A Phase 1/2 multicenter trial of DKN-01 as monotherapy or in combination with docetaxel for the treatment of metastatic castration-resistant prostate cancer (mCRPC).

BACKGROUND: Dickkopf-related protein 1 (DKK1) is a Wingless-related integrate site (Wnt) signaling modulator that is upregulated in prostate cancers (PCa) with low androgen receptor expression. DKN-01, an IgG4 that neutralizes DKK1, delays PCa growth in pre-clinical DKK1-expressing models. These data provided the rationale for a clinical trial testing DKN-01 in patients with metastatic castration-resistant PCa (mCRPC). METHODS: This was an investigator-initiated parallel-arm phase 1/2 clinical trial testing DKN-01 alone (monotherapy) or in combination with docetaxel 75 mg/m2 (combination) for men with mCRPC who progressed on ≥1 AR signaling inhibitors. DKK1 status was determined by RNA in-situ expression. The primary endpoint of the phase 1 dose escalation cohorts was the determination of the recommended phase 2 dose (RP2D). The primary endpoint of the phase 2 expansion cohorts was objective response rate by iRECIST criteria in patients treated with the combination. RESULTS: 18 pts were enrolled into the study-10 patients in the monotherapy cohorts and 8 patients in the combination cohorts. No DLTs were observed and DKN-01 600 mg was determined as the RP2D. A best overall response of stable disease occurred in two out of seven (29%) evaluable patients in the monotherapy cohort. In the combination cohort, five out of seven (71%) evaluable patients had a partial response (PR). A median rPFS of 5.7 months was observed in the combination cohort. In the combination cohort, the median tumoral DKK1 expression H-score was 0.75 and the rPFS observed was similar between patients with DKK1 H-score ≥1 versus H-score = 0. CONCLUSION: DKN-01 600 mg was well tolerated. DKK1 blockade has modest anti-tumor activity as a monotherapy for mCRPC. Anti-tumor activity was observed in the combination cohorts, but the response duration was limited. DKK1 expression in the majority of mCRPC is low and did not clearly correlate with anti-tumor activity of DKN-01 plus docetaxel.

Peripheral Intravenous Catheter Insertion: Professionals' Performance and Implications for Patient Safety: A Cross-Sectional Study.

This study evaluated peripheral intravenous catheter insertion by licensed practical nurses in a simulated scenario. This cross-sectional and descriptive study was performed in a general hospital's simulation center located in Brazil, from January to October 2020. The authors developed a tool from the leading guidelines to measure peripheral intravenous catheter insertion performance in 60 licensed practical nurses. Data were analyzed using descriptive statistics, with proportions for categorical variables and analytical statistics to denote significance, using SPSS version 22.0. Ethical aspects were respected. Despite the sample comprising professionals who declared an average experience with peripheral intravenous catheter insertion of 6.4 years, at least 50% failed in some tool element. This low score on peripheral intravenous catheter insertion performance is because automation is possible without efforts to improve it. Adding years of practice does not generate better performance. The licensed practical nurses' performance was lower than expected, considering their reported experience, which poses a risk to patient safety. The training of these professionals needs to be discussed in countries where the practice is legal. Skills training should include simulation to approximate clinical practice; nurses must exercise their role in supervising the team.

Browning of the white adipose tissue regulation: new insights into nutritional and metabolic relevance in health and diseases.

Adipose tissues are dynamic tissues that play crucial physiological roles in maintaining health and homeostasis. Although white adipose tissue and brown adipose tissue are currently considered key endocrine organs, they differ functionally and morphologically. The existence of the beige or brite adipocytes, cells displaying intermediary characteristics between white and brown adipocytes, illustrates the plastic nature of the adipose tissue. These cells are generated through white adipose tissue browning, a process associated with augmented non-shivering thermogenesis and metabolic capacity. This process involves the upregulation of the uncoupling protein 1, a molecule that uncouples the respiratory chain from Adenosine triphosphate synthesis, producing heat. ß-3 adrenergic receptor system is one important mediator of white adipose tissue browning, during cold exposure. Surprisingly, hyperthermia may also induce beige activation and white adipose tissue beiging. Physical exercising copes with increased levels of specific molecules, including Beta-Aminoisobutyric acid, irisin, and Fibroblast growth factor 21 (FGF21), which induce adipose tissue browning. FGF21 is a stress-responsive hormone that interacts with beta-klotho. The central roles played by hormones in the browning process highlight the relevance of the individual lifestyle, including circadian rhythm and diet. Circadian rhythm involves the sleep-wake cycle and is regulated by melatonin, a hormone associated with UCP1 level upregulation. In contrast to the pro-inflammatory and adipose tissue disrupting effects of the western diet, specific food items, including capsaicin and n-3 polyunsaturated fatty acids, and dietary interventions such as calorie restriction and intermittent fasting, favor white adipose tissue browning and metabolic efficiency. The intestinal microbiome has also been pictured as a key factor in regulating white tissue browning, as it modulates bile acid levels, important molecules for the thermogenic program activation. During embryogenesis, in which adipose tissue formation is affected by Bone morphogenetic proteins that regulate gene expression, the stimuli herein discussed influence an orchestra of gene expression regulators, including a plethora of transcription factors, and chromatin remodeling enzymes, and non-coding RNAs. Considering the detrimental effects of adipose tissue browning and the disparities between adipose tissue characteristics in mice and humans, further efforts will benefit a better understanding of adipose tissue plasticity biology and its applicability to managing the overwhelming burden of several chronic diseases.

Judicialização dos eventos adversos na assistência à saúde no Brasil: uma revisão integrativa / Judicialization of adverse events in health care in Brazil: an integrative review / Judicialización de los eventos adversos en la atención a la salud en Brasil: una revisión integradora

Objetivo: identificar, na literatura, quais eventos adversos decorrentes da assistência à saúde foram judicializados no Brasil e os fatores contribuintes para tais eventos. Metodologia: trata-se de revisão integrativa da literatura. As bases selecionadas para a busca bibliográfica foram Biblioteca Virtual em Saúde (BVS), Pubmed, Embase, Scientific Electronic Library Online (Scielo) e Scopus. A busca, realizada sem um recorte temporal específico, resultou em 510 estudos, dos quais foram selecionados 14 artigos para análise. Resultados: os resultados foram divididos em duas categorias: i) eventos adversos judicializados no Brasil e seus fatores contribuintes; ii) estratégias para a redução da judicialização de eventos adversos. As referências selecionadas foram publicadas entre os anos de 2010 e 2019. As especialidades mais mencionadas nos processos de judicialização foram ginecologia, obstetrícia e cirurgia. O setor de urgência e emergência foi o local mais frequentemente mencionado e os eventos adversos mais citados foram relacionados às infecções e às cirurgias. Considerações finais: ressalta-se a importância de incentivar a discussão acerca da judicialização da saúde, no que tange aos eventos adversos, contribuindo para a sua prevenção, mitigação e, ao mesmo tempo, para a redução das ações judiciais e consequente melhoria na qualidade do cuidado de saúde e segurança do paciente.

Objective: to examine the adverse events related to health care in Brazil that were judicially sanctioned and the factors that contributed to these events. Methods: this was an integrative literature review. The Virtual Health Library (VHL), Pubmed, Embase, Scientific Electronic Library Online (Scielo) and Scopus were selected for the bibliographic search. The search, conducted without a specific time frame, yielded 510 studies, of which 14 articles were selected for analysis. Results: The results were classified into two categories: i) adverse events reported in Brazil and the contributing factors; ii) strategies to reduce the legalization of adverse events. The selected references were published between 2010 and 2019. The most frequently mentioned specialties in the legalization processes were gynecology, obstetrics, and surgery. The emergency sector was the most frequently mentioned site, and the most frequently mentioned adverse events were related to infections and surgery. Final considerations: we emphasize the importance of encouraging the discussion about the health's judicialization of adverse events, contributing to their prevention, mitigation and, simultaneously, to the reduction of lawsuits and consequent improvement in the quality of health care and patient safety.

Objetivo: identificar, en la literatura, qué eventos adversos resultantes de la atención a la salud fueron judicializados en Brasil y los factores contribuyentes para tales eventos. Metodología: se trata de una revisión integrativa de la literatura. Las bases seleccionadas para la búsqueda bibliográfica fueron la Biblioteca Virtual en Salud (BVS), Pubmed, Embase, Scientific Electronic Library Online (Scielo) y Scopus. La búsqueda, realizada sin un marco de tiempo específico, resultó en 510 estudios, de los cuales 14 artículos fueron seleccionados para el análisis. Resultados: los resultados se dividieron en dos categorías: i) eventos adversos registrados en Brasil y sus factores contribuyentes; ii) estrategias para reducir la legalización de eventos adversos. Las referencias seleccionadas fueron publicadas entre 2010 y 2019. Las especialidades más mencionadas en los procesos de judicialización fueron ginecología, obstetricia y cirugía. El sector de urgencias y emergencias fue el lugar mencionado con mayor frecuencia y los eventos adversos más citados estuvieron relacionados con infecciones y cirugías. Consideraciones finales: destacamos la importancia de incentivar la discusión sobre la judicialización de la salud, en lo que se refiere a los eventos adversos, contribuyendo para su prevención, mitigación y, al mismo tiempo, para la reducción de procesos judiciales y consecuente mejora en la calidad de la atención. cuidado de la salud y seguridad del paciente.

Obesity and adipose tissue impact on T-cell response and cancer immune checkpoint blockade therapy.

Many different types of cancer are now well known to have increased occurrence or severity in individuals with obesity. The influence of obesity on cancer and the immune cells in the tumor microenvironment has been thought to be a pleiotropic effect. As key endocrine and immune organs, the highly plastic adipose tissues play crucial roles in obesity pathophysiology, as they show alterations according to environmental cues. Adipose tissues of lean subjects present mostly anti-inflammatory cells that are crucial in tissue remodeling, favoring uncoupling protein 1 expression and non-shivering thermogenesis. Oppositely, obese adipose tissues display massive proinflammatory immune cell infiltration, dying adipocytes, and enhanced crown-like structure formation. In this review, we discuss how obesity can lead to derangements and dysfunctions in antitumor CD8+ T lymphocytes dysfunction. Moreover, we explain how obesity can affect the efficiency of cancer immunotherapy, depicting the mechanisms involved in this process. Cancer immunotherapy management includes monoclonal antibodies targeting the immune checkpoint blockade. Exhausted CD8+ T lymphocytes show elevated programmed cell death-1 (PD-1) expression and highly glycolytic tumors tend to show a good response to anti-PD-1/PD-L1 immunotherapy. Although obesity is a risk factor for the development of several neoplasms and is linked with increased tumor growth and aggressiveness, obesity is also related to improved response to cancer immunotherapy, a phenomenon called the obesity paradox. However, patients affected by obesity present higher incidences of adverse events related to this therapy. These limitations highlight the necessity of a deeper investigation of factors that influence the obesity paradox to improve the application of these therapies.

Hypersensitivity pneumonia associated with metallic straw of mate (chimarrão): A case report.

This case report describes a 61-year-old male who sought treatment for sudden symptoms of dry cough, chest pain and severe dyspnea. On admission, the patient had hypoxemia and predominantly medullary infiltrate that we could observe on his imaging exams. After hospital discharge, he presented two similar episodes, with clinical and radiological improvement with oxygen therapy alone. He denied exposure to birds, mold or chemical agents. However, the patient noticed the onset of symptoms soon after drinking chimarrão. Given the compatible clinical, radiological and laboratory history, the diagnosis of hypersensitivity pneumonitis was performed. The patient was instructed by the medical team not to consume the drink anymore, remaining asymptomatic for more than two years.

Perfil de diagnósticos de enfermería en un hospital brasileño especializado en cuidados paliativos oncológicos / Profile of nursing diagnoses in a Brazilian hospital specializing in palliative care in cancer

La finalidad de este estudio fue trazar el perfil de diagnósticos de enfermería en el contexto de la hospitalización en cuidados paliativos oncológicos y las respectivas intervenciones de enfermería. Estudio transversal, retrospectivo, cuantitativo, llevado a cabo en hospital público especializado en cuidados paliativos, en Río de Janeiro, Brasil. La muestra abarcó 280 registros de personas hospitalizadas entre julio y diciembre de 2010. Se evidenció la prevalencia de individuos con déficit de autocuidados, movilidad física afectada, riesgo para e integridad de la piel perjudicada, riesgo de infección, nutrición desequilibrada, fatiga, mucosa oral perjudicada y dolor. En general, el conocimiento del perfil de los diagnósticos de enfermería contribuye con el retrato de la realidad, a partir de la identificación de los principales problemas que presentan los pacientes y sus familiares. Este perfil coloca en evidencia los recursos necesarios para la atención de una enfermería adecuada, siendo esencial para la organización, planificación y para el establecimiento de prioridades por parte del enfermero.

This study aimed to outline the nursing diagnosis profile during hospitalization in cancer palliative care and related nursing interventions. A cross-sectional, retrospective and quantitative approach, was performed in a palliative care specialized hospital, at Rio de Janeiro, Brazil. Records of 280 patients hospitalized between July and December 2010 comprised the sample. The prevalence of patients with high degree of dependence, impaired physical mobility, risk for and impaired skin integrity, risk for infection, imbalanced nutrition, fatigue, impaired oral mucous membrane and pain, was revealed. In general, knowledge of the profile of nursing diagnosis contributes to document the reality, based on a survey of the main problems presented by patients and their families. This profile shows the resources needed for adequate nursing care and is essential to the organization, planning and priority setting by nurses.

Memórias E Lembranças Das Enfermeiras do Hospital dos Servidores do Estado (HSE): 1947-2009 / Memories And Remembrances Of The Nurses From The Hospital Of The Public Servers (HSE): 1947-2009

Estudo de natureza histórico social cujo objetivo é analisar as memórias e lembranças das enfermeiras do Hospital dos Servidores do Estado desde sua inauguração em 1947 até 2009. É um estudo em que as lembranças das Enfermeiras adquirem força à medida que se refletem no seu convívio na instituição. Desdobramos o conceito entre lembranças e memória na construção de uma realidade social. A historia oral foi utilizada como método e fonte primária, uma vez que nos proporcionou abordar o contexto estudado e, como fontes secundárias, elegemos livros sobre o contexto histórico em que foi criado o Hospital dos Servidores do Estado. Concluímos que o caminho percorrido pelas Enfermeiras implicou em conhecermos ora o passado (das mais antigas), ora o presente (das mais jovens), o que nos permite conhecer as experiências mediante seus próprios depoimentos, contribuindo assim para a história viva e verdadeira da enfermagem

Metodologia da assistência de enfermagem no pós-operatório de cirurgia cardíaca: um estudo de caso / Nursing assistance methodology in postoperative cardiac surgery

As doenças cardiovasculares são as principais causas de morbi-mortalidade no Brasil, gerando um aumento no número de internações hospitalares e de cirurgias cardíacas. O cuidado de enfermagem prestado no pós-operatório de cirurgia cardíaca é geralmente complexo, dada a instabilidade do quadro clínico do paciente, o que exige uma atuação precisa da equipe de enfermagem. O presente estudo trata sobre a aplicação da metodologia da assistência de enfermagem ao paciente no pós-operatório de cirurgia cardíaca. Os objetivos são: descrever as necessidades do paciente no pós-operatório de cirurgia cardíaca, identificadas pela enfermeira; identificar as fragilidades e potencialidades das enfermeiras no planejamento do cuidado de enfermagem ao paciente no pós-operatório de cirurgia cardíaca; e elaborar subsídios para a construção de uma metodologia de assistência de enfermagem aplicada ao paciente no pós-operatório de cirurgia cardíaca. Foi utilizada a abordagem qualitativa, com método de estudo de caso. O cenário da pesquisa foi a Unidade Cardio-Intensiva (UCI) de um Hospital Público Federal da cidade do Rio de Janeiro. Os sujeitos do estudo foram 21 enfermeiros atuantes na Unidade, sendo adotado como critério de inclusão a atuação destes enfermeiros no setor por mais de seis meses...

Liderança em enfermagem psiquiátrica / Leadership in psychiatric nursing

O processo de liderança em enfermagem psiquiátrica é uma temática que deve ser cuidadosamente abordada e amplamente discutida. Contudo, poucas são as fontes científicas acerca do assunto. Assim sendo, buscou-se através deste ensaio refletir a liderança e as suas várias formas de abordagem em psiquiatria ao longo dos tempos, sendo possível certificar sua evolução...

Clientes com hipertensão arterial: perspectiva da gerência do cuidado de enfermagem / Customers with arterial hypertension: perspective of the management of the care of nursing

Investiga-se o grau de controle da hipertensão arterial e a aderência dos clientes ao tratamento, além da exposição destes aos diversos fatores de risco para as coronariopatias. Os obejtivos são descrever o perfil epidemiológico dos clientes hipertensos que frequentam o ambulatório de uma clínica médica de um Hospital Universitário do Município do Rio de Janeiro e discutir as estratégias de gerenciamento do cuidado de enfermagem aos clientes em convívio com os fatores de risco cardiovasculares. O estudo é de natureza qualitativa com amostra de 57 clientes, escolhida de forma aleatória. Percebeu-se um elevado número de clientes expostos a tais fatores, o que denuncia a falta de aderência aos programas de controle e prevenção. É importante a atuação da Enfermeira nesses programas e em atividades educativas planejando cuidados nos diferentes níveis de intervenção.