Hematopoietic stem cell transplantation (HSCT) is a frequent therapeutic approach to restore hematopoiesis in patients with hematologic diseases. Patients receive a hematopoietic stem cell (HSC)-enriched donor cell infusion also containing immune cells, which may have a beneficial effect by eliminating residual neoplastic cells. However, the effect that donor innate immune cells may have on the donor HSCs has not been deeply explored. Here, we evaluate the influence of donor natural killer (NK) cells on HSC fate, concluded that NK cells negatively affect HSC frequency and function, and identified interferon-gamma (IFNg) as a potential mediator. Interestingly, improved HSC fitness was achieved by NK cell depletion from murine and human donor infusions or by blocking IFNg activity. Thus, our data suggest that suppression of inflammatory signals generated by donor innate immune cells can enhance engraftment and hematopoietic reconstitution during HSCT, which is particularly critical when limited HSC numbers are available and the risk of engraftment failure is high.

Objectives To describe the care provided by Brazilian nurses to patients with Juvenile Systemic Lupus Erythematosus (JSLE) using a self-administered questionnaire and to evaluate the possible association of demographic data and knowledge of the disease with availability of tools for diagnosis and treatment in Brazilian pediatric services. Method This is a cross-sectional observational descriptive study that analyzed the care provided by Brazilian nurses to patients with JSLE based on the answers to a self-administered questionnaire. Questions included demographics of professionals, nursing consultation, usage of tools to assess disease activity, diagnostic criteria, general care, available practices, transition program, and practices needed for better care. Results A total of 111/373 (29.4%) questionnaires were completed, most professionals were female (90.1%). Hospitalization (45.9%) and poor medication adherence (27.9%) were the most reported problems, and lack of knowledge about the institutional transition process to adult care was mentioned by half of the professionals (50.5%). Comparisons of professionals on expected care of patients regarding the type of service, hospitalized patient care, and care provided to patients with JSLE did not reveal statistically significant differences ( p > 0.05). Nurses who care for patients with JSLE are more likely to work in a public setting (14.5% vs. 36.8%, p = 0.048) and less likely to verify vaccination records (0.12.9% vs. 36.8%, p = 0.038). Nurses who worked in the inpatient setting with patients with JSLE were less likely to address pain concerns (11.7% vs. 61.6%, p < 0.0001) compared to nurses who didn’t work with JSLE patients. However, they were more likely to discuss sunscreen use (54.9% vs. 25%, p < 0.05) and be part of a multi-disciplinary team (84.3 vs. 50%, p < 0.0001). Conclusions This study demonstrates that the care provided by nurses to patients with JSLE does not consider all the resources available to assess the disease and occurs differently in the inpatient versus outpatient settings. Future research should address this gap in care. Lack of JSLE awareness was commonly reported among professionals, confirming the need for greater knowledge about JSLE, its treatment, and ways to improve adherence.

Objective: to assess mental health issues in pediatric nurses during coronavirus pandemic in 2019. Method: cross-sectional study was conducted with pediatric nurses at the Instituto da Criança e do Adolescente based on online self-rated survey about clinical practice and mental health impact during COVID-19 pandemic. Validated self-reported scales for anxiety, depression and burnout were used for assessing these professionals. Results: 107/298 (36%) nurses answered, 90% were female, median age was 41(23-64) years, 68% worked with adolescents, 66% in frontline. Burnout, anxiety and moderate/severe depression occurred in 65%, 72% and 74%, respectively. Lack of standardized treatment protocol for nurses (27%vs.10%, p=0.049), moderate/severe depression (74% vs. 16%, p=0.002) and burnout (82% vs. 58%, p=0.01) were significantly higher in pediatric nurses with anxiety compared to those without. Pediatric nurses that worked with adolescents compared to those that did not showed higher frequency of burnout in the former group (77% vs. 32%, p=0.0001). Multivariable analysis revealed that adequate quarantine adherence increased the presence of anxiety in 4.6 times [OR4.6(CI 1.1-20.2), p=0.04]. Conclusion: most pediatric nurses who had worked in the frontline of COVID-19 were under precarious conditions, working with reduced team, and with an expressive changes in their monthly income. Current anxiety was a relevant issue, burnout was also an important mental condition for these professionals, reinforcing culture of good teamwork, collaboration practices and psychological/psychiatric approach.

Resumo Objetivo: avaliar problemas de saúde mental em enfermeiros pediátricos durante a pandemia causada pelo coronavírus 2019. Método: estudo transversal realizado com enfermeiros pediátricos do Instituto da Criança e do Adolescente, por meio de uma pesquisa online de autoavaliação sobre prática clínica e impacto na saúde mental, durante a pandemia de COVID-19. Foram avaliadas escalas de autoavaliação validadas para ansiedade, depressão e burnout. Resultados: 107/298(36%) enfermeiros responderam, dos quais 90% eram do sexo feminino, a mediana de idade atual era 41(23-64) anos, 68% trabalhavam com adolescentes, 66% trabalhavam na linha de frente. Burnout, ansiedade e depressão moderada/grave ocorreram em 65%, 72% e 74% dos enfermeiros, respectivamente. Falta de protocolo de tratamento padronizado nas enfermarias (27% vs. 10%, p=0,049), depressão moderada/grave (74% vs. 16%, p=0,002) e burnout (82% vs. 58%, p=0,01) foram significativamente maiores em enfermeiros pediátricos com ansiedade, em comparação com enfermeiros sem essa condição. Os enfermeiros pediátricos que trabalhavam com adolescentes apresentaram maior frequência de burnout, quando comparados aos que não trabalhavam com esse grupo (77% vs. 32%, p=0,0001). A análise multivariada revelou que o cumprimento adequado da quarentena aumentou a presença de ansiedade em 4,6 vezes [OR 4.6(IC 1,1-20,2), p=0,04]. Conclusão: a maioria dos enfermeiros pediátricos atuava na linha de frente da COVID-19, em condições precárias, trabalhando com equipe reduzida e enfrentando perdas expressivas de renda. A ansiedade atual foi um tema relevante e o burnout também foi uma condição mental importante para esses profissionais, reforçando a cultura do bom trabalho em equipe, das práticas de colaboração e do cuidado psicológico/psiquiátrico.

In cancer, tumor cells and their neoplastic microenvironment can sculpt the immunogenic phenotype of a developing tumor. In this context, natural killer (NK) cells are subtypes of lymphocytes of the innate immune system recognized for their potential to eliminate neoplastic cells, not only through direct cytolytic activity but also by favoring the development of an adaptive antitumor immune response. Even though the protective effect against leukemia due to NK-cell alloreactivity mediated by the absence of the KIR-ligand has already been shown, and some data on the role of NK cells in myeloproliferative neoplasms (MPN) has been explored, their mechanisms of immune escape have not been fully investigated. It is still unclear whether NK cells can affect the biology of BCR-ABL1-negative MPN and which mechanisms are involved in the control of leukemic stem cell expansion. Aiming to investigate the potential contribution of NK cells to the pathogenesis of MPN, we characterized the frequency, receptor expression, maturation profile, and function of NK cells from a conditional Jak2V617F murine transgenic model, which faithfully resembles the main clinical and laboratory characteristics of human polycythemia vera, and MPN patients. Immunophenotypic analysis was performed to characterize NK frequency, their subtypes, and receptor expression in both mutated and wild-type samples. We observed a higher frequency of total NK cells in JAK2V617F mutated MPN and a maturation arrest that resulted in low-numbered mature CD11b+ NK cells and increased immature secretory CD27+ cells in both human and murine mutated samples. In agreement, inhibitory receptors were more expressed in MPN. NK cells from Jak2V617F mice presented a lower potential for proliferation and activation than wild-type NK cells. Colonies generated by murine hematopoietic stem cells (HSC) after mutated or wild-type NK co-culture exposure demonstrated that NK cells from Jak2V617F mice were deficient in regulating differentiation and clonogenic capacity. In conclusion, our findings suggest that NK cells have an immature profile with deficient cytotoxicity that may lead to impaired tumor surveillance in MPN. These data provide a new perspective on the behavior of NK cells in the context of myeloid malignancies and can contribute to the development of new therapeutic strategies, targeting onco-inflammatory pathways that can potentially control transformed HSCs.

Resumo Objetivo: o cuidado de adolescentes com ou sem doença crônica deve ser completo, padronizado e focado nas demandas individuais e no processo de transição para a assistência ao adulto e adesão ao tratamento. Este estudo teve como objetivo caracterizar a assistência prestada por enfermeiros do estado de São Paulo que atuam com adolescentes. Método: trata-se de um estudo transversal e descritivo sobre a assistência prestada a adolescentes por enfermeiros de São Paulo, a partir das respostas a um questionário autoaplicável, disponível no instrumento REDCap entre agosto de 2018 e outubro de 2019. Resultados: os participantes responderam a 1632 questionários. Apenas 38% dos enfermeiros trabalham com adolescentes, e 11,2% deles de forma exclusiva. Os profissionais foram divididos de acordo com a mediana de tempo de experiência profissional nos Grupos A e B (≤ 5 anos e > 5 anos). A dependência de drogas (p=0,01) e o trabalho com uma equipe multidisciplinar (p=0,04) foram significativamente mais relatados no Grupo B. O acompanhamento rotineiro (p=0,02) e o questionamento sobre violência sexual ou física (p=0,03) foram significativamente mais realizados pelos profissionais do Grupo A. Conclusão: este estudo identificou a necessidade de um protocolo de assistência que possa ser replicado em larga escala e que inclua o tratamento e as particularidades dos adolescentes para melhorar a adesão e a transição para o cuidado do adulto.

Resumen Objetivo: el cuidado de los adolescentes con o sin enfermedad crónica debe ser completo, estandarizado y centrado en las demandas individuales y en el proceso de transición a la atención para adultos y la adherencia al tratamiento. Este estudio tuvo como objetivo caracterizar los cuidados prestados por el personal de enfermería del estado de São Paulo que trabaja con adolescentes. Método: se trata de un estudio transversal y descriptivo sobre los cuidados prestados a los adolescentes por el personal de enfermería de São Paulo, a partir de las respuestas a un cuestionario autoadministrado, disponible en la herramienta REDCap entre agosto de 2018 y octubre de 2019. Resultados: los participantes respondieron a 1.632 cuestionarios. Solo el 38% del personal de enfermería trabaja con adolescentes, el 11,2% de forma exclusiva. Los profesionales se dividieron según la duración media de la experiencia profesional en los grupos A y B (≤5 años y >5 años). La drogadicción (p=0,01) y el trabajo con un equipo multidisciplinar (p=0,04) fueron significativamente más reportados en el grupo B. El seguimiento rutinario (p=0,02) y las preguntas sobre violencia sexual o física (p=0,03) fueron significativamente más realizadas por los profesionales del grupo A. Conclusión: este estudio identificó la necesidad de un protocolo de atención que pueda ser replicado a gran escala y que incluya el tratamiento y las particularidades de los adolescentes para mejorar la adherencia y la transición a la atención de adultos.

Objective: the care of adolescents with or without a chronic disease must complete, standardized and focused on individual demands and the transition process to adult care and adherence to treatment. This study aimed to characterize the care provided by nurses from the state of São Paulo who work with adolescents. Method: this is a cross-sectional and descriptive study on the care provided to adolescents by nurses in São Paulo, based on the answers to a self-administered questionnaire, available in the REDCap tool between August 2018 and October 2019. Results: participants answered 1632 questionnaires. Only 38% of nurses work with adolescents, 11.2% exclusively. Professionals were divided according to the median length of professional experience in groups A and B (≤5 years and >5 years). Drug addiction (p=0.01) and working with a multidisciplinary team (p=0.04) were significantly more reported in group B. Routine follow-up (p=0.02) and questioning about sexual or physical violence (p=0.03) were significantly more performed by professionals from group A. Conclusion: this study identified the need for a care protocol that can be replicated on a large scale and that includes the treatment and the particularities of adolescents to improve adherence and the transition into adult care.