activity score 28 with C-reactive protein (DAS28 [CRP] ≥2.6), the worsening of subclinical atherosclerosis indices was detectable exclusively in the group of patients with active disease. Our longitudinal study supports the hypothesis of a key role of both traditional CV risk factors and the inflammatory activity of arthritic disease in the progression of subclinical atherosclerosis in RA patients. In addition, corticosteroids might have a deleterious effect.

Early sST2 Liberation after Implantation of a Left Ventricular Assist Device in Patients with Advanced Heart Failure.

Background: The use of left ventricular assist device (LVAD) has increased considerably over the past decade; however, there is limited literature to assist in patient selection and monitoring. The frequency of adverse events remains high. We examined the early expression of circulating soluble ST2 (sST2), a biomarker with immunosuppressive and profibrotic activity, and assessed the risk of death at 1 year in patients receiving LVAD implant. Methods: We prospectively enrolled 20 heart failure patients and measured sST2, IL-33, and IL-6 serum concentrations over three weeks after LVAD implantation. We compared the kinetics of IL-6, sST2, and IL-33 release in survivors with those of nonsurvivors using mixed model two-way analysis of variance for repeated measures. We also collected data on hemodynamic parameters (i.e., cardiac output) and frequency of infections during the hospital stay. Results: LVAD therapy led to an immediate and significant improvement of the hemodynamic parameters in 1-year survivors and nonsurvivors alike. The 1-year survival rate was 65%. IL-6 concentrations showed a significant (p = 0.03) peak at admission to the intensive care unit following LVAD implantation, whereas sST2 levels were massively increased (p < 0.0003) on day 1. While 1-year survivors had persistently lower sST2 values compared to nonsurvivors during the first 3 weeks after LVAD implantation (p = 0.012), no differences were observed in the temporal pattern of IL-6 or IL-33. The odds of detecting Candida species in the bronchoalveolar lavage fluid were 14 times higher in nonsurvivors than in survivors (OR 13.7, CI 1.4-127, p = 0.02). Conclusion: In patients implanted with LVAD, circulating sST2 levels and frequency of Candida colonisation were associated with higher mortality. Awareness of this early immune response can guide physicians in risk-benefit analysis.

On Error-Related Potentials During Sensorimotor-Based Brain-Computer Interface: Explorations With a Pseudo-Online Brain-Controlled Speller.

Objective: Brain-computer interface (BCI) spelling is a promising communication solution for people in paralysis. Currently, BCIs suffer from imperfect decoding accuracy which calls for methods to handle spelling mistakes. Detecting error-related potentials (ErrPs) has been early identified as a potential remedy. Nevertheless, few works have studied the elicitation of ErrPs during engagement with other BCI tasks, especially when BCI feedback is provided continuously. Methods: Here, we test the possibility of correcting errors during pseudo-online Motor Imagery (MI) BCI spelling through ErrPs, and investigate whether BCI feedback hinders their generation. Ten subjects performed a series of MI spelling tasks with and without observing BCI feedback. Results: The average pseudo-online ErrP detection accuracy was found to be significantly above the chance level in both conditions and did not significantly differ between the two (74% with, and 78% without feedback). Conclusions: Our results support the possibility to detect ErrPs during MI-BCI spelling and suggest the absence of any BCI feedback-related interference.