Efficacy and safety of induction chemotherapy in oral cavity cancer: An eight-year experience at a Portuguese reference center.

BACKGROUND: Induction chemotherapy has been described as an option in locally advanced oral cavity squamous cell carcinoma when the surgical morbidity is expected to be high. This work aimed to evaluate the outcome and safety of induction chemotherapy in this setting. METHODS: We performed a retrospective and observational study including patients with oral cavity squamous cell carcinoma, treated with induction chemotherapy between January 2010 and December 2018. Outcomes included induction chemotherapy toxicity, treatment response, disease-free survival and overall survival. RESULTS: A total of 108 oral cavity squamous cell carcinoma patients were included. Ninety-six (88.9%) had stage IV disease, while 12 (11.1%) had stage III. Eighty-four patients (80.8%) achieved at least a partial response to induction chemotherapy at clinical evaluation, and 75 (72.1%) at radiological evaluation. Seventy-eight patients have been proposed for subsequent definitive treatments, with no differences obtained in prognosis, when comparing surgical to non-surgical approaches. In patients treated with definitive treatments, improved five-year disease-free survival was obtained if at least a clinical (56.3%; p=0.001) or radiological (52.9%; p=0.001) partial response was achieved after induction chemotherapy. Similarly, superior five-year overall survival was verified for those achieving at least clinical (51.1%; p<0.0001) or radiological (52.6%; p=0.001) partial response. Also, accomplishing a pathologic complete response (n=22.6%) significantly improved disease-free survival (p=0.039) and overall survival (p=0.005). Grade 3 and 4 toxicities were observed in 52 patients (41.8%). CONCLUSION: Responses to induction chemotherapy predicted prognosis in our population, however important toxicities were observed. Further studies are necessary to identify induction chemotherapy response predictors and subgroups who may benefit from this approach.

Filarial disease in the Brazilian Amazon and emerging opportunities for treatment and control.

Following the successful eradication of Wuchereria bancrofti, there are now just three species of conventional microfilaremic human filarial parasites endemic to the Brazilian Amazon region: Mansonella ozzardi, Mansonella perstans and Onchocerca volvulus. The zoonotic filarial parasite Dirofilaria immitis is also found in the Amazon region as are several sylvatic filarial parasites, some of which have been recorded causing zoonoses and some of which have never been recorded outside the region. Onchocerca volvulus is only found in the Amazonia onchocerciasis focus in the Brazilian state of Roraima where it affects the people of the Yanomami tribe living around the densely forested Venezuela border region. Mansonella ozzardi is by far the most common filarial parasite in Brazil and has a broad but patchy distribution throughout the western Amazon region. Recorded in the Brazilian states of Acre, Roraima, Matto Grosso, and within almost every municipality of Amazonas state, it is believed that pollution of the urban stream and river systems prevents the development of the simuliid vectors of M. ozzardi and explains the parasite's reduced distribution within urban areas and an absence of recent reports from the state capital Manaus. Decades of WHO-led periodic ivermectin treatment of Yanomami tribe's people have resulted in the partial suppression of O. volvulus transmission in this focus and has also probably affected the transmission of M. ozzardi in the region. Mansonella perstans, O. volvulus and very probably M. ozzardi infections can all be treated and most likely cured with a 4-6-week treatment course of doxycycline. The Brazilian Ministry of Health does not, however, presently recommend any treatment for mansonellosis infections and thus parasitic infections outside the Amazonia focus are typically left untreated. While the long treatment courses required for doxycycline-based mansonellosis therapies preclude their use in control programmes, new fast-acting filarial drug treatments are likely to soon become available for the treatment of both onchocerciasis and mansonellosis in the Amazon region. Filarial disease management in the Brazilian Amazon is thus likely to become dramatically more viable at a time when the public health importance of these diseases is increasingly being recognized.

Meaning of sustainability of innovations in healthcare organizations: A systematic review.

BACKGROUND: There is pressure on healthcare organizations to provide high-quality care to all patients while innovating the way care is delivered. As they take on the challenge of delivering high-quality, innovative services, any gains made tend to stall before a radical change impacts key outcomes given the difficulty in sustaining innovations over time. METHODS: A systematic search was performed in 5 electronic databases using the PRISMA structure that resulted in 1313 articles, of which 260 were duplicated, leaving 1053 articles. After reading their abstracts, 877 had an inadequate scope for analysis because they did not deal with research on the sustainability of innovations. After a full assessment of the remaining 176 articles, only 10 studies met the inclusion criteria with the snowball strategy generating one additional paper, leading to 11 empirical studies. A theoretical discussion and the proposition of a framework were used to analyze the data. RESULTS: Studies in university hospitals shed light on determining sustainability factors of innovations not yet fully explored such as the meaning given by individuals to innovation, culture, partnerships, and multidisciplinary collaboration, which complement the literature. This research sought to contribute to the dialogue between management theory and practice in studies on the sustainability of health innovations based on experiences observed in university hospitals. Health managers can verify how sustainability relates to the challenges presented and identify a path that helps them overcome the limitations imposed on the process. The literature shows that the understanding of sustainability as a mediating dimension can collaborate in sustained innovations in order to allow managers to identify actions related to the individual-organization dimension that may be compromising the process and thus act in a more efficient, assertive way in determining the factors that sustain ongoing innovations. CONCLUSIONS: A relevant point is that innovation sustainability needs to be an objective to be achieved where managers/individuals must incorporate this perspective of innovation continuity since the beginning of the process, otherwise this may represent a greater propensity for discontinuity. This analysis can potentially be applied in university hospitals, but it can also be applicable to other types of hospitals and public or private institutions as long as it is an organization that adopts, implements, and seeks to sustain innovations in service delivery.

Leadership to promote patient safety culture in public hospitals managed by social health organizations.

PURPOSE: This paper aims to identify the kind of internal climate leaders should offer health-care professionals to promote a patient safety culture in public hospitals managed by social health organizations in Brazil. DESIGN/METHODOLOGY/APPROACH: Two surveys were applied to health-care professionals working at three Brazilian public hospitals. The internal climate survey reached 1,013 respondents, and the patient safety culture survey reached 1,302 participants. Both factor and regression analyses were used to analyze the study model and determine how internal climate influences patient safety culture. FINDINGS: Results indicate that to promote a patient safety culture among health-care professionals, leaders should generate an internal climate based on trust to foster pride in working in the hospital. Possibly, the trust dimension is the most important one and must be developed to achieve job satisfaction and provide better services to patients. RESEARCH LIMITATIONS/IMPLICATIONS: All the hospitals studied were managed by the same Organização Social de Saúde. Due to the limited responses concerning the respondents' profiles, demographic variables were not analyzed. PRACTICAL IMPLICATIONS: This research reveals that the trust and pride dimensions can most strongly influence a positive patient safety culture, helping hospital leaders face this huge managerial challenge of consistently delivering high standards of patient safety. ORIGINALITY/VALUE: This research studies the promotion of a patient safety culture in public hospitals managed by social health organizations, characterized by greater flexibility and autonomy in health-care management and by a greater need for accountability.

Service design activities in health services: A systematic literature review based on ecosystem perspective and transformative approach.

Service Design (SD) represents a breakthrough in searching for solutions to health systems challenges, but the activities that support these solutions remain underexplored. This research investigates how SD has been applied in the healthcare sector based on two conceptual models: multilevel ecosystem perspective and SD transformative approach. First, we conducted a systematic literature review in eight comprehensive databases in March 2021. Eligibility criteria returned 990 articles filtered by a search protocol, resulting in 47 studies. After this, we identified 23 studies (49%) with a transformative approach through a thematic analysis. Also, the analysis of these 23 studies allowed the identification of five key aspects necessary for enabling a transformative character of SD initiatives: (1) identification of all the actors that make up the provision of healthcare services, (2) identification of users by ecosystem level, (3) knowledge about the SD tools arsenal, (4) use of technology, and (5) applying the Experience-Based Design and Co-Design (EBD/EBCD) approach. The study underlines the role of management for the success of SD in the health sector and suggests an instrument (checklist) to help managers implement SD initiatives successfully.

Service design for the transformation of healthcare systems: A systematic review of literature.

There is a growing interest in applying the Service Design (SD) approach to innovate and transform healthcare systems. However, comprehensive studies are scarce. This study systematically reviews the literature on SD initiatives towards healthcare system transformation. The research questions are: How has the SD approach been applied to the healthcare sector? To what extent are the SD initiatives contributing to transform the health systems? What are the main challenges faced by SD initiatives to transform the health system? Which are the main stakeholders involved in the process, and how could they change according to the type of initiative? The search was conducted in March 2021 in eight databases and returned 990 articles evaluated through a research protocol, resulting in 47 studies included in this review. These studies were explored through thematic analysis and considering two conceptual models: the SD approach (Patrício et al., 2020) and the ecosystem perspective (Beirão et al., 2017). The findings show that SD initiatives have been implemented at all levels of the ecosystem, but only 49% (47/23 studies) present a transformative character. The SD initiatives challenges were organized into four themes: (1) Planning SD initiatives as a lever in transforming health systems; (2) Using SD tools creatively; (3) Considering the use of new technologies to transform health systems positively, and (4) Facing the challenges of applying the Experience-Based Design and Experience Based in Co-Design approaches in project development. This study is relevant for helping managers and researchers in their efforts to design truly transformative services with a focus on improving health systems and social wellbeing.

Hidradenocarcinoma of the Female Breast: A Surgical Approach to a Rare Skin Tumor.

Clear-cell hidradenocarcinomas are extremely uncommon sweat gland tumors with a predilection for the head and neck. In the limited number of articles reporting breast involvement, the primary focus concerns this entity's histological and immunohistochemical characteristics. Since hidradenocarcinomas of the breast have the potential to resemble a primary breast carcinoma closely, diagnosis may be challenging. Therefore, the authors report the first case of hidradenocarcinoma of the breast, which features its macroscopic morphology. In addition, to increase physicians' awareness of this rare neoplasm, the article also aims to detail its surgical approach.

Corrigendum: Neonatal NET-Inhibitory Factor improves survival in the cecal ligation and puncture model of polymicrobial sepsis by inhibiting neutrophil extracellular traps.

[This corrects the article DOI: 10.3389/fimmu.2022.1046574.].

Endothelial function, arterial stiffness and heart rate variability of patients with cardiovascular diseases hospitalized due to COVID-19.

BACKGROUND: The novel coronavirus disease (COVID-19) may cause vascular (e.g., endothelial dysfunction, and arterial stiffness), cardiac, autonomic (e.g., heart rate variability [HRV]), and systemic inflammatory response via direct viral attack, hypoxia-induced injury, or immunological dysregulation, especially in those patients with pre-existing cardiovascular diseases (CVD). However, to date, no study has shown prevalence of endothelial dysfunction, arterial stiffness and heart rate variability assessed by bedside peripheral arterial tonometry in patients with previous CVD hospitalized in the acute phase of COVID-19. OBJECTIVE: This study aimed to assess the prevalence of endothelial dysfunction, arterial stiffness, and altered HRV in patients with CVD hospitalized due to COVID-19. METHODS: This cross-sectional study was conducted from July 2020 to February 2021. Included male and female adult patients aged 40 to 60 years with previous CVD and diagnosed with COVID-19. Anthropometric data, comorbidities, and blood tests were analyzed. Endothelial function, arterial stiffness, and HRV were assessed using peripheral arterial tonometry (PAT), and the statistical significance was set at 5%. RESULTS: Fourteen (51.8%) patients presented endothelial dysfunction (reactive hyperemia index = 1.2 ± 0.3) and enhancement in the high-frequency component of HRV (p < 0.05). There was a high prevalence of endothelial dysfunction, especially in patients with chronic heart failure (10 (71.4%)). Patients with preserved endothelial function showed a high augmentation index normalized to a heart rate of 75 bpm (p < 0.01), suggesting arterial stiffness. CONCLUSION: Patients with CVD hospitalized due to COVID-19 presented endothelial dysfunction assessed using PAT, which could be used as a biomarker for arterial stiffness and altered HRV. The possibility of detecting vascular and autonomic changes during phase II of COVID-19 may help to prevent possible long-term complications.

The Effect of Educational Initiatives on the Attitude and Knowledge of Health Care Professionals Regarding Organ Donation and Transplantation: An Integrative Literature Review.

BACKGROUND: This integrative literature review synthesizes evidence on the effect of educational initiatives (EI) on the attitude and knowledge of health care professionals regarding organ donation and transplantation (ODT), and the EI effect considering the risks of the ODT process related to the professionals' attitudes and knowledge. METHODS: This search included 8 databases, with search terms across 4 groups: ODT activities, health professionals, attitude/knowledge, and EI. We applied the PICO framework to select articles: Population - health care professionals; Intervention - any EI; Comparison - pre/post or intervention/control designs; and Outcomes - indicators of attitudes or knowledge toward ODT. After the appraisal of 2,221 citations, 21 studies were included in this review. RESULTS: The EI varied to a great extent in terms of format (seminars, workshops, video lectures; online or in-person training), duration (from 15 minutes to 3 months), and the number of participants (from 12 to 1011). The effects reported were positive, increasing professionals' knowledge and attitude regarding the ODT process for all EI formats. Most articles (14; 67%) presented positive results with statistical significance for all indicators analyzed, and the remaining studies (7; 35%) reported statistical significance for some of the indicators analyzed. All EIs focused on donation or post-transplantation activities, lacking studies on the transplantation stage. CONCLUSIONS: Results suggest that different types of EIs may positively affect the attitude and knowledge of health care professionals regarding the ODT process. This study provides an up-to-date overview of the main themes examined in this literature, highlighting critical knowledge gaps and methodological flaws.

A Collaborative Approach for the Development of a Standardized Set of Patient-Centered Outcomes in Head and Neck Cancers.

INTRODUCTION: Head and neck cancers remain a significant health burden worldwide. Standardizing the care provided to these patients through the systematic measurement of established indicators is key to improve their outcomes. The aim of this study was to establish a relevant set of outcome indicators in this condition and identify measurement tools and requirements to do so. MATERIAL AND METHODS: One scientific committee and two regional working groups worked in a stepwise manner to narrow down an initial list of potential outcome indicators retrieved from an exhaustive literature review to a smaller set of outcome indicators according to their clinical practice. This was assessed by one representative of a head and neck cancer patient association until a final set of indicators was reached. RESULTS: A total of 164 outcome indicators comprising case-mix, outcomes, and adverse events dimensions were retrieved from the literature. These were reduced to a working set of 79 outcome indicators by the Scientific Committee and divided into seven categories including demographics, clinical status, tumor-related parameters, nutritional status, treatment, health and quality of life parameters and survival. Subsequently, these indicators were further reduced to a set of 50 indicators by the regional working groups and to a set of 49 indicators by the final Scientific Committee assessment. Finally, the discussed indicators were appraised by a head and neck cancer patient association, which added the 'rehabilitation' category, a key parameter to these patients. CONCLUSION: An initial set of outcome indicators for head and neck cancer was systematically developed aiming to standardize the care provided to these patients across institutions at national level and identify measurement tools and requirements to measure those indicators. This standard set should be continuously improved and consistently adopted in the different clinical and national settings.

Neutrophil extracellular trap inhibition improves survival in neonatal mouse infectious peritonitis.

BACKGROUND: Treatment of neonatal peritonitis and sepsis is challenging. Following infection, neutrophils elaborate neutrophil extracellular traps (NETs)-extracellular lattices of decondensed chromatin decorated with antimicrobial proteins. NETs, however, can augment pathogenic inflammation causing collateral damage. We hypothesized that NET inhibition would improve survival in experimental neonatal infectious peritonitis. METHODS: We induced peritonitis in 7 to 10-day-old mice by intraperitoneal injection with cecal slurry. We targeted NETs by treating mice with neonatal NET-Inhibitory Factor (nNIF), an endogenous NET-inhibitor; Cl-amidine, a PAD4 inhibitor; DNase I, a NET degrading enzyme, or meropenem (an antibiotic). We determined peritoneal NET and cytokine levels and circulating platelet-neutrophil aggregates. Survival from peritonitis was followed for 6 days. RESULTS: nNIF, Cl-amidine, and DNase I decreased peritoneal NET formation and inflammatory cytokine levels at 24 h compared to controls. nNIF, Cl-amidine, and DNase I decreased circulating platelet-neutrophil aggregates, and NET-targeting treatments significantly increased survival from infectious peritonitis compared to controls. Finally, nNIF administration significantly improved survival in mice treated with sub-optimal doses of meropenem even when treatment was delayed until 2 h after peritonitis induction. CONCLUSIONS: NET inhibition improves survival in experimental neonatal infectious peritonitis, suggesting that NETs participate pathogenically in neonatal peritonitis and sepsis. IMPACT: 1. Neutrophil extracellular trap formation participates pathogenically in experimental neonatal infectious peritonitis. 2. NET-targeting strategies improve outcomes in a translational model of neonatal infectious peritonitis. 3. NET inhibition represents a potential target for drug development in neonatal sepsis and infectious peritonitis.

Comprimento de inserção de sonda gástrica em recém-nascidos: práticas dos enfermeiros / Length of gastric tube insertion in newborn: nurse's practices / Longitud de inserción de sonda gástrica en neonatos: prácticas de enfermería

Objetivo: avaliar a prática de enfermeiros que atuam em unidade neonatal sobre a mensuração do comprimento de sondas gástricas. Método: estudo transversal, realizado em quatro unidades neonatais públicas do Recife. Os dados foram coletados por meio de questionário e submetidos à análise estatística descritiva e analítica. Protocolo de pesquisa aprovado pelo Comitê de Ética em Pesquisa. Resultados: a medida orelha-nariz-xifoide apareceu como a mais frequente para sondagem orogástrica (28,4%) e a medida nariz-orelha-xifoide para sondagem nasogástrica (35,8%); 7,5% dos enfermeiros declararam usar as estratégias de medição de sonda atualmente recomendadas tanto para via oral quanto para nasogástrica. Não houve associação significativa entre a escolha das estratégias de medição adequadas e tempo de formação, tempo de experiência em neonatologia, formação complementar ou unidade de atuação. Conclusão: a prática de sondagem gástrica em recém-nascido, da maior parte dos profissionais, está desalinhada com as atuais evidências que recomendam o uso da medida nariz-orelha-metade da distância entre xifoide e cicatriz umbilical.

Objective: to evaluate the practice of nurses from a neonatal unit on measuring the length of gastric tubes. Method: cross-sectional study, carried out in four public neonatal units from Recife. Data were collected through a questionnaire and submitted to descriptive and analytical statistical analysis. Research protocol approved by the Research Ethics Committee. Results: the ear-nose-xiphoid measurement appeared as the most frequent for orogastric tube (28.4%) and the nose-ear-xiphoid measurement for nasogastric tube (35.8%); 7.5% of nurses reported using the currently recommended tube measurement strategies for both the oral and nasogastric routes. There was no significant association between the choice of appropriate measurement strategies and training time, length of experience in neonatology, additional training or unit of work. Conclusion: the practice of perform gastric tube in newborns, by most professionals, is out of line with current evidence that recommends the use of nose-ear-half the distance between xiphoid and umbilicus.

Objetivo: evaluar la práctica de los enfermeros que actúan en una unidad neonatal en cuanto a la medición de la longitud de las sondas gástricas. Método: estudio transversal, realizado en cuatro unidades neonatales públicas de Recife. Los datos se recolectaron a través de un cuestionario y se sometieron a análisis estadístico descriptivo y analítico. El Comité de Ética en Investigación aprobó el protocolo de investigación. Resultados: la medida oído-nariz-xifoideo apareció como siendo la más frecuente en cuanto a la sonda orogástrica (28,4%) y la medida nariz-oído-xifoideo respecto a la sonda nasogástrica (35,8%); el 7,5% de los enfermeros informó que utilizan las estrategias de medición de sonda actualmente recomendadas tanto para la vía oral y como para la nasogástrica. No hubo asociación significativa entre la elección de estrategias de medición apropiadas y el tiempo de formación, la duración de la experiencia en neonatología, la formación adicional o la unidad de trabajo. Conclusión: la práctica del sondaje gástrico en recién nacidos, por la mayoría de los profesionales, no se ajusta con la evidencia actual que recomienda el uso de la medida nariz-oreja- mitad de la distancia entre el xifoides y la cicatriz umbilical.

Initiatives to reduce the waiting time to initiate oncological treatment: a scoping literature review.

Objective: To identify the managerial actions proposed and employed to reduce the waiting time to initiate oncological treatments in the public health system and its application in Latin America. Method: We searched seven databases in December 2020. Search terms were conceptualized into three groups: waiting time, cancer, and terms related to public sector. The eligibility criteria included theoretical or empirical academic articles written in English, Spanish, or Portuguese, that focused on managerial solutions to face oncological healthcare queues' dilemma. Results: The search returned 1 255 articles, and 20 were selected and analysed in this review. Results show that most of the proposals are related to the process and people dimensions. The actions related to the process dimension were mainly associated with programming new treatment pathways and integrating cancer systems. People's dimension initiatives referred mostly to task forces and groups of specialists. Some initiatives were related to implementing technological solutions and the technology dimension, mainly concerning radiotherapy devices' acquisition. Conclusion: Few studies focus on analysing actions to minimize waiting time to initiate oncological treatments. The prevalence of conceptual and illustrative case studies indicates the lack of research maturity on this theme. Future studies should focus on setting the field's theoretical foundations, considering the existing paradigms, or developing new ones. There is a need for empirical studies applying a multidisciplinary approach to face the oncological treatment waiting time challenge and proposing new and innovative initiatives.

Initiatives to reduce the waiting time to initiate oncological treatment: a scoping literature review

[ABSTRACT]. Objective. To identify the managerial actions proposed and employed to reduce the waiting time to initiate oncological treatments in the public health system and its application in Latin America. Method. We searched seven databases in December 2020. Search terms were conceptualized into three groups: waiting time, cancer, and terms related to public sector. The eligibility criteria included theoretical or empirical academic articles written in English, Spanish, or Portuguese, that focused on managerial solutions to face oncological healthcare queues' dilemma. Results. The search returned 1 255 articles, and 20 were selected and analysed in this review. Results show that most of the proposals are related to the process and people dimensions. The actions related to the pro­ cess dimension were mainly associated with programming new treatment pathways and integrating cancer systems. People's dimension initiatives referred mostly to task forces and groups of specialists. Some initia­ tives were related to implementing technological solutions and the technology dimension, mainly concerning radiotherapy devices' acquisition. Conclusion. Few studies focus on analysing actions to minimize waiting time to initiate oncological treatments. The prevalence of conceptual and illustrative case studies indicates the lack of research maturity on this theme. Future studies should focus on setting the field's theoretical foundations, considering the existing par­ adigms, or developing new ones. There is a need for empirical studies applying a multidisciplinary approach to face the oncological treatment waiting time challenge and proposing new and innovative initiatives.

[RESUMEN]. Objetivo. Identificar las medidas gerenciales propuestas y empleadas para reducir el tiempo de espera para iniciar el tratamiento oncológico y su aplicación en el sistema público de salud en América Latina. Método. Se realizaron búsquedas en siete bases de datos en diciembre del 2020. Se conceptualizaron los términos de búsqueda en tres grupos: tiempo de espera, cáncer y términos relacionados con el sector público. Entre los criterios de aceptabilidad se incluyeron artículos académicos teóricos o empíricos escritos en inglés, español o portugués acerca de soluciones gerenciales para enfrentar el dilema de los tiempos de espera en la atención médica oncológica. Resultados. La búsqueda arrojó como resultado 1 255 artículos; para esta revisión se seleccionaron y anali­ zaron 20. Los resultados muestran que la mayoría de las propuestas están relacionadas con dos dimensiones: el proceso y los pacientes. Las medidas relacionadas con el proceso se asociaron principalmente con la planificación de nuevas vías de tratamiento y la integración de los sistemas oncológicos. Las iniciativas rela­ cionadas con los pacientes se referían principalmente a equipos de trabajo y grupos de especialistas. Algunas iniciativas estuvieron relacionadas con la dimensión de tecnología y soluciones tecnológicas, principalmente con la compra de equipos de radioterapia. Conclusiones. Pocos estudios se centran en analizar medidas que minimicen el tiempo de espera para ini­ ciar los tratamientos oncológicos. La prevalencia de estudios de casos conceptuales e ilustrativos indica la falta de madurez de la investigación sobre este tema. Los estudios futuros deben centrarse en establecer las bases teóricas del campo, considerar los paradigmas existentes o elaborar nuevos paradigmas. Es necesa­ rio realizar estudios empíricos que apliquen un enfoque multidisciplinario para afrontar el reto del tiempo de espera para recibir tratamiento oncológico y que propongan iniciativas nuevas e innovadoras.

[RESUMO]. Objetivo. Identificar ações gerenciais propostas e adotadas para reduzir o tempo de espera para o início do tratamento oncológico no sistema de saúde pública e sua aplicação na América Latina. Método. Foram feitas buscas em sete bancos de dados em dezembro de 2020. Os termos de busca foram conceituados em três grupos: tempo de espera, câncer e termos relacionados ao setor público. Os critérios de elegibilidade incluíam artigos acadêmicos teóricos ou empíricos escritos em inglês, espanhol ou portu­ guês, cujo foco fossem soluções gerenciais para enfrentar o dilema das filas para atendimento oncológico. Resultados. A busca retornou 1255 artigos, dos quais 20 foram selecionados e analisados nesta revisão. Os resultados mostram que a maioria das propostas está relacionada às dimensões de processo e pessoas. As ações relacionadas à dimensão de processo estavam associadas principalmente ao desenvolvimento de novos percursos assistenciais e à integração dos sistemas de atendimento oncológico. Já as iniciativas na dimensão de pessoas se referiam principalmente a forças­tarefa e grupos de especialistas. Algumas iniciati­vas estavam relacionadas à implementação de soluções tecnológicas e à dimensão tecnológica, sobretudo no que se refere à aquisição de dispositivos de radioterapia. Conclusão. Poucos estudos se concentram na análise de ações para minimizar o tempo de espera para início do tratamento oncológico. A prevalência de estudos de caso conceituais e ilustrativos indica a falta de maturidade da pesquisa sobre esse tema. Futuros estudos devem se concentrar em definir fundamentos teóricos da área, considerar os paradigmas existentes ou desenvolver novos paradigmas. São necessários estudos empíricos que utilizem uma abordagem multidisciplinar para enfrentar o desafio do tempo de espera para o tratamento oncológico e que proponham iniciativas novas e inovadoras.

Brazilian Health Care Professionals` Attitudes and Knowledge Regarding Organ Donation and Transplantation: A Systematic Review.

PURPOSE: This systematic literature review synthesizes evidence on Brazilian health care professionals' attitudes and knowledge regarding organ donation transplantation. METHOD: This search included 5 databases-EBSCO, PubMed, Web of Science, Scopus, and Virtual Health Library. Search terms were conceptualized into 4 groups-organ transplantation/donation, health care professionals, attitude/knowledge, and Brazil. The eligibility criteria included academic articles that applied quantitative methods to examine the attitudes and/or knowledge of health care professionals toward organ donation-transplantation (ODT). After a critical appraisal of the citations initially retrieved, 13 studies were included in this review. RESULTS: Although most studies pointed to an overall positive attitude of participants toward ODT, insufficient knowledge level among participants was also observed in most studies, especially knowledge gaps regarding aspects such as legal requirements and the functioning of the ODT processes in Brazil. In convergence with the broader ODT literature, education was highlighted as a central point in ODT processes. CONCLUSION: The results reveal the scarcity of studies on the subject in Brazil and indicate an opportunity for educational efforts to improve the knowledge of health care professionals regarding the ODT process. This study enriches the academic literature and encourages new investigations on the issue, especially in the North and Northeast of Brazil.

Neutrophil extracellular traps regulate ischemic stroke brain injury.

Ischemic stroke prompts a strong inflammatory response, which is associated with exacerbated outcomes. In this study, we investigated mechanistic regulators of neutrophil extracellular trap (NET) formation in stroke and whether they contribute to stroke outcomes. NET-forming neutrophils were found throughout brain tissue of ischemic stroke patients, and elevated plasma NET biomarkers correlated with worse stroke outcomes. Additionally, we observed increased plasma and platelet surface-expressed high-mobility group box 1 (HMGB1) in stroke patients. Mechanistically, platelets were identified as the critical source of HMGB1 that caused NETs in the acute phase of stroke. Depletion of platelets or platelet-specific knockout of HMGB1 significantly reduced plasma HMGB1 and NET levels after stroke, and greatly improved stroke outcomes. We subsequently investigated the therapeutic potential of neonatal NET-inhibitory factor (nNIF) in stroke. Mice treated with nNIF had smaller brain infarcts, improved long-term neurological and motor function, and enhanced survival after stroke. nNIF specifically blocked NET formation without affecting neutrophil recruitment after stroke. Importantly, nNIF also improved stroke outcomes in diabetic and aged mice and was still effective when given 1 hour after stroke onset. These results support a pathological role for NETs in ischemic stroke and warrant further investigation of nNIF for stroke therapy.

Neonatal NET-Inhibitory Factor improves survival in the cecal ligation and puncture model of polymicrobial sepsis by inhibiting neutrophil extracellular traps.

Introduction: Neutrophil extracellular traps (NETs) clear pathogens but may contribute Q8 pathogenically to host inflammatory tissue damage during sepsis. Innovative therapeutic agents targeting NET formation and their potentially harmful collateral effects remain understudied. Methods: We investigated a novel therapeutic agent, neonatal NET-Inhibitory Factor (nNIF), in a mouse model of experimental sepsis - cecal ligation and puncture (CLP). We administered 2 doses of nNIF (1 mg/ kg) or its scrambled peptide control intravenously 4 and 10 hours after CLP treatment and assessed survival, peritoneal fluid and plasma NET formation using the MPO-DNA ELISA, aerobic bacterial colony forming units (CFU) using serial dilution and culture, peritoneal fluid and stool microbiomes using 16S rRNA gene sequencing, and inflammatory cytokine levels using a multiplexed cytokine array. Meropenem (25 mg/kg) treatment served as a clinically relevant treatment for infection. Results: We observed increased 6-day survival rates in nNIF (73%) and meropenem (80%) treated mice compared to controls (0%). nNIF decreased NET formation compared to controls, while meropenem did not impact NET formation. nNIF treatment led to increased peritoneal fluid and plasma bacterial CFUs consistent with loss of NET-mediated extracellular microbial killing, while nNIF treatment alone did not alter the peritoneal fluid and stool microbiomes compared to vehicle-treated CLP mice. nNIF treatment also decreased peritoneal TNF-a inflammatory cytokine levels compared to scrambled peptide control. Furthermore, adjunctive nNIF increased survival in a model of sub-optimal meropenem treatment (90% v 40%) in CLP-treated mice. Discussion: Thus, our data demonstrate that nNIF inhibits NET formation in a translationally relevant mouse model of sepsis, improves survival when given as monotherapy or as an adjuvant with antibiotics, and may play an important protective role in sepsis.

Initiatives to reduce the waiting time to initiate oncological treatment: a scoping literature review / Iniciativas para reducir el tiempo de espera para iniciar el tratamiento oncológico: revisión exploratoria / Iniciativas para reduzir o tempo de espera para o início do tratamento oncológico: revisão de escopo da literatura

ABSTRACT Objective. To identify the managerial actions proposed and employed to reduce the waiting time to initiate oncological treatments in the public health system and its application in Latin America. Method. We searched seven databases in December 2020. Search terms were conceptualized into three groups: waiting time, cancer, and terms related to public sector. The eligibility criteria included theoretical or empirical academic articles written in English, Spanish, or Portuguese, that focused on managerial solutions to face oncological healthcare queues' dilemma. Results. The search returned 1 255 articles, and 20 were selected and analysed in this review. Results show that most of the proposals are related to the process and people dimensions. The actions related to the process dimension were mainly associated with programming new treatment pathways and integrating cancer systems. People's dimension initiatives referred mostly to task forces and groups of specialists. Some initiatives were related to implementing technological solutions and the technology dimension, mainly concerning radiotherapy devices' acquisition. Conclusion. Few studies focus on analysing actions to minimize waiting time to initiate oncological treatments. The prevalence of conceptual and illustrative case studies indicates the lack of research maturity on this theme. Future studies should focus on setting the field's theoretical foundations, considering the existing paradigms, or developing new ones. There is a need for empirical studies applying a multidisciplinary approach to face the oncological treatment waiting time challenge and proposing new and innovative initiatives.

RESUMEN Objetivo. Identificar las medidas gerenciales propuestas y empleadas para reducir el tiempo de espera para iniciar el tratamiento oncológico y su aplicación en el sistema público de salud en América Latina. Método. Se realizaron búsquedas en siete bases de datos en diciembre del 2020. Se conceptualizaron los términos de búsqueda en tres grupos: tiempo de espera, cáncer y términos relacionados con el sector público. Entre los criterios de aceptabilidad se incluyeron artículos académicos teóricos o empíricos escritos en inglés, español o portugués acerca de soluciones gerenciales para enfrentar el dilema de los tiempos de espera en la atención médica oncológica. Resultados. La búsqueda arrojó como resultado 1 255 artículos; para esta revisión se seleccionaron y analizaron 20. Los resultados muestran que la mayoría de las propuestas están relacionadas con dos dimensiones: el proceso y los pacientes. Las medidas relacionadas con el proceso se asociaron principalmente con la planificación de nuevas vías de tratamiento y la integración de los sistemas oncológicos. Las iniciativas relacionadas con los pacientes se referían principalmente a equipos de trabajo y grupos de especialistas. Algunas iniciativas estuvieron relacionadas con la dimensión de tecnología y soluciones tecnológicas, principalmente con la compra de equipos de radioterapia. Conclusiones. Pocos estudios se centran en analizar medidas que minimicen el tiempo de espera para iniciar los tratamientos oncológicos. La prevalencia de estudios de casos conceptuales e ilustrativos indica la falta de madurez de la investigación sobre este tema. Los estudios futuros deben centrarse en establecer las bases teóricas del campo, considerar los paradigmas existentes o elaborar nuevos paradigmas. Es necesario realizar estudios empíricos que apliquen un enfoque multidisciplinario para afrontar el reto del tiempo de espera para recibir tratamiento oncológico y que propongan iniciativas nuevas e innovadoras.

RESUMO Objetivo. Identificar ações gerenciais propostas e adotadas para reduzir o tempo de espera para o início do tratamento oncológico no sistema de saúde pública e sua aplicação na América Latina. Método. Foram feitas buscas em sete bancos de dados em dezembro de 2020. Os termos de busca foram conceituados em três grupos: tempo de espera, câncer e termos relacionados ao setor público. Os critérios de elegibilidade incluíam artigos acadêmicos teóricos ou empíricos escritos em inglês, espanhol ou português, cujo foco fossem soluções gerenciais para enfrentar o dilema das filas para atendimento oncológico. Resultados. A busca retornou 1255 artigos, dos quais 20 foram selecionados e analisados nesta revisão. Os resultados mostram que a maioria das propostas está relacionada às dimensões de processo e pessoas. As ações relacionadas à dimensão de processo estavam associadas principalmente ao desenvolvimento de novos percursos assistenciais e à integração dos sistemas de atendimento oncológico. Já as iniciativas na dimensão de pessoas se referiam principalmente a forças-tarefa e grupos de especialistas. Algumas iniciativas estavam relacionadas à implementação de soluções tecnológicas e à dimensão tecnológica, sobretudo no que se refere à aquisição de dispositivos de radioterapia. Conclusão. Poucos estudos se concentram na análise de ações para minimizar o tempo de espera para início do tratamento oncológico. A prevalência de estudos de caso conceituais e ilustrativos indica a falta de maturidade da pesquisa sobre esse tema. Futuros estudos devem se concentrar em definir fundamentos teóricos da área, considerar os paradigmas existentes ou desenvolver novos paradigmas. São necessários estudos empíricos que utilizem uma abordagem multidisciplinar para enfrentar o desafio do tempo de espera para o tratamento oncológico e que proponham iniciativas novas e inovadoras.