The Large-Scale Implementation of a Health Information System in Brazilian University Hospitals: Process and Outcomes.

Governments around the globe are paving the way for healthcare services that can have a profound impact on the overall well-being and development of their nations. However, government programs to implement health information technologies on a large-scale are challenging, especially in developing countries. In this article, the process and outcomes of the large-scale implementation of a hospital information system for the management of Brazilian university hospitals are analyzed. Based on a qualitative approach, this research involved 21 hospitals and comprised a documentary search, interviews with 24 hospital managers and two system user focus groups, and a questionnaire of 736 respondents. Generally, we observed that aspects relating to the wider context of system implementation (macro level), the managerial structure, cultural nuances, and political dynamics within each hospital (meso level), as well as the technology, work activities, and individuals themselves (micro level) acted as facilitators and/or obstacles to the implementation process. The dynamics and complex interactions established between these aspects had repercussions on the process, including the extended time necessary to implement the national program and the somewhat mixed outcomes obtained by hospitals in the national network. Mostly positive, these outcomes were linked to the eight emerging dimensions of practices and work processes; planning, control, and decision making; transparency and accountability; optimization in the use of resources; productivity of professionals; patient information security; safety and quality of care; and improvement in teaching and research. We argued here that to maximize the potential of information technology in healthcare on a large-scale, an integrative and cooperative vision is required, along with a high capacity for change management, considering the different regional, local, and institutional contexts.

Full recovery of a stage IV cancer patient facing COVID-19 pandemic.

Coronavirus disease 2019 (COVID-19), first recognized in Wuhan, China, was recently declared a global pandemic by the World Health Organization (WHO). Advanced age and comorbid disease, well-known characteristics in the solid tumor population, have been reported as risk factors for severe disease and death. Cancer-related immunosuppression and its treatments also seem to play an active role in the prognosis, response, and clinical outcomes of these patients. The most effective combination therapy for COVID-19 is still under investigation, and the use of corticosteroids is controversial. Although, as a group, metastatic cancer patients are often considered not to be good candidates for ICU treatment, the individual prognosis should always come into consideration, even in a context of high pressure on medical facilities. We report the case of a stage IV prostate cancer patient infected with SARS-CoV-2 who required ICU admission and recovered from COVID-19 infection. Further studies are needed in order to identify accurate clinical prognostic criteria and provide the best treatment for these challenging patients.

Full recovery of a stage IV cancer patient facing COVID-19 pandemic

Coronavirus disease 2019 (COVID-19), first recognized in Wuhan, China, was recently declared a global pandemic by the World Health Organization (WHO). Advanced age and comorbid disease, well-known characteristics in the solid tumor population, have been reported as risk factors for severe disease and death. Cancer-related immunosuppression and its treatments also seem to play an active role in the prognosis, response, and clinical outcomes of these patients. The most effective combination therapy for COVID-19 is still under investigation, and the use of corticosteroids is controversial. Although, as a group, metastatic cancer patients are often considered not to be good candidates for ICU treatment, the individual prognosis should always come into consideration, even in a context of high pressure on medical facilities. We report the case of a stage IV prostate cancer patient infected with SARS-CoV-2 who required ICU admission and recovered from COVID-19 infection. Further studies are needed in order to identify accurate clinical prognostic criteria and provide the best treatment for these challenging patients.

5-lipoxygenase-dependent recruitment of neutrophils and macrophages by eotaxin-stimulated murine eosinophils.

The roles of eosinophils in antimicrobial defense remain incompletely understood. In ovalbumin-sensitized mice, eosinophils are selectively recruited to the peritoneal cavity by antigen, eotaxin, or leukotriene(LT)B4, a 5-lipoxygenase (5-LO) metabolite. 5-LO blockade prevents responses to both antigen and eotaxin. We examined responses to eotaxin in the absence of sensitization and their dependence on 5-LO. BALB/c or PAS mice and their mutants (5-LO-deficient ALOX; eosinophil-deficient GATA-1) were injected i.p. with eotaxin, eosinophils, or both, and leukocyte accumulation was quantified up to 24 h. Significant recruitment of eosinophils by eotaxin in BALB/c, up to 24 h, was accompanied by much larger numbers of recruited neutrophils and monocytes/macrophages. These effects were abolished by eotaxin neutralization and 5-LO-activating protein inhibitor MK886. In ALOX (but not PAS) mice, eotaxin recruitment was abolished for eosinophils and halved for neutrophils. In GATA-1 mutants, eotaxin recruited neither neutrophils nor macrophages. Transfer of eosinophils cultured from bone-marrow of BALB/c donors, or from ALOX donors, into GATA-1 mutant recipients, i.p., restored eotaxin recruitment of neutrophils and showed that the critical step dependent on 5-LO is the initial recruitment of eosinophils by eotaxin, not the secondary neutrophil accumulation. Eosinophil-dependent recruitment of neutrophils in naive BALB/c mice was associated with increased binding of bacteria.

Essential roles of endogenous glucocorticoids and TNF/TNFR1 in promoting bone-marrow eosinopoiesis in ovalbumin-sensitized, airway-challenged mice.

AIMS: Stress mechanisms paradoxically contribute to allergic episodes in humans and mice. Glucocorticoids (GC) and interleukin (IL)-5 synergically upregulate murine bone-marrow eosinophil production. Here we explored the role of endogenous GC in allergen-stimulated bone-marrow eosinophil production in ovalbumin-sensitized/challenged mice. MAIN METHODS: In BALB/c or C57BL/6 mice, sensitized and intranasally challenged with ovalbumin, we monitored eosinophil numbers in freshly harvested or cultured bone-marrow, and plasma corticosterone levels. Metyrapone (MET) was used to inhibit GC synthesis, and RU486 to block GC actions. In sensitized mice challenged intraperitoneally, we examined the relationship between eosinophilia of bone-marrow and peritoneal cavity, in the absence or presence of RU486. In experiments involving in vivo neutralization of tumor necrosis factor-α (TNF) by specific antibodies, or using mice which lack functional type I TNF receptors (TNFRI), we evaluated the relationship between TNF blockade, corticosterone levels, RU486 or MET treatment and challenge-induced bone-marrow eosinophilia. KEY FINDINGS: RU486 or MET pretreatments abolished challenge-induced increases in eosinophil numbers in bone-marrow (in vivo and ex vivo), and in the peritoneal cavity. MET, but not RU486, prevented the challenge-induced increase in corticosterone levels. Challenge-induced bone-marrow eosinophilia and corticosterone surge were abolished in TNFRI-deficient mice. Anti-TNF-treatment very effectively prevented challenge-induced bone-marrow eosinophilia, in the absence of RU486 or MET, but had no independent effect in the presence of either drug. SIGNIFICANCE: Endogenous GC was essential for allergen challenge-induced increases in eosinophil numbers inside bone-marrow. This effect required TNF and TNFRI, which suggests an immunoendocrine mechanism.

Essential roles of PKA, iNOS, CD95/CD95L, and terminal caspases in suppression of eosinopoiesis by PGE2 and other cAMP-elevating agents.

Up- and downregulation of eosinopoiesis control pulmonary eosinophilia in human asthma. In mice, eosinopoiesis is suppressed in vitro by prostaglandin E2 (PGE2) and in vivo by diethylcarbamazine, through a proapoptotic mechanism sequentially requiring inducible NO synthase (iNOS) and the ligand for death receptor CD95 (CD95L). We examined the roles of iNOS, cAMP-mediated signaling, caspases, and CD95L/CD95 in suppression of eosinopoiesis by PGE2 and other agents signaling through cAMP. Bone-marrow collected from BALB/c mice, or from iNOS-, CD95-, or CD95L-deficient mutants (and wild-type controls), was cultured with interleukin-5 (IL-5), alone or associated with PGE2, cAMP-inducing/mimetic agents, caspase inhibitor zVAD-fmk, iNOS inhibitor aminoguanidine, or combinations thereof, and eosinopoiesis was evaluated at various times. PGE2, added up to 24 hours of culture, dose-dependently suppressed eosinopoiesis, by inducing apoptosis. This effect was (a) paralleled by induction of iNOS in eosinophils; (b) duplicated by sodium nitroprusside, isoproterenol, and cAMP-inducing/mimetic agents; (c) prevented by protein kinase A inhibition. NO was produced through iNOS by dibutyryl-cAMP-stimulated bone-marrow. Overall, PGE2 and isoproterenol shared a requirement for four effector elements (iNOS, CD95L, CD95, and terminal caspases), which together define a pathway targeted by several soluble up- and downmodulators of eosinopoiesis, including drugs, mediators of inflammation, and cytokines.

Prediction of sepsis-related outcomes in neonates through systematic genotyping of polymorphisms in genes for innate immunity and inflammation: a narrative review and critical perspective.

CONTEXT AND OBJECTIVE: Neonatal sepsis is associated with premature birth and maternal infection. Large-scale studies seek to define markers that identify neonates at risk of developing sepsis. Here, we examine whether the scientific evidence supports systematic use of polymorphism genotyping in cytokine and innate immunity genes, to identify neonates at increased risk of sepsis. DESIGN AND SETTING: Narrative literature review conducted at Fernandes Figueira Institute, Brazil. METHODS: The literature was searched in PubMed, Embase (Excerpta Medica Database), Lilacs (Literatura Latino-Americana e do Caribe em Ciências da Saúde), SciELO (Scientific Electronic Library Online) and Cochrane Library. From > 400,000 references, 548 were retrieved based on inclusion/exclusion criteria; 22 were selected for detailed analysis after quality assessment. RESULTS: The studies retrieved addressed the impact of gene polymorphisms relating to immune mechanisms (most often TNF-a, LT-a, IL-6, IL-1ß, IL-1ra, L-selectin, CD14 and MBL) or inflammatory mechanisms (ACE and angiotensin II receptors; secretory PLA2; and hemostatic factors). Despite initial reports suggesting positive associations between specific polymorphisms and increased risk of sepsis, the accumulated evidence has not confirmed that any of them have predictive power to justify systematic genotyping. CONCLUSIONS: Sepsis prediction through systematic genotyping needs to be reevaluated, based on studies that demonstrate the functional impact of gene polymorphisms and epidemiological differences among ethnically distinct populations.

Prediction of sepsis-related outcomes in neonates through systematic genotyping of polymorphisms in genes for innate immunity and inflammation: a narrative review and critical perspective / Previsao de desfechos relacionados a sepse em neonatos atraves da genotipagem sistematica de polimorfismos de genes da imunidade inata e inflamacao: uma revisao narrativa e perspectiva critica

CONTEXT AND OBJECTIVE: Neonatal sepsis is associated with premature birth and maternal infection. Large-scale studies seek to define markers that identify neonates at risk of developing sepsis. Here, we examine whether the scientific evidence supports systematic use of polymorphism genotyping in cytokine and innate immunity genes, to identify neonates at increased risk of sepsis. DESIGN AND SETTING: Narrative literature review conducted at Fernandes Figueira Institute, Brazil. METHODS: The literature was searched in PubMed, Embase (Excerpta Medica Database), Lilacs (Literatura Latino-Americana e do Caribe em Ciências da Saúde), SciELO (Scientific Electronic Library Online) and Cochrane Library. From > 400,000 references, 548 were retrieved based on inclusion/exclusion criteria; 22 were selected for detailed analysis after quality assessment. RESULTS: The studies retrieved addressed the impact of gene polymorphisms relating to immune mechanisms (most often TNF-a, LT-a, IL-6, IL-1β, IL-1ra, L-selectin, CD14 and MBL) or inflammatory mechanisms (ACE and angiotensin II receptors; secretory PLA2; and hemostatic factors). Despite initial reports suggesting positive associations between specific polymorphisms and increased risk of sepsis, the accumulated evidence has not confirmed that any of them have predictive power to justify systematic genotyping. CONCLUSIONS: Sepsis prediction through systematic genotyping needs to be reevaluated, based on studies that demonstrate the functional impact of gene polymorphisms and epidemiological differences among ethnically distinct populations. .

CONTEXTO E OBJETIVO: A sepse neonatal está associada ao parto prematuro e à infecção materna. Estudos em grande escala buscam marcadores que identifiquem neonatos em risco de desenvolver sepse. Examinamos aqui se a evidência científica apoia o uso sistemático de genotipagem dos polimorfismos em genes de citocinas e imunidade inata, para identificar neonatos com risco elevado de sepse. TIPO DE ESTUDO E LOCAL: Revis ão narrativa da literatura, Instituto Fernandes Figueira, Brasil. M ÉTODOS: Busca online da literatura foi feita no PubMed, Embase (Excerpta Medica Database), Lilacs (Literatura Latino-Americana e do Caribe em Ciências da Saúde), SciELO (Scientific Electronic Library Online) e Cochrane Library. De mais de 400.000 referências, 548 foram recuperadas com base nos critérios de inclusão/exclusão, e 22, selecionadas para análise detalhada após verificação da qualidade. RESULTADOS: Recuperamos estudos de impacto dos polimorfismos em genes relacionados com mecanismos imunes (mais frequentemente, TNF-a, LT-a, IL-6, IL-1 β, IL-1ra, L-selectin, CD14, e MBL) ou inflamatórios (ACE e receptores de angiotensina II; PLA2 secretória; fatores hemostáticos). Contrariando estudos que inicialmente sugeriram associação positiva entre polimorfismos específicos e risco aumentado de sepse, a evidência acumulada não confirmou, para qualquer deles, valor preditivo que justifique genotipagem sistemática para orientar antibioticoterapia. CONCLUSÕES: A previsão da sepse por meio de genotipagem sistemática precisa ser reavaliada, com base em estudos que demonstram o impacto funcional de polimorfismos gênicos e as diferenças epidemiológicas entre populações etnicamente distintas. .

G-CSF suppresses allergic pulmonary inflammation, downmodulating cytokine, chemokine and eosinophil production.

AIMS: Granulocyte Colony-Stimulating Factor (G-CSF), which mobilizes hemopoietic stem cells (HSC), is believed to protect HSC graft recipients from graft-versus-host disease by enhancing Th2 cytokine secretion. Accordingly, G-CSF should aggravate Th2-dependent allergic pulmonary inflammation and the associated eosinophilia. We evaluated the effects of G-CSF in a model of allergic pulmonary inflammation. MAIN METHODS: Allergic pulmonary inflammation was induced by repeated aerosol allergen challenge in ovalbumin-sensitized C57BL/6J mice. The effects of allergen challenge and of G-CSF pretreatment were evaluated by monitoring: a) eosinophilia and cytokine/chemokine content of bronchoalveolar lavage fluid, pulmonary interstitium, and blood; b) changes in airway resistance; and c) changes in bone-marrow eosinophil production. KEY FINDINGS: Contrary to expectations, G-CSF pretreatment neither induced nor enhanced allergic pulmonary inflammation. Instead, G-CSF: a) suppressed accumulation of infiltrating eosinophils in bronchoalveolar, peribronchial and perivascular spaces of challenged lungs; and b) prevented ovalbumin challenge-induced rises in airway resistance. G-CSF had multiple regulatory effects on cytokine and chemokine production: in bronchoalveolar lavage fluid, levels of IL-1 and IL-12 (p40), eotaxin and MIP-1a were decreased; in plasma, KC, a neutrophil chemoattractant, was increased, while IL-5 was decreased and eotaxin was unaffected. In bone-marrow, G-CSF: a) prevented the increase in bone-marrow eosinophil production induced by ovalbumin challenge of sensitized mice; and b) selectively stimulated neutrophil colony formation. SIGNIFICANCE: These observations challenge the view that G-CSF deviates cytokine production towards a Th2 profile in vivo, and suggest that this neutrophil-selective hemopoietin affects eosinophilic inflammation by a combination of effects on lung cytokine production and bone-marrow hemopoiesis.

Implantação de um sistema de custos hospitalares como instrumento de gestão participativa

O presente projeto de intervenção em serviço propõe a implantação de um sistema de custos hospitalares como instrumento para potencializar a gestão participativa na Fundação Hospital Centenário de São Leopoldo. Para elaborar o sistema de custos é necessário um levantamento minucioso das divisões setoriais, insumos utilizados e produtos produzidos pelos serviços de saúde, incluindo, os recursos humanos. A combinação destes elementos e suas similaridades permitem identificar e criar os centros de custos. Este projeto tem por objetivo transformar o sistema numa ferramenta gerencial para a Administração, bem como, de fiscalização, acompanhamento e debate para os servidores da instituição a partir de um relatório eletrônico e físico que expresse minuciosamente, e de forma leiga, os custos de cada unidade. Os resultados, portanto, devem se expressar no conhecimento e compreensão conjunto dos custos, sua permanente readequação concatenada com a manutenção e/ou ampliação da qualidade no atendimento aos usuários

[Thyroid carcinoma with thymus-like differentiation (CASTLE): case report and review of the literature]. / Carcinoma da tireóide com diferenciação semelhante a timo (CASTLE): relato de caso e revisão da literatura.

Carcinoma with thymus-like differentiation (CASTLE) is a rare malignant epithelial tumor which arises on soft tissue of the neck or thyroid gland. It is important to differentiate CASTLE from primary or metastatic squamous cell carcinoma of head and neck, and from squamous cell thyroid carcinoma, because it has a different prognosis. CD5 immunoreactivity might be helpful in CASTLE diagnosis. CASTLE behaves generally in an indolent fashion, even though it has a high relapse rate, while the other have a dismal prognosis due its high dissemination rate. Treatment includes surgical excision and radiotherapy. Chemotherapy can be offered, although its efficacy is not clear. Authors present a case of a 52 year-old male that complaints with cough, disphony, asthenia, and thyroid mass. Thyroidectomy was performed and the pathology revealed a CASTLE. After radiotherapy and chemotherapy, minimal response was obtained. The authors intend to discuss the differential pathologic diagnosis and the best therapy of this indolent but recurrent neoplasm, that demands strict long term follow-up.

Carcinoma da tireóide com diferenciação semelhante a timo (CASTLE): relato de caso e revisão da literatura / Thyroid carcinoma with thymus-like differentiation (CASTLE): case report and review of the literature

O carcinoma com diferenciação semelhante a timo (CASTLE) é uma neoplasia epitelial maligna rara, que surge nos tecidos moles do pescoço ou na glândula tireóide. O diagnóstico diferencial deve ser estabelecido com carcinoma pavimento-celular primário ou secundário da cabeça e do pescoço ou da tireóide, visto que têm prognósticos distintos. A imunorreatividade para CD5 pode ser útil no diagnóstico de CASTLE. O CASTLE possui elevada taxa de recidiva local, apesar de o seu curso clínico indolente, ao contrário das neoplasias previamente referidas, que têm um prognóstico muito reservado, dada a elevada taxa de disseminação sistêmica. O tratamento inclui excisão cirúrgica e radioterapia. A quimioterapia também tem sido realizada, apesar de até a presente data não existir evidência clara da sua eficácia. Relata-se caso de doente de sexo masculino, com 52 anos, que surge com tosse seca, disfonia e massa da tireóide, que foi submetido à tireoidectomia. O exame anatomopatológico da peça operatória permitiu o diagnóstico de CASTLE. O doente efetuou radioterapia e quimioterapia e obteve resposta mínima. Pretende-se discutir o diagnóstico anatomopatológico diferencial e a abordagem terapêutica mais adequada de uma patologia com prognóstico favorável, mas de natureza recidivante, que exige seguimento rigoroso a longo prazo.

Carcinoma with thymus-like differentiation (CASTLE) is a rare malignant epithelial tumor wich arises on soft tissue of the neck or thyroid gland. It is important to differentiate CASTLE from primary or metastatic squamous cell carcinoma of head and neck, and from squamous cell thyroid carcinoma, because it has a different prognosis. CD5 immunoreactivity might be helpful in CASTLE diagnosis. CASTLE behaves generally in an indolent fashion, even though it has a high relapse rate, while the other have a dismal prognosis due its high dissemination rate. Treatment includes surgical excision and radiotherapy. Chemotherapy can be offered, although its efficacy is not clear. Authors present a case of a 52 year-old male that complaints with cough, disphony, asthenia, and thyroid mass. Thyroidectomy was performed and the pathology revealed a CASTLE. After radiotherapy and chemotherapy, minimal response was obtained. The authors intend to discuss the differential pathologic diagnosis and the best therapy of this indolent but recurrent neoplasm, that demands strict long term follow-up.

Estudo comparativo da regulação da apoptose mediada por agentes pró-E anti inflamatórios em granulócitos humanos / Comparative study of the regulation of apoptosis mediated by agents pro-and anti inflammatory in human granulocytes

A morte celular programada, reconhecida através do quadro morfológico de apoptose, é um mecanismo central de regulação de populações celulares em animais multicelulares, que, no sistema imunológico, permite a resolução dos processos inflamatórios, o controle fino da expansão clonal e a prevenção da auto-imunidade. O presente estudo se ocupa dos mecanismos pelos quais a apoptose é modulada por agentes externos. em dois diferentes tipos de granulócitos humanos, neutrófilos e eosinófilos, que compartilham uma origem comum na medula óssea, assim como muitas características morfológicas e funcionais, mas desempenham papéis diferentes na defesa do hospedeiro... A indometacina revelou-se uma forte indutora de apoptose om neutrófilos humanos, na ausência de outros fatores exógenos, um efeito igualmente ainda não descrito na literatura. Estas observações indicam que: a) embora neutrófilos humanos possam apresentar respostas ao ATRA e à dexametasona semelhantes às observadas durante o desenvolvimento de eosinófilos murinos, mas distintas das de eosinófilos humanos maduros, esta semelhança não se estende aos efeitos de outros agentes; b) as vias de sinalização iniciadas pelo ATRA e pela dexametasona em neutrófilos humanos maduros apresentam forte interação (cross-talk), cujo mecanismo precisa ser estabelecido; c) a indometacina pode apresentar, neste modelo, ações prá-apoptóticas distintas para outros agentes anti-inflamatórios não esteroidais, como a aspirina e o salicilato de sódio.

Quantification and localization of platelet-derived growth factor in gingiva of periodontitis patients.

BACKGROUND: Platelet-derived growth factor (PDGF) is a mitogen and chemoattractant for cells of mesenchymal origin. Over-expression of PDGF-B can promote formation of inflammatory lesions in the lungs of transgenic mice. Moreover, continuous exposure to PDGF inhibits collagen production by osteoblastic cells. Thus, the expression of mitogenic factors in an inflammatory context may limit the differentiated function of cells, and thereby limit repair following periodontal attachment and bone loss. The goals of the present study were to test whether PDGF is present at increased levels in inflamed gingiva and to localize its expression in gingival biopsies from individuals with chronic periodontitis. METHODS: Tissues obtained during therapeutic procedures from inflamed and control sites of 9 patients were subjected to protein extraction, descriptive histology by hematoxylin and eosin, or immunohistochemistry assays. Quantification was calculated with an enzyme-linked immunosorbent assay (ELISA) kit specific for PDGF-AB. For the immunolocalization, anti-PDGF-A and -B antibodies were employed. RESULTS: PDGF concentration in the total protein extract was approximately 3 times higher in the inflamed sites (0.60 +/- 0.18 ng/mg versus 0.20 +/- 0.05 ng/mg; P = 0.03). Immunohistochemistry revealed prominent expression of PDGF in the pocket epithelial cells as well as the adjacent connective tissue. In contrast, little or no expression was detected in control biopsies devoid of the pocket epithelium and granulation tissue. CONCLUSIONS: PDGF is present in increased levels in the human inflamed gingiva and is mainly localized to the pocket epithelium. It is possible that chronic expression of PDGF contributes to the inflammatory changes that occur during periodontal diseases.