Neuroprotective Effect of Vitamin D on Behavioral and Oxidative Parameters of Male and Female Adult Wistar Rats Exposed to Mancozeb (manganese/zinc ethylene bis-dithiocarbamate).

The constant exposure of rural workers to pesticides is a serious public health problem. Mancozeb (MZ) is a pesticide  linked to hormonal, behavioral, genetic, and neurodegenerative effects, mainly related to oxidative stress. Vitamin D is a promising molecule that acts as a protector against brain aging. This study aimed to evaluate the neuroprotective role of vitamin D in adult male and female Wistar rats exposed to MZ. Animals received 40 mg/kg of MZ i.p. and 12.5 µg/kg or 25 µg/kg vitamin D by gavage, twice a week, for 6 weeks. The concentration of manganese had a significant increase in the hippocampus of both sexes and in the striatum of females, unlike zinc, which did not show a significant increase. MZ poisoning led to mitochondrial changes in brain tissues and promoted anxiogenic effects, especially in females. Alterations in antioxidant enzymes, mainly in the catalase activity were observed in intoxicated rats. Taken together, our results showed that exposure to MZ leads to the accumulation of manganese in brain tissues, and the behavior and metabolic/oxidative impairment were different between the sexes. Furthermore, the administration of Vitamin D was effective in preventing the damage caused by the pesticide.

Immediate and long-term effects of manual chest compression and decompression maneuver on patients receiving invasive mechanical ventilation.

BACKGROUND: It has been reported that the manual chest compression and decompression (MCCD) maneuver can increase lung volume in patients receiving invasive mechanical ventilation (IMV), but some important questions related to this maneuver require answers: how long the effects of MCCD on lung volume remain, and whether there are effects on other respiratory and hemodynamic variables. METHODS: Patients receiving IMV support in an intensive care unit (ICU) with signs of hypoventilation, hypoexpansion, or atelectasis were eligible to receive the MCCD maneuver. Immediately before the maneuver, respiratory and hemodynamic parameters were collected. Then, 20 MCCD maneuvers were performed while measured the same parameters. After 10 min, all parameters were measured again. The primary outcome was the tidal volume (Vt ) during the MCCD maneuver and after 10 min compared to the previous Vt . RESULTS: Of the 255 patients who were mechanically ventilated in the study period, 105 patients composed the final cohort. The MCCD increased inspiratory tidal volume (iVt ), expiratory tidal volume (eVt ), and chest dynamic compliance (Cdyn ) during the application of the maneuver, but after 10 min, these parameters returned to their basal levels. The MCCD maneuver did not change the peak pressure, respiratory rate, peripheral oxygen saturation (SpO2 ), heart rate, or blood pressure. There was no difference in increased iVt in patients with sedation, respiratory comorbidity, or obesity. Further, there was no association between the iVt response to the MCCD and the admission diagnosis, and no correlation with the ICU length of stay, IMV duration, or APACHE II score. IMPLICATIONS OF PHYSIOTHERAPY PRACTICE: We concluded that MCCD increased iVt , eVt , and Cdyn during the application of the maneuver, but this effect was not observed after 10 min. Randomized controlled trials should be performed in the future to investigate the mechanism involved in increasing Vt and the possible impact of the MCCD maneuver on ICU outcomes.

Emergence of Two Distinct SARS-CoV-2 Gamma Variants and the Rapid Spread of P.1-like-II SARS-CoV-2 during the Second Wave of COVID-19 in Santa Catarina, Southern Brazil.

The western mesoregion of the state of Santa Catarina (SC), Southern Brazil, was heavily affected as a whole by the COVID-19 pandemic in early 2021. This study aimed to evaluate the dynamics of the SARS-CoV-2 virus spreading patterns in the SC state from March 2020 to April 2021 using genomic surveillance. During this period, there were 23 distinct variants, including Beta and Gamma, among which the Gamma and related lineages were predominant in the second pandemic wave within SC. A regionalization of P.1-like-II in the Western SC region was observed, concomitant to the increase in cases, mortality, and the case fatality rate (CFR) index. This is the first evidence of the regionalization of the SARS-CoV-2 transmission in SC and it highlights the importance of tracking the variants, dispersion, and impact of SARS-CoV-2 on the public health systems.

Predictive Factors of Extubation Failure in COVID-19 Mechanically Ventilated Patients.

Purpose: We investigated whether COVID-19 patients on mechanical ventilation (MV) had a different extubation outcome compared to non-COVID-19 patients while identifying predictive factors of extubation failure in the former. Methods: A retrospective, single-center, and observational study was done on 216 COVID-19 patients admitted to an intensive care unit (ICU) between March 2020 and March 2021, aged ≥ 18 years, in use of invasive MV for more than 24 h, which progressed to weaning. The primary outcome that was evaluated was extubation failure during ICU stay. A statistical analysis was performed to evaluate the association of patient characteristics with extubation outcome, and a Poisson regression model determined the predictive value. Results: Seventy-seven patients were extubated; the mean age was 57.2 years, 52.5% were male, and their mean APACHE II score at admission was 17.8. On average, MV duration until extubation was 8.7 ± 3.7 days, with 14.9 ± 10.1 days of ICU stay and 24.6 ± 14.0 days with COVID-19 symptoms. The rate of extubation failure (ie, the patient had to be reintubated during their ICU stay) was 22.1% (n = 17), while extubation was successful in 77.9% (n = 60) of cases. Failure was observed in only 7.8% of cases when evaluated 48 hours after extubation. The mean reintubation time was 4.28 days. After adjusting the analysis for age, sex, during of symptoms, days under MV, dialysis, and PaO2/FiO2 ratio, some parameters independently predicted extubation failure: age ≥ 66 years (APR = 5.12 [1.35-19.46]; p = 0.016), ≥ 31 days of symptoms (APR = 5.45 [0.48-62.19]; p = 0.016), and need for dialysis (APR = 5.10 [2.00-13.00]; p = 0.001), while a PaO2/FiO2 ratio >300 decreased the probability of extubation failure (APR = 0.14 [0.04-0.55]; p = 0.005). The presence of three predictors (ie, age ≥ 66 years, time of symptoms ≥ 31 days, need of dialysis, and PaO2/FiO2 ratio < 200) increased the risk of extubation failure by a factor of 23.0 (95% CI, 3.34-158.5). Conclusion: COVID-19 patients had an extubation failure risk that was almost three times higher than non-COVID-19 patients, with the extubation of the former being delayed compared to the latter. Furthermore, an age ≥ 66 years, time of symptoms ≥ 31 days, need of dialysis, and PaO2/FiO2 ratio > 200 were independent predictors for extubation failure, and the presence of three of these characteristics increased the risk of failure by a factor of 23.0.

Protective Effects of Probucol on Different Brain Cells Exposed to Manganese.

Manganese (Mn) is an essential metal for many functions in the body. However, in excess, it can be neurotoxic and cause a Parkinson-like syndrome, known as manganism. Here, we aimed to identify a protective effect of probucol, a lipid-lowering agent with anti-inflammatory and antioxidant properties, against Mn-induced toxicity in human neuroblastoma (SH-SY5Y) and glioblastoma (C6) cell lines. The cells were incubated with increasing concentrations of Mn followed by probucol addition 1, 3, 6, and/or 24 h to assess the metal toxic doses and measure the protective effect of probucol against Mn-induced oxidative damage. Longer exposition to Mn showed decreased SH-SY5Y cellular viability in concentrations higher than 100 µM, and probucol was able to prevent this effect. The C6 cells were more sensitive to the Mn deleterious actions, decreasing the cell viability after 6 h of 500 µM Mn exposure. In addition, probucol prevents the complex I and II of the mitochondrial respiratory chain (MRC) inhibition caused by Mn and decreased the intracellular ROS production. Taken together, our results showed that Mn toxicity affects differently both cell lines and probucol has a protective effect against the oxidative imbalance in the central nervous system.

Prediction of extubation outcome in mechanically ventilated patients: Development and validation of the Extubation Predictive Score (ExPreS).

Despite the best efforts of intensive care units (ICUs) professionals, the extubation failure rates in mechanically ventilated patients remain in the range of 5%-30%. Extubation failure is associated with increased risk of death and longer ICU stay. This study aimed to identify respiratory and non-respiratory parameters predictive of extubation outcome, and to use these predictors to develop and validate an "Extubation Predictive Score (ExPreS)" that could be used to predict likelihood of extubation success in patients receiving invasive mechanical ventilation (IMV). Derivation cohort was composed by patients aged ≥18 years admitted to the ICU and receiving IMV through an endotracheal tube for >24 hours. The weaning process followed the established ICU protocol. Clinical signs and ventilator parameters of patients were recorded during IMV, in the end phase of weaning in pressure support ventilation (PSV) mode, with inspiratory pressure of 7 cm H2O over the PEEP (positive end expiratory pressure). Patients who tolerated this ventilation were submitted to spontaneous breathing trial (SBT) with T-tube for 30 minutes. Those who passed the SBT and a subsequent cuff-leak test were extubated. The primary outcome of this study was extubation success at 48 hours. Parameters that showed statistically significant association with extubation outcome were further investigated using the receiver operating characteristics (ROC) analysis to assess their predictive value. The area under the curve (AUC) values were used to select parameters for inclusion in the ExPreS. Univariable logistic regression analysis and ROC analysis were performed to evaluate the performance of ExPreS. Patients' inclusion and statistical analyses for the prospective validation cohort followed the same criteria used for the derivation cohort and the decision to extubate was based on the ExPreS result. In the derivation cohort, a total of 110 patients were extubated: extubation succeeded in 101 (91.8%) patients and failed in 9 (8.2%) patients. Rapid shallow-breathing index (RSBI) in SBT, dynamic lung compliance, duration of IMV, muscle strength, estimated GCS, hematocrit, and serum creatinine were significantly associated with extubation outcome. These parameters, along with another parameter-presence of neurologic comorbidity-were used to create the ExPreS. The AUC value for the ExPreS was 0.875, which was higher than the AUCs of the individual parameters. The total ExPreS can range from 0 to 100. ExPreS ≥59 points indicated high probability of success (OR = 23.07), while ExPreS ≤44 points indicated low probability of success (OR = 0.82). In the prospective validation cohort, 83 patients were extubated: extubation succeeded in 81 (97.6%) patients and failed in 2 (2.4%) patients. The AUC value for the ExPreS in this cohort was 0.971. The multiparameter score that we propose, ExPreS, shows good accuracy to predict extubation outcome in patients receiving IMV in the ICU. In the prospective validation, the use of ExPreS decreased the extubation failure rate from 8.2% to 2.4%, even in a cohort of more severe patients.

Salivary cytokines as biomarkers of oral cancer: a systematic review and meta-analysis.

BACKGROUND: Oral cancer (OC) is usually diagnosed at advanced clinical stages due to its asymptomatic nature and absence of pathognomonic signs in its early development phase. Delayed diagnosis is one of the major causes of OC treatment failure and poor prognosis. Development of alternative diagnostic approaches are imperative for improving early detection and therapeutic success rates. Salivary cytokines (SC) have been studied as potential diagnostic biomarkers for OC and may represent a potential tool for improvement of its early detection. METHODS: In this systematic review and meta-analysis we identified SC studied as OC biomarkers by systematically reviewing the PubMed and Cochrane Library databases using the terms: "oral cancer", "cytokine", and "saliva", and also combined with "interleukin" or "interferon". Only case-control studies that measured SC by ELISA from treatment naïve patients were included in the qualitative review. For the meta-analysis were included all comparable studies that provided enough data (sample size, mean and standard deviation or standard error of the mean) for SC levels in OC patients, non-cancer controls and patients with oral potentially malignant disorders (OPMD), including leukoplakia. Comparisons with patients with oral lichen planus (OLP) and gingivitis were included in the qualitative analysis. RESULTS: A total of 28 articles (from 2004 to 2018) were included in the systematic review, describing 10 different SC, being IL-8 and IL-6 the most studied ones. SC levels were consistently higher among OC patients when compared to healthy controls and to patients with OPMD, OLP and gingivitis. Meta-analysis including 23 eligible studies showed that IL-8, IL-6, TNF-α, IL-1ß and IL-10 salivary levels were significantly higher in OC patients compared to controls; and that IL-8, IL-6, TNF-α and IL-1ß salivary levels were also higher in OC patients compared to individuals with OPMD. When compared to healthy controls, OPMD patients showed significantly higher IL-6 and TNF-α salivary levels. CONCLUSIONS: Our analyses showed that the salivary levels of some cytokines are consistently different among OC, OPMD and healthy patients, indicating that these SC may represent potential diagnostic biomarkers for OC and OPMD. Despite of that, SC levels were highly variable among studies, suggesting that further technical improvement and standardization for SC measurement by ELISA is needed in order to successfully translate these biomarkers to the clinical practice.

Conflitos morais na prática fisioterapêutica: percepção de fisioterapeutas e alunos / Moral conflicts in physiotherapy practice: perception of physiotherapists and students

Os conflitos morais são inerentes à prática da fisioterapia, tanto mais que manifestações da evolução científica estão cada vez mais presentes na práxis profissional do fisioterapeuta, o que exige um contato próximo entre o profissional e o paciente. O objetivo deste estudo foi analisar a percepção de fisioterapeutas e alunos de um curso de fisioterapia sobre os conflitos morais na prática clínica. Foi realizado um estudo transversal por meio de questionário aplicado aos alunos das etapas inicial (Grupo 1) e final (Grupo 2) de um curso de fisioterapia e também a fisioterapeutas (Grupo 3) que atuam em cidades do Meio-Oeste de Santa Catarina, Brasil. A amostra foi composta por 110 alunos, sendo 59 do Grupo 1 e 51 do Grupo 2, com média de idade de 22,7 anos e predominantemente do sexo feminino. Além disso, havia 36 fisioterapeutas incluídos no Grupo 3, a maioria do sexo feminino, com idades variando de 31 a 40 anos e com 11 a 20 anos de formação. Quase todos os alunos e profissionais relataram que a abordagem da ética profissional e da bioética na formação profissional são particularmente importantes. Os alunos de estágios mais avançados, que realizaram o curso de bioética, apresentaram maior conhecimento geral quando comparados aos demais grupos, indicando a importância do ensino dessa temática na graduação. A maioria dos profissionais (75%) relatou pouco conhecimento sobre os temas abordados no Código de Ética e Deontologia da Fisioterapia; 72% afirmaram ter lido parcialmente o documento, mas apenas 47% recebem atualizações anuais sobre o código de ética. Os conflitos mais citados pelos profissionais foram sigilo e confidencialidade (61,1%), relacionamento intra e interprofissional (33,3%), honorários (30,5%), autonomia profissional (25%), veracidade das informações (19,4%), relacionamento terapeuta / paciente (16,7%) e autonomia, decência e intimidade do paciente (5,5%). Os conflitos morais fazem parte da prática da fisioterapia, mesmo que não tenham sido suficientemente reconhecidos pelos participantes em alguns casos. Com base neste estudo, algumas medidas são necessárias quanto ao ensino, à atualização profissional e à inclusão de temas no código profissional da fisioterapia, visto que algumas questões constituem um desafio para a formação ética. Infelizmente, eles não são abordados no código de ética profissional do fisioterapeuta e os profissionais que concluíram o treinamento antes não tiveram um aprendizado adequado sobre os temas discutidos.

Moral conflicts are inherent to the practice of physiotherapy, more so as manifestations of the scientific evolution are increasingly more present in the professional praxis of the physiotherapist, which demands a close contact between the professional and the patient. The objective of this study was to analyze the perception of physiotherapists and students in a physiotherapy program towards moral conflicts in clinical practice. A cross-sectional study was performed by means of a questionnaire applied to students in initial (Group 1) and final (Group 2) stages of a physiotherapy course as well as to physiotherapists (Group 3) working in cities in the Midwest of Santa Catarina, Brazil. The sample consisted of 110 students, 59 in Group 1 and 51 in Group 2, with a mean age of 22.7 years old and were predominantly females. Moreover, there were 36 physiotherapists included in Group 3, most of whom were female, with ages ranging from 31 to 40 years old and with 11 to 20 years of training. Almost all students and professionals reported that approaching professional ethics and bioethics in professional training is particularly important. The students in the more advanced stages, who had taken the bioethics course, showed greater general knowledge when compared to the other groups, indicating the importance of teaching this theme at the undergraduate level. Most professionals (75%) self-reported little knowledge on the topics discussed in the Ethics and Deontology Code of Physiotherapy; 72% affirmed having partially read the document, but only 47% get annual updates on the ethics code. The conflicts most frequently mentioned by the professionals were secrecy and confidentiality (61.1%), intra- and interprofessional relationship (33.3%), fees (30.5%), professional autonomy (25%), truthfulness of information (19.4%), therapist/patient relationship (16.7%), and patient autonomy, decency, and intimacy (5.5%). Moral conflicts are part of the practice of physiotherapy, even if it was not sufficiently acknowledged by the participants in some cases. Based on this study, some measures are needed regarding teaching, professional recycling, and the inclusion of themes in the professional code of physiotherapy, considering that some issues constitute a challenge for ethical training. Unfortunately, but they are not addressed in the physiotherapist's professional code of ethics and professionals who finished training before did not have adequate learning on the topics discussed.

IL-10 Cytokine as Potential Biomarkers in Women with Fibromyalgia Who Underwent to a Short Balneotherapy Treatment

Abstract Fibromyalgia (FM) is a nonarticular rheumatic syndrome that leads to diffuse myalgia, sleep disturbances and morning stiffness. Balneotherapy has been shown an effective strategy to improve the health conditions of patients; however, the treatment follow-up is based on patient report due to the lack of biomarkers. Thus, this study evaluated the application of cytokines and phosphoglycerate mutase I (PGAM-I) to monitoring FM patient underwent to balneotherapy treatment. Eleven healthy and eleven women with FM were submitted to daily sessions of balneotherapy during 10 days. Clinical and quality of life parameters were assessed through a FIQ questionnaire. Blood levels of TNF-(, interleukins (IL-1, IL-2 and IL-10) and PGAM-I expression in patients' saliva were also evaluated. Patients with FM showed significant improvements in their clinical status after treatment. Also, FM patients has IL-10 levels lower than healthy women and the balneotherapy increased the expression of this cytokine in both groups, concomitantly to pain relief. Although inflammatory cytokines (IL-1, IL-2 and TNF-() were more expressed in FM patients than healthy patients their levels did not reduce after treatment. A slight increase of PGAM-I expression was observed. In conclusion, IL-10 levels could be a useful biomarker to balneotherapy follow-up of FM patients. However, these findings must be analyzed in a larger number of patients in order to validate IL-10 as an effective biomarker.

Translation and cultural adaptation of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer Module for quality of life assessment in patients with lung cancer in Brazil.

OBJECTIVE: To translate the European Organisation for Research and Treatment of Cancer (EORTC) 29-item Quality of Life Questionnaire-Lung Cancer Module (QLQ-LC29, developed for the assessment of quality of life in patients with lung cancer) to Portuguese, conducting a pilot study of the Portuguese-language version and adapting it for use in Brazil. METHODS: For the translation, cultural adaptation, and pilot testing of the QLQ-LC29, we followed the guidelines established by the EORTC. The translation (English → Portuguese) and back-translation (Portuguese → English) were both carried out by translators, working independently, who were native speakers of one language and fluent in the other. After review, a draft version was created for pilot testing in lung cancer patients in Brazil. RESULTS: A total of 15 patients diagnosed with lung cancer completed the Portuguese-language version of the questionnaire. At the end of the process, we conducted a structured interview to identify any patient difficulty in understanding any of the questions. The final versions were sent to the EORTC and were approved. CONCLUSIONS: The Portuguese-language version of the EORTC QLQ-LC29 appears to be a useful, important, reliable questionnaire that is a valid tool for assessing quality of life in patients with lung cancer in Brazil.

Relação terapeuta paciente e dimensões da humanização em reabilitação ortopédica / Therapist-patient relationship and humanization in orthopedic rehabilitation

Para promover a qualidade de vida aos pacientes atendidos em um programa de reabilitação, há a necessidade e obrigação de humanizar o atendimento. O fisioterapeuta exerce um papel fundamental na reabilitação dos pacientes com sequelas ortopédicas, e, além de qualidade técnica, deve prezar pela qualidade relacional de sua assistência. avaliar a relação terapeuta paciente, investigando se há humanização do atendimento fisioterapêutico na especialidade de ortopedia. Estudo de corte transversal, no qual foi aplicado um questionário adaptado avaliativo individual, contendo 15 questões fechadas em nove domínios, em uma amostra de 59 indivíduos, os quais receberam atendimento na especialidade de fisioterapia ortopédica. Os dados foram analisados e apresentados em frequência e porcentagem. O atendimento fisioterapêutico foi caracterizado como humanizado, obtendo-se resposta com 100% em todos os domínios do questionário, nos quesitos que dizem respeito à relação terapeuta-paciente. A assistência fisioterápica, na especialidade de ortopedia, foi caracterizada como humanizada pelos pacientes.

Care should be humanized to promote the life quality of patients attended in a rehabilitation program. The physiotherapist has an important role in the rehabilitation of patients with orthopedic sequels. Besides technical quality, physiotherapists should appreciate the quality of their relationship. To evaluate the therapist-patient relationship by investigating whether humanization exists in physiotherapist attendance, especially in orthopedics. Transversal research applied a questionnaire adapted for individual evaluation, with 15 questions within nine dominions, in a sample of 59 agents receiving care in orthopedic physiotherapy. Data were analyzed, with frequency and percentages. Physiotherapeutic attendance was characterized as humanized, with one hundred percent response in all the domains of the questionnaire with regard to therapist-patient relationship. Physiotherapy, especially orthopedics, was characterized as humanized by patients.

Rab5C enhances resistance to ionizing radiation in rectal cancer.

Rectal cancer represents one third of the colorectal cancers that are diagnosed. Neoadjuvant chemoradiation is a well-established protocol for rectal cancer treatment reducing the risk of local recurrence. However, a pathologic complete response is only achieved in 10-40% of cases and the mechanisms associated with resistance are poorly understood. To identify potential targets for preventing therapy resistance, a proteomic analysis of biopsy specimens collected from stage II and III rectal adenocarcinoma patients before neoadjuvant treatment was performed and compared with residual tumor tissues removed by surgery after neoadjuvant therapy. Three proteins, Ku70, Ku80, and Rab5C, exhibited a significant increase in expression after chemoradiation. To better understand the role of these proteins in therapy resistance, a rectal adenocarcinoma cell line was irradiated to generate a radiotherapy-resistant lineage. These cells overexpressed the same three proteins identified in the tissue samples. Furthermore, radiotherapy resistance in this in vitro model was found to involve modulation of epidermal growth factor receptor (EGFR) internalization by Rab5C in response to irradiation, affecting expression of the DNA repair proteins, Ku70 and Ku80, and cell resistance. Taken together, these findings indicate that EGFR and Rab5C are potential targets for the sensitization of rectal cancer cells and they should be further investigated. KEY MESSAGES: • Rab5C orchestrates a mechanism of radioresistance in rectal adenocarcinoma cell. • Rab5C modulates EGFR internalization and its relocalization to the nucleus. • In the nucleus, EGFR can modulate the expression of the DNA repair proteins, Ku70 and Ku80. • Rab5C, Ku70, and Ku80 are overexpressed in tumor tissues that contain tumor cells that are resistant to chemoradiation treatment.

Translation and cultural adaptation of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer Module for quality of life assessment in patients with lung cancer in Brazil / Tradução e adaptação cultural do Quality of Life Questionnaire-Lung Cancer Module da European Organisation for Research and Treatment of Cancer para avaliação da qualidade de vida relacionada à saúde em pacientes com câncer de pulmão no Brasil

ABSTRACT Objective: To translate the European Organisation for Research and Treatment of Cancer (EORTC) 29-item Quality of Life Questionnaire-Lung Cancer Module (QLQ-LC29, developed for the assessment of quality of life in patients with lung cancer) to Portuguese, conducting a pilot study of the Portuguese-language version and adapting it for use in Brazil. Methods: For the translation, cultural adaptation, and pilot testing of the QLQ-LC29, we followed the guidelines established by the EORTC. The translation (English → Portuguese) and back-translation (Portuguese → English) were both carried out by translators, working independently, who were native speakers of one language and fluent in the other. After review, a draft version was created for pilot testing in lung cancer patients in Brazil. Results: A total of 15 patients diagnosed with lung cancer completed the Portuguese-language version of the questionnaire. At the end of the process, we conducted a structured interview to identify any patient difficulty in understanding any of the questions. The final versions were sent to the EORTC and were approved. Conclusions: The Portuguese-language version of the EORTC QLQ-LC29 appears to be a useful, important, reliable questionnaire that is a valid tool for assessing quality of life in patients with lung cancer in Brazil.

RESUMO Objetivo: O objetivo deste estudo foi traduzir, adaptar culturalmente e realizar um ensaio piloto para criar a versão em português do Brasil do questionário da European Organisation for Research and Treatment of Cancer (EORTC) denominado Quality of Life Questionnaire-Lung Cancer (QLQ-LC29, lung module), desenvolvido para a avaliação da qualidade de vida em doentes com câncer de pulmão. Métodos: Foram seguidas as orientações da EORTC para a tradução, a adaptação cultural e a realização de um ensaio piloto do QLQ-LC29. Foi realizado o processo de tradução (inglês → português) e tradução reversa (português → inglês) por tradutores independentes nativos em um dos idiomas e fluentes no outro idioma. Após revisão, uma versão preliminar for criada para o ensaio piloto com pacientes no Brasil. Resultados: No total, 15 pacientes com diagnóstico de câncer de pulmão preencheram a versão em português do Brasil do questionário. No final, foi conduzida uma entrevista estruturada para identificar qualquer dificuldade em alguma das perguntas. As versões finais foram enviadas para a EORTC e aprovadas. Conclusões: A versão em português do Brasil do EORTC QLQ-LC29 (lung module) é uma ferramenta útil, importante, fidedigna e válida para a aferição da qualidade de vida relacionada à saúde em pacientes com neoplasia pulmonar.

Weight loss as a prognostic factor for recurrence and survival in oropharyngeal squamous cell carcinoma patients.

Although the mortality rate of oropharyngeal squamous cell carcinoma (OPSCC) has been decreasing over the last 30 years, there has been a significant increase in the frequency of diagnosis of this type of cancer in several countries. Beyond the classic prognostic factors, such as TNM stage, there is a lack of predictive factors for recurrence and treatment response. A retrospective analysis of patients with OPSCC treated at the Oncology Department of the Santa Terezinha University Hospital between 2007 and 2012 was performed, with the aim of identifying new prognostic factors. In addition to the significance of clinical stage as a prognostic factor for recurrence, OPSCC patients with advanced TNM stage and those treated with radiotherapy, chemoradiation or palliative measures, had a worse prognosis. Patients with moderate or severe weight loss (>5%) at diagnosis had a higher tumor recurrence rate compared with those with mild or no weight loss (P=0.007). Furthermore, 76.9% of patients with moderate or severe weight loss, as opposed to 13.3% of patients with mild or no weight loss, eventually succumbed to the disease (P=0.0001). These data suggest that moderate and severe weight loss at diagnosis is a prognostic factor for OPSCC and it is associated with disease recurrence.

Predictive factors of weaning from mechanical ventilation and extubation outcome: A systematic review.

PURPOSE: To identify, describe and discuss the parameters used to predict weaning from mechanical ventilation and extubation outcomes. METHODS: Systematic review of scientific articles using four electronic databases: PubMed, Embase, PEDro and Cochrane Library. Search terms included "weaning", "extubation", "withdrawal" and "discontinuation", combined with "mechanical ventilation" and "predictive factors", "predictive parameters" and "predictors for success". In this study, we included original articles that presented predictive factors for weaning or extubation outcomes in adult patients and not restricted to a single disease. Articles not written in English were excluded. RESULTS: A total of 43 articles were included, with a total of 7929 patients and 56 different parameters related to weaning and extubation outcomes. Rapid Shallow Breathing Index (RSBI) was the most common predictor, discussed in 15 studies (2159 patients), followed by Age and Maximum Inspiratory Pressure in seven studies. The other 53 parameters were found in less than six studies. CONCLUSION: There are several parameters used to predict weaning and extubation outcomes. RSBI was the most frequently studied and seems to be an important measurement tool in deciding whether to wean/extubate a patient. Furthermore, the results demonstrated that weaning and extubation should be guided by several parameters, and not only to respiratory ones.

FIP1L1-PDGFRA fusion-negative hypereosinophilic syndrome with uncommon cardiac involvement responding to imatinib treatment: A case report.

Hypereosinophilic syndrome is a rare, chronic hematological disease characterized by a persistently elevated eosinophil count exceeding 1.5×109/l, following the exclusion of other potential etiologies. The systemic involvement of the disease causes tissue damage through eosinophil infiltration, and may affect various organs; cardiac complications are observed in 50-60% of cases, which are predominately attributed to endomyocardial fibrosis. The treatment is based initially on determining the presence of the FIP1L1-PDGFRA fusion. Patients with positive results for this mutation tend to achieve a complete response with imatinib treatment, which is thus the first line of treatment for this condition. However, patients who are negative for this mutation initially undergo treatment with corticosteroids. This study reports the case of a male 53-year-old patient diagnosed with hypereosinophilic syndrome in 2012, with negative results for the FIP1L1-PDGFRA mutation, and persistently high eosinophil levels, despite receiving the second line of standard treatment for this condition with hydroxyurea, and having already used corticosteroids without success. At the time of admission, the patient presented with acute decompensated heart failure due to severe mitral regurgitation, without any evidence of prior myocardial fibrosis or restrictive cardiomyopathy, and without suggestion of an associated ventricular hypertrophy. This clinical presentation is uncommon, as valvular involvement usually appears in the third stage of the development of cardiac involvement, and is usually associated with fibrosis and thrombotic events. Alternative therapeutic possibilities were evaluated due to the significant progression of the disease, and it was decided to attempt the use of imatinib, despite its use being preferably recommended for FIPIL1-PDGFRA-positive patients. The patient exhibited an evident and immediate response to imatinib, with normalization of the eosinophil count within 24 h of the first dose, which was maintained for at least the next 19 months. This clinical presentation is uncommon, as patients negative for FIPIL1-PDGFRA fusion do not frequently respond to imatinib treatment, and symptomatic heart failure usually appears in the third stage of disease progression.

Avaliação nutricional de pacientes com câncer em atendimento ambulatorial / Nutritional assessment of cancer patients in outpatient care / Evaluación nutricional de pacientes con cáncer en atención ambulatoria

Objetivou-se analisar o aspecto nutricional de pacientes oncológicos em atendimento ambulatorial, em Joaçaba-SC. Estudo transversal, que utilizou a avaliação subjetiva global produzida pelo paciente e questionário de consumo alimentar, do Ministério da Saúde. Participaram 70 pacientes, idade média 60,3±13,9 anos, 38 (54,3%) homens, 57 (81,4%) sem acompanhamento nutricional, 48 (68,6%) com alimentação regular, 16 (22,9%) alimentação adequada e seis (8,6%) boa alimentação. O fumo teve associação com câncer de pulmão e orofaringe e o consumo de carne com câncer de intestino. A redução de peso foi elevada, 36 (52,2%) reduziram mais de 5% do peso corporal. Pessoas bem nutridas reduziram menos o peso comparado às desnutridas, tiveram melhor aceitação da dieta e menos queixas alimentares. Desnutridos totalizaram 58 indivíduos (83%), todos em estágio avançado da doença. A desnutrição teve elevada prevalência neste estudo, devendo ser implantadas estratégias de acompanhamento eficazes com equipe multiprofissional para melhorar o tratamento nutricional desta população (AU).

The objective was to analyze the nutritional aspect of cancer patients in outpatient care in Joaçaba-SC. Cross-sectional study using global subjective assessment by the patient and the food consumption questionnaire of the Brazilian Health Department. Seventy patients participated with a mean age of 60.3±13.9 years, 38 (54.3%) men, 57 (81.4%) without nutritional monitoring, 48 (68.6%) with a regular diet, 16 (22.9%) appropriate diet and (8.6%) good diet. Smoking was associated with lung and oropharyngeal cancer and meat consumption with bowel cancer. The weight reduction was high, as 36 (52.2%) lost more than 5% of their body weight. Well-nourished people lost less weight when compared to malnourished individuals, accepted the diet better and had less food complaints. In total, 58 individuals (83%) were malnourished, all of them in the advanced stage of the disease. The prevalence of malnourishment was high in this study. Effective monitoring strategies need to be implemented with a multiprofessional team to improve the nutritional treatment in this population (AU).

La finalidad fue analizar el aspecto nutricional de pacientes oncológicos en atención ambulatoria en Joaçaba-SC. Estudio transversal, que utilizó la evaluación subjetiva global producida por el paciente y cuestionario de consumo alimentario del Ministerio de la Salud brasileño. Participaron 70 pacientes, promedio de edad 60,3±13,9 años, 38 (54,3%) hombres, 57 (81,4%) sin seguimiento nutricional, 48 (68,6%) con alimentación regular, 16 (22,9%) alimentación adecuada y seis (8,6%) buena alimentación. El humo estaba asociado al cáncer de pulmón y faringe inferior y el consumo de carne con cáncer intestinal. La reducción de peso fue alta, 36 (52,2%) redujeron más del 5% del peso corporal. Personas bien nutridas redujeron menos el peso comparado a las desnutridas, aceptaron mejor la dieta y tuvieron menos quejas alimentarias. Desnutridos totalizaron 58 individuos (83%), todos en estado avanzado de la enfermedad. La prevalencia de la desnutrición fue alta en este estudio. Deben ser implantadas estrategias de seguimiento eficaces con equipo multiprofesional para mejorar el tratamiento nutricional de esta población (AU).

Perfil nutricional de pacientes oncológicos internados em um Hospital Universitário da Região Meio Oeste de Santa Catarina / Nutritional profile of cancer patients hospitalized at a University Hospital in the Midwest Region of Santa Catarina

Introdução: O câncer é considerado uma das doenças crônicas não transmissíveis que mais afeta a população mundial. Essa afecção crônica provoca muitas alterações relacionadas ao metabolismo, como o aumento na demanda nutricional causada pelo tumor e pelos tratamentos realizados. Objetivo: Avaliar o perfil nutricional de pacientes oncológicos internados no Hospital Universitário Santa Terezinha (HUST), localizado na Região Meio Oeste de Santa Catarina. Método: Este estudo é de natureza aplicada, transversal, de cunho quantitativo, descritivo, realizado no período de maio a dezembro de 2016. Os dados clínicos foram obtidos pela análise de prontuário e a avaliação do estado nutricional por meio da avaliação subjetiva global produzida pelo paciente (ASG-PPP), índice de massa corporal (IMC) e percentual de redução de peso corporal. A análise estatística foi realizada com o programa Statistical Package for the Social Sciences (SPSS) versão 21.0. Resultados: 57 pacientes oncológicos hospitalizados no HUST, portadores de neoplasias de cabeça e pescoço (31,6%) e do trato gastrointestinal, destacando-se cólon (28,1%), prevalência de homens 61,4%, a média de idade 60,1 anos, 75,4% dos pacientes estavam desnutridos. Os pacientes no estadiamento III foram os que mais tiveram o peso reduzido, sendo que os pacientes com redução superior a 20% encontravam-se nos estadiamentos III e IV. 90% não realizavam acompanhamento nutricional e 65% não faziam uso de terapia nutricional. Conclusões: A desnutrição é condição clínica prevalente nos pacientes oncológicos, portadores de neoplasias de cabeça e pescoço, e no trato gastrointestinal internados no HUST.(AU)

Introduction: Cancer is considered one of the chronic non-communicable diseases that most affects the world population. This chronic disease causes many changes related to metabolism such as increased nutritional demand caused by the tumor and the treatments performed. Objective: To evaluate the nutritional profile of cancer patients hospitalized at the Santa Terezinha University Hospital (HUST), located in the Midwest Region of Santa Catarina. Methods: This is a cross-sectional, quantitative, descriptive study from May to December 2016. Clinical data were obtained through chart analysis and evaluation of nutritional status through the global subjective evaluation produced by the patient (ASG-PPP), body mass index (BMI) and percentage of body weight reduction. Statistical analysis was performed using the Statistical Package for Social Sciences (SPSS) version 21.0. Results: 57 cancer patients hospitalized in HUST, with head and neck neoplasias (31.6%) and gastrointestinal tract, with colon (28.1%), men's prevalence 61.4%, mean age 60.1 years, 75.4% of the patients were malnourished, the patients in stage III were the ones that most reduced weight, and patients with a reduction greater than 20% were hiding in the III and IV stations. 90% did not perform nutritional monitoring and 65% did not use nutritional therapy. Conclusions: Malnutrition is a prevalent clinical condition in cancer patients with head and neck neoplasias and in the gastrointestinal tract admitted to HUST.(AU)

Immature teratoma presenting as a soft-tissue mass with no evidence of other sites of involvement: a case report.

BACKGROUND: Germ cell tumors are tumors composed of tissues derived from more than one of the three germinal layers. They are more common in the testes and ovaries, but can present in many different regions in the midline, including the sacral region, retroperitoneum, mediastinum, and brain. Testicular germ cell tumors generally metastasize to the retroperitoneum, lungs, and brain; metastases to soft tissue are very rare. CASE PRESENTATION: Here we describe a case of a single soft-tissue mass in the thigh of a 27-year-old man, with histology showing areas of mature teratoma tissues derived from the ectodermal and mesodermal lineages, and areas of immature teratoma tissue composed of small undifferentiated cells, with primitive neuroectodermal differentiation foci forming neuroepithelial elements - thus classified as immature teratoma. The patient had no other clinical or radiological evidence of involvement, besides the lymph nodes. CONCLUSION: The case presented suggests a rare and unexpected primary immature teratoma of the thigh.

Marcadores e mecanismos de resistência à terapia neoadjuvante e o papel das vesículas extracelulares secretadas pelas células tumorais no câncer de reto / Biomarkers and mechanisms of resistance to neoadjuvnat therapy and the role of extracelular vesicles secreted by tumor cells in rectal cancer

O câncer de reto é o segundo tumor mais comum no intestino grosso correspondendo a um terço do total de casos de câncer colorretal (CCR). Pacientes com câncer de reto em estádios II e III são tratados com radioquimioterapia neoadjuvante seguida de ressecção cirúrgica do tumor. Análises das peças cirúrgicas ressecadas mostraram que apenas 10-45% dos pacientes obtém resposta patológica completa (RCp) à terapia neoadjuvante, estando essa associada com uma diminuição da recorrência local, melhora da sobrevida livre de doença e aumento na preservação esfincteriana. Apesar da melhora na sobrevida nas últimas décadas, a resposta à terapia neoadjuvante continua variável e imprevisível e não é possível identificar e separar clinicamente os grupos de pacientes que terão ou não resposta completa ao tratamento neoadjuvante. Além disso, os mecanismos de resistência à radioquimioterapia nos tumores de reto são pouco compreendidos. Dessa forma, o objetivo principal deste estudo foi identificar marcadores e mecanismos celulares relacionados à resistência à terapia neoadjuvante em adenocarcinoma de reto e o papel das vesículas extracelulares (VEs) nesse processo. O estudo proteômico comparativo entre biópsias obtidas de tumores pré-tratamento com o tumor residual removido cirurgicamente pós-tratamento radioquimioterápico mostrou uma importante alteração no perfil de expressão proteica. Entre as proteínas que aumentam a expressão após a neoadjuvância estão as proteínas de reparo de dano de DNA, Ku70 e Ku80, e a proteína de tráfego intracelular Rab5C. Em um modelo in vitro, foi demonstrado que Rab5C orquestra um mecanismo de resistência à radioterapia nos tumores de reto através da modulação da internalização de EGFR promovida por radiação ionizante (RI). O EGRF intracelular por sua vez é essencial para regular a expressão de Ku70 e Ku80 e a resistência celular à RI. Estes dados apontam Rab5C e EGFR como potenciais alvos terapêuticos para sensibilizar células de câncer de reto resistentes ao tratamento neoadjuvante. Também foi observado que a RI promove alterações epigenéticas predominantemente de hipometilação, e entre os genes alterados estão SPG20 e TBC1D16, sendo o primeiro importante para a internalização de EGFR e o segundo para a regulação de Rab5C e modulação de EGFR. O perfil de expressão proteica foi ainda comparado entre biópsias pré-tratamento de pacientes com RCp e sem resposta patológica, e o resultado mostrou que esses dois grupos de pacientes apresentam um diferente perfil de expressão proteica. Nos pacientes com RCp as proteínas com aumento da expressão estão atuando em vias que favorecem a resposta à terapia, como a detoxificação de glutationa e degradação de glicogênio, enquanto as proteínas com aumento da expressão em pacientes sem RCp estão envolvidas em vias do metabolismo energético do tumor as quais contribuem para a resistência tumoral à terapia. As diferenças observadas nestes grupos devem ser amplamente exploradas uma vez que podem ser marcadores preditivos de resposta ao tratamento radioquimioterápico. A realização de estudos funcionais foi viabilizada pela geração de um modelo celular de tumor de reto resistente à radioterapia. Ao analisar as VEs secretadas por estas células foi observado que a RI não altera a quantidade e o tamanho médio das VEs secretadas, porém é capaz de alterar o carregamento proteico das mesmas. De fato, as VEs de células irradiadas apresentam um perfil proteico diferente quando comparadas as VEs de células não irradiadas, onde encontramos aumento da expressão de Ku70, Ku80 e Rab5C, além das metiltransferases NSUN2 e GLYM nas VEs de células pós RI. Interessantemente, as VEs secretadas por células irradiadas são capazes de transmitir a resistência à RI às células não irradiadas. Além disso os resultados mostraram que o tratamento com VEs de células irradiadas promove metilação em 98% do DNA avaliado em células SW837 em comparação ao tratamento com VEs de células não irradiadas. Os genes hipermetilados estão envolvidos em vias relacionadas ao sistema imune, como a apresentação de antígeno, sinalização de imunodeficiência primária e maturação de células dendríticas. Por fim, foi identificado que a expressão da proteína A33 está relacionada ao grau de diferenciação dos tumores colorretais, e que essa proteína está presente em VEs secretadas por células de adenocarcinoma de reto, indicando que a mesma pode ser usada para isolar VEs específicas do tecido colorretal. Os dados obtidos neste trabalho apontam mecanismos relacionados à resistência à terapia neoadjuvante no adenocarcinoma de reto e que em conjunto permitirão identificar novos alvos terapêuticos com potencial de melhorar a resposta à radioquimioterapia, além de identificar marcadores de resposta à terapia neoadjuvante antes do tratamento e dessa forma, poupar os pacientes não respondedores de terapias tóxicas e melhorar a sustentabilidade na saúde poupando os custos com drogas não eficientes para um grupo de pacientes.

Rectal cancer is the second most common cancer in large intestine, corresponding to one third of total cases of colorectal cancer (CRC). Patients with rectal cancer in stage II and III are treated with neoadjuvant chemoradiation followed by surgical resection. Analyzes of the resected tumor demonstrated that only 10-45% of the patients achieve pathological complete response (pCR) after neoadjuvant therapy, which is associated with a decrease in local recurrence, improvement of disease free survival and increase in sphincter preservation. Despite the improvement in survival in the last decades, the response to neoadjuvant therapy is still variable and unpredictable, and before the surgery it is not possible to identify and separate clinically the group of patients that will or will not have complete response to neoadjuvant treatment. Moreover, the mechanisms of resistance of rectal tumors to chemoradiation are poorly understood. Thus, the main objective of this work was to identify biomarkers and cellular mechanisms related to the resistance to neoadjuvant therapy in rectal adenocarcinomas and the role of extracellular vesicles (EVs) in this process. The comparative proteomic study between biopsy obtained from tumors pretreatment with residual tumor, post chemoradiation treatment, removed by surgery showed an important alteration in the protein expression profile. Among the proteins with increased expression after neoadjuvant therapy are the DNA repair proteins Ku70 and Ku80, and the protein involved in the intracellular trafficking, Rab5C. It was demonstrated in vitro that Rab5C orchestrates a mechanism of radioresistance in rectal tumors by modulating the EGFR internalization promoted by ionizing radiation (IR). The intracellular EGFR is essential to regulate Ku70 and Ku80 expression and the cell resistance to IR. These data pointed Rab5C and EGFR as potential therapeutic targets to sensitize rectal cancer cells resistant to neoadjuvant treatment. It was also observed that IR promotes epigenetic alterations, predominantly hypomethylation, and between the altered genes are SPG20 and TBC1D16, the first is important to EGFR internalization, while the second regulates Rab5C and modulates EGFR. The protein expression profile was further compared between biopsy pretreatment of patients with and without pCR, and the results showed that these two groups of patients present a different protein expression profile. In patients with pCR the proteins with increased expression are involved in pathways favoring the response to therapy, as glutathione-mediated detoxification and glycogen degradation, while the proteins with increased expression in patients without pCR are involved in tumor energetic metabolism pathways that contribute to tumor resistance to therapy. The observed differences in these groups should be widely explored since they may be predictive markers of response to chemoradiation treatment. The performance of functional studies was possible by generation of a cellular model of rectal tumor resistant to radiotherapy. The analysis of the EVs secreted by these cells showed that IR does not alter the amount and the medium size of secreted EVs, but is able to change their protein content. EVs from irradiated cells presented a different protein profile when compared to EVs from non-irradiated cells, where it was found the increased expression of Ku70, Ku80 and Rab5C, besides the methyltransferases NSUN2 and GLYM in EVs after irradiation. Interestingly, the EVs secreted by irradiated cells are capable of transfering resistance to IR to non-irradiated cells. Moreover, the results showed that the treatment of SW837 cells with EVs from irradiated cells promoted methylation in 98% of the analyzed DNA in comparison with the treatment with EVs from non-irradiated cells. The hypermethylated genes are involved in pathways related to immune system, as antigen presentation, primary immunodeficiency signaling and dendritic cells maturation. Lastly, it was identified that the A33 expression is related to the colorectal tumors differentiation degree, and this protein is present in EVs secreted by rectal adenocarcinoma, indicating that it may be used to isolate EVs specific from colorectal tissues. The data obtained in this work pointed to mechanisms related to resistance to neoadjuvant therapy in rectal adenocarcinoma that together will allow to identify new therapeutic targets with the potential to improve the response to chemoradiation, as well as to identify markers of response to neoadjuvant therapy before the treatment, and, in this way, avoid the non-responder patients to receive toxic therapies and improve health sustainability, sparing cost with non-efficient drugs for a group of patients.