Sarcoidosis and mechanisms of unexpected death

Sarcoidosis is a multisystem disease of uncertain etiology characterized by multifocal areas of discrete and confluent granulomatous inflammation that may rarely be responsible for sudden and unexpected death. Two cases are reported to demonstrate disparate pathological features in fatal cases, one involving cardiac sarcoidosis, and the other neurosarcoidosis with hypothalamic infiltration. Sarcoidosis in individuals dying suddenly may be completely unrelated to the death, contributory or causal. Cardiovascular causes of sudden death in sarcoidosis include arrhythmias associated with cardiomyopathy and ischemia, ventricular rupture, and cor pulmonale due to pulmonary hypertension; respiratory causes include hemorrhage and upper airway obstruction; central nervous system causes include arrhythmias from infiltration of autonomic centers, epilepsy, and obstructive hydrocephalus from brainstem involvement; and gastrointestinal deaths may be due to hemorrhage from esophageal varices associated with portal hypertension. The diagnosis relies on the demonstration of typical noncaseating granulomas and the exclusion of other infective and environmental diseases with similar histopathological findings.     

Pathologic Findings of Coronary Stents: A Comparison of Sudden Coronary Death Versus Non‐cardiac Death

There are few histologic studies of intracoronary stents found at autopsy. We studied histologic findings of 87 intracoronary stents from 45 autopsy hearts. There were 40 patients with chronically implanted stents and five shorter than 30 days. Of five patients with recent stent placement, the cause of death was related to the stent (in‐stent thrombosis) in one case. Of the 40 patients with chronic stents, there were 16 sudden coronary deaths and 24 noncoronary deaths (controls). There were no late stent thromboses in the coronary deaths. In the coronary deaths, 26% of stents showed restenosis versus 11% in controls (p = 0.1). The rate of healed infarcts and cardiomegaly was similar in the coronary and noncoronary groups, and acute thrombi in native arteries were seen only in three hearts in the coronary group. We conclude that the cause of death is rarely impacted by in‐stent findings at autopsy, especially in chronically implanted stents.     

Sudden death in right ventricular dysplasia with minimal gross abnormalities

Arrhythmogenic right ventricular cardiomyopathy is emerging as a relatively common cause of exercise-induced sudden death in the young. The diagnostic criteria at autopsy are, however, not fully established, leading to both over- and underdiagnosis. We report a young man and a young woman dying suddenly of right ventricular dysplasia during exercise, in whom the gross autopsy findings in the right ventricle were minimal or even absent. However, the histologic features in both right and left ventricles were typical of the disease, and consisted of fibrofatty infiltrates with typical myocyte degeneration of the right ventricle and subepicardial regions of the left ventricle. These cases illustrate that microscopic findings are diagnostic and may be present in the absence of gross findings. Marked fat replacement is not essential for the diagnosis of right ventricular dysplasia, and the right ventricle should be extensively sampled histologically in all cases of sudden unexpected death, especially those that are exercise related.     

Undetermined Manner of Death: An Autopsy Series

A manner of death may be ruled undetermined by the forensic pathologist when there is insufficient information about the circumstances surrounding the death to make a ruling. The aim of our study was to retrospectively analyze a series of autopsy cases that were classified as undetermined manner of death after complete investigations. In all, 48 cases were examined. In 23 cases (48%), the cause of death was determined. The most frequent cause of death was toxic death (n = 11). More than one manner of death was deemed conceivable for most cases (n = 39). The most frequent and the most probable manner of death was accident (n = 37). Homicide was not excluded in about 23% of the cases. Our study showed that the manner of death may remain undetermined despite an established cause of death, and even when two or more conceivable causes of death are considered. Our study pointed out that undetermined manner of death covers a wide range of situations and that homicide may be underestimated.     

The Institution of a Standardized Investigation Protocol for Sudden Infant Death in the Eastern Metropole,Cape Town,South Africa,,

The rate for the sudden infant death syndrome (SIDS) in Cape Town, South Africa, is estimated to be among the highest in the world (3.41/1000 live births). In several of these areas, including those of extreme poverty, only sporadic, nonstandardized infant autopsy, and death scene investigation (DSI) occurred. In this report, we detail a feasibility project comprising 18 autopsied infants with sudden and unexpected death whose causes of death were adjudicated according to the 1991 NICHD definitions (SIDS, n = 7; known cause of death, n = 7; and unclassified, n = 4). We instituted a standardized autopsy and infant DSI through a collaborative effort of local forensic pathology officers and clinical providers. The high standard of forensic investigation met international standards, identified preventable disease, and allowed for incorporation of research. We conclude that an effective infant autopsy and DSI protocol can be established in areas with both high sudden unexpected infant death, and elsewhere. (SUID)/SIDS risk and infrastructure challenges.     

A case of sudden infant death due to a primary cardiac sarcoma

The case reported herein concerns the unexpected death of a 3-month-old female newborn who suddenly collapsed in her mother's arms and was dead on arrival at the hospital. The clinical histories of the baby and her parents were negative for symptoms or signs of illness, even those of cardiovascular origin. Furthermore, no clinical appearance of a pathologic status was noted by pediatricians after the birth until the last emergency recovery. The autopsy excluded external and internal signs of violence but revealed a large primary cardiac tumor arising from the free wall of the left ventricle, which had totally invaded the heart causing mitral valve deformation. Histological examination showed a low-grade sarcoma that completely infiltrated the myocardial tissue. The pathogenesis of this sudden infant death was postulated as being owing to a fatal ventricular fibrillation combined with a tumor-related restrictive cardiomyopathy obstructing left ventricular filling.     

Aortic Dissection and Sudden Unexpected Deaths: A Retrospective Study of 31 Forensic Autopsy Cases

Acute aortic dissection (AAD) is the most common cause of sudden unexpected death related to aortic diseases. A retrospective study of 31 sudden unexpected deaths caused by AAD was conducted at Xi'an Jiaotong University Forensic Center from 2001 to 2012. We summarized the forensic characteristics of AAD and assessed the clinically diagnostic accuracy of AAD. The characteristics of sudden unexpected death due to AAD were male predominant (male: female = 6.7:1), relatively young with the mean age of 44, and predominance of type A dissection (77.4%). Cardiac tamponade was the most frequent cause of sudden death (87.1%). Of the 31 cases, 26 (83.9%) patients were not recognized clinically and were misdiagnosed with acute myocardial infarction, coronary artery disease, cholecystitis, acute gastroenteritis, renal/urinary lithiasis, or acute pancreatitis. In summary, AAD can be difficult to recognize, diagnosis is therefore sometimes delayed or missed. The medicolegal death investigation can help physicians have a better understanding of AAD.     

病毒性心肌炎和扩张性心肌病中Dystrophin蛋白的表达

目的探讨病毒性心肌炎和扩张性心肌病的发病机制及相互关系,从而提高心性猝死法医学鉴定的可靠性和准确性。方法对17例对照(包括正常心脏、冠心病、高血压性心脏病等),25例病毒性心肌炎和28例扩张性心肌病的心肌组织进行改良的病理学dystrophin免疫组织化学研究。结果dystrophin蛋白在对照组,病毒性心肌炎组和扩张性心肌病组中阳性表达率分别为100%,88%,57%,三组表达差异有显著性(P<0.05),且在病毒性心肌炎和扩张性心肌病组间表达有显著差异(P<0.05),经Spearman等级相关分析呈显著负相关(r=-0.526)。结论病毒性心肌炎和扩张性心肌病心肌中细胞骨架蛋白均有破坏,且随着由病毒性心肌炎进展为扩张性心肌病,dystrophin蛋白表达逐渐降低,说明在病毒性心肌炎和扩张性心肌病的发病机制中可能与dystrophin的被破坏有关,病毒感染并破坏心肌细胞骨架蛋白并最终导致心肌细胞坏死,心功能受损,从而使病毒性心肌炎进展为扩张性心肌病。     

Asymmetric septal hypertrophy of the heart. New findings concerning the possible etiology of sudden deaths in five males

This report describes certain interesting postmortem findings in the hearts of five subjects who died suddenly, silently, and unexpectedly, and in whom the only significant abnormality at autopsy was asymmetric septal hypertrophy (ASH) of the heart. Deep clefts, cystic faults, and dilated vascular channels were not only seen within the septal myocardium in all the hearts, but also within the left ventricular free walls of two hearts. The septal myocardium and the left ventricular free walls of two hearts and the A-V node and His bundle of one heart demonstrated mural and luminal thrombi of several dilated vascular channels. In another heart, foci of cardiocytic myofibrillar degeneration were seen, especially close to narrowed small coronary vessels. Fetal dispersion and fibrosis of the A-V node and His bundle were evident in one heart. These abnormalities in the conducting system and the ventricular myocardium suggest that the hearts of subjects with ASH are not only excellent anatomic substrates for lethal arrhythmias, but also are bound to be hemodynamically impaired. We believe that conditions such as hypoxia, increased oxygen demand by the heart or abnormal sympathetic stimulus may easily trigger fatal arrhythmias in such individuals, thereby causing sudden death.     

原发性心肌病猝死心肌mtDNA~(4977)缺失变化

目的探讨原发性心肌病(PCM)猝死者心肌线粒体DNA(m tDNA4977)缺失情况及其与猝死的关系。方法对18例PCM猝死和28例对照组病例心肌组织蜡块,用常规方法提取心肌m tDNA,以PCR、琼脂糖紫外凝胶成像技术确定扩增产物激光密度,初步定量检测m tDNA4977缺失率。结果PCM猝死18例中,检见13例m tDNA4977缺失,占72.44%。对照组28例中,检见3例m tDNA4977缺失,占10.71%;两组病例m tDNA4977缺失率均值分别为0.5795和0.0744,差异有非常显著性意义。结论多数PCM,特别是扩张型心肌病猝死者心肌可检见m tDNA4977缺失;提示其心肌m tDNA4977缺失变化与PCM猝死的发生可能有一定关系。     

Post-mortem investigation of calcium content in liver, heart, and skeletal muscle in accidental hypothermia cases

The identification of hypothermia as cause of the death was always quite problematic in the field of forensic medicine. The aim of the present study was to verify the determination of calcium content in post-mortem liver, heart, and skeletal muscle samples as the biochemical marker defining hypothermia as the cause of death. The study involved 43 autopsy cases in which the circumstances of death indicated the effects of overcooling. The control group consisted of material collected from the corpses of 30 persons who were not exposed to low temperatures but died due to technical injuries (n = 5), asphyxia (n = 6), intoxication with ethanol and other substances (n = 8), and acute myocardial infarction/ischemia (n = 11). The concentration of calcium in autopsy samples was determined applying flame atomic absorption spectroscopy. Our study showed no significant differences of calcium content in tissues of persons who died due to hypothermia, over those who died in normothermic conditions.     

A retrospective analysis of cardiovascular deaths: A 5-year autopsy study of 1045 cases in Antalya,Turkey

This study aims to identify the macroscopic and microscopic changes that occur in the heart in different causes of cardiovascular death and sudden cardiac death in autopsy cases and evaluate the difficulties that a forensic practitioner may encounter during autopsies. All forensic autopsy cases in the Morgue Department of the Council of Forensic Medicine, Antalya Group Administration between January 1, 2015, and December 31, 2019, were examined, retrospectively. The cases were chosen according to inclusion and exclusion criteria, and their autopsy reports were examined in detail. It was determined that 1045 cases met the study criteria, 735 of which were also met the sudden cardiac death criteria. The top three common causes of death were ischemic heart disease (n = 719, 68.8%), left ventricular hypertrophy (n = 105, 10%), and aortic dissection (n = 58, 5.5%). The frequency of myocardial interstitial fibrosis was significantly higher in deaths due to left ventricular hypertrophy than in deaths due to ischemic heart disease and other causes (χ²(2) = 33.365, p < 0.001). Despite detailed autopsy and histopathological examinations, some heart diseases that cause sudden death may still not be detected.     

Staphylococcal scalded skin syndrome mimicking child abuse by burning

Determining the cause for the sudden death in young adults tends to be complex and difficult. Two cases of death of young people were autoptically investigated who died suddenly while carrying out their hobbies (a 22-year-old male musician and a 20-year-old female dancer). In both cases neither the police investigation, the autopsy, nor the toxicological investigations gave any relevant results. However, when investigating the histology fatty and fibrotic tissue in the right ventricle of the myocardium were found, whereas the myocytes proved to be degenerated--typical for arrhythmogenic right ventricular cardiomyopathy (ARVC). It is important to consider the possibility of heart rhythm failure if a clear reason for sudden death in young adults cannot be detected. Heart rhythm failure often involves the genetic background of the case, which suggests that genetic analysis should be carried out as a supportive means of diagnostics.     

Myocardial Cx43 expression in the cases of sudden death due to dilated cardiomyopathy

PURPOSE: Probing into myocardial connexin (Cx) 43 expression in the cases of sudden death due to dilated cardiomyopathy (DCM) and relationship between Cx43 expression and sudden death. METHOD: Myocardial Cx43 was detected with immunohistochemical staining in the cases of 11 sudden death caused by DCM and 14 cases of control group who died of violent reasons and other diseases, which were autopsied in our department from 1997 to 2003. RESULT: Of 11 cases of DCM, there were 10 men and 1 woman with ranging in age from 7 to 49 years old (x (37.8) years old for 9 adult cases). Of 14 cases in the control group, there were 10 men and 4 women with ranging in age from 11 to 53 years old (x (29.9) years old for 11 adult cases). Myocardial Cx43 expression was obviously decreased in DCM group. Positive dyeing spots were different in size, distribution, color and disparity, some of them were distributed in the form of particle. Obvious change had not been observed in the cases of control group or with only slight changes in coloring degree and expressive area. The quantitative data showed that there was significant difference between two groups (p=0.0075) about Cx43 expressive area, but there was no difference between the left and right ventricles (p>0.05) in each group itself. And there was not difference between the two groups about average optical density of expression. CONCLUSION: Myocardial Cx43 expression is obviously reduced in the patients with DCM who die suddenly. The alteration of quantity and distribution of myocardial Cx43 expression is probably related to sudden death of the patients with DCM.     

心肌病猝死者心肌连接蛋白43的免疫组化染色观察

目的探讨心肌病猝死者心肌连接蛋白43(Cx43)染色变化及其与猝死的关系。方法运用免疫组化和图像分析技术,分2组(A和B组)检测20例心肌病猝死者心室肌的Cx43染色情况;并与14例非心肌病猝死者(C组)的检测结果对照。结果扩张型心肌病(DCM)猝死组(A组,11例)心肌Cx43染色明显减弱,阳性着色斑点大小不等、深浅不一、分布不均,有的呈散在颗粒状;其它类型的心肌病猝死组(B组,9例)亦见类似变化;非心肌病猝死的对照组(C组,14例)未见明显变化。定量检测并经统计分析发现,Cx43蛋白染色阳性的面积,A组与B组和C组的差异有非常显著性意义(P<0.01),B组与C组的差异无显著性意义(P>0.05);而平均光密度各组之间的差异无显著性意义(P>0.05)。结论心肌病猝死者心肌Cx43免疫组化染色明显减弱,尤以扩张型心肌病明显;心肌病猝死者心肌Cx43变化可能与其猝死有一定关系。     

The accuracy and reliability of the Suchey–Brooks pubic symphysis age estimation method: Systematic review and meta-analysis

Suchey–Brooks method has been studied many times with varying reports of accuracy and reliability. A systematic review and meta-analyses were utilized to quantitatively determine the accuracy and reliability of the Suchey–Brooks (S-B) method. A systematic search of PubMed and EBSCO health and medical databases was performed. Meta-analyses were performed to quantify the relationship between actual known age at death and the S-B method using Spearman's Rho and Pearson's r for (1) combined males and females estimates, (2) male-only estimates, and (3) female-only estimates. Overall correlation coefficient using Cohen's kappa, Spearman's Rho, and Pearson's r was also calculated to determine the interrater and intrarater reliability using the S-B method. Eighteen studies classified as moderate-to-high methodological quality met the inclusion criteria. The sample sizes were different for the combined male and female (n = 2620), male-only (n = 2602), and female-only (n = 1431) meta-analyses. The effect size of the age at death meta-analyses was large and significant for combined males and females (Spearman's Rho = 0.62; Pearson's r = 0.65), male-only (Spearman's Rho = 0.77; Pearson's r = 0.75), and female-only (Spearman's Rho = 0.71; Pearson's r = 0.71). The overall correlation coefficients of the interrater (Kappa = 0.76; Spearman's Rho = 0.73; Pearson's r = 0.80) and intrarater (Kappa = 0.81; Spearman's Rho = 0.91; Pearson's r = 0.83) reliability meta-analyses were large and significant. A significant degree of heterogeneity was present in all meta-analyses, with minimal evidence of publication bias. The meta-analyses results suggest the S-B method is highly reliable with a moderate-to-high degree of accuracy. Our results also identified sample size and accuracy differences between male and female individuals.     

Sudden death due to right ventricular cardiomyopathy

A 21-year-old man died suddenly at a small party. He had had no clinical signs of cardiac disease except for a slightly abnormal electrocardiogram (occasional premature ventricular contractions) since he was 15 years of age. Autopsy examination revealed cardiomegaly (469 g), with right atrial and ventricular dilatation. The right ventricular myocardium was massively replaced with adipose tissue, and there was one isolated fatty lesion in the right side of the ventricular septum. There were no congenital malformations such as a septal defect or valvular deformity. Histologically, muscular fibers remaining in the right ventricular wall showed neither degenerative nor inflammatory changes. An isolated lesion of the ventricular septum consisted of almost complete replacement of the muscle bundles with adipose tissue. Such a pathologic condition has recently been termed right ventricular cardiomyopathy. Postmortem examination is necessary to make a definite diagnosis of the disease, because in most adult cases of the disease, sudden death occurs before there have been any critical signs.     

心脏性猝死心肌组织N-Cadherin、Bax表达变化及评价

目的观察心脏性猝死者(SCD)心肌组织的神经性钙粘附蛋白(N-Cadherin)和Bax的表达变化,探讨其法医学意义。方法分别选取心脏性猝死和排除心脏疾病死因的尸检案例心肌组织标本各33例、29为SCD组和对照组。光镜下观察心肌组织病理学改变,检测N-Cadherin和Bax在心肌组织中的表达变化,并进行统计学分析。结果 N-Cadherin在SCD组心肌中表达呈弱阳性,排列紊乱,显著低于正常心肌,正常心肌组织中N-Cadherin呈强阳性表达,细胞间界限明显,排列整齐。Bax在SCD组表达呈阳性,显著高于正常心肌。结论 N-Cadherin和Bax的变化表达对心脏性猝死鉴定有意义。     

Evaluation of Agonal Cardiac Function for Sudden Cardiac Death in Forensic Medicine with Postmortem Brain Natriuretic Peptide (BNP) and NT-proBNP: A Meta-analysis

Sudden cardiac death (SCD) is an unexpected death caused by a sudden loss of cardiac function, which is currently a global public health problem. Evaluation of the agonal cardiac function of the deceased is a quite important task for the diagnosis of SCD in forensic medicine. Brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are currently considered as significant biomarkers for the diagnosis of heart failure in both clinical and forensic practices. To investigate the postmortem evaluation roles of postmortem BNP and NT-proBNP levels for SCD, the present study meta-analyzed eight related studies from Embase, Cochrane Library, PubMed, China Biomedical Literature Database, China National Knowledge Infrastructure, and Wanfang Data. Newcastle–Ottawa Quality Assessment Scale was used to assess the quality of the included literature, and the meta-analysis was performed by RevMan 5.3.5 software. Postmortem NT-proBNP in pericardial fluid showed higher levels in the SCD group than that of the non-SCD group with the weighted mean difference = 3665.74, 95% confidence interval: 1812.89–5518.59, and p = 0.0001. However, postmortem levels of BNP in pericardial fluid and NT-proBNP in serum revealed no statistical difference between SCD and non-SCD subjects. The results of present meta-analysis demonstrated that postmortem NT-proBNP in the pericardial fluid could be used as an ancillary indicator for evaluation of agonal cardiac function in forensic medicine.     

Is there progress in the autopsy diagnosis of sudden unexpected death in adults?

Sudden death is now currently described as natural unexpected death occurring within 1h of new symptoms. Most studies on the subject focused on cardiac causes of death because most of the cases are related to cardiovascular disease, especially coronary artery disease. The incidence of sudden death varies largely as a function of coronary heart disease prevalence and is underestimated. Although cardiac causes are the leading cause of sudden death, the exact incidence of the other causes is not well established because in some countries, many sudden deaths are not autopsied. Many risk factors of sudden cardiac death are identified: age, gender, heredity factors such as malignant mutations, left ventricular hypertrophy and left ventricle function impairment. The role of the police surgeon in the investigation of sudden death is very important. This investigation requires the interrogation of witnesses and of the family members of the deceased. The interrogation of physicians of the rescue team who attempted resuscitation is also useful. Recent symptoms before death and past medical history must be searched. Other sudden deaths in the family must be noted. The distinction between sudden death at rest and during effort is very important because some lethal arrhythmia are triggered by catecholamines during stressful activity. The type of drugs taken by the deceased may indicate a particular disease linked with sudden death. Sudden death in the young always requires systematic forensic autopsy performed by at least one forensic pathologist. According to recent autopsy studies, coronary artery disease is still the major cause of death in people aged more than 35 years. Cardiomyopathies are more frequently encountered in people aged less than 35 years. The most frequent cardiomyopathy revealed by sudden death is now arrhythmogenic right ventricular cardiomyopathy also known simply as right ventricular cardiomyopathy (RVC). The postmortem diagnosis of cardiomyopathies is very important because the family of the deceased will need counseling and the first-degree relatives may undergo a possible screening to prevent other sudden deaths. In each case of sudden death, one important duty of the forensic pathologist is to inform the family of all autopsy results within 1 month after the autopsy. Most of the recent progress in autopsy diagnosis of sudden unexpected death in the adults comes from molecular biology, especially in case of sudden death without significant morphological anomalies. Searching mutations linked with functional cardiac pathology such as long-QT syndrome, Brugada syndrome or idiopathic ventricular fibrillation is now the best way in order to explain such sudden death. Moreover, new syndromes have been described by cardiologists, such as short-QT syndrome and revealed in some cases by a sudden death. Molecular biology is now needed when limits of morphological diagnosis have been reached.