RENATA APARECIDA DE ALMEIDA MONTEIRO
Projetos de Pesquisa
Unidades Organizacionais
LIM/05 - Laboratório de Poluição Atmosférica Experimental, Hospital das Clínicas, Faculdade de Medicina
16 resultados
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Agora exibindo 1 - 10 de 16
- Postmortem chest computed tomography in COVID-19: A minimally invasive autopsy method(2024) SAVOIA, Paulo; SAWAMURA, Marcio Valente Yamada; MONTEIRO, Renata Aparecida de Almeida; DUARTE-NETO, Amaro Nunes; MARTIN, Maria da Graca Morais; DOLHNIKOFF, Marisa; MAUAD, Thais; SALDIVA, Paulo Hilario Nascimento; LEITE, Claudia da Costa; SILVA, Luiz Fernando Ferraz da; CARDOSO, Ellison FernandoObjectives: Performing autopsies in a pandemic scenario is challenging, as the need to understand pathophysiology must be balanced with the contamination risk. A minimally invasive autopsy might be a solution. We present a model that combines radiology and pathology to evaluate postmortem CT lung findings and their correlation with histopathology. Methods: Twenty-nine patients with fatal COVID-19 underwent postmortem chest CT, and multiple lung tissue samples were collected. The chest CT scans were analyzed and quantified according to lung involvement in five categories: normal, ground-glass opacities, crazy-paving, small consolidations, and large or lobar consolidations. The lung tissue samples were examined and quantified in three categories: normal lung, exudative diffuse alveolar damage (DAD), and fibroproliferative DAD. A linear index was used to estimate the global severity of involvement by CT and histopathological analysis. Results: There was a positive correlation between patient mean CT and histopathological severity score indexesPearson correlation coefficient (R) = 0.66 (p = 0.0078). When analyzing the mean lung involvement percentage of each finding, positive correlations were found between the normal lung percentage between postmortem CT and histopathology (R=0.65, p = 0.0082), as well as between ground -glass opacities in postmortem CT and normal lungs in histopathology (R=0.65, p = 0.0086), but negative correlations were observed between groundglass opacities extension and exudative diffuse alveolar damage in histological slides (R=-0.68, p = 0.005). Additionally, it was found is a trend toward a decrease in the percentage of normal lung tissue on the histological slides as the percentage of consolidations in postmortem CT scans increased (R =-0.51, p = 0.055). The analysis of the other correlations between the percentage of each finding did not show any significant correlation or correlation trends (p >= 0.10). Conclusions: A minimally invasive autopsy is valid. As the severity of involvement is increased in CT, more advanced disease is seen on histopathology. However, we cannot state that one specific radiological category represents a specific pathological correspondent. Ground -glass opacities, in the postmortem stage, must be interpreted with caution, as expiratory lungs may overestimate disease.
- Ultrasound assessment of pulmonary fibroproliferative changes in severe COVID-19: a quantitative correlation study with histopathological findings(2021) MONTEIRO, Renata Aparecida de Almeida; DUARTE-NETO, Amaro Nunes; SILVA, Luiz Fernando Ferraz da; OLIVEIRA, Ellen Pierre de; NASCIMENTO, Ellen Caroline Toledo do; MAUAD, Thais; SALDIVA, Paulo Hilario do Nascimento; DOLHNIKOFF, MarisaPurpose This study was designed to evaluate the usefulness of lung ultrasound (LUS) imaging to characterize the progression and severity of lung damage in cases of COVID-19. Methods We employed a set of combined ultrasound parameters and histopathological images obtained simultaneously in 28 patients (15 women, 0.6-83 years) with fatal COVID-19 submitted to minimally invasive autopsies, with different times of disease evolution from initial symptoms to death (3-37 days, median 18 days). For each patient, we analysed eight post-mortem LUS parameters and the proportion of three histological patterns (normal lung, exudative diffuse alveolar damage [DAD] and fibroproliferative DAD) in eight different lung regions. The relationship between histopathological and post-mortem ultrasonographic findings was assessed using various statistical approaches. Results Statistically significant positive correlations were observed between fibroproliferative DAD and peripheral consolidation (coefficient 0.43, p = 0.02) and pulmonary consolidation (coefficient 0.51, p = 0.005). A model combining age, time of evolution, sex and ultrasound score predicted reasonably well (r = 0.66) the proportion of pulmonary parenchyma with fibroproliferative DAD. Conclusion The present study adds information to previous studies related to the use of LUS as a tool to assess the severity of acute pulmonary damage. We provide a histological background that supports the concept that LUS can be used to characterize the progression and severity of lung damage in severe COVID-19.
- Histological-ultrasonographical correlation of pulmonary involvement in severe COVID-19(2020) MONTEIRO, Renata Aparecida Almeida; OLIVEIRA, Ellen Pierre de; SALDIVA, Paulo Hilario Nascimento; DOLHNIKOFF, Marisa; DUARTE-NETO, Amaro Nunes
- What else in times of COVID-19? The role of minimally invasive autopsy for the differential diagnosis of acute respiratory failure in a case of kala-azar(2023) GEBER-JUNIOR, Joao Carlos; MONTEIRO, Renata Aparecida de Almeida; ROCHA, Joao Wilson Pedro da; DUARTE, Edson Luiz Tarsia; NICODEMO, Elizabete; MUNHOZ, Olavo; PAIVA, Edison Ferreira de; MAUAD, Thais; SILVA, Luiz Fernando Ferraz da; SALDIVA, Paulo Hilario Nascimento; DOLHNIKOFF, Marisa; DUARTE-NETO, Amaro NunesVisceral leishmaniasis (VL) is a chronic vector-borne zoonotic disease caused by trypanosomatids, considered endemic in 98 countries, mainly associated with poverty. About 50,000-90,000 cases of VL occur annually worldwide, and Brazil has the second largest number of cases in the world. The clinical picture of VL is fever, hepatosplenomegaly, and pancytopenia, progressing to death in 90% of cases due to secondary infections and multi-organ failure, if left untreated. We describe the case of a 25-year-old female who lived in the metropolitan area of Sao Paulo, who had recently taken touristic trips to several rural areas in Southeastern Brazil and was diagnosed post-mortem. During the hospitalization in a hospital reference for the treatment of COVID-19, the patient developed acute respiratory failure, with chest radiographic changes, and died due to refractory shock. The ultrasound-guided minimally invasive autopsy diagnosed VL (macrophages containing amastigote forms of Leishmania in the spleen, liver and bone marrow), as well as pneumonia and bloodstream infection by gram-negative bacilli.
- Tracking the time course of pathological patterns of lung injury in severe COVID-19(2021) MAUAD, Thais; DUARTE-NETO, Amaro Nunes; SILVA, Luiz Fernando Ferraz da; OLIVEIRA, Ellen Pierre de; BRITO, Jose Mara de; NASCIMENTO, Ellen Caroline Toledo do; MONTEIRO, Renata Aparecida de Almeida; FERREIRA, Juliana Carvalho; CARVALHO, Carlos Roberto Ribeiro de; SALDIVA, Paulo Hilario do Nascimento; DOLHNIKOFF, MarisaBackground: Pulmonary involvement in COVID-19 is characterized pathologically by diffuse alveolar damage (DAD) and thrombosis, leading to the clinical picture of Acute Respiratory Distress Syndrome. The direct action of SARS-CoV-2 in lung cells and the dysregulated immuno-coagulative pathways activated in ARDS influence pulmonary involvement in severe COVID, that might be modulated by disease duration and individual factors. In this study we assessed the proportions of different lung pathology patterns in severe COVID-19 patients along the disease evolution and individual characteristics. Methods: We analysed lung tissue from 41 COVID-19 patients that died in the period March-June 2020 and were submitted to a minimally invasive autopsy. Eight pulmonary regions were sampled. Pulmonary pathologists analysed the H&E stained slides, performing semiquantitative scores on the following parameters: exudative, intermediate or advanced DAD, bronchopneumonia, alveolar haemorrhage, infarct (%), arteriolar (number) or capillary thrombosis (yes/no). Histopathological data were correlated with demographic-clinical variables and periods of symptoms-hospital stay. Results: Patient ' s age varied from 22 to 88 years (18f/23 m), with hospital admission varying from 0 to 40 days. All patients had different proportions of DAD in their biopsies. Ninety percent of the patients presented pulmonary microthrombosis. The proportion of exudative DAD was higher in the period 0-8 days of hospital admission till death, whereas advanced DAD was higher after 17 days of hospital admission. In the group of patients that died within eight days of hospital admission, elderly patients had less proportion of the exudative pattern and increased proportions of the intermediate patterns. Obese patients had lower proportion of advanced DAD pattern in their biopsies, and lower than patients with overweight. Clustering analysis showed that patterns of vascular lesions (microthrombosis, infarction) clustered together, but not the other patterns. The vascular pattern was not influenced by demographic or clinical parameters, including time of disease progression. Conclusion: Patients with severe COVID-19 present different proportions of DAD patterns over time, with advanced DAD being more prevalent after 17 days, which seems to be influenced by age and weight. Vascular involvement is present in a large proportion of patients, occurs early in disease progression, and does not change over time.
- Salivary glands are a target for SARS-CoV-2: a source for saliva contamination(2021) MATUCK, Bruno Fernandes; DOLHNIKOFF, Marisa; DUARTE-NETO, Amaro Nunes; MAIA, Gilvan; GOMES, Sara Costa; SENDYK, Daniel Isaac; ZARPELLON, Amanda; ANDRADE, Nathalia Paiva de; MONTEIRO, Renata Aparecida; PINHO, Joao Renato Rebello; GOMES-GOUVEA, Michele Soares; SOUZA, Suzana C. O. M.; KANAMURA, Cristina; MAUAD, Thais; SALDIVA, Paulo Hilario Nascimento; BRAZ-SILVA, Paulo H.; CALDINI, Elia Garcia; SILVA, Luiz Fernando Ferraz daThe ability of the new coronavirus SARS-CoV-2 to spread and contaminate is one of the determinants of the COVID-19 pandemic status. SARS-CoV-2 has been detected in saliva consistently, with similar sensitivity to that observed in nasopharyngeal swabs. We conducted ultrasound-guided postmortem biopsies in COVID-19 fatal cases. Samples of salivary glands (SGs; parotid, submandibular, and minor) were obtained. We analyzed samples using RT-qPCR, immunohistochemistry, electron microscopy, and histopathological analysis to identify SARS-CoV-2 and elucidate qualitative and quantitative viral profiles in salivary glands. The study included 13 female and 11 male patients, with a mean age of 53.12 years (range 8-83 years). RT-qPCR for SARS-CoV-2 was positive in 30 SG samples from 18 patients (60% of total SG samples and 75% of all cases). Ultrastructural analyses showed spherical 70-100 nm viral particles, consistent in size and shape with the Coronaviridae family, in the ductal lining cell cytoplasm, acinar cells, and ductal lumen of SGs. There was also degeneration of organelles in infected cells and the presence of a cluster of nucleocapsids, which suggests viral replication in SG cells. Qualitative histopathological analysis showed morphologic alterations in the duct lining epithelium characterized by cytoplasmic and nuclear vacuolization, as well as nuclear pleomorphism. Acinar cells showed degenerative changes of the zymogen granules and enlarged nuclei. Ductal epithelium and serous acinar cells showed intense expression of ACE2 and TMPRSS receptors. An anti-SARS-CoV-2 antibody was positive in 8 (53%) of the 15 tested cases in duct lining epithelial cells and acinar cells of major SGs. Only two minor salivary glands were positive for SARS-CoV-2 by immunohistochemistry. Salivary glands are a reservoir for SARS-CoV-2 and provide a pathophysiological background for studies that indicate the use of saliva as a diagnostic method for COVID-19 and highlight this biological fluid's role in spreading the disease. (C) 2021 The Pathological Society of Great Britain and Ireland.
- Postmortem Chest Computed Tomography in Fatal COVID-19: A Valuable Diagnostic Tool for Minimally Invasive Autopsy(2021) SILVA, Paulo Savoia Dias da; SAWAMURA, Marcio Valente Yamada; MONTEIRO, Renata Aparecida de Almeida; DUARTE-NETO, Amaro Nunes; MARTIN, Maria da Graca Morais; DOLHNIKOFF, Marisa; MAUAD, Thais; SALDIVA, Paulo Hilario Nascimento; LEITE, Claudia Costa; SILVA, Luiz Fernando Ferraz da; CARDOSO, Ellison Fernando
- COVID-19 induces more pronounced extracellular matrix deposition than other causes of ARDS(2023) COSTA, Natalia de Souza Xavier; RIBEIRO JUNIOR, Gabriel; NASCIMENTO, Ellen Caroline Toledo do; BRITO, Jose Mara de; ANTONANGELO, Leila; FARIA, Caroline Silverio; MONTEIRO, Jhonatas Sirino; SETUBAL, Joao Carlos; PINHO, Joao Renato Rebello; PEREIRA, Roberta Verciano; SEELAENDER, Marilia; CASTRO, Gabriela Salim de; LIMA, Joanna D. C. C.; MONTEIRO, Renata Aparecida de Almeida; DUARTE-NETO, Amaro Nunes; SALDIVA, Paulo Hilario Nascimento; SILVA, Luiz Fernando Ferraz da; DOLHNIKOFF, Marisa; MAUAD, ThaisBackgroundLung fibrosis is a major concern in severe COVID-19 patients undergoing mechanical ventilation (MV). Lung fibrosis frequency in post-COVID syndrome is highly variable and even if the risk is proportionally small, many patients could be affected. However, there is still no data on lung extracellular matrix (ECM) composition in severe COVID-19 and whether it is different from other aetiologies of ARDS.MethodsWe have quantified different ECM elements and TGF-beta expression in lung tissue of 28 fatal COVID-19 cases and compared to 27 patients that died of other causes of ARDS, divided according to MV duration (up to six days or seven days or more). In COVID-19 cases, ECM elements were correlated with lung transcriptomics and cytokines profile.ResultsWe observed that COVID-19 cases presented significant increased deposition of collagen, fibronectin, versican, and TGF-beta, and decreased decorin density when compared to non-COVID-19 cases of similar MV duration. TGF-beta was precociously increased in COVID-19 patients with MV duration up to six days. Lung collagen was higher in women with COVID-19, with a transition of upregulated genes related to fibrillogenesis to collagen production and ECM disassembly along the MV course.ConclusionsFatal COVID-19 is associated with an early TGF-beta expression lung environment after the MV onset, followed by a disordered ECM assembly. This uncontrolled process resulted in a prominent collagen deposition when compared to other causes of ARDS. Our data provides pathological substrates to better understand the high prevalence of pulmonary abnormalities in patients surviving COVID-19.
- Ultrasound-Guided Minimally Invasive Tissue Sampling: A Minimally Invasive Autopsy Strategy During the COVID-19 Pandemic in Brazil, 2020(2021) DUARTE-NETO, Amaro Nunes; SILVA, Luiz Fernando Ferraz da; MONTEIRO, Renata Aparecida de Almeida; FILHO, Jair Theodoro; LEITE, Thabata Larissa Luciano Ferreira; MOURA, Catia Sales de; GOMES-GOUVEA, Michele Soares; PINHO, Joao Renato Rebellho; KANAMURA, Cristina Takami; OLIVERIA, Ellen Pierre de; BISPO, Kely Cristina Soares; ARRUDA, Cassia; SANTOS, Aline Brito dos; AQUINO, Flavia Cristina Goncalves; CALDINI, Elia Garcia; MAUAD, Thais; SALDIVA, Paulo Hilario Nascimento; DOLHNIKOFF, MarisaBackground: Minimally invasive autopsies, also known as minimally invasive tissue sampling (MITS), have proven to be an alternative to complete diagnostic autopsies (CDAs) in places or situations where this procedure cannot be performed. During the coronavirus disease 2019 (COVID-19) pandemic, CDAs were suspended by March 2020 in Brazil to reduce biohazard. To contribute to the understanding of COVID-19 pathology, we have conducted ultrasound (US)-guided MITS as a strategy. Methods: This case series study includes 80 autopsies performed in patients with COVID-19 confirmed by laboratorial tests. Different organs were sampled using a standardized MITS protocol. Tissues were submitted to histopathological analysis as well as immunohistochemical and molecular analysis and electron microscopy in selected cases. Results: US-guided MITS proved to be a safe and highly accurate procedure; none of the personnel were infected, and accuracy ranged from 69.1% for kidney, up to 90.1% for lungs, and reaching 98.7% and 97.5% for liver and heart, respectively. US-guided MITS provided a systemic view of the disease, describing the most common pathological findings and identifying viral and other infectious agents using ancillary techniques, and also allowed COVID-19 diagnosis confirmation in 5% of the cases that were negative in premortem and postmortem nasopharyngeal/oropharyngeal swab real-time reverse-transcription polymerase chain reaction. Conclusions: Our data showed that US-guided MITS has the capacity similar to CDA not only to identify but also to characterize emergent diseases.
- An autopsy study of the spectrum of severe COVID-19 in children: From SARS to different phenotypes of MIS-C(2021) DUARTE-NETO, Amaro Nunes; CALDINI, Elia Garcia; GOMES-GOUVEA, Michele Soares; KANAMURA, Cristina Takami; MONTEIRO, Renata Aparecida de Almeida; FERRANTI, Juliana Ferreira; VENTURA, Andrea Maria Cordeiro; REGALIO, Fabiane Aliotti; FIORENZANO, Daniela Matos; GIBELLI, Maria Augusta Bento Cicaroni; CARVALHO, Werther Brunow de; LEAL, Gabriela Nunes; PINHO, Joao Renato Rebello; DELGADO, Artur Figueiredo; CARNEIRO-SAMPAIO, Magda; MAUAD, Thais; SILVA, Luiz Fernando Ferraz da; SALDIVA, Paulo Hilario Nascimento; DOLHNIKOFF, MarisaBackground: COVID-19 in children is usually mild or asymptomatic, but severe and fatal paediatric cases have been described. The pathology of COVID-19 in children is not known; the proposed pathogenesis for severe cases includes immune-mediated mechanisms or the direct effect of SARS-CoV-2 on tissues. We describe the autopsy findings in five cases of paediatric COVID-19 and provide mechanistic insight into the mechanisms involved in the pathogenesis of the disease. Methods: Children and adolescents who died with COVID-19 between March 18 and August 15, 2020 were autopsied with a minimally invasive method. Tissue samples from all vital organs were analysed by histology, electron microscopy (EM), reverse-transcription polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC). Findings: Five patients were included, one male and four female, aged 7 months to 15 years. Two patients had severe diseases before SARS-CoV-2 infection: adrenal carcinoma and Edwards syndrome. Three patients were previously healthy and had multisystem inflammatory syndrome in children (MIS-C) with distinct clinical presentations: myocarditis, colitis, and acute encephalopathy with status epilepticus. Autopsy findings varied amongst patients and included mild to severe COVID-19 pneumonia, pulmonary microthrombosis, cerebral oedema with reactive gliosis, myocarditis, intestinal inflammation, and haemophagocytosis. SARSCoV-2 was detected in all patients in lungs, heart and kidneys by at least one method (RT-PCR, IHC or EM), and in endothelial cells from heart and brain in two patients with MIS-C (IHC). In addition, we show for the first time the presence of SARS-CoV-2 in the brain tissue of a child with MIS-C with acute encephalopathy, and in the intestinal tissue of a child with acute colitis. Interpretation: SARS-CoV-2 can infect several cell and tissue types in paediatric patients, and the target organ for the clinical manifestation varies amongst individuals. Two major patterns of severe COVID-19 were observed: a primarily pulmonary disease, with severe acute respiratory disease and diffuse alveolar damage, or a multisystem inflammatory syndrome with the involvement of several organs. The presence of SARS-CoV-2 in several organs, associated with cellular ultrastructural changes, reinforces the hypothesis that a direct effect of SARS-CoV-2 on tissues is involved in the pathogenesis of MIS-C. (c) 2021 The Author(s).