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Background: Immunotherapy with immune checkpoint inhibitors (ICIs) enhances the host immune reaction against tumour cells by inhibiting intrinsic down-regulators of the T cell-mediated immune response. Although the advent of ICIs has dramatically changed oncology, ICIs may also trigger an overactivation of T cells against non-cancerous tissues, leading to off-target immune-related adverse events (irAEs). Case summary: A 64-year-old man with a history of seven courses of atezolizumab, an ICI, for small-cell lung cancer and coronavirus disease 2019 (COVID-19) was admitted to the hospital complaining of acute chest pain. Transthoracic echocardiography showed preserved ejection fraction (EF), but electrocardiography indicated precordial ST-elevations and marked increases in biomarkers for myocardial injury were observed. Emergent cardiac catheterization showed no significant coronary stenosis. On the fifth hospital day, EF decreased to 25% and pericardial effusion occurred. Endomyocardial biopsy was immediately performed, and prednisolone (60 mg/day) was administered. Troponin I level rapidly reduced, ST changed, and EF improved. Histological examinations demonstrated CD8-predominant T lymphocytic infiltration with myocardial cell injury, consistent with irAE-myocarditis. Discussion: In irAEs, myocarditis is the most common and severe cardiac manifestation with a high mortality. Even at 20 weeks after the initial ICI treatment, irAE-myocarditis occurs and the clinical presentation may mimic ST-elevation myocardial infarction. The histopathological findings suggested the high possibility of irAE-myocarditis rather than COVID-19-induced myocarditis, but COVID-19 has possibly played a role in the development of late-onset irAE-myocarditis. This educational case implies the importance of immediate recognition of irAE even after stable ICI treatment.
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The medical burden of stroke extends beyond the brain injury itself and is largely determined by chronic comorbidities that develop secondarily. We hypothesized that these comorbidities might share a common immunological cause, yet chronic effects post-stroke on systemic immunity are underexplored. Here, we identify myeloid innate immune memory as a cause of remote organ dysfunction after stroke. Single-cell sequencing revealed persistent pro-inflammatory changes in monocytes/macrophages in multiple organs up to 3 months after brain injury, notably in the heart, leading to cardiac fibrosis and dysfunction in both mice and stroke patients. IL-1ß was identified as a key driver of epigenetic changes in innate immune memory. These changes could be transplanted to naive mice, inducing cardiac dysfunction. By neutralizing post-stroke IL-1ß or blocking pro-inflammatory monocyte trafficking with a CCR2/5 inhibitor, we prevented post-stroke cardiac dysfunction. Such immune-targeted therapies could potentially prevent various IL-1ß-mediated comorbidities, offering a framework for secondary prevention immunotherapy.
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Background: Coronavirus disease 2019 (COVID-19) is predominantly known to cause respiratory injury; however, the present case series highlights four instances in which the infection resulted in significant cardiac complications. Among such cases, some represent severe cardiogenic shock, which necessitates the immediate introduction of mechanical circulatory support (MCS) for salvage. Case summary: This case series involved patients with COVID-19-associated myocardial injury leading to fulminant cardiogenic shock. These patients required immediate implementation of peripheral MCS, followed by an instant upgrade to a central MCS system due to anatomical limitations and severe biventricular dysfunction. Central MCS provided effective ventricular unloading, resulting in a significant and prompt improvement in ventricular function. The treatment timeline showed rapid deterioration followed by remarkable recovery within 2 weeks of MCS initiation, demonstrating the effectiveness of aggressive and tailored MCS strategies in managing severe COVID-19-related cardiac complications. Discussion: This study provides significant insights into the cardiovascular implications of COVID-19, particularly in the context of severe myocardial injury that leads to cardiogenic shock. The report underscores the importance of early recognition and intervention in such cases, focusing on the use of MCS as a life-saving modality. The findings also revealed unique pathological features of COVID-19-associated myocardial injury, including macrophage-predominant infiltration and microthrombosis, which are distinct from the features of conventional myocarditis. These findings highlight the need for further research on the pathophysiology of COVID-19-related cardiac injuries and the development of targeted therapeutic strategies.
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OBJECTIVE: Plaque ulceration in carotid artery stenosis is a risk factor for cerebral ischemic events; however, the characteristics that determine plaque vulnerability are not fully understood. We thus assessed the association between plaque ulceration sites and cerebrovascular ischemic attack. METHODS: We retrospectively collected the clinical data of 72 consecutive patients diagnosed with carotid artery stenosis with plaque ulcers. After excluding patients with pseudo-occlusion, a history of previous carotid endarterectomy or carotid artery stenting before the ulcer was first discovered, follow-up data of less than 1 month, or carotid endarterectomy or carotid artery stenting performed within 1 month after the ulcer was first discovered, 60 patients were ultimately included. Patients were divided into proximal and distal groups based on the ulcer location relative to the most stenotic point. The primary endpoints were ipsilateral cerebrovascular ischemic events ("ischemic events"), such as amaurosis fugax, transient ischemic attack, or ischemic stroke due to carotid artery stenosis with plaque ulceration. The association between ulcer location and ischemic events was also assessed. RESULTS: In the patients with plaque ulcer, more patients had proximal than distal plaque ulcers (39 vs 21; P = .028). The median follow-up duration was 3.8 years (interquartile range, 1.5-6.2 years). Nineteen patients (32%) experienced ischemic event. Ischemic events occurred more frequently in the distal than in the proximal group (18% vs 59%; P = .005). Kaplan-Meier curves demonstrated a significantly shorter event-free time in the distal group (log-rank P = .021). In univariate analysis, distal ulcer location was associated with ischemic events (odds ratio [OR], 2.94; 95% confidence interval [CI], 1.13-7.65; P = .03). Multivariate analysis using two different models also showed that distal ulcer location was independently associated with ischemic events (Model 1: OR, 3.85; 95% CI, 1.26-11.78; P = .03; Model 2: OR, 4.31; 95% CI, 1.49-12.49; P = .009). CONCLUSIONS: Patients with carotid artery stenosis and plaque ulcers located distal to the most stenotic point are more likely to experience cerebrovascular ischemic attacks. Therefore, carotid plaques with ulcers located distal to the most stenotic point may be a potential indication for surgical treatment.
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Pulmonary arterial hypertension (PAH) is characterized by stenosis and occlusions of small pulmonary arteries, leading to elevated pulmonary arterial pressure and right heart failure. Although accumulating evidence shows the importance of interleukin (IL)-6 in the pathogenesis of PAH, the target cells of IL-6 are poorly understood. Using mice harboring the floxed allele of gp130, a subunit of the IL-6 receptor, we found substantial Cre recombination in all hematopoietic cell lineages from the primitive hematopoietic stem cell level in SM22α-Cre mice. We also revealed that a CD4+ cell-specific gp130 deletion ameliorated the phenotype of hypoxia-induced pulmonary hypertension in mice. Disruption of IL-6 signaling via deletion of gp130 in CD4+ T cells inhibited phosphorylation of signal transducer and activator of transcription 3 (STAT3) and suppressed the hypoxia-induced increase in T helper 17 cells. To further examine the role of IL-6/gp130 signaling in more severe PH models, we developed Il6 knockout (KO) rats using the CRISPR/Cas9 system and showed that IL-6 deficiency could improve the pathophysiology in hypoxia-, monocrotaline-, and Sugen5416/hypoxia (SuHx)-induced rat PH models. Phosphorylation of STAT3 in CD4+ cells was also observed around the vascular lesions in the lungs of the SuHx rat model, but not in Il6 KO rats. Blockade of IL-6 signaling had an additive effect on conventional PAH therapeutics, such as endothelin receptor antagonist (macitentan) and soluble guanylyl cyclase stimulator (BAY41-2272). These findings suggest that IL-6/gp130 signaling in CD4+ cells plays a critical role in the pathogenesis of PAH.
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Hipertensão Pulmonar , Interleucina-6 , Animais , Camundongos , Ratos , Linfócitos T CD4-Positivos/patologia , Receptor gp130 de Citocina/genética , Hipertensão Pulmonar/genética , Hipertensão Pulmonar/patologia , Hipóxia/patologia , Interleucina-6/genética , Artéria Pulmonar/patologiaRESUMO
OBJECTIVES: Intracerebral hemorrhage (ICH) and cerebral microbleeds (CMB) in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy are more common in East Asian populations than in people of white European ancestry. We hypothesized that the ethnic difference is explained by the East Asian-specific NOTCH3 p.R75P mutation. METHODS: This retrospective observational study included 118 patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy in Japanese and Korean cohorts. We investigated whether the p.R75P mutation is associated with symptomatic ICH and multiple CMB (>5) using quasi-Poisson regression models. We predicted the NOTCH3 extracellular domain protein structures in silico and graded NOTCH3 extracellular domain immunostaining in skin vessels of some patients, with subsequent comparisons between p.R75P and other conventional mutations. RESULTS: Among 63 Japanese patients (median age 55 years; 56% men), 15 had a p.R75P mutation, significantly associated with symptomatic ICH (adjusted relative risk 9.56, 95% CI 2.45-37.31), multiple CMB (3.00, 1.34-6.71), and absence of temporopolar lesions (4.91, 2.29-10.52) after adjustment for age, sex, hypertension, and antithrombotics. In the Korean cohort (n = 55; median age 55 years; 51% men), the p.R75P mutation (n = 13) was also associated with symptomatic ICH (8.11, 1.83-35.89), multiple CMB (1.90, 1.01-3.56), and absence of temporopolar lesions (2.32, 1.08-4.97). Structural analysis revealed solvent-exposed free cysteine thiols in conventional mutations, directly causing aggregation, whereas a stereochemically incompatible proline residue structure in p.R75P lowers correct disulfide bond formation probability, indirectly causing aggregation. Pathologically, the p.R75P mutation resulted in less vascular NOTCH3 extracellular domain accumulation than the other conventional mutations. INTERPRETATION: NOTCH3 p.R75P mutation is associated with hemorrhagic presentations, milder temporopolar lesions, and distinct mutant protein structure properties. ANN NEUROL 2024;95:1040-1054.
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CADASIL , Hemorragia Cerebral , Mutação , Receptor Notch3 , Humanos , Masculino , Feminino , Receptor Notch3/genética , Pessoa de Meia-Idade , CADASIL/genética , Estudos Retrospectivos , Hemorragia Cerebral/genética , Idoso , Mutação/genética , Adulto , Japão , República da Coreia , Povo Asiático/genéticaRESUMO
OBJECTIVE: Surgical indications for low-grade carotid stenosis have not yet been established. This study aimed to clarify the characteristics of low-grade carotid stenosis refractory to medical treatment. METHODS: We retrospectively analyzed 48 patients with symptomatic low-grade carotid stenosis (<50%). Recurrence was defined as an ipsilateral ischemic event in the symptomatic lesions during the follow-up period. Patient demographics and imaging findings were compared between the recurrence and nonrecurrence groups to investigate risk factors associated with medical treatment. RESULTS: The mean age was 74.1 (58-90 years), and the mean follow-up period was 35.4 months (2.0-97 months). Recurrence occurred in 15 of the symptomatic patients. Ulceration was significantly associated with recurrence under medical treatment (P = 0.001). The median time to recurrence was 26.1 months in patients with ulcers and 54.3 months in those without ulcers (P = 0.04). Pathological study with recurrence showed plaque rupture with multilayered lesions, indicating lesions refractory to medical treatment. CONCLUSIONS: In cases of low-grade carotid stenosis, lesions with ulcerations are likely refractory to medical therapy. Consideration of the indications for surgical treatment may be warranted for lesions with ulceration, even if the degree of stenosis is low.
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Isquemia Encefálica , Estenose das Carótidas , Placa Aterosclerótica , Acidente Vascular Cerebral , Humanos , Idoso , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/cirurgia , Estudos Retrospectivos , Úlcera/complicações , Úlcera/diagnóstico por imagem , Úlcera/cirurgia , Placa Aterosclerótica/patologia , Isquemia Encefálica/etiologia , Fatores de Risco , Recidiva , Acidente Vascular Cerebral/etiologiaRESUMO
AIMS: Myocardial fibrosis of the left ventricle (LV) is a prognostic factor in dilated cardiomyopathy (DCM). This study aims to evaluate whether fibrosis of right ventricular (RV) endomyocardial biopsy (EMB) can predict the degree of LV fibrosis beforehand in DCM. METHODS AND RESULTS: Fibrosis extent in 70 RV-EMB specimens of DCM diagnosis was compared with that in the whole cross-sectional LV of excised hearts in the same patients (52 explanted hearts for transplant and 18 autopsied hearts). The median interval between biopsy and excision was 4.1 (0.13-19.3) years. The fibrosis area ratio of the EMBs and excised hearts were evaluated via image analysis. The distribution of cardiovascular magnetic resonance-late gadolinium enhancement (LGE) in the intraventricular septum was classified into four quartile categories. The fibrosis area ratio in RV-EMB correlated significantly with that in the short-axis cut of the LV of excised hearts (r = 0.82, P < 0.0001) and with a diffuse pattern of LGE (r = 0.71, P = 0.003). In a multivariate model, after adjusting for the interval between biopsy performance and heart excision, the fibrosis area ratio in RV-EMB was associated with that in LV-excised heart (regression coefficient, 0.82; 95% confidence interval, 0.68-0.95; P < 0.0001). CONCLUSIONS: The fibrosis observed in RV-EMB positively correlated with the extent of fibrosis in the LV of excised hearts in patients with DCM. The study findings may help predict LV fibrosis, considered a prognostic factor of DCM through relatively accessible biopsy techniques.
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Cardiomiopatia Dilatada , Humanos , Cardiomiopatia Dilatada/diagnóstico , Miocárdio/patologia , Ventrículos do Coração , Meios de Contraste , Estudos Transversais , Gadolínio , Fibrose , Biópsia/métodosRESUMO
Primary cardiac sarcomas are rare and sometimes difficult to discern from benign tumors and intracardiac thrombi. We describe the ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT findings in a case of left atrial undifferentiated pleomorphic sarcoma with osteosarcomatous differentiation, presenting with severe mitral regurgitation and pulmonary hypertension. The tumor presented as a broad-base mass protruding into the cardiac lumen, accompanied by punctate calcification-like high attenuation on CT. 18F-FDG PET/CT revealed high 18F-FDG uptake in the mass. Severe mitral regurgitation, a rare manifestation, was caused by tumor extension to the mitral valve leaflets and subvalvular tissue, which was best visualized on transesophageal echocardiography. This case illustrates the importance of multimodal diagnostic approaches including 18F-FDG PET/CT, which can facilitate accurate diagnosis and timely initiation of curative treatment, ultimately saving the patient's life. Learning objective: Firstly, cardiac sarcomas, particularly those with calcification/ossification, are rare and may mimic benign tumors and chronic intracardiac thrombi. Multimodal imaging approach, including 18F-FDG PET/CT, may be helpful in the accurate diagnosis of malignancies. Second, left atrial undifferentiated pleomorphic sarcoma has the potential to extensively spread along the endocardium and can extend to involve the valve leaflets, resulting in mitral regurgitation and pulmonary hypertension.
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AIM: To investigate the role of pentraxin 3 (PTX3) in atherosclerotic disease progression and plaque destabilization, as well as in coronary restenosis after directional coronary atherectomy (DCA). MATERIALS AND METHODS: PTX3 contents of early and advanced atherosclerotic lesions of the aorta obtained at autopsy were determined by ELISA and Western blot. Also, coronary plaques of patients with acute coronary syndrome (ACS) or stable angina pectoris (SAP) obtained by DCA were analyzed by immunohistochemistry for PTX3. The effects of PTX3 on smooth muscle cells (SMCs) and thrombogenesis were investigated with cultured human coronary artery SMCs and a flow chamber system, respectively. RESULTS: Advanced atherosclerotic lesions contained a significantly larger amount of PTX3 than early lesions (ELISA: 9.96 ± 2.77 ng/100 mg tissue, n = 8 vs 0.24 ± 0.18 ng/100 mg tissue, n = 6, P = 0.0097). Also, ACS plaques contained a significantly larger amount of PTX3 than SAP plaques (PTX3 immunohistochemistry-positive area percentage: 2.88 ± 0.53 %, n = 22 vs 0.67 ± 0.27 %, n = 23, P = 0.0009). Curiously, the patients who would remain free of post-DCA restenosis (n = 19) had plaques with a significantly higher PTX3 immunohistochemistry-positive area percentage than those who would develop restenosis (n = 12) (2.32 ± 0.49 % vs 0.49 ± 0.17 %, P = 0.002). In the mechanistic part of the study, PTX3 inhibited SMC proliferation and migration. PTX3 also inhibited platelet thrombus formation in the condition simulating arterial blood flow. CONCLUSIONS: PTX3 is increased in advanced (vs early) atherosclerotic lesions and unstable (vs stable) coronary plaques. The inhibitory effects of PTX3 on SMCs and thrombogenesis suggest that intraplaque PTX3 might have atheroprotective effects.
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Síndrome Coronariana Aguda , Aterosclerose , Doença da Artéria Coronariana , Placa Aterosclerótica , Componente Amiloide P Sérico , Trombose , Humanos , Proteína C-Reativa/análise , Trombose/etiologia , Trombose/prevenção & controle , Progressão da DoençaRESUMO
Aims: Doxorubicin is used in classical chemotherapy for several cancer types. Doxorubicin-induced cardiomyopathy (DOX-CM) is a critical issue among cancer patients. However, differentiating the diagnosis of DOX-CM from that of other cardiomyopathies is difficult. Therefore, in this study, we aimed to determine novel histopathological characteristics to diagnose DOX-CM. Methods and results: Twelve consecutive patients with DOX-CM who underwent cardiac histopathological examination in two medical centres were included. Twelve patients with dilated cardiomyopathy, who were matched with DOX-CM patients in terms of age, sex, and left ventricular ejection fraction, formed the control group. Another control group comprised five consecutive patients with cancer therapy-related cardiac dysfunction induced by tyrosine kinase inhibitors or vascular endothelial growth factor inhibitors were the controls. The positive area of tenascin-C, number of infiltrating macrophages, and presence of p62- and ubiquitin-positive cardiomyocytes were evaluated. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were used for in vitro investigation. The myocardium exhibited significantly greater tenascin-C-positive area and macrophage number in the DOX-CM group than in the control groups (P < 0.01). The tenascin-C-positive area correlated with the number of both CD68- and CD163-positive cells (r = 0.748 and r = 0.656, respectively). Immunostaining for p62 was positive in 10 (83%) patients with DOX-CM. Furthermore, western blotting analysis revealed significant increase in tenascin-C levels in hiPSC-CMs upon doxorubicin treatment (P < 0.05). Conclusion: The combined histopathological assessment for tenascin-C, macrophages, and p62/ubiquitin may serve as a novel tool for the diagnosis of DOX-CM. Doxorubicin may directly affect the expression of tenascin-C in the myocardium.
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We present a diagnostically challenging case of intimal sarcoma of the pulmonary artery (PA) due to the histologic finding of a sclerosing appearance with no appreciable spindle/pleomorphic cell proliferation. Initial endarterectomy specimens were composed of sclerosing extracellular matrix with a few bland cells, some recanalization, and fibrin thrombi, impeding the confirmation of intimal sarcoma as these findings were also consistent with chronic thromboembolic pulmonary hypertension. However, the patient experienced recurrence 5 years later, and the second endarterectomy specimens revealed more firm and solid mass and the proliferation of atypical spindle/pleomorphic cells within a myxomatous matrix in the distal PA, leading to the definitive diagnosis of undifferentiated intimal sarcoma of the PA. The archival specimens from the endarterectomy confirmed intense MDM2 expression by immunohistochemistry, suggesting its role as a potential diagnostic marker for intimal sarcoma. This case highlights that prominent sclerosing extracellular matrix with very few atypical cells should raise the possibility of intimal sarcoma of the PA and that high index of suspicion, generous sampling, and ancillary tests are critical for accurate diagnosis. In this case, the tumor was incidentally removed by endarterectomy, resulting in 5 years of survival.
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Electrocardiography abnormalities have been occasionally reported at the onset of stroke. Simultaneous electrocardiographic abnormalities and stroke require a rapid differentiated diagnosis among several diseases. However, direct causal relationships remain unclear. A 92-year-old woman presented to our emergency department in a sudden-onset coma. The patient suffered from huge acute ischemic stroke with bilateral internal carotid artery occlusion assessed by brain magnetic resonance imaging, and her electrocardiography showed ST-segment elevation at II, III, aVF and V4-6, and atrial fibrillation (AF). However, the etiology of the medical condition was clinically unknown. Eventually, the patient died on day 4 of hospitalization before the diagnosis could be completed. Therefore, an autopsy was performed to investigate pathological findings after obtaining informed consent from the family. A postmortem pathological evaluation demonstrated that fibrin mural thrombi in the left atrial appendage (LAA), and the cerebral and coronary arteries possessed CD31-positive endothelial cells, and CD68-positive and CD168-positive macrophages in a similar fashion, suggesting the fibrin thrombi observed in the three sites implicated to be identical. We concluded that nearly concurrent cerebral and coronary artery embolism because of the fibrin thrombi in LAA developed by AF. Simultaneous cerebral infarction and myocardial infarction are referred to as cardiocerebral infarction (CCI), a rare disorder for which clear pathomechanisms remain unknown, although several mechanisms of CCI have been proposed. We first revealed the clear pathology of CCI using the autopsy. Additional pathological studies are warranted to establish clear pathomechanisms and preventive strategies of CCI.
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OBJECTIVE: This study was aimed at assessing intraplaque neovessels, focusing on neovascularization from the vascular luminal side using contrast-enhanced ultrasound (CEUS) and determining that this contrast effect indicates that the neovessel is connected to the vessel lumen histopathologically. Whether plaque vulnerability can be assessed more accurately was also investigated. METHODS: We enrolled consecutive patients with internal carotid artery stenosis who underwent carotid endarterectomy (CEA) and pre-operative CEUS with perflubutane of the carotid arteries. We graded the contrast effect semi-quantitatively from the vascular luminal and adventitial sides. We compared the contrast effect with the pathological findings, especially the neovascularization of the CEA specimens. RESULTS: In total, 68 carotid arterial atheromatous plaques (47 symptomatic) were analyzed. Symptomatic plaques were significantly correlated with stronger contrast effects from the luminal side than from the adventitial side (p = 0.0095). Microbubbles from the luminal side appeared to flow mainly into the plaque shoulder. The contrast effect value for the plaque shoulder and neovessel density were significantly correlated (ρ = 0.35, p = 0.031). Neovessel density was significantly higher in symptomatic than in asymptomatic plaques (56.2 ± 43.7/mm2 and 18.1 ± 15.2/mm2, respectively, p < 0.0001). Serial histological sections of CEA specimens in a symptomatic plaque with a strong contrast effect from the luminal side revealed multiple neovessels fenestrated to the vessel lumen with endothelial cells, consistent with the CEUS findings. CONCLUSION: Contrast-enhanced ultrasound can be used to evaluate neovessels originating from the luminal side, histopathologically confirmed in serial sections. Symptomatic vulnerable plaque is correlated more significantly with intraplaque neovascularization from the luminal side than with neovascularization from the adventitia.
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Estenose das Carótidas , Endarterectomia das Carótidas , Placa Aterosclerótica , Humanos , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/cirurgia , Placa Aterosclerótica/patologia , Células Endoteliais , Meios de Contraste , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/cirurgia , Artérias Carótidas/patologia , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/cirurgia , Estenose das Carótidas/patologia , Ultrassonografia , Neovascularização Patológica/diagnóstico por imagemRESUMO
A 52-year-old male with complaints of pain and cold sensation on left upper-extremity was admitted to a hospital. He was diagnosed with acute left brachial artery occlusion and accordingly underwent emergency thrombectomy. Contrast-enhanced computed tomography (CT) revealed an ascending aortic mural thrombus (AMT). After his transferring to our institution, the AMT was removed, and the ascending aorta was replaced under cardiac arrest. Based on histopathological findings, the thrombus was caused by the destruction of an atheromatous plaque. The patient's postoperative course was uneventful, and no recurrence of AMT was presented for 12 months after operation.
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Doenças da Aorta , Cardiopatias , Placa Aterosclerótica , Tromboembolia , Trombose , Masculino , Humanos , Pessoa de Meia-Idade , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/cirurgia , Doenças da Aorta/diagnóstico por imagem , Doenças da Aorta/etiologia , Doenças da Aorta/cirurgia , Trombose/diagnóstico por imagem , Trombose/etiologia , Trombose/cirurgia , Aorta/diagnóstico por imagem , Aorta/cirurgiaRESUMO
BACKGROUND: In 2019, 2020 and 2022, the Japanese Government approved the use of tafamidis and two technetium-scintigraphies for transthyretin amyloid (ATTR) cardiomyopathy, and announced the patient criteria for tafamidis therapy. In 2018, we had started a nation-wide pathology consultation of amyloidosis. OBJECTIVE: To reveal the impact of approval of tafamidis and technetium-scintigraphy on the diagnosis of ATTR cardiomyopathy. METHODS: Ten institutes participated in this study on the pathology consultation of amyloidosis and shared rabbit polyclonal anti-κ116-133, anti-λ118-134, and anti-transthyretin115-124 antibodies. Proteomic analysis was performed when the typing diagnosis by immunohistochemistry was unavailable. RESULTS: Out of 5400 consultation cases received from April 2018 to July 2022, the type of amyloidosis by immunohistochemistry was determined in 4119 of the 4420 Congo-red positive cases. The incidences of AA, ALκ, ALλ, ATTR, Aß2M and others were 3.2, 11.3, 28.3, 54.9, 0.6 and 1.8%, respectively. Out of 2208 cardiac biopsy cases received, 1503 cases were ATTR positive. There were 4.0 and 4.9 times more total cases and ATTR-positive cases, respectively, in the last 12 months as compared to the first 12 months. CONCLUSIONS: The approval of tafamidis and technetium-scintigraphy raised the awareness of ATTR cardiomyopathy, leading to an upsurge in ATTR-positive cardiac biopsy cases.
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Neuropatias Amiloides Familiares , Cardiomiopatias , Coelhos , Animais , Neuropatias Amiloides Familiares/diagnóstico por imagem , Neuropatias Amiloides Familiares/genética , Tecnécio , Japão/epidemiologia , Proteômica , Cardiomiopatias/diagnóstico , Cardiomiopatias/genética , Pré-Albumina/genética , BiópsiaRESUMO
Coronavirus disease 2019 (COVID-19) is often accompanied by pneumonia and can be fatal. We report a case of COVID-19-associated myocardial injury mimicking fulminant myocarditis. Endomyocardial biopsy revealed numerous von Willebrand factor-rich microthrombi with small myocardial necrotic areas, complement deposits in small vessels/microthrombi, and macrophage-predominant interstitial infiltration. These findings, distinct from those of typical lymphocytic myocarditis, show diffuse endothelial injury, complement activation, and activated macrophages as characteristic features of COVID-19-associated pathogenesis. Dysregulated serum cytokine profiles predicting severe/critical COVID-19-associated myocardial injury were also determined. This case emphasizes the occurrence of fatal cardiac manifestation with microthrombotic injury in the early stage of COVID-19.
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COVID-19 , Infarto do Miocárdio , Miocardite , Humanos , COVID-19/complicações , Miocardite/diagnóstico , Miocardite/etiologia , SARS-CoV-2 , CoraçãoRESUMO
BACKGROUND: This study investigated the association between placental pathology and fetal heart failure.MethodsâandâResults: Singletons with a congenital heart defect (CHD) and/or arrhythmia (n=168) and gestational age-matched controls (n=52) were included in the study. The associations between macro- and microscopic abnormal findings of the placenta and the severity of fetal heart failure were evaluated using the cardiovascular profile (CVP) score. Nine features were microscopically identified and assessed in sections of the placenta: premature villi, edematous villi, fibrotic villi, chorioamnionitis, chorangiosis, fibrin deposition, subchorionic hematoma, infarcted villi, and nucleated red blood cells in villous vessels. Among singletons with CHD and/or arrhythmia, the final CVP score was ≥8 in 140 cases, 6 or 7 in 15 cases, and ≤5 in 13 cases. Microscopic analysis showed that the frequency and severity of premature and edematous villi and increased nucleated red blood cells in villous vessels were greater in cases of fetal heart failure. These microscopic findings were more common and severe in cases with a final CVP score ≤5 than in gestational age-matched controls. The prevalence of abnormal macroscopic findings of the placenta and umbilical cord was similar regardless of the severity of fetal heart failure. CONCLUSIONS: Premature and edematous villi and increased nucleated red blood cells in villous vessels were correlated with the severity of fetal heart failure in cases of CHD and/or arrhythmia.