Jair Theodoro Filho’s research while affiliated with Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo and other places

Although the stifle joint of wild felines shares several characteristics observed in domestic cats, others are specific to each species. This study aimed to evaluate the stifle joints of eight Puma concolor, including two young and six adults, through different imaging examinations. All stifles were assessed using radiographs and computed tomography (CT). Magnetic resonance imaging (MRI) was performed on the stifles of one animal using 7 Tesla equipment. In all imaging modalities, the four sesamoid bones were detected. Meniscal mineralization was identified in the stifles of three adult animals and one young animal. The cruciate ligaments and menisci were identified on CT, with MRI providing better visualization. The mean values of CT measurements (cm2) in the sagittal section included patella (2.475), medial fabella (0.481), lateral fabella (0.772), popliteal sesamoid (0.222), and medial meniscus (0.051). No differences were found in HU values between the central trabecular bone of the patella and popliteal sesamoid, cortical bone of the patella and lateral and medial fabellas, or cortical bone of the patella and popliteal sesamoid. In conclusion, the descriptions of the stifle of Puma concolor in the different imaging methods contribute to understanding the species and can serve as a basis for identifying alterations.

Background Severe COVID-19 lung disease exhibits a high degree of spatial and temporal heterogeneity, with different histological features coexisting within a single individual. It is important to capture the disease complexity to support patient management and treatment strategies. We provide spatially decoded analyses on the immunopathology of diffuse alveolar damage (DAD) patterns and factors that modulate immune and structural changes in fatal COVID-19. Methods We spatially quantified the immune and structural cells in exudative, intermediate, and advanced DAD through multiplex immunohistochemistry in autopsy lung tissue of 18 COVID-19 patients. Cytokine profiling, viral, bacteria, and fungi detection, and transcriptome analyses were performed. Findings Spatial DAD progression was associated with expansion of immune cells, macrophages, CD8+ T cells, fibroblasts, and (lymph)angiogenesis. Viral load correlated positively with exudative DAD and negatively with disease/hospital length. In all cases, enteric bacteria were isolated, and Candida parapsilosis in eight cases. Cytokines correlated mainly with macrophages and CD8+T cells. Pro-coagulation and acute repair were enriched pathways in exudative DAD whereas intermediate/advanced DAD had a molecular profile of elevated humoral and innate immune responses and extracellular matrix production. Interpretation Unraveling the spatial and molecular immunopathology of COVID-19 cases exposes the responses to SARS-CoV-2-induced exudative DAD and subsequent immune-modulatory and remodeling changes in proliferative/advanced DAD that occur side-by-side together with secondary infections in the lungs. These complex features have important implications for disease management and the development of novel treatments. Funding CNPq, Bill and Melinda Gates Foundation, HC-Convida, FAPESP, Regeneron Pharmaceuticals, and the Swedish Heart & Lung Foundation.

Background: 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.

Aims Brazil ranks high in the number of COVID‐19 cases and COVID‐19’s mortality rate. In this context, autopsies are important to confirm the disease, determine associated conditions, and study the pathophysiology of this novel disease. In order to follow biosafety recommendations, we used Ultrasound‐Guided Minimally Invasive Autopsy (MIA‐US) to assess the systemic involvement of COVID‐19 and present the results of ten initial autopsies. Methods and results We used MIA‐US for tissue sampling of lungs, liver, heart, kidneys, spleen, brain, skin, skeletal muscle and testis for histology and RT‐PCR to detect SARS‐COV‐2‐RNA. All patients presented exudative/proliferative Diffuse Alveolar Damage. There were intense pleomorphic cytopathic effects on the respiratory epithelium, including airway and alveolar cells. Fibrinous thrombi in alveolar arterioles were present in eight patients and all patients presented a high density of alveolar megakaryocytes. Small thrombi were less frequently observed in glomeruli, spleen, heart, dermis, testis, and liver sinusoids. The main systemic findings were associated with comorbidities, age, and sepsis, in addition to possible tissue damage due to the viral infection such as myositis, dermatitis, myocarditis and orchitis. Conclusions MIA‐US is safe and effective for the study of severe COVID‐19. Our findings show that COVID‐19 is a systemic disease with major events in the lungs and involvement of various organs and tissues. Pulmonary changes are the result of severe epithelial injury and microthrombotic vascular phenomena. These findings indicate that both epithelial and vascular injury should be addressed in therapeutic approaches.