Fatal Rupture of Occult Posttraumatic Left Ventricular Aneurysm in a Child.

Left ventricular aneurysm is a potentially serious but rare condition in children. This case describes delayed but fatal rupture of an occult posttraumatic left ventricular aneurysm in an 11-year-old boy with a history of blunt chest trauma from a high-impact automobile collision 7 months earlier. (Level of Difficulty: Intermediate.).

Genetically determined cardiomyopathies at autopsy: the pivotal role of the pathologist in establishing the diagnosis and guiding family screening.

Cardiomyopathies (CMP) comprise a heterogenous group of diseases affecting primarily the myocardium, either genetic and/or acquired in origin. While many classification systems have been proposed in the clinical setting, there is no internationally agreed pathological consensus concerning the diagnostic approach to inherited CMP at autopsy. A document on autopsy diagnosis of CMP is needed because the complexity of the pathologic backgrounds requires proper insight and expertise. In cases presenting with cardiac hypertrophy and/or dilatation/scarring with normal coronary arteries, a suspicion of inherited CMP must be considered, and a histological examination is essential. Establishing the actual cause of the disease may require a number of tissue-based and/or fluid-based investigations, be it histological, ultrastructural, or molecular. A history of illicit drug use must be looked for. Sudden death is frequently the first manifestation of disease in case of CMP, especially in the young. Also, during routine clinical or forensic autopsies, a suspicion of CMP may arise based on clinical data or pathological findings at autopsy. It is thus a challenge to make a diagnosis of a CMP at autopsy. The pathology report should provide the relevant data and a cardiac diagnosis which can help the family in furthering investigations, including genetic testing in case of genetic forms of CMP. With the explosion in molecular testing and the concept of the molecular autopsy, the pathologist should use strict criteria in the diagnosis of CMP, and helpful for clinical geneticists and cardiologists who advise the family as to the possibility of a genetic disease.

Deaths caused by medication in persons not using illicit narcotic drugs: An autopsy study from Western Denmark.

Information regarding deaths caused by poisoning or adverse effects of medication in Danish persons not using illicit narcotic drugs (PNUIDs) is sparse. To characterize aetiology, demographics, and death scene, we reviewed all legal autopsies performed at Aarhus University from 2017 to 2019 and isolated 96 deaths caused by medications in PNUIDs. Suicides caused by medication overdose accounted for 38%. Opioids and psychotropic medications were the main cause of death in 48% and 35% of the 96 cases, respectively. Morphine, tramadol, and quetiapine were the most commonly involved individual medications. A single medication caused death in 50% of cases, and multiple substances were involved in 50%. The median total number [interquartile range] of detected medications was 5 [4-6], with a higher number in females (5 [4-7]) than males (4 [2-5]), p = 0.009. Median age was 51 [42.5-61.5] years, and 57% were female. Scene of death most frequently involved a body on a bed or couch in the decedent's own home (72%). In conclusion, opioids and psychotropic medications dominated by morphine, tramadol and quetiapine most frequently caused medication-related deaths in PNUIDs. Monitoring this type of death may yield important knowledge to direct prophylactic initiatives regarding medication use and prescription.

Can shelter dog observers score behavioural expressions consistently over time?

A substantial number of dogs live in animal shelters worldwide. Stressors within the shelter environment can compromise their welfare, and scientific evaluations of feasible welfare assessment methods are therefore needed. Qualitative Behaviour Assessment (QBA) is a "whole-animal" approach used to assess welfare by observing animals' expressive behaviour. To investigate whether observers can score dogs' behavioural expressions consistently over time, this study replicated and extended previous research, by evaluating intra- and inter-observer reliability of QBA based on video recordings of shelter dogs. In Part I, nine veterinary nurse students received theoretical and practical training, and then scored 12 2 min video recordings of shelter dogs using a fixed list of behavioural descriptors. Three of the students undertook further practice and calibration using direct observations of dog behaviour in a local shelter. In Part II, the videos from Part I were scored by these three observers a second time, 15 months later. QBA data were analysed using principal component analysis (PCA), and reliability was assessed using Kendall's coefficient of concordance (W). In Part I, the inter-observer reliability was high for both components (0.78 for PC1 and 0.85 for PC2). In Part II, the inter-observer reliability was very high and moderate for PC1 and PC2, respectively (0.90 for PC1 and 0.65 for PC2). The intra-observer reliability was high for both components (W ≥ 0.86). Our results indicate that the fixed list of behavioural descriptors for shelter dogs can be used reliably when assessing videos, and that observers can score dogs' behavioural expressions consistently after a break of 15 months following the initial assessment. Nevertheless, the reduction in inter-observer-reliability of PC2 in Part II can indicate that some retraining and calibration may be required to avoid observer drift.

Targeted molecular genetic testing in young sudden cardiac death victims from Western Denmark.

Sudden unexpected death in the young continues to be an important unsolved challenge. A significant proportion of the deaths are suspected to be caused by inherited cardiac diseases and are referred to as sudden cardiac deaths (SCD). We performed targeted molecular testing of 70 deceased individuals under 40 years of age that after forensic autopsy were suspected to have died of SCD. The individuals were previously genetically investigated using smaller numbers of genes associated with specific cardiac diseases. In our previous studies, seven (10%) individuals had pathogenic or likely pathogenic variants according to the 2015 ACMG guidelines. In order to investigate the value of expanding the panel to 100 genes associated with cardiac diseases, we histopathologically re-examined the 70 suspected SCD cases and grouped them according to phenotypes into suspected cardiomyopathy (the cardiomyopathy group), left ventricular hypertrophy (the hypertrophy group) and structural normal hearts (the SUD group). DNA was captured with the Haloplex target enrichment system and sequenced using an Illumina MiSeq. We found that 11 (16%) individuals harboured pathogenic or likely pathogenic variants. In the cardiomyopathy, hypertrophy and SUD groups, 22%, 6% and 17% of the individuals, respectively, harboured pathogenic or likely pathogenic variants. Our findings show that testing of a broad panel of genes associated with cardiac diseases identify potential pathogenic variants of cardiac diseases in a significant proportion of SCD cases, and this may have important implications in family screening to prevent future deaths.

Pericardial Cyst: Cause of Sudden Cardiac Death?

Cardiovascular disease is the leading cause of sudden death in the world. The etiology of sudden cardiac death involves a wide range of diseases, but seldom pericardial cysts. A pericardial cyst is an uncommon cyst usually located in the middle mediastinum and rarely in the posterior part. They are usually harmless and asymptomatic. Here, we present a case of a 63-year-old woman who presented with dyspnea and hoarseness, but died suddenly after a CT scan was attempted. The detailed forensic pathologic and histologic examination revealed a pericardial cyst located in the posterior mediastinum. Toxicology and biochemistry tests, including tryptase, found no competing cause of death.

Genetic investigations of sudden unexpected deaths in infancy using next-generation sequencing of 100 genes associated with cardiac diseases.

Sudden infant death syndrome (SIDS) is the most frequent manner of post-perinatal death among infants. One of the suggested causes of the syndrome is inherited cardiac diseases, mainly channelopathies, that can trigger arrhythmias and sudden death. The purpose of this study was to investigate cases of sudden unexpected death in infancy (SUDI) for potential causative variants in 100 cardiac-associated genes. We investigated 47 SUDI cases of which 38 had previously been screened for variants in RYR2, KCNQ1, KCNH2 and SCN5A. Using the Haloplex Target Enrichment System (Agilent) and next-generation sequencing (NGS), the coding regions of 100 genes associated with inherited channelopathies and cardiomyopathies were captured and sequenced on the Illumina MiSeq platform. Sixteen (34%) of the SUDI cases had variants with likely functional effects, based on conservation, computational prediction and allele frequency, in one or more of the genes screened. The possible effects of the variants were not verified with family or functional studies. Eight (17%) of the SUDI cases had variants in genes affecting ion channel functions. The remaining eight cases had variants in genes associated with cardiomyopathies. In total, one third of the SUDI victims in a forensic setting had variants with likely functional effect that presumably contributed to the cause of death. The results support the assumption that channelopathies are important causes of SUDI. Thus, analysis of genes associated with cardiac diseases in SUDI victims is important in the forensic setting and a valuable supplement to the clinical investigation in all cases of sudden death.

The prevalence of mutations in KCNQ1, KCNH2, and SCN5A in an unselected national cohort of young sudden unexplained death cases.

INTRODUCTION: Sudden unexplained death account for one-third of all sudden natural deaths in the young (1-35 years). Hitherto, the prevalence of genopositive cases has primarily been based on deceased persons referred for postmortem genetic testing. These deaths potentially may represent the worst of cases, thus possibly overestimating the prevalence of potentially disease causing mutations in the 3 major long-QT syndrome (LQTS) genes in the general population. We therefore wanted to investigate the prevalence of mutations in an unselected population of sudden unexplained deaths in a nationwide setting. METHODS: DNA for genetic testing was available for 44 cases of sudden unexplained death in Denmark in the period 2000-2006 (equaling 33% of all cases of sudden unexplained death in the age group). KCNQ1, KCNH2, and SCN5A were sequenced and in vitro electrophysiological studies were performed on novel mutations. RESULTS: In total, 5 of 44 cases (11%) carried a mutation in 1 of the 3 genes corresponding to 11% of all investigated cases (R190W KCNQ1, F29L KCNH2 (2 cases), P297S KCNH2 and P1177L SCN5A). P1177L SCN5A has not been reported before. In vitro electrophysiological studies of P1177L SCN5A revealed an increased sustained current suggesting a LQTS phenotype. CONCLUSION: In a nationwide setting, the genetic investigation of an unselected population of sudden unexplained death cases aged 1-35 years finds a lower than expected number of mutations compared to referred populations previously reported. We therefore conclude that the prevalence of mutations in the 3 major LQTS associated genes may not be as abundant as previously estimated.

Sudden cardiac death in young adults: environmental risk factors and genetic aspects of premature atherosclerosis.

Familial hypercholesterolemia (FH) is a genetic disorder that may lead to premature coronary heart disease (CHD) and sudden cardiac death (SCD). Mutations in the LDLR or APOB genes cause FH. We have screened the LDLR and the ligand-binding region of APOB genes in 52 cases of SCD. Deceased patients were younger than 40 years of age and were suspected of having FH. The LDLR and APOB genes were examined via PCR, high-resolution melting, and DNA sequencing. Therein, it was observed that 7.7% of the screened patients exhibited a rare sequence variant in the LDLR gene, with 5.7% suspected of being pathogenic mutations. Lipid profiles and genetic testing for FH could be considered when autopsy reveals significant atherosclerosis of the coronary arteries in young adults. First-degree family members are advised to seek medical advice and testing to determine their own risks of atherosclerosis to prevent premature CHD and SCD.

[Overlooked Wolff-Parkinson-White syndrome]. / Overset Wolff-Parkinson-White-syndrom.

An autopsy in a 28-year-old man did not explain the cause of sudden unexpected death. However, a history of episodes with tachycardia and dizziness and a reassessed previous electrocardiogram exhibiting ventricular pre-excitation was consistent with Wolff-Parkinson-White (WPW) syndrome. In this patient we believe that the occurrence of atrial fibrillation caused sudden cardiac death from ventricular fibrillation due to a short refractory period of an accessory atrioventricular pathway and a very rapid ventricular rate in atrial fibrillation.

[Sudden unexpected death--hypertrophic cardiomyopathy--genetically verified post-mortem]. / Pludselig uventet død--hypertrofisk kardiomyopati--genetisk verificeret ved obduktionen.

Hypertrophic cardiomyopathy (HCM) may have sudden death as its first presentation. This case presentation describes a 25-year-old man with post-mortem finding of previously unknown left ventricular hypertrophy. Genetic analysis revealed a mutation in the myosin-binding protein C (MYBPC3). Autopsy combined with molecular genetic screening for mutations may give the relatives certainty of cause of death and the opportunity for genetic screening for diagnosis and treatment as well as prevention of sudden cardiac death.

[A retrospective review of children hospitalised with urinary tract calculi]. / En retrospektiv analyse af børn indlagt med sten i urinvejene.

INTRODUCTION: The incidence of urinary stones in Danish children is unknown. An estimate from The National Diagnosis Registry in Denmark is approximately 1:13,500. The purpose was to estimate the incidence of urinary stones and their composition in children in relation to sex, age and family history. MATERIALS AND METHODS: A retrospective review of all children presented at Aarhus University Hospital, Skejby, or Roskilde Hospital from October 1999 through October 2005 with urinary tract calculi. RESULTS: 42 patients with an average age of 7.9 years. The sex ratio was 1.7 boys to 1 girl. 7 were of an ethnic origin other than Danish. 12, all boys, had inborn urogenital tract malformation. Two had secondary malformation and one had inborn error of metabolism. The incidence of urogenital infection was higher in children with malformation. In 26 patients, stone analysis and composition were available. 54% of the stones had a calcium component. One third of the children had a family history of urolithiasis. CONCLUSION: Urinary tract stone is a rather difficult pediatric diagnosis. The most frequent symptom is abdominal pain. Ultrasound established the diagnosis in 50% of cases. All concrements were diagnosed with excretory urogram or computerized tomography. 30% of the children had a family history of urolithiasis. This confirms the importance of metabolic screening and stone analysis in children.