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SARS-CoV-2 infection is clinically heterogeneous, ranging from asymptomatic to deadly. A few patients with COVID-19 appear to recover from acute viral infection but nevertheless progress in their disease and eventually die, despite persistent negativity at molecular tests for SARS-CoV-2 RNA. Here, we performed post-mortem analyses in 27 consecutive patients who had apparently recovered from COVID-19 but had progressively worsened in their clinical conditions despite repeated viral negativity in nasopharyngeal swabs or bronchioalveolar lavage for 11-300 consecutive days (average: 105.5 days). Three of these patients remained PCR-negative for over 9 months. Post-mortem analysis revealed evidence of diffuse or focal interstitial pneumonia in 23/27 (81%) patients, accompanied by extensive fibrotic substitution in 13 cases (47%). Despite apparent virological remission, lung pathology was similar to that observed in acute COVID-19 individuals, including micro- and macro-vascular thrombosis (67% of cases), vasculitis (24%), squamous metaplasia of the respiratory epithelium (30%), frequent cytological abnormalities and syncytia (67%), and the presence of dysmorphic features in the bronchial cartilage (44%). Consistent with molecular test negativity, SARS-CoV-2 antigens were not detected in the respiratory epithelium. In contrast, antibodies against both spike and nucleocapsid revealed the frequent (70%) infection of bronchial cartilage chondrocytes and para-bronchial gland epithelial cells. In a few patients (19%), we also detected positivity in vascular pericytes and endothelial cells. Quantitative RT-PCR amplification in tissue lysates confirmed the presence of viral RNA. Together, these findings indicate that SARS-CoV-2 infection can persist significantly longer than suggested by standard PCR-negative tests, with specific infection of specific cell types in the lung. Whether these persistently infected cells also play a pathogenic role in long COVID remains to be addressed. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
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COVID-19 , Humanos , SARS-CoV-2 , RNA Viral/genética , Células Endoteliais , Síndrome de COVID-19 Pós-AgudaRESUMO
Cardiac sarcomas are rare and aggressive tumors that could have a multiorgan involvement and unfavorable prognosis. We present an extremely rare situation of cardiac sarcoma in a fragile elderly patient with a dramatic presentation of cardiogenic shock.
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Infarto do Miocárdio , Sarcoma , Idoso , Ventrículos do Coração/patologia , Humanos , Infarto do Miocárdio/patologia , Prognóstico , Sarcoma/complicações , Sarcoma/diagnóstico , Sarcoma/cirurgia , Choque Cardiogênico/etiologiaRESUMO
INTRODUCTION: Fetal endoscopic tracheal occlusion in congenital diaphragmatic hernia (CDH) may reduce pulmonary hypertension and ameliorate postnatal cardiac output. The effects of sustained early (ETO) and late (LTO) tracheal occlusion on left ventricular (LV) cells in the lamb model have not been described. MATERIALS AND METHODS: CDH was created in lambs at 70 days' gestation (term = 145 days). ETO (85 days) or LTO (105 days) was sustained till term. After cesarean section (140 days) fetuses were euthanized and hearts harvested. LV myocardial cells were studied by histological and immunofluorescence (TGF-beta 1, endothelin-1) assays in CDH, ETO, LTO, and the control group (two subjects per group). Small intramyocardial arteries were evaluated by traditional histology. RESULTS: LV myocardial histology in CDH and LTO was similar. ETO-induced LV myocardial cell enlargement and increased endothelin-1 and TGF-beta 1 staining; a weaker immunofluorescence signal was observed in LTO compared with ETO. Myocardial vascular wall thickness was greater in CDH than in controls. ETO was associated with a vascular wall thickness within the range of controls. CONCLUSION: With only two fetuses in each group, only an explorative evaluation was possible. The time point at which TO is performed seems to have an effect on cardiac morphology. Functional studies as well as confirmation in clinical samples are mandatory.
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Fetoscopia , Ventrículos do Coração/patologia , Hérnias Diafragmáticas Congênitas/cirurgia , Miocárdio/patologia , Traqueia/cirurgia , Animais , Hérnias Diafragmáticas Congênitas/fisiopatologia , Projetos Piloto , OvinosRESUMO
OBJECTIVE: Despite growing evidence about myocardial injury in hospitalized COronaVIrus Disease 2019 (COVID-19) patients, the mechanism behind this injury is only poorly understood and little is known about its association with SARS-CoV-2-mediated myocarditis. Furthermore, definite evidence of the presence and role of SARS-CoV-2 in cardiomyocytes in the clinical scenario is still lacking. METHODS: We histologically characterized myocardial tissue of 40 patients deceased with severe SARS-CoV-2 infection during the first wave of the pandemic. Clinical data were also recorded and analyzed. In case of findings supportive of myocardial inflammation, histological analysis was complemented by RT-PCR and immunohistochemistry for SARS-CoV-2 viral antigens and in situ RNA hybridization for the detection of viral genomes. RESULTS: Both chronic and acute myocardial damage was invariably present, correlating with the age and comorbidities of our population. Myocarditis of overt entity was found in one case (2.5%). SARS-CoV-2 genome was not found in the cardiomyocytes of the patient with myocarditis, while it was focally and negligibly present in cardiomyocytes of patients with known viral persistence in the lungs and no signs of myocardial inflammation. The presence of myocardial injury was not associated with myocardial inflammatory infiltrates. CONCLUSIONS: In this autopsy cohort of COVID-19 patients, myocarditis is rarely found and not associated with SARS-CoV-2 presence in cardiomyocytes. Chronic and acute forms of myocardial damage are constantly found and correlate with the severity of COVID-19 disease and pre-existing comorbidities.
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COVID-19/complicações , Inflamação/virologia , Miocardite/virologia , Miocárdio/patologia , Idoso , Idoso de 80 Anos ou mais , Autopsia , Estudos de Coortes , Feminino , Humanos , Inflamação/epidemiologia , Masculino , Miocardite/epidemiologia , Miócitos Cardíacos/virologia , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de DoençaRESUMO
BACKGROUND: COVID-19 is a deadly pulmonary disease with peculiar characteristics, which include variable clinical course and thrombophilia. A thorough understanding of the pathological correlates of the disease is still missing. METHODS: Here we report the systematic analysis of 41 consecutive post-mortem samples from individuals who died of COVID-19. Histological analysis is complemented by immunohistochemistry for cellular and viral antigens and the detection of viral genomes by in situ RNA hybridization. FINDINGS: COVID-19 is characterized by extensive alveolar damage (41/41 of patients) and thrombosis of the lung micro- and macro-vasculature (29/41, 71%). Thrombi were in different stages of organization, consistent with their local origin. Pneumocytes and endothelial cells contained viral RNA even at the later stages of the disease. An additional feature was the common presence of a large number of dysmorphic pneumocytes, often forming syncytial elements (36/41, 87%). Despite occasional detection of virus-positive cells, no overt signs of viral infection were detected in other organs, which showed non-specific alterations. INTERPRETATION: COVID-19 is a unique disease characterized by extensive lung thrombosis, long-term persistence of viral RNA in pneumocytes and endothelial cells, along with the presence of infected cell syncytia. Several of COVID-19 features might be consequent to the persistence of virus-infected cells for the duration of the disease. FUNDING: This work was supported by a King's Together Rapid COVID-19 Call grant from King's College London. MG is supported by the European Research Council (ERC) Advanced Grant 787971 "CuRE" and by Programme Grant RG/19/11/34633 from the British Heart Foundation.
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Betacoronavirus/genética , Infecções por Coronavirus/patologia , Pneumonia Viral/patologia , RNA Viral/metabolismo , Trombose/etiologia , Idoso , Idoso de 80 Anos ou mais , Células Epiteliais Alveolares/citologia , Células Epiteliais Alveolares/virologia , Autopsia , Betacoronavirus/isolamento & purificação , COVID-19 , Infecções por Coronavirus/complicações , Infecções por Coronavirus/virologia , Cuidados Críticos , Células Endoteliais/virologia , Feminino , Células Gigantes/citologia , Células Gigantes/virologia , Humanos , Pulmão/patologia , Pulmão/virologia , Masculino , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/virologia , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/metabolismoRESUMO
AIM: We examined evidence on infective and non-infective endocarditis obtained from a database of 50,403 clinical autopsies performed at an Italian general hospital between January 1983 and December 2006. MATERIALS AND METHODS: Out of 814 endocarditis cases, 409 were of infective endocarditis (IE) and 405 non-infective (NIE). The median age at the time of death was 78 years for those with IE and 83 for those with NIE. Data were collected on gender, clinical history, comorbidities, kind of affected valve (non-prosthetic/mechanical/biological), pathological features of endocarditis, endocarditis complications and microbiological agents. RESULTS: The diagnosis of IE was frequently missed and these conditions were often complicated by cardiovascular events. IE was more common among patients with prior valve infection or cardiovascular surgery, while malignancies were frequent comorbidities of NIE. CONCLUSION: In general, we found several data that differ from those generally present in the scientific literature, and this could be explained by the fact that data on IE and NIE are generally obtained from surgical and clinical databases, while we analysed only autoptic cases.
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Endocardite/diagnóstico , Endocardite/etiologia , Idoso , Idoso de 80 Anos ou mais , Autopsia , Diagnóstico Diferencial , Endocardite Bacteriana/diagnóstico , Endocardite não Infecciosa/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Cardiac remodeling after acute myocardial infarction (AMI) is characterized by molecular and cellular mechanisms involving both the left (LV) and right ventricular (RV) walls. Cardiomyoycte apoptosis in the peri-infarct and remote LV myocardium has a central role in cardiac remodeling. Whether apoptosis also occurs in the right ventricle of patients with ischemic heart disease has not been investigated. The aim of the present study was to investigate the presence of cardiomyocyte apoptosis in the right ventricle in patients with AMI. We assessed the number of apoptotic cardiomyocytes using multiple samplings in the LV and RV walls of 12 patients selected at autopsy who died 4 to 42 days after AMI. Five patients without cardiac disease were also selected at autopsy as controls. Apoptotic rates were calculated from the number of cardiomyocytes showing double positive staining for in situ end-labeling of DNA fragmentation (TUNEL) and for activated caspase-3. Potentially false-positive results (DNA synthesis and RNA splicing) were excluded from cell counts. The apoptotic rate in the right ventricle in patients with AMI was significantly higher than in control hearts (median 0.8%, interquartile range 0.3 to 1.0 vs median 0.01%, interquartile range 0.01 to 0.03, p <0.001). RV apoptosis significantly correlated with such parameters of global adverse remodeling as cardiac diameter to LV free wall thickness (R = +0.57, p = 0.050). RV apoptosis was significantly higher in five cases (42%) with infarct involving the ventricular septum and an adjacent small area of the RV walls (median 1.0%, interquartile range 0.8 to 2.2 vs median 0.5%, interquartile range 0.2 to 1.0, p = 0.048, p <0.001 vs controls). The association between apoptotic rate in the right ventricle and cardiac remodeling was apparent even after exclusion of cases with RV AMI involvement (R = +0.82, p = 0.023 for diameter to LV wall thickness ratio and R = -0.91, p = 0.002 for RV free wall thickness). In conclusion, patients with cardiac remodeling after AMI had a significant increase in RV apoptosis even when ischemic involvement of the RV wall was not apparent.
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Apoptose , Ventrículos do Coração/patologia , Infarto do Miocárdio/patologia , Miócitos Cardíacos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Septos Cardíacos/patologia , Humanos , Marcação In Situ das Extremidades Cortadas , Masculino , Pessoa de Meia-Idade , Remodelação VentricularRESUMO
Heart failure is a complex syndrome characterized by impaired emptying and/or impaired filling of the heart chambers. The use of parameters of diastolic function has provided novel tools for risk stratification and management of patients with heart failure. This study evaluated the potential correlation between apoptosis at time of death and left ventricular (LV) diastolic function after acute myocardial infarction. We selected, at routine postmortem examination, 14 subjects who died 10 to 62 days after an acute myocardial infarction and had an available echocardiographic report from the most recent hospital admission. The apoptotic rate was calculated at the region bordering the infarct, using co-localization of in situ end-labeling for deoxyribonucleic acid fragmentation and immunohistochemistry for caspase-3. Transthoracic echocardiographic studies were retrospectively reevaluated and pulse-wave Doppler spectra of mitral inflow were analyzed. LV diastolic function was assessed by measuring the ratio of E peak velocity to A peak velocity and E-wave deceleration time; a ratio of E peak velocity to A peak velocity >or=2 and deceleration time <115 ms were considered a restrictive filling pattern. A restrictive pattern was found in 4 cases (29%). All subjects with a restrictive pattern were symptomatic for New York Heart Association class IV heart failure (100% vs 20%, p = 0.015) and had larger transverse heart diameters at pathology (p = 0.014). The apoptotic rate in the peri-infarct region was significantly higher in patients with a restrictive versus nonrestrictive diastolic pattern (13%, 10 to 14, vs 3%, 1 to 6, p = 0.014). At multivariable analysis that included the restrictive pattern, class IV heart failure, and cardiac diameters, the restrictive pattern remained an independent predictor of increased apoptosis (p = 0.030). In conclusion, patients with severe postinfarction LV diastolic dysfunction had significantly higher rates of cardiomyocyte loss by apoptosis, which may partly explain their unfavorable outcome.
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Apoptose , Ecocardiografia Doppler , Ventrículos do Coração/patologia , Contração Miocárdica/fisiologia , Infarto do Miocárdio , Função Ventricular Esquerda/fisiologia , Idoso , Idoso de 80 Anos ou mais , Diástole , Feminino , Seguimentos , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Myocardial apoptosis persists beyond the acute phases of acute myocardial infarction (AMI) and is associated with left ventricular (LV) remodeling. Infarct-related artery (IRA) patency is considered a favorable prognostic factor after AMI and may be associated with more favorable LV remodeling because of reduced apoptosis at the site of AMI. The aim of this study was to assess the influence of IRA status on apoptotic rate (AR) in the hearts of subjects dying late after AMI. METHODS AND RESULTS: We used colocalization for in situ end-labeling of DNA fragmentation and immunohistochemistry for caspase-3 to calculate the AR at time of death (12 to 62 days after AMI) in 16 hearts with persistently occluded IRAs and in 8 hearts with patent IRAs. No significant differences were found when comparing the clinical characteristics of the 2 groups. Occluded IRA was associated with significantly higher AR at site of infarction (25.8% [interquartile range 20.9% to 28.5%] versus 2.3% [interquartile range 0.6% to 5.0%], P<0.001). This strong correlation between IRA occlusion and AR remained statistically significant even after correction for clinical characteristics such as sex, age, history of previous additional AMI or heart failure, transmural AMI, anterior AMI, fibrinolytic treatment, time from AMI to death, trauma as cause of death, and multivessel coronary disease (P=0.003). CONCLUSIONS: A significantly higher AR was associated with persistent IRA occlusion late post-AMI. These data may suggest that the post-AMI benefits observed with a patent IRA (the "open-artery hypothesis") may in part be due to reduced myocardial apoptosis.
Assuntos
Apoptose , Doença das Coronárias/patologia , Vasos Coronários/patologia , Infarto do Miocárdio/patologia , Miocárdio/patologia , Grau de Desobstrução Vascular , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Caspase 3 , Caspases/biossíntese , Doença das Coronárias/complicações , Fragmentação do DNA , Feminino , Humanos , Marcação In Situ das Extremidades Cortadas , Masculino , Infarto do Miocárdio/complicações , Miocárdio/enzimologia , Análise de Regressão , Remodelação VentricularRESUMO
BACKGROUND: Diffuse coronary vascular inflammation is associated with acute coronary syndromes. However, it is unknown whether inflammation also occurs within the myocardium. Therefore, this study was aimed at assessing the presence of activated cells in unaffected remote myocardium of patients with acute myocardial infarction (AMI), in comparison to the peri-infarct region from the same cases, and in comparison to myocardial specimens from control hearts. METHODS AND RESULTS: Sixteen patients dying 1 to 12 weeks after AMI and 16 control subjects were selected at autopsy. Myocardial specimens were taken at remote unaffected viable regions and at peri-infarct regions in cases with AMI. Confocal microscopy was performed to measure the number of activated cells (DR+), T-lymphocytes (CD3+), and activated T-lymphocytes (CD3+/DR+). Activated cells and activated T-lymphocytes were found in remote unaffected regions in 11 of 16 cases (69%), in peri-infarct zone in all cases (100%), and in none of the control hearts (0%, P<0.001 versus others). A greater myocardial inflammatory burden in remote regions but not in peri-infarct regions was associated with persistent infarct-related artery occlusion (P<0.05). CONCLUSIONS: This study for the first time shows the presence of activated T-lymphocytes in remote unaffected myocardial regions in approximately two thirds of patients with recent AMI. Because these cells are associated with persistent infarct-related artery occlusion, our data may suggest that an antigenic stimulus present also in the myocardium triggers an immune response that may be critical to precipitate artery occlusion.
Assuntos
Infarto do Miocárdio/imunologia , Miocardite/imunologia , Idoso , Vasos Coronários/patologia , Feminino , Humanos , Masculino , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/patologia , Miocardite/patologia , Recidiva , Síndrome , Linfócitos T/imunologia , Grau de Desobstrução VascularRESUMO
OBJECTIVES: The purpose of this study was to evaluate a potential correlation between apoptotic rate (AR), post-infarction left ventricular (LV) remodeling, and clinical characteristics in subjects who died late (>or=10 days) after an acute myocardial infarction (AMI) with evidence of persistent occlusion of the infarct-related artery at autopsy. BACKGROUND: Apoptosis contributes to myocardiocyte loss in cardiac disease and may have a pathophysiologic role in post-infarction LV remodeling. METHODS: The AR was calculated at the site of infarction and in remote unaffected LV regions, using co-localization of in situ end labeling for deoxyribonucleic acid fragmentation and immunohistochemistry for caspase-3, in 14 subjects who died within two months after AMI. Correlation between AR and clinical characteristics such as age, site of AMI, transmural extension, multivessel coronary disease, and signs and/or symptoms of heart failure (HF), at the time of initial hospitalization for AMI or subsequently before death, was assessed using non-parametric statistical tests. Parameters of LV remodeling including diameters, free wall thickness, diameter-to-wall-thickness ratio, and mass were measured at gross examination at autopsy. Values are expressed as median (interquartile range). RESULTS: Among clinical variables, early symptomatic post-infarction HF (9 cases, 64%) was associated with nearly fourfold increased AR at the site of infarction (26.2% [24.5% to 28.8%] vs. 6.4% [1.9% to 13.3%], p = 0.001). Moreover, AR both at the site of infarction and in unaffected regions was significantly correlated with parameters of progressive LV remodeling (p < 0.05). CONCLUSIONS: Our data show that in patients dying >or=10 days after AMI, myocardial apoptosis is strongly associated with and may be a major determinant of unfavorable LV remodeling and early symptomatic post-infarction HF.
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Apoptose/fisiologia , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/patologia , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/patologia , Remodelação Ventricular/fisiologia , Idoso , Autopsia , Técnicas de Cultura , Feminino , Humanos , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Modelos Logísticos , Masculino , Células Musculares/patologia , Probabilidade , Fatores de Risco , Sensibilidade e Especificidade , Estatísticas não Paramétricas , Fatores de TempoRESUMO
BACKGROUND: Physiopathology of barochemoreception is hindered by the scarce information on its morphology in disease. The baroreflex is of major importance for the maintenance of arterial pressure during orthostatic stress. The purpose of this paper was to characterize the morphological alterations of carotid glomus in old patients who died from stroke and suffering obstructive carotid atheromatosis. METHODS: Bilateral carotid segments were obtained at autopsy from 17 patients (51-89 years old). Specimens were stained with hematoxylin and eosin; Azan trichrome, Grimelius silver stain for catecholamine detection, and were immunophenotyped for CD34 and S-100. Similar segments of both carotid arteries of six patients (62-77 years old) who died by accidents were used as controls. RESULTS: The carotid glomus of patients who died from stroke presented atrophy and fibrosis (2.59+/-0.5 vs. 1.17+/-0.39 in the control group; p<0.0001). There was a loss of chief cells and of the argyrophilic staining granules. A focal diminution of glomus vascularization was observed in the areas of atrophy and fibrosis (2.73+/-0.45 vs. 1.5+/-0.52 in the control group; p<0.0001). The arterioles to glomus showed severe fibrointimal proliferation, disruption of internal elastic lamina and luminal narrowing, and luminal thrombi. CONCLUSION: A severe carotid glomic damage does exist in old patients who died from stroke and suffering from carotid atheromatosis, independent from aging, of note, a "culprit" marked narrowing of the corresponding arterioles was observed.
Assuntos
Barorreflexo/fisiologia , Artéria Carótida Interna/fisiopatologia , Acidente Vascular Cerebral/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Arteríolas/patologia , Artéria Carótida Externa/patologia , Artéria Carótida Interna/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/patologiaRESUMO
We report hypoxia-inducible factor-1 (HIF-1) expression in myocardium of patients with recent acute myocardial infarction (AMI), supporting the hypothesis of HIF-1 as a possible mediator of response to ischemia. A potential diagnostic role of determining tissue expression of HIF-1 as a marker of ischemia, and potential therapeutic implications by trying to modulate HIF-1 activity in order to promote beneficial effects of HIF-1 related genes (e.g. expression of vascular endothelial growth factor (VEGF)) may derive.
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Proteínas de Ligação a DNA/biossíntese , Expressão Gênica/fisiologia , Infarto do Miocárdio/metabolismo , Miocárdio/metabolismo , Proteínas Nucleares/biossíntese , Fatores de Transcrição/biossíntese , Idoso , Animais , Cadáver , Modelos Animais de Doenças , Feminino , Humanos , Fator 1 Induzível por Hipóxia , Subunidade alfa do Fator 1 Induzível por Hipóxia , Masculino , Infarto do Miocárdio/patologia , Miocárdio/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Ratos , Ratos Sprague-Dawley , Fatores de TempoRESUMO
In recent years, the diagnosis and management of leptomeningeal carcinomatosis have gained increased attention as patients with neoplasms live longer and the condition becomes more common. Conclusive hallmarks of this disease have yet to be identified. We report and discuss a case of massive invasion of the cerebral leptomeninges by neoplastic cells from a malignant melanoma in a shoulder. Symptoms of cerebral dysfunction were the first indication of neoplasm. The onset of symptoms, magnetic resonance imaging, and patient death all occurred within a brief time span. To our knowledge, this is the first case of meningeal melanomatosis in a patient not treated with chemotherapeutic drugs in which the radiologic evidence is virtually synchronous with direct anatomic observation. Thus the images provided with this report may be of use in the radiographic diagnosis of cerebrospinal metastatic colonization.
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Melanoma/secundário , Neoplasias Meníngeas/secundário , Neoplasias Cutâneas/patologia , Córtex Cerebral/fisiopatologia , Evolução Fatal , Humanos , Imageamento por Ressonância Magnética , Masculino , Melanoma/complicações , Neoplasias Meníngeas/complicações , Pessoa de Meia-Idade , Paresia/etiologia , Neoplasias Cutâneas/complicaçõesRESUMO
BACKGROUND: Multivessel coronary disease after myocardial infarction is a major risk factor for unfavorable cardiac remodeling and death due to pump failure, but underlying pathophysiologic mechanisms are still uncompletely established. Post-infarction myocardial apoptosis has been recently implicated as a cause of ongoing cell loss leading to cardiac failure. Our aim was to assess the role of post-infarction myocardial apoptosis and pro-apoptotic factor expression in the non-infarcted remote myocardium of subjects with multivessel coronary disease. METHODS: Twenty-one males dying after recent myocardial infarction with permanent occlusion of the infarct-related artery were selected at autopsy. Apoptosis was assessed at viable myocardial regions remote from infarction by co-staining for in situ end-labeling of DNA fragmentation and cleaved caspase-3. Expression of pro-apoptotic factor bax and hypoxia-induced factor-1alpha was evaluated by immunohistochemistry. RESULTS: Subjects with multivessel disease (N=11) showed a significantly two-fold higher myocardial apoptosis in comparison to subjects with single vessel disease (N=10) (0.9% vs. 0.5%, p=0.013). Similarly, myocardial bax expression was increased in patients with multivessel disease (3.0% vs. 1.4%, p=0.029). Stratification for the number of diseased coronary vessels confirmed the association between extent of coronary disease and apoptotic rates (p=0.022). Even in subjects dying over 30 days after infarction multivessel disease remained predictive of enhanced myocardiocyte apoptosis at remote regions (p=0.033). CONCLUSIONS: Post-infarction myocardial apoptosis and bax expression in remote left ventricular regions are significantly increased in male patients with multivessel coronary disease in comparison to those with isolated infarct-related artery occlusion. These findings suggest that apoptotic cell loss in the viable non-infarcted myocardium, possibly due ongoing ischemia, may play a relevant role in the unfavorable clinical course typical of multivessel disease after myocardial infarction.
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Apoptose , Doença das Coronárias/patologia , Vasos Coronários/patologia , Infarto do Miocárdio/patologia , Autopsia , Humanos , Imuno-Histoquímica , Masculino , Infarto do Miocárdio/mortalidade , Remodelação VentricularRESUMO
Adrenal cortical carcinoma (ACC), a rare and highly malignant neoplasm of the cortical tract of the adrenal gland, is usually diagnosed at an advanced stage of development and often when metastatic spread already has begun. We report a very rare case of low-stage, non-metastasized ACC, the first clinical appearance of which was a large retroperitoneal hemorrhage caused by the rupture of the neoplastic mass. To the best of our knowledge, this is the third reported case of ACC rupture.
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Neoplasias do Córtex Suprarrenal/complicações , Neoplasias do Córtex Suprarrenal/patologia , Carcinoma Adrenocortical/complicações , Carcinoma Adrenocortical/patologia , Hemorragia/etiologia , Espaço Retroperitoneal , Neoplasias do Córtex Suprarrenal/metabolismo , Carcinoma Adrenocortical/metabolismo , Adulto , Feminino , Humanos , Imuno-Histoquímica , Estadiamento de NeoplasiasRESUMO
BACKGROUND: Autopsy studies report a frequency of myocarditis ranging from 0.11 to 5.5% in the general population, reaching almost 50% in selected groups. Myocarditis is often undiagnosed and the incidence of fatal course myocarditis has never been evaluated. The aim of our study was to assess the frequency of fatal course myocarditis in a consecutive series of autopsies and to describe the clinical, histological and morphologic features of the disease. METHODS: From January 1, 1995 to January 31, 1996, 2560 autopsies were performed, and 143 cases of active myocarditis were diagnosed (5.6%). RESULTS: In 39 cases (1.5%; 12 males; 4/39 aged < or = 35 years) active myocarditis was identified as the final cause of death. Only in 1 case was myocarditis suspected ante-mortem. The histological pattern was lymphocytic in 64% of cases. A mixed inflammatory infiltration was found in 33% and a granulomatous infiltration in 3%. In 49% of cases myocarditis was localized in both ventricles and the interventricular septum. The clinical presentation of myocarditis was heart failure in 18/39 patients (46%), cardiac arrest in 4/39 patients (10%) and syncope and chest pain in 1/39 patient (3%). The mean creatine phosphokinase levels were 890 +/- 2742 IU/I (assessed in 11/39 patients, 28%) but they were increased only in 7/39 (18%). ECG (performed in 29/39 patients, 74%) showed sinus rhythm in 16/39 patients (55%, > 100 b/min in 41%), atrioventricular or interventricular conduction defects in 10/39 patients (34%) and a pathological Q wave in 4/39 patients (14%). At echocardiography (performed in 7/39 patients, 18%), right and/or left ventricular dysfunction was found to be present in 5 cases (71%) and a pericardial effusion in 4 cases (57%). CONCLUSIONS: Myocarditis is underdiagnosed ante-mortem. A high index of clinical suspicion is mandatory for prompt diagnosis and treatment of this fatal disease seen also in the young.
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Causas de Morte , Miocardite/mortalidade , Miocardite/patologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Autopsia , Biópsia por Agulha , Estudos de Coortes , Feminino , Humanos , Imuno-Histoquímica , Incidência , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Distribuição por SexoRESUMO
Dilated cardiomyopathy (DCM), a heart muscle disease characterized by ventricular dilation and dysfunction, is a leading cause of mortality and morbidity. In the present paper we will consider the main results of studies on the natural history of DCM in 581 consecutive patients prospectively enrolled and systematically followed in the Heart Muscle Disease Registry of Trieste in the last 25 years. In the last decades prognosis of DCM significantly improved over time, mainly as a consequence of optimized treatment with ACE-inhibitors and beta-blockers. However, a strong heterogeneity of prognosis was observed among patients both in familial and sporadic cases. Early diagnosis and treatment allowed to recognize two distinct subgroups, one with a rapidly progressive downhill course, high mortality and urgent indication to heart transplantation, another with a more favorable outcome. Long-term optimized treatment with ACE-inhibitors (in 90% of cases) and beta-blockers (in 87% of cases) was associated with a remarkable clinical improvement in 50% of patients and apparent "healing" in 16% of cases. A systematic and accurate echocardiographic follow-up showed in these cases a significant improvement of the left ventricular ejection fraction (LVEF) with "reverse remodeling", frequently associated with a decrease of severity of functional mitral regurgitation and regression of the restrictive filling pattern. The response to optimal treatment showed a strong relation to long-term outcome. The 8-year transplant-free survival, starting from the evaluation at 2 years, was 31% in patients with persistent NYHA class III-IV, 64% in NYHA class I-II and LVEF < or = 40%, 83% in NYHA class I-II and LVEF > 40% and 94% in patients with apparent "healing" (p < 0.0001). Long-term follow-up showed a significant clinical progression of the disease in 33% of cases, independently of the initial clinical response to treatment. Predictive factors of a favorable response to beta-blocker treatment associated with ACE-inhibitors were a history of mild hypertension, an early diagnosis and treatment and the presence of sinus tachycardia. The risk of sudden death was increased particularly in patients with long-term persistent or progressive left ventricular dilation and dysfunction. A rigorous pharmacological approach (optimization of beta-blockers, withdrawal or decrease of dosage of digitalis), and selective non-pharmacological strategy (automated implantable cardioverter-defibrillators for primary prevention in high-risk patients) are potentially effective to decrease the incidence of sudden death during long-term follow-up. In conclusion, the Heart Muscle Disease Registry of Trieste gave us in the last 25 years new insights into the natural history of DCM, underlying the importance of a rigorous and systematic approach both at clinical presentation and during long-term follow-up on optimized medical treatment.
Assuntos
Cardiomiopatia Dilatada , Arritmias Cardíacas/etiologia , Cardiomiopatia Dilatada/complicações , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/tratamento farmacológico , Cardiomiopatia Dilatada/mortalidade , Cardiomiopatia Dilatada/fisiopatologia , Morte Súbita Cardíaca/etiologia , Humanos , Itália , Prognóstico , Sistema de Registros , Taxa de Sobrevida , Fatores de Tempo , Função Ventricular EsquerdaRESUMO
Dilated cardiomyopathy (DCM), a heart muscle disease characterized by ventricular dilation and dysfunction, is a leading cause of mortality and morbidity. In the present paper we will consider the main results of studies on the natural history of DCM in 581 consecutive patients prospectively enrolled and systematically followed in the Heart Muscle Disease Registry of Trieste in the last 25 years. In the last decades prognosis of DCM significantly improved over time, mainly as a consequence of optimized treatment with ACE-inhibitors and beta-blockers. However, a strong heterogeneity of prognosis was observed among patients both in familial and sporadic cases. Early diagnosis and treatment allowed to recognize two distinct subgroups, one with a rapidly progressive downhill course, high mortality and urgent indication to heart transplantation, another with a more favorable outcome. Long-term optimized treatment with ACE-inhibitors (in 90% of cases) and beta-blockers (in 87% of cases) was associated with a remarkable clinical improvement in 50% of patients and apparent "healing" in 16% of cases. A systematic and accurate echocardiographic follow-up showed in these cases a significant improvement of the left ventricular ejection fraction (LVEF) with "reverse remodeling", frequently associated with a decrease of severity of functional mitral regurgitation and regression of the restrictive filling pattern. The response to optimal treatment showed a strong relation to long-term outcome. The 8-year transplant-free survival, starting from the evaluation at 2 years, was 31% in patients with persistent NYHA class III-IV, 64% in NYHA class I-II and LVEF < or = 40%, 83% in NYHA class I-II and LVEF > 40% and 94% in patients with apparent "healing" (p < 0.0001). Long-term follow-up showed a significant clinical progression of the disease in 33% of cases, independently of the initial clinical response to treatment. Predictive factors of a favorable response to beta-blocker treatment associated with ACE-inhibitors were a history of mild hypertension, an early diagnosis and treatment and the presence of sinus tachycardia. The risk of sudden death was increased particularly in patients with long-term persistent or progressive left ventricular dilation and dysfunction. A rigorous pharmacological approach (optimization of beta-blockers, withdrawal or decrease of dosage of digitalis), and selective non-pharmacological strategy (automated implantable cardioverter-defibrillators for primary prevention in high-risk patients) are potentially effective to decrease the incidence of sudden death during long-term follow-up. In conclusion, the Heart Muscle Disease Registry of Trieste gave us in the last 25 years new insights into the natural history of DCM, underlying the importance of a rigorous and systematic approach both at clinical presentation and during long-term follow-up on optimized medical treatment.