Trends associated with stillbirth in a maternity hospital school in the north zone of são paulo: a cross-sectional study / Tendências associadas à natimortalidade em umamaternidadeescola na zona norte de São Paulo: um estudo transversal

Abstract Objective To evaluate conditions associated with stillbirth (SB), and possible trends related with it, in a maternity hospital school in the North zone of São Paulo. Methods An observational, cross-sectional study conducted at the Hospital Maternidade- escola de Vila Nova Cachoeirinha with 1,139 SBs in the period of 2003 to 2017. Cases of intermediate SB (ISB) (weight between 500 and 999 g) and late SB (LSB) (weight ≥ 1,000 g) were compared. We evaluated clinical data, laboratory tests, and fetal and placental studies. Data were stored in Windows Excel (Microsoft Corp., Redmond, WA, USA) worksheets, according to which graphs and tables were constructed. We used the statistical software SPSS for Windows version 18.0 (SPSS In., Chicago, IL, USA), estimating the prevalence ratio (PR) and odds ratio (OR), considering the 95% confidence interval (95% CI). Results The general SB rate was 11.9%, and the in-hospital SB rate was 2.8%. Pregnant women younger than 16 years of age were more likely to have ISB (OR 0.32, 0.15- 0.76), while patients older than 40 years old had a higher chance of LSB (PR 0.85, 0.72- 0.99). A total of 25.7% of the general population did not have prenatal care, and 77.1% of the cases presented fetal death at admission. The cases of ISB had a statistically significant association with home birth (OR 0.61, 0.46-0.80). Cesarean section was performed in 16.1% of the subjects, and misoprostol was the most used method for induction. Necropsy and placental study of the fetuses were performed, respectively, in 94.2% and 97.3% of the cases. Associated causes were not identified in 22.1% of the cases, and the main causes identified were amniotic sac infections (27.9%), fetal malformations (12.5%), placental abruption (11.2%), hypertensive syndromes (8.5%), and maternal syphilis (3.9%), the latter with an increasing trend. Conclusion Among the factors associated to SB were: hypertensive syndromes, amniotic sac infections, fetal malformations, placental abruption and syphilis. There was a growing trend in the number of cases of syphilis, which translates an alert. Diagnostic limitations justify indeterminate causes.

Resumo Objetivo Avaliar aspectos relacionados à ocorrência da condição de natimortalidade em uma maternidade-escola na zona norte de São Paulo e possíveis tendências associadas aos fatores causais. Métodos Estudo observacional, transversal, realizado no Hospital Maternidadeescola Vila Nova Cachoeirinha com 1.139 óbitos fetais (OF) no período de 2003 a 2017. Foram comparados os casos de OF intermediários (OFI) (peso entre 500 e 999 g) e OF tardios (OFT) (≥ 1,000 g). Avaliamos dados clínicos, exames laboratoriais, e estudos do feto e da placenta; estes foram armazenados em planilhas de Windows Excel (Microsoft Corp., Redmond, WA USA0, utilizando-se para avaliação estatística o programa SPSS v.18 (SPSS Inc., Chicago, IL, EUA). Foram ainda estimadas a razão de prevalência (RP) e a razão de chances (RC), com intervalo de confiança de 95% (IC 95%). Resultados Ocoeficiente de natimortalidade geral foi de 11,9% e o intra-hospitalar foi de 2,8%. Gestantes com menos de 16 anos de idade apresentaram maior chance de ter OFI (RC 0.32, 0.15-0.76) enquanto que pacientes com mais de 40 anos de idade apresentaram maior chance de OFT (RP 0,85; 0,72-0,99). Não fizeram prenatal 25,7% da população geral, sendo que em 77,1% dos casos, a morte fetal já tinha sido apresentada na internação. Os casos de OFI apresentaram associação estatisticamente significante com parto domiciliar (RC 0,42; 0,23-0,75). A cesárea foi realizada em 16,1% das pacientes, sendo o misoprostol o método mais utilizado para indução. Necropsia foi feita em 94,2% dos fetos, e 97,3% das placentas foram para estudo. As causas associadas não foram identificadas em 22,1% dos casos, sendo que as principais causas identificadas foram infecções do saco amniótico e membranas (27,9%), malformações (12,5%), descolamento prematuro de placenta (11,2%), síndromes hipertensivas (8,5%), e sífilis (3,9%), sendo esta última com uma tendência crescente. Conclusão Destacaram-se como fatores associados à natimortalidade: síndromes hipertensivas, corioamnionites, malformações fetais, descolamento placentário e sífilis. Houve tendência de aumento no número de casos de sífilis, o que traduz uma alerta. Limitações diagnósticas justificam as causas indeterminadas.

Trends Associated with Stillbirth in a Maternity Hospital School in the North Zone of São Paulo: A Cross-Sectional Study.

OBJECTIVE: To evaluate conditions associated with stillbirth (SB), and possible trends related with it, in a maternity hospital school in the North zone of São Paulo. METHODS: An observational, cross-sectional study conducted at the Hospital Maternidade-escola de Vila Nova Cachoeirinha with 1,139 SBs in the period of 2003 to 2017. Cases of intermediate SB (ISB) (weight between 500 and 999 g) and late SB (LSB) (weight ≥ 1,000 g) were compared. We evaluated clinical data, laboratory tests, and fetal and placental studies. Data were stored in Windows Excel (Microsoft Corp., Redmond, WA, USA) worksheets, according to which graphs and tables were constructed. We used the statistical software SPSS for Windows version 18.0 (SPSS In., Chicago, IL, USA), estimating the prevalence ratio (PR) and odds ratio (OR), considering the 95% confidence interval (95% CI). RESULTS: The general SB rate was 11.9%, and the in-hospital SB rate was 2.8%. Pregnant women younger than 16 years of age were more likely to have ISB (OR 0.32, 0.15-0.76), while patients older than 40 years old had a higher chance of LSB (PR 0.85, 0.72-0.99). A total of 25.7% of the general population did not have prenatal care, and 77.1% of the cases presented fetal death at admission. The cases of ISB had a statistically significant association with home birth (OR 0.61, 0.46-0.80). Cesarean section was performed in 16.1% of the subjects, and misoprostol was the most used method for induction. Necropsy and placental study of the fetuses were performed, respectively, in 94.2% and 97.3% of the cases. Associated causes were not identified in 22.1% of the cases, and the main causes identified were amniotic sac infections (27.9%), fetal malformations (12.5%), placental abruption (11.2%), hypertensive syndromes (8.5%), and maternal syphilis (3.9%), the latter with an increasing trend. CONCLUSION: Among the factors associated to SB were: hypertensive syndromes, amniotic sac infections, fetal malformations, placental abruption and syphilis. There was a growing trend in the number of cases of syphilis, which translates an alert. Diagnostic limitations justify indeterminate causes.

OBJETIVO: Avaliar aspectos relacionados à ocorrência da condição de natimortalidade em uma maternidade-escola na zona norte de São Paulo e possíveis tendências associadas aos fatores causais. MéTODOS: Estudo observacional, transversal, realizado no Hospital Maternidade-escola Vila Nova Cachoeirinha com 1.139 óbitos fetais (OF) no período de 2003 a 2017. Foram comparados os casos de OF intermediários (OFI) (peso entre 500 e 999 g) e OF tardios (OFT) (≥ 1,000 g). Avaliamos dados clínicos, exames laboratoriais, e estudos do feto e da placenta; estes foram armazenados em planilhas de Windows Excel (Microsoft Corp., Redmond, WA USA0, utilizando-se para avaliação estatística o programa SPSS v.18 (SPSS Inc., Chicago, IL, EUA). Foram ainda estimadas a razão de prevalência (RP) e a razão de chances (RC), com intervalo de confiança de 95% (IC 95%). RESULTADOS: O coeficiente de natimortalidade geral foi de 11,9% e o intra-hospitalar foi de 2,8%. Gestantes com menos de 16 anos de idade apresentaram maior chance de ter OFI (RC 0.32, 0.15­0.76) enquanto que pacientes com mais de 40 anos de idade apresentaram maior chance de OFT (RP 0,85; 0,72­0,99). Não fizeram prenatal 25,7% da população geral, sendo que em 77,1% dos casos, a morte fetal já tinha sido apresentada na internação. Os casos de OFI apresentaram associação estatisticamente significante com parto domiciliar (RC 0,42; 0,23­0,75). A cesárea foi realizada em 16,1% das pacientes, sendo o misoprostol o método mais utilizado para indução. Necropsia foi feita em 94,2% dos fetos, e 97,3% das placentas foram para estudo. As causas associadas não foram identificadas em 22,1% dos casos, sendo que as principais causas identificadas foram infecções do saco amniótico e membranas (27,9%), malformações (12,5%), descolamento prematuro de placenta (11,2%), síndromes hipertensivas (8,5%), e sífilis (3,9%), sendo esta última com uma tendência crescente. CONCLUSãO: Destacaram-se como fatores associados à natimortalidade: síndromes hipertensivas, corioamnionites, malformações fetais, descolamento placentário e sífilis. Houve tendência de aumento no número de casos de sífilis, o que traduz uma alerta. Limitações diagnósticas justificam as causas indeterminadas.

MyD88 activation in cardiomyocytes contributes to the heart immune response to acute Trypanosoma cruzi infection with no effect on local parasite control.

Cardiomyopathy is the most serious consequence of Chagas disease, a neglected human disorder caused by Trypanosoma cruzi infection. Because T. cruzi parasites invade cardiomyocytes, we sought to investigate whether these cells recognize the parasite in vivo by receptors signaling through the MyD88 adaptor, which mediates the activation pathway of most Toll-like receptors (TLRs) and IL-1/IL-18 receptors, and influence the development of acute cardiac pathology. First, we showed that HL-1 cardiac muscle cell line expresses MyD88 gene and protein at resting state and after T. cruzi infection. To evaluate the role in vivo of MyD88 expression in cardiomyocytes, we generated Mer+MyD88flox+/+ mice in which tamoxifen treatment is expected to eliminate the MyD88 gene exclusively in cardiomyocytes. This Cre-loxP model was validated by both PCR and western blot analysis; tamoxifen treatment of Mer+MyD88flox+/+ mice resulted in decreased MyD88 gene and protein expression in the heart, but not in the spleen, while had no effect on littermates. The elimination of MyD88 in cardiomyocytes determined a lower increase in CCL5, IFNγ and TNFα gene transcription during acute infection by T. cruzi parasites of the Y strain, but it did not significantly modify heart leukocyte infiltration and parasitism. Together, our results show that cardiomyocytes can sense T. cruzi infection through MyD88-mediated molecular pathways and contribute to the local immune response to the parasite. The strong pro-inflammatory response of heart-recruited leukocytes may overshadow the effects of MyD88 deficiency in cardiomyocytes on the local leukocyte recruitment and T. cruzi control during acute infection.

Programmed Cell Death Protein 1-PDL1 Interaction Prevents Heart Damage in Chronic Trypanosoma cruzi Infection.

Chagas disease is a neglected parasitic infection that affects around six to seven million people, mainly in Latin America. About 30-35% of infected people present chronic Chagas cardiomyopathy (CCC), which eventually leads to death. This condition is characterized by local parasite persistence and leukocyte infiltration. In a murine model of CCC, we observed that among infiltrating leukocytes, CD4+ and CD8+ T cells were in higher frequency in the heart of chronically infected mice, although elevated expression of the regulatory molecules programmed cell death protein 1 (PD1) and PDL1 suggested these cells could be inhibited. To investigate if PD1-PDL1 interaction in the heart of chronically infected mice negatively impacts on the local immune response, facilitating parasite persistence, and progression to CCC, we attempted to recover the local immune response by treating chronically infected mice with anti-PD1 and anti-PDL1-blocking antibodies together with irradiated Trypanosoma cruzi, which provides immune response boosting. Irradiated parasites promote expression of costimulatory molecules in dendritic cells and provide specific parasite antigen, which should aid T cell reactivation upon checkpoint blockade. Following treatment, there was an increased frequency of heart-infiltrating CD4+ and CD8+ T cells with an effector memory phenotype, an increased histopathology score and decreased heart rate, supporting our previous hypothesis of local immunosuppression induced by this pathway during CCC. In addition, blood parasitemia was reduced, which was associated with increased T. cruzi-specific immunoglobulin G 1 antibodies. However, no difference was observed in cytokine production or T. cruzi burden in the hearts of treated mice. Taken together, our results suggest PD1-PDL1 interaction protects the heart from excessive immune response.

Splenic Macrophage Subsets and Their Function during Blood-Borne Infections.

The spleen is one of the major immunological sites for maintaining blood homeostasis. Previous studies showed that heterogeneous splenic macrophage populations contribute in complimentary ways to control blood-borne infections and induce effective immune responses. Marginal metallophilic macrophages (MMMΦs) and marginal zone macrophages (MZMΦs) are cells with great ability to internalize blood-borne pathogens such as virus or bacteria. Their localization adjacent to T- and B-cell-rich splenic areas favors the rapid contact between these macrophages and cells from adaptive immunity. Indeed, MMMΦs and MZMΦs are considered important bridges between innate and adaptive immunity. Although red pulp macrophages (RpMΦs) are mainly considered scavengers for senescent erythrocytes, several data indicate a role for RpMΦs in control of infections such as blood-stage malaria as well as in the induction of innate and adaptive immunity. Here, we review current data on how different macrophage subsets recognize and help eliminate blood-borne pathogens, and, in turn, how the inflammatory microenvironment in different phases of infection (acute, chronic, and after pathogen clearance) influences macrophage function and survival.

Chagas disease: still many unsolved issues.

Over the past 20 years, the immune effector mechanisms involved in the control of Trypanosoma cruzi, as well as the receptors participating in parasite recognition by cells of the innate immune system, have been largely described. However, the main questions on the physiopathology of Chagas disease remain unanswered: "Why does the host immune system fail to provide sterile immunity?" and "Why do only a proportion of infected individuals develop chronic pathology?" In this review, we describe the mechanisms proposed to explain the inability of the immune system to eradicate the parasite and the elements that allow the development of chronic heart disease. Moreover, we discuss the possibility that the inability of infected cardiomyocytes to sense intracellular T. cruzi contributes to parasite persistence in the heart and the development of chronic pathology.

A importância da autonomia como princípio bioético / The importance of autonomy as a bioethical principle

Objetivo: uma revisão sistemática da literatura acerca da importância e evolução da autonomia dopaciente como princípio bioético, em respeito ao processo de cidadania. Método: realizado umcriterioso levantamento bibliográfico, a partir de trabalhos publicados na base de dados LILACS eem livros sobre o tema. Atualização/revisão: derivada do grego: Autos = próprio; Nomos = norma,a autonomia pressupõe que a pessoa deve ser livre de coações para que possa escolher a alternativaque melhor lhe convém, podendo sofrer mudanças decorrentes de fatores como a idade ou doenças.A autonomia materializa-se no consentimento livre e esclarecido, que decorre do direito da pessoaconsentir ou recusar propostas de caráter preventivo, diagnóstico ou terapêutico que afetem ouvenham a afetar sua integridade físico-psíquico-social. Considerações finais: o princípio daautonomia rompeu com o antigo conceito paternalista de medicina, no qual o médico era a únicaparte da relação que detinha o poder de decisão, bem como determinava o tratamento que opaciente deveria realizar. No Brasil, este princípio ganhou importância, sendo incorporado aoCódigo de Ética Médica do ano de 2010.

Purpose: to accomplish a systematic review of the literature about the importance and evolution ofpatient autonomy as a bioethical principle, in regard to the citizenship process. Methods: to thisend, the authors conducted a search of scientific articles published on Lilacs and books, related toethics, bioethics and deontology. Literature review: Derived from Greek autos = self, nomos =rule, autonomy presupposes that the person should be free of constraints so that can choose thealternative that best suits, and may be restricted due to factors such as age or illness. The autonomymaterializes in the free and informed consent, which derives from the right of the person to consentor to refuse preventive, diagnostic or therapeutic proposals that affects or will affect their physical,psychological and social integrity. Conclusion: the autonomy principle broke with the ancientconcept of paternalistic medicine, which the doctor was the only part of the relationship that hadthe power to decide and determine the treatment that the patient should make. In Brazil, thisprinciple has gained importance and was incorporated in the Medical Ethics Code of 2010.