Effect of an exercise-based cardiac rehabilitation program on quality of life of patients with chronic Chagas cardiomyopathy: results from the PEACH randomized clinical trial.

To investigate the effect of an exercise-based cardiac rehabilitation program on the quality of life (QoL) of patients with chronic Chagas cardiomyopathy (CCC). PEACH study was a single-center, superiority randomized clinical trial of exercise training versus no exercise (control). The sample comprised Chagas disease patients with CCC, left ventricular ejection fraction < 45%, without or with HF symptoms (CCC stages B2 or C, respectively). QoL was assessed at baseline, after three months, and at the end of six months of follow-up using the SF-36 questionnaire. Patients randomized for the exercise group (n = 15) performed exercise training (aerobic, strength and stretching exercises) for 60 min, three times a week, during six months. Patients in the control group (n = 15) were not provided with a formal exercise prescription. Both groups received identical nutritional and pharmaceutical counseling during the study. Longitudinal analysis of the effects of exercise training on QoL, considering the interaction term (group × time) to estimate the rate of changes between groups in the outcomes (represented as beta coefficient), was performed using linear mixed models. Models were fitted adjusting for each respective baseline QoL value. There were significant improvements in physical functioning (ß = + 10.7; p = 0.02), role limitations due to physical problems (ß = + 25.0; p = 0.01), and social functioning (ß = + 19.2; p < 0.01) scales during the first three months in the exercise compared to the control group. No significant differences were observed between groups after six months. Exercise-based cardiac rehabilitation provided short-term improvements in the physical and mental aspects of QoL of patients with CCC.Trial registration: ClinicalTrials.gov Identifier: NCT02517632; August 7, 2015.

Consistency and applicability of return to function guidelines in tactical-athletes with exertional heat illness. A systematic review.

OBJECTIVE: To assess the consistency of return to sport and occupation recommendations following EHI provided in published clinical practice guidelines, consensus statements, position statements, and practice alerts. The agreement between medical policies governing the return to duty following EHI between the branches of the United States Armed Forces and published recommendations was assessed. METHODS: Ovid MEDLINE, Web of Science, and CINAHL databases were searched for clinical practice guidelines and position statements published at any time that guided return to activity in individuals with EHI. Methodological quality was assessed, and the specific recommendations for clinical management were extracted. Consistency of recommendations was evaluated. Agreement between published guidelines and the policies governing return to activity in military tactical athletes with heat injury were also evaluated. RESULTS: Guidelines developed by two civilian sports medicine societies in the United States detailing recommendations for return to function following EHI were identified. There was consistency between guidelines regarding recommendations that addressed abstinence from activity; medical follow-up; graded resumption of activity; and return to function. Pertaining military policy, contemporary regulations published in recent years reflected the recommendations provided in the professional guidelines. The greatest incongruence was noted in older military policies. CONCLUSIONS: This systematic review highlights the need for consistent recommendations across all branches of the military and medical specialties pertaining to returning servicemembers to duty after EHI .

The Association Between Physical Performance and Health-Related Quality of Life Based on the EQ-5D-3L Questionnaire in Patients With Chagas Disease.

OBJECTIVES: Chagas disease (CD) is a chronic disease to millions worldwide, and many patients develop heart disease. In addition, they are part of an aging population. These characteristics can be associated with a reduction in physical performance and health-related quality of life (HRQoL). This study evaluated HRQoL, and the relationship between physical performance and HRQoL in patients with chronic CD. METHODS: We used the 3-level version of EuroQol 5-dimensional questionnaire (EQ-5D-3L), with the visual analog scale (VAS). Physical performance was measured with 30-s chair-stand test (30sCST) and timed up and go test (TUGT). RESULTS: Sixty-three patients were evaluated. The majority were women (68.2%) aged 67.7 ± 9.7 years. Overall EQ-5D-3L utility index was 0.65 ± 0.28, and VAS score was 68.4 ± 25.1. Most patients with intermediate and high performance in 30sCST referred no problems in the domains "mobility," "usual activities," and "pain/feeling ill" (P < .001, P = .01, and P = .025, respectively). In a similar way, most patients with intermediate and high performance in TUGT referred no problems in "mobility" (P < .0001) and "usual activities" (P = .001). Higher performance in both tests was associated with higher overall EQ-5D-3L utility and VAS scores. HRQoL measured by EQ-5D-3L was associated with physical status in a cohort of patients with chronic CD. The results underscore the contribution of physical performance, measured by 2 inexpensive and safe physical tests, to HRQoL in these patients. CONCLUSION: Strategies aiming the improvement of HRQoL in patients with CD may focus on mobility skills and force. Future studies evaluating interventions in physical performance should be a priority in these patients.

Inflammatory Pathophysiology as a Contributor to Myeloproliferative Neoplasms.

Myeloid neoplasms, including acute myeloid leukemia (AML), myeloproliferative neoplasms (MPNs), and myelodysplastic syndromes (MDS), feature clonal dominance and remodeling of the bone marrow niche in a manner that promotes malignant over non-malignant hematopoiesis. This take-over of hematopoiesis by the malignant clone is hypothesized to include hyperactivation of inflammatory signaling and overproduction of inflammatory cytokines. In the Ph-negative MPNs, inflammatory cytokines are considered to be responsible for a highly deleterious pathophysiologic process: the phenotypic transformation of polycythemia vera (PV) or essential thrombocythemia (ET) to secondary myelofibrosis (MF), and the equivalent emergence of primary myelofibrosis (PMF). Bone marrow fibrosis itself is thought to be mediated heavily by the cytokine TGF-ß, and possibly other cytokines produced as a result of hyperactivated JAK2 kinase in the malignant clone. MF also features extramedullary hematopoiesis and progression to bone marrow failure, both of which may be mediated in part by responses to cytokines. In MF, elevated levels of individual cytokines in plasma are adverse prognostic indicators: elevated IL-8/CXCL8, in particular, predicts risk of transformation of MF to secondary AML (sAML). Tumor necrosis factor (TNF, also known as TNFα), may underlie malignant clonal dominance, based on results from mouse models. Human PV and ET, as well as MF, harbor overproduction of multiple cytokines, above what is observed in normal aging, which can lead to cellular signaling abnormalities separate from those directly mediated by hyperactivated JAK2 or MPL kinases. Evidence that NFκB pathway signaling is frequently hyperactivated in a pan-hematopoietic pattern in MPNs, including in cells outside the malignant clone, emphasizes that MPNs are pan-hematopoietic diseases, which remodel the bone marrow milieu to favor persistence of the malignancy. Clinical evidence that JAK2 inhibition by ruxolitinib in MF neither reliably reduces malignant clonal burden nor eliminates cytokine elevations, suggests targeting cytokine mediated signaling as a therapeutic strategy, which is being pursued in new clinical trials. Greater knowledge of inflammatory pathophysiology in MPNs can therefore contribute to the development of more effective therapy.

The Association Between Physical Performance and Health-Related Quality of Life Based on the EuroQol 5-Dimensional Questionnaire in Patients With Chagas Disease.

OBJECTIVES: Chagas disease (CD) is a chronic disease to millions worldwide, and many patients develop heart disease. In addition, they are part of an aging population. These characteristics can be associated with a reduction in physical performance and health-related quality of life (HRQoL). This study evaluated HRQoL, and the relationship between physical performance and HRQoL in patients with chronic CD. METHODS: We used the 3-level version of EuroQol 5-dimensional questionnaire (EQ-5D-3L), with the visual analog scale (VAS). Physical performance was measured with 30-s chair-stand test (30sCST) and timed up and go test (TUGT). RESULTS: Sixty-three patients were evaluated. The majority were women (68.2%) aged 67.7 ± 9.7 years. Overall EQ-5D-3L utility index was 0.65 ± 0.28, and VAS score was 68.4 ± 25.1. Most patients with intermediate and high performance in 30sCST referred no problems in the domains "mobility," "usual activities," and "pain/feeling ill" (P < .001, P = .01, and P = .025, respectively). In a similar way, most patients with intermediate and high performance in TUGT referred no problems in "mobility" (P < .0001) and "usual activities" (P = .001). Higher performance in both tests was associated with higher overall EQ-5D-3L utility and VAS scores. HRQoL measured by EQ-5D-3L was associated with physical status in a cohort of patients with chronic CD. The results underscore the contribution of physical performance, measured by 2 inexpensive and safe physical tests, to HRQoL in these patients. CONCLUSION: Strategies aiming the improvement of HRQoL in patients with CD may focus on mobility skills and force. Future studies evaluating interventions in physical performance should be a priority in these patients.

Systemic microvascular endothelial dysfunction is associated with left ventricular ejection fraction reduction in chronic Chagas disease patients.

OBJECTIVE: This study compares microvascular reactivity (MR) in chronic Chagas disease (CD) patients with healthy individuals, matched for sex and age. In addition, we evaluated the association between MR and left ventricular ejection fraction (LVEF) in patients. METHODS: Acetylcholine iontophoresis was performed on the forearm skin, using laser speckle contrast imaging, to evaluate endothelium-dependent vasodilation. Clinical data were obtained from medical records. RESULTS: Thirty-six patients were compared to 25 healthy individuals (controls). Vasodilation was higher in controls, when compared to patients (p < .0001). There was a significant association between LVEF, stratified into quartiles, and MR (p-value for linear trend = .002). In addition, there was no difference in MR between patients with normal LVEF and the control group. In patients, MR was independent of the presence of arterial hypertension or diabetes. CONCLUSIONS: We have shown for the first time that the reduction of MR is associated with a decrease of LVEF in a cohort of chronic CD patients. The results were not affected by comorbidities, such as hypertension or diabetes. The evaluation of systemic endothelial function may be useful to tailor therapeutic and preventive approaches, targeted at systolic left ventricular failure associated with chronic CD cardiomyopathy.

COVID-19 and Microvascular Disease: Pathophysiology of SARS-CoV-2 Infection With Focus on the Renin-Angiotensin System.

The recently described severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of people, with thousands of fatalities. It has prompted global efforts in research, with focus on the pathophysiology of coronavirus disease-19 (COVID-19), and a rapid surge of publications. COVID-19 has been associated with a myriad of clinical manifestations, including the lungs, heart, kidneys, central nervous system, gastrointestinal system, skin, and blood coagulation abnormalities. The endothelium plays a key role in organ dysfunction associated with severe infection, and current data suggest that it is also involved in SARS-CoV-2-induced sepsis. This critical review aimed to address a possible unifying mechanism underlying the diverse complications of COVID-19: microvascular dysfunction, with emphasis on the renin-angiotensin system. In addition, research perspectives are suggested in order to expand understanding of the pathophysiology of the infection.

Gout, Hyperuricaemia and Crystal-Associated Disease Network (G-CAN) consensus statement regarding labels and definitions of disease states of gout.

OBJECTIVE: There is a lack of standardisation in the terminology used to describe gout. The aim of this project was to develop a consensus statement describing the recommended nomenclature for disease states of gout. METHODS: A content analysis of gout-related articles from rheumatology and general internal medicine journals published over a 5-year period identified potential disease states and the labels commonly assigned to them. Based on these findings, experts in gout were invited to participate in a Delphi exercise and face-to-face consensus meeting to reach agreement on disease state labels and definitions. RESULTS: The content analysis identified 13 unique disease states and a total of 63 unique labels. The Delphi exercise (n=76 respondents) and face-to-face meeting (n=35 attendees) established consensus agreement for eight disease state labels and definitions. The agreed labels were as follows: 'asymptomatic hyperuricaemia', 'asymptomatic monosodium urate crystal deposition', 'asymptomatic hyperuricaemia with monosodium urate crystal deposition', 'gout', 'tophaceous gout', 'erosive gout', 'first gout flare' and 'recurrent gout flares'. There was consensus agreement that the label 'gout' should be restricted to current or prior clinically evident disease caused by monosodium urate crystal deposition (gout flare, chronic gouty arthritis or subcutaneous tophus). CONCLUSION: Consensus agreement has been established for the labels and definitions of eight gout disease states, including 'gout' itself. The Gout, Hyperuricaemia and Crystal-Associated Disease Network recommends the use of these labels when describing disease states of gout in research and clinical practice.

Embolization of Ruptured Renal Angiomyolipoma in Puerpera.

Angiomyolipomas (AMLs) are rare benign tumors derived from mesenchymal tissue and composed of varying degrees of adipose tissue, muscle and blood vessels. Renal AMLs (RAMLs) are the result of a sporadic event, and, in most of cases, the diagnosis is usually incidental, but hemorrhage and shock may be present. During pregnancy, the size of AMLs may increase and they may rupture, probably due to the high expression of hormone receptors, and the increase in maternal circulation and abdominal pressure. The authors present a case of a woman with ruptured RAML submitted to urgent endovascular treatment four days after giving birth by cesarean section.

Angiomiolipomas (AMLs) são tumores benignos raros derivados do tecido mesenquimal, compostos em graus variados de tecido adiposo, muscular e de vasos sanguíneos. Os AMLs renais (AMLRs) resultam de um evento esporádico e, na maioria dos casos, o diagnóstico costuma ser fortuito, mas quadros de hemorragia e choque podem estar presentes. Durante a gestação, os AMLs podem aumentar de tamanho e romper, provavelmente pela alta expressão de receptores hormonais, e pelo aumento da circulação materna e da pressão abdominal. Os autores apresentam um caso de uma paciente com AMLR roto submetida a tratamento endovascular de urgência no quarto dia pós-operatório de uma cesariana.

Embolization of ruptured renal angiomyolipoma in puerpera / Embolização de angiomiolipoma renal roto em puérpera

Abstract Angiomyolipomas (AMLs) are rare benign tumors derived from mesenchymal tissue and composed of varying degrees of adipose tissue, muscle and blood vessels. Renal AMLs (RAMLs) are the result of a sporadic event, and, in most of cases, the diagnosis is usually incidental, but hemorrhage and shock may be present. During pregnancy, the size of AMLs may increase and they may rupture, probably due to the high expression of hormone receptors, and the increase in maternal circulation and abdominal pressure. The authors present a case of a woman with ruptured RAML submitted to urgent endovascular treatment four days after giving birth by cesarean section.

Resumo Angiomiolipomas (AMLs) são tumores benignos raros derivados do tecido mesenquimal, compostos em graus variados de tecido adiposo, muscular e de vasos sanguíneos. Os AMLs renais (AMLRs) resultam de um evento esporádico e, na maioria dos casos, o diagnóstico costuma ser fortuito, mas quadros de hemorragia e choque podem estar presentes. Durante a gestação, os AMLs podem aumentar de tamanho e romper, provavelmente pela altaexpressãodereceptoreshormonais,epeloaumentodacirculaçãomaternaedapressão abdominal. Os autores apresentam um caso de uma paciente com AMLR roto submetida a tratamento endovascular de urgência no quarto dia pós-operatório de uma cesariana.

Impaired voice processing in reward and salience circuits predicts social communication in children with autism.

Engaging with vocal sounds is critical for children's social-emotional learning, and children with autism spectrum disorder (ASD) often 'tune out' voices in their environment. Little is known regarding the neurobiological basis of voice processing and its link to social impairments in ASD. Here, we perform the first comprehensive brain network analysis of voice processing in children with ASD. We examined neural responses elicited by unfamiliar voices and mother's voice, a biologically salient voice for social learning, and identified a striking relationship between social communication abilities in children with ASD and activation in key structures of reward and salience processing regions. Functional connectivity between voice-selective and reward regions during voice processing predicted social communication in children with ASD and distinguished them from typically developing children. Results support the Social Motivation Theory of ASD by showing reward system deficits associated with the processing of a critical social stimulus, mother's voice, in children with ASD. Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that minor issues remain unresolved (see decision letter).

Influence of tramadol on functional recovery of acute spinal cord injury in rats

Abstract Purpose: To evaluate the influence tramadol on functional recovery of acute spinal cord injury in rats. Methods: Ten rats were divided into two groups (n = 5). All animals were submitted by a laminectomy and spinal cord injury at eighth thoracic vertebra. In control group, the rats didn't receive any analgesic. In tramadol group, the rats received tramadol 4mg/Kg at 12/12h until 5 days by subcutaneous. Animals were following by fourteen days. Was evaluated the Basso, Beattie, Bresnahan scale (locomotor evaluation) and Rat Grimace Scale (pain evaluation) at four periods. Results: There no difference between the groups in locomotor evaluation in all periods evaluated (p>0.05) and in both groups there was a partial recover of function. The tramadol group show a lower pain levels at the first, third and seventh postoperatively days when comparing to the control group. Conclusion: The tramadol as an analgesic agent don't influence on functional recovery of acute spinal cord injury in rats

Research proposal: inflammation and oxidative stress in coronary artery bypass surgery graft: comparison between diabetic and non-diabetic patients.

BACKGROUND: Diabetes mellitus patients (DM) have more severe progression of atherosclerotic disease than non-diabetic (NDM) individuals. In situ inflammation and oxidative stress are key points in the pathophysiology of atherosclerosis, a concept largely based on animal model research. There are few studies comparing inflammation and oxidative stress parameters in medium-sized arteries between DM and NDM patients. A fragment of the internal mammary artery used in coronary artery bypass grafting (CABG) will be employed for this purpose OBJECTIVE: To assess the expression of inflammatory markers tumor necrosis factor-α, transforming growth factor-ß1, nuclear factor kappa B, the enzymes superoxide dismutase, and catalase in the vascular wall of the arterial graft used in CABG, comparing DM and NDM patients RESULTS: The present study will add information to the vascular degenerative processes occurring in diabetic patients.