Tele-Intensive Care Unit Program in Brazil: Implementation and Expansion.

In this scientific report, we aimed to describe the implementation and expansion of a Tele-Intensive Care Unit (Tele-ICU) program in Brazil, highlighting the pillars of success, improvements, and perspectives. Tele-ICU program emerged during the COVID-19 pandemic at the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), focusing on clinical case discussions and training of health practitioners in public hospitals of the state of São Paulo in Brazil, to support health care professionals for treating COVID-19 patients. The success of implementing this initiative endorsed the project expansion to other five hospitals from different macroregions of the country, leading to the Tele-ICU-Brazil. These projects assisted 40 hospitals, allowing more than 11,500 teleinterconsultations (exchange of medical information between health care professionals using a licensed online platform) and training more than 14,800 health care professionals, reducing mortality and length of hospitalized patients. A segment in telehealth for the obstetrics health care was implemented after detecting these were a susceptible group of patients to COVID-19 severity. As a perspective, this segment will be expanded to 27 hospitals in the country. The Tele-ICU projects reported here were the largest digital health ICU programs ever established in Brazilian National Health System until know. Their results were unprecedented and proved to be crucial for supporting health care professionals nationwide during the COVID-19 pandemic and guide future initiatives in digital health in Brazil's National Health System.

Cardiovascular diseases worsen the maternal prognosis of COVID-19.

Cardiovascular diseases (CVD) are a risk factor for severe cases of COVID-19. There are no studies evaluating whether the presence of CVD in pregnant and postpartum women with COVID-19 is associated with a worse prognosis. In an anonymized open database of the Ministry of Health, we selected cases of pregnant and postpartum women who were hospitalized due to COVID-19 infection and with data regarding their CVD status. In the SIVEP GRIPE data dictionary, CVD is defined as "presence of cardiovascular disease", excluding those of neurological and nephrological causes that are pointed out in another field. The patients were divided into two groups according to the presence or absence of CVD (CVD and non-CVD groups). Among the 1,876,953 reported cases, 3,562 confirmed cases of pregnant and postpartum women were included, of which 602 had CVD. Patients with CVD had an older age (p<0,001), a higher incidence of diabetes (p<0,001) and obesity (p<0,001), a higher frequency of systemic (p<0,001) and respiratory symptoms (p<0,001). CVD was a risk factor for ICU admission (p<0,001), ventilatory support (p = 0.004) and orotracheal intubation in the third trimester (OR 1.30 CI95%1.04-1.62). The group CVD had a higher mortality (18.9% vs. 13.5%, p<0,001), with a 32% higher risk of death (OR 1.32 CI95%1.16-1.50). Moreover, the risk was increased in the second (OR 1.94 CI95%1.43-2.63) and third (OR 1.29 CI95%1.04-1.60) trimesters, as well as puerperium (OR 1.27 CI95%1.03-1.56). Hospitalized obstetric patients with CVD and COVID-19 are more symptomatic. Their management demand more ICU admission and ventilatory support and the mortality is higher.

Use of Mirtazapine and Olanzapine in the Treatment of Refractory Hyperemesis Gravidarum: A Case Report and Systematic Review.

Hyperemesis gravidarum (HG) is a rare condition (1.1%) characterized by excessive vomiting, malnutrition, dehydration, and laboratorial alterations. Herein, we describe the even rarer and serious presentation of refractoriness to the usual treatment of antiemetics and parenteral nutrition, with improvement only after the use of olanzapine and mirtazapine. Two subsequent pregnancies of the same woman with HG are described, which were associated with severe weight loss, anemia, hyponatremia, hypokalemia, and mild dysfunction of liver enzymes. In the third pregnancy, the usual treatment for HG was not successful, requiring enteral nutrition and the introduction of olanzapine. In the fourth pregnancy, the patient refused to use enteral nutrition for refractory HG. Hence, the patient was started on mirtazapine at an initial dose of 15 mg/day, which was gradually increased to 30 mg/day. The patient responded well to the new regimen, as demonstrated by the decrease in symptoms, the gain of 10 kg in the pregnancy, and delivering a healthy newborn. A systematic review of literature showed 11 articles and 30 cases that successfully used mirtazapine in HG. Good clinical outcomes were seen with 4 days of the treatment and at an initial dose of 15 mg/day. However, most of these reports were from psychiatric profiles, with a predominance of depression and anxiety symptoms, and a poor description of the obstetric conditions and the disease progression itself. Pulmonary hypertension was described in one case and neonatal hyperexcitability in another. The case described in this paper reinforces the idea that mirtazapine and olanzapine can be considered in refractory HG, with good results. In the world literature, this is the second case of HG that has been successfully treated with olanzapine and the first in Latin America treated with mirtazapine.

Whole transcriptomic analysis of mesenchymal stem cells cultured in Nichoid micro-scaffolds.

Mesenchymal stem cells (MSCs) are known to be ideal candidates for clinical applications where not only regenerative potential but also immunomodulation ability is fundamental. Over the last years, increasing efforts have been put into the design and fabrication of 3D synthetic niches, conceived to emulate the native tissue microenvironment and aiming at efficiently controlling the MSC phenotype in vitro. In this panorama, our group patented an engineered microstructured scaffold, called Nichoid. It is fabricated through two-photon polymerization, a technique enabling the creation of 3D structures with control of scaffold geometry at the cell level and spatial resolution beyond the diffraction limit, down to 100 nm. The Nichoid's capacity to maintain higher levels of stemness as compared to 2D substrates, with no need for adding exogenous soluble factors, has already been demonstrated in MSCs, neural precursors, and murine embryonic stem cells. In this work, we evaluated how three-dimensionality can influence the whole gene expression profile in rat MSCs. Our results show that at only 4 days from cell seeding, gene activation is affected in a significant way, since 654 genes appear to be differentially expressed (392 upregulated and 262 downregulated) between cells cultured in 3D Nichoids and in 2D controls. The functional enrichment analysis shows that differentially expressed genes are mainly enriched in pathways related to the actin cytoskeleton, extracellular matrix (ECM), and, in particular, cell adhesion molecules (CAMs), thus confirming the important role of cell morphology and adhesions in determining the MSC phenotype. In conclusion, our results suggest that the Nichoid, thanks to its exclusive architecture and 3D cell adhesion properties, is not only a useful tool for governing cell stemness but could also be a means for controlling immune-related MSC features specifically involved in cell migration.

Pregnancy in Women with Complex Congenital Heart Disease. A Constant Challenge / Gravidez em Portadoras de Cardiopatias Congênitas Complexas: Um Constante Desafio

Abstract Background: The improvement in surgical techniques has contributed to an increasing number of childbearing women with complex congenital heart disease (CCC). However, adequate counseling about pregnancy in this situation is uncertain, due to a wide variety of residual cardiac lesions. Objectives: To evaluate fetal and maternal outcomes in pregnant women with CCC and to analyze the predictive variables of prognosis. Methods: During 10 years we followed 435 consecutive pregnancies in patients (pts) with congenital heart disease. Among of them, we selected 42 pregnancies in 40 (mean age of 25.5 ± 4.5 years) pts with CCC, who had been advised against pregnancy. The distribution of underlying cardiac lesions were: D-Transposition of the great arteries, pulmonary atresia, tricuspid atresia, single ventricle, double-outlet ventricle and truncus arteriosus. The surgical procedures performed before gestation were: Fontan, Jatene, Rastelli, Senning, Mustard and other surgical techniques, including Blalock, Taussing, and Glenn. Eight (20,0%) pts did not have previous surgery. Nineteen 19 (47.5%) pts had hypoxemia. The clinical follow-up protocol included oxygen saturation recording, hemoglobin and hematocrit values; medication adjustment to pregnancy, anticoagulation use, when necessary, and hospitalization from 28 weeks, in severe cases. The statistical significance level considered was p < 0.05. Results: Only seventeen (40.5%) pregnancies had maternal and fetal uneventful courses. There were 13 (30.9%) maternal complications, two (4.7%) maternal deaths due to hemorrhage pos-partum and severe pre-eclampsia, both of them in women with hypoxemia. There were 7 (16.6%) stillbirths and 17 (40.5%) premature babies. Congenital heart disease was identified in two (4.1%) infants. Maternal and fetal complications were higher (p < 0.05) in women with hypoxemia. Conclusions: Pregnancy in women with CCC was associated to high maternal and offspring risks. Hypoxemia was a predictive variable of poor maternal and fetal outcomes. Women with CCC should be advised against pregnancy, even when treated in specialized care centers.

Resumo Fundamento: A contínua habilidade na conduta das cardiopatias congênitas complexas (CCC) tem permitido o alcance da idade fértil. Contudo, a heterogeneidade das lesões cardíacas na idade adulta limita a estimativa do prognóstico da gravidez. Objetivo: Estudar a evolução materno-fetal das gestantes portadoras de CCC e analisar as variáveis presumíveis de prognóstico. Método: No período de 10 anos, 435 gestantes portadoras de cardiopatias congênitas foram consecutivamente incluídas no Registro do Instituto do Coração (Registro-InCor). Dentre elas, foram selecionadas 42 gestações em 40 mulheres com CCC (24,5 ± 3,4 anos) que haviam sido desaconselhadas a engravidar. As cardiopatias de base distribuíram-se em: transposição das grandes artérias, atresia pulmonar, atresia tricúspide, ventrículo único, dupla via de saída de ventrículo direito, dupla via de entrada de ventrículo esquerdo e outras lesões estruturais. As cirurgias realizadas foram Rastelli, Fontan, Jatene, Senning, Mustard e outros procedimentos combinados, como tunelização, Blalock Taussing e Glenn. Oito pacientes (20%) não haviam sido operadas, e 19 (47,5%) apresentavam hipoxemia. O protocolo de atendimento incluiu: registro da saturação de oxigênio, hemoglobina sérica, hematócrito, ajuste das medicações, anticoagulação individualizada e hospitalização a partir de 28 semanas de gestação, em face da gravidade do quadro clínico e obstétrico. Na análise estatística, o nível de significância adotado foi de 0,05. Resultado: Somente 17 gestações (40,5%) não tiveram complicações maternas nem fetais. Houve 13 problemas maternos (30,9%) e 2 mortes (4,7%) causadas por hemorragia pós-parto e pré-eclâmpsia grave, ambas em pacientes que apresentavam hipoxemia. Houve 7 perdas fetais (16,6%), 17 bebês prematuros (40,5%) e 2 recém-nascidos (4,7%) com cardiopatia congênita. As complicações materno-fetais foram significativamente maiores em pacientes que apresentavam hipoxemia (p < 0,05). Conclusão: O alcance da idade reprodutiva em pacientes com CCC é crescente; contudo, a má evolução materno-fetal desaconselha a gravidez, particularmente nas pacientes que apresentam hipoxemia.

Pregnancy in Women with Complex Congenital Heart Disease. A Constant Challenge.

BACKGROUND: The improvement in surgical techniques has contributed to an increasing number of childbearing women with complex congenital heart disease (CCC). However, adequate counseling about pregnancy in this situation is uncertain, due to a wide variety of residual cardiac lesions. OBJECTIVES: To evaluate fetal and maternal outcomes in pregnant women with CCC and to analyze the predictive variables of prognosis. METHODS: During 10 years we followed 435 consecutive pregnancies in patients (pts) with congenital heart disease. Among of them, we selected 42 pregnancies in 40 (mean age of 25.5 ± 4.5 years) pts with CCC, who had been advised against pregnancy. The distribution of underlying cardiac lesions were: D-Transposition of the great arteries, pulmonary atresia, tricuspid atresia, single ventricle, double-outlet ventricle and truncus arteriosus. The surgical procedures performed before gestation were: Fontan, Jatene, Rastelli, Senning, Mustard and other surgical techniques, including Blalock, Taussing, and Glenn. Eight (20,0%) pts did not have previous surgery. Nineteen 19 (47.5%) pts had hypoxemia. The clinical follow-up protocol included oxygen saturation recording, hemoglobin and hematocrit values; medication adjustment to pregnancy, anticoagulation use, when necessary, and hospitalization from 28 weeks, in severe cases. The statistical significance level considered was p < 0.05. RESULTS: Only seventeen (40.5%) pregnancies had maternal and fetal uneventful courses. There were 13 (30.9%) maternal complications, two (4.7%) maternal deaths due to hemorrhage pos-partum and severe pre-eclampsia, both of them in women with hypoxemia. There were 7 (16.6%) stillbirths and 17 (40.5%) premature babies. Congenital heart disease was identified in two (4.1%) infants. Maternal and fetal complications were higher (p < 0.05) in women with hypoxemia. CONCLUSIONS: Pregnancy in women with CCC was associated to high maternal and offspring risks. Hypoxemia was a predictive variable of poor maternal and fetal outcomes. Women with CCC should be advised against pregnancy, even when treated in specialized care centers.