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2.
Virchows Arch ; 479(1): 79-94, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33740097

RESUMO

Since cardiac hypertrophy may be considered a cause of death at autopsy, its assessment requires a uniform approach. Common terminology and methodology to measure the heart weight, size, and thickness as well as a systematic use of cut off values for normality by age, gender, and body weight and height are needed. For these reasons, recommendations have been written on behalf of the Association for European Cardiovascular Pathology. The diagnostic work up implies the search for pressure and volume overload conditions, compensatory hypertrophy, storage and infiltrative disorders, and cardiomyopathies. Although some gross morphologic features can point to a specific diagnosis, systematic histologic analysis, followed by possible immunostaining and transmission electron microscopy, is essential for a final diagnosis. If the autopsy is carried out in a general or forensic pathology service without expertise in cardiovascular pathology, the entire heart (or pictures) together with mapped histologic slides should be sent for a second opinion to a pathologist with such an expertise. Indication for postmortem genetic testing should be integrated into the multidisciplinary management of sudden cardiac death.


Assuntos
Cardiomegalia/patologia , Miocárdio/patologia , Autopsia , Cardiomegalia/genética , Cardiomegalia/mortalidade , Cardiomegalia/fisiopatologia , Causas de Morte , Testes Genéticos , Humanos , Tamanho do Órgão , Valor Preditivo dos Testes , Fatores de Risco , Terminologia como Assunto
3.
Forensic Sci Med Pathol ; 17(2): 334-337, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33247412

RESUMO

A 58-year old woman presented for autopsy after having been found unresponsive in a public bathroom surrounded by a pool of blood. During attempts at resuscitation, blood was noted in her airway. She had a past medical history that included surgical repair of Tetralogy of Fallot as a child. At autopsy, a shard of glass was identified projecting from the surface of the left lung, having formed densely fibrotic adhesions at the pleural surface. The glass also penetrated through a bronchiole lumen and into a previously surgically repaired bulging right ventricular outflow tract, forming a bronchiole-cardiac fistula, allowing for the massive hemoptysis that led to her death. After further inquiry, it was discovered that the decedent also had a history of seizure disorder and had fallen through a glass door during a seizure many years ago, requiring several shards of glass to be removed from her chest wall.


Assuntos
Fístula , Hematemese , Bronquíolos , Evolução Fatal , Feminino , Ventrículos do Coração , Hematemese/etiologia , Humanos , Pessoa de Meia-Idade
4.
Eur Heart J ; 41(30): 2878-2890, 2020 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-32533187

RESUMO

AIMS: Brugada syndrome (BrS) is characterized by a unique electrocardiogram (ECG) pattern and life-threatening arrhythmias. However, the Type 1 Brugada ECG pattern is often transient, and a genetic cause is only identified in <25% of patients. We sought to identify an additional biomarker for this rare condition. As myocardial inflammation may be present in BrS, we evaluated whether myocardial autoantibodies can be detected in these patients. METHODS AND RESULTS: For antibody (Ab) discovery, normal human ventricular myocardial proteins were solubilized and separated by isoelectric focusing (IEF) and molecular weight on two-dimensional (2D) gels and used to discover Abs by plating with sera from patients with BrS and control subjects. Target proteins were identified by mass spectrometry (MS). Brugada syndrome subjects were defined based on a consensus clinical scoring system. We assessed discovery and validation cohorts by 2D gels, western blots, and ELISA. We performed immunohistochemistry on myocardium from BrS subjects (vs. control). All (3/3) 2D gels exposed to sera from BrS patients demonstrated specific Abs to four proteins, confirmed by MS to be α-cardiac actin, α-skeletal actin, keratin, and connexin-43, vs. 0/8 control subjects. All (18/18) BrS subjects from our validation cohorts demonstrated the same Abs, confirmed by western blots, vs. 0/24 additional controls. ELISA optical densities for all Abs were elevated in all BrS subjects compared to controls. In myocardium obtained from BrS subjects, each protein, as well as SCN5A, demonstrated abnormal protein expression in aggregates. CONCLUSION: A biomarker profile of autoantibodies against four cardiac proteins, namely α-cardiac actin, α-skeletal actin, keratin, and connexin-43, can be identified from sera of BrS patients and is highly sensitive and specific, irrespective of genetic cause for BrS. The four involved proteins, along with the SCN5A-encoded Nav1.5 alpha subunit are expressed abnormally in the myocardium of patients with BrS.


Assuntos
Síndrome de Brugada , Arritmias Cardíacas , Autoanticorpos , Síndrome de Brugada/diagnóstico , Eletrocardiografia , Ventrículos do Coração , Humanos
5.
Circulation ; 140(21): 1706-1716, 2019 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-31630535

RESUMO

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is considered a leading cause of sudden cardiac death (SCD) in younger people. The incidence of HCM-related SCD and its relationship to exercise have not been well studied in large comprehensive studies outside of tertiary care settings. This study sought to estimate the incidence of HCM-related SCD and its association with exercise in a large unselected population. METHODS: Using the Office of the Chief Coroner of Ontario database encompassing all deaths attended by the coroner, we identified all HCM-related SCDs in individuals 10 to 45 years of age between 2005 and 2016 (70 million person-years). Confirmation of HCM was based on typical macroscopic and microscopic features (definite HCM-related SCD). Sudden deaths with a prior clinical diagnosis of HCM but no autopsy were considered probable HCM-related SCDs. Cases with typical features but no myofiber disarray were considered possible HCM. The completeness of data was verified in a subset of patients in the Toronto area with the use of a registry of all emergency medical services-attended cardiac arrests, with an autopsy rate of 94%. To estimate the number of HCM-related aborted cardiac arrests and lives potentially saved by implantable cardioverter-defibrillators, all de novo implantations for secondary prevention and all implantations and appropriate shocks for primary prevention in patients with HCM 10 to 45 years of age, respectively, were identified with the use of a registry containing data on implantable cardioverter-defibrillator implantations from all implanting sites throughout Ontario. RESULTS: Forty-four, 3, and 6 cases of definite, probable, and possible HCM-related SCDs, respectively, were identified, corresponding to estimated annual incidence rates of 0.31 per 1000 HCM person-years (95% CI, 0.24-0.44) for definite HCM-related SCD, 0.33 per 1000 HCM person-years (95% CI, 0.34-0.62) for definite or probable HCM-related SCD, and 0.39 per 1000 HCM person-years (95% CI, 0.28-0.49) for definite, probable, or possible HCM-related SCD (estimated 140 740 HCM person-years of observation). The estimated annual incidence rate for HCM-related SCD plus aborted cardiac arrest and HCM-related life-threatening arrhythmia (SCD, aborted cardiac arrest, and appropriate implantable cardioverter-defibrillator shocks) was 0.84 per 1000 HCM person-years (95% CI, 0.70-1.0). The majority (70%) of SCDs occurred in previously undiagnosed individuals. Most SCDs occurred during rest (64.8%) or light activity (18.5%). CONCLUSIONS: The incidence of HCM-related SCD in the general population 10 to 45 years of age is substantially lower than previously reported, with most cases occurring in previously undiagnosed individuals. SCDs are infrequently related to exercise.


Assuntos
Cardiomiopatia Hipertrófica/mortalidade , Morte Súbita Cardíaca/epidemiologia , Adolescente , Adulto , Fatores Etários , Cardiomiopatia Hipertrófica/diagnóstico , Cardiomiopatia Hipertrófica/terapia , Causas de Morte , Criança , Morte Súbita Cardíaca/prevenção & controle , Desfibriladores Implantáveis , Cardioversão Elétrica/instrumentação , Exercício Físico , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Ontário/epidemiologia , Prevenção Primária/instrumentação , Sistema de Registros , Medição de Risco , Fatores de Risco , Prevenção Secundária/instrumentação , Fatores Sexuais , Fatores de Tempo , Adulto Jovem
6.
Forensic Sci Res ; 4(3): 223-240, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31489388

RESUMO

Ventricular hypertrophy is a common pathological finding at autopsy that can act as a substrate for arrhythmogenesis. Pathologists grapple with the significance of ventricular hypertrophy when assessing the sudden and unexpected deaths of young people and what it could mean for surviving family members. The pathological spectrum of left ventricular hypertrophy (LVH) is reviewed herein. This article is oriented to the practicing autopsy pathologist to help make sense of various patterns of increased heart muscle, particularly those that are not clearly cardiomyopathic, yet present in the setting of sudden cardiac death. The article also reviews factors influencing arrhythmogenesis as well as genetic mutations most commonly associated with ventricular hypertrophy, especially those associated with hypertrophic cardiomyopathy (HCM).

9.
Acad Forensic Pathol ; 7(4): 551-566, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31240006

RESUMO

Molecular autopsy is changing the practice of forensic pathology. Under some circumstances, one must contemplate the involvement of genetic factors to help explain why someone has died unexpectedly. Such considerations most commonly occur when a young person dies by natural means. However, there are deaths that occur by nonnatural means that the forensic pathologist will be asked to investigate, which could involve natural disease that has a significant genetic underpinning. Elucidation of genetic mutations may not only further an understanding of the pathophysiology at hand, but also speak to underlying susceptibilities in an individual who dies that may not have been recognized. In addition, one may occasionally identify pathological findings that are confused for trauma that may actually be better explained by an underlying disease process. Using molecular medicine as a tool to explore such possibilities can improve the quality of death investigations and provide a new lens to probe challenging and contentious forensic cases that have proved resistant to traditional methods.

12.
Cardiovasc Pathol ; 23(4): 238-40, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24661792

RESUMO

Atrial fibrillation (AF) is associated with significant morbidity and mortality. Hemodynamic compromise and formation of thrombi within the fibrillating atrium or atrial appendage can occur. Surgical treatment aims to eliminate dysrhythmia-triggering foci in the pulmonary veins and posterior left atrium by radiofrequency ablation techniques using ohmic heat. As medical treatment may be ineffective, radiofrequency catheter ablation is increasingly being used by interventional cardiac electrophysiologists for AF. Serious complications have been observed among patients who have undergone radiofrequency ablation, atrioesophageal fistula being a very rare example. This case describes a 43-year-old man who died after the development of an atrioesophageal fistula following radiofrequency ablation of the left atrium and pulmonary veins for treatment of AF.


Assuntos
Fibrilação Atrial/cirurgia , Ablação por Cateter/efeitos adversos , Fístula Esofágica/etiologia , Átrios do Coração , Cardiopatias/etiologia , Adulto , Fístula Esofágica/patologia , Evolução Fatal , Átrios do Coração/patologia , Átrios do Coração/cirurgia , Cardiopatias/patologia , Humanos , Masculino , Veias Pulmonares/cirurgia
13.
Leg Med (Tokyo) ; 14(5): 252-4, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22622258

RESUMO

Excited delirium syndrome (EDS) has become a controversial and vexing forensic issue due to its association with restraint and sudden unexpected death. Although some authorities and jurisdictions recognised EDS as a cause of death there is no consensus among the medical community in this regard. The overlapping nature of the spectrum of antemortem behaviours and signs with many natural disease processes complicates this issue further. We describe two deaths which initially presented as EDS-like behaviour during restraint. In the first case, the deceased was travelling on a long distance flight when he died while in the custody of air cabin crew. The autopsy revealed the cause of death as air travel-related pulmonary thromboembolism. Acute alcoholic intoxication, nicotine withdrawal, hypoxia due to acute pulmonary thromboembolism, and hypobaric environment in the air plane cabin appeared as the potential reasons for EDS-like behaviour. In the second case, the deceased died while in the custody of immigration officials. At autopsy the cause of death turned out to be tense pericardial effusion due to fibrinous pericarditis. In this case, hypoperfusion of the brain following systemic hypotension as a result of cardiac tamponade associated with pericardial effusion likely led to the EDS-like behaviour. Clinicopathologic correlation in these two cases would strongly suggest EDS as the cause of death, had the decedents not had fatal anatomical causes of death. This alerts the forensic pathologist that not all the individuals dying with signs and symptoms of EDS during restraint are accounted for EDS as the immediate cause of death.


Assuntos
Tamponamento Cardíaco/etiologia , Morte Súbita/etiologia , Delírio/etiologia , Patologia Legal , Pericardite/complicações , Embolia Pulmonar , Adulto , Aeronaves , Autopsia , Causas de Morte , Transtornos Autoinduzidos/diagnóstico , Humanos , Masculino , Restrição Física/efeitos adversos , Viagem
14.
Pulm Med ; 2012: 746358, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22448327

RESUMO

Background. Recurrent bacterial infections play a key role in the pathogenesis of bronchiectasis, but conventional microbiologic methods may fail to identify pathogens in many cases. We characterized and compared the pulmonary bacterial communities of cystic fibrosis (CF) and non-CF bronchiectasis patients using a culture-independent molecular approach. Methods. Bacterial 16S rRNA gene libraries were constructed from lung tissue of 10 non-CF bronchiectasis and 21 CF patients, followed by DNA sequencing of isolates from each library. Community characteristics were analyzed and compared between the two groups. Results. A wide range of bacterial diversity was detected in both groups, with between 1 and 21 bacterial taxa found in each patient. Pseudomonas was the most common genus in both groups, comprising 49% of sequences detected and dominating numerically in 13 patients. Although Pseudomonas appeared to be dominant more often in CF patients than in non-CF patients, analysis of entire bacterial communities did not identify significant differences between these two groups. Conclusions. Our data indicate significant diversity in the pulmonary bacterial community of both CF and non-CF bronchiectasis patients and suggest that this community is similar in surgically resected lungs of CF and non-CF bronchiectasis patients.

15.
Arch Pathol Lab Med ; 133(12): 1965-8, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19961253

RESUMO

CONTEXT: -Epithelioid hemangioendothelioma (EHE) is a vascular neoplasm that occasionally is difficult to distinguish from primary/metastatic carcinomas, particularly when EHEs express keratins. We recently encountered an EHE with strong CD10 positivity mimicking renal cell carcinoma. OBJECTIVE: -To examine sensitivity and specificity of CD10 in EHE. DESIGN: -Nine EHEs were stained with keratins, factor VIII, CD31, CD34, and CD10. Mimics of EHE were also retrieved and stained with CD10. RESULTS: -The EHE patients included 5 men and 4 women. Patients ranged in age from 24 to 74 years. Tumors were located in liver (3), skin (2), lung/pleura (2), and sternomastoid and mediastinum (1 each). Two had skin metastases. All EHEs were positive for vascular markers. A total of 7 of 9 primary tumors expressed cytoplasmic and intracytoplasmic luminal CD10. The 2 skin metastases were positive, whereas 2 primary skin EHEs were negative. Of the mimics, CD10 showed staining in 7 of 23 cases: 3 of 3 renal cell carcinomas, 1 of 7 other carcinomas, 2 of 3 epithelioid angiosarcomas, 1 of 3 melanomas, 0 of 3 mesotheliomas, and 0 of 4 epithelioid hemangiomas. CONCLUSIONS: -CD10 has a sensitivity of 78% (confidence interval, 63.6%-92.4%) and specificity of 70% (confidence interval, 54%-85.9%) for EHE. There is a growing list of tumors that show expression of CD10. Pathologists should be aware of this diagnostic pitfall.


Assuntos
Hemangioendotelioma Epitelioide/diagnóstico , Hemangioendotelioma Epitelioide/metabolismo , Neprilisina/biossíntese , Adulto , Idoso , Antígenos CD34/análise , Biomarcadores Tumorais/análise , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/metabolismo , Diagnóstico Diferencial , Células Epitelioides/química , Células Epitelioides/patologia , Feminino , Hemangiossarcoma/diagnóstico , Hemangiossarcoma/metabolismo , Humanos , Imuno-Histoquímica , Neoplasias Renais/diagnóstico , Neoplasias Renais/metabolismo , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Adulto Jovem
16.
J Thorac Cardiovasc Surg ; 135(4): 823-9, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18374762

RESUMO

OBJECTIVE: The aim of the study was to determine the impact of tumor-infiltrating lymphocytes on survival in patients with malignant pleural mesothelioma treated with induction chemotherapy followed by extrapleural pneumonectomy. METHODS: We performed an immunohistochemical analysis of 32 extrapleural pneumonectomy specimens to assess the distribution of T-cell subtypes (CD3(+), CD4(+), and CD8(+)), regulatory subtypes (CD25(+) and FOXP3(+)), and memory subtype (CD45RO(+)) within the tumor. RESULTS: Patients with high levels of CD8(+) tumor-infiltrating lymphocytes demonstrated better survival than those with low levels (3-year survival: 83% vs 28%; P = .06). Moreover, high levels of CD8(+) tumor-infiltrating lymphocytes were associated with a lower incidence of mediastinal node disease (P = .004) and longer progression-free survival (P = .05). Higher levels of CD8(+) tumor-infiltrating lymphocytes were observed in patients treated with cisplatin and pemetrexed than in those treated with cisplatin and vinorelbine (P = .02). Patients presenting high levels of CD4(+) or CD25(+) tumor-infiltrating lymphocytes or low levels of CD45RO(+) also demonstrated a trend toward shorter survival. However, the presence of FOXP3(+) tumor-infiltrating lymphocytes did not affect survival. After multivariate adjustment, high levels of CD8(+) tumor-infiltrating lymphocytes remained an independent prognostic factor associated with delayed recurrence (hazard ratio = 0.38; confidence interval = 0.09-0.87; P = .02) and better survival (hazard ratio = 0.39; confidence interval = 0.09-0.89; P = .02). CONCLUSION: The presence of high levels of CD8(+) tumor-infiltrating lymphocytes is associated with better prognosis in patients undergoing extrapleural pneumonectomy for malignant pleural mesothelioma. The stimulation of CD8(+) lymphocytes can be a potential therapeutic strategy to improve outcome.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Linfócitos do Interstício Tumoral/imunologia , Mesotelioma/terapia , Neoplasias Pleurais/terapia , Subpopulações de Linfócitos T/imunologia , Adulto , Idoso , Antineoplásicos/uso terapêutico , Feminino , Humanos , Masculino , Mesotelioma/imunologia , Pessoa de Meia-Idade , Terapia Neoadjuvante , Neoplasias Pleurais/imunologia , Pneumonectomia , Prognóstico , Análise de Sobrevida
17.
Cardiovasc Pathol ; 17(3): 183-5, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18402790

RESUMO

Infarction of the cardiac atria occurs more frequently than is commonly considered. Ischemic damage to the atrial myocardium is usually associated with infarction of cardiac ventricles, but isolated infarction of an atrium can occur and may be of clinical significance. We present an unusual case of an isolated right atrial infarct with an infarction-related endocardial thrombus that mimicked a mass lesion near the inferior vena cava. The presentation and causes of isolated atrial infarction are discussed.


Assuntos
Átrios do Coração/patologia , Infarto do Miocárdio/patologia , Idoso , Anemia/complicações , Doença Crônica , Ecocardiografia , Evolução Fatal , Feminino , Humanos , Infarto do Miocárdio/complicações , Osteoartrite/complicações , Osteoporose/complicações , Doenças Vasculares Periféricas/complicações , Úlcera Gástrica/complicações , Tomografia Computadorizada por Raios X
18.
Cardiovasc Pathol ; 16(5): 258-67, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17868876

RESUMO

BACKGROUND: The Medtronic Freestyle valve is fixed in glutaraldehyde at zero pressure on the cusps and treated with alpha-amino oleic acid. This valve reportedly has excellent clinical and hemodynamic results, but little has been reported about its long-term pathology. METHODS AND RESULTS: Nine Freestyle valves explanted between 2003 and 2005 were reviewed to assess the reasons for bioprosthesis failure (six implanted at our institution). All valves were examined in detail, using histochemistry and immunohistochemistry to identify the cellular response. One Freestyle valve, explanted for mitral valve endocarditis on the fifth postoperative day, was excluded from analysis. Average implant duration was 52.8+/-35.5 months. Four valves were explanted for infective endocarditis, three for aortic insufficiency, two for aortic stenosis with cusp calcification seen in five valves, pannus and thrombus in all valves and a chronic inflammatory reaction involving the xenograft arterial wall seen in eight of nine valves. This was associated with significant damage to the porcine aortic wall in seven cases, and cusp myocardial shelf damage in six cases. CONCLUSIONS: In this series of valves, we found (1) infective endocarditis; (2) pannus, thrombus, and calcification; and (3) unusual and significant inflammatory reaction and aortic tissue damage, which could by itself lead to aortic incompetence.


Assuntos
Valva Aórtica/cirurgia , Bioprótese , Remoção de Dispositivo , Implante de Prótese de Valva Cardíaca/efeitos adversos , Próteses Valvulares Cardíacas , Inflamação/etiologia , Falha de Prótese , Infecções Relacionadas à Prótese/etiologia , Adulto , Idoso , Animais , Valva Aórtica/patologia , Calcinose/etiologia , Análise de Falha de Equipamento , Feminino , Fixadores , Glutaral , Implante de Prótese de Valva Cardíaca/instrumentação , Humanos , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Infecções Relacionadas à Prótese/patologia , Estudos Retrospectivos , Suínos , Trombose/etiologia , Fatores de Tempo , Fixação de Tecidos/métodos , Resultado do Tratamento
20.
Cardiovasc Pathol ; 16(1): 4-13, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17218209

RESUMO

BACKGROUND: Bioprosthetic heart valves are more frequently being used in valve replacement procedures today. Although second-generation bioprosthetic valves have improved functionality over their first-generation counterparts, they still often fail due to primary tissue degeneration. METHODS: This study examines two second-generation porcine valves after surgical explantation, the Hancock-II (HAN; Medtronic Heart Valve Division, Irvine, CA, USA) and the Carpentier-Edwards supraannular (CE-SAV; Baxter Healthcare Corporation, now Edwards LifeSciences, Irvine, CA, USA), with special attention to morphological/histological changes and reasons for valve failure. A total of 98 HAN and 65 CE-SAV valves were explanted and seen over a 10-year period. RESULTS: CE-SAV valves had a longer average implant duration than HAN valves (13.9+/-3.9 years vs. 10.0+/-5.1 years). Compared with HAN valves, CE-SAV valves also had a higher incidence of stent deformation (41.5% vs. 14.3%), calcification (75.4% vs. 54.1%), and pannus (100% vs. 91.8%). CONCLUSIONS: The greater degenerative changes seen with CE-SAV valves over HAN valves may be due to the longer implant duration of CE-SAV valves in this series. To our knowledge, the present study is the first direct morphological comparison of these two valve models.


Assuntos
Bioprótese , Próteses Valvulares Cardíacas , Falha de Prótese , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Remoção de Dispositivo , Análise de Falha de Equipamento , Feminino , Doenças das Valvas Cardíacas/patologia , Doenças das Valvas Cardíacas/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Suínos
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