BACKGROUND: Sudden non-cardiac death (SNCD) is a clinical entity comprising deaths lacking previous clinically significant symptoms, and in which the mechanisms of death do not involve the heart. Infection is a major cause of SNCD, particularly in children, and viruses are frequently involved in the disease process. Nevertheless, SNCD of viral infectious causes remains poorly characterized. Thus, a systematic review of the literature describing the association between viral infection and the development of SNCD was performed.
METHODS: PRISMA statement guidelines were followed in this systematic review. A literature search was conducted across MEDLINE, Scopus and Web of Science databases. Studies considered eligible were autopsy series or cohort studies of sudden death cases, in which evidence of viral disease as a cause of death was demonstrated, along with identification of causative agents.
RESULTS: Twelve studies published between 1996 and 2020 were included in this review. Selected studies were categorized into three groups according to the study population: infants and young children (up to four years of age); presumed sudden infant death syndrome patients; and older individuals (five years of age and older). SNCD with viral implication represents a minority of sudden death cases in all age groups, with infants and young children having a higher prevalence across studies. Respiratory infection was the main cause of viral SNCD, with influenza virus and respiratory syncytial virus being the most commonly identified agents in older individuals, and infants and young children respectively. Disseminated infection, gastrointestinal infection, and meningitis were other identified causes of SNCD in children.
CONCLUSIONS: No studies have directly assessed the frequency and causes of viral SNCD. Infants and young children show a considerable, but variable, prevalence of this clinical entity. Wider implementation of post-mortem virological molecular testing may help uncover previously unknown cases. More research into viral SNCD is needed, especially in the adult population.

Frequent and excessive consumption of alcohol, be it episodic or sustained misuse, ranks among the top causes of mortality globally. This comprehensive analysis seeks to elucidate how alcohol misuse precipitates death, with a particular focus on associated cardiac anomalies. Notably, the phenomenon of \"Holiday Heart Syndrome\", linked to binge drinking, is recognized for inducing potentially fatal cardiac arrhythmias. Moreover, persistent alcohol consumption is implicated in the development of alcoholic cardiomyopathy, a condition that underlies heart failure and arrhythmic disturbances of the heart. Additionally, individuals undergoing withdrawal from alcohol frequently exhibit disruptions in normal heart rhythm, posing a risk of death. This review further delves into additional alcohol-related mortality factors, including the heightened likelihood of hypertension, cerebrovascular accidents (strokes), and the connection between excessive alcohol use and Takotsubo syndrome.

Sudden unexpected deaths often remain unresolved despite forensic examination, posing challenges for pathologists. Molecular autopsy, through genetic testing, can reveal hidden causes undetectable by standard methods. This review assesses the role of molecular autopsy in clarifying SUD cases, examining its methodology, utility, and effectiveness in autopsy practice. This systematic review followed PRISMA guidelines and was registered with PROSPERO (registration number: CRD42024499832). Searches on PubMed, Scopus, and Web of Science identified English studies (2018-2023) on molecular autopsy in sudden death cases. Data from selected studies were recorded and filtered based on inclusion/exclusion criteria. Descriptive statistics analyzed the study scope, tissue usage, publication countries, and journals. A total of 1759 publications from the past 5 years were found, with 30 duplicates excluded. After detailed consideration, 1645 publications were also excluded, leaving 84 full-text articles for selection. Out of these, 37 full-text articles were chosen for analysis. Different study types were analyzed. Mutations were identified in 17 studies, totaling 47 mutations. Molecular investigations are essential when standard exams fall short in determining sudden death causes. Expertise in molecular biology is crucial due to diverse genetic conditions. Discrepancies in post-mortem protocols affect the validity of results, making standardization necessary. Multidisciplinary approaches and the analysis of different tissue types are vital.

Sudden death from haemopericardium as a result of a right atrial rupture is uncommon, most particularly when this occurs spontaneously without any prior trauma or evidence of atrial wall pathology. The deceased was a 32-year-old man. At lunchtime his symptoms of unease, giddiness and unconsciousness began and within 45 minutes he arrived at the hospital. His vitals could not be recorded in the emergency department, and after CPR, he was pronounced dead. At autopsy, an isolated right atrial rupture, without any disease of the heart wall, was discovered. The right atrium has the weakest wall and is frequently the site of spontaneous rupture brought on by increased intraluminal pressure. Both liquid blood and clotted blood were found in the pericardial cavity. Low atrial pressure encourages clot formation because it causes considerably slower blood entry into the pericardium at the time of atrial rupture compared with entry at the time of ventricular rupture. Evidence of chronic lung disease was found which explains the raised intraluminal pressure of the heart chambers. Even with no history of trauma or myocardial infarction, the Beck triad - an engorged neck vein, a muffled heart sound, and low blood pressure - should alert the emergency room staff to the possibility of cardiac tamponade because, in a very unlikely scenario, spontaneous cardial wall rupture might occur.

Hypertrophic cardiomyopathy (HCM) is a common contemporary, treatable, genetic disorder that can be compatible with normal longevity. While current medical therapies are ubiquitous, they are limited by a lack of solid evidence, are often inadequate, poorly tolerated, and do not alter the natural disease course. As such, there has long been a need for effective, evidence-based, and targeted disease-modifying therapies for HCM. In this review, we redefine HCM as a treatable condition, evaluate current strategies for therapeutic intervention, and discuss novel myosin inhibitors. The majority of patients with HCM have elevated left ventricular outflow tract gradients, which predicts worse symptoms and adverse outcomes. Conventional pharmacological therapies for symptomatic HCM can help improve symptoms but are often inadequate and poorly tolerated. Septal reduction therapies (surgical myectomy and alcohol septal ablation) can safely and effectively reduce refractory symptoms and improve outcomes in patients with obstructive HCM. However, they require expertise that is not universally available and are not without risks. Currently, available therapies do not alter the disease course or the progressive cardiac remodeling that ensues, nor subsequent heart failure and arrhythmias. This has been regarded as an unmet need in the care of HCM patients. Novel targeted pharmacotherapies, namely cardiac myosin inhibitors, have emerged to reverse key pathophysiological changes and alter disease course. Their favorable outcomes led to the early Food and Drug Administration approval of mavacamten, a first-in-class myosin modulator, changing the paradigm for the pharmacological treatment of HCM.

OBJECTIVE: Primary brain tumors have the potential to present a substantial health hazard, ultimately resulting in unforeseen fatalities. Despite the enhanced comprehension of many diseases, the precise prediction of disease progression continues to pose a significant challenge. The objective of this study is to investigate cases of unexpected mortality resulting from primary brain tumors and analyze the variables that contribute to such occurrences.
METHODS: This systematic review explores research on individuals diagnosed with primary brain tumors who experienced unexpected deaths. It uses PRISMA standards and searches PubMed, Google Scholar, and Scopus. Variables considered include age, gender, symptoms, tumor type, WHO grade, postmortem findings, time of death - time taken from first medical presentation or hospital admission to death, comorbidity, and risk factors.
RESULTS: This study examined 46 studies to analyze patient-level data from 76 individuals with unexpected deaths attributed to intracranial lesions, deliberately excluding colloid cysts. The cohort\'s age distribution showed an average age of 37 years, with no significant gender preference. Headache was the most common initial symptom. Astrocytomas, meningiomas, and glioblastoma were the most common lesions, while the frontal lobe, temporal lobe, and cerebellum were common locations. Meningiomas and astrocytomas showed faster deaths within the first hour of hospital admission.
CONCLUSIONS: The etiology of unforeseen fatalities resulting from cerebral tumors elucidates an intricate and varied phenomenon. Although unexpected deaths account for a very tiny proportion of total fatalities, it is probable that their actual occurrence is underestimated as a result of underreporting and misdiagnosis.

Over the past decade, the treatment landscape of chronic lymphocytic leukemia (CLL) has dramatically changed, shifting from cytotoxic chemotherapy to targeted therapies. Bruton\'s tyrosine kinase (BTK) inhibitors have revolutionized the treatment of CLL and are increasingly applied in many other malignancies. However, ibrutinib, the first BTK inhibitor approved, is associated with serious toxicities, including atrial fibrillation in up to 38% of patients, ventricular arrhythmias, and other cardiovascular toxicities. Emerging data suggest several newer BTK inhibitors (eg, acalabrutinib, zanubrutinib) are still associated with cardiotoxic risks. This review examines the current state of evidence, including incidence rates, risk factors, mechanisms, and management strategies of cardiovascular toxicities with BTK inhibitors and other CLL therapies. We specifically focus on atrial fibrillation, ventricular arrhythmias/sudden death, hypertension, heart failure, bleeding, and stroke. We also touch on other emerging BTK therapies (eg, pirtobrutinib). Finally, we highlight key unanswered questions and future directions of research.

Chronic kidney disease (CKD) is classified into five stages with kidney failure being the most severe stage (stage G5). CKD conveys a high risk for coronary artery disease, heart failure, arrhythmias, and sudden cardiac death. Cardiovascular complications are the most common causes of death in patients with kidney failure (stage G5) who are maintained on regular dialysis treatment. Because of the high death rate attributable to cardiovascular (CV) disease, most patients with progressive CKD die before reaching kidney failure. Classical risk factors implicated in CV disease are involved in the early stages of CKD. In intermediate and late stages, non-traditional risk factors, including iso-osmotic and non-osmotic sodium retention, volume expansion, anaemia, inflammation, malnutrition, sympathetic overactivity, mineral bone disorders, accumulation of a class of endogenous compounds called \'uremic toxins\', and a variety of hormonal disorders are the main factors that accelerate the progression of CV disease in these patients. Arterial disease in CKD patients is characterized by an almost unique propensity to calcification and vascular stiffness. Left ventricular hypertrophy, a major risk factor for heart failure, occurs early in CKD and reaches a prevalence of 70-80% in patients with kidney failure. Recent clinical trials have shown the potential benefits of hypoxia-inducible factor prolyl hydroxylase inhibitors, especially as an oral agent in CKD patients. Likewise, the value of proactively administered intravenous iron for safely treating anaemia in dialysis patients has been shown. Sodium/glucose cotransporter-2 inhibitors are now fully emerged as a class of drugs that substantially reduces the risk for CV complications in patients who are already being treated with adequate doses of inhibitors of the renin-angiotensin system. Concerted efforts are being made by major scientific societies to advance basic and clinical research on CV disease in patients with CKD, a research area that remains insufficiently explored.

The aim of this review is to examine the links among the different factors that determine harmful or even deadly events in professional and semiprofessional intensive Esports players. Cases of serious injuries or even death in young (<35 years old) male professional Esports players are reported every year. Fatalities and injuries in professional Esports players (PEGS) have only affected male players, and these events have mostly been concentrated in Asia. Studies in the literature have reported several causes and mechanisms of injuries. Links between injuries and previous comorbidities have emerged from the extant literature; obesity and/or metabolic disorders, seizures (associated with overstimulation of the eyes), heart malfunctions, high basal and abrupt increases in systolic blood pressure (SBP), prolonged stress, and poor posture have been associated with injuries. Several clinical signs have been identified and the question emerges whether or not self-regulation by Esports associations or public health authorities is necessary.

Sudden unexpected death (SUD) is one of the challenging situations encountered in forensic medicine. As a rule, a comprehensive forensic assessment is performed to identify the cause of death in such cases; however, the absence of findings suggestive of a cause, i.e., a negative autopsy, warrants further investigation such as a molecular autopsy. In this review, we aim to highlight the genetic causes of SUD, tools used in a molecular autopsy, and the role of screening in surviving relatives. As per several guidelines, the most preferred samples for DNA extraction are whole blood and fresh frozen tissues. Furthermore, Sanger sequencing and next-generation sequencing are the technologies that are used for genetic analysis; the latter overcomes the former\'s drawbacks in terms of cost-effectiveness, time consumption, and the ability to sequence the whole exome. SUD have diverse etiologies; we can generally classify them into cardiac and non-cardiac causes. Regarding cardiac causes, many conditions having an underlying genetic basis are included, such as channelopathies and cardiomyopathies. Regarding non-cardiac causes of SUD, the main etiologies are epilepsy and metabolic disorders. Nevertheless, it has been proposed that there is a genetic overlap between channelopathies, especially long QT syndromes and epilepsy. Additionally, fatty acid oxidation disorders are major metabolic conditions that are caused by certain genetic mutations that can lead to SUD in infancy. Since many SUD causes have an underlying genetic mutation, it is important to understand the genetic variations not only to recognize the cause of death but also to undertake further preventive measures for surviving relatives. In conclusion, a molecular autopsy has a major role in the forensic examination of cases of SUD.