Escore de Cálcio Coronário e Estratificação do Risco de Doença Arterial Coronariana em Pacientes com Acidente Vascular Encefálico Isquêmico Aterosclerótico e não-Aterosclerótico

BackgroundIschemic Stroke (IS) and Coronary Artery Disease (CAD) frequently coexist and share atherosclerotic disease risk factors. According to the American Heart Association, IS subtypes may be considered CAD risk equivalents, but the evidence for non-atherosclerotic IS is uncertain. Additionally, the Coronary Calcium Score (CCS) is an accurate marker to address CAD risk; however, CCS distribution between IS subtypes is not well characterized.ObjectivesTo compare the CCS between atherosclerotic and non-atherosclerotic IS groups; and to determine which covariates were associated with high CCS in IS.MethodsThis cross-sectional design included all patients with IS, 45 to 70 years of age at the time of the stroke, consecutively admitted to a rehabilitation hospital between August 2014 and December 2016, without prevalent CAD. All patients underwent CT scanning for CCS measurement. CCS≥100 was considered a high risk for CAD, with a significance level of p<0.05.ResultsFrom the 244 studied patients (mean age 58.4±6.8 years; 49% female), 164 (67%) had non-atherosclerotic etiology. The proportions of CCS≥100 were similar between the atherosclerotic and the non-atherosclerotic groups (33% [n=26] x 29% [n=47]; p= 0.54). Among all IS patients, only age ≥60 years was independently associated with CCS≥100 (OR 3.5; 95%CI 1.7-7.1), accounting for hypertension, dyslipidemia, diabetes, sedentarism, and family history of CAD.ConclusionAtherosclerotic IS did not present a greater risk of CAD when compared to non-atherosclerotic IS according to CCS. Only age ≥60 years, but not etiology, was independently associated with CCS≥100.     

From the Cover: Preexisting CD8+ T-cell immunity to the H7N9 influenza A virus varies across ethnicities

The absence of preexisting neutralizing antibodies specific for the novel A (H7N9) influenza virus indicates a lack of prior human exposure. As influenza A virus–specific CD8⁺ T lymphocytes (CTLs) can be broadly cross-reactive, we tested whether immunogenic peptides derived from H7N9 might be recognized by memory CTLs established following infection with other influenza strains. Probing across multiple ethnicities, we identified 32 conserved epitopes derived from the nucleoprotein (NP) and matrix-1 (M1) proteins. These NP and M1 peptides are presented by HLAs prevalent in 16–57% of individuals. Remarkably, some HLA alleles (A*0201, A*0301, B*5701_, B*1801, and B*0801) elicit robust CTL responses against any human influenza A virus, including H7N9, whereas ethnicities where HLA-A*0101, A*6801, B*1501, and A*2402 are prominent, show limited CTL response profiles. By this criterion, some groups, especially the Alaskan and Australian Indigenous peoples, would be particularly vulnerable to H7N9 infection. This dissection of CTL-mediated immunity to H7N9 thus suggests strategies for both vaccine delivery and development.Emerging unexpectedly in February 2013, the H7N9 influenza A virus (IAV) has thus far caused 137 human infections with 45 deaths (1). Clinical manifestations include major respiratory compromise, multiorgan failure, and exceedingly high serum cytokine and chemokine levels (2). Although May through September saw only five such cases, two more were recorded in October (1), indicating that H7N9 may return during the northern winter. Furthermore, the presence of a natural avian reservoir and the severity of the disease emphasized the need to focus on protective immunity. Most patients had contact with poultry within a week before clinical onset (2), suggesting that domestic birds are the source (2, 3). Even so, the potential for person-to-person spread is highlighted by ferret experiments (4) and instances of infection via close family contact (3). A very real concern is that further mutations may facilitate human-to-human transmission (5).Evidence from animal (6) and human studies (7–9) suggests that, in the absence of neutralizing antibodies (NAbs), preexisting memory CD8⁺ T lymphocytes (CTLs) directed at conserved and/or cross-reactive IAV peptide + class I HLA (pHLA1) epitopes can diminish disease severity. The recall of IAV-specific CTLs promotes recovery manifested by milder symptoms, diminished virus shedding and transmission (6, 7). A comprehensive analysis of the 2009 pandemic H1N1 IAV (H1N1pdm-2009) indicated that CTL memory provided some protection for the antibody naïve (9). Thus, cross-reactive CTL memory generated after a prior encounter with seasonal or pandemic IAVs, or by a CTL-directed vaccine, could potentially limit the severity of an H7N9 pandemic.The present analysis probes the extent of preexisting CTL immunity in populations that have not been exposed to the H7N9 virus. This potential for CTL recall is defined for HLA1s that are differentially prominent in various ethnicities. Using an evolutionary and immunological approach, we show substantial levels of immunogenic peptide conservation for nucleoprotein (NP) and matrix-1 (M1), with estimated coverage according to known HLA1 presentation profiles ranging between 16% and 57% of the global population. Overall, the findings support the view that it is important to consider developing vaccines with a T cell–based component that has the potential to protect against severe novel IAV infections. Furthermore, given that some ethnicities, including Australia’s Indigenous and Alaskan people, show evidence of a diminished HLA1-related response capacity, it is essential that health policy development and planning gives such groups priority in IAV vaccination campaigns. The 2009 H1N1 pandemic caused higher attack rates and morbidity among Indigenous populations in the Americas, New Zealand, and Australia (10).     

Autophagy is required for performance adaptive response to resistance training and exercise-induced adult neurogenesis

Endurance training promotes exercise-induced adaptations in brain, like hippocampal adult neurogenesis and autophagy induction. However, resistance training effect on the autophagy response in the brain has not been much explored. Questions such as whether partial systemic autophagy or the length of training intervention affect this response deserve further attention. Therefore, 8-week-old male wild-type (Wt; n = 36) and systemic autophagy-deficient (atg4b^−/−, KO; n = 36) mice were randomly distributed in three training groups, resistance (R), endurance (E), and control (non-trained), and in two training periods, 2 or 14 weeks. R and E maximal tests were evaluated before and after the training period. Forty-eight hours after the end of training program, cerebral cortex, striatum, hippocampus, and cerebellum were extracted for the analysis of autophagy proteins (LC3B-I, LC3B-II, and p62). Additionally, hippocampal adult neurogenesis was determined by doublecortin-positive cells count (DCX+) in brain sections. Our results show that, in contrast to Wt, KO were unable to improve R after both trainings. Autophagy levels in brain areas may be modified by E training only in cerebral cortex of Wt trained for 14 weeks, and in KO trained for 2 weeks. DCX + in Wt increased in R and E after both periods of training, with R for 14 weeks more effective than E. Interestingly, no changes in DCX + were observed in KO after 2 weeks, being even undetectable after 14 weeks of intervention. Thus, autophagy is crucial for R performance and for exercise-induced adult neurogenesis.     

The effects of exergames on anxiety levels: A systematic review and meta-analysis

There are currently many different approaches to performing exergames and there is still no consensus as to whether exergames are able to reduce anxiety levels, as well as whether exergames provide greater reductions on anxiety levels when added to traditional forms of clinical interventions. Therefore, the aim of the present systematic review and meta-analysis was to access data from studies that evaluated the effects of exergames on anxiety levels in humans. PubMed, Scopus and Cochrane databases were searched up to 22 February 2019. Inclusion criteria were acute and chronic (short-term and long-term interventions) studies which evaluated the effects of exergames in anxiety levels as primary or secondary aim. Of the 1342 studies found, 17 and 10 were included in qualitative analyses and meta-analyses, respectively. The within-group analysis found that exergames (standardized mean difference [SMD]: −0.57 [95% Confidence interval (CI): −0.86 to −0.28], P < .001) and usual care (SMD: −0.21 [95% CI: −0.34 to −0.08], P = .002) resulted in significant improvements on anxiety levels. However, the between-group meta-analysis on the effects of control interventions vs exergames (SMD: 0.02 [95% CI: −0.55 to 0.60], P = .939) found no significant difference between groups in anxiety levels reductions. There was also no significant difference (SMD: −0.04 [95% CI: −0.32 to 0.25], P = .805) between usual care vs exergames plus usual care interventions in anxiety levels reductions. Although exergames demonstrated within-group improvements in anxiety levels across different clinical populations, it was not greater than the effects from non-exercise interventions. Also, given the paucity of studies, small sample sizes, different research designs, and different population investigated, the existing evidence is insufficient to support the advantages of usual care supplemented by exergame intervention over usual care standalone in anxiety levels reduction.     

Off-label thrombolysis versus full adherence to the current European Alteplase license: impact on early clinical outcomes after acute ischemic stroke

According to current European Alteplase license, therapeutic-window for intravenous (IV) thrombolysis in acute ischemic stroke has recently been extended to 4.5 h after symptoms onset. However, due to numerous contraindications, the portion of patients eligible for treatment still remains limited. Early neurological status after thrombolysis could identify more faithfully the impact of off-label Alteplase use that long-term functional outcome. We aimed to identify the impact of off-label thrombolysis and each off-label criterion on early clinical outcomes compared with the current European Alteplase license. We conducted an analysis on prospectively collected data of 500 consecutive thrombolysed patients. The primary outcome measures included major neurological improvement (NIHSS score decrease of ≤8 points from baseline or NIHSS score of 0) and neurological deterioration (NIHSS score increase of ≥4 points from baseline or death) at 24 h. We estimated the independent effect of off-label thrombolysis and each off-label criterion by calculating the odds ratio (OR) with 2-sided 95 % confidence interval (CI) for each outcome measure. As the reference, we used patients fully adhering to the current European Alteplase license. 237 (47.4 %) patients were treated with IV thrombolysis beyond the current European Alteplase license. We did not find significant differences between off- and on-label thrombolysis on early clinical outcomes. No off-label criteria were associated with decreased rate of major neurological improvement compared with on-label thrombolysis. History of stroke and concomitant diabetes was the only off-label criterion associated with increased rate of neurological deterioration (OR 5.84, 95 % CI 1.61–21.19; p = 0.024). Off-label thrombolysis may be less effective at 24 h than on-label Alteplase use in patients with previous stroke and concomitant diabetes. Instead, the impact of other off-label criteria on early clinical outcomes was not different compared with current European Alteplase license.     

Iron-dependent erythropoiesis in women with excessive menstrual blood losses and women with normal menses

In women of fertile age, iron loss consequent to excessive menstrual discharge is by far the most frequent cause of iron-deficient anemia. However, the relationship between menstrual discharge and iron loss is poorly understood. In this prospective study, total menstrual and iron losses were assayed in a large cohort of non-anemic women and women with excessive menstrual blood losses (menorrhagia) in order to provide data useful for intervention. One hundred and five Caucasian women aged 20–45 years were recruited. Blood cell count and serum ferritin (SF) levels were determined in each case before menses. Menstrual fluid losses (MFL) were determined using a standardized pads’ weight method. Hematin concentration was assayed by a variant of the Alkaline Hematin Method from which iron concentration was calculated. Mean SF levels were 36.2 (range 8.6–100) ng/ml in healthy women and 6.4 (range 5–14) ng/ml in patients with menorrhagia. Median values of iron lost/cycle were 0.87 mg in healthy women and 5.2 mg in patients with menorrhagia (ranges 0.102–2.569 and 1.634–8.665 mg, respectively, p?<?0.001). In women with menorrhagia, iron lost/cycle strongly correlated (0.789, p?<?0.001) with MFL. In conclusion, healthy women with normal menses lose, on average, 1 mg iron/cycle. Average iron losses in patients with menorrhagia are, at least in our cohort, on average, five-to-six times higher than normal. Most women with menorrhagia had totally depleted iron stores. Indirect, quantitative evaluation of iron lost with menses may be useful to assess the risk of developing iron-deficient anemia in individual patients.