Death In Young Adults Research Articles

Rare Congenital Anomalous Origin of the Coronary Arteries: A Series of Three Cases

Introduction: Congenital coronary anomalies are found in 0.3% to 5.6% of the population and can be classified according to alterations in origin, distribution or course. Although benign in most cases, they can be associated with sudden death in young adults, especially after strenuous physical exercise. We report three rare cases of anomalous coronary arteries found incidentally by coronary angiography. Case Report: The first case refers to a 79-year-old man who underwent cardiac catheterization for etiological investigation of heart failure, showing a non-obstructive interruption of the left anterior descending artery (LAD) after the origin of the first diagonal branch, with the continuation of its middle and distal segments from the right coronary artery (RCA), which crosses to the left side at the atrial level and reaches the apex cordis. The second case is a 56-year-old woman with stable angina and a treadmill exercise test suggestive of myocardial ischemia. Coronary angiography revealed an anomalous origin of the RCA from the distal segment of the left circumflex artery (LCxA). The third and last case is a 64-year-old woman in whom coronary angiography revealed an anomalous origin of the LCxA from the proximal third of the RCA. Discussion: Coronary artery anomalies are a heterogeneous group whose diagnosis mostly occurs incidentally. They differ from anatomical variations in their rarity and greater association with adverse events, such as myocardial ischemia and sudden death. The cases presented address different anomalous origins: a LAD with duplicated origin, a single coronary artery with the emergence of the RCA in the distal third of the LCxA, and the anomalous origin of the LCxA from the RCA, one of the most common coronary anomalies. The three cases reported were patients over 50 years old, which shows the need to individualize cases and risks as regarding to anomalous origins of the coronary arteries.

School performance and the social gradient in young adult death in Norway.

Young adults from low socioeconomic backgrounds face an increased risk of early mortality. Here we utilize population-wide data from 17 Norwegian birth cohorts (N = 986,573) to assess whether this risk gradient was explained by early-life educational performance, specifically grade point average at 16 years of age. We show that the gradients in both parental education and income largely disappeared when adjusting for school performance in the models. Specifically, among boys, those with the lowest parental education had an unadjusted hazard ratio (HR) of 2.04 (95% confidence interval (CI) 1.86-2.22) compared with peers with the highest parental education, while for girls, the HR was 1.64 (95% CI 1.35-1.93). After adjusting for school performance, these estimates dropped to 0.99 (95% CI 0.79-1.19) for boys and 0.87 (95% CI 0.55-1.19) for girls. Similarly, the mortality risk for those from the lowest parental income quartile decreased from 1.79 (95% CI 1.67-1.91) to 1.25 (95% CI 1.12-1.38) for boys and from 1.63 (95% CI 1.44-1.83) to 1.24 (95% CI 1.03-1.46) for girls. Low educational performance remained strongly associated with early mortality in analyses accounting for unobserved heterogeneity at the family level; boys with a grade point average in the lowest quartile had an HR of 3.04 (95% CI 2.38-3.89), while for girls, the HR was 1.79 (95% CI 1.22-2.63). External causes of death, particularly accidents and poisoning, were most overrepresented among individuals with poor school performance.

Factors Affecting Cancer Mortality in Young Adults: Findings from a Prospective Cohort Study.

Cancer incidence in young adults or those aged 15-49 years old has increased during the past decade. Knowledge about the risk factors for cancer-related deaths in young adults is limited, particularly in low- and middle-income countries (LMICs). This analysis was based on the Hanoi Prospective Cohort Study, an ongoing study of 39,401 participants aged 15 or older in Northern Vietnam in the 2007-2019 period. A Cox proportional hazard regression model was used to calculate the hazard ratio (HR) and 95% confidence intervals (95% CIs) for the association between potential factors and the risk of cancer-related deaths. With a median follow-up of 11.01 years, we identified 164 deaths in young adults out of 554 total deaths. Overall, family history of cancer (HR = 7.34; 95% CI: 3.30-16.36), drinking alcohol (HR = 1.82; 95% CI: 1.18-2.81), and smoking (HR = 2.22; 95% CI: 1.36-3.63) were found to be risk factors, while drinking coffee was found to be a protective factor (HR = 0.49; 95% CI: 0.24-1.00) for cancer-related deaths in young adults. Young male adults were found to be at a higher risk due to excessive cigarette smoking (HR = 1.91; 95% CI: 1.00-3.68) and alcohol consumption (HR = 2.15; 95% CI: 1.32-3.53) than those aged 50 years and older (HR = 1.36 and 95% CI: 0.96-1.93 and 1.27 and 95% CI: 0.97-1.67, respectively). The risk of death from cancer in women compared with men in the young population was twice as high as that in the older population (HR = 1.18 and 95% CI: 0.72-1.94 vs. 0.47 and 95% CI: 0.35-0.63, respectively). Our data suggest that the young Vietnamese population is vulnerable to the risk of cancer-related deaths and that cancer in women will increase rapidly in the future.

A Rare Noncoding Enhancer Variant in SCN5A Contributes to the High Prevalence of Brugada Syndrome in Thailand.

Brugada syndrome (BrS) is a cardiac arrhythmia disorder that causes sudden death in young adults. Rare genetic variants in the SCN5A gene encoding the Nav1.5 sodium channel and common noncoding variants at this locus are robustly associated with the condition. BrS is particularly prevalent in Southeast Asia but the underlying ancestry-specific factors remain largely unknown. Genome sequencing of BrS probands and population-matched controls from Thailand was performed to identify rare noncoding variants at the SCN5A-SCN10A locus that were enriched in patients with BrS. A likely causal variant was prioritized by computational methods and introduced into human induced pluripotent stem cell (hiPSC) lines using CRISPR-Cas9. The effect of the variant on SCN5A expression and Nav1.5 sodium channel current was then assessed in hiPSC-derived cardiomyocytes (hiPSC-CMs). A rare noncoding variant in an SCN5A intronic enhancer region was highly enriched in patients with BrS (detected in 3.9% of cases with a case-control odds ratio of 45.2). The variant affects a nucleotide conserved across all mammalian species and predicted to disrupt a Mef2 transcription factor binding site. Heterozygous introduction of the enhancer variant in hiPSC-CMs caused significantly reduced SCN5A expression from the variant-containing allele and a 30% reduction in Nav1.5-mediated sodium current density compared with isogenic controls, confirming its pathogenicity. Patients with the variant had severe phenotypes, with 89% experiencing cardiac arrest. This is the first example of a functionally validated rare noncoding variant at the SCN5A locus and highlights how genome sequencing in understudied populations can identify novel disease mechanisms. The variant partly explains the increased prevalence of BrS in this region and enables the identification of at-risk variant carriers to reduce the burden of sudden cardiac death in Thailand.

Improved survival and decreased cancer deaths in young adults with cancer after passage of the Affordable Care Act Dependent Coverage Expansion.

The Patient Protection and Affordable Care Act (ACA) allowed Americans aged 19-25 years to remain on their parents' health insurance plans until age 26 years (the Dependent Care Expansion [DCE]). Have those with cancer diagnoses benefited? The ACE DCE 7-year age range of 19-25 years was compared for changes in cancer survival and mortality before and after enactment of the ACA with groups that were younger and older (in 7-year age spans: ages 12-18 and 26-32 years, respectively). Cancer death data for the entire United States were obtained from the Centers for Disease Control and Prevention, and relative survival data of patients who were diagnosed with cancer were obtained from the National Cancer Institute Surveillance, Epidemiology, and End Results regions representing 42%-44% of the country. Joinpoint analysis identified the DCE-eligible cohort as the only age group of the three groups evaluated that have had improvements in both cancer survival and death rate trends after ACA implementation and that 2010, the year the ACA was passed, was the inflection year for both survival and deaths. By 6 years, the relative survival after cancer diagnosis was 2.6 and 3.9 times greater in the DCE-eligible age group than in the younger and older control groups, respectively (both p<.001), and the cancer death rate in the DCE-eligible age group improved 2.1 and 1.5 times greater than in the younger and older control age groups, respectively (both p<.01). During the first decade of the ACA, eligible young adults with cancer have had significantly improved survival and mortality. Additional policies expanding insurance coverage and enabling earlier cancer diagnosis among young adults are needed. The Patient Protection and Affordable Care Act (ACA) Dependent Care Expansion (DCE) that began in the United States in 2011 allowed young adults aged 19-25 years to remain on their parents' health insurance plans until age 26 years. The survival rate at 6 years in young adult patients diagnosed with cancer was 2.6 to 3.9 times greater in the DCE-eligible age group compared with the younger and older age groups, and the rate of deaths from cancer improved 1.5 to 2.1 times more. During the first decade of the ACA, young adults with cancer who were in the eligible group had significantly longer survival and reduced deaths from cancer. Additional policies that expand insurance coverage and allow the diagnosis of cancer sooner are needed in young adults.

Desmoplakin CSM models unravel mechanisms regulating the binding to intermediate filaments and putative therapeutics for cardiocutaneous diseases.

Arrhythmogenic cardiomyopathy (AC) is a common cause of sudden cardiac arrest and death in young adults. It can be induced by different types of mutations throughout the desmoplakin gene including the R2834H mutation in the extreme carboxyterminus tail of desmoplakin (DP CT) which remains structurally uncharacterized and poorly understood. Here, we have created 3D models of DP CT which show the structural effects of AC-inducing mutations as well as the implications of post-translational modifications (PTMs). Our results suggest that, in absence of PTMs, positively charged wildtype DP CT likely folds back onto negatively-charged plectin repeat 14 of nearby plakin repeat domain C (PRD C) contributing to the recruitment of intermediate filaments (IFs). When phosphorylated and methylated, negatively-charged wildtype DP CT would then fold back onto positively-charged plectin repeat 17 of PRD C, promoting the repulsion of intermediate filaments. However, by preventing PTMs, the R2834H mutation would lead to the formation of a cytoplasmic mutant desmoplakin with a constitutively positive DP CT tail that would be aberrantly recruited by cytoplasmic IFs instead of desmosomes, potentially weakening cell-cell contacts and promoting AC. Virtual screening of FDA-approved drug libraries identified several promising drug candidates for the treatment of cardiocutaneous diseases through drug repurposing.

Association between cardiovascular risk factors and dilated and hypertrophic cardiomyopathy: Mendelian randomization analysis

Background and aimDilated cardiomyopathy is a major cause of heart failure, and hypertrophic cardiomyopathy is a common cause of sudden cardiac death in young adults. Epidemiological studies reporting the association between these cardiomyopathies and common cardiovascular risk factors, including smoking, alcohol, and obesity, are limited, and the published studies are mostly observational, making them vulnerable to bias. Methods and resultsWe performed a two-sample Mendelian randomization analysis to assess whether cardiovascular risk factors were causally associated with dilated and hypertrophic cardiomyopathies. Independent genetic variants associated with body mass index, smoking, and alcohol were selected as instrumental variables, with two sets of instrumental variables utilized for alcohol. Dilated cardiomyopathy data on 355,318 samples and hypertrophic cardiomyopathy data on 489,727 samples were obtained from a European population-based genome-wide association study (GWAS) meta-analysis. The large GWAS data sample size improved the statistical power. Our results showed significant associations between a genetic predisposition for smoking and the risk of dilated cardiomyopathy (odds ratio (OR) = 1.33; 95 % confidence level (CI): 1.07–1.67; p = 0.012) and between a genetic predisposition for obesity and the risk of dilated cardiomyopathy (OR = 1.62; 95 % CI, 1.30–2.02; p = 1.51 × 10−5). The results of the other associations were not significant. ConclusionsThis study suggests that smoking and obesity are causally associated with an increased risk of dilated cardiomyopathy.

Idiopathic Ventricular Fibrillation - Just How Much Idiopathic is it?

Idiopathic ventricular fibrillation is diagnosed in survivors of sudden cardiac death that has been caused by ventricular fibrillation without known structural or electrical abnormalities, even after extensive investigation. It is a common cause of sudden death in young adults. Although idiopathic ventricular fibrillation is a diagnosis of exclusion, in many cases only a partial investigation algorithm is performed. The aim of this review is to present a comprehensive diagnostic evaluation algorithm with a focus on diagnostic assessment of inherited arrhythmic syndromes and genetic background.

Heart Failure Predictive Analysis Using Decision Tree Classification

With an average age of 28 compared to Western countries, India's young population accounts for half of heart attacks in South Asia, which happen to people under 52. Autopsy reports, which identify the actual cause of death, frequently concentrate on sudden deaths in young adults that have no apparent reason or warning signs. Fat accumulation in the blood vessels of the heart is the cause of abrupt, unexpected natural deaths. The heart stops beating and loses blood as a result of these arteries narrowing or blocking. The body may exhibit subtle symptoms prior to abrupt death, such as shortness of breath, palpitations, tightness in the chest, and chest discomfort. A decision tree classification is a death dataset model that generates labelled classes at leaf nodes and makes judgments at edges to predict class labels for subsequent records. The purpose of the proposed paper study is to predict abrupt natural deaths, which are frequently brought on by smoking, by using regression analysis, a statistical technique that establishes the relationship between independent and dependent variables. The experiment's outcome, which looks at how Artificial Neural Networks (ANN) may be used to forecast heart failure, shows five records out of 50,000 patients from different hospitals. Perceptron’s, both single- and multi-layer, were used to gather patient information. Keywords: Artificial Neural Network, Linear Regression Analysis, Sudden and Unexpected Natural Deaths etc.

From parents to children: associations of traffic risks with impulsivity, family relationships and serotonin transporter genotype.

Road traffic injuries are the leading cause of death for young adults, and parents play a major role in shaping their traffic behaviour. Higher impulsivity (predictor of higher traffic risk) has been shown to be dependent on family relations and the serotonin transporter gene promoter polymorphism (5-HTTLPR). The specific mechanisms for the inheritance of risky traffic behaviour from parents to children are not clear, and the genetic aspect has not been studied before. We used data of Estonian Children Personality Behaviour and Health Study subjects (n = 596, mean age = 25.2 ± 0.6) and their parents (mothers, n = 460, mean age = 52.1 ± 5.8; fathers, n = 339, mean age = 54.1 ± 6.5). Family relationships scale, traffic risk questionnaires and Adaptive and Maladaptive Impulsivity Scale were filled out. The increased risk-taking behaviour of parents and worse quality of family relationship were significant predictors of higher traffic risk among subjects. Family support and impulsivity of fathers significantly predicted the subjects' traffic risk score in interaction with 5-HTTLPR genotype: l'/l' homozygous subjects with adaptively impulsive fathers had higher traffic risk, whereas for s'-allele carrying subjects family support was more significant. Parental role modelling and family relationships are significant predictors of future traffic behaviour of the child. Whether the behavioural example of the father or the influence of family relationships is more important in predicting future risky traffic behaviour, depends on the 5-HTTLPR genotype of the child.

Young Adult Alcohol and Cannabis Impaired Driving After the Opening of Cannabis Retail Stores in Washington State.

Motor vehicle crashes are a leading cause of death for young adults (YA) in the USA, and driving under the influence of alcohol (DUIA), cannabis (DUIC), and simultaneous use of both substances (DUIAC) are prominent risk factors. Trends in YA impaired driving behaviors after opening of cannabis retail stores have been understudied. We examined YA trends in DUIA, DUIC, and DUIAC from immediately prior through 5years following the opening of cannabis retail outlets in Washington State (2014-2019). Differences in trends were assessed across age, sex, and urbanicity. Weighted logistic regressions assessed yearly change in prevalence of DUIA, DUIC, and DUIAC from 2014 to 2019, using annual statewide data from the Washington Young Adult Health Survey (n = 12,963; ages 18-25). Moderation of trends by age, sex, and urbanicity was assessed. Prevalence of DUIA decreased overall (AOR = 0.93, 95% CI 0.90, 0.97) and among drinkers (AOR = 0.95, 95% CI 0.91, 0.99) but remained at concerning levels in 2019 (10% overall; 16% among drinkers). Overall DUIC did not change significantly (AOR = 0.99, 95% CI 0.96, 1.03; 11% by 2019) but decreased among those who used cannabis (AOR = 0.91, 95% CI 0.86, 0.96; 33% by 2019). DUIAC decreased but not significantly (overall: AOR = 0.89, 95% CI 0.78, 1.01; those who used alcohol and cannabis: AOR = 0.84, 95% CI 0.74, 1.04). Prevalence of YA DUI remained concerning. Trends may reflect some success in reducing DUI, but additional detection and prevention are needed.

Genetics in the diagnosis and treatment of cardiovascular diseases

Cardiovascular diseases (CVDs) remain one of the leading causes of morbidity and mortality worldwide, with genetics being a major risk factor. Genetic cardiovascular disease can occur either because of single variant (Mendelian) or polygenic influences and has been linked to inherited cardiovascular conditions (ICC) such as arrhythmias, cardiomyopathies, dyslipidemias, and aortopathies which are significant factors leading to sudden cardiac death in young adults. Timely screening, diagnosis, and management of ICC can not only provide life-saving treatment to a patient, but also identify at-risk family members. The field of pharmacogenomics (PGx) helped to understand the variable action of medications such as clopidogrel, aspirin, warfarin, and statin according to genotype. Newer technologies such as multi-omics can combine data from multiple sources such as genomics, epigenomics, transcriptomics, proteomics, metabolomics, and microbiome. These advancements can contribute to the development of polygenic prediction scores and precision medicine tailored to individual genotypes. Substantial strides have been made in genetic-based therapeutics, gene editing technologies, and drug delivery systems, which have significantly expanded treatment options for patients with acquired or inherited CVDs. Although variable, the country- and society-specific guidelines on genetic testing for ICC and PGx and treatment are being continuously updated to keep up with ongoing research in the field. Along with appropriate knowledge, other factors including cost and availability of genetic testing play a vital role in the usage by both physicians and patients. With the advent of newer genetic testing for CVDs, a key factor is the availability of genetic counselors (GCs) who are specifically trained in cardiovascular genomics. The current review provides a concise summary of the major influences of genetics in the diagnosis and treatment of CVDs.

Acute Adenoviral Infection Elicits an Arrhythmogenic Substrate Prior to Myocarditis.

Viral cardiac infection represents a significant clinical challenge encompassing several etiological agents, disease stages, complex presentation, and a resulting lack of mechanistic understanding. Myocarditis is a major cause of sudden cardiac death in young adults, where current knowledge in the field is dominated by later disease phases and pathological immune responses. However, little is known regarding how infection can acutely induce an arrhythmogenic substrate before significant immune responses. Adenovirus is a leading cause of myocarditis, but due to species specificity, models of infection are lacking, and it is not understood how adenoviral infection may underlie sudden cardiac arrest. Mouse adenovirus type-3 was previously reported as cardiotropic, yet it has not been utilized to understand the mechanisms of cardiac infection and pathology. We have developed mouse adenovirus type-3 infection as a model to investigate acute cardiac infection and molecular alterations to the infected heart before an appreciable immune response or gross cardiomyopathy. Optical mapping of infected hearts exposes decreases in conduction velocity concomitant with increased Cx43Ser368 phosphorylation, a residue known to regulate gap junction function. Hearts from animals harboring a phospho-null mutation at Cx43Ser368 are protected against mouse adenovirus type-3-induced conduction velocity slowing. Additional to gap junction alterations, patch clamping of mouse adenovirus type-3-infected adult mouse ventricular cardiomyocytes reveals prolonged action potential duration as a result of decreased IK1 and IKs current density. Turning to human systems, we find human adenovirus type-5 increases phosphorylation of Cx43Ser368 and disrupts synchrony in human induced pluripotent stem cell-derived cardiomyocytes, indicating common mechanisms with our mouse whole heart and adult cardiomyocyte data. Together, these findings demonstrate that adenoviral infection creates an arrhythmogenic substrate through direct targeting of gap junction and ion channel function in the heart. Such alterations are known to precipitate arrhythmias and likely contribute to sudden cardiac death in acutely infected patients.

School personnel suicide prevention training: No clear option

Youth and young adult deaths from suicide have been increasing in the United States over the past two decades. According to the Centers for Disease Control and Prevention's National Center for Health Statistics for those between the ages of 10 and 24 from 2011 to 2021 the death by suicide rate rose 60% to 11.0 per 100,000. Paralleling these highly troubling rates of death by suicide is information from the Centers for Disease Control (CDC) Youth Risk Behavior Survey Data Summary and Trends Report: 2011–2021. The report reinforces a picture of our nation's youth in serious mental health crisis. In response to the 2021 survey an increasing number of students reported persistent feelings of sadness and hopelessness. This included 57% of girls, 29% of boys and 69% of LGBTQ students. More than 20% of teens reported having seriously considered suicide!

Causes of fatal traumatic brain injury in Finland.

The phenotype of patients who suffer fatal traumatic brain injury (TBI) is poorly characterized. The authors examined the external causes, contributing diseases, and preinjury medication in adult patients with fatal TBI in a nationwide Finnish cohort. Deaths caused by TBIs in Finland were examined among decedents aged ≥ 16 years during 2005-2020 from the national Cause of Death Registry. Usage of prescription medications prior to TBI was studied using medication purchase data from the Social Insurance Institution of Finland. The cohort consisted of 71,488,347 person-years, 821,259 total deaths, and 14,630 TBI-related deaths during 2005-2020, of which 67% (n = 9792) occurred in men. Women were older than men among those who suffered TBI-related death (mean age 77.2 ± 17.1 vs 64.5 ± 19.5 years, p < 0.0001). The overall crude incidence rate of fatal TBIs was 20.5/100,000 person-years (28.1/100,000 in men and 13.2/100,000 in women). TBI was the cause of death in 1.8% of all deaths in the Finnish population during the study years, but in patients aged 16-19 years, TBIs caused more than 17% of all deaths. The most common external cause of fatal TBI was a fall (70%), followed by poisoning or toxic effects (20%) and violence or self-harm (15%) overall. In men, the order of the most common causes of fatal TBI was similar to overall results (64%, 25%, and 19%, respectively), while in women, the most common cause was a fall (82%), followed by complications in healthcare (10%) and poisoning or toxic effects (9%). Cardiovascular diseases, psychiatric diseases, and infections were the most common diseases contributing to death. Blood pressure (lowering) medications were the most common type of medications used before fatal TBI. CNS medications were the second most common medication group. In the context of fatal TBI in Europe, Finland remains at the upper end of fatal TBI incidence. TBI is a common cause of death in young adults, whereas the incidence of fatal TBI becomes increasingly higher with age in Finland. Cardiovascular diseases and psychiatric conditions were the most common diseases related to death, with opposite age trends. Healthcare facility complications were an alarmingly common cause of death in women with fatal TBI.

Association between anti-cardiac autoantibodies in acute myocarditis and downstream clinical outcomes

Abstract Introduction Myocarditis is an inflammatory heart muscle disease that can result in cardiac dysfunction and arrhythmias. Its aetiology includes infectious, toxic or autoimmune causes. Myocarditis is responsible for sudden cardiac death in young adults (1) and can result in heart failure due to dilated cardiomyopathy in 20% of patients (2). The pathogenesis of myocarditis may involve immune system dysregulation leading to a cascade of inflammation and myocardial damage (3). For those patients that rapidly progress to end-stage dilated cardiomyopathy, an important dilemma is whether there is any prospect of heart function recovery. Therefore, there is an unmet need for a better understanding of key causal pathways and for developing a biological signature of disease progression. Hypothesis The progression of acute myocarditis depends on a persistent adaptive immune response against the heart, leading to ongoing inflammation, myocardial fibrosis and ultimately tissue destruction and remodelling. Aims We sought to explore anti-cardiac IgG serum levels, their temporal profile throughout follow up and their association with clinical and imaging data, in patients presenting with acute myocarditis. Methods We prospectively recruited 80 patients with a clinical diagnosis of acute myocarditis. We measured their total anti-cardiac IgG levels at admisssion, 3- and 12-months follow-up using an enzyme-linked immunosorbent assay (ELISA). We explored the association between the anti-cardiac IgG levels, cardiac MRI parameters (CMR) and clinical data. Results We detect an adaptive immune response against the heart in a subgroup of patients with acute myocarditis. 20% of patients develop high systemic titres of anti-cardiac IgG (OD threshold &amp;gt;0.65), within the first 7 days of presentation (Figure 1a). These patients continue to have persistent and significantly higher anti-cardiac IgG levels at 12 months (Figure 1b). Importantly, patients that mount a strong initial adaptive immune response against the heart, are more likely to show evidence of persistent oedema on CMR at 12 months(Figure 1c). Clinical event rates in our cohort have remained low at five-year follow-up. A small signal exists to indicate potentially higher rates of persistent symptoms (70% vs 47%), hospitalisations for heart failure (12% vs 8%) and new heart failure diagnosis (18% vs 11%), in patients that mount a strong adaptive immune response compared to those that do not. Conclusion A subset of patients with acute myocarditis develops a strong and persistent adaptive immune response against the heart. This may be associated with more myocardial oedema on cardiac MRI, persistent symptoms and higher rates of heart failure diagnoses and hospitalisations. Further work Plasma proteomics (targeted and un-targeted discovery) with validation in myocardial tissue. Analysis of CMR data with a focus on fibrosis assessment. ELISA for IgG subtypes and total IgG against myosin and troponin I.

Childhood contact with social services and risk of suicide or sudden death in young adulthood: identifying hidden risk in a population-wide cohort study

BackgroundChildhood out-of-home care is associated with premature death in adulthood, in particular death by suicide, accidents and violence. However, little is known about the mortality risk in the much larger...

On Scene Injury Severity Prediction (OSISP) model for trauma developed using the Swedish Trauma Registry

BackgroundProviding optimal care for trauma, the leading cause of death for young adults, remains a challenge e.g., due to field triage limitations in assessing a patient’s condition and deciding on transport destination. Data-driven On Scene Injury Severity Prediction (OSISP) models for motor vehicle crashes have shown potential for providing real-time decision support. The objective of this study is therefore to evaluate if an Artificial Intelligence (AI) based clinical decision support system can identify severely injured trauma patients in the prehospital setting.MethodsThe Swedish Trauma Registry was used to train and validate five models – Logistic Regression, Random Forest, XGBoost, Support Vector Machine and Artificial Neural Network – in a stratified 10-fold cross validation setting and hold-out analysis. The models performed binary classification of the New Injury Severity Score and were evaluated using accuracy metrics, area under the receiver operating characteristic curve (AUC) and Precision-Recall curve (AUCPR), and under- and overtriage rates.ResultsThere were 75,602 registrations between 2013–2020 and 47,357 (62.6%) remained after eligibility criteria were applied. Models were based on 21 predictors, including injury location. From the clinical outcome, about 40% of patients were undertriaged and 46% were overtriaged. Models demonstrated potential for improved triaging and yielded AUC between 0.80–0.89 and AUCPR between 0.43–0.62.ConclusionsAI based OSISP models have potential to provide support during assessment of injury severity. The findings may be used for developing tools to complement field triage protocols, with potential to improve prehospital trauma care and thereby reduce morbidity and mortality for a large patient population.

P21-Activated Kinases Present a New Drug Target for Hypertrophic Cardiomyopathy

Expert review p21-Activated Kinases Present a New Drug Target for Hypertrophic Cardiomyopathy He Yu , and Lei Ming , * Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, UK * Correspondence: ming.lei@pharm.ox.ac.uk Received: 17 February 2023 Accepted: 26 March 2023 Published: 21 August 2023 Abstract: Hypertrophic cardiomyopathy (HCM), primarily involving mutations in sarcomeric proteins, is the most common form of inherited heart disease and a leading cause of sudden death in young adults and athletes. HCM patients present with cardiac hypertrophy, fibrosis, and diastolic dysfunction often in a progressive manner. Despite significant progress made in understanding the molecular genetic basis of HCM, there remains a lack of effective and specific treatment for preventing disease progression in HCM. This article first provides an overview of recent progress in understanding the pathogenic basis of disease progression in HCM, in particular dysfunctional calcium handling, mitochondrial impairment, and endoplasmic reticulum stress. This article then analyses the evidence for critical roles of the multifunctional enzymes P21-activated kinase-1 and 2 (Pak1/2) in the heart and our opinion on their therapeutic value as a promising druggable target in pathological hypertrophy and associated ventricular arrhythmias.

Sudden cardiac death and thymic hyperplasia in adults: myth or reality? A case report

BackgroundSudden cardiac death is a major public health concern. The incidence of sudden cardiac death in young adults remains unclear and is generally underestimated.Case presentationThis is a case report of a 24-year-old man with a silent pathological history, who suddenly collapsed in a restaurant during dinner with his workmates. Autopsy and ancillary examination revealed focal atrioventricular node fibrosis and thymic hyperplasia.ConclusionsThymic hyperplasia has been considered a cause of sudden death in the past century. The mode of death was explained through nosographic entities such as status lymphaticus or thymic asthma, which are currently consigned to history books. Nevertheless, recent studies have sought to determine the relationship between thymic hyperplasia and sudden unexpected deaths in adults. Moreover, isolated fibrosis of the atrioventricular node is a rare condition that can remain undiagnosed even after a full autopsy. This report aims to provide a concise review of the existing literature concerning sudden cardiac death and discuss the so-called “thymic death” theory, which is now considered a myth. Was the finding of thymic hyperplasia and atrioventricular node fibrosis a coincidence? Should the myth surrounding “thymic death” be re-examined?