Review of the Determination of the Cause and Manner of Death, in Deaths Related to Medical Care / 대한법의학회지

A death certificate (DC) can be considered a legal document and in terms of societal use, it is a public document. A DC includes facts such as the time and place of death, as well as judgments as to the cause and manner of death. Whether it pertains to facts or judgments, recording false information results in a false DC. According to the National Association of Medical Examiners (NAME) in the United States, it is acknowledged that there are varying opinions and approaches when it comes to classifying the manner of death. Therefore, it may require a final judgment, including input from the legal system. Generally, deaths resulting from complications that occur during drug administration or medical procedures are classified as natural deaths, while deaths due to unforeseen complications that occur suddenly, are categorized as accidental deaths. Applying this classification by NAME to the principles and legal precedents related to the duty of explanation and medical lowas of the Korean Medical Association, it is reasonable to classify deaths resulting from complication, during medical care, as natural death. However, if the death occurs due to injury or poisoning during medical care, it falls under external causes, according to the principle of following the primary cause. In conclusion, it is considered reasonable to classify complications that occur during medical treatment as natural deaths when they are foreseeable and within the accepted range of complications determined by medical standards at that the time.

Effect of body mass index on the prognostic value of N-terminal pro-B-type natriuretic peptide in pneumonia: a comparative study between normal-weight and obese adults

Objective@#Body mass index (BMI) is a major determinant of N-terminal pro-brain natriuretic peptide (NT-proBNP). However, the relationship of BMI with pneumonia has not been entirely characterized. @*Methods@#Adult patients with pneumonia, who visited the emergency department from January 2017 to December 2019, were included. According to BMI, they were divided into two groups, including normal-weight and obesity groups. Data were retrospectively reviewed via the prospectively collected pneumonia registry and medical chart. NT-proBNP, BMI and pneumonia severity index (PSI) were determined for all subjects. The moderating effect between NT-proBNP and BMI was examined by entering interaction terms into the multivariable regression model predicting mortality. Using the area under the curve (AUC), the predictive performance of NT-proBNP was evaluated. @*Results@#Of 327 enrolled patients, 118 patients belonged to the obesity group. In a multivariable model including BMI, NT-proBNP was identified as an independent predictor of mortality. The AUC of the adjusted NT-proBNP including BMI, significantly increased the AUC of the adjusted NT-proBNP excluding BMI and tended to be superior to that of PSI. A positively significant BMI-by-NT-proBNP interaction for mortality was observed. NT-proBNP showed significant prognostic power in both BMI groups, but NT-proBNP of the obesity group had significantly higher AUC than that of the normalweight group. In the obesity group, the AUC of NT-proBNP tended to be higher than that of PSI. @*Conclusion@#BMI is a significant factor enhancing the prognostic power of NT-proBNP in pneumonia. The prognostic utility of NT-proBNP was significantly differed by BMI groups, which is more useful in the obesity group than the normalweight group.

Cytotoxicity of natural killer cells on canine mammary carcinoma cells

Natural killer (NK) cells play have a crucial role in the early phase of immune responses against various pathogens. We compared characteristics of canine NK cells against two canine mammary carcinoma cell lines, REM134 and CF41.Mg. REM134 showed higher expression of progesterone receptor, proliferative cell nuclear antigen, Ki67, multiple drug resistance, Bmi-1, c-myc, E-cadherin, and human epidermal growth factor receptor type-2 than that of CF41.Mg. For specific expansion and activation of NK cells, we isolated CD5 negative cells from canine peripheral blood mononuclear cells and co-cultured K562 cells in the presence of interleukin (IL)-2, IL-15, and IL-21 for 21 days. As a result, we found that expression markers of activated NK cells such as NKp30, NKp44, NKp46, NKG2D, CD244, perforin, granzyme B, and tumor necrosis factor alpha were highly upregulated. In addition, we found there was upregulated production of interferon gamma of activated NK cells against target cells such as REM134 and CF41.Mg.Specifically, we observed that cytotoxicity of NK cells against target cells was more sensitively reacted to CF41.Mg than REM134. Based on the results of this study, we recommend the development of an experimental application of CF41Mg, which has not been reported in canine mammary carcinoma research.

Proposal of the Autopsy Guideline for Infectious Diseases: Preparation for the Post-COVID-19 Era / 대한법의학회지

With the rapidly spreading coronavirus disease 2019 (COVID-19) pandemic over the past few months, the world is facing an unprecedented crisis. Innumerable lives have been lost to this novel infectious disease, the nature of which supersedes conventional medical understanding. People around the world are sacrificing their daily lives and enduring the crisis regardless of national boundaries and cultural backgrounds. The COVID-19 pandemic is not just a global health crisis, several aspects of life in the post-COVID-19 era are also being contemplated. Experts in unison are warning that the upcoming changes in all areas of life could potentially be far more drastic than ever experienced in the entire human civilization. The medical community is no exception, and therefore, personnel involved in forensic medicine also need to be adequately prepared for the future. Forensic medicine is a branch of medicine dedicated to one of the most important stages of the human lifecycle and has always been at the forefront in times of unprecedented social change. We present new autopsy guidelines in forensic medicine, formulated based on the various infectious diseases that we presently live with and may encounter in the future. In formulation of these guidelines several considerations have been taken into account, namely, the role forensic pathologists should play in the post-COVID-19 era and the necessary preparations as well as the support needed from society to fulfill that role. The present COVID-19 outbreak should be a starting point for formulating improvements in current practices in forensic science, including autopsy biosafety practices and the medicolegal death investigation system.

Death from 2,4-Dinitrophenol Poisoning: An Autopsy Case / 대한법의학회지

DNP (2,4-dinitrophenol) has been commonly used as a weight loss aid; in particular, it has been used by body builders to achieve significant fat loss while maintaining muscle mass. The sale of DNP was banned due to some cases of fatal poisoning. We describe an autopsy case of a 39-year-old man who died from taking DNP to treat obesity. He was 183 cm tall and weighed 101 kg (body mass index of 31). External examination did not reveal any specific findings implicating the cause of death. Gross examination revealed that the heart weight was 450 g, and there were no significant findings in the coronary arteries and myocardium, except for a few petechiae of the epicardium. The DNP concentration in the subject’s blood was 38.28 mg/L. According to references, a DNP blood concentration of 28 mg/L or higher would result in death. Therefore, the cause of death in this autopsy case was DNP toxicity.

Vasa Vasorum Densities in Human Carotid Atherosclerosis Is Associated with Plaque Development and Vulnerability

Objective@#: The extensive vasa vasorum network functions as a conduit for the entry of inflammatory cells or factors that promote the progression of angiogenesis and plaque formation. Therefore, we investigated the correlation between the carotid vasa vasorum activities and carotid plaque vulnerability using indocyanine green video angiography (ICG-VA) during carotid endarterectomy (CEA). @*Methods@#: Sixty-nine patients who underwent CEA were enrolled prospectively from September 2015 to December 2017. During CEA, a bolus of ICG was injected intravenously before and after resecting the atheroma. Additionally, we performed immunohistochemistry using CD68 (a surface marker of macrophages), CD117 (a surface marker of mast cells), and CD4 and CD8 (surface markers of T-cells) antibodies to analyze the resected plaque specimens. @*Results@#: The density of active vasa vasorum was observed in all patients using ICG-VA. The vasa vasorum externa (VVE) and interna (VVI) were seen in 11 (16%) and 57 patients (82.6%), respectively. Macroscopically, the VVE-type patterns were strongly associated with preoperative angiographic instability (81.8%, p=0.005) and carotid plaque vulnerability (90.9%, p=0.017). In contrast, the VVI-type patterns were weakly associated with angiographic instability (31.6%) and plaque vulnerability (49.1%). CD68-stained macrophages and CD117-stained mast cells were observed more frequently in unstable plaques than in stable plaques (p<0.0001, p=0.002, respectively). @*Conclusion@#: The early appearance of VVE, along with the presence of many microvessel channels that provided nutrients to the developing and expanding atheroma during ICG-VA, was strongly associated with unstable carotid plaques. The degree of infiltration of macrophages and mast cells is possibly related to the formation of unstable plaques.

An Autopsy-Proven Case of Limbic-Predominant Age-Related TDP-43 Encephalopathy

Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a recently established neurodegenerative disease entity. LATE neuropathological change (LATE-NC) is characterized by a TDP-43 proteinopathy that mainly involves the amygdala and medial temporal structures, with or without hippocampal sclerosis. LATE-NC is typically observed in individuals aged 80 years or older and manifests clinically as amnestic memory decline. Herein, we report a case of LATE diagnosed by brain autopsy in an 82-year-old male who had an 11-year history of memory impairment. Pathological examination revealed high Alzheimer disease neuropathological changes, as well as amygdala-predominant Lewy body pathology. In addition, immunohistochemistry for TDP-43 revealed neuronal and glial cytoplasmic inclusions in the dentate gyrus of the hippocampus, amygdala, and inferior temporal cortex. Increasing awareness of the newly defined entity LATE will enhance our understanding of the neurodegenerative processes that occur in the oldest individuals.

Proposal of the Autopsy Guideline for Infectious Diseases: Preparation for the Post-COVID-19 Era (abridged translation)

With the rapidly spreading coronavirus disease 2019 (COVID-19) pandemic over the past few months, the world is facing an unprecedented crisis. Innumerable lives have been lost to this novel infectious disease, the nature of which supersedes conventional medical understanding. The COVID-19 pandemic is not just a global health crisis, several aspects of life in the post-COVID-19 era are also being contemplated. Experts in unison are warning that the upcoming changes in all areas of life could potentially be far more drastic than ever experienced in the entire human civilization. The medical community is no exception, and therefore, personnel involved in forensic medicine also need to be adequately prepared for the future. Forensic medicine is a branch of medicine dedicated to one of the most important stages of the human lifecycle and has always been at the forefront in times of unprecedented social change. The autopsy, one of the most important tools of forensic medicine, is also useful to infectious diseases because it identifies the causal relationship between death and infection, reveals medical and epidemiological knowledge, and provides objective evidence for legal disputes. We present new autopsy guidelines in forensic medicine, formulated based on the various infectious diseases that we presently live with and may encounter in the future. In formulation of these guidelines several considerations have been taken into account, namely, the role forensic pathologists should play in the post-COVID-19 era and the necessary preparations as well as the support needed from society to fulfill that role. The present COVID-19 outbreak should be a starting point for formulating improvements in current practices in forensic science, including autopsy biosafety practices and the medicolegal death investigation system.

Clinical Outcomes of Idiopathic Epiretinal Membrane Removal in Patients 80 Years or Older

PURPOSE: To evaluate clinical outcomes of idiopathic epiretinal membrane removal in patients ≥ 80 years of age.METHODS: A retrospective review of medical records was performed with 56 patients who underwent vitrectomy and removal of idiopathic epiretinal membrane. In the ≥ 80 years of age group (n = 28), the best-corrected visual acuity (BCVA) and central macular thickness (CMT) before surgery were compared with those at the final follow-up. The amount of change in the BCVA after surgery was also compared between the ≥ 80 years of age group and the < 80 years of age group (n = 28).RESULTS: In the ≥ 80 years of age group, the mean follow-up period was 19.1 ± 17.0 months. Before surgery, 11 eyes were pseudophakic and 17 eyes were phakic. Combined cataract surgery was performed with epiretinal membrane removal in all 17 phakic eyes. The mean logarithm of the minimal angle of resolution BCVA was 0.75 ± 0.30 before surgery, which improved to 0.50 ± 0.30 at the final follow-up (p < 0.001). The CMT was 458.0 ± 79.7 µm before surgery, which decreased to 367.2 ± 83.4 µm at the final follow-up (p < 0.001). There was no significant difference in the amount of change in the BCVA after the surgery between the ≥ 80 years of age group and the < 80 years of age group (p = 0.547).CONCLUSIONS: In patients with idiopathic epiretinal membrane who were ≥ 80 years of age, the visual acuity was improved or maintained, and was accompanied with anatomical improvement after epiretinal membrane removal with or without cataract surgery. These results suggest the usefulness of epiretinal membrane removal in older patients.

Primary Age-Related Tauopathy: An Elderly Brain Pathology Frequently Encountered during Autopsy

Due to the progressive aging of Korean society and the introduction of brain banks to the Korean medical system, the possibility that pathologists will have access to healthy elderly brains has increased. The histopathological analysis of an elderly brain from a subject with relatively well-preserved cognition is quite different from that of a brain from a demented subject. Additionally, the histology of elderly brains differs from that of young brains. This brief review discusses primary age-related tauopathy; this term was coined to describe elderly brains with Alzheimer’s diseasetype neurofibrillary tangles mainly confined to medial temporal structures, and no β-amyloid pathology.

Case of making maxillary palatal augmentation complete denture for patient with dysphagia after partial glossectomy

If complication arises after glossectomy which leads to trouble in forming food bolus or transfer of the food, it is possible that either food bolus may block the airway or dysphagia may occur as the food bolus goes down into the airway. To solve the issue, palatal augmentation prosthesis could be used. In this case, the patient with an oral cancer is having difficulties swallowing food after glossectomy. Through taking impressions of polishing surface of his denture referring his tongue movement, the complete denture for the upper jaw was created using the concept of palatal augmentation prosthesis. This new upper denture increases the palatal-tongue contact pressure, allowing the patient to perform better swallowing and better pronunciation.

An Experimental Infarct Targeting the Internal Capsule: Histopathological and Ultrastructural Changes

BACKGROUND: Stroke involving the cerebral white matter (WM) has increased in prevalence, but most experimental studies have focused on ischemic injury of the gray matter. This study was performed to investigate the WM in a unique rat model of photothrombotic infarct targeting the posterior limb of internal capsule (PLIC), focusing on the identification of the most vulnerable structure in WM by ischemic injury, subsequent glial reaction to the injury, and the fundamental histopathologic feature causing different neurologic outcomes. METHODS: Light microscopy with immunohistochemical stains and electron microscopic examinations of the lesion were performed between 3 hours and 21 days post-ischemic injury. RESULTS: Initial pathological change develops in myelinated axon, concomitantly with reactive change of astrocytes. The first pathology to present is nodular loosening to separate the myelin sheath with axonal wrinkling. Subsequent pathologies include rupture of the myelin sheath with extrusion of axonal organelles, progressive necrosis, oligodendrocyte degeneration and death, and reactive gliosis. Increase of glial fibrillary acidic protein (GFAP) immunoreactivity is an early event in the ischemic lesion. WM pathologies result in motor dysfunction. Motor function recovery after the infarct was correlated to the extent of PLIC injury proper rather than the infarct volume. CONCLUSIONS: Pathologic changes indicate that the cerebral WM, independent of cortical neurons, is highly vulnerable to the effects of focal ischemia, among which myelin sheath is first damaged. Early increase of GFAP immunoreactivity indicates that astrocyte response initially begins with myelinated axonal injury, and supports the biologic role related to WM injury or plasticity. The reaction of astrocytes in the experimental model might be important for the study of pathogenesis and treatment of the WM stroke.

Analysis of Death due to Poisoning in Gwangju and Jeollanam-do Areas / 대한법의학회지

This study examined 190 cases of confirmed poisoning, as determined by autopsy findings, as well as alcohol and toxicant concentrations in post-mortem specimens. Judicial autopsies were performed from January 2007 to December 2014 at Department of Legal Medicine, Chonnam National University Medical School, the National Forensic Service Gwangju Institute, and St. Carollo Hospital. We analyzed the incidence of poisoning according to region and season in terms of year, sex, age, and classification of toxicants. In the regional classification, the number of deaths due to poisoning in Jeollanam-do and Gwangju areas was similar when considering autopsy numbers. The incidence was higher in autumn and spring than in summer and winter, and a large number of deaths occurred in 2008 and 2014. Additionally, the number of male deaths was approximately twice the number of female deaths, with the age of 50-59 being the most common age group. Pesticides comprised the largest number of deaths due to poison, followed by alcoholism, carbon monoxide, treatment drugs, and cyanic acid, in that order.

A Historical Review of the Korean Journal of Legal Medicine: In Commemoration of the 40th Anniversary of the Founding Korean Society for Legal Medicine / 대한법의학회지

The Korean Society for Legal Medicine (KSLM) was founded in 1976 and launched its official journal, the Korean Journal of Legal Medicine (KJLM), in 1977. They have played an important role in Korea's forensic medicine and science, the demand for which has increased in Korean society over the years. A historical review is important and has a significant value in the advancement of forensic medicine and science in Korea. Accordingly, this study reviews and analyzes all papers published in KJLM for 39 years, from Volume 1, Issue No. 1 in 1977 to Volume 39, Issue No. 4 in 2015. There are 891 published papers, which are categorized into 318 review articles, 339 original articles, and 234 case reports. Of the total 891 papers, 377 (42.3%) are related to forensic pathology, whereas 111 (12.5%) concern forensic genetics. The major submitting institutes are forensic medicine departments of universities and the National Forensic Service. KJLM's history can be divided into two phases. The first phase is from the 1970s to the 1990s, and the second, from the 2000s to the present. Many review articles were published in the first phase; approximately 10% of these articles concern clinical forensic medicine and law. Articles on forensic genetics, identification, and entomology also started to be published in the first phase. In the next phase, many case reports from the National Forensic Service were published, and the number of articles on forensic pathology and forensic genetics multiplied. The results of this study provide KSLM and KJLM with direction toward sustainable development. This study is part of the organization's 40th anniversary celebration, and in commemoration of its contribution to advancing human rights and social stability in Korea.

Proteomic Analysis of a Rat Cerebral Ischemic Injury Model after Human Cerebral Endothelial Cell Transplantation

OBJECTIVE: Cerebral endothelial cells have unique biological features and are fascinating candidate cells for stroke therapy. METHODS: In order to understand the molecular mechanisms of human cerebral endothelial cell (hCMEC/D3) transplantation in a rat stroke model, we performed proteomic analysis using 2-dimensional electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Protein expression was confirmed by quantitative real-time PCR and Western blot. RESULTS: Several protein spots were identified by gel electrophoresis in the sham, cerebral ischemia (CI), and CI with hCMEC/D3 treatment cerebral ischemia with cell transplantation (CT) groups, and we identified 14 differentially expressed proteins in the CT group. Proteins involved in mitochondrial dysfunction (paraplegin matrix AAA peptidase subunit, SPG7), neuroinflammation (peroxiredoxin 6, PRDX6), and neuronal death (zinc finger protein 90, ZFP90) were markedly reduced in the CT group compared with the CI group. The expression of chloride intracellular channel 4 proteins involved in post-ischemic vasculogenesis was significantly decreased in the CI group but comparable to sham in the CT group. CONCLUSION: These results contribute to our understanding of the early phase processes that follow cerebral endothelial cell treatment in CI. Moreover, some of the identified proteins may present promising new targets for stroke therapy.

Analysis of Cisternal Puncture Results during a Postmortem Examination / 대한법의학회지

Examination of cerebrospinal fluid (CSF) samples is important in postmortem examinations. CSF samples can be collected by performing lumbar or cisternal punctures. Additionally, if bloody fluid is aspirated during a spinal puncture, intracranial hemorrhage could be diagnosed. However, vascular injury and hemorrhage can occur during these procedures. The authors performed cisternal punctures during routine autopsies; further, to evaluate the usefulness of the former, the results were analyzed. Out of 50 cases, bloody fluid was aspirated in CSF samples of 20, while CSF samples of the other 30 were clear. Cases in which bloody fluid was aspirated were divided into blood-tinged and blood aspiration groups according to hemoglobin levels in the aspirated fluids. Cisternal punctures were characterized by high specificity and sensitivity; further, positive and negative predictive values were obtained that enabled detection of head and neck injuries including non-traumatic basal subarachnoid hemorrhage. Main head and neck injuries in blood aspiration group were skull base fracture, cervical fracture, and dislocation.

A Comparative Study of Postmortem Bacterial Culture and Identification Methods / 대한법의학회지

Postmortem bacterial culture can be valuable for investigating deaths and determining the cause of death. However, there are many concerns regarding postmortem bacterial culture such as postmortem transmigration and agonal spread of bacteria. The two main methods for identification of the bacteria are biochemical and genetic methods. In Korea, the genetic method has been used for postmortem bacterial culture and identification in forensic medicine. However, there is a lack of consensus on the method to be used for postmortem bacterial culture and identification. Herein, we compared the genetic and biochemical methods of postmortem bacterial culture in autopsy practice. Both analyses were performed on the same samples. Bacteria were identified in 28 of the 34 cases (82.4%). Of the 74 comparable samples, only 28 (37.8%) showed consistent results by both methods. In addition, the biochemical method had a shorter reporting time and was more sensitive. In conclusion, we analyzed the causes of the inconsistency between the two methods and provided appropriate conditions and protocols for postmortem bacterial culture and identification.

Chordoid Glioma with Intraventricular Dissemination: A Case Report with Perfusion MR Imaging Features

Chordoid glioma is a rare low grade tumor typically located in the third ventricle. Although a chordoid glioma can arise from ventricle with tumor cells having features of ependymal differentiation, intraventricular dissemination has not been reported. Here we report a case of a patient with third ventricular chordoid glioma and intraventricular dissemination in the lateral and fourth ventricles. We described the perfusion MR imaging features of our case different from a previous report.

Study of the Test for Postmortem C-Reactive Protein in Routine Autopsy Practice / 대한법의학회지

C-Reactive protein (CRP) is an acute phase response protein synthesized in the liver as a response to various inflammation. CRP is extensively used as a general marker for inflammation in clinical medicine. A forensic applications of the CRP using postmortem samples have been studied in oversea. We have compared CRP in the between antemortem and postmortem samples and studied stability of postmortem blood samples for CRP test. In 69 consecutive autopsy cases, we have analysed heart blood samples (69 cases), peripheral blood samples (33 cases), and vitreous humor samples (60 cases). Postmortem CRP was elevated in 25 cases (36.2%) and possible causes of CRP elevation were inflammatory disease except one case (unknown). Postmortem CRP test shows sensitivity 86.7%, specificity 80%, positive predictive value 92.9%, and negative predictive value 66.7% for inflammation based on 20 cases with antemortem CRP results. The postmortem CRP levels were similar in the heart blood samples and peripheral blood samples. Vitreous humor samples are not useful in postmortem CRP testing. And both whole blood and serum samples are stable in room temperature until 31 days. We conclude that serum from heart blood is best suitable sample for postmortem CRP test and postmortem CRP test is useful in routine autopsy practice to detect inflammatory disease such as sepsis. From the view of postmortem point, we desire that this valuable test should be used in routine autopsy practice in Korea.

Death due to Pulmonary Thromboembolism with Cerebral Venous Thrombosis / 대한법의학회지

Cerebral venous thrombosis is an uncommon cause of cerebral infarction. A 31-year-old man complained of headache, weakness, and numbness of the left leg a day before being admitted to the hospital. After admission, brain computed tomography and brain magnetic resonance imaging revealed superior sagittal sinus thrombosis with cerebral infarction in the right hemisphere. He had no significant medical history. On the fourth hospital day, he suddenly collapsed and died. Medicolegal autopsy was performed 3 days later; medical malpractice was suspected. External examination revealed a few conjunctival petechiae. Internal examination revealed thrombi in the superior sagittal sinus and superficial cortical veins. Thrombi were noted in the pulmonary trunk and both pulmonary arteries. Upon dissection of the left leg, we found thrombi in the posterior tibial vein. A microscopic examination revealed vasculitis of the same cortical veins, and we therefore assumed that vasculitis of the cortical veins gave rise to thrombosis. In typical autopsy practice, an examination of the dura mater is often overlooked, but careful examination of this region should be performed in cases of cerebral infarction in young adults, such as this one.