Postmortem Identification of Genetic Variations Associated with Sudden Unexpected Death in Young People.

Sudden unexpected death in the young (SUDY) is a traumatic occurrence for their family; however, information on the genetic variations associated with the condition is currently lacking. It is important to carry out postmortem genetic analyses in cases of sudden death to provide information for relatives and to allow appropriate genetic counselling and clinical follow-up. This study aimed to investigate the genetic variations associated with the occurrence of SUDY in Japan, using next-generation sequencing (NGS). The study included 18 cases of SUDY (16 males, 2 females; age 15-47 years) who underwent autopsy, including NGS DNA sequencing for molecular analysis. A total of 168 genes were selected from the sequencing panel and filtered, resulting in the identification of 60 variants in cardiac disease-related genes. Many of the cases had several of these genetic variants and some cases had a cardiac phenotype. The identification of genetic variants using NGS provides important information regarding the pathogenicity of sudden death.

Bleeding-Source Exploration in Subdural Hematoma: Observational Study on the Usefulness of Postmortem Computed Tomography Angiography.

In a few cases, postmortem computed tomography angiography (PMCTA) is effective in postmortem detection of cortical artery rupture causing subdural hematoma (SDH), which is difficult to detect at autopsy. Here, we explore the usefulness and limitations of PMCTA in detecting the sites of cortical arterial rupture for SDH. In 6 of 10 cases, extravascular leakage of contrast material at nine different places enabled PMCTA to identify cortical arterial rupture. PMCTA did not induce destructive arterial artifacts, which often occur during autopsy. We found that, although not in all cases, PMCTA could show the site of cortical arterial rupture causing subdural hematoma in some cases. This technique is beneficial for cases of SDH autopsy, as it can be performed nondestructively and before destructive artifacts from the autopsy occur.

Accuracy of ZedView, the Software for Three-Dimensional Measurement and Preoperative Planning: A Basic Study.

Background and Objectives: In the field of orthopedic surgery, novel techniques of three-dimensional shape modeling using two-dimensional tomographic images are used for bone-shape measurements, preoperative planning in joint-replacement surgery, and postoperative evaluation. ZedView® (three-dimensional measurement instrument and preoperative-planning software) had previously been developed. Our group is also using ZedView® for preoperative planning and postoperative evaluation for more accurate implant placement and osteotomy. This study aimed to evaluate the measurement error in this software in comparison to a three-dimensional measuring instrument (3DMI) using human bones. Materials and Methods: The study was conducted using three bones from cadavers: the pelvic bone, femur, and tibia. Three markers were attached to each bone. Study 1: The bones with markers were fixed on the 3DMI. For each bone, the coordinates of the center point of the markers were measured, and the distances and angles between these three points were calculated and defined as "true values." Study 2: The posterior surface of the femur was placed face down on the 3DMI, and the distances from the table to the center of each marker were measured and defined as "true values." In each study, the same bone was imaged using computed tomography, measured with this software, and the measurement error from the corresponding "true values" was calculated. Results: Study 1: The mean diameter of the same marker using the 3DMI was 23.951 ± 0.055 mm. Comparisons between measurements using the 3DMI and this software revealed that the mean error in length was <0.3 mm, and the error in angle was <0.25°. Study 2: In the bones adjusted to the retrocondylar plane with the 3DMI and this software, the average error in the distance from the planes to each marker was 0.43 (0.32-0.58) mm. Conclusion: This surgical planning software could measure the distance and angle between the centers of the markers with high accuracy; therefore, this is very useful for pre- and postoperative evaluation.

Detection and Morphological Analysis of Micro-Ruptured Cortical Arteries in Subdural Hematoma: Three-Dimensional Visualization Using the Tissue-Clearing Clear, Unobstructed, Brain/Body Imaging Cocktails and Computational Analysis Method.

One of the causes of bleeding in subdural hematoma is cortical artery rupture, which is difficult to detect at autopsy. Therefore, reports of autopsy cases with this condition are limited and hence, the pathogenesis of subdural hematoma remains unclear. Herein, for the detection and morphological analysis of cortical artery ruptures as the bleeding sources of subdural hematoma, we used the tissue-clearing CUBIC (clear, unobstructed, brain/body imaging cocktails and computational analysis) method with light-sheet fluorescence microscopy and reconstructed the two-dimensional and three-dimensional images. Using the CUBIC method, we could clearly visualize and detect cortical artery ruptures that were missed by conventional methods. Indeed, the CUBIC method enables three-dimensional morphological analysis of cortical arteries including the ruptured area, and the creation of cross-sectional two-dimensional images in any direction, which are similar to histopathological images. This highlights the effectiveness of the CUBIC method for subdural hematoma analysis.

PROS1 variant in sudden death case of pulmonary embolism caused by calcification in the inferior vena cava: The importance of postmortem genetic analysis.

A Japanese man in his 30s died suddenly. Postmortem computed tomography and autopsy revealed a pulmonary embolism from an organizing thrombus in the inferior vena cava as the cause of death. Genomic analysis of congenital thrombophilia-related genes (i.e., SERPINC1, PROC, PROS1, F2, F5, PLG, and MTHFR) revealed a heterozygous variant of PROS1 (p.A139V), which has been reported in patients with congenital protein S deficiency. After a genetic conference that included forensic pathologists, molecular scientists, genetic researchers, genetic clinicians, and clinical physicians, the results of the genetic analysis were explained to the family. Biochemical analyses of protein S (PS) activity and total PS antigen levels were performed with samples from the deceased's family and genetic analysis was not performed until clinical symptoms appear. Herein we demonstrate the importance of genetic background in cases of a sudden death due to pulmonary embolism.

The usefulness of postmortem computed tomography angiography for subdural hematoma caused by rupture of the cortical artery: A report of two autopsy cases and a literature review.

Acute subdural hematoma (SDH) occurs following severe head trauma with brain contusion or rupture of bridging veins. Conversely, SDH caused by rupture of a cortical artery without trauma or with minor trauma is also possible. Although over 180 cases of the latter SDH have been reported, they were predominantly diagnosed only during surgery, and therefore, no adequate histological evaluation has been performed. Therefore, essential etiology of this SDH type has remained unclear. In addition, the scarcity of autopsy cases may be attributed to arterial rupture being missed if the microscopic findings are too minimal to detect during autopsy. Here, we describe two autopsy cases of SDH of cortical artery origin. Extravasation on postmortem computed tomography angiography and arterial leakage on macroscopic observation during autopsy facilitated detection of the ruptured artery and allowed detailed histological evaluation of the ruptured artery and adjacent dura mater. The etiology of arterial rupture is briefly described on the basis of histopathological findings in this study and the available literature.

Formulas for estimating living stature based on bony pelvic measurements reconstructed from computed tomography images.

Introduction: A major challenge in anthropology is the estimation of human stature based on human bones since the stature of cadavers is slightly different from that of living humans. This study aimed to investigate the feasibility of estimating living stature in Japanese subjects based on sacral and coccygeal lengths as measured on three-dimensional (3D) models of the femur and pelvis reconstructed from cross-sectional computed tomography (CT) images. Subjects and methods: For this cross-sectional study, 106 healthy Japanese subjects (54 men and 52 women) were recruited. We measured the distances from the anterosuperior iliac spine (ASIS) to the most posterior point of the ischial spine (IS) (ASIS-IS), and from the ASIS to the most inferior point of the ischial tuberosity (IT) (ASIS-IT) on 3D bone models reconstructed from multi-slice CT images. Correlations of living stature with ASIS-IS and/or ASIS-IT on the left and right sides of the pelvis were evaluated. Multiple regression equations were derived and used as formulas for living stature estimation. Results: In men, living stature had strong correlations with ASIS-IS + ASIS-IT on both the left and right sides; Pearson's correlation coefficients were 0.717 and 0.706, respectively. In contrast, in women, living stature showed stronger correlations with all of the studied parameters; Pearson's correlation coefficients were highest for ASIS-IS + ASIS-IT on both the left and right sides (r = 0.753 and 0.744, respectively) compared with those in men. Formulas based on ASIS-IS + ASIS-IT provided the best estimation in both men and women, while ASIS-IS alone demonstrated a better estimation than ASIS-IT on both the left and right sides. Conclusions: This study revealed that ASIS-IS and ASIS-IT measured from CT images were reliable predictors of living stature in the Japanese population. Our estimation formulas were derived from measurements of living stature that were not affected by the physiological changes observed in cadavers. To the best of our knowledge, this is the first study to derive estimation formulas based on living stature. Our method may be useful in the identification of disaster victims, wherein long bones are usually not found intact but pelvic bones are. Furthermore, the findings could be relevant to the field of anthropology for estimating living stature.

Stature estimation formulae based on bony pelvic dimensions and femoral length.

We investigated the feasibility of estimating living stature in Japanese subjects using femoral length and pelvic dimensions measured on three-dimensional (3D) pelvic models reconstructed from cross-sectional computed tomography (CT) images. For this cross-sectional study, we recruited 106 healthy Japanese subjects. Maximum and bicondylar femoral length, as well as pelvic width, depth, and height, were measured on 3D bone models reconstructed from multi-slice CT images. The correlation of stature with each parameter was evaluated, and multiple regression equations were derived as formulae for living stature estimation. Prediction accuracy was evaluated as the mean absolute difference (MAD) between the measured and estimated statures. Maximum and bicondylar femoral lengths were similar and showed strong correlations with stature (> 0.8 in both males and females). Among the pelvic dimensions, height (craniocaudal length) showed the strongest correlation with stature in both males (r = 0.649) and females (r = 0.684). Formulae using femoral length plus pelvic height provided the best estimation of living stature in both males and females (MAD, 25-26 mm). Among the studied pelvic dimensions, height provided the best estimation of living stature when used alone (MAD, 34-36 mm) in both males and females. The intraclass correlation coefficients were high (> 0.9) for both intraobserver and interobserver reliability. Femoral length and pelvic height measured on CT images are reliable predictors of living stature in the Japanese population. Such tools are particularly useful in disaster victim identification, when the long bones are often not intact but the pelvic bones are.

An autopsy case of peliosis hepatis with X-linked myotubular myopathy.

This report describes the autopsy case of a 4-year-old boy who died from hepatic hemorrhage and rupture caused by peliosis hepatis with X-linked myotubular myopathy. Peliosis hepatis is characterized by multiple blood-filled cavities of various sizes in the liver, which occurs in chronic wasting disease or with the use of specific drugs. X-linked myotubular myopathy is one of the most serious types of congenital myopathies, in which an affected male infant typically presents with severe hypotonia and respiratory distress immediately after birth. Although each disorder is rare, 12 cases of pediatric peliosis hepatis associated with X-linked myotubular myopathy have been reported, including our case. Peliosis hepatis should be considered as a cause of hepatic hemorrhage despite its low incidence, and it requires adequate gross and histological investigation for correct diagnosis.

Ascaris lumbricoides found in ashore corpses from Korean peninsula to Japan.

Yearly, several reports of unknown boats and corpses brought by the Tsushima Current are found ashore Japanese coast. Niigata prefecture had the highest number of the drifting ashore corpses in Japan with 45.7% (16/35) in 2017. Corpses from North Korea, confirmed by documents and photos were autopsied and in 3/16 was possible to recover worms full of eggs, morphologically identified as ascarids. Further molecular analysis of ITS1, 5.8S rDNA and ITS2 sequences confirmed all specimens were Ascaris lumbricoides. The contamination level by Ascaris lumbricoides eggs in the coast, the health impact and consequences of the epidemiological bridging produced by this forced migration in public health should be investigated. Moreover, control of helminthiases might be a necessary task in North Korea.

An autopsy case of prolonged asphyxial death caused by the impacted denture in the esophagus.

A foreign body impacted in the esophagus is not a rare incident among adults or children. In adults, a dental prosthesis is prone to become impacted in the esophagus. The diagnostic difficulty of this often causes a delay in its removal, which can lead to serious complications, including death. This report describes the autopsy case of a man who died of prolonged asphyxiation induced by the delayed removal of an impacted denture, which was misdiagnosed on his first visit notwithstanding that a part of the denture could be seen on X-rays. Cases in which an impacted denture led to death have rarely been reported in contrast to numerous papers about recovered cases.

Changes in aortic shape and diameters after death: comparison of early postmortem computed tomography with antemortem computed tomography.

PURPOSE: The purpose of this study is to evaluate the postmortem deformation of the aorta on postmortem computed tomography (CT) by comparison with the antemortem CT in the same patient. MATERIALS AND METHODS: A total of 58 non-traumatic patients without hemorrhagic events who underwent torso CT before and shortly after death were enrolled. Antemortem chest and abdominal CT were obtained in 44 cases and in 57 cases, respectively. The lengths of the major and minor axes of the ascending and descending thoracic aorta and the abdominal aorta were measured on both antemortem and postmortem CT in the same patient. To evaluate the shape of the aorta, the major axis-minor axis ratio (Ma-MiR) was calculated. Mean values of the diameters of the aorta and Ma-MiRs on postmortem CT were compared with those on antemortem CT using the Wilcoxon signed-rank test. We also evaluated the major and minor axes and Ma-MiRs on both antemortem and postmortem CT in two age groups: 65 years and under (n=13) and over 65 years (n=45). RESULTS: At each level tested, the aorta significantly shrank after death (p<0.001) (ascending thoracic aorta, descending thoracic aorta, and abdominal aorta: 38.5 mm × 33.5 mm, 28.0 mm × 25.9 mm, and 24.4 mm × 21.8 mm on antemortem CT, 30.0 mm × 26.2 mm, 24.4 mm × 20.7 mm, and 21.5 mm × 14.5 mm on postmortem CT, respectively). The postmortem Ma-MiRs significantly increased at the descending thoracic aorta and the abdominal aorta (p<0.001). The diameters of the aorta are longer in older cases at all levels on both antemortem and postmortem CT. The reduction rates were larger in younger cases than older cases at all levels. CONCLUSIONS: After death, the aorta shrunk at all levels, and became oval in shape in descending thoracic and abdominal aorta. The contraction was greater in younger cases than older cases. Investigators who interpret postmortem imaging should be aware of the postmortem deformation of the aorta.

The effectiveness of postmortem multidetector computed tomography in the detection of fatal findings related to cause of non-traumatic death in the emergency department.

OBJECTIVES: To investigate the diagnostic performance of postmortem multidetector computed tomography (PMMDCT) for the detection of fatal findings related to causes of non-traumatic death in the emergency department (ED). METHODS: 494 consecutive cases of clinically diagnosed non-traumatic death in ED involving PMMDCT were enrolled. The fatal findings were detected on PMMDCT and classified as definite or possible findings. These findings were confirmed by autopsy in 20 cases. RESULTS: The fatal findings were detected in 188 subjects (38.1%) including 122 with definite (24.7%) and 66 with possible finding (13.4%). Definite findings included 21 cases of intracranial vascular lesions, 84 with intra-thoracic haemorrhage, 13 with retroperitoneal haemorrhage and one with oesophagogastric haemorrhage. In three patients who had initially been diagnosed with non-traumatic death, PMMDCT revealed fatal traumatic findings. Two definite findings (two haemopericardiums) and seven possible findings (two intestinal obstructions, one each of multiple liver tumours central pulmonary artery dilatation, pulmonary congestion, peritoneal haematoma, and brain oedema) were confirmed by autopsy. The causes of death were not determined in cases with possible findings without autopsy. CONCLUSIONS: PMMDCT is a feasible tool for detecting morphological fatal findings in non-traumatic death in ED. It is important to know the ability and limitation of PMMDCT.