Post-mortem genetic testing in sudden cardiac death and genetic screening of relatives at risk: lessons learned from a Czech pilot multidisciplinary study.

Sudden cardiac death (SCD) might have an inherited cardiac condition background. Genetic testing supports post-mortem diagnosis and screening of relatives at risk. Our aim is to determine the feasibility of a Czech national collaboration group and to establish the clinical importance of molecular autopsy and family screening. From 2016 to 2021, we have evaluated 100 unrelated SCD cases (71.0% males, age: 33.3 (12.8) years). Genetic testing was performed by next-generation sequencing utilizing a panel of 100 genes related to inherited cardiac/aortic conditions and/or whole exome sequencing. According to autopsy, cases were divided into cardiomyopathies, sudden arrhythmic death syndrome, sudden unexplained death syndrome, and sudden aortic death. We identified pathogenic/likely pathogenic variants following ACMG/AMP recommendations in 22/100 (22.0%) of cases. Since poor DNA quality, we have performed indirect DNA testing in affected relatives or in healthy parents reaching a diagnostic genetic yield of 11/24 (45.8%) and 1/10 (10.0%), respectively. Cardiological and genetic screening disclose 83/301 (27.6%) relatives at risk of SCD. Genetic testing in affected relatives as starting material leads to a high diagnostic yield offering a valuable alternative when suitable material is not available. This is the first multidisciplinary/multicenter molecular autopsy study in the Czech Republic which supports the establishment of this type of diagnostic tests. A central coordinator and proper communication among centers are crucial for the success of a collaboration at a national level.

Concurrent Infection of the Human Brain with Multiple Borrelia Species.

Lyme disease (LD) spirochetes are well known to be able to disseminate into the tissues of infected hosts, including humans. The diverse strategies used by spirochetes to avoid the host immune system and persist in the host include active immune suppression, induction of immune tolerance, phase and antigenic variation, intracellular seclusion, changing of morphological and physiological state in varying environments, formation of biofilms and persistent forms, and, importantly, incursion into immune-privileged sites such as the brain. Invasion of immune-privileged sites allows the spirochetes to not only escape from the host immune system but can also reduce the efficacy of antibiotic therapy. Here we present a case of the detection of spirochetal DNA in multiple loci in a LD patient's post-mortem brain. The presence of co-infection with Borrelia burgdorferi sensu stricto and Borrelia garinii in this LD patient's brain was confirmed by PCR. Even though both spirochete species were simultaneously present in human brain tissue, the brain regions where the two species were detected were different and non-overlapping. The presence of atypical spirochete morphology was noted by immunohistochemistry of the brain samples. Atypical morphology was also found in the tissues of experimentally infected mice, which were used as a control.

Suicide or not? Issues in the demonstration of anaphylaxis, a review of the literature.

The authors review the literature on the determination of post-mortem serum tryptase values and present the case of a young man who was hit by a train. However, his family believes he has no motivation to commit suicide. Collision with a train is one of the most common methods of suicide, especially among young men under 40 years of age. (1). The forensic autopsy showed that the man died due to the collision with the train, with traumatic hemorrhagic shock stated as a cause of death. Following toxicological, biochemical, and immunological tests created a supposition that the incident was not a result of suicidal action but a consequence of a possible allergic or anaphylactic reaction of the organism combined with a state of mild alcohol intoxication.

Burden of sudden cardiac death in persons aged 1-40 years in the Czech Republic.

OBJECTIVES: The aim of the study was to ascertain the incidence, circumstances and causes of sudden cardiac death in persons aged 1-40 years in the Czech Republic. METHODS: De-identified autopsy reports of all individuals who died suddenly between the ages of 1-40 years during the period 2014-2019 inclusive in a selected area of the Czech Republic were analysed retrospectively. Persons with substantial cardiovascular pathology defined by histopathological criteria and those with a negative autopsy were included in the study. The latter were designated as sudden arrhythmic death syndrome. RESULTS: In total, 245 sudden cardiac death cases were identified resulting in an incidence rate of 2.4/100,000 person-years. Among the deceased, we found an enormous gender gap with men representing 81% of cases. More than 80% of deaths occurred during everyday activities or sleep, whereas only 7% were sports-related. The most common cause of death was coronary artery disease detected in 38%, which was followed by cardiomyopathies in 15%, sudden arrhythmic death syndrome in 12%, left ventricular hypertrophy in 10%, and congenital heart defects in 7%. CONCLUSIONS: Coronary artery disease is the predominant cause of sudden cardiac death in the young population of the Czech Republic. Hence, effective preventive measures targeted at the reduction of risk factors associated with early coronary artery disease should be reinforced. The second most prevalent cause in our population are potentially heritable heart conditions such as cardiomyopathies and sudden arrhythmic death syndrome. This fact has already prompted the introduction of molecular autopsy and cardiogenetic care for relatives in the Czech Republic.

Penile carcinoma - a rare cause of sudden death.

Penile carcinoma is an uncommon but potentially mutilating disease with a heterogeneous etiology. We present a case in which a man died due to severe blood loss from an amputated penis. It was initially regarded as a violent death with an external cause. Autopsy found irregular defects with smooth edges in the external genital area and on both sides of the groin, with yellowish-gray callus-like structures and dried blood at the base of where the penis would have been located. Histological examination revealed the presence of squamous cell carcinoma with signs of keratinization. Subsequent investigation, along with information from the autopsy, revealed that the man suffered from penile carcinoma, thus death was attributed to exsanguination from an ulcerated femoral artery in a patient with penile carcinoma.

Manner of Death of Older People with Regard to Blood Alcohol Concentration.

OBJECTIVE: Alcohol abuse is related to a wide variety of negative health outcomes including mortality in older people. Alcohol abuse in older people is characterised by certain specific features uncommon in general adult population. The main objective of this study was to analyse the autopsy protocols of deceased older people in relation to blood alcohol concentration (BAC), sex, age, and manner of death. As a positive BAC, >0.20 g/kg was accepted. METHODS: The sample consists of 1,012 deceased older people (i.e. aged 65 years and over) selected out of 2,377 autopsied subjects in the period from 2003­2013. Subjects included into the sample were chosen via the proportional sampling method. Data (BAC, sex, age, and manner of death) was recorded in a single structured protocol. Data was evaluated statistically (Kolmogorov-Smirnov two-sample test, Wilcoxon two-sample test, risk ratio). RESULTS: Among older people, there has been a statistically significant correlation of natural death with sex (men died earlier) and with increased BAC (people with positive BAC died earlier). In case of violent death there is a difference in the types of accidents in older people with positive BAC (>0.2 g/kg) and with negative BAC (≤0.2 g/kg). Drowning is more common in older people with positive BAC. CONCLUSIONS: Health campaigns in Europe and the Czech Republic aimed at reducing alcohol consumption mainly deal with young people. Alcohol abuse has an impact on premature mortality even in older people. As shown by this study, older people with positive BAC die significantly earlier.

[Benefits of otoscopy in forensic autopsy practice: A prospective study]. / Význam otoskopie v soudnelékarské diagnostice: prospektivní studie.

The otoscopy is an examination of the external auditory canal, the eardrum, and the middle ear with an instrument called an otoscope. It is a simple, inexpensive, and time-saving endoscopic method typically used by general practitioners and otorhinolaryngologists. Authors present a prospective study of otoscopic findings investigated consecutively at autopsy. Of the 250 examined persons, 50 positive findings were identified: 38 cases with petechial hemorrhages and 12 cases with tympanic membrane perforation or hemotympanon. Hemorrhages of the tympanic membrane detected through the otoscopy may serve as evidence of congestion within head and neck potentially associated with asphyxiation either in the death or in the living (similar to periorbital and conjuctival petechial hemorrhages). In our study, hemorrhages of the tympanic membrane were related to heart failure, hanging and asphyxiation. Perforated tympanic membrane and hemotympanum have been sporadically reported in victims of fatal lightning strike and rarely in strangulation. This findings were in our study associated with craniocerebral injuries: traffic accidents, falls from height and gunshot injuries. The otoscopy may help to reveal various traumatic and pathological changes within the outer and the middle ear, and, thus, provide important forensic evidence. The otoscopy is also highly recommended in the investigation of the sudden deaths in the young.

Fat embolism and COVID-19 infection: autopsy and post-mortem laboratory findings in SARS-CoV-2 positive patients.

INTRODUCTION: The article is one of the very first autopsy reports worldwide, which associates COVID-19 infection and pulmonary fat embolism. AIMS: To point to a crucial connection between a severe acute respiratory syndrome caused by coronavirus 2 (SARS-CoV-2) infection and pulmonary fat embolism as one of the possible major mechanisms of severe COVID-19 symptoms. METHODS: Lung, brain and kidney tissues examination of 16 full human autopsy cases. All deceased suffered from COVID-19 infection, none of them was admitted to hospital prior to death, immediate causes of death vary. Autopsies accompanied by microbiological examination and histological examination using Oil Red O staining were performed. Consequently, we have implemented a control cohort consisting of 16 deceased with no presence of pulmonary infection and various immediate causes of death. RESULTS: Of the 16 autopsy cases, 11 (68.8%) were males and 5 (31.3%) females, with overall mean age 68.1 (39-86) years. Causes of death of studied subjects were natural, mostly from respiratory failure (in 12 cases, 75%). Cardiopulmonary resuscitation was performed in 7 cases (43.8%). None of dissected persons had larger signs of body trauma. Pulmonary fat embolism was found in 11 cases (68.8%), which generalised to kidneys in 8 patients (50% of all cases, 72.3% of cases with pulmonary fat embolism) and to brain tissue in 1 case. CONCLUSION: We demonstrated a reasonable relation between a COVID-19 disease and a variously severe fat embolism, severity of which does not directly correlate with body weight. Further investigation or even change of medical treatment needs to be considered in patients with COVID-19.

Indeterminacy of the Diagnosis of Sudden Infant Death Syndrome Leading to Problems with the Validity of Data.

The validity of infant mortality data is essential in assessing health care quality and in the setting of preventive measures. This study explores different diagnostic procedures used to determine the cause of death across forensic settings and thus the issue of the reduced validity of data. All records from three forensic medical departments that conducted autopsies on children aged 12 months or younger (n = 204) who died during the years 2007-2016 in Moravia were included. Differences in diagnostic procedures were found to be statistically significant. Each department works with a different set of risk factors and places different emphasis on different types of examination. The most significant differences could be observed in sudden infant death syndrome and suffocation diagnosis frequency. The validity of statistical data on the causes of infant mortality is thus significantly reduced. Therefore, the possibilities of public health and social policy interventions toward preventing sudden and unexpected infant death are extraordinarily complicated by this lack of data validity.

Intracranial electrophysiological recordings from the human brain during memory tasks with pupillometry.

Data comprise intracranial EEG (iEEG) brain activity represented by stereo EEG (sEEG) signals, recorded from over 100 electrode channels implanted in any one patient across various brain regions. The iEEG signals were recorded in epilepsy patients (N = 10) undergoing invasive monitoring and localization of seizures when they were performing a battery of four memory tasks lasting approx. 1 hour in total. Gaze tracking on the task computer screen with estimating the pupil size was also recorded together with behavioral performance. Each dataset comes from one patient with anatomical localization of each electrode contact. Metadata contains labels for the recording channels with behavioral events marked from all tasks, including timing of correct and incorrect vocalization of the remembered stimuli. The iEEG and the pupillometric signals are saved in BIDS data structure to facilitate efficient data sharing and analysis.

Traumatic dislocation of the eye into the maxillary sinus: Case report and literature review.

Traumatic dislocation of the eye is usually encountered in high-energy injuries. These include traffic accidents, accidents at work, sporting accidents, falling from a height, impact of the hooves or horns of animals, gunshot injuries, and physical assault. Such incidents are accompanied by facial soft tissue damage and injuries to the facial skeleton, especially the orbit, and can be associated with varying degrees of dislocation of the eye. We describe a rare case of non-fatal traumatic eye dislocation into the maxillary sinus, coupled with an orbital fracture resulting from a physical assault on a 63-year-old woman. The cause of death was asphyxiation due to manual strangulation and mechanical asphyxia. Even though dislocations of the eye are relatively rare, forensic pathologists should be aware of such injuries to correct assessment of injury mechanism. The available literature regarding eye dislocation is summarized, and the forensic issues applicable to the assessment of such cases are reviewed.

Fatal Hemorrhage from an Arteriovenous Fistula.

In this study, we present two cases of sudden deaths of people with end-stage kidney with arteriovenous fistulas for long-term hemodialysis treatment. This procedure is associated with a number of known complications. While stenosis, thrombosis, and infection are well known, lethal hemorrhage from arteriovenous fistula is much less commonly encountered. Inspection of the bodies at the scene of the death by a medical examiner suggested that the deaths were due to exsanguination. Autopsies revealed visible defects on the front wall of the arteriovenous fistulas. Microscopic examination showed wall necrosis with infiltration of various inflammatory cells. Deaths were due to exsanguination from the ulcerated arteriovenous fistulas in patients with chronic renal failure. Further investigation revealed that complications in the area around the arteriovenous fistulas were known and were being treated until a sudden rupture of the vessels and hemorrhage from the arteriovenous fistulas resulted in the deaths.

Circumstances and causes of fatal cycling crashes in the Czech Republic.

OBJECTIVES: The circumstances and causes of death of 129 cyclists registered in the Olomouc and the Zlín regions, the Czech Republic, between 2005 and 2013 were the subject of this study. METHODS: We analyzed the autopsy reports, where the principal cause of death was stated, and obtained a detailed description of the circumstances recorded by the police officers. RESULTS: Eighty-three cases (64.3% of the set) were collisions involving a motor vehicle. The driver was the guilty party in 57 cases (68.7%) and the cyclist in the remaining 26 cases (31.3%). The most frequent cause of the crash was connected with right of way (29 cases). Cars were involved in 52 cases; heavy vehicles, including buses, in 26 cases; and motorcycles in 5 cases. Single-vehicle crashes consisted of 43 (33.3%) cases. We divided this group into 3 subgroups based on whether the particular case could be attributed to a cyclist having lost control of the bicycle (31 cases) or to other particular causes. Sixty-eight cases (52.7%) of fatal outcomes were directly linked to intracranial injuries. Multiple injuries were the principal cause of death in 19 cases (14.7%), followed by hemorrhagic traumatic shock (12 cases, 9.3%). Seventy-two (55.8%) cyclists died immediately after the crash and 23 (17.8%) cyclists died within a day of the accident. CONCLUSIONS: Trucks were more dangerous to cyclists than cars at intersections, whereas cars were more dangerous on straight sections. The most important pattern was identified as a motor vehicle hitting a cyclist from behind on a straight road section. We identified a strong underestimation of natural death as a cause of cycling fatalities in the official police reports.

Multi-drug intoxication fatality involving atorvastatin: A case report.

Mixed antihypertensive drug intoxication poses a significant risk for patient mortality. In tandem to antihypertensives, hypolipidemic medicines (especially statins) are often prescribed. Among their well-known adverse effects belongs rhabdomyolysis. We report a case of fatal multi-drug overdose in a 65-year-old female alcoholic. The patient was unconscious at admission. Empty blister packs indicated the abuse of 250 tablets of urapidil, 42 tablets of verapamil/trandolapril, 50 tablets of moxonidin, 80 tablets of atorvastatin and 80 tablets of diacerein. Standard measures (gastric lavage, activated charcoal, mechanical ventilation, massive doses of vasopressors, volume expansion, diuretics and alkalinization) failed to provide sufficient drug elimination and hemodynamic support and the sufferer deceased on the fourth day. Dramatic elevations of serum myoglobin (34,020 µg/L) and creatine kinase (219 µkat/L) were accompanied by rise in cardiac troponin I and creatinine. Gas chromatography revealed ethanol 1.17 g/kg (blood) and 2.81 g/kg (urine). Thin layer chromatography and gas chromatography of gastric content and urine verified verapamil, moxonidin and urapidil fragment (diacerein method was unavailable). Atorvastatin and trandolapril concentrations (LC-MS(n)) equaled 277.7 µg/L and 57.5 µg/L, resp. (serum) and 8.15 µg/L and 602.3 µg/L, resp. (urine). Histology confirmed precipitates of myoglobin with acute necrosis of proximal renal tubules in association with striated muscle rhabdomyolysis and myocardial dystrophy. Cardiogenic-distributive shock in conjunction with acute renal failure due to the combined self-poisoning with vasoactive agents and atorvastatin were determined to be this decedent's immediate cause of death. The manner of death was assigned to be suicidal.

Dehiscent scar in the lower uterine segment after Caesarean section and IVF infertility treatment: a case report.

AIMS: Caesarean section is the most common obstetric operation associated with short and long term risks, one of which is uterine scar dehiscence. In this case report we describe four cases of in vitro fertilization and embryo transfer (IVF+ET) treatment where the embryo was transferred into the uterus with known scar dehiscence in the lower uterine segment after a previous Caesarean section (SC). METHODS: All transfers of embryos were ultrasound guided directly into the middle of uterine cavity. All resulting pregnancies continued without problems related to the dehiscent scar and babies were delivered in the third trimester by elective/emergency SC. RESULTS: Our cases suggest that IVF+ET can be offered as an infertility treatment option despite a dehiscent scar in the lower uterine segment after previous SC.