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Identifying cell types and states remains a time-consuming and error-prone challenge for spatial biology. While deep learning is increasingly used, it is difficult to generalize due to variability at the level of cells, neighborhoods, and niches in health and disease. To address this, we developed TACIT, an unsupervised algorithm for cell annotation using predefined signatures that operates without training data, using unbiased thresholding to distinguish positive cells from background, focusing on relevant markers to identify ambiguous cells in multiomic assays. Using five datasets (5,000,000-cells; 51-cell types) from three niches (brain, intestine, gland), TACIT outperformed existing unsupervised methods in accuracy and scalability. Integration of TACIT-identified cell with a novel Shiny app revealed new phenotypes in two inflammatory gland diseases. Finally, using combined spatial transcriptomics and proteomics, we discover under- and overrepresented immune cell types and states in regions of interest, suggesting multimodality is essential for translating spatial biology to clinical applications.
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Atopic dermatitis (AD) is an inflammatory skin disease with intense pruritus, and chronic skin colonization by Staphylococcus aureus. To understand the inflammatory status in AD, we investigated the inflammasome complex, that activates ASC (Apoptosis-associated speck-like protein containing a CARD), caspase-1 and GSDMD (gasdermin-D), and production of IL-1ß and IL-18. We aimed to evaluate the expression of the inflammasome pathway in the skin of adults with AD. Thirty patients with moderate to severe AD and 20 healthy controls were enrolled in the study. We performed the analysis of the inflammasome components NLRP1, NLRP3, AIM-2, IL-1ß, IL-18, Caspase-1, ASC, GSDMD, and CD68 expression (macrophage marker) by immunohistochemistry and immunofluorescence. The main findings included increased expression of NLRP3, NLRP1 and AIM-2 at dermal level of severe AD; augmented IL-18 and IL-1ß expression at epidermis of moderate and severe patients, and in the dermis of severe AD; augmented expression of ASC, caspase-1 and GSDMD in both epidermis and dermis of moderate and severe AD. We detected positive correlation between caspase-1, GSDMD and IL-1ß (epidermis) and caspase-1 (dermis) and AD severity; NLRP3, AIM-2 and IL-1ß, and NLRP3 with IL-18 in the epidermis; ASC, GSDMD and IL-1ß, and NLRP3, AIM-2, caspase-1, and IL-18 in the dermis. We also evidenced the presence of CD68+ macrophages secreting GSDMD, ASC and IL-1ß in moderate and severe AD. Cutaneous macrophages, early detected in moderate AD, have its role in the disease inflammatory mechanisms. Our study indicates a canonical activation pathway of inflammasomes, reinforced by the chronic status of inflammation in AD. The analysis of the inflammasome complex evidenced an imbalance in its regulation, with increased expression of the evaluated components, which is remarkably in severe AD, emphasizing its relevance as potential disease biomarkers and targets for immunomodulatory interventions.
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Proteínas Adaptadoras de Sinalização CARD , Caspase 1 , Dermatite Atópica , Inflamassomos , Macrófagos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas Adaptadoras de Sinalização CARD/metabolismo , Estudos de Casos e Controles , Caspase 1/metabolismo , Molécula CD68 , Dermatite Atópica/imunologia , Dermatite Atópica/metabolismo , Dermatite Atópica/patologia , Proteínas de Ligação a DNA , Epiderme/imunologia , Epiderme/metabolismo , Epiderme/patologia , Gasderminas , Inflamassomos/metabolismo , Inflamassomos/imunologia , Interleucina-18/metabolismo , Interleucina-1beta/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Macrófagos/metabolismo , Macrófagos/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteínas NLR/metabolismo , Proteínas de Ligação a Fosfato/metabolismo , Índice de Gravidade de Doença , Pele/patologia , Pele/imunologia , Pele/metabolismoRESUMO
BACKGROUND: Acute respiratory distress syndrome (ARDS) is a common cause of respiratory failure in critically ill patients, and diffuse alveolar damage (DAD) is considered its histological hallmark. Sepsis is one of the most common aetiology of ARDS with the highest case-fatality rate. Identifying ARDS patients and differentiate them from other causes of acute respiratory failure remains a challenge. To address this, many studies have focused on identifying biomarkers that can help assess lung epithelial injury. However, there is scarce information available regarding the tissue expression of these markers. Evaluating the expression of elafin, RAGE, and SP-D in lung tissue offers a potential bridge between serological markers and the underlying histopathological changes. Therefore, we hypothesize that the expression of epithelial injury markers varies between sepsis and ARDS as well as according to its severity. METHODS: We compared the post-mortem lung tissue expression of the epithelial injury markers RAGE, SP-D, and elafin of patients that died of sepsis, ARDS, and controls that died from non-pulmonary causes. Lung tissue was collected during routine autopsy and protein expression was assessed by immunohistochemistry. We also assessed the lung injury by a semi-quantitative analysis. RESULTS: We observed that all features of DAD were milder in septic group compared to ARDS group. Elafin tissue expression was increased and SP-D was decreased in the sepsis and ARDS groups. Severe ARDS expressed higher levels of elafin and RAGE, and they were negatively correlated with PaO2/FiO2 ratio, and positively correlated with bronchopneumonia percentage and hyaline membrane score. RAGE tissue expression was negatively correlated with mechanical ventilation duration in both ARDS and septic groups. In septic patients, elafin was positively correlated with ICU admission length, SP-D was positively correlated with serum lactate and RAGE was correlated with C-reactive protein. CONCLUSIONS: Lung tissue expression of elafin and RAGE, but not SP-D, is associated with ARDS severity, but does not discriminate sepsis patients from ARDS patients.
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Lesão Pulmonar Aguda , Síndrome do Desconforto Respiratório , Sepse , Humanos , Elafina , Proteína D Associada a Surfactante Pulmonar , Pulmão , Síndrome do Desconforto Respiratório/diagnóstico , Sepse/diagnóstico , Sepse/complicaçõesRESUMO
An ideal blood biomarker for stroke should provide reliable results, enable fast diagnosis, and be readily accessible for practical use. Neuron-specific enolase (NSE), an enzyme released after neuronal damage, has been studied as a marker for brain injury, including cerebral infarction. However, different methodologies and limited sample sizes have restricted the applicability of any potential findings. This work aims to determine whether NSE levels at Emergency Department (ED) admission correlate with stroke severity, infarcted brain volume, functional outcome, and/or death rates. A systematic literature review was performed using PubMed, Embase, and Scopus databases. Each reviewer independently assessed all published studies identified as potentially relevant. All relevant original observational studies (cohort, case-control, and cross-sectional studies) were included. Eleven studies (1398 patients) met the inclusion criteria. Among these, six studies reported a significant correlation between NSE levels and stroke severity, while only one found no association. Four studies indicated a positive relationship between infarcted brain volume assessed by imaging and NSE levels, in contrast to the findings of only one study. Four studies identified an association related to functional outcome and death rates, while three others did not reach statistical significance in their findings. These data highlight that NSE levels at ED admissions proved to be a promising tool for predicting the outcome of ischemic stroke patients in most studies. However, they presented high discrepancies and low robustness. Therefore, further research is necessary to establish and define the role of NSE in clinical practice.
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AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Biomarcadores , Estudos Transversais , Infarto , AVC Isquêmico/diagnóstico por imagem , Fosfopiruvato Hidratase , Prognóstico , Acidente Vascular Cerebral/diagnóstico por imagem , Volume SistólicoRESUMO
Abstract Background: Methotrexate (MTX) is an alternative treatment for patients with moderate/severe atopic dermatitis (AD). Objective: The authors evaluated the effect of MTX on the cutaneous expression of cytokines and chemokines that are involved in the inflammatory response in adult AD patients who received treatment with methotrexate for 24 weeks. Methods: The authors conducted a prospective single-institution cohort study with 12 adults with moderate/severe AD who received oral MTX (15 mg/wk for 24 wks) and 10 non-atopic matched controls. The comparison was made of skin biopsies of lesional and non-lesional skin, pre- and post MTX treatment. The authors analyzed mean epidermal thickness and expression of IL-31, IL-31RA, OSMR, TSLP, Ki67, IL-4 mRNA, IL-6, IL-10, TNF-α, IFN-γ, TARC, and CCL-22. Results: There was a reduction in mean epidermal thickness (p = 0.021), an increase in IL-31RA expression (immunohistochemistry) in the epidermis (p = 0.016) and a decrease in IL-31 gene expression (p = 0.019) on lesional AD skin post-MTX treatment. No significant changes in the cutaneous expression of the other evaluated markers were identified. Study limitations: Small sample size and limited length of follow-up. Conclusions: Treatment with MTX in adults with moderate/severe AD reduced epidermal hyperplasia and changed the cutaneous expression of inflammatory cytokines and receptors that are mainly related to pruritus, including IL-31 and IL-31RA.
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BACKGROUND: Methotrexate (MTX) is an alternative treatment for patients with moderate/severe atopic dermatitis (AD). OBJECTIVE: The authors evaluated the effect of MTX on the cutaneous expression of cytokines and chemokines that are involved in the inflammatory response in adult AD patients who received treatment with methotrexate for 24 weeks. METHODS: The authors conducted a prospective single-institution cohort study with 12 adults with moderate/severe AD who received oral MTX (15 mg/wk for 24 wks) and 10 non-atopic matched controls. The comparison was made of skin biopsies of lesional and non-lesional skin, pre- and post MTX treatment. The authors analyzed mean epidermal thickness and expression of IL-31, IL-31RA, OSMR, TSLP, Ki67, IL-4 mRNA, IL-6, IL-10, TNF-α, IFN-γ, TARC, and CCL-22. RESULTS: There was a reduction in mean epidermal thickness (p = 0.021), an increase in IL-31RA expression (immunohistochemistry) in the epidermis (p = 0.016) and a decrease in IL-31 gene expression (p = 0.019) on lesional AD skin post-MTX treatment. No significant changes in the cutaneous expression of the other evaluated markers were identified. STUDY LIMITATIONS: Small sample size and limited length of follow-up. CONCLUSIONS: Treatment with MTX in adults with moderate/severe AD reduced epidermal hyperplasia and changed the cutaneous expression of inflammatory cytokines and receptors that are mainly related to pruritus, including IL-31 and IL-31RA. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03327116.
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Dermatite Atópica , Adulto , Humanos , Dermatite Atópica/tratamento farmacológico , Metotrexato/uso terapêutico , Estudos de Coortes , Estudos Prospectivos , CitocinasRESUMO
OBJECTIVE: Gastroschisis (GS) is a congenital anomaly in the abdominal wall with the intestinal loops exiting laterally to the umbilicus. The contact of the loops with Amniotic Fluid (AF) causes an inflammatory process in the exposed part, leading to an extended hospital stay and an increased risk of morbidity due to alterations related to intestinal motility. The authors aimed to evaluate the time of exposure to the AF in the experimental GS and to search for potential biomarkers of intestinal inflammation by measuring microRNAs. METHODS: Rat fetuses were divided into three groups: a) CONTROL, b) GS reared on day 18 (GS = 18), and c) GS reared on day 19.5 (GS = 19) (term = 22 days). On day 21.5, the fetuses were removed for biometric parameters and biochemical analyses: 1) Biometrics: Body and Intestinal Weight (BW, IW), and intestinal-body weight ratio (IW/BW); 2) Descriptive histopathology and 3) miR-143 quantification by real-time Polymerase Chain Reaction (PCR). RESULTS: BW was higher in CONTROL than GS 18 and G19 (p < 0.05). IW, IW/BW, intestinal water, and mRNA-143 were higher in GS 18 and GS 19 than in CONTROL, and GS 18 was higher than GS 19 (p < 0.05). The average of the inflammation score from the intestinal wall with mucosal inflammation and intra-epithelial lymphocytes shows worst in GS 18 and GS 19 vs. CONTROL (p < 0.05). CONCLUSIONS: The tissue expression of mRNA-143 and the morphological changes in the intestine of GS worsened according to the time of exposure to AF, which could be a possible marker of fetal intestinal damage.
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Gastrosquise , MicroRNAs , Animais , Ratos , Líquido Amniótico/metabolismo , Gastrosquise/genética , Gastrosquise/complicações , Gastrosquise/metabolismo , Inflamação , Intestinos/patologiaRESUMO
Endothelial dysfunction is a key phenomenon in COVID-19, induced by direct viral endothelial infection and secondary inflammation, mainly affecting the microvascular circulation. However, few studies described the subcellular aspects of the lung microvasculature and the associated thrombotic phenomena, which are widely present in severe COVID-19 cases. To that end, in this transversal observational study we performed transmission and scanning electron microscopy in nine lung samples of patients who died due to COVID-19, obtained via minimally invasive autopsies in Sao Paulo, Brazil, in 2020. All patients died due to acute respiratory failure and had microvascular thrombosis at histology. Electron microscopy revealed areas of endothelial damage with basal lamina disruption and virus infection in endothelial cells. In the capillary lumens, the ultrastructure of the thrombi is depicted, with red blood cells stacking, dysmorphism and hemolysis, fibrin meshworks, and extracellular traps. Our description illustrates the complex pathophysiology of microvascular thrombosis at the cellular level, which leads to some of the peculiar characteristics of severe COVID-19.NEW & NOTEWORTHY In this study, electron microscopy was used to explain the pathophysiology of respiratory failure in severe COVID-19. Before the advent of vaccination, as the virus entered the respiratory system, it rapidly progressed to the alveolar capillary network and, before causing exudative alveolar edema, it caused mainly thrombosis of the pulmonary microcirculation with preserved lung compliance explaining "happy hypoxia." Timing of anticoagulation is of pivotal importance in this disease.
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COVID-19 , Insuficiência Respiratória , Trombose , Humanos , COVID-19/complicações , SARS-CoV-2 , Células Endoteliais/patologia , Brasil , Pulmão/patologia , Insuficiência Respiratória/etiologiaRESUMO
Visceral 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.
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COVID-19 , Leishmaniose Visceral , Insuficiência Respiratória , Feminino , Humanos , Adulto , Leishmaniose Visceral/complicações , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/tratamento farmacológico , Diagnóstico Diferencial , Autopsia , COVID-19/diagnóstico , Brasil , Insuficiência Respiratória/diagnóstico , Teste para COVID-19RESUMO
Obesity is increasing in incidence worldwide, especially in women, which can affect the outcome of pregnancy. During this period, viral infections represent a risk to the mother, the placental unit, and the fetus. The Zika virus (ZIKV) outbreak in Brazil has been the cause of congenital Zika syndrome (CZS), with devastating consequences such as microcephaly in newborns. Herein, we analyzed the impact of maternal overweight/obesity on the antiviral factors' expression in the placental tissue of Zika-infected mothers. We accessed placentas from women with and without obesity from 34 public health units (São Paulo) and from Zika-infected mothers with and without obesity from the Clinical Cohort Study of ZIKV pregnant women (Rio de Janeiro, Brazil). We first verified that obesity, without infection, did not alter the constitutive transcriptional expression of antiviral factors or IFN type I/III expression. Interestingly, obesity, when associated with ZIKV infection, showed a decreased transcriptional expression of RIG-I and IFIH1 (MDA-5 protein precursor gene). At the protein level, we also verified a decreased RIG-I and IRF-3 expression in the decidual placenta from the Zika-infected obese group, regardless of microcephaly. This finding shows, for the first time, that obesity associated with ZIKV infection leads to an impaired type I IFN downstream signaling pathway in the maternal-fetal interface.
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Interferon Tipo I , Microcefalia , Infecção por Zika virus , Zika virus , Recém-Nascido , Gravidez , Feminino , Humanos , Antivirais , Gestantes , Infecção por Zika virus/complicações , Estudos de Coortes , Brasil/epidemiologia , Placenta , ObesidadeRESUMO
ABSTRACT Visceral 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.
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Abstract Objective Gastroschisis (GS) is a congenital anomaly in the abdominal wall with the intestinal loops exiting laterally to the umbilicus. The contact of the loops with Amniotic Fluid (AF) causes an inflammatory process in the exposed part, leading to an extended hospital stay and an increased risk of morbidity due to alterations related to intestinal motility. The authors aimed to evaluate the time of exposure to the AF in the experimental GS and to search for potential biomarkers of intestinal inflammation by measuring microRNAs. Methods Rat fetuses were divided into three groups: a) CONTROL, b) GS reared on day 18 (GS = 18), and c) GS reared on day 19.5 (GS = 19) (term = 22 days). On day 21.5, the fetuses were removed for biometric parameters and biochemical analyses: 1) Biometrics: Body and Intestinal Weight (BW, IW), and intestinal-body weight ratio (IW/BW); 2) Descriptive histopathology and 3) miR-143 quantification by real-time Polymerase Chain Reaction (PCR). Results BW was higher in CONTROL than GS 18 and G19 (p < 0.05). IW, IW/BW, intestinal water, and mRNA-143 were higher in GS 18 and GS 19 than in CONTROL, and GS 18 was higher than GS 19 (p < 0.05). The average of the inflammation score from the intestinal wall with mucosal inflammation and intra-epithelial lymphocytes shows worst in GS 18 and GS 19 vs. CONTROL (p < 0.05). Conclusions The tissue expression of mRNA-143 and the morphological changes in the intestine of GS worsened according to the time of exposure to AF, which could be a possible marker of fetal intestinal damage.
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From 2016 to 2019, the largest outbreak caused by the Yellow Fever virus (YFV) in the 21st century in the Americas occurred in southeastern Brazil. A sylvatic cycle of transmission was reported near densely populated areas, such as the large metropolitan area of the city of São Paulo. Here, we describe the origin, spread, and movement of the YFV throughout the state of São Paulo. Whole-genome sequences were obtained from tissues of two patients who died due to severe yellow fever, during 2018-2019. Molecular analysis indicated that all analyzed tissues were positive for YFV RNA, with the liver being the organ with the highest amount of viral RNA. Sequence analysis indicates that genomes belonged to the South American genotype I and were grouped in the epidemic clade II, which includes sequences from the states of Goiás, Minas Gerais, and São Paulo of previous years. The analysis of viral dispersion indicates that the outbreak originated in Goiás at the end of 2014 and reached the state of São Paulo through the state of Minas Gerais after 2016. When the virus reached near the urban area, it spread towards both the east and south regions of the state, not establishing an urban transmission cycle in the metropolitan region of São Paulo. The virus that moved towards the east met with YFV coming from the south of the state of Rio de Janeiro, and the YFV that was carried to the south reached the Brazilian states located in the south region of the country.
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Febre Amarela , Vírus da Febre Amarela , Brasil/epidemiologia , Surtos de Doenças , Humanos , Filogeografia , RNA Viral/genética , Vírus da Febre Amarela/genéticaRESUMO
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.
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COVID-19 , Citocinas , Humanos , Pulmão/patologia , SARS-CoV-2RESUMO
BACKGROUND: Reliable mortality data are essential for the development of public health policies. In Brazil, although there is a well-consolidated universal system for mortality data, the quality of information on causes of death (CoD) is not even among Brazilian regions, with a high proportion of ill-defined CoD. Verbal autopsy (VA) is an alternative to improve mortality data. This study aimed to evaluate the performance of an adapted and reduced version of VA in identifying the underlying causes of non-forensic deaths, in São Paulo, Brazil. This is the first time that a version of the questionnaire has been validated considering the autopsy as the gold standard. METHODS: The performance of a physician-certified verbal autopsy (PCVA) was evaluated considering conventional autopsy (macroscopy plus microscopy) as gold standard, based on a sample of 2060 decedents that were sent to the Post-Mortem Verification Service (SVOC-USP). All CoD, from the underlying to the immediate, were listed by both parties, and ICD-10 attributed by a senior coder. For each cause, sensitivity and chance corrected concordance (CCC) were computed considering first the underlying causes attributed by the pathologist and PCVA, and then any CoD listed in the death certificate given by PCVA. Cause specific mortality fraction accuracy (CSMF-accuracy) and chance corrected CSMF-accuracy were computed to evaluate the PCVA performance at the populational level. RESULTS: There was substantial variability of the sensitivities and CCC across the causes. Well-known chronic diseases with accurate diagnoses that had been informed by physicians to family members, such as various cancers, had sensitivities above 40% or 50%. However, PCVA was not effective in attributing Pneumonia, Cardiomyopathy and Leukemia/Lymphoma as underlying CoD. At populational level, the PCVA estimated cause specific mortality fractions (CSMF) may be considered close to the fractions pointed by the gold standard. The CSMF-accuracy was 0.81 and the chance corrected CSMF-accuracy was 0.49. CONCLUSIONS: The PCVA was efficient in attributing some causes individually and proved effective in estimating the CSMF, which indicates that the method is useful to establish public health priorities.
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Médicos , Adulto , Autopsia/métodos , Brasil , Causas de Morte , Humanos , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To investigate Incidental Thyroid Carcinoma (ITC) by comparing the results of Fine Needle Aspiration Biopsy (FNAB) cytology and the postoperative pathological findings. METHODS: Data of 1479 patients who underwent total thyroidectomy were retrieved. Three hundred eighty-six patients were excluded due to insufficient data. Each surgical specimen studied received two histopathological diagnoses: the local diagnosis â for the same area in which the FNAB was performed; and the final diagnosis, which includes a study of the entire surgical specimen. RESULTS: A thousand and ninety-three patients were investigated. FNAB result was malignant in 187 patients, benign in 204, suspicious or indeterminate in 668 cases, and inconclusive in 34 cases. The prevalence of ITC was 15.1%. Most of the ITC in this series was less than 0.5 cm. The incidence of ITC was higher in Bethesda III (17.5% ITC) and IV (19% ITC) than in Bethesda II cases (1.5% false negatives and 9% ITC). CONCLUSION: Although the incidence of false-negative results in Bethesda II nodules is only 1.5%, 9% of these patients had ITC in the thyroid parenchyma outside the nodule that underwent preoperative FNAB. The incidence of ITC in the same scenario was even higher in Bethesda III (17.5%) and Bethesda IV cases (19%). Ultrasonography-guided FNAB is an excellent method for the assessment of thyroid nodules. However, biopsy sites should be carefully selected. Despite the high incidence of incidentalomas, total thyroidectomy should not always be the treatment of choice due to its rare but potentially serious complications. The findings of the present study can assist future clinical decisions towards active surveillance strategies for the management of papillary thyroid carcinoma.
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Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Biópsia por Agulha Fina/métodos , Humanos , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/cirurgia , Nódulo da Glândula Tireoide/epidemiologia , Nódulo da Glândula Tireoide/cirurgia , TireoidectomiaRESUMO
Background Inflammation of the perivascular adipose tissue (PvAT) may be related to atherosclerosis; however, the association of polarized macrophages in the pericoronary PvAT with measurements of atherosclerosis components in humans has not been fully investigated. Methods and Results Coronary arteries were dissected with surrounding PvAT. We evaluated the percentage of arterial obstruction, intima-media thickness, fibrous cap thickness, plaque components, and the number of vasa vasorum. The number of proinflammatory (M1) and anti-inflammatory (M2) macrophages in the periplaque and control PvAT were evaluated using immunohistochemistry. Regression models adjusted for sociodemographic and clinical variables were used. In 319 segments from 82 individuals, we found a correlation of the M1/M2 macrophage density ratio with an increase in arterial obstruction (P=0.02) and lipid content (P=0.01), and a decrease in smooth muscle cells (P=0.02). M1 and the ratio of M1/M2 macrophages were associated with an increased risk of thrombosis (P=0.03). In plaques with thrombosis, M1 macrophages were correlated with a decrease in fibrous cap thickness (P=0.006), an increase in lipid content (P=0.008), and the number of vasa vasorum in the adventitia layer (P=0.001). M2 macrophages were correlated with increased arterial obstruction (P=0.01), calcification (P=0.02), necrosis (P=0.03) only in plaques without thrombosis, and decrease of the number of vasa vasorum in plaques with thrombosis (P=0.003). Conclusions M1 macrophages in the periplaque PvAT were associated with a higher risk of coronary thrombosis and were correlated with histological components of plaque progression and destabilization. M2 macrophages were correlated with plaque size, calcification, necrotic content, and a decrease in the number of vasa vasorum in the adventitia layer.
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Aterosclerose , Calcinose , Doença da Artéria Coronariana , Placa Aterosclerótica , Trombose , Tecido Adiposo/patologia , Aterosclerose/patologia , Calcinose/patologia , Espessura Intima-Media Carotídea , Doença da Artéria Coronariana/patologia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Humanos , Lipídeos , Macrófagos/patologia , Placa Aterosclerótica/patologia , Trombose/patologiaRESUMO
Emerging variants of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) may have an impact on the virus's transmissibility and pathogenicity and an increased risk of reinfection. Antimicrobial photodynamic therapy (aPDT) is a promising technique to decontaminate the oral cavity to minimize and inactivate microorganisms' load. This article reports through a case series, a proposal for efficient oral decontamination for hospitalized patients with COVID 19 using aPDT. Samples of oral tissues were obtained after aPDT and analyzed using two methods of RT-qPCR to elucidate qualitative and quantitative viral profiles of SARS-CoV-2 RNA in the oral cavity. There was a reduction of viral load in the oral cavity immediately or one hour after the use of aPDT. This method could be a good option to decontaminate the oral cavity to minimize and inactivate microorganism load.