Intensidade de Exercício durante o Teste de Caminhada de 6 Minutos em Pacientes com Doença Arterial Periférica

Background Non-supervised ground walking has been recommended for patients with symptomatic peripheral artery disease (PAD). However, the magnitude of the effort required by this activity and the characteristics of patients whose ground walking is more intense are unclear.Objectives To determine whether ground walking exceeds the ventilatory threshold (VT), a recognized marker of exercise intensity, in patients with symptomatic PAD.Methods Seventy patients (61.4% male and aged 40 to 85 years old) with symptomatic PAD were recruited. Patients performed a graded treadmill test for VT determination. Then, they were submitted to a 6-minute walk test so the achievement of VT during ground ambulation could be identified. Multiple logistic regression was conducted to identify predictors of VT achievement during the 6-minute walk test. The significance level was set at p < 0.05 for all analyses.Results Sixty percent of patients achieved VT during the 6-minute walk test. Women (OR = 0.18 and 95%CI = 0.05 to 0.64) and patients with higher cardiorespiratory fitness (OR = 0.56 and 95%CI = 0.40 to 0.77) were less likely to achieve VT during ground walking compared to men and patients with lower cardiorespiratory fitness, respectively.Conclusion More than half of patients with symptomatic PAD achieved VT during the 6-minute walk test. Women and patients with higher cardiorespiratory fitness are less likely to achieve VT during the 6-minute walk test, which indicates that ground walking may be more intense for this group. This should be considered when prescribing ground walking exercise for these patients. (Arq Bras Cardiol. 2020; 114(3):486-492)     

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.     

Alterações Precoces nas Interleucinas Circulantes e no Risco Inflamatório Residual após Infarto Agudo do Miocárdio

BackgroundPatients with acute myocardial infarction may have a large infarcted area and ventricular dysfunction despite early thrombolysis and revascularization.ObjectiveTo investigate the behavior of circulating cytokines in patients with ST-segment elevation myocardial infarction (STEMI) and their relationship with ventricular function.MethodsIn the BATTLE-AMI (B and T Types of Lymphocytes Evaluation in Acute Myocardial Infarction) trial, patients with STEMI were treated with a pharmacoinvasive strategy. The plasma levels of cytokines (IL-1 β , IL-4, IL-6, IL-10, and IL-18) were tested using enzyme-linked immunosorbent assay (ELISA) at baseline and after 30 days. Infarcted mass and left ventricular ejection fraction (LVEF) were examined by 3-T cardiac magnetic resonance imaging. All p-values < 0.05 were considered statistically significant.ResultsCompared to baseline, lower levels were detected for IL-1 β (p = 0.028) and IL-18 (p < 0.0001) 30 days after STEMI, whereas higher levels were observed for IL-4 (p = 0.001) and IL-10 (p < 0.0001) at that time point. Conversely, no changes were detected for IL-6 levels (p = 0.63). The levels of high-sensitivity C-reactive protein and IL-6 correlated at baseline (rho = 0.45, p < 0.0001) and 30 days after STEMI (rho = 0.29, p = 0.009). At baseline, correlation between IL-6 levels and LVEF was also observed (rho = -0.50, p = 0.004).ConclusionsDuring the first month post-MI, we observed a marked improvement in the balance of pro- and anti-inflammatory cytokines, except for IL-6. These findings suggest residual inflammatory risk. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)     

Badger responses to small-scale culling may compromise targeted control of bovine tuberculosis

Where wildlife disease requires management, culling is frequently considered but not always effective. In the British Isles, control of cattle tuberculosis (TB) is hindered by infection in wild badger (Meles meles) populations. Large-scale badger culling can reduce the incidence of confirmed cattle TB, but these benefits are undermined by culling-induced changes in badger behavior (termed perturbation), which can increase transmission among badgers and from badgers to cattle. Test–vaccinate/remove (TVR) is a novel approach that entails testing individual badgers for infection, vaccinating test-negative animals, and killing test-positive animals. Imperfect capture success, diagnostic sensitivity, and vaccine effectiveness mean that TVR would be expected to leave some infected and some susceptible badgers in the population. Existing simulation models predict that TVR could reduce cattle TB if such small-scale culling causes no perturbation, but could increase cattle TB if considerable perturbation occurs. Using data from a long-term study, we show that past small-scale culling was significantly associated with four metrics of perturbation in badgers: expanded ranging, more frequent immigration, lower genetic relatedness, and elevated prevalence of Mycobacterium bovis, the causative agent of TB. Though we could not reject the hypothesis that culling up to three badgers per social group might avoid perturbation, we also could not reject the hypothesis that killing a single badger prompted detectable perturbation. When considered alongside existing model predictions, our findings suggest that implementation of TVR, scheduled for 2014, risks exacerbating the TB problem rather than controlling it. Ongoing illegal badger culling is likewise expected to increase cattle TB risks.Infectious diseases are often difficult to control where wildlife hosts contribute to pathogen persistence. Wildlife culling is a frequently considered control option, which is sometimes effective (1, 2), but often ineffective (3–6).In the United Kingdom, the cattle farming industry is seriously affected by bovine tuberculosis (TB) caused by Mycobacterium bovis (7). Selective culling of test-positive cattle has helped to eradicate TB across much of the developed world, but eradication from the United Kingdom is impeded by M. bovis infection in European badgers (Meles meles) (8), as well as by continued transmission among cattle (9–11). Transmission has also been documented among badgers (12), from cattle to badgers (13), and from badgers to cattle (14, 15). Because badgers are clearly a contributing factor to the UK’s TB problem, successive TB control policies have included culling of badgers (7, 8). To date, cattle controls have emphasized selective slaughter of test-positive animals, whereas badger culls have typically been nonselective, with no testing of live animals before culling (but see ref. 16).The impacts of nonselective badger culling on M. bovis transmission are well established. Such culling reduces badger density (17), but also promotes dispersal into the culled area (18) as well as expanding badger ranging in and around the areas where culls occurred (19). In Britain these behavioral changes—termed social perturbation—have been linked to increases in the proportion of badgers infected with M. bovis (13, 20), and reductions in the spatial clustering of infection (21). In cattle, the incidence of confirmed TB was reduced inside large culling areas where badger numbers were substantially suppressed by annual “proactive” culling. However, on adjoining unculled lands, and in areas receiving localized “reactive” culling, reductions in badger numbers were smaller, the incidence of confirmed cattle TB was elevated (14, 15, 22–24), and spatial clustering of cattle infection was reduced (21).This propensity of nonselective badger culling to prompt social perturbation and hence increase disease transmission is a major constraint on its utility as a tool for controlling cattle TB. An alternative approach, first proposed in the 1980s, would be to target culling at test-positive badgers, just as current controls target test-positive cattle (16, 25). A further elaboration, termed test–vaccinate/remove (TVR), involves killing test-positive badgers while vaccinating test-negative badgers. A pilot TVR program is scheduled to take place across 100 sq km in Northern Ireland in 2014 (26).Selective culling approaches (such as TVR) are likely to remove relatively small numbers of badgers. First, constraints on capture success limit testing to 56–85% of the badger population (27, 28). Second, not all captured badgers will be infected with M. bovis: in the 10 initial proactive culls of the Randomized Badger Culling Trial (RBCT), 2–38% of badgers had infection detectable by bacterial culture at standard necropsy (29). Third, not all infected badgers are detectable by available live tests: the only available trap-side test detected 49% of badgers that were culture-positive at necropsy (30), and standard necropsy itself detected only 55% of infected badgers (31). This combination of imperfect capture success, low average infection prevalence, and imperfect test sensitivity means that the numbers of badgers to be killed by selective culling would probably be low, usually just one or two badgers within a social group (32). The same factors, combined with incomplete vaccine efficacy (33), mean that some infected and some susceptible badgers would be expected to remain despite implementation of TVR.Simulations indicate that the likely consequences of TVR for cattle TB control are highly sensitive to assumptions about whether culling small numbers of badgers prompts social perturbation (34, 35). Neither cage trapping for testing nor vaccination has been found to cause behavioral change. If the culling component of TVR likewise causes no perturbation, then TVR is predicted to reduce the prevalence of M. bovis infection in badgers and hence the incidence of cattle TB (34, 35). However, if TVR causes perturbation similar to that associated with past large- and small-scale culling, then it is projected to prompt sustained (34) or transient (35) increases in cattle TB. Unfortunately, it is not known which of these scenarios is more likely. Although the behavioral and epidemiological consequences of nonselective culling are relatively well understood, there have been no empirical studies of badgers’ behavioral responses to killing small numbers of animals per social group, as would occur under TVR and other forms of selective culling.In this paper, we use data from a large-scale study to assess whether killing small numbers of badgers would be expected to prompt social perturbation. We compare patterns of badger movement and M. bovis infection at the start of the RBCT (conducted 1998–2005) (14) with two indices of badger mortality. Our first measure, road density, provides an index of the numbers of badgers killed in road accidents (36), an important cause of badger mortality in Britain (37, 38). Our second measure is prior nonselective culling, conducted during the period 1986–1998 as small-scale badger removal operations (BROs), which typically targeted single farms (8). We hypothesized that high road densities and intense prior culling would each lead to expanded badger movement and elevated M. bovis prevalence. Further, we hypothesized that perturbation might be avoided if the number of badgers killed remained below a certain threshold, and sought to estimate this threshold.     

Recent advances towards tuberculosis control: vaccines and biomarkers

Of all infectious diseases, tuberculosis (TB) remains one of the most important causes of morbidity and mortality. Recent advances in understanding the biology of Mycobacterium tuberculosis (Mtb) infection and the immune response of the infected host have led to the development of several new vaccines, a number of which are already undergoing clinical trials. These include pre‐exposure prime vaccines, which could replace bacille Calmette–Guérin (BCG), and pre‐exposure booster vaccines given in addition to BCG. Infants are the target population of these two types of vaccines. In addition, several postexposure vaccines given during adolescence or adult life, in addition to BCG as a priming vaccine during infancy, are undergoing clinical testing. Therapeutic vaccines are currently being assessed for their potential to cure active TB as an adjunct to chemotherapy. BCG replacement vaccines are viable recombinant BCG or double‐deletion mutants of Mtb. All booster vaccines are composed of one or several antigens, either expressed by viral vectors or formulated with adjuvants. Therapeutic vaccines are killed mycobacterial preparations. Finally, multivariate biomarkers and biosignatures are being generated from high‐throughput data with the aim of providing better diagnostic tools to specifically determine TB progression. Here, we provide a technical overview of these recent developments as well of the relevant computational approaches and highlight the obstacles that still need to be overcome.