Autopsy for Medical Diagnostics

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (31 May 2021) | Viewed by 23851

Special Issue Editors


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Guest Editor
Lino Rossi Research Center, Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy
Interests: anatomic pathology; cardiovascular pathology; autopsy for medical diagnostics; pathology of sudden unexpected death
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Co-Guest Editor
Departamento de Patologia e Medicina Legal, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, 14049-900 Ribeirão Preto, São Paulo, Brasil
Interests: cardiovascular pathology; post-mortem investigation; autopsy; perinatal pathology; sudden unexpected death; sudden cardiac death; sudden infant death syndrome; cardiac conduction system; general pathology; surgical pathology; pulmonary pathology
Special Issues, Collections and Topics in MDPI journals

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Co-Guest Editor
“Lino Rossi” Research Center for the Study and Prevention of Unexpected Perinatal Death and SIDS, Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy
Interests: neuropathology; autonomic nervous system; brain development; neurotransmitters; molecular neurology; SIDS
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue of Diagnostics addresses the scope of the practice of autopsy for medical diagnostics. 

Autopsy is the post-mortem examination of the deceased body and organs to determine the cause of death and to study the pathological changes. Autopsy is an anatomo-pathological professional activity that requires a high level of technical ability and knowledge for its performance and interpretation.

The importance of post-mortem investigations for the documentation of cause of death will be discussed in this Special Issue, including the expanding roles of molecular autopsy.  The indications and dissection techniques of autopsy will also be reviewed in this Special Issue, along with interpretations of post-mortem findings, described in relation to clinical diagnostics, with discussions about clinico-pathological correlations.  The role of the pathologist, especially the cardiovascular pathologist, will be discussed in terms of the evaluation of cause of death. The objectives of the autopsy will be considered, including assessments of the validity and appropriateness of diagnostic, medical, and surgical procedures. The provision of information to the patient’s relatives, to colleague physicians, to the society at large and to medical literature, as discovered during the evaluation of subjects that died suddenly and unexpectedly, will also be addressed.

Basic information on virtual autopsies based on diagnostic imaging studies will be provided.  The increasing need for quality assurance in relation to autopsies, medical education and training will also be presented. The teaching of autopsy procedures is “vital” in preserving and increasing medical knowledge, in order to diminish undiagnosed medical illnesses, as stated in an old Latin aphorism: “Hic mors gaudet surrurrere vitae”, literally: “Here death is pleased to help life”.

Dr. Giulia Ottaviani
Dr. Anna M. Lavezzi
Dr. Simone G. Ramos
Guest Editors

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • autopsy
  • post-mortem investigation
  • cardiovascular pathology
  • sudden cardiac death
  • sudden unexpected death
  • perinatal autopsy
  • molecular autopsy
  • virtual autopsy
  • COVID-19
  • SARS-CoV-2

Published Papers (8 papers)

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Editorial

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7 pages, 234 KiB  
Editorial
Why Should Clinical Autopsies Continue to Exist?
by Simone Gusmão Ramos, Giulia Ottaviani, Luiz Cesar Peres, Bruna Amanda Cruz Rattis, Patricia Santos Leão, Thamiris Nadaf Akel, Leticia Ussem, Caio Antonio Campos Prado, Elaine Christine Dantas Moises, Lilian Christiane Andrade Grimm and Eliane Pedra Dias
Diagnostics 2021, 11(8), 1482; https://doi.org/10.3390/diagnostics11081482 - 16 Aug 2021
Cited by 1 | Viewed by 1791
Abstract
At some point in history, medicine was integrated with pathology, more precisely, with pathological anatomy [...] Full article
(This article belongs to the Special Issue Autopsy for Medical Diagnostics)

Research

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18 pages, 6842 KiB  
Article
Postmortem Cardiopulmonary Pathology in Patients with COVID-19 Infection: Single-Center Report of 12 Autopsies from Lausanne, Switzerland
by Sabina Berezowska, Karine Lefort, Kalliopi Ioannidou, Daba-Rokhya Ndiaye, Damien Maison, Constantinos Petrovas, Samuel Rotman, Nathalie Piazzon, Dina Milowich, Nathalie Sala, Chun-Yi Tsai, Eleonore Multone, Pierre-Yves Bochud, Mauro Oddo, Bettina Bisig and Laurence de Leval
Diagnostics 2021, 11(8), 1357; https://doi.org/10.3390/diagnostics11081357 - 28 Jul 2021
Cited by 10 | Viewed by 2940
Abstract
We report postmortem cardio-pulmonary findings including detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in formalin-fixed paraffin embedded tissue in 12 patients with COVID-19. The 5 women and 7 men (median age: 73 years; range 35–96) died 6–38 days after onset of [...] Read more.
We report postmortem cardio-pulmonary findings including detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in formalin-fixed paraffin embedded tissue in 12 patients with COVID-19. The 5 women and 7 men (median age: 73 years; range 35–96) died 6–38 days after onset of symptoms (median: 14.5 days). Eight patients received mechanical ventilation. Ten patients showed diffuse alveolar damage (DAD), 7 as exudative and 3 as proliferative/organizing DAD. One case presented as acute fibrinous and organizing pneumonia. Seven patients (58%) had acute bronchopneumonia, 1/7 without associated DAD and 1/7 with aspergillosis and necrotic bronchitis. Microthrombi were present in 5 patients, only in exudative DAD. Reverse transcriptase quantitative PCR detected high virus amounts in 6 patients (50%) with exudative DAD and symptom-duration ≤14 days, supported by immunohistochemistry and in-situ RNA hybridization (RNAscope). The 6 patients with low viral copy levels were symptomatic for ≥15 days, comprising all cases with organizing DAD, the patient without DAD and one exudative DAD. We show the high prevalence of DAD as a reaction pattern in COVID-19, the high number of overlying acute bronchopneumonia, and high-level pulmonary virus detection limited to patients who died ≤2 weeks after onset of symptoms, correlating with exudative phase of DAD. Full article
(This article belongs to the Special Issue Autopsy for Medical Diagnostics)
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23 pages, 3227 KiB  
Article
Sudden Unexpected Death Associated with Arrhythmogenic Cardiomyopathy: Study of the Cardiac Conduction System
by Giulia Ottaviani, Graziella Alfonsi, Simone G. Ramos and L. Maximilian Buja
Diagnostics 2021, 11(8), 1323; https://doi.org/10.3390/diagnostics11081323 (registering DOI) - 23 Jul 2021
Cited by 3 | Viewed by 2399
Abstract
A retrospective study was conducted on pathologically diagnosed arrhythmogenic cardiomyopathy (ACM) from consecutive cases over the past 34 years (n = 1109). The anatomo-pathological analyses were performed on 23 hearts diagnosed as ACM (2.07%) from a series of 1109 suspected cases, while [...] Read more.
A retrospective study was conducted on pathologically diagnosed arrhythmogenic cardiomyopathy (ACM) from consecutive cases over the past 34 years (n = 1109). The anatomo-pathological analyses were performed on 23 hearts diagnosed as ACM (2.07%) from a series of 1109 suspected cases, while histopathological data of cardiac conduction system (CCS) were available for 15 out of 23 cases. The CCS was removed in two blocks, containing the following structures: Sino-atrial node (SAN), atrio-ventricular junction (AVJ) including the atrio-ventricular node (AVN), the His bundle (HB), the bifurcation (BIF), the left bundle branch (LBB) and the right bundle branch (RBB). The ACM cases consisted of 20 (86.96%) sudden unexpected cardiac death (SUCD) and 3 (13.04%) native explanted hearts; 16 (69.56%) were males and 7 (30.44%) were females, ranging in age from 5 to 65 (mean age ± SD, 36.13 ± 16.06) years. The following anomalies of the CCS, displayed as percentages of the 15 ACM SUCD cases in which the CCS has been fully analyzed, have been detected: Hypoplasia of SAN (80%) and/or AVJ (86.67%) due to fatty-fibrous involvement, AVJ dispersion and/or septation (46.67%), central fibrous body (CFB) hypoplasia (33.33%), fibromuscular dysplasia of SAN (20%) and/or AVN (26.67%) arteries, hemorrhage and infarct-like lesions of CCS (13.33%), islands of conduction tissue in CFB (13.33%), Mahaim fibers (13.33%), LBB block by fibrosis (13.33%), AVN tongue (13.33%), HB duplicity (6.67%%), CFB cartilaginous meta-hyperplasia (6.67%), and right sided HB (6.67%). Arrhythmias are the hallmark of ACM, not only from the fatty-fibrous disruption of the ventricular myocardium that accounts for reentrant ventricular tachycardia, but also from the fatty-fibrous involvement of CCS itself. Future research should focus on application of these knowledge on CCS anomalies to be added to diagnostic criteria or at least to be useful to detect the patients with higher sudden death risks. Full article
(This article belongs to the Special Issue Autopsy for Medical Diagnostics)
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18 pages, 1815 KiB  
Article
Causes of Death and Survival in Alcoholic Cirrhosis Patients Undergoing Liver Transplantation: Influence of the Patient’s Clinical Variables and Transplant Outcome Complications
by J. M. Bolarín, M. D. Pérez-Cárceles, J. P. Hernández del Rincón, A. Luna, A. Minguela, M. Muro and I. Legaz
Diagnostics 2021, 11(6), 968; https://doi.org/10.3390/diagnostics11060968 - 27 May 2021
Cited by 4 | Viewed by 4173
Abstract
Background. Clinical and molecular mechanisms involved in the cause and time of death of alcoholic cirrhosis (AC) patients undergoing liver transplantation (LT) are not entirely understood. In sudden death cases, judicial autopsy practice is mandatory for determining the cause and circumstances of death. [...] Read more.
Background. Clinical and molecular mechanisms involved in the cause and time of death of alcoholic cirrhosis (AC) patients undergoing liver transplantation (LT) are not entirely understood. In sudden death cases, judicial autopsy practice is mandatory for determining the cause and circumstances of death. The medico-legal autopsy data are essential for helping health authorities to guide future public health activities, assess the effectiveness of health systems, and adopt the necessary preventive measures to improve and adapt the treatments in order to increase these patients’ survival. Objective. Our study aimed to determine the different clinical and sociodemographic causes that influence the different causes of death and the short- and long-term survival of AC patients undergoing liver transplantation. Methods. A total of 122 deceased AC patients undergoing LT were analyzed at different times post-transplantation. The main pre- and post-transplant complications were analyzed in relation to the cause of death and the patient’s survival, as well as the causes and time at which the patient’s death occurred. Results. A total of 53.3% of non-sudden death was observed. A large number of the deaths of AC patients undergoing transplantation were due to non-sudden death, sepsis, and graft failure (GF), the main causes of death in the sample being similar in both sexes. In non-sudden deaths, there were no significant differences between the death rates either related or not related to the liver transplant. Sepsis was the main cause, with the highest percentage (21.3%) of mortality, followed by GF (18.9%) and multiorgan failure (15.6%) at ten years. Furthermore, our results showed how pre-transplant clinical complications, such as viral infections and encephalopathy, influence the age at which multiorgan failure occurs in the transplanted patient. Conclusion. Multiorgan failure is the leading cause of sudden death, with higher mortality during the first year after transplantation, followed by sepsis and GF. Our results show the vulnerability of AC patients, both in the hospital period after the transplant and outside. Full article
(This article belongs to the Special Issue Autopsy for Medical Diagnostics)
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12 pages, 1736 KiB  
Article
Frequency and Significance of Pathologic Pulmonary Findings in Postmortem Examinations—A Single Center Experience before COVID-19
by Sabina Berezowska, Andreas Schmid, Tereza Losmanová, Mafalda Trippel, Annika Blank, Yara Banz, Stephan M. Jakob and Rupert Langer
Diagnostics 2021, 11(5), 894; https://doi.org/10.3390/diagnostics11050894 - 18 May 2021
Cited by 3 | Viewed by 3349
Abstract
Coronavirus disease 2019 (COVID-19) has shown the importance of postmortem investigation of deceased patients. For a correct interpretation of the pulmonary findings in this new era, it is, however, crucial to be familiar with pathologic pulmonary conditions observed in postmortem investigations in general. [...] Read more.
Coronavirus disease 2019 (COVID-19) has shown the importance of postmortem investigation of deceased patients. For a correct interpretation of the pulmonary findings in this new era, it is, however, crucial to be familiar with pathologic pulmonary conditions observed in postmortem investigations in general. Adequate postmortem histopathological evaluation of the lungs may be affected by suboptimal gross work up, autolysis or poor fixation. Using a standardized preparation approach which consisted in instillation of 4% buffered formaldehyde through the large bronchi for proper fixation and preparing large frontal tissue sections of 1–2 cm thickness after at least 24 h fixation, we comprehensively analyzed postmortem pulmonary findings from consecutive adult autopsies of a two-year period before the occurrence of COVID-19 (2016–2017). In total, significant pathological findings were observed in 97/189 patients (51%), with 28 patients showing more than one pathologic condition. Acute pneumonia was diagnosed 33/128 times (26%), embolism 24 times (19%), primary pulmonary neoplasms 18 times (14%), organizing pneumonia and other fibrosing conditions 14 times (11%), pulmonary metastases 13 times (10%), diffuse alveolar damage 12 times (9%), severe emphysema 9 times (7%) and other pathologies, e.g., amyloidosis 5/128 times (4%). Pulmonary/cardiopulmonary disease was the cause of death in 60 patients (32%). Clinical and pathological diagnoses regarding lung findings correlated completely in 75 patients (40%). Autopsy led to confirmation of a clinically suspected pulmonary diagnosis in 57 patients (39%) and clarification of an unclear clinical lung finding in 16 patients (8%). Major discrepant findings regarding the lungs (N = 31; 16%) comprised cases with clinical suspicions that could not be confirmed or new findings not diagnosed intra vitam. A significant proportion of acute pneumonias (N = 8; 24% of all cases with this diagnosis; p = 0.011) was not diagnosed clinically. We confirmed the frequent occurrence of pulmonary pathologies in autopsies, including inflammatory and neoplastic lesions as the most frequent pathological findings. Acute pneumonia was an important cause for discrepancy between clinical and postmortem diagnostics Full article
(This article belongs to the Special Issue Autopsy for Medical Diagnostics)
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8 pages, 439 KiB  
Article
Diagnostic Application of Postmortem Cardiac Troponin I Pericardial Fluid/Serum Ratio in Sudden Cardiac Death
by Diana Hernández-Romero, María del Rocío Valverde-Vázquez, Juan Pedro Hernández del Rincón, José A. Noguera-Velasco, María D. Pérez-Cárceles and Eduardo Osuna
Diagnostics 2021, 11(4), 614; https://doi.org/10.3390/diagnostics11040614 - 30 Mar 2021
Cited by 5 | Viewed by 1943
Abstract
In approximately 5% of unexpected deaths, establishing a conclusive diagnosis exclusively on the basis of anatomo-pathological findings in a classic autopsy is difficult. Postmortem biomarkers have been actively investigated as complementary indicators to help to reach valid conclusions about the circumstances of death. [...] Read more.
In approximately 5% of unexpected deaths, establishing a conclusive diagnosis exclusively on the basis of anatomo-pathological findings in a classic autopsy is difficult. Postmortem biomarkers have been actively investigated as complementary indicators to help to reach valid conclusions about the circumstances of death. Several studies propose either the pericardial fluid or peripheral veins as a location for troponin determination, but the optimum sampling site is still a matter of debate. Our objective was to evaluate the association between the ratio of troponin values in the pericardial fluid and serum (determined postmortem) and the diagnosis of acute myocardial infarction (AMI) in the context of sudden cardiac death. We included 175 forensic cases. Two groups were established: AMI deaths (48; 27.4%) and the control group (127; 72.6%). The cardiac Troponin I (cTnI) values in the pericardial fluid and the troponin ratio were found to be associated with the cause of death. Univariate regression analyses showed that both age and the cTnI ratio were significantly associated with the diagnosis of AMI death. In a multivariate analysis, adjusting for confounding factors, the age and cTnI ratio were independent predictors of death from myocardial infarction. We performed a receiver operating characteristic (ROC) curve for the cTnI ratio for AMI death and selected a cut-off point. Our biomarker was found to be a valuable and highly effective tool for use in the forensic field as a complementary method to facilitate diagnosis in nonconclusive autopsies. Full article
(This article belongs to the Special Issue Autopsy for Medical Diagnostics)
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23 pages, 10467 KiB  
Article
Morphofunctional Characterization of Different Tissue Factors in Congenital Diaphragmatic Hernia Affected Tissue
by Ricards Kaulins, Laura Ramona Rozite, Mara Pilmane and Aigars Petersons
Diagnostics 2021, 11(2), 289; https://doi.org/10.3390/diagnostics11020289 - 12 Feb 2021
Cited by 1 | Viewed by 3485
Abstract
Congenital diaphragm hernia (CDH) is a congenital disease that occurs during prenatal development. Although the morbidity and mortality rate is rather significant, the pathogenesis of CDH has been studied insignificantly due to the decreased accessibility of human pathological material. Therefore the aim of [...] Read more.
Congenital diaphragm hernia (CDH) is a congenital disease that occurs during prenatal development. Although the morbidity and mortality rate is rather significant, the pathogenesis of CDH has been studied insignificantly due to the decreased accessibility of human pathological material. Therefore the aim of our work was to evaluate growth factors (transforming growth factor-beta (TGF-β), basic fibroblast growth factor (bFGF), insulin-like growth factor 1 (IGF-1), hepatocyte growth factor (HGF)) and their receptors (fibroblast growth factor receptor 1 (FGFR1), insulin-like growth factor 1 (IGF-1R)), muscle (dystrophin, myosin, alpha actin) and nerve quality (nerve growth factor (NGF), nerve growth factor receptor (NGFR), neurofilaments (NF)) factors, local defense factors (ß-defensin 2, ß-defensin 4), programmed cell death (TUNEL), and separate gene (Wnt-1) expression in human pathological material to find immunohistochemical marker differences between the control and the CDH patient groups. A semi-quantitative counting method was used for the evaluation of the tissues and structures in the Biotin-Streptavidin-stained slides. Various statistically significant differences were found in immunoreactive expression between the patient and the control group tissue and the morphological structures as well as very strong, strong, and moderate correlations between immunoreactives in different diaphragm cells and structures. These significant changes and various correlations indicate that multiple morphopathogenetic pathways are affected in CDH pathogenesis. This work contains the evaluation of the causes for these changes and their potential involvement in CDH pathogenesis. Full article
(This article belongs to the Special Issue Autopsy for Medical Diagnostics)
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Other

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8 pages, 753 KiB  
Opinion
Acute Heart Failure, 90-Day Mortality, and Gravitational Ischemia in the Brain
by J. Howard Jaster and Giulia Ottaviani
Diagnostics 2022, 12(6), 1473; https://doi.org/10.3390/diagnostics12061473 - 15 Jun 2022
Cited by 1 | Viewed by 1747
Abstract
During the 90 days following hospitalization for acute heart failure, the ejection fraction and type of discharge medications have been shown in clinical trials to have little effect on mortality. We examined the recent literature addressing brain-related etiologies of sudden death following heart [...] Read more.
During the 90 days following hospitalization for acute heart failure, the ejection fraction and type of discharge medications have been shown in clinical trials to have little effect on mortality. We examined the recent literature addressing brain-related etiologies of sudden death following heart failure. Two mechanisms of sudden unexpected death have been suggested to possibly result from four significant influences on pathophysiology in the brain. The two causes of sudden death are (1) severe cardiac arrhythmia and (2) neurogenic pulmonary edema. They are both mediated through the brainstem autonomic nuclei generally and executed specifically through the dorsal motor nucleus of the vagus nerve. The four significant influences on pathophysiology, all contributing to ischemia in the brainstem autonomic nuclei, are: (1) Hyper-stimulation of neurons in the solitary tract nucleus, increasing their metabolic requirements; (2) Inadequate blood flow at a vascular watershed terminus, perfusing the autonomic nuclei; (3) Additionally decreased blood flow, globally throughout the brain, following vasoconstriction related to relative hyperventilation and decreased pCO2 levels; (4) Gravitational ischemia in the brainstem caused by the weight of the cerebral hemispheres sitting above the brainstem. Changes in head tilt release gravitational ischemia in the brain. There is no specific head position relative to gravity that is considered favorable or unfavorable for an extended period of time, longer than 24 h. Even a small degree of head elevation, used in managing pulmonary congestion, may increase gravitational ischemia in the posterior fossa and brainstem. In this paper, we suggest a new and important research avenue for intervening in cardiac arrhythmias and preventing their occurrence through the non-invasive use of head-tilting and other head repositioning maneuvers. This could potentially help many geriatric patients with heart failure, who have decreased mobility in bed, and who tend to stay in one position longer, thereby increasing gravitational ischemia in the brain. Full article
(This article belongs to the Special Issue Autopsy for Medical Diagnostics)
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