A novel homozygous variant in REN in a family presenting with classic features of disorders involving the renin-angiotensin pathway, without renal tubular dysgenesis.

Autosomal recessively inherited pathogenic variants in genes associated with the renin-angiotensin-aldosterone system (RAAS) result in early onset oligohydramnios and clinical features of the Potter sequence, typically in association with proximal renal tubules dysgenesis. We describe two siblings and a first cousin who had severe oligohydramnios in the second trimester, and presented at birth with loose skin, wide fontanelles and sutures, and pulmonary insufficiency. Two had refractory hypotension during their brief lives and one received palliative care after birth. All were found to have a homozygous nonsense variant, REN: c.891delG; p.Tyr287*, on exome sequencing. Autopsy limited to the genitourinary system in two of the children revealed normal renal tubular histology in both. Immunoblotting confirmed diminished expression of renin within cultured skin fibroblasts. To our knowledge, this is the first identification of an association between biallelic variants in REN and oligohydramnios in the absence of renal tubular dysgenesis. Due to its role in the RAAS, it has previously been proposed that the decreased expression of REN results in hypotension, ischemia, and decreased urine production. We suggest sequencing of genes in the RAAS, including REN, should be considered in cases of severe early onset oligohydramnios, even when renal morphology and histology are normal.

A Self-Inflicted Gunshot Wound With an Unusual Hand Injury.

Self-inflicted gunshot wounds are a common cause of firearm-related deaths. The appearance and location of the entry wound, other concomitant findings at autopsy, and correlation with the scene and circumstances are critical in determining the manner of death. A case of a 72-year-old man with a self-inflicted gunshot wound with an unusual injury pattern is described. There was a contact range gunshot entry in the right temple, and an exit wound was seen in the left parietal region. There was a re-entry with an associated exit wound on the left hand.

A Case Report of Sudden Death From Intracardiac Leiomyomatosis.

Sudden death resulting from intracardiac leiomyomatosis is rare. In this case, a 50-year-old woman was found to have intracardiac leiomyomatosis, which originated in veins in the broad ligament. Tumor filled the entire inferior vena cava and extended into the right heart where it had embolized and occluded the right main pulmonary artery. The mechanism of death was sudden right heart failure.

A New Reference Source for Postmortem Body Measurements and Organ Weights in Neonates and Infants: A Statistical Analysis Based on Sudden Death Classification (Part 2).

Reference charts for body and organ measurements of neonates and infants were derived from data on 900 investigations done by the Office of the Chief Coroner for Ontario. The statistical analyses in this new reference source addressed deficiencies in sources currently available to pathologists.The present study also considered whether organ weights differed based on the classification of infant deaths using the original definition of either sudden infant death syndrome (SIDS) or sudden unexplained death (SUDS) which considers cases occurring in an unsafe sleeping environment or under adverse socioeconomic conditions. Cases of SUDS for both sexes peaked in 5 to 16 weeks of age. The thymus in the SUDS/SIDS age groups less than 25 weeks weighed more than the control group. Adrenal weights in SUDS cases between 9 and 16 weeks weighed less than SIDS cases. This could mean that deaths in unsafe sleep environments are truly sudden in infants who may have a limited adrenal response to acute hypoxia but have been unaffected by preceding chronic stressors.

Postmortem Body and Organ Measurements in Neonates and Infants: A Review of Reference Resources Used by Ontario Pathologists (Part 1).

It is common practice in pediatric autopsies to compare the body and organ measurements of the deceased child against the existing reference data. Although a number of resources are available, many are outdated and have significant limitations. The goal of this study was to assess the reference sources currently used by the Ontario pathologists in pediatric autopsies. A survey of 14 Ontario pathologists, who do coroners' pediatric autopsies, identified 20 publications commonly referenced for body and organ measurements. Of all the cited sources, only a few had all the features regarded by the pathologists as ideal for a reference source. These features included accessibility to the source, large sample size, defined control populations, statistical analyses, and sex distinctions. The results of this study will be used to guide the development of a new reference, based on Ontario data, that will enhance measurement standards in pediatric autopsy practice.

Delayed Fatal Hemorrhage Due to Small Bowel Mesenteric Laceration.

Injuries of small bowel and its mesentery due to blunt trauma are uncommon. Of deaths due to delayed intra-abdominal hemorrhage, mesenteric laceration is a rare cause of hemoperitoneum.A case of a 33-year-old man, who was hospitalized with chest and retroperitoneal trauma after a forklift rollover, is presented. He died 10 days after the incident. At autopsy, he had a massive hemoperitoneum due to a small bowel mesenteric laceration, which was not diagnosed during his clinical course. Microscopic examination of the hematoma around the laceration revealed healing and ruptured pseudoaneurysms in the distal branches of the superior mesenteric artery.

Injury patterns in motor vehicle collision-youth pedestrian deaths.

OBJECTIVE: The objective of this study was to describe fatal pedestrian injury patterns in youth aged 15 to 24 years old and correlate them with motor vehicle collision (MVC) dynamics and pedestrian kinematics using data from medicolegal death investigations of MVCs occurring in the current Canadian motor vehicle (MV) fleet. METHODS: Based on a systematic literature review, MVC-pedestrian injuries were collated in an injury data collection form (IDCF). The IDCF was coded using the Abbreviated Injury Scale (AIS) 2015 revision. The AIS of the most frequent severe injury was noted for individual body regions. The Maximum AIS (MAIS) was used to define the most severe injury to the body overall and by body regions (MAISBR). This study focused on serious to maximal injuries (AIS 3-6) that had an increasing likelihood of causing death. The IDCF was used to extract collision and injury data from the Office of the Chief Coroner for Ontario (OCCO) database of postmortem examinations done at the Provincial Forensic Pathology Unit (PFPU) in Toronto, Canada, and other provincial facilities between 2013 and 2019. Injury data were correlated with data about the MVs and MV dynamics and pedestrian kinematics.The study was approved by the Western University Health Science Research Ethics Board (Project ID: 113440; Lawson Health Research Institute Approval No. R-19-066). RESULTS: There were 88 youth, including 54 (61.4%) males and 34 (38.6%) females. Youth pedestrians comprised 13.1% (88/670) of all autopsied pedestrians. Cars (n = 25/88, 28.4%) were the most frequent type of vehicle in single-vehicle impacts, but collectively vehicles with high hood edges (i.e., greater distance between the ground and hood edge) were in the majority. Forward projection (n = 34/88, 38.6%) was the most frequent type of pedestrian kinematics. Regardless of the type of vehicle, there was a tendency in most cases for the median MAISBR ≥ 3 to involve the head and thorax. A similar trend was seen in most of the pedestrian kinematics involving the various frontal impacts. Of the 88 cases, at least 63 (71.6%) were known to be engaged in risk-taking behaviors (e.g., activity on roadway). At least 12 deaths were nonaccidental (8 suicides and 4 homicides). Some activities may have been impairment related, because 26/63 (41.3%) pedestrians undertaking risk-taking behavior on the roadway were impaired. Toxicological analyses revealed that over half of the cases (47/88, 53.4%) tested positive for a drug that could have affected behavior. Ethanol was the most common. Thirty-one had positive blood results. CONCLUSION: A fatal dyad of head and thorax trauma was observed for pedestrians struck by cars. For those pedestrians hit by vehicles with high hood edges, which were involved in the majority of cases, a fatal triad of injuries to the head, thorax, and abdomen/retroperitoneum was observed. Most deaths occurred from frontal collisions and at speeds more than 35 km/h.

A Neuropathological Study of Diffuse Vascular Injury in Fatal Motor Vehicle Collisions.

In Canada, 42 929 people were involved in fatal motor vehicle collisions (MVCs) between 1999 and 2018. Traumatic brain injuries (TBIs), including diffuse vascular injury (DVI), were the most frequent cause of death. The neuroanatomical injury pattern and severity of DVI in relation to data on MVC dynamics and other MVC factors were the focus of the current study. Five cases of fatal MVCs investigated by Western University's Motor Vehicle Safety (MOVES) Research Team with the neuropathological diagnosis of DVI were reviewed. DVI was seen in single and multiple vehicle collisions, with/without rollover and with/without partial occupant ejection. DVI occurred regardless of seatbelt use and airbag deployment and in vehicles equipped with/without antilock brakes. All DVI cases sustained head impacts and had focal TBIs, including basal skull fractures and subarachnoid hemorrhages. DVI was seen in MVCs that ranged in severity based on the change in velocity (delta-V) during the crash (minimum 31 km/hour) and occupant compartment intrusion (minimum 25 cm). In all cases, DVI in frontal white matter, corpus callosum and pontine tegmentum were common. In cases with more extensive DVI, pronounced vehicle rotation occurred before the final impact. Extensive DVI was seen in drivers who experienced sudden acceleration during vehicle rotation and deceleration.

Injury patterns in motor vehicle collision-pediatric pedestrian deaths.

OBJECTIVE: To describe fatal pediatric pedestrian injury patterns and correlate them with motor vehicle collision (MVC) characteristics and pedestrian kinematics using data from medicolegal death investigations of MVCs occurring in the current Canadian MV fleet and determine the applicability of the classical "Waddell's triad" comprising knee, hip (femur) or pelvis and craniocerebral injuries to present data injury patterns. METHODS: An Injury Data Collection Form was used to extract MV, MVC, pedestrian demographic and injury information from the Office of the Chief Coroner for Ontario database using autopsy data from 2013 to 2018. Injuries were coded using the Abbreviated Injury Scale (AIS) 2015 revision. The study focused on AIS ≥3 injuries utilizing the Maximum Abbreviated Injury Scale (MAIS), MAIS by Body Region (MAISBR) and Injury Severity Score (ISS). RESULTS: Between 2013 and 2018, there were 25 pediatric deaths. The pedestrians were either struck and run over (n = 17, 68%; 56% low speed) or struck and projected (n = 8, 32%). Twenty-two deaths were from frontal impacts; three were from reversing vehicles. Fourteen of the 17 (82.4%) run over cases occurred at low speed (<30 km/h). In 9 (36%) cases, the vehicle was turning at impact (right n = 3, left n = 6). A majority of the vehicles had a high hood edge. The head was the most severely injured (median MAISBR = 5 overall and ≤10 years; median MAISBR = 6 for 11-14 years old) followed by the neck (MAISBR = 3 overall; 6-14 years old), and the thorax (median MAISBR = 3 overall; all age groups). For the early adolescents (11-14 years old), the serious injury pattern included the abdomen (median MAISBR = 3.5). Nearly half (n = 11, 44%) sustained brainstem injuries. Over fifty percent of the 16 cases with neck injuries (n = 9, 56.3%) had atlanto-occipital or axial dislocation. CONCLUSION: More than half of the deaths occurred during low speed run overs. MAIS ≥3 injuries trended to a dyad of head and thorax in ≤5 years old, a triad of head, neck, and thorax injuries in children 6-10 years old and a tetrad with the addition of abdominal injuries in pedestrians ≥11 years old. Waddell's triad was not applicable to the fatal cases in the present study.

Injury Patterns Sustained in Fatal Motor Vehicle Collisions with Driver's Third-Generation Airbag Deployment.

The Office of the Chief Coroner for Ontario database for 2011-2012 was used to compare fatal injury patterns in drivers whose third-generation airbags deployed compared to first- and second-generation airbag deployments and airbag nondeployments with and without seatbelt use. There were 110 frontal and offset frontal crashes analyzed. The small sample size meant that the odds of craniocerebral, cervical spinal, thoracic, and abdominal injuries were not statistically different for airbag generation, deployment status, and seatbelt use; however, the risk of fatal thoracic injuries in third- and second-generation cases was increased. Seatbelt usage in third- and second-generation deployment cases reduced the risk of all injuries except abdominal trauma. High severity impacts and occupant compartment intrusion were frequently observed. The analyses in this retrospective study were challenged by data that were not collated in a standardized way and were limited in details about scene, vehicle, and driver variables.

Retrospective Analysis of Hanging Deaths in Ontario.

Hanging deaths from investigation standpoint are rarely problematic. Unusual circumstances can on occasion raise suspicion of foul play. Associated neck injuries are reported in the literature with variable frequency (from 0% to 76.8%). This study retrospectively analyzed 755 hanging deaths in Ontario (Canada) to evaluate the demographic features and circumstances of hanging fatalities, and the frequency of hanging-related neck injuries. A number of cases showed unusual/special circumstances (e.g., complex, double suicides, restraints). Among 632 cases with complete autopsies, hyoid and larynx fractures were present in 46 cases (7.3%) with the most common being isolated hyoid fractures. The incidence of cricoid fractures was 0.5% and cervical spine injuries, 1.1%. A higher incidence of neck injuries occurred among males, long drop hangings, and in cases with complete suspension. There was a tendency for the number of fractures to increase with increasing age and weight of the deceased.

Febrile Illness in an Infant With an Intracardiac Inflammatory Myofibroblastic Tumor.

We report a case of a child with a right ventricular inflammatory myofibroblastic tumor (IMT) who presented with fever, viral symptoms, and abdominal discomfort. Including this case, 49 intracardiac tumors have been previously reported in all age groups. The majority of intracardiac IMTs occur in pediatric patients, with approximately half presenting in children aged <12 months. Intracardiac IMTs are generally described as benign tumors; however, depending on their location, the initial presentation may involve heart failure or sudden death.(1) In addition to cardiac signs and symptoms, the clinical presentation of IMTs may also include constitutional signs such as fever, anemia, and elevated inflammatory markers. This case report reviews the diagnosis and management of IMTs, as well as the histopathologic features of this rare tumor type. Clinicians should be aware of their clinical presentation because early diagnosis and treatment can significantly reduce morbidity and mortality.

Driver and front seat passenger fatalities associated with air bag deployment. Part 1: A Canadian study.

Real world motor vehicle collision research of injuries due to deployment of "first-generation" air bags has been conducted by Transport Canada since 1993. Fifty-three fatal crashes (36 frontal impacts; 17 side collisions) involving 48 drivers and 10 right front passengers were reviewed. In the Canadian data, air bag deployment in five of nine low severity frontal crashes (delta-V (deltaV) < 25 km/h or 15 mph) was linked to five deaths, four of whom were autopsied (four adults with craniocervical (basal skull and C2 fracture with brainstem avulsion; "closed head injury"--no autopsy) or chest trauma (aortic or pulmonary artery tears); one child with atlanto-occipital dislocation). An occupant who is close ("out-of-position") to the air bag at the time of deployment is at risk for injury. In 27 high severity frontal impacts, unusual (e.g., pulmonary "blast" hemorrhage in one autopsied case) or isolated potentially survivable injuries (e.g., clinically documented ruptured right atrium; probable flail chest observed during the autopsy on a decomposed body) localized to the head, neck or chest in three possibly out-of-position drivers pointed to the deployed air bag as a source of injury. In one of 17 side collisions an out-of-position driver sustained a radiographically confirmed C1-C2 dislocation in a minimally intruded vehicle.

Driver and front seat passenger fatalities associated with air bag deployment. Part 2: A review of injury patterns and investigative issues.

Assessment of the role of air bag deployment in injury causation in a crash of any severity requires analysis of occupant, vehicle, and impact data. The potential injurious role of an air bag is independent of crash severity and is more obvious in minor collisions, particularly those involving "out-of-position" occupants. Factors such as occupant height and other constitutional and medical factors, intoxication, age, type, and proper use of other restraint systems, pre-impact braking and multiple impacts can contribute to an occupant being "out-of-position." Two injury mechanisms are described in out-of-position occupants: "punch-out" when the individual covers the air bag module before deployment and "membrane-force" when the occupant contacts a partly deployed air bag. Each mechanism is associated with injury patterns. In adults, "punch-out" can cause thoraco-abdominal trauma and "membrane-force" loading can lead to craniocervical injury. This can also occur in short-statured occupants including children subjected to both types of loading. In more severe collisions, other factors, e.g., intrusion, steering column and seatbelt loading and other occupant compartment contacts, can contribute to trauma.