Sudden death after a mountain bike race.

Presented case study deals with the sudden death of a 47 years old male, shortly after a mountain bike race after reported nausea and chest pain followed by loss of consciousness and resuscitation. Cardiopulmonary resuscitation was unsuccessful. An autopsy was enacted due to the sudden death in a seemingly healthy person. An acute infarction of the anterior cardiac wall on the basis of stenosis of the anterior interventricular branch of the left coronary artery with histopathological findings of eosinophilic coronary periarteritis was assessed. Sudden death during sport activities represents a complex problem which forensic physicians have to face. An external and internal examination of the body is not always sufficient. It is crucial for the forensic physician to have sufficient knowledge and enough information about the circumstances of the death and anamnestic records. Eosinophilic coronary periarteritis occurs rarely, predominantly in males and with uncertain etiology.

[Forensic characteristic of sudden death cases in subjects with metabolic syndrome]. / Sudebno-meditsinskaya kharakteristika sluchaev vnezapnoi smerti lits s metabolicheskim sindromom.

Comparing pace and standard of living of the world population these days and in the end of the last century, it's quiet true that there has been a significant increase. Therewith, the number of deaths from cardiovascular diseases has increased in recent decades. Scientists around the world attribute this fact to the increase in the number of people with overweight and other metabolic disorders. Unhealthy lifestyle, namely unbalanced diet, stress, bad habits (smoking, alcohol abuse) leads to metabolic disorders and metabolic syndrome development, that, in turn, can be the main risk factor for complications of associated diseases leading to fatal outcome. The present study gives a forensic description of sudden death in metabolic syndrome, its pathomorphological features were investigated, the causes of death were shown, as well as their relationship with biochemical abnormalities in the body.

[Forensic assessment of meteorological conditions as risk factors of sudden death from arterial hypertension]. / Sudebno-meditsinskaya otsenka meteouslovii v kachestve faktorov riska vnezapnoi smerti pri gipertonicheskoi bolezni.

Arterial hypertension is a disease that significantly increases the risk of sudden death in different age groups. It is of high scientific interest to study the relationship of arterial hypertension manifestations with different weather conditions. The article provides a review of literature data on the variability of arterial hypertension course depending on meteorological conditions as a risk factor for sudden death.

Heart proteomic profiling discovers MYH6 and COX5B as biomarkers for sudden unexplained death.

Sudden unexplained death (SUD) is not uncommon in forensic pathology. Yet, diagnosis of SUD remains challenging due to lack of specific biomarkers. This study aimed to screen differentially expressed proteins (DEPs) and validate their usefulness as diagnostic biomarkers for SUD cases. We designed a three-phase investigation, where in the discovery phase, formalin-fixed paraffin-embedded (FFPE) heart specimens were screened through label-free proteomic analysis of cases dying from SUD, mechanical injury and carbon monoxide (CO) intoxication. A total of 26 proteins were identified to be DEPs for the SUD cases after rigorous criterion. Bioinformatics and Adaboost-recursive feature elimination (RFE) analysis further revealed that three of the 26 proteins (MYH6, COX5B and TNNT2) were potential discriminative biomarkers. In the training phase, MYH6 and COX5B were verified to be true DEPs in cardiac tissues from 29 independent SUD cases as compared with a serial of control cases (n = 42). Receiver operating characteristic (ROC) analysis illustrated that combination of MYH6 and COX5B achieved optimal diagnostic sensitivity (89.7 %) and specificity (84.4 %), with area under the curve (AUC) being 0.91. A diagnostic software based on the logistic regression formula derived from the training phase was then constructed. In the validation phase, the diagnostic software was applied to eight authentic SUD cases, seven (87.5 %) of which were accurately recognized. Our study provides a valid strategy towards practical diagnosis of SUD by integrating cardiac MYH6 and COX5B as dual diagnostic biomarkers.

Sudden Unexpected Death in Epilepsy (SUDEP). Full forensic approach in two cases and review of literature.

Background: The SUDEP is defined as a sudden unexpected death in patients affected by epilepsy, with or without evidence of a seizure, excluding documented status epilepticus, in which postmortem examination does not reveal a toxicologic or anatomic cause of death. Materials and Method: Here we report two cases observed at the Institute of Forensic Medicine of Messina, regarding the phenomenon, that were analyzed by a multidisciplinary approach. Meantime a systematic review of literature was performed using PubMed and Scopus databases. Conclusion: Although the mechanisms of SUDEP are not fully understood, several studies have allowed the identification of different brain areas whose anomalous stimulation, during epileptic seizures, could interfere with the correct control of cardiovascular and respiratory activities. The study highlights the importance of a complete multidisciplinary forensic approach analyzing different aspects in people affected by epilepsy, with no other cause of death. Furthermore, reinforce the definition of SUDEP for uniform cause-of death certification in these cases.

Sudden unexpected death after initial infusion of rituximab for Waldenström macroglobulinemia/lymphoplasmacytic lymphoma: an autopsy case.

BACKGROUND: Waldenström's macroglobulinemia (WM) is defined as a lymphoplasmacytic lymphoma (LPL) involving the bone marrow (BM) with presence of IgM monoclonal protein, and comprises > 95% of all LPL cases. Rituximab-based regimens have been predominant in the management of WM. Infusion-related reactions (IRRs) are a primary concern with rituximab, although it is generally better tolerated with less toxicity than conventional anticancer agents. Here, we present an autopsy case of an elderly man who died suddenly after receiving the initial infusion of rituximab for WM/LPL. CASE PRESENTATION: An 84-year-old man was found dead in his bedroom. He had undergone the initial intravenous rituximab infusion for progressive anemia related to Waldenström's macroglobulinemia/lymphoplasmacytic lymphoma (WM/LPL) approximately 15 h before death. Although the protocol for rituximab administration and additional medication was considered appropriate, he exhibited several symptoms consistent with infusion-related reactions (IRRs) during the infusion. Autopsy revealed monotonous proliferation of small-to-medium-sized lymphocytic cells in the bone marrow, consistent with the premortem diagnosis of WM/LPL. Additionally, immunoglobulin λ-light chain-derived amyloid (ALλ) deposition was identified in all organs other than the brain. Although ALλ deposition and LPL infiltration were found in the heart, they were not severe enough to cause severe functional impairment. Severe congestion and/or edema were observed in the lungs, liver, and brain. Although significant inflammatory cell infiltration was not found in any organs, laboratory tests revealed elevated serum levels of inflammatory cytokines, including interleukin-1ß, interleukin-6, tumor necrosis factor-α and the presence of IgM-λ monoclonal protein. CONCLUSION: Acute IRRs associated with the initial rituximab infusion were the major contributing factor to his sudden unexpected death. The autopsy findings of present case suggest the necessity for thorough monitoring of older patients with WM/LPL undergoing rituximab treatment, particularly when pronounced IRRs occur during the first administration, in addition to investigating complications of WM/LPL before infusion.

Fine particulate matter-sudden death association modified by ventricular hypertrophy and inflammation: a case-crossover study.

Background: Sudden death accounts for approximately 10% of deaths among working-age adults and is associated with poor air quality. Objectives: To identify high-risk groups and potential modifiers and mediators of risk, we explored previously established associations between fine particulate matter (PM2.5) and sudden death stratified by potential risk factors. Methods: Sudden death victims in Wake County, NC, from 1 March 2013 to 28 February 2015 were identified by screening Emergency Medical Systems reports and adjudicated (n = 399). Daily PM2.5 concentrations for Wake County from the Air Quality Data Mart were linked to event and control periods. Potential modifiers included greenspace metrics, clinical conditions, left ventricular hypertrophy (LVH), and neutrophil-to-lymphocyte ratio (NLR). Using a case-crossover design, conditional logistic regression estimated the OR (95%CI) for sudden death for a 5 µg/m3 increase in PM2.5 with a 1-day lag, adjusted for temperature and humidity, across risk factor strata. Results: Individuals having LVH or an NLR above 2.5 had PM2.5 associations of greater magnitude than those without [with LVH OR: 1.90 (1.04, 3.50); NLR > 2.5: 1.25 (0.89, 1.76)]. PM2.5 was generally less impactful for individuals living in areas with higher levels of greenspace. Conclusion: LVH and inflammation may be the final step in the causal pathway whereby poor air quality and traditional risk factors trigger arrhythmia or myocardial ischemia and sudden death. The combination of statistical evidence with clinical knowledge can inform medical providers of underlying risks for their patients generally, while our findings here may help guide interventions to mitigate the incidence of sudden death.

Delivering the diagnosis of multiple system atrophy: a multicenter survey on Japanese neurologists' perspectives.

BACKGROUND: Multiple system atrophy (MSA) is a progressive, incurable, life-threatening neurodegenerative disease uniquely characterized by the risk of sudden death, which makes diagnosis delivery challenging for neurologists. Empirical studies on breaking a diagnosis of MSA are scarce, with no guidelines currently established. This study aimed to investigate neurologists' current practices and experiences in delivering the diagnosis of MSA. METHODS: We conducted a multicenter online survey and employed a mixed-methods (quantitative and qualitative) study design in which responses to open-ended questions were analyzed qualitatively using critical incident technique. RESULTS: Among the 194 neurologists surveyed, 166 opened the survey (response rate = 85.6%), of whom 144 respondents across various Japanese regions completed the survey. Accordingly, 92.3% and 82.8% of the participating neurologists perceived delivering the diagnosis of MSA and explaining the risk of sudden death as difficult, respectively. Factors independently associated with difficulties in diagnosis delivery included explaining the importance of the family decision making process in life-prolonging treatment, perceived difficulties in delivering information regarding the risk of sudden death, and perceived difficulties in differential diagnosis of MSA. CONCLUSIONS: Our findings showed that the majority of neurologists perceived delivering the diagnosis of MSA and explaining the risk of sudden death as difficult, which could have been associated with the difficulty of breaking the diagnosis of MSA. Difficulty in conveying bad news in MSA are caused by various factors, such as empathic burden on neurologists caused by the progressive and incurable nature of MSA, the need to explain complex and important details, including the importance of the family decision-making process in life-prolonging treatment, difficulty of MSA diagnosis, and communication barriers posed by mental status and cognitive impairment in patients or their family members. Neurologists consider various factors in explaining the risk of sudden death (e.g., patient's personality, mental state, and degree of acceptance and understanding) and adjust their manner of communication, such as limiting their communication on such matters or avoiding the use of the term "sudden death" in the early stages of the disease. Although neurologists endeavor to meet the basic standards of good practice, there is room for the multiple aspects for improvement.

Molecular Autopsy With Banked Cord Blood Reveals Brugada Syndrome in Past Sudden Death Case.

Molecular autopsy has recently been gaining attention as a means of postmortem diagnosis; however, it is usually performed using the victim's blood sample at the time of death. Here, we report the first case of a deceased infant with Brugada syndrome whose diagnosis was made with banked cord blood. A seemingly healthy 1-year-old male infant collapsed while having a fever; this collapse was witnessed by his mother. Despite cardiopulmonary resuscitation, he died of ventricular fibrillation. No abnormalities of cardiac structure were identified on autopsy. Genomic samples were not stored at the time because of a lack of suspicion for familial arrhythmia. Five years later, his sister showed Brugada electrocardiogram pattern while febrile from Kawasaki disease. Their father showed a spontaneous type 1 Brugada electrocardiogram pattern. A heterozygous SCN5A p.R893C variant was found by genetic testing in the proband's father and sister. Furthermore, the proband's genetic testing was performed using his banked cord blood, which identified the same variant. Family history of Brugada syndrome with an SCN5A-R893C variant and clinical evidence led to a postmortem diagnosis of Brugada syndrome in the proband. Identification of this variant in this case later contributed to verifying SCN5A-R893C as a pathogenic variant through data accumulation. Banked cord blood may prove useful for conducting molecular autopsies in previously undiagnosed cases of sudden death in which genomic samples were not stored.

Detection of macropodid alphaherpesvirus 2 infection and lesions in sudden death of a captive Virginia opossum and a water opossum.

Macropodid alphaherpesvirus 2 (MaAHV2) is best described in macropods and has been implicated in outbreaks among captive marsupial populations in Australia. Natural disease caused by herpesviruses has not been reported previously in opossum species, to our knowledge. One Virginia opossum (Didelphis virginiana) and 1 water opossum (Chironectes minimus) were submitted for postmortem examination from a zoo that housed 6 opossums, all of which died within several weeks. Red kangaroos (Macropus rufus) and red-necked wallabies (Macropus rufogriseus) were also present at the facility. Liver samples from both opossums were submitted for transmission electron microscopy and whole-genome sequencing. Microscopically, both opossums had multifocal necrosis in the liver and lung, with intranuclear inclusion bodies within hepatocytes and pneumocytes. Another significant finding in the Virginia opossum was sepsis, with isolation of Streptococcus didelphis from various organs. Ultrastructural analysis of formalin-fixed liver tissue identified herpesviral replication complexes in both opossums; negative-stain electron microscopy of unfixed liver tissue repeatedly yielded a negative result. The herpesvirus had >99% nucleotide identity with MaAHV2. These 2 cases indicate that both opossum species are susceptible to MaAHV2 infection, and the outbreak has implications for mixed-species facilities that house macropods.

An In Silico Cardiomyocyte Reveals the Impact of Changes in CaMKII Signalling on Cardiomyocyte Contraction Kinetics in Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is characterised by asymmetric left ventricular hypertrophy, ventricular arrhythmias, and cardiomyocyte dysfunction that may cause sudden death. HCM is associated with mutations in sarcomeric proteins and is usually transmitted as an autosomal-dominant trait. The aim of this in silico study was to assess the mechanisms that underlie the altered electrophysiological activity, contractility, regulation of energy metabolism, and crossbridge cycling in HCM at the single-cell level. To investigate this, we developed a human ventricular cardiomyocyte model that incorporates electrophysiology, metabolism, and force generation. The model was validated by its ability to reproduce the experimentally observed kinetic properties of human HCM induced by (a) remodelling of several ion channels and Ca2+-handling proteins arising from altered Ca2+/calmodulin kinase II signalling pathways and (b) increased Ca2+ sensitivity of the myofilament proteins. Our simulation showed a decreased phosphocreatine-to-ATP ratio (-9%) suggesting a negative mismatch between energy expenditure and supply. Using a spatial myofilament half-sarcomere model, we also compared the fraction of detached, weakly bound, and strongly bound crossbridges in the control and HCM conditions. Our simulations showed that HCM has more crossbridges in force-producing states than in the control condition. In conclusion, our model reveals that impaired crossbridge kinetics is accompanied by a negative mismatch between the ATP supply and demand ratio. This suggests that improving this ratio may reduce the incidence of sudden death in HCM.

[An increasing prevalence of epilepsy and stagnating or decreasing health care resources makes nationwide implementation challenging]. / Följsamhet till ordination en av utmaningarna i epilepsivården.

The Swedish national guidelines for epilepsy stipulate regular health care contacts in the years following diagnosis, referral for epilepsy surgery in cases of pharmacoresistant epilepsy, multidisciplinary teams, and adequate patient information particularly for women of childbearing age. The last years have seen advances in many research areas of relevance for the basic epilepsy care, and Sweden has contributed regarding pharmacotherapy, seizure-related risks, sudden unexpected death in epilepsy (SUDEP), and digital tools. An increasing prevalence of epilepsy and stagnating or decreasing health care resources makes nationwide implementation of this knowledge challenging and increases the risk of unequal access to care. Innovation and focus on prioritized groups, such as newly diagnosed and persons with pharmacoresistant epilepsy or comorbidities, will be needed.

É possível determinar a massa ventricular esquerda em pacientes com miocardiopatia hipertrófica baseada na aferição do intervalo QTPICO pela derivação D1? / Is it possible to determine left ventricular mass in patients with hypertrophic cardiomyopathy based on measuring the QTPICO interval using the D1 lead?

INTRODUÇÃO: A hipertrofia ventricular esquerda está associada à maior risco de arritmias ventriculares potencialmente malignas e, é um fator de risco para morte súbita em pacientes com miocardiopatia hipertensiva e hipertrófica (MCH). O ecocardiograma é o padrão ouro para a determinação dessa variável pois detecta anatomicamente o aumento da massa muscular. O eletrocardiograma é uma ferramenta de investigação disponível no consultório médico. A duração do intervalo entre o início da onda Q e o pico da onda T por essa técnica, avalia o processo de despolarização até o final da repolarização do epicárdio e pode refletir assim, o remodelamento elétrico cardíaco, antes mesmo que se estabeleça a hipertrofia ao ECO. Estudos clínicos indicam que esse intervalo quando maior que 350 ms associa-se a maior grau de hipertrofia ventricular esquerda em hipertensos. OBJETIVO: Avaliar se o intervalo QTpico na derivação D1 é capaz de estimar a massa ventricular esquerda em pacientes com MCH. MÉTODOS: 55 pacientes (24 ♀, 31 ♂; média de idade 38±14 anos, variando entre 12 e 61 a) foram consecutivamente avaliados em ambulatório de Miocardiopatias, quando tiveram registrados o ECG e submetidos ao ECO bidimensional para confirmação diagnóstica de MCH. Considerou-se aumento da massa de VE valores ≥95 g/m2 em ♀ e ≥115 g/m2 em ♂. Foram obtidos os valores dos intervalos QT, QTc, QTpico e QTpicoc na derivação D1. Com os valores das medidas foi obtida a curva ROC para se determinar a sensibilidade, especificidade e área sob a curva, além da razão de chances positiva e negativa considerando-se um valor de 350 ms para se estimar a massa a indexada do VE. Considerou-se essa associação quando os valores P < 0,05. RESULTADOS: A duração média das variáveis do ECG foram: QT 425±50 ms (variando entre 300 e 520 ms); QTc de 450±46 ms (350 a 638 ms); QTpico foi 333±43 ms (236 a 427 ms); QTpicoc de 349±36ms (275 a 471 ms). A média da massa estimada do VE foi de 178±57 g/ m2 (73 a 371 g/m2). Quando se obteve a curva ROC, a sensibilidade e especificidade do intervalo QTpicoc foram de 52,4% e 81,5% respectivamente, (razão de chances positiva de 2,83 e negativa de 0,58) para se estimar a massa de VE > 199 g/m2 (c=0,665; p<0,03). CONCLUSÕES: 1. O intervalo QTpicoc na derivação D1 apresenta moderada capacidade para detectar a massa ventricular esquerda em pacientes com MCH; 2. Essa variável pode ser útil para se estimar a gravidade da MCH, particularmente considerando-se a disponibilidade e a grande utilidade do eletrocardiograma no consultório médico.

Sudden unexpected postnatal collapse and BUB1B mutation: first forensic case report.

Sudden unexpected postnatal collapse (SUPC) is a sudden collapse of the clinical conditions of a full-term or near-term newborn, within the first 7 days of life, that requires resuscitation with positive ventilation and who either dies, has hypoxic-ischemic encephalopathy, or requires intensive care. The incidence of SUPC is very low, and most often presents a negative prognosis. The BUB1B gene is a mitotic checkpoint of serine/threonine kinase B that encodes a protein crucial for maintaining the correct number of chromosomes during cell division. Mutations in the BUB1B gene are linked to mosaic variegated aneuploidy syndrome 1 (MVA1), a rare autosomal recessive disorder characterized by diffuse mosaic aneuploidies involving several chromosomes and tissues. This paper discusses a case of a newborn who had a spontaneous delivery. After 2 h and 10 min, the infant showed generalized hypotonia and cyanosis, and his doctors performed orotracheal intubation, cardiac massage, pharmacological hemodynamic therapy, mechanical ventilation, antibiotic therapy, and hypothermic treatment. The newborn was discharged after 5 months with the diagnosis of hypoxic-ischemic encephalopathy. Suspecting an SUPC, a complete genetic analysis was performed demonstrating a compound heterozygous mutations in the BUB1B gene. The newborn died at 6 months of life, 1 month after discharge. A complete autopsy was performed, determining that the cause of death was due to sepsis starting from a brocopneumonic process, with outcomes of hypoxic-ischemic encephalopathy (HIE). In this scenario, it is not possible to demonstrate the causal effect of this mutation, considering that it could play a causal or concausal role in the onset of SUPC. Further research based on multicenter studies, as well as on animal models, could be very useful to clarify the pathological effect of this mutation.

Analysis of ventricular arrhythmias and sudden death from prospective, randomized clinical trials of acalabrutinib.

This analysis investigated the incidence of sudden deaths (SDs) and non-fatal and fatal ventricular arrhythmias (VAs) in five acalabrutinib clinical trials. In total, 1299 patients received acalabrutinib (exposure, 4568.4 patient-years). Sixteen (1.2%) patients experienced SD or VA (event rate, 0.350/100 patient-years). Non-fatal VAs occurred in 11 (0.8%) patients, nine (0.7%) of whom had premature ventricular contractions only. SD and fatal VAs occurred in five (0.4%) patients (event rate, 0.109/100 patient-years; median time to event: 46.2 months). SDs and VAs with acalabrutinib occurred at low rates, and there are insufficient data to point to an increased risk of SD or VA with acalabrutinib.