Strong desmin immunoreactivity in the myocardial sleeves around pulmonary veins, superior caval vein and coronary sinus supports the presumed arrhythmogenicity of these regions.

Myocardial sleeve around human pulmonary veins plays a critical role in the pathomechanism of atrial fibrillation. Besides the well-known arrhythmogenicity of these veins, there is evidence that myocardial extensions into caval veins and coronary sinus may exhibit similar features. However, studies investigating histologic properties of these structures are limited. We aimed to investigate the immunoreactivity of myocardial sleeves for intermediate filament desmin, which was reported to be more abundant in Purkinje fibers than in ventricular working cardiomyocytes. Sections of 16 human (15 adult and 1 fetal) hearts were investigated. Specimens of atrial and ventricular myocardium, sinoatrial and atrioventricular nodes, pulmonary veins, superior caval vein and coronary sinus were stained with anti-desmin monoclonal antibody. Intensity of desmin immunoreactivity in different areas was quantified by the ImageJ program. Strong desmin labeling was detected at the pacemaker and conduction system as well as in the myocardial sleeves around pulmonary veins, superior caval vein, and coronary sinus of adult hearts irrespective of sex, age, and medical history. In the fetal heart, prominent desmin labeling was observed at the sinoatrial nodal region and in the myocardial extensions around the superior caval vein. Contrarily, atrial and ventricular working myocardium exhibited low desmin immunoreactivity in both adults and fetuses. These differences were confirmed by immunohistochemical quantitative analysis. In conclusion, this study indicates that desmin is abundant in the conduction system and venous myocardial sleeves of human hearts.

A COVID-19-association-dependent categorization of death causes in 100 autopsy cases.

From March through December 2020, 100 autopsies were performed (Semmelweis University, Budapest, Hungary), with chart review, of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection demonstrated by real-time reverse-transcription polymerase chain reaction testing (mean age, 74.73 years, range 40-102 years; 50 males, mean age 71.96 years, and 50 females, mean age 77.5 years). Classified by the date of death, 21 cases were from the pandemic's "first wave" (March through July) and 79 from the "second wave" (August through December). Three mortality categories were defined by relevance of SARS-CoV-2 infection: (1) "strong" association (n=57), in which COVID-19 was primary responsible for death; (2) "contributive" association (n=27), in which a pre-existing condition independent of COVID-19 was primary responsible for death, albeit with substantial COVID-19 co-morbidity; (3) "weak" association (n=16), in which COVID-19 was minimally or not at all responsible for death. Distributions among categories differed between the first wave, in which the "contributive" association cases dominated (strong: 24%, contributive: 48%, weak: 28%), and the second wave, in which the "strong" association cases dominated (strong: 66%, contributive: 21%, weak: 13%). Charted co-morbidities included hypertension (85 %), cardiovascular diseases (71 %), diabetes (40 %), cerebrovascular diseases (31 %), chronic respiratory diseases (30 %), malignant tumors (20 %), renal diseases (19 %), diseases of the central nervous system (15 %), and liver diseases (6 %). Autopsy evaluation analyzed alterations on macroscopy as well as findings on microscopy of scanned and scored sections of formalin-fixed, paraffin-embedded tissue samples (50-80 blocks/case). Severity of histological abnormalities in the lung differed significantly between "strong" and "contributive" (p<0.0001) and between "strong" and "weak" categories (p<0.0001). Abnormalities included diffuse alveolar damage, macrophage infiltration, and vascular and alveolar fibrin aggregates (lung), with macro- and microvascular thrombi and thromboemboli (lung, kidney, liver). In conclusion, autopsies clarified in what extent COVID-19 was responsible for death, demonstrated the pathological background of clinical signs and symptoms, and identified organ alterations that led to the death. Clinicopathologic correlation, with conference discussions of severity of co-morbidities and of direct pathological signs of disease, permitted accurate categorization of cause of death and COVID-19 association as "strong," "contributive," or "weak." Lung involvement, with reduced ventilatory capacity, was the primary cause of death in the "strong" and "contributive" categories. Shifts in distribution among categories, with "strong" association between COVID-19 and death dominating in the second wave, may reflect improved clinical management of COVID-19 as expertise grew.

Neurodegenerative proteinopathies associated with neuroinfections.

Infectious agents, including viruses and bacteria, are proposed to be involved in the pathogenesis of Alzheimer's disease (AD). According to this hypothesis, these agents have capacity to evade the host immune system leading to chronic infection, inflammation, and subsequent deposition of Aß and phosphorylated-tau in the brain. Co-existing proteinopathies and age-related pathologies are common in AD and the brains of elderly individuals, but whether these are also related to neuroinfections remain to be established. This study determined the prevalence and distribution of neurodegenerative proteinopathies in patients with infection-induced acute or chronic inflammation associated with herpes simplex virus (HSV) encephalitis (n = 13) and neurosyphilis (n = 23). The mean age at death in HSV patients was 53 ± 12 years (range 24-65 years) and survival was 9 days-6 years following initial infection. The mean age at death and survival in neurosyphilis patients was 60 ± 15 years (range 36-86 years) and 1-5 years, respectively. Neuronal tau-immunoreactivity and neurites were observed in 8 HSV patients and 19 neurosyphilis patients, and in approximately half of these, this was found in regions associated with inflammation and expanding beyond regions expected from the Braak stage of neurofibrillary degeneration. Five neurosyphilis patients had cortical ageing-related tau astrogliopathy. Aß-plaques were found in 4 HSV patients and 11 neurosyphilis patients. Lewy bodies were observed in one HSV patient and two neurosyphilis patients. TDP-43 pathology was absent. These observations provide insights into deposition of neurodegenerative proteins in neuroinfections, which might have implications for COVID-19 patients with chronic and/or post-infectious neurological symptoms and encephalitis.

Prognosis of the non-ST elevation myocardial infarction complicated with early ventricular fibrillation at higher age.

Early ventricular fibrillation (EVF) predicts mortality in ST-segment elevation myocardial infarction (STEMI) patients. Data are lacking about prognosis and management of non-ST-segment elevation myocardial infarction (NSTEMI) EMI with EVF, especially at higher age. In the daily clinical practice, there is no clear prognosis of patients surviving EVF. The present study aimed to investigate the risk factors and factors influencing the prognosis of NSTEMI patients surviving EVF, especially at higher age. Clinical data, including 30-day and 1-year mortality of 6179 NSTEMI patients, were examined; 2.44% (n=151) survived EVF and were further analyzed using chi-square test and uni- and multivariate analyses. Patients were divided into two age groups below and above the age of 70 years. Survival time was compared with Kaplan-Meier analysis. EVF was an independent risk factor for mortality in NSTEMI patients below (HR: 2.4) and above the age of 70 (HR: 2.1). Mortality rates between the two age groups of NSTEMI patients with EVF did not differ significantly: 30-day mortality was 24% vs 40% (p=0.2709) and 1-year mortality was 39% vs 55% (p=0.2085). Additional mortality after 30 days to 1 year was 15% vs 14.6% (p=0.9728). Clinical characteristics of patients with EVF differed significantly from those without in both age groups. EVF after revascularization-within 48 h-had 11.2 OR for 30-day mortality above the age of 70. EVF in NSTEMI was an independent risk factor for mortality in both age groups. Invasive management and revascularization of NSTEMI patients with EVF is highly recommended. Closer follow-up and selection of patients (independent of age) for ICD implantation in the critical first month is essential.

The effects of changing meteorological parameters on fatal aortic catastrophes.

BACKGROUND: Over the span of the last decade, medical research has been increasingly putting greater emphasis on the study of meteorological parameters due to their connection to cardiovascular diseases. The main goal of this study was to explore the relationship between fatal aortic catastrophes and changes in atmospheric pressure and temperature. METHODS: We used a Cox process model to quantify the effects of environmental factors on sudden deaths resulting from aortic catastrophes. We used transfer entropy to draw conclusion about the causal connection between mortality and meteorological parameters. Our main tool was a computer program which we developed earlier in order to evaluate the relationship between pulmonary embolism mortality and weather on data sets comprised of aortic aneurysm (AA) and acute aortic dissection (AAD) cases, where one of these two medical conditions had led to fatal rupture of the aorta. Our source for these cases were the autopsy databases of Semmelweis University, from the time period of 1994 to 2014. We have examined 160 aneurysm and 130 dissection cases in relation to changes in meteorological parameters. The algorythm implemented in our program is based on a non-parametric a Cox process model. It is capable of splitting slowly varying unknown global trends from fluctuations potentially caused by weather. Furthermore, it allows us to explore complex non-linear interactions between meteorological parameters and mortality. RESULTS: Model measures the relative growth of the expected number of events on the nth day caused by the deviation of environmental parameters from its mean value. The connection between ruptured aortic aneurysms (rAA) and changes in atmospheric pressure is more significant than their connection with mean daily temperatures. With an increase in atmospheric pressure, the rate of rAA mortality also increased. The effects of meteorological parameters were weaker for deaths resulting from acute aortic dissections (AAD), although low mean daily temperatures increased the intensity of occurrence for AAD-related deaths. CONCLUSION: The occurrence rate of fatal aortic catastrophes showed a slight dependence on the two examined parameters within our groups.

[The effect of alternating meteorological parameters on fatally ruptured aortic aneurysms (autopsy-based data)]. / Meteorológiai paraméterek változásának hatása a halálos kimenetelu aortaaneurysma-rupturákra.

INTRODUCTION: There are several statements about the connection between cardiovascular diseases and climate change. On behalf of our observation-based knowledge we hypothesized a relationship between the occurence of aortic aneurysm (AA) rupture and weather changes. AIM: The purpose of our study was to explore the relationship between fatal aortic catastrophe and changes in atmospheric pressure and temperature. By using a new method we could even measure the intensity of the connection. METHOD: We have developed a software earlier to examine the link between pulmonary embolism mortality and the weather on data sets comprised of aortic aneurysm cases, where the medical condition had led to the fatal rupture of the aorta. For the events mentioned earlier we used the autopsy database of Semmelweis University between January 1, 2005 and January 1, 2014. Altogether we examined 152 aneurysm-related aortic catastrophes. We reported the exact day of the incident and the weather conditions on that day and the day before. RESULTS AND CONCLUSION: We have defined that the occurrence rate of fatal aortic catastrophe showed a slight dependence on the two examined parameters within our groups. We have found the connection related to ruptured aortic aneurysm and changes in atmospheric pressure more significant than their connection with mean daily temperatures. With the increase in atmospheric pressure, the rate of AA mortality also increased. In the knowledge of our results we believe that the mathematical model we used can be an effective starting point for population-based and prospective studies. Orv Hetil. 2018; 159(37): 1501-1505.

Evaluation of meteorological and epidemiological characteristics of fatal pulmonary embolism.

The objective of the present study was to identify risk factors among epidemiological factors and meteorological conditions in connection with fatal pulmonary embolism. Information was collected from forensic autopsy records in sudden unexpected death cases where pulmonary embolism was the exact cause of death between 2001 and 2010 in Budapest. Meteorological parameters were detected during the investigated period. Gender, age, manner of death, cause of death, place of death, post-mortem pathomorphological changes and daily meteorological conditions (i.e. daily mean temperature and atmospheric pressure) were examined. We detected that the number of registered pulmonary embolism (No 467, 211 male) follows power law in time regardless of the manner of death. We first described that the number of registered fatal pulmonary embolism up to the nth day can be expressed as Y(n) = α ⋅ n (ß) where Y denotes the number of fatal pulmonary embolisms up to the nth day and α > 0 and ß > 1 are model parameters. We found that there is a definite link between the cold temperature and the increasing incidence of fatal pulmonary embolism. Cold temperature and the change of air pressure appear to be predisposing factors for fatal pulmonary embolism. Meteorological parameters should have provided additional information about the predisposing factors of thromboembolism.

Evidence for Infection and Inflammation in Infant Deaths in a Country with Historically Low Incidences of Sudden Infant Death Syndrome.

Total infant mortality in Hungary has been higher than other European countries; however, the reported incidence of sudden infant death syndrome (SIDS) has been lower. The low incidence of SIDS in Hungary has been supported by evidence obtained from the high rate of scene of death investigation and medico-legal autopsy mandatory since the 1950s. In this study, we compared the incidence of explained and unexplained infant deaths in Hungary for three periods: 1979-1989 when the incidence of SIDS was high in western Europe; 1990-1999 when the incidence of infant deaths was falling following introduction of the public health campaigns to reduce the risk factors associated with SIDS; and 2000-2012 to determine if introduction of Haemophilus influenzae type b or pneumococcal vaccines or introduction of an earlier immunization schedule during this period had an effect on SIDS. Explained infant deaths fell consistently during this period; however, SIDS rose during the second period when the incidence of SIDS was falling in other European countries. Evidence for infection and/or inflammation was observed for the majority of SIDS during each period. The results are discussed in relation to campaigns to reduce infant mortality in Hungary and the introduction of new vaccines and an earlier immunization schedule in 2006.

Examination of the Suicide Characteristics Based on the Scene Investigation in Capital Budapest (2009-2011).

Medicolegal evaluation of postmortem findings at the death scene represents an important part of forensic medicine. The aim of this study was to investigate the occurrence and characteristics of suicide events. Data collection was performed from the police scene investigation reports in capital Budapest between 2009 and 2011. In this study, epidemiological parameters such as age, gender, time and place of death, postmortem changes, suicidal method, seasonal and daily distribution, natural diseases, earlier psychiatric treatment, socioeconomic risks, supposed cause of death, final notes, earlier suicide attempts, and suicide ideations were analyzed. There were 892 suicide cases (619 males, 273 females) detected in the investigated period. Hanging, overdose of prescription medications, jumping, use of firearms, drowning, and electrotrauma showed statistical differences among genders (p<0.05). The most common methods of suicide among men and women were hanging (57.4%) and overdose of prescription medications (33%), respectively. Death scene characteristics represent the important factors for forensic medicine.

A Common Polymorphism of the Human Cardiac Sodium Channel Alpha Subunit (SCN5A) Gene Is Associated with Sudden Cardiac Death in Chronic Ischemic Heart Disease.

Cardiac death remains one of the leading causes of mortality worldwide. Recent research has shed light on pathophysiological mechanisms underlying cardiac death, and several genetic variants in novel candidate genes have been identified as risk factors. However, the vast majority of studies performed so far investigated genetic associations with specific forms of cardiac death only (sudden, arrhythmogenic, ischemic etc.). The aim of the present investigation was to find a genetic marker that can be used as a general, powerful predictor of cardiac death risk. To this end, a case-control association study was performed on a heterogeneous cohort of cardiac death victims (n=360) and age-matched controls (n=300). Five single nucleotide polymorphisms (SNPs) from five candidate genes (beta2 adrenergic receptor, nitric oxide synthase 1 adaptor protein, ryanodine receptor 2, sodium channel type V alpha subunit and transforming growth factor-beta receptor 2) that had previously been shown to associate with certain forms of cardiac death were genotyped using sequence-specific real-time PCR probes. Logistic regression analysis revealed that the CC genotype of the rs11720524 polymorphism in the SCN5A gene encoding a subunit of the cardiac voltage-gated sodium channel occurred more frequently in the highly heterogeneous cardiac death cohort compared to the control population (p=0.019, odds ratio: 1.351). A detailed subgroup analysis uncovered that this effect was due to an association of this variant with cardiac death in chronic ischemic heart disease (p=0.012, odds ratio = 1.455). None of the other investigated polymorphisms showed association with cardiac death in this context. In conclusion, our results shed light on the role of this non-coding polymorphism in cardiac death in ischemic cardiomyopathy. Functional studies are needed to explore the pathophysiological background of this association.

The utility of the combination of the corrosion cast method and post mortem MSCT scans.

A careful post-mortem investigation is needed to determine the cause of death of patients bearing coronary stents and to describe complications of stent implantation. The main purpose of this study was to combine post mortem methods of CT angiography and corrosion cast preparation for the visualization of coronary stenoses, coronary stents, instent restenosis, and stent occlusion. Injection-corrosion method was combined with post-mortem MSCT angiography to characterize the pathomorphological changes after stent implantation in 6 male cadaver hearts. Multi-slice computed tomography was employed to visualize the coronary artery system. For image post processing, multiplanar reconstructions, maximal intensity projections and three dimensional reconstructions were used. This study was assessing the feasibility of post mortem MSCT for intracoronary stent evaluation. We described a method for characterization of the coronary side branch stenosis caused by stent implantation. Post mortem CT imaging proved to be a feasible and highly reproducible technique for the characterization of pathological changes in the coronary system.

Characteristics of cardiovascular deaths in forensic medical cases in Budapest, Vilnius and Tallinn.

Evaluation of the pathomorphological characteristics of cases involving natural and sudden cardiovascular death is essential for the determination of the cause of death. The main purpose of this study is to investigate sudden unexpected cardiovascular death and to study how different geographical climatic influences may affect cardiac mortality in three capitals: Budapest, Vilnius and Tallinn. There were 8482 (5753 male, 2729 female) cardiovascular deaths between 2005 and 2009. The highest rate was observed in the age group between 71 and 80 years (35.17%) and 51-60 years (24.45%). The highest number of cardiovascular deaths occur in January (805/9.49%) and December (770/9.07%). Seasonal distribution was observed, with winter prevalence in Tallinn (279/3.20%) and spring prevalence in Vilnius (760/8.90%). Though in Vilnius and Budapest a great number of deaths occurred in winter and spring, any correlation with other factors (e.g. age, gender, BAC) was not statistically significant. Based on our results we can conclude that environmental-geographical parameters may affect natural cardiovascular death. Examination of pathological patterns and predisposing environmental parameters may help to improve prevention strategies.

Psychosocial, educational, and somatic factors in chronic nonspecific low back pain.

Analysis of the effect of psychosocial factors and co-morbidities on the health status of patients with chronic nonspecific low back pain and patients with surgical intervention because of disk herniation was performed. One hundred and two nonselected consecutive inpatients with chronic nonspecific low back pain were included in the study. Their average age was 56.7 (SD = 10.9) years. The control group consisted of 199 subjects matched according to age and sex, chosen from the database of the national representative health survey Hungarostudy 2006, which involved 4,527 subjects. We measured quality of life including mental health with the SF-36 questionnaire validated for use in Hungary, the short 9-item version of the Beck Depression Inventory, the WHO-Five Well-Being Index, and the Hospital Anxiety-Depression Scale. We characterized the socio-demographic status with variables on age, sex, marital status, and education. Data on symptoms and signs of low back pain, other musculoskeletal diseases, and their treatments including spinal surgery were recorded. Co-morbidity and body mass index were considered as independent indicators of health. Depression as measured by Beck Depression Inventory and severity of depression did not vary significantly according to marital status, education, hypertension, diabetes, and gastrointestinal disease. Only half of the patients (52 %) were in the normal range of the scale; 22 % suffered from mild, 16 % from moderate, and 12 % from severe depression. Average values for anxiety and depression as measured by Hospital Anxiety-Depression Scale and Beck Depression Inventory were both significantly higher in the patient than in the control group (Hospital Anxiety Scale: p = 0.0001; Beck Depression Inventory: p = 0.0001). According to the WHO Well-Being Index-5 scale, the difference between patients and the control group was significant (p = 0.0001). Furthermore, correlation was found between the incidence of depression and surgery. Depression was demonstrated in 47.4 % of those patients who had no surgery, in 50 % of patients who had one round of surgery, and in 62.5 % of those who had undergone surgery more than once; the contingence coefficient was 0.211. According to different measurements, the psychological state of patients with chronic nonspecific low back pain was significantly altered as compared to the matched Hungarian population. Higher anxiety and depression markers occurred in 48 % of the patients. There was no correlation between the depression of patients with low back pain and variables such as marital status, education, and co-morbidities. Our study is the first to demonstrate that depression runs parallel with the number of surgical procedures. Therefore, if there is a relative indication for surgery, depression and severity of depression should be assessed and considered when deciding on the intervention.

Sudden death due to infiltration of left bundle branches by interventricular septal cardiac fibroma.

Cardiac fibromas are benign conditions; however, their location and size may cause ventricular arrhythmias and sudden cardiac death. We report a case of a 68-year-old female who died suddenly. Postmortem investigation detected a huge cardiac fibroma in the pars muscularis of the interventricular septum, occupying almost the entire muscular septum, and restricting the volume of left ventricular chamber. Histological examination revealed numerous foci of calcification in the alternating complex interlacing or strictly parallel collagenous fiber mass. Tumor mass was mainly demarcated, but in some places, fibrous infiltration of surrounding working cardiac muscle was found. We present a case when direct tumor involvement in the descending left bundle branches was evidenced. Mainly, the branches of septal fascicle were disrupted, entrapped, and degenerated by the tumor mass. This case report emphasizes that postmortem histological examination of conduction system in all sudden cardiac death cases may substantially improve the accuracy of postmortem diagnosis.

Pellagra encephalopathy as a differential diagnosis for Creutzfeldt-Jakob disease.

In the present study we evaluated cases referred as suspected Creutzfeldt-Jakob disease (CJD). Five out of 59 without prion disease showed neuropathological features of pellagra encephalopathy with widespread chromatolytic neurons (age range 40-48 years at death; one woman). These patients presented with a progressive neuropsychiatric disorder lasting for 2 to 24 months. Common symptoms included gait disorder, para- or tetraspasticity, extrapyramidal symptoms, incontinence, and myoclonus. Protein 14-3-3 in the cerebrospinal fluid was examined in a single patient and was positive, allowing the clinical classification as probable sporadic CJD. Pellagra encephalopathy may be considered as a differential diagnosis of CJD including detection of protein 14-3-3.

Fatal idiopathic pulmonary haemosiderosis in association with pregnancy - medico-legal evaluation.

Idiopathic pulmonary haemosiderosis is a rare disorder characterised by repeated episodes of intra-alveolar bleeding in association with consecutive anaemia, pulmonary fibrosis, pulmonary hypertension and respiratory failure. Pregnancy may exacerbate the symptoms of idiopathic pulmonary haemosiderosis typically worsening in the third trimester. A 32-year-old female after delivery was admitted to hospital with progressive dyspnoea of about 1-month duration. Sudden circulatory collapse caused fatal complication. During the post-mortem investigation, lung haemorrhage and histologically abundant iron deposition in macrophages and interstitial fibrosis were found. Medico-legal post-mortem evaluation of fatal cases may support the clinico-pathological context of the diagnosis of this entity.

Cervical pulmonary herniation due to blunt chest trauma.

Traumatic lung herniation through the superior thoracic aperture rarely occurs. In this case report we present a motor vehicle accident of a 40 year old male victim with cervical lung herniation. After an enormous blunt trauma to the chest, the disrupted and lacerated lung tissue left the thoracic cavity and was pushed into the laryngeal and oral cavity. Extrathoracic post-traumatic lung herniation through the thoracic inlet and connective tissue spaces of the neck into the oral cavity is a unique complication of blunt trauma to the chest, and the post-mortem medico-legal investigations may collect more information about this phenomenon.

Fatal traffic injuries among children and adolescents in three cities (capital Budapest, Vilnius, and Tallinn).

Motor vehicle accidental injuries are a frequent cause of death among young children and adolescents. The goal of this study was to compare patterns of injury between three capitals (Budapest, Vilnius, and Tallinn). Information on 190 fatal traffic accidents (69 pedestrians, 14 bicyclists, and 107 motor vehicle occupants) between 2002 and 2006 was collected from databases of medico-legal autopsies. The role of victims in accidents, the location of injuries, cause of death, survival period, and blood alcohol levels were evaluated. One-hundred and forty-one (74%) victims had a passive role in traffic as pedestrians, passengers in cars, or public transport. In victims who died at the scene, the rate of head injury was higher than in cases who received medical treatment (odds ratio = 2.58, CI = 1.2-5.55, p = 0.0127). These results underline the importance of postmortem studies to examine the pathomechanism of fatal traffic accidental injuries and to provide information for the prevention of road traffic accidents against children and adolescents.

Expression and function of C5a receptor in a fatal anaphylaxis after honey bee sting.

The mechanisms leading to death from anaphylaxis after insect sting involve antigen cross-linkage of antibody molecules that activate immunoglobulin receptors on inflammatory cells. The aim of our study was to investigate the pathomorphology and the expression of C5aR in fatal anaphylaxis in a patient after a fatal insect sting. A 38-year-old women was stung by a honeybee. C5R1 expression was detected in many dilated capillaries in the lungs. Pulmonary epithelial cells did not bind the monoclonal antibody for C5R1; however, intensive cytoplasmic staining was detected in endothelial cells. The findings of this case provide evidence for an active role of complement in fatal anaphylaxis elicited by bee venom. C5aR detection could be useful in the identification of sudden death cases because of unwitnessed fatal insect sting cases. Authors can recommend this immunohistochemical analysis on all sudden unexpected deaths outdoors where a possible bee sting might occur.