Electrical Stimulation for Treatment of Dysphagia Post Head Neck Cancer: A Systematic Review and Meta-Analysis.

Introduction Dysphagia induced by radiotherapy in the head and neck region comprises a challenging scenario and sometimes difficult rehabilitation due to the severity of the adverse effects. Some resources such as electrical stimulation have emerged as an alternative to complement the therapeutic process, but there is still no consensus on its use. Objective The purpose of the present study was to evaluate, through a meta-analysis, the effect of electrical stimulation on the rehabilitation of dysphagia generated after head and neck cancer treatment. Data Synthesis Four randomized controlled trials with a total of 146 participants were included. The age of the participants was 58.37 ± 1.8 years old and there was a predominance of males. The time to start the intervention ranged from 50.96 ± 40.12 months after cancer treatment. The intervention showed great heterogeneity regarding the positioning of the electrodes, parameters, duration of the stimulus, number of sessions, and intensity. No difference was identified in the following aspects: oral transit time, hyoid elevation, penetration and/or aspiration after electrostimulation. The quality of the evidence ranged from very low to moderate and high risk of bias. Conclusion In this meta-analysis, we found weak evidence for small and moderate swallowing benefits in patients after radiotherapy for head and neck cancer in short-term clinical trials.

Ferritin heavy chain supports stability and function of the regulatory T cell lineage.

Regulatory T (TREG) cells develop via a program orchestrated by the transcription factor forkhead box protein P3 (FOXP3). Maintenance of the TREG cell lineage relies on sustained FOXP3 transcription via a mechanism involving demethylation of cytosine-phosphate-guanine (CpG)-rich elements at conserved non-coding sequences (CNS) in the FOXP3 locus. This cytosine demethylation is catalyzed by the ten-eleven translocation (TET) family of dioxygenases, and it involves a redox reaction that uses iron (Fe) as an essential cofactor. Here, we establish that human and mouse TREG cells express Fe-regulatory genes, including that encoding ferritin heavy chain (FTH), at relatively high levels compared to conventional T helper cells. We show that FTH expression in TREG cells is essential for immune homeostasis. Mechanistically, FTH supports TET-catalyzed demethylation of CpG-rich sequences CNS1 and 2 in the FOXP3 locus, thereby promoting FOXP3 transcription and TREG cell stability. This process, which is essential for TREG lineage stability and function, limits the severity of autoimmune neuroinflammation and infectious diseases, and favors tumor progression. These findings suggest that the regulation of intracellular iron by FTH is a stable property of TREG cells that supports immune homeostasis and limits the pathological outcomes of immune-mediated inflammation.

Antimicrobial prescription and bacterial resistance in a Brazilian Intensive Care Unit / Prescrição antimicrobiana e resistência bacteriana em uma Unidade de Terapia Intensiva Brasileira / Prescripción antimicrobiana y resistencia bacteriana en una Unidad de Cuidados Intensivos Brasileña

Background and Objectives: antimicrobial resistance is one of the main public health concerns worldwide. Intensive Care Units have a high prevalence of resistant microorganisms and infections, and the rational use of antibiotics is one of the main strategies for tackling this problem. This work aimed to describe patterns associated with antimicrobial drugs as well as the resistance profile of microorganisms. Methods: an observational study was carried out using data from patients hospitalized in the Intensive Care Unit who used antimicrobial agents. Results: respiratory and cardiological causes were the most frequent reasons for admission, with cephalosporins (29.02%), with penicillin (25.84%) and macrolides (16.10%) being the most used classes of antibiotics. The predominant microorganisms were Klebsiella pneumoniae (13.98%), Staphylococcus aureus (13.44%) and Acinetobacter baumannii (11.83%). Urine cultures and tracheal aspirate were the culture tests with the highest growth of gram-negative microorganisms. Patients with bacteria isolated in tracheal aspirate had longer hospital stays; 20 patients had positive surveillance cultures; and the mortality rate found was 55.45%. Conclusion: the study combined the institution's epidemiological profile with patient characteristics, isolated microorganisms and outcomes.(AU)

Justificativa e Objetivos: a resistência antimicrobiana é uma das principais preocupações de saúde pública em todo o mundo. As Unidades de Terapia Intensiva têm uma alta prevalência de microorganismos resistentes e infecções, e o uso racional de antibióticos é uma das principais estratégias para lidar com esse problema. Este trabalho teve como objetivo descrever padrões associados a medicamentos antimicrobianos, bem como o perfil de resistência dos microorganismos. Métodos: foi realizado um estudo observacional utilizando dados de pacientes hospitalizados na Unidade de Terapia Intensiva que utilizaram agentes antimicrobianos. Resultados: causas respiratórias e cardiológicas foram os motivos mais frequentes de admissão, com cefalosporinas (29,02%), penicilina (25,84%) e macrolídeos (16,10%) sendo as classes de antibióticos mais utilizadas. Os microorganismos predominantes foram Klebsiella pneumoniae (13,98%), Staphylococcus aureus (13,44%) e Acinetobacter baumannii (11,83%). Culturas de urina e aspirado traqueal foram os testes de cultura com maior crescimento de microorganismos gram-negativos. Pacientes com bactérias isoladas no aspirado traqueal tiveram internações mais longas; 20 pacientes tiveram culturas de vigilância positivas; e a taxa de mortalidade encontrada foi de 55,45%. Conclusão: o estudo combinou o perfil epidemiológico da instituição com características dos pacientes, microorganismos isolados e resultados.(AU)

Antecedentes y Objetivos: la resistencia antimicrobiana es una de las principales preocupaciones de salud pública en todo el mundo. Las Unidades de Cuidados Intensivos tienen una alta prevalencia de microorganismos resistentes e infecciones, y el uso racional de antibióticos es una de las principales estrategias para abordar este problema. Este trabajo tuvo como objetivo describir patrones asociados con medicamentos antimicrobianos, así como el perfil de resistencia de los microorganismos. Métodos: se llevó a cabo un estudio observacional utilizando datos de pacientes hospitalizados en la Unidad de Cuidados Intensivos que utilizaron agentes antimicrobianos. Resultados: las causas respiratorias y cardiológicas fueron las razones más frecuentes de admisión, con cefalosporinas (29,02%), penicilina (25,84%) y macrólidos (16,10%) siendo las clases de antibióticos más utilizadas. Los microorganismos predominantes fueron Klebsiella pneumoniae (13,98%), Staphylococcus aureus (13,44%) y Acinetobacter baumannii (11,83%). Los cultivos de orina y el aspirado traqueal fueron las pruebas de cultivo con mayor crecimiento de microorganismos gramnegativos. Los pacientes con bacterias aisladas en el aspirado traqueal tuvieron estancias hospitalarias más largas; 20 pacientes tuvieron cultivos de vigilancia positivos; y la tasa de mortalidad encontrada fue del 55,45%. Conclusión: el estudio combinó el perfil epidemiológico de la institución con las características de los pacientes, los microorganismos aislados y los resultados.(AU)

Electrical Stimulation for Treatment of Dysphagia Post Head Neck Cancer: A Systematic Review and Meta-Analysis

Abstract Introduction Dysphagia induced by radiotherapy in the head and neck region comprises a challenging scenario and sometimes difficult rehabilitation due to the severity of the adverse effects. Some resources such as electrical stimulation have emerged as an alternative to complement the therapeutic process, but there is still no consensus on its use. Objective The purpose of the present study was to evaluate, through a meta-analysis, the effect of electrical stimulation on the rehabilitation of dysphagia generated after head and neck cancer treatment. Data Synthesis Four randomized controlled trials with a total of 146 participants were included. The age of the participants was 58.37 ± 1.8 years old and there was a predominance of males. The time to start the intervention ranged from 50.96 ± 40.12 months after cancer treatment. The intervention showed great heterogeneity regarding the positioning of the electrodes, parameters, duration of the stimulus, number of sessions, and intensity. No difference was identified in the following aspects: oral transit time, hyoid elevation, penetration and/or aspiration after electrostimulation. The quality of the evidence ranged from very low to moderate and high risk of bias. Conclusion In this meta-analysis, we found weak evidence for small and moderate swallowing benefits in patients after radiotherapy for head and neck cancer in short-term clinical trials.

Validation of a speech therapy guidelines booklet for dysphagic cancer patients / Validação de cartilha de orientações fonoaudiológicas para pacientes oncológicos disfágicos

ABSTRACT Purpose: to validate the content and appearance of a booklet of speech therapy guidelines on dysphagia for adult oncology patients presented with dysphagia. Methods: a methodological study with a mixed approach, developed for the validation of a guidebook. The validation of the guidebook was made by five expert judges and eleven non-specialist ones. For validation, the Content Validity Index was used: CVI for each item, as well as for the general items. Results: the expert judges assigned the Content Validity Index value above 80% and of 92.20%, and the non-specialist judges attributed values above 90.9% and of 98.0%, which were considered excellent. Conclusion: the proposed guidebook was validated according to content and appearance. It is believed that this material can contribute to the understanding of the health-disease process, promote self-care and arouse the interest of other health professionals in the development of educational technologies in search of better health conditions for the target population.

RESUMO Objetivo: validar conteúdo e aparência de uma cartilha de orientações fonoaudiológicas sobre disfagia para pacientes adultos oncológicos disfágicos. Métodos: trata-se de um estudo metodológico de abordagem mista, desenvolvido para a validação de uma cartilha de orientações. A validação da cartilha, quanto ao conteúdo, foi feita por cinco juízes especialistas e, quanto à aparência, por onze juízes não especialistas. Para a validação utilizou-se o Índice de Validade de Conteúdo para cada item, bem como para todos os itens juntos. Resultados: os juízes especialistas atribuíram valor acima de 80% e de 92,20% para a escala geral de análise. E os juízes não especialistas atribuíram valores acima de 90,9% e de 98,0%, também para a escala geral, sendo considerados excelentes. Conclusão: a cartilha de orientações proposta foi validada segundo conteúdo e aparência. Acredita-se que o referido material possa contribuir para a compreensão do processo saúde-doença, promover o autocuidado e despertar o interesse de outros profissionais da área da saúde para o desenvolvimento de tecnologias educativas em busca de melhores condições de saúde para a população destinada.

Hematological Events Potentially Associated with CDK4/6 Inhibitors: An Analysis from the European Spontaneous Adverse Event Reporting System.

Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors are a recent targeted therapy approved for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer. Abemaciclib, palbociclib and ribociclib demonstrated great efficacy and safety during clinical studies. However, differences in their adverse-event profiles have been observed. This work aims to describe the suspected adverse drug reactions (ADRs), such as leukopenia and thrombocytopenia, reported for each CDK4/6 inhibitor in the EudraVigilance (EV) database. Data on individual case safety reports (ICSRs) were obtained by accessing the European spontaneous reporting system via the EV website. Information on concomitant drug therapy, including fulvestrant, letrozole, anastrozole and exemestane, was also analyzed. A total of 1611 ICSRs were collected from the EV database. Most reports of palbociclib and ribociclib were classified as serious cases for both suspected leukopenia and thrombocytopenia ADRs. However, most patients had their leukopenia and thrombocytopenia recovered/resolved. On the contrary, reports of abemaciclib were mostly characterized as non-serious cases. Abemaciclib and palbociclib were often combined with fulvestrant, while ribociclib was generally associated with letrozole. Pharmacovigilance studies are crucial for the early identification of potential ADRs and to better differentiate the toxicity profile of the different CDK4/6 inhibitors, particularly in a real-world setting.

Preventive measures for the progression of dysphagia in patients with cancer of head and neck subjected to radiotherapy: a systematic review with meta-analysis. / Medidas de prevenção da progressão da disfagia em pacientes com câncer de cabeça e pescoço submetidos a radioterapia: uma revisão sistemática com meta-análise.

PURPOSE: To identify the effects of prophylactic, non-pharmacological measures on the progression of dysphagia in patients with head and neck cancer undergoing radiotherapy. RESEARCH STRATEGIES: The search was performed in Medline (via PubMed), Scopus, and Embase databases, as well as in the gray literature. SELECTION CRITERIA: Randomized clinical trials were included, with adult patients (≥ 18 years old) and diagnosed with head and neck cancer, treated with radiotherapy (with or without surgery and chemotherapy), and submitted to non-pharmacological protocols for the prevention of dysphagia. DATA ANALYSIS: The risk of bias was assessed using the PEDRO scale and the overall quality of evidence was assessed using the GRADE instrument. RESULTS: Four studies were considered eligible, and of these, two were included in the meta-analysis. The result favored the intervention group, with a mean difference of 1.27 [95% CI: 0.74 to 1.80]. There was low heterogeneity and the mean score for risk of bias was 7.5 out of 11 points. The lack of detail in the care with selection, performance, detection, attrition, and reporting biases contributed to the judgment of the quality of the evidence, considered low. CONCLUSION: Prophylactic measures to contain dysphagia can promote important benefits on the oral intake of patients with head and neck cancer when compared to those who did not undergo such a therapeutic measure during radiotherapy.

OBJETIVO: Identificar os efeitos de medidas profiláticas, não farmacológicas, sobre a progressão da disfagia em pacientes com câncer de cabeça e pescoço submetidos a radioterapia. ESTRATÉGIA DE PESQUISA: A busca foi realizada nas bases de dados Medline (via PubMed), Scopus e Embase, assim como na literatura cinzenta. CRITÉRIOS DE SELEçÃO: Foram incluídos ensaios clínicos randomizados, com pacientes adultos (≥ 18 anos) e diagnóstico de câncer de cabeça e pescoço, tratados com radioterapia (associada ou não à cirurgia e quimioterapia) submetidos a protocolos não farmacológicos de prevenção da disfagia. ANÁLISE DOS DADOS: O risco de viés foi avaliado por meio da escala PEDRO e a qualidade global da evidência foi avaliada de acordo com o instrumento GRADE. RESULTADOS: Foram considerados elegíveis 4 estudos, e desses, dois foram incluídos na metanálise. O resultado favoreceu o grupo intervenção, com diferença média de 1,27 [IC 95%: 0,74 à 1,80]. Houve baixa heterogeneidade e a pontuação média para risco de viés foi de 7,5 de um total de 11 pontos. A falta de detalhamento nos cuidados com os vieses de seleção, performance, detecção, atrito e de relato contribuíram para o julgamento da qualidade da evidência, considerada baixa. CONCLUSÃO: Medidas profiláticas de contenção da disfagia podem promover importantes benefícios sobre a ingesta oral dos pacientes com câncer de cabeça e pescoço, quando comparados aqueles que não realizaram tal medida terapêutica ao longo da radioterapia.

Medidas de prevenção da progressão da disfagia em pacientes com câncer de cabeça e pescoço submetidos a radioterapia: uma revisão sistemática com meta-análise / Preventive measures for the progression of dysphagia in patients with cancer of head and neck subjected to radiotherapy: a systematic review with meta-analysis

RESUMO Objetivo Identificar os efeitos de medidas profiláticas, não farmacológicas, sobre a progressão da disfagia em pacientes com câncer de cabeça e pescoço submetidos a radioterapia. Estratégia de pesquisa A busca foi realizada nas bases de dados Medline (via PubMed), Scopus e Embase, assim como na literatura cinzenta. Critérios de seleção Foram incluídos ensaios clínicos randomizados, com pacientes adultos (≥ 18 anos) e diagnóstico de câncer de cabeça e pescoço, tratados com radioterapia (associada ou não à cirurgia e quimioterapia) submetidos a protocolos não farmacológicos de prevenção da disfagia. Análise dos dados O risco de viés foi avaliado por meio da escala PEDRO e a qualidade global da evidência foi avaliada de acordo com o instrumento GRADE. Resultados Foram considerados elegíveis 4 estudos, e desses, dois foram incluídos na metanálise. O resultado favoreceu o grupo intervenção, com diferença média de 1,27 [IC 95%: 0,74 à 1,80]. Houve baixa heterogeneidade e a pontuação média para risco de viés foi de 7,5 de um total de 11 pontos. A falta de detalhamento nos cuidados com os vieses de seleção, performance, detecção, atrito e de relato contribuíram para o julgamento da qualidade da evidência, considerada baixa. Conclusão Medidas profiláticas de contenção da disfagia podem promover importantes benefícios sobre a ingesta oral dos pacientes com câncer de cabeça e pescoço, quando comparados aqueles que não realizaram tal medida terapêutica ao longo da radioterapia.

ABSTRACT Purpose To identify the effects of prophylactic, non-pharmacological measures on the progression of dysphagia in patients with head and neck cancer undergoing radiotherapy. Research strategies The search was performed in Medline (via PubMed), Scopus, and Embase databases, as well as in the gray literature. Selection criteria Randomized clinical trials were included, with adult patients (≥ 18 years old) and diagnosed with head and neck cancer, treated with radiotherapy (with or without surgery and chemotherapy), and submitted to non-pharmacological protocols for the prevention of dysphagia. Data analysis The risk of bias was assessed using the PEDRO scale and the overall quality of evidence was assessed using the GRADE instrument. Results Four studies were considered eligible, and of these, two were included in the meta-analysis. The result favored the intervention group, with a mean difference of 1.27 [95% CI: 0.74 to 1.80]. There was low heterogeneity and the mean score for risk of bias was 7.5 out of 11 points. The lack of detail in the care with selection, performance, detection, attrition, and reporting biases contributed to the judgment of the quality of the evidence, considered low. Conclusion Prophylactic measures to contain dysphagia can promote important benefits on the oral intake of patients with head and neck cancer when compared to those who did not undergo such a therapeutic measure during radiotherapy.

Conciliação medicamentosa na admissão de pacientes transplantados renais em um hospital universitário / Medication reconciliation in the admission of kidney transplant patients to a university hospital

Introdução:O presente estudo considerou conciliações medicamentosas realizadas na admissão hospitalar de pacientes transplantados renais e intervenções farmacêuticas decorrentes desse processo.Métodos:Trata-se de um estudo transversal realizado no período de julho de 2018 a julho de 2019 no Hospital de Clínicas de Porto Alegre. Foram coletadas as características dos pacientes, as conciliações medicamentosas realizadas pelo farmacêutico clínico, as discrepâncias identificadas pelo mesmo (intencionais e não intencionais) e o resultado das intervenções. Os medicamentos foram classificados de acordo com a Anatomic Therapeutic Chemical (ATC).Resultados:Dos 719 pacientes acompanhados pelo farmacêutico clínico, 175 tiveram a conciliação medicamentosa de admissão realizada, desses, 56 apresentaram discrepâncias não intencionais. Encontramos a média de 2,2 medicamentos omissos por prescrição com desvio padrão de 1,3 medicamentos. No total, foram realizadas 122 intervenções farmacêuticas, sendo que em 61,5% houve adesão por parte da equipe médica. A classe terapêutica com maior ocorrência (43,4%) de discrepâncias não intencionais foi a que atuava sobre o aparelho cardiovascular. As variáveis observadas foram sexo, número de medicamentos nas intervenções (ambas com associação significativa com a adesão médica), idade, tempo de internação, número de medicamentos na internação e número de medicamentos de uso prévio (estas últimas sem associação significativa com a adesão médica). Conclusões:A conciliação medicamentosa previne possíveis erros de medicação, uma vez que a identificação das discrepâncias não intencionais na prescrição médica gera sinalizações que são levadas pelo farmacêutico clínico à equipe assistente, a fim garantir o uso seguro e correto dos medicamentos durante a internação hospitalar.

Introduction:This study considered medication reconciliations performed on hospital admission of kidney transplant patients and pharmaceutical interventions resulting from this process.Methods:This is a cross-sectional study carried out from July 2018 to July 2019 at Hospital de Clínicas de Porto Alegre. The characteristics of the patients, the medication reconciliations performed by the clinical pharmacist, the discrepancies identified by the same (intentional and unintentional) and the result of the interventions were collected. The drugs were classified according to the Anatomic Therapeutic Chemical (ATC). Results:Of the 719 patients monitored by the clinical pharmacist, 175 had medication reconciliation on admission performed, of which 56 had unintentional discrepancies. We found an average of 2.2 missing medications per prescription with a standard deviation of 1.3 medications. In total, 122 pharmaceutical interventions were performed, and in 61.5% there was adherence by the medical team. The therapeutic class with the highest occurrence (43.4%) of unintentional discrepancies was that which acted on the cardiovascular system. The variables observed were gender, number of medications in interventions (both with a significant association with medical adherence), age, length of stay, number of medications in hospitalization and number of medications previously used (the latter without a significant association with medical adherence).Conclusions:Medication reconciliation prevents possible medication errors, since the identification of unintentional discrepancies in the medical prescription generates signals that are taken by the clinical pharmacist to the assistant team, in order to guarantee the safe and correct use of medications during hospitalization.

Educar para a bioética: desafio em enfermagem / Educating for bioethics: a challenge in nursing / Educar en bioética: desafío en la enfermería

Resumo Educar para a bioética é um desafio na atualidade. Ainda maior se torna este desafio, quando pensamos no ensino da bioética a estudantes de enfermagem, que irão desempenhar uma profissão que tem como expoente máximo o cuidar da outra pessoa. Tratando-se de uma profissão que implica a relação com o outro e a prestação de cuidados humanizados e adequados a cada situação específica, torna-se importante desenvolver ferramentas de ensino que promovam não só o desenvolvimento técnico e o conhecimento de como fazer, mas essencialmente o desenvolvimento de competências morais, pessoais e profissionais que conduzam a cuidados de saúde de excelência. Este artigo pretende apresentar uma reflexão sobre o ensino da bioética e a sua relação com o desenvolvimento da competência moral dos estudantes de enfermagem, assim como sugerir algumas estratégias no ensino da Bioética que potenciem a formação de enfermeiros cada vez mais competentes.

Abstract Educating for bioethics is a challenge today. This challenge is even greater when we think of the teaching of bioethics to nursing students, who will perform a profession that has as its maximum target the care of other people. Because it is a profession that implies the relationship with the other and the provision of humanized and appropriate care to each situation, it is important to develop teaching tools that promote not only technical improvement and knowledge of how to do a task, but also the development of moral, personal and professional skills that lead to excellent health care. This article presents a reflection on the teaching of bioethics and its relationship with the development of moral competence of nursing students, suggesting some strategies that enhance the teaching of bioethics and the education of increasingly competent nurses.

Resumen Educar en bioética es un desafío en la actualidad. Esto se vuelve más grande cuando pensamos en la enseñanza de bioética a estudiantes de enfermería, quienes desempeñarán una profesión que tiene la máxima expresión la asistencia a las personas. Por ser una profesión que involucra la relación con el otro y la prestación de una asistencia humanizada y adecuada a cada situación específica, es importante desarrollar herramientas didácticas que promuevan no solo el desarrollo técnico y el conocimiento de cómo hacerlo, sino fundamentalmente el desarrollo de competencias morales, personales y profesionales que promuevan una excelente atención en salud. Este artículo reflexiona sobre la enseñanza de la bioética y su relación con el desarrollo de la competencia moral de los estudiantes de enfermería, así como sugiere algunas estrategias para la enseñanza de la Bioética que promueva una formación de profesionales cada vez más competentes.

Biomarkers of Response and Resistance to Palbociclib Plus Letrozole in Patients With ER+/HER2- Breast Cancer.

PURPOSE: To determine (i) the relationship between candidate biomarkers of the antiproliferative (Ki67) response to letrozole and palbociclib alone and combined in ER+/HER2- breast cancer; and (ii) the pharmacodynamic effect of the agents on the biomarkers. EXPERIMENTAL DESIGN: 307 postmenopausal women with ER+/HER2- primary breast cancer were randomly assigned to neoadjuvant treatment with letrozole for 14 weeks; letrozole for 2 weeks, then letrozole+palbociclib to 14 weeks; palbociclib for 2 weeks, then letrozole+palbociclib to 14 weeks; or letrozole+palbociclib for 14 weeks. Biopsies were taken at baseline, 2 and 14 weeks and surgery at varying times after stopping palbociclib. Immunohistochemical analyses were conducted for Ki67, c-PARP, ER, PgR, RB1, CCNE1, and CCND1. RESULTS: Higher baselines ER and PgR were significantly associated with a greater chance of complete cell-cycle arrest (CCCA: Ki67 <2.7%) at 14 weeks and higher baseline Ki67, c-PARP, and CCNE1 with a lower chance. The interaction with treatment was significant only for c-PARP. CCND1 levels were decreased c.20% by letrozole at 2 and 14 weeks but showed a tendency to increase with palbociclib. CCNE1 levels fell 82% (median) in tumors showing CCCA but were unchanged in those with no CCCA. Only 2/9 tumors showed CCCA 3-9 days after stopping palbociclib. ESR1 mutations were found in 2/4 tumors for which surgery took place ≥6 months after starting treatment. CONCLUSIONS: High CCNE1 levels were confirmed as a biomarker of resistance to letrozole+palbociclib. Ki67 recovery within 3-9 days of discontinuing palbociclib indicates incomplete suppression of proliferation during the "off" week of its schedule.

Atuação fonoaudiológica em pacientes com câncer de esôfago submetidos a tratamento radioterápico: Série de casos / Speech therapy performance in patients with esophagus cancer receiving radiotherapy treatment: A case series / Actuación fonoaudiológica en pacientes con cáncer de esófago en radioterapia: Serie de casos

Introdução: A atuação fonoaudiológica na disfagia decorrente do câncer de esôfago ainda é recente. Não foi encontrado até o momento, estudos que descrevam a atuação fonoaudiológica em pacientes com câncer de esôfago submetidos a radioterapia. Sendo assim, este trabalho teve como objetivo descrever a atuação fonoaudiológica em pacientes com câncer de esôfago, submetidos a tratamento radioterápico com queixa de disfagia. Métodos: Trata-se de uma série de cinco casos, que receberam acompanhamento fonoaudiológico ambulatorial. Os pacientes foram avaliados por meio de avaliação clínica da deglutição, classificação do grau de alteração de deglutição com aplicação de escala visual analógica e protocolos de qualidade de vida utilizados na área da oncologia. Foram submetidos ainda a uma abordagem terapêutica para deglutição. Resultados: Os pacientes obtiveram melhora da deglutição, apresentando, ao término do tratamento, diminuição dos sintomas de disfagia, possibilidade de ingesta de alimentos via oral e melhora da qualidade de vida. Conclusão: A fonoterapia, compreendendo a avaliação clínica da deglutição, seguida de treino da deglutição e exercício miofuncional para abertura do esfíncter esofágico superior (Shaker), auxiliou na reabilitação da disfagia esofágica.

Introduction: Speech therapy performance in dysphagia resulting from esophageal cancer is still a recent subject. To date, there are no studies describing the speech therapy performance of patients with esophageal cancer undergoing radiotherapy. For this reason, the aim of this study was to describe speech therapy performance in patients with esophageal cancer receiving radiotherapy treatment and with complaints of dysphagia. Methods: This is a series of five cases, with patients that received outpatient speech therapy. The patients were assessed using clinical swallowing evaluation, classification of the degree of swallowing alteration with application of visual analog scale and quality of life protocols used in oncology. They also underwent a therapeutic approach to swallowing. Results: The patients' swallowing was improved and, at the end of the treatment, there were reduced symptoms of dysphagia, possibility of oral intake of food and improved quality of life. Conclusions: Speech therapy, comprising the clinical assessment of the swallowing function, followed by swallowing training and myofunctional exercise to open the upper esophageal sphincter, supported the rehabilitation of esophageal dysphagia.

Introducción: La actuación fonoaudiológica en disfagia decurrente de cáncer del esófago es todavía reciente. Hasta ahora, no se han encontrado estudios que describan la actuación fonoaudiológica en pacientes con cáncer de esófago sometidos a radioterapia. De esta forma, este trabajo tuvo como objetivo describir la actuación del fonoaudiologo en pacientes con cáncer de esófago sometidos a tratamiento de radioterapia con queja de disfagia.Métodos: Esta es una serie de cinco casos, que recibieron terapia fonoaudiologica en ambulatorio. Los pacientes fueron evaluados mediante evaluación clínica de deglución, clasificación del nivel de alteración de la deglución con aplicación de escala visual analógica y protocolos de calidad de vida utilizados en el área de oncología. También fueron sometidos a un enfoque terapéutico para la deglución. Resultados: Los pacientes mejoraron su deglución, presentando, al final del tratamiento, una reducción en los síntomas de disfagia, la posibilidad de ingesta de alimentos por vía oral y una mejora en la calidad de vida. Conclusión: La terapia fonoaudiologica, que comprende la evaluación clínica de deglución, seguida del entrenamiento de deglución y ejercicio miofuncional para abrir el esfínter esofágico superior, ayudó en la rehabilitación de la disfagia esofágica.

Peptidylprolyl isomerase C (Ppic) regulates invariant Natural Killer T cell (iNKT) differentiation in mice.

Peptidyl-prolyl cis-trans isomerase C (Ppic) is expressed in several bone marrow (BM) hematopoietic progenitors and in T-cell precursors. Since the expression profile of Ppic in the hematoimmune system was suggestive that it could play a role in hematopoiesis and/or T lymphocyte differentiation, we sought to test that hypothesis in vivo. Specifically, we generated a Ppic-deficient mouse model by targeting the endogenous locus by CRISPR/Cas9 and tested the requirement of Ppic in hematopoiesis. Several immune cell lineages covering BM progenitors, lymphocyte precursors, as well as mature cells at the periphery were analyzed. While most lineages were unaffected, invariant NKT (iNKT) cells were reduced in percentage and absolute cell numbers in the Ppic-deficient thymus. This affected the most mature stages in the thymus, S2 and S3, and the phenotype was maintained at the periphery. Additionally, immature transitional T1 and T2 B lymphocytes were increased in the Ppic-deficient spleen, but the phenotype was lost in mature B lymphocytes. In sum, our data show that Ppic is dispensable for myeloid cells, platelets, erythrocytes, αß, and γδ T lymphocytes in vivo in the steady state, while being involved in B- and iNKT cell differentiation.

Self-renewal of double-negative 3 early thymocytes enables thymus autonomy but compromises the ß-selection checkpoint.

T lymphocyte differentiation in the steady state is characterized by high cellular turnover whereby thymocytes do not self-renew. However, if deprived of competent progenitors, the thymus can temporarily maintain thymopoiesis autonomously. This bears a heavy cost, because prolongation of thymus autonomy causes leukemia. Here, we show that, at an early stage, thymus autonomy relies on double-negative 3 early (DN3e) thymocytes that acquire stem-cell-like properties. Following competent progenitor deprivation, DN3e thymocytes become long lived, are required for thymus autonomy, differentiate in vivo, and include DNA-label-retaining cells. At the single-cell level, the transcriptional programs of thymopoiesis in autonomy and the steady state are similar. However, a new cell population emerges in autonomy that expresses an aberrant Notch target gene signature and bypasses the ß-selection checkpoint. In summary, DN3e thymocytes have the potential to self-renew and differentiate in vivo if cell competition is impaired, but this generates atypical cells, probably the precursors of leukemia.

Cell competition in hematopoietic cells: Quality control in homeostasis and its role in leukemia.

Cell competition contributes to optimal organ function by promoting tissue homogeneity. In the hematopoietic system, cell competition has been described in two distinct cell populations: in hematopoietic stem cells, and in differentiating T lymphocytes, or thymocytes. In hematopoietic stem cells, cell competition was studied in the context of mild irradiation, whereby the levels of p53 determined the outcome of the cellular interactions and the cells with lower p53 were in advantage. In the thymus, cell competition was addressed in thymus transplantation experiments, and found to be a homeostatic process that contributes to thymus turnover. Cell competition in the thymus depends on the capacity of T lymphocyte precursors to respond to interleukin 7 (IL-7). Failed cell competition permitted thymocyte self-renewal and autonomous thymopoiesis for several weeks, that culminated with leukemia onset. Beyond the work addressing cell competition in these cells, we discuss current hypotheses and observations that could be explained by cell competition. These include the clonal dynamics of hematopoietic stem cells in the ageing organism and initiation of leukemia.

Speech therapy aspects in patients' palliative care / Aspectos fonoaudiológicos de pacientes em cuidados paliativos

ABSTRACT Purpose: to describe the speech therapy aspects of patients treated by the palliative care team in a hospital. Methods: an observational and cross-sectional study, performed from medical records of patients treated under Palliative Care Program, in a hospital, from July to September 2018. Information from the anamnesis and speech-language assessments, which were analyzed by frequency measures, were collected. Results: the sample was composed by 41 medical records, including 25 males and 16 females, with an average age of 61.2 years and hospitalization average time of 20.7 days. Oral feeding was present in 73% of the sample. It was observed that 24% of the patients had impaired expressive language, 56% had reduced maximum phonation times and 34% showed altered mobility phonoarticulatory organs. For swallowing, 22% showed difficulty in some consistency. A nutritional feeding was verified in 74% of the sample and the remaining was making use of comfort feeding. In relation to assistance, 46% of the sample was under management, 7% in therapy, and the remaining did not have follow-up indication. Conclusion: relevant alterations to orofacial motricity, voice, language and swallowing were found in patients under palliative care.

RESUMO Objetivo: caracterizar aspectos fonoaudiológicos de pacientes atendidos pela equipe de cuidados paliativos em complexo hospitalar. Métodos: estudo transversal, observacional, realizado a partir de dados de prontuários de pacientes internados pelo Programa de Cuidados Paliativos de um hospital, no período entre julho e setembro de 2018. Foram coletadas informações da anamnese e avaliações fonoaudiológicas, as quais foram analisadas por medidas de frequência para as variáveis categóricas e medidas de tendência central e dispersão para as variáveis contínuas. Resultados: a amostra foi composta por 41 prontuários, referentes a 25 homens e 16 mulheres, com média de idade de 61,2 anos e tempo médio de internação de 20,7 dias. A alimentação oral esteve presente em 73% da amostra. Observou-se que 24% dos pacientes apresentavam linguagem expressiva prejudicada, 56% apresentaram tempos máximos de fonação reduzidos e 34% mobilidade de órgãos fonoarticulatórios alterada. Quanto à deglutição, 22% apresentaram dificuldade em alguma consistência. Dieta para nutrição foi verificada em 74% da amostra e o restante fazia uso de dieta para conforto. Sobre a assistência, 46% da amostra estava em gerenciamento, 7% em terapia, demais sem acompanhamento. Conclusão: foram encontradas alterações pertinentes à motricidade orofacial, voz, linguagem e deglutição em pacientes em cuidados paliativos.

Cell Competition, the Kinetics of Thymopoiesis, and Thymus Cellularity Are Regulated by Double-Negative 2 to 3 Early Thymocytes.

Cell competition in the thymus is a homeostatic process that drives turnover. If the process is impaired, thymopoiesis can be autonomously maintained for several weeks, but this causes leukemia. We aimed to understand the effect of cell competition on thymopoiesis, identify the cells involved, and determine how the process is regulated. Using thymus transplantation experiments, we found that cell competition occurs within the double-negative 2 (DN2) and 3 early (DN3e) thymocytes and inhibits thymus autonomy. Furthermore, the expansion of DN2b is regulated by a negative feedback loop that is imposed by double-positive thymocytes and determines the kinetics of thymopoiesis. This feedback loop affects the cell cycle duration of DN2b, in a response controlled by interleukin 7 availability. Altogether, we show that thymocytes do not merely follow a pre-determined path if provided with the correct signals. Instead, thymopoiesis dynamically integrates cell-autonomous and non-cell-autonomous aspects that fine-tune normal thymus function.

Atuação fonoaudiológica no paciente oncológico disfágico: uso de indicadores / Speech therapy performance in dysphagic cancer patients: use of indicators / Rendimiento de la terapia del habla en pacientes con cáncer de disfagia: uso de indicadores

Objetivo: Descrever a atuação fonoaudiológica hospitalar no paciente oncológico disfágico. Métodos: Estudo transversal, retrospectivo, descritivo, quantitativo, desenvolvido em um hospital oncológico. A amostra foi composta por prontuários de pacientes com câncer que realizaram acompanhamento fonoaudiológico para disfagia. Foram aplicados indicadores fonoaudiológicos de disfagia e comparada a escala de ingestão de alimentação por via oral (FOIS) antes e após terapia fonoaudiológica. Resultados: A amostra contou com 400 prontuários, 189 foram incluídos no GA (grupo ambulatório) e 211 no GI (grupo internação). A média geral da idade da amostra corresponde a 60,35±12,63, sendo o predomínio de homens 263 (65,8%). Quanto às neoplasias apresentadas pelos pacientes: 247 cabeça e pescoço e 43 esôfago e estômago. No GA 143 (75,7%) pacientes melhoraram a escala FOIS pós-terapia, 33 pacientes (17,5%) mantiveram o mesmo nível e 13 pacientes (6,9%) apresentaram piora na FOIS após o processo terapêutico. No GI 103 (48,8%) pacientes melhoraram pós-terapia, 81 pacientes (38,4%) mantiveram o mesmo nível na escala, e 27 pacientes (12,8%) apresentaram piora após a terapia fonoaudiológica. Conclusão: O estabelecimento de indicadores na atuação junto ao paciente disfágico permite identificar e quantificar as melhorias dos processos assistenciais, trazendo benefícios diretos aos pacientes, auxiliando na caracterização da população atendida, otimizando e aprimorando os processos e resultados, visando o aprimoramento da qualidade dos serviços prestados, bem como redução do tempo de internação e dos custos hospitalares.

Objective: To describe hospital speech therapy in dysphagic cancer patients. Methods: Crosssectional, retrospective, descriptive, quantitative study, developed in an oncology hospital. The sample consisted of medical records of cancer patients who underwent speech therapy follow-up for dysphagia. Speech therapy indicators of dysphagia were applied and the oral food intake scale (FOIS) was compared before and after speech therapy. Results: The sample had 400 medical records, 189 were included in the GA (outpatient group) and 211 in the IG (hospitalization group). The general mean age of the sample corresponds to 60.35 ± 12.63, with a predominance of men 263 (65.8%). In relation to the neoplasms presented by the patients: 247 head and neck, and 43 esophagus and stomach. In GA 143 (75.7%) patients improved the FOIS scale after therapy, 33 patients (17.5%) maintained the same level and 13 patients (6.9%) presented worsening in FOIS after the therapeutic process. In GI 103 (48.8%) patients improved after therapy, 81 patients (38.4%) maintained the same level on the scale, and 27 patients (12.8%) presented worsening after speech therapy. Conclusion: The establishment of indicators in the performance of dysphagic patients allows identifying and quantifying improvements in care processes, bringing direct benefits to patients, assisting in the characterization of the population served, optimizing and improving processes and results, aiming at improving the quality of services, as well as reducing length of stay and hospital costs.

Objetivo: describir la logopedia hospitalaria en pacientes con cáncer de disfagia. Métodos: Estudio transversal, retrospectivo, descriptivo, cuantitativo, desarrollado en un hospital de oncología. La muestra consistió en registros médicos de pacientes con cáncer que se sometieron a terapia del habla por disfagia. Se aplicaron indicadores de disfagia a la terapia del habla y se comparó la escala de ingesta de alimentos orales (FOIS) antes y después de la terapia del habla. Resultados: La muestra tenía 400 registros médicos, 189 se incluyeron en el GA (grupo de pacientes ambulatorios) y 211 en el IG (grupo de hospitalización). La edad media general de la muestra corresponde a 60,35 ± 12,63, con predominio de hombres 263 (65,8%). En cuanto a las neoplasias presentadas por los pacientes: 247 cabeza y cuello y 43 esófago y estómago. En GA 143 (75.7%) los pacientes mejoraron la escala FOIS después de la terapia, 33 pacientes (17.5%) mantuvieron el mismo nivel y 13 pacientes (6.9%) presentaron empeoramiento en FOIS después del proceso terapéutico. En GI 103 (48.8%) los pacientes mejoraron después de la terapia, 81 pacientes (38.4%) mantuvieron el mismo nivel en la escala y 27 pacientes (12.8%) presentaron empeoramiento después de la terapia del habla. Conclusión: El establecimiento de indicadores en el trabajo con el paciente con disfagia permite identificar y cuantificar las mejoras de los procesos de atención, brindando beneficios directos a los pacientes, ayudando en la caracterización de la población atendida, optimizando y mejorando los procesos y resultados, con el objetivo de mejorar la calidad de los servicios. proporcionado, así como la reducción de la estancia hospitalaria y los costos hospitalarios.

Early Enrichment of ESR1 Mutations and the Impact on Gene Expression in Presurgical Primary Breast Cancer Treated with Aromatase Inhibitors.

PURPOSE: To investigate the presence of ESR1 mutations in primary estrogen-receptor-positive (ER+) breast cancer treated with extended (>4 weeks) neoadjuvant (presurgical) aromatase inhibitor (NAI) therapy and to identify patients who may gain less benefit from aromatase inhibition (AI) alone based upon on-treatment changes in gene expression. EXPERIMENTAL DESIGN: We evaluated ER, progesterone receptor, and Ki67 by immunostaining, ESR1 mutations by droplet-digital PCR and expression of over 800 key breast cancer genes in paired pre- and post-NAI tumor samples from 87 ER+ breast cancer patients. RESULTS: Cell proliferation and estrogen-regulated genes (ERG) remained suppressed in most tumors indicative of persistent response to NAI. Enrichment of ESR1 mutations was found in five tumors and predominantly in patients receiving therapy for >6 months. ESR1-mutant tumors showed increased expression of ESR1 transcript and limited suppression of ERGs and proliferation-associated genes in response to NAI. ESR1 wild-type tumors with high residual proliferation (Ki67r ≥10%; 15/87 tumors) showed lower ESR1/ER expression pre- and post-therapy and lower ERGs. Tumors with ESR1 mutations or Ki67r ≥10% showed less inhibition of estrogen response, cell cycle, and E2F-target genes. CONCLUSIONS: Ligand-independent ER signaling, as a result of ESR1 mutation or reduced ER dependence, identified after extended NAI therapy, can guide early selection of patients who would benefit from combination therapy.

Effects of transcutaneous electrical nerve stimulation on the salivary flow of patients with hyposalivation induced by radiotherapy in the head and neck region-A randomised clinical trial.

Hyposalivation is a frequent complication after treatment with radiotherapy. To evaluate the efficacy of transcutaneous electrical nerve stimulation (TENS) on the hyposalivation assessed through stimulated salivary flow (SSF). In this clinical trial, 68 patients (with hyposalivation) were randomly assigned to control (n = 31) or TENS (n = 37) group. Participants in control group received habitual care, while those in TENS group received 8 sessions (20 minutes each) delivered twice a week for four weeks. The electrodes were attached over the skin covering the salivary glands. The electric pulse was adjusted at a frequency of 50 Hz, pulse width of 250 µs and as intense as tolerated. SSF was evaluated through sialometry. Self-perception of salivary flow (SPSF) and quality of life (QL) was evaluated prior to, during and at 1, 3 and 6 months after treatment. Although no changes were observed in the control group for SSF at any timepoints, TENS group showed a progressive increase in SSF from the third session until the end of the treatment. Significant improvements were also found in SPSF, especially when the SSF reached values ≥0.7 mL/minute. The most expressive results were evident at 6 months after treatment so that SSF, SPSF and QL remained significantly higher (F = 9.5, P = 0.0001; H = 143.77, P < 0.0001; χ2  = 9.162, P = 0.02, respectively). TENS was effective at improving hyposalivation. The benefits on SSF, SPSF and QL give base to a promising therapeutic strategy for patients with hyposalivation after radiotherapy treating head and neck cancer.