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Introduction: Major depressive disorder (MDD) is a prevalent condition which has a well-known association with ischemic cardiomyopathy, probably explained by an inflammatory mediator mechanism. Statins, besides reducing cholesterol production, have pleiotropic effects including anti-inflammatory activity. The goal was to evaluate the effect of statins as an addition to standard therapy on mood status, brain perfusion, and neurocognitive performance in MDD. Methods: We studied 20 MDD patients with brain single-photon emission tomography and Cambridge Neuropsychological Test Automated Battery (CANTAB), half randomized to 10 mg of Rosuvastatin or placebo, in addition to selective serotonin reuptake inhibitors (SSRIs) therapy and being reevaluated 3 months later. The images were compared using Statistical Parametric Mapping; clinical scores (Hamilton Depression Score with 17 items and Beck's Depression Inventory) as well as neurocognitive parameters were applied as covariances (CoV) to estimate regional cerebral blood flow (rCBF) changes with both therapies. Results: Clinical scores decreased in both groups (p = 0.0001); Beck's presented a larger decrease with statins. We observed significantly rCBF changes expressed as significant larger clusters of voxels (p < 0.05) in the pre/subgenual anterior cingulate plus orbitofrontal cortex and a small area in the posterior cingulate gyrus in the statins group, whereas it was not observed with placebo, when using clinical scores as CoV. A similar pattern of rCBF changes was present with emotions recognition, attentional, paired associates learning, spatial planning, and working memory tasks. Conclusion: Short-term use of low-dose statins in MDD patients under SSRIs results in important rCBF changes in key mood associated areas to improvement in neurocognitive performance. These findings, even though demonstrated in a small sample, could open a new therapeutic tool in the comprehensive management of this disorder. [ABSTRACT FROM AUTHOR]

Introduction: Currently, severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection is a major public health problem worldwide. Although most patients present a mild infection, effective strategies are required for patients who develop the severe disease. Anti-inflammatory treatment with JAK inhibitors has been considered in SARS-CoV-2. Methods: In this study, we presented our experience in a group of severe SARS-CoV-2 Chilean patients. This prospective study was performed on consecutive patients presenting severe respiratory failure owing to COVID-19 or high-risk clinical condition associated with SARS-CoV-2, and who were treated with ruxolitinib for management of associated inflammation. Overall, 18 patients presenting SARS-CoV-2 viral-induced hyperinflammation were treated with ruxolitinib, with 16 patients previously treated with steroids, 4 with tocilizumab, and 3 with both treatments. Results: Ten patients evolved with favorable response, including 7 patients admitted with severe respiratory failure (PaFi less than 200 mm Hg in high-flow nasal cannula), presenting complete regression of hyperinflammation, regression of the lung lesions, and subsequent discharge. In the remaining 8 patients, 25% showed reduced inflammation, but early discharge was not achieved owing to the slow evolution of respiratory failure. Unfortunately, 3 patients demonstrated a severe respiratory failure. The early initiation of ruxolitinib was found to be associated with better clinical evolution (p < 0.005). Conclusion: In this study, ruxolitinib resolved hyperinflammatory state in 55% of the patients, regardless of the previous steroid or tocilizumab therapy. Unfortunately, few patients demonstrated severe evolution despite ruxolitinib therapy. Notably, the treatment starting time appears to play an important role in achieving good outcomes. Further validation in randomized controlled trials is crucial. [ABSTRACT FROM AUTHOR]

Background: Today, cancer ranks as one of the leading causes of death. Despite the large number of novel available therapies, radiotherapy (RT) remains as the most effective non-surgical method to cure cancer patients. In fact, approximately 50% of all cancer patients receive some type of RT and among these 60% receive RT-treatment with a curative intent. However, as occurs with any other oncological therapy, RT treated patients may experience toxicity side effects that range from moderate to severe. Among these, cardiotoxicity represents a significant threat for premature death. Current methods evaluate cardiotoxic damage based on volumetric changes in the Left Ventricle Ejected Fraction (LVEF). Indeed, a 10% drop in LVEF is commonly used as indicator of cardiotoxicity. More recently, a number of novel techniques have been developed that significantly improve specificity and sensitivity of heart's volumetric changes and early detection of cardiotoxicity even in asymptomatic patients. Among these, the Strain by Speckle Tracking (SST) is a technique based on echocardiographic analysis that accurately evaluates myocardial deformation during the cardiac cycle (ventricular and atrial function). Studies also suggest that Magnetic Resonance Imaging (MRI) is a high-resolution technique that enables a better visualization of acute cardiac damage.Methodology: This protocol will evaluate changes in SST and MRI in cancer patients that received thoracic RT. Concomitantly, we will assess changes in serum biomarkers of cardiac damage in these patients, including: high-sensitivity cardiac Troponin-T (hscTnT), N-Terminal pro-Brain Natriuretic Peptide (NTproBNP) and Circulating Endothelial Cells (CECs), a marker of endothelial dysfunction and vascular damage.Discussion: The presented protocol is to our knowledge the first to prospectively and with a multimodal approach, study serological and image biomarkers off early cardiac damage due to radiotherapy. With a practical clinical approach we will seek early changes that could potentially be in the future be linked to clinical mayor events with consequences for cancer survivors. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the maternal and perinatal outcomes in a cohort of pregnant women at high risk of venous thromboembolism (VTE). Methods: Women at high risk of VTE were evaluated in a multidisciplinary program using a complete diagnostic workup, and specific prophylactic or therapeutic treatment. Results: Women were considered at high risk of VTE in 57% (85/148) because of prior (75) or current (10) thromboembolism, and in 27% (40/148) of the cases due to adverse obstetric history. Thrombophilia was diagnosed in 57% of the cases (85/148), either in patients with previous thromboembolism (48%, 41/85) or without a history of thrombosis (70%, 44/63). The most common thrombophilia was antiphospholipid syndrome in 34% (29/85) of the cases. Under respective prophylactic or therapeutic treatment, there were no VTE during pregnancy (0%, 0/148), whereas four events occurred during the puerperium (3%, 4/148). An adverse obstetric outcome was present in 5% (7/148) of all pregnancies, with four early spontaneous abortions (3%, 4/148) and three late miscarriages (2%, 3/148). Conclusion: Pregnant women at high risk of VTE can be effectively managed using a risk‐adapted treatment. Our results support prospective enrollment and a multidisciplinary assessment of VTE in high‐risk pregnant women. Synopsis: Pregnant women at high risk of venous thromboembolism can be effectively managed using risk‐adapted treatment by a multidisciplinary team. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder (MDD) is an important independent risk factor for cardiovascular disease. Cumulative data suggest that depressive patients exhibit derangement in regional cerebral blood flow (rCBF), although underlying mechanisms remain mostly unknown. Endothelial dysfunction (ED), defined as different forms of abnormal endothelial activity, plays a key role in the pathogenesis of vascular disease. ED is associated with several clinical conditions characterized by high cardiovascular risk. Diverse ED markers have been found in mood disorders. Purpose: To evaluate the association between rCBF and peripheral ED markers in MDD patients, at baseline and after selective serotonin receptor inhibitors (SSRIs) therapy. Patients and Methods: Twenty-seven untreated unipolar MDD patients in their first episode were evaluated with the Hamilton Depression Rating Scale (HAM-D) and brain perfusion SPECT at baseline and after 2 months of SSRIs. Statistical Parametric Mapping (SPM) was employed to evaluate rCBF; circulating endothelial cells (CECs), plasma soluble intercellular adhesion molecule (sICAM), and high-sensitivity C-reactive protein (hsCRP) were used as independent covariates. Results: Baseline CECs and sICAM were increased in MDD patients compared with matching controls (p = 0.0001) and hsCRP (p = 0.03). HAM-D scores (21 items) and CECs diminished after SSRI therapy in MDD patients (p < 0.0001). There was a significant rCBF decrease, mainly in deep central structures. HAM-D change was associated with rCBF decrease at the left amygdala, right striatum levels, and Brodmann area 25. CEC change was associated with rCBF at deep brain level and sICAM with large rCBF areas at the left caudate and tectum; hsCRP was associated, to a lesser extent, with the left dorsal striatum and mesencephalic tectum. Conclusion: ED markers in patients with MDD are associated with significant changes in rCBF which are features of depression. These findings suggest that systemic damage/activation of the endothelium may contribute to the abnormal rCBF observed in MDD patients. [ABSTRACT FROM AUTHOR]

Background and aims High plasma LDL-cholesterol (LDL-C) and platelet responses have major pathogenic roles in atherothrombosis. Thus, statins and anti-platelet drugs constitute mainstays in cardiovascular prevention/treatment. However, the role of platelet tissue factor-dependent procoagulant activity (TF-PCA) has remained unexplored in hypercholesterolemia. We aimed to study platelet TF-PCA and its relationship with membrane cholesterol in vitro and in 45 hypercholesterolemic patients (HC-patients) (LDL-C >3.37 mmol/L, 130 mg/dL) and 37 control subjects (LDL-C <3.37 mmol/L). The effect of 1-month administration of 80 mg/day atorvastatin (n = 21) and 20 mg/day rosuvastatin (n = 24) was compared. Methods Platelet TF-PCA was induced by GPIbα activation with VWF-ristocetin. Results Cholesterol-enriched platelets in vitro had augmented aggregation/secretion and platelet FXa generation (1.65-fold increase, p = 0.01). HC-patients had 1.5-, 2.3- and 2.5-fold increases in platelet cholesterol, TF protein and activity, respectively; their platelets had neither hyper-aggregation nor endogenous thrombin generation (ETP). Rosuvastatin, but not atorvastatin, normalized platelet cholesterol, TF protein and FXa generation. It also increased slightly the plasma HDL-C levels, which correlated negatively with TF-PCA. Conclusions Platelets from HC-patients were not hyper-responsive to low concentrations of classical agonists and had normal PRP-ETP, before and after statin administration. However, washed platelets from HC-patients had increased membrane cholesterol, TF protein and TF-PCA. The platelet TF-dependent PCA was specifically expressed after VWF-induced GPIbα activation. Rosuvastatin, but not atorvastatin treatment, normalized the membrane cholesterol, TF protein and TF-PCA in HC-patients, possibly unveiling a new pleiotropic effect of rosuvastatin. Modulation of platelet TF-PCA may become a novel target to prevent/treat atherothrombosis without increasing bleeding risks. [ABSTRACT FROM AUTHOR]

Abstract: Background: Atrial fibrillation (AF) is associated to a high risk of systemic embolism. The mechanisms that contribute to thrombogenesis in these patients are still poorly understood. Systemic and/or local inflammation could be involved in the process of thrombogenesis and contribute to the perpetuation of the arrhythmia. The purpose of the study was to evaluate the role of inflammation and its relation to thrombogenesis and cardiac rhythm in AF. Methods: We prospectively studied 130 patients with newly diagnosed non-valvular AF in absence of antithrombotic therapy. Determinations of C-reactive protein (CRP) and thrombin–antithrombin complex (TAT) plasma levels, along with a transesophageal echocardiogram were performed in all the patients at admission. Results: Mean age of the group was 67±14 years. CRP levels were significantly elevated in AF patients versus controls (matched by age, gender and cardiovascular risk factors) (1.0±1.8 versus 0.3±0.4 mg/dl, respectively, p <0.01). Baseline TAT levels were also significantly elevated in AF patients but no correlation was found between CRP and TAT. At 1-year of follow-up, mean CRP levels were still elevated in patients that remained in AF compared to those who converted to sinus rhythm (1.2±1.8 compared to 0.5±1.5 mg/dl, p =0.03). CRP was the only biochemical predictor of sinus rhythm maintenance at 1-year follow-up independently of clinical (including adjustment for risk factors and antiarrhythmic drugs), biochemical and echo parameters. Conclusions: There is evidence for the presence of inflammation in patients with non-valvular AF, which is not related to activation of the coagulation cascade. The persistence of inflammation is associated with chronic AF at 1-year follow up. [Copyright &y& Elsevier]

Abstract: Diabetes mellitus (DM) is complicated by vascular and neurological events. Antiphospholipid (aPL) antibodies have already been associated with many clinical conditions, including venous and arterial thrombosis, as well as recurrent fetal loss. However, a significant association between aPL antibodies and DM has not been widely reported yet. In the present study, we investigated the prevalence of aPL antibodies in diabetic patients. This study included 100 Chilean diabetic patients (67 of them with some complications and 33 without complications; 28 with Type 1 and 72 with Type 2 DM) and 100 healthy blood donor controls. Each sample was analyzed for IgG, IgM and IgA anticardiolipin (aCL), anti-ß2 glycoprotein I (anti-ß2GPI), antiprothrombin (aPT) antibodies, and lupus anticoagulant (LA). Fourteen out of 100 (14%) diabetic patients presented some type of aPL antibodies. Four patients were positive for aCL antibodies, two for anti-ß2GPI antibodies, and nine for aPT antibodies. All patients were LA negative. The incidence of different isotypes was similar in each of the aPL antibodies studied, and their activities were low. No significant correlation was observed between aPL antibodies and vascular complications. [Copyright &y& Elsevier]

Inflammation, not hyperhomocysteinemia, is related to oxidative stress and hemostatic and endothelial dysfunction in uremia. Background. Several cardiovascular risk factors are present in patients with chronic renal failure (CRF), among which are systemic inflammation and hyperhomocysteinemia. Increased oxidative stress, endothelial activation/dysfunction, and coagulation activation are considered integral components of the inflammatory response, but have also been proposed as mediators of plasma homocysteine (tHcy)-induced cell damage. Using correlation analysis, we assessed the relative contributions of inflammation and hyperhomocysteinemia in the abnormal oxidative stress, endothelial activation/dysfunction, and hemostasis activation in patients with CRF. Methods. The relationships of inflammatory proteins and tHcy with plasma markers of these processes were studied in 64 patients with CRF (serum creatinine 526 ± 319 μmol/L) on conservative treatment, comparing the results with healthy controls (N = 15 to 40, depending on the measured variable) of similar sex and age. Results. Patients had significant increases in inflammatory cytokines (TNF-α and IL-8) and acute-phase proteins (C-reactive protein, fibrinogen and α1-antitrypsin). tHcy was increased in 87.5% of patients (mean = 27.1 μmol/L, range 6.5 to 118). Patients had significant increases in (1) indices of oxidative stress: TBARS (thiobarbituric acid-reactive species), a marker of lipid peroxidation and AOPP (advanced oxidation protein products), a marker of protein oxidation; (2) endothelial cell markers such as von Willebrand factor (vWF:Ag), soluble ICAM-1 and soluble thrombomodulin (sTM); (3) markers of intravascular thrombin generation: thrombin-antithrombin complexes (TAT) and prothrombin fragment F1+2 (PF1+2); and (4) indices of activation of fibrinolysis: plasmin-antiplasmin complexes (PAP), fibrin degradation products (FnDP) and fibrinogen... [ABSTRACT FROM AUTHOR]

Abstract: Background: Cocaine use has been related with the development of accelerated atherosclerosis and with an increased risk of cardiac and cerebrovascular events, such as myocardial infarction, sudden cardiac death, and ischemic stroke. The underlying mechanisms leading to these complications are not fully understood, although thrombus formation and altered vascular function are prominent findings. Objectives: Our aim was to evaluate markers of endothelial dysfunction in chronic cocaine consumers before and after drug withdrawal. Patients/Methods: We determined circulating endothelial cells (CECs) and plasma levels of stromal cell-derived factor-1 (SDF-1), monocyte chemotactic protein-1(MCP-1), soluble intracellular adhesion molecule (sICAM), high-sensitivity C reactive protein (hsCRP) and endothelin-1(ET-1), in DSM-IV cocaine addicts at baseline and after one month of cocaine abstinence. Results: Cocaine users showed a strikingly higher numbers of CEC (62.35±18.4 vs 8.25±13.8CEC/mL) and significantly elevated plasma levels for all the markers evaluated as compared to the control group. After cocaine withdrawal, patients improved SDF-1, ET-1, hsCRP and sICAM levels. However, CEC number and MCP-1 plasma levels remained significantly elevated. All the results were adjusted for blood levels of cholesterol and triglycerides and for smoking habit. Conclusions: Our results demonstrated that chronic cocaine consumption alters several functions of the endothelium towards a pro-thrombotic condition and that some of those functions remain abnormal even after short-term drug withdrawal. These observations support the notion that endothelial dysfunction may play a key role in the pathogenesis of ischemic vascular disease observed in cocaine abusers. [Copyright &y& Elsevier]

Abstract: The source and significance of blood-borne tissue factor (TF) are controversial. The presence of TF in platelets was initially attributed to transfer of the protein from other cells (e.g., monocytes) and/or TF-bearing microparticles. Recently, TF-mRNA, neo-synthesis of the protein and TF-dependent procoagulant activity (PCA) have been reported in human platelets. The storage of “encrypted”, potentially active TF in circulating, non-stimulated platelets remains debatable. One report strongly suggests that the starting of platelet PCA depends on de novo TF synthesis induced by platelet activation, whereas others provide persuasive evidence that platelets circulate with preformed TF, readily functional upon demand. These findings may have an impact on our current ideas of physiological hemostasis and thrombus formation. In fact, platelets would lead not only the formation of the primary plug, but in this microenvironment they would also contribute to the triggering of thrombin generation, fibrin deposition, clot consolidation and initial protection from fibrinolysis. Much research is needed to validate this platelet-based hemostasis model. [Copyright &y& Elsevier]

Most clinical neurofeedback studies based on functional magnetic resonance imaging use the patient's own neural activity as feedback. The objective of this study was to create a subject-independent brain state classifier as part of a real-time fMRI neurofeedback (rt-fMRI NF) system that can guide patients with depression in achieving a healthy brain state, and then to examine subsequent clinical changes. In a first step, a brain classifier based on a support vector machine (SVM) was trained from the neural information of happy autobiographical imagery and motor imagery blocks received from a healthy female participant during an MRI session. In the second step, 7 right-handed female patients with mild or moderate depressive symptoms were trained to match their own neural activity with the neural activity corresponding to the "happiness emotional brain state" of the healthy participant. The training (4 training sessions over 2 weeks) was carried out using the rt-fMRI NF system guided by the brain-state classifier we had created. Thus, the informative voxels previously obtained in the first step, using SVM classification and Effect Mapping, were used to classify the Blood-Oxygen-Level Dependent (BOLD) activity of the patients and converted into real-time visual feedback during the neurofeedback training runs. Improvements in the classifier accuracy toward the end of the training were observed in all the patients [Session 4-1 Median = 6.563%; Range = 4.10-27.34; Wilcoxon Test (0), 2-tailed p = 0.031]. Clinical improvement also was observed in a blind standardized clinical evaluation [HDRS CE2-1 Median = 7; Range 2 to 15; Wilcoxon Test (0), 2-tailed p = 0.016], and in self-report assessments [BDI-II CE2-1 Median = 8; Range 1-15; Wilcoxon Test (0), 2-tailed p = 0.031]. In addition, the clinical improvement was still present 10 days after the intervention [BDI-II CE3-2&#95;Median = 0; Range -1 to 2; Wilcoxon Test (0), 2-tailed p = 0.50/ HDRS CE3-2 Median = 0; Range -1 to 2; Wilcoxon Test (0), 2-tailed p = 0.625]. Although the number of participants needs to be increased and a control group included to confirm these findings, the results suggest a novel option for neural modulation and clinical alleviation in depression using noninvasive stimulation technologies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pereira, Ray, Rana, Silva, Salinas, Zamorano, Irani, Opazo, Sitaram and Ruiz.)

One of the most important and early impairments in autism spectrum disorder (ASD) is the abnormal visual processing of human faces. This deficit has been associated with hypoactivation of the fusiform face area (FFA), one of the main hubs of the face-processing network. Neurofeedback based on real-time fMRI (rtfMRI-NF) is a technique that allows the self-regulation of circumscribed brain regions, leading to specific neural modulation and behavioral changes. The aim of the present study was to train participants with ASD to achieve up-regulation of the FFA using rtfMRI-NF, to investigate the neural effects of FFA up-regulation in ASD. For this purpose, three groups of volunteers with normal I.Q. and fluent language were recruited to participate in a rtfMRI-NF protocol of eight training runs in 2 days. Five subjects with ASD participated as part of the experimental group and received contingent feedback to up-regulate bilateral FFA. Two control groups, each one with three participants with typical development (TD), underwent the same protocol: one group with contingent feedback and the other with sham feedback. Whole-brain and functional connectivity analysis using each fusiform gyrus as independent seeds were carried out. The results show that individuals with TD and ASD can achieve FFA up-regulation with contingent feedback. RtfMRI-NF in ASD produced more numerous and stronger short-range connections among brain areas of the ventral visual stream and an absence of the long-range connections to insula and inferior frontal gyrus, as observed in TD subjects. Recruitment of inferior frontal gyrus was observed in both groups during FAA up-regulation. However, insula and caudate nucleus were only recruited in subjects with TD. These results could be explained from a neurodevelopment perspective as a lack of the normal specialization of visual processing areas, and a compensatory mechanism to process visual information of faces. RtfMRI-NF emerges as a potential tool to study visual processing network in ASD, and to explore its clinical potential., (Copyright © 2019 Pereira, Sepulveda, Rana, Montalba, Tejos, Torres, Sitaram and Ruiz.)

Introduction: Screening for Autism Spectrum Disorders (ASD) using the Modified Checklist for Autism in Toddlers, Revised with Follow-up (M-CHAT-R/F) increases early detection, allowing early interventions and improving prognosis. This tool is part of the management in case of suspected ASD in several clinical guidelines. The objective of this article was to conduct the concurrent and discrimi nant validation and the reliability analysis of M-CHAT-R/F in the Chilean population., Patients and Method: This is the second stage of the cross-cultural adaptation of cross-sectional design. M-CHAT- R/F was applied to a sample of 20 children with suspected ASD and 100 randomly selected healthy control children, aged between 16-30 months. Autism Diagnostic Observation Schedule (ADOS-2), considered as reference, was applied to the 20 patients of the clinical sample, to 20 children of the healthy control sample and to those cases of the healthy control sample with M-CHAT-R/F positive. Cronbach alpha was calculated, as well as M-CHAT-R/F and ADOS-2 correlation, sensitivity, and specificity analyses., Results: In the healthy sample, M-CHAT-R/F was positive in two patients, with one of them positive and the other one negative for ASD with ADOS-2 test. In the clinical sample, M- CHAT-R/F was positive in all cases, three of them were negative in the ADOS-2 test. The Alfa relia bility of M-CHART-R/T was 0,889, the discriminant sensitivity and specificity were 100% and 98%, and the concurrent ones were 100% and 87.5% respectively., Conclusions: The Chilean M-CHAT- R/F version was reliable, sensitive and specific, similar to the original test, which opens the possibility for its use in clinical samples and for research. Validating M-CHAT-R/F is an ongoing process which must be further developed.