Reduction on Proinflammatory Cytokines after Application of Transcutaneous Electrical Nerve Stimulation (TENS) in Patients with a Breast Cancer: A Nonrandomized, Open, and Single-Arm Study Protocol with Paired Analysis.

BACKGROUND: Transcutaneous electrical nerve stimulation (TENS) has been used as analgesic therapy in many diseases. It is already known that studies that have observed the relationship between pain and cytokines have found that patients who report less severe pain have less production of proinflammatory cytokines. However, one another accepted mechanism is that decreasing proinflammatory cytokines results in decreased pain intensity. Analyzing the literature, the authors describe that, in addition to the analgesic effect, TENS has shown systemic effects, and clinically, the reduction of proinflammatory cytokines could be a protective factor against inflammation. To test the inflammatory effect of TENS, we researched the literature for clinical conditions that suggest that proinflammatory cytokines are one of the main mediators of the disease process. Chronic inflammation is one of the risk factors mentioned for the development of a new cancer; at the same time, it is indicated as an indicator of the worst prognosis. Studies also suggest that the worst prognosis of breast cancer, one of the types with the highest incidence in the world, may be related to increased inflammatory activity. Considering that inflammation is increased in breast cancer and that TENS can reduce proinflammatory cytokines even without blocking the pain pathway, our hypothesis is that the anti-inflammatory effect of TENS can bring benefits to these patients. The aim of this study will be to evaluate the effect of TENS on blood reduction of proinflammatory cytokines in breast cancer patients. METHODS: This study will evaluate at least 59 patients, over 18 years of age, diagnosed with breast cancer, but who have not yet started any treatment. All patients will be submitted to TENS intervention (Ibramed, Model Neurodyn III, parameters: VIF-turn on, frequency-2-247 Hz, pulse size-50-500 µs, and intensity (mA)-maximum tolerated by the patient), and the data will be analyzed in the pre- and postintervention of each patient. The application has a total duration of 30 minutes, and 8 ml of blood will be collected before and after the intervention. Proinflammatory (IL-1, IL-2, IL-6, IL-7, and TNF-α) and anti-inflammatory (IL-4, IL-10, IL-13, and FTCß) cytokines will be analyzed. As a primary endpoint, we will analyze the reduction in blood concentration of proinflammatory cytokines, and as secondary endpoints, we will analyze the size of the effect according to each type of proinflammatory cytokine, describe the effect size of the reduction according to the breast cancer immunohistochemistry, and analyze the effect of TENS on anti-inflammatory cytokines. This study is approved by the Research Ethics Committee (Centro Universitário FMABC, Brazil) and registered in the Brazilian Clinical Trials (Search text: RBR-10jbwh47).

Effects of Transcutaneous Electrical Nerve Stimulation on Proinflammatory Cytokines: Systematic Review and Meta-Analysis.

The mechanism of pain reduction involves bidirectional processes of pain blocking (nociception) and reductions in the levels of proinflammatory cytokines in the blood. Does transcutaneous electrical nerve stimulation (TENS) reduce blood levels of proinflammatory cytokines? For this systematic review, we searched in six databases to identify randomized controlled trials with the criteria: humans older than 18 years (adults), use of TENS in the experimental group, and having at least one pre- and postintervention blood level of at least one proinflammatory cytokine. The risk of bias and the level of evidence were assessed. Five studies were included involving 240 participants. The heterogeneity of the studies was high (I2: 85%); therefore, we used a random-effects meta-analysis. It was observed through the meta-analysis synthesis measures that there were statistically significant differences following the use of TENS to reduce the general group of cytokines. When grouped by chronic disease, by postoperative settings, or by individual studies in the case of IL-6, it was observed that the significant reduction of cytokines related to the use of TENS was maintained. The use of TENS reduced the blood levels of proinflammatory cytokines (we observed a protective factor of TENS in relation to inflammation). The protocol of the systematic review was registered in PROSPERO, CRD42017060379.

Evaluation of the impact of single-nucleotide polymorphisms on treatment response, survival and toxicity with cytarabine and anthracyclines in patients with acute myeloid leukaemia: a systematic review protocol.

INTRODUCTION: Acute myeloid leukaemia is the most common type of acute leukaemia in the world. Thus, the study of genetic alterations, such as single-nucleotide polymorphisms (SNPs), has contributed to a better understanding of the mechanisms underlying leukaemogenesis, to improve the prognosis and to increase the survival of these patients. However, there is no synthesis of evidence in the literature evaluating the quality of evidence and the risk of bias in the studies such that the results can be translated. Thus, this systematic review protocol aims to assess the impact of SNPs on genes involved in the metabolism of cytarabine and anthracyclines with respect to survival, treatment response and toxicity in patients with AML. METHODS: This systematic review protocol is based on PRISMA guidelines and includes searches in six electronic databases, contact with authors, repositories of clinical trials, and cancer research. Studies published in peer-reviewed journals will be included if they meet the eligibility criteria: (a) samples composed of individuals of any age, of both sexes, with a diagnosis of AML, regardless of the time of diagnosis of disease; (b) participants who have undergone or are undergoing cytarabine- and anthracycline-associated chemotherapy or cytarabine-only chemotherapy; and (c) in vivo studies. Studies that include patients with promyelocytic leukaemia (Fab type 3) will be excluded because this disease has different treatment. The process of study selection, data extraction, and evaluation/synthesis will be performed in duplicate. Assessment of methodological quality and risk of bias will be performed using the Cochrane Risk of Bias Tool for randomized clinical studies and the Downs-Black Checklist for cohort and case-control studies. The synthesis of evidence will include the level of evidence based on the GRADE protocol. A meta-analysis of the association between SNPs and outcomes may be performed based on Cochrane guidelines. DISCUSSION: It is expected that clinical decisions for AML patients will consider evidence-based practices to contribute to better patient management. In this way, we will be able to define how to treat patients with AML to improve their survival and quality of life. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018100750.

Correlation between municipal human development index and stroke mortality: a study of Brazilian capitals.

OBJECTIVE: To analyze the correlation between municipal human development indices (MHDIs) and stroke mortality in residents of Brazilian state capitals in 2010. A secondary data analysis was conducted in 2015 using data for the MHDI and the following dimensions: income, longevity and education which were obtained from the United Nations Development Program. Additionally, we analyzed age-standardized stroke mortality data from the Department of System Information Unified Health of Brazil. RESULTS: We observed a correlation between stroke mortality and MHDIs overall (Pearson r = - 0.563; p = 0.002) and within the following dimensions: income (Spearman's ρ = - 0.479; p = 0.011), longevity (Pearson r = - 0.510; p = 0.006) and education (Pearson r = - 0.592; p = 0.001). We identified moderate but significant negative correlations between MHDI overall and in its individual dimensions (income, longevity, and age) and stroke mortality in Brazilian capitals. Stroke is the second leading cause of death in industrialized countries and the leading cause of death in Brazil. Therefore, the discovery of factors that may influence the epidemiology of stroke is important for the construction of adequate policies considering to the socioeconomic status in these places and with an emphasis in lower socioeconomic status places.

Evaluation of functional rehabilitation physiotherapy protocol in the postoperative patients with anterior cruciate ligament reconstruction through clinical prognosis: an observational prospective study.

BACKGROUND: The aim of the study was to evaluate the evolution of patients subject to physical treatment based on guidelines of functional rehabilitation after surgery anterior cruciate ligament reconstruction. METHODS: This is a prospective study of 177 patients with anterior cruciate ligament injury, who underwent surgery and physical therapy guideline conducted in an orthopedic clinic in São Paulo, southeastern Brazil. The clinical evolution of patients was made according to Lysholm and IKDC questionnaire on the 1st day after surgery with 30, 90 and 180 days of treatment. RESULTS: There was statistically significant increase in the gross values of Lysholm and IKDC questionnaires during the treatment (p < 0.001), which indicates progressive gain of function. According to the scores obtained from the IKDC, it can be observed that in stage 1 the average progress was 53.5 %, falling to 50 % in stage 2, and 26.1 % in stage 3. As to Lysholm score, it started with 87.7 %, falling to 62.6 % in the second stage and 7 % in the third stage, both statistically significant (p < 0.001). The rehabilitation-oriented functional objectives priority is to quickly get the exercises to gain breadth, strength and proprioception, optimizing and improving the integration of the athlete back to sport. CONCLUSION: Synthesizing the gradual gain of function and according to clinical outcomes assessed by IKDC and Lysholm, the functional guideline presented may be considered an alternative for rehabilitation of patients in postoperative anterior cruciate ligament.