Severe hypoxemia after generalized convulsive seizures (GCSs) can trigger neural injury and is a potential biomarker for sudden unexpected death in epilepsy (SUDEP). Some degree of variability in interbreath interval is normal, but increased variability may suggest dysfunctional breathing control and may be associated with severe postictal hypoxemia. We evaluated the relationship between interictal breathing variability and severity and duration of hypoxemia after GCS. We prospectively collected video-EEG, respiratory flow and effort, pulse oximetry (SpO2), and ECG from people with epilepsy (PWE). Measures of interictal interbreath interval variability (coefficient of variation, root mean square of successive differences [RMSSD], and long-term [SD-2] variability from Poincaré plots) from interictal asleep and awake periods and other relevant variables were evaluated as covariates for primary outcomes: (1) hypoxemia duration (length of time SpO2 <90%) and (2) severity of hypoxemia (SpO2 nadir), and secondary outcome: occurrence of combined prolonged and pronounced hypoxemia. Univariable and multivariable models were created for primary outcomes, but only univariable analyses were performed for the secondary outcome. Of 2,506 participants enrolled, 257 (141 [∼54%] female; mean age = 37.9 years) had ≥1 GCS, but only 152 GCS in 123 had evaluable respiratory data. Multivariable model for hypoxemia duration showed that SpO2 nadir (mean ratio [MR] = 0.88, 95% CI 0.81-0.96, p = 0.002) and SD-2 of the awake interbreath interval (MR = 1.06, 95% CI 1.01-1.13, p = 0.04) were significantly associated. RMSSD of the non-REM interbreath interval (mean difference = -5.01, 95% CI -8.10 to -1.93, p = 0.002) was the only variable significantly associated with hypoxemia severity after controlling for duration of postictal generalized EEG suppression, SD-2 of the awake interbreath interval, and body mass index. Univariable analyses for combined prolonged and pronounced hypoxemia showed SD-2 of the awake interbreath interval, temporal lobe epilepsy, ictal central apnea, and a shorter tonic phase duration were significantly associated. Measures of interictal respiratory variability are associated with severe and prolonged hypoxemia after GCS. Increased interictal respiratory variability suggests baseline respiratory dysregulation in some PWE and may be a surrogate for SUDEP risk.

The growing use and improved accessibility of noninvasive imaging modalities have increased the detection of incidental intracranial findings, such as unruptured brain arteriovenous malformations (AVMs). At the same time, existing literature presents conflicting findings regarding whether the incidence of ruptured AVMs has increased or decreased. Considering these developments, we hypothesized that the detection rate of unruptured AVMs has increased, and the detection rate of ruptured AVMs has changed over the period of 18 years, potentially reflecting shifts in underlying vascular risk profiles and preventive health behaviors. In this retrospective population-based study, we identified all hospitalized and nonhospitalized (prehospital sudden death) individuals with AVMs in Southern Finland between 1998 and 2015 from the National Cause of Death Register autopsy reports (using ICD-10 codes I60.8, I61.0-I61.9, Q28.0-Q28.3) and the Helsinki AVM Register. European Standard Population age-standardized detection rates with 95% CIs were determined in 3-year intervals for both ruptured and unruptured AVMs. Significance in detection rate trends was analyzed with Poisson regression on 3-year sliding averages. Between 1998 and 2015, 288 individuals (minimum age 0.2 years, mean age 41.1 years, SD = 18.0 years, 48.3% women) with AVMs were identified; 284 were hospitalized, and 4 died from AVM at home (diagnosed at medicolegal autopsy). The overall (men and women) detection rate of both ruptured and unruptured AVMs decreased from 0.91 (95% CI 0.66-1.17) to 0.40 (95% CI 0.24-0.56)/100,000 person-years during 1998-2015. The annual decrease for ruptured and unruptured AVMs was 5.7% in men (95% CI 3.6%-7.8%), 5.9% in patients <30 years (95% CI 3.2%-8.7%), 4.8% in patients aged 30-59 years (95% CI 2.7%-7.0%), and 2.2% in women (95% CI 0.0%-4.3%). Detection rates decreased by 4.6% annually for ruptured AVMs (95% CI 2.6%-6.6%) and 3.1% for unruptured AVMs (95% CI 0.7%-5.4%). Contrary to our hypothesis, we observed a decline in the overall detection rate of unruptured AVMs over the 18-year study period. Moreover, we found a substantial reduction in the number of ruptured AVMs among men, women, and patients younger than 60 years. The reasons for these rapid changes remain unclear and warrant further investigation.

Sudden unexpected death in infancy (SUDI) is a leading cause of infant mortality. Although ambient temperature affects many health outcomes, evidence on its association with SUDI remains limited. We examined short-term effects of high and low temperatures on SUDI in France. We performed a time-stratified case-crossover study including lag periods up to six days before death. Conditional logistic regression models assessed associations with both binary temperature indicators (based on percentiles) and continuous metrics using a distributed lag nonlinear model (DLNM). Effect modification by season, sex, social deprivation, urban or rural residence, age at death, and sleeping position was examined. We included 1078 SUDI cases in France from 2015 to 2022. Results suggested an increased risk with heat on days close to death. Estimates were imprecise due to the limited sample size, leading to wide confidence intervals for several associations. However, we observed a linear association between temperature and SUDI during summer, particularly for minimum temperature in the last week of life (OR: 1.16, 1.07-1.26). DLNM analyses suggested similar patterns, with elevated risk for minimum temperatures above 15°C and below 0°C, though these estimates remain uncertainty. Short-term exposure to both high and low temperatures showed patterns of association with SUDI, with particularly notable effects of heat during summer. Although statistical support for many trends was limited, the alignment of these signals with previous studies suggests that preventive measures to reduce temperature-related risks for infants may be considered, particularly in the context of rising temperatures.

The sudden unexpected death in epilepsy grief study.

Sleep biomarkers of sudden unexpected death in epilepsy: Data from the Kv1.1 mouse model.

Supervised machine learning methods for short-term prediction of a sudden cardiac death from electrocardiogram

KCNQ2 downregulation in left stellate ganglion neurons exacerbates malignant ventricular arrhythmias after myocardial infarction.

Prognostic value of 18F-fluorodeoxyglucose positron emission tomography one month after initiation of prednisolone therapy in patients with cardiac sarcoidosis.

Unveiling the unpredictable: A comprehensive inquiry into sudden and unexpected deaths undergoing medico-legal investigation at Tygerberg Forensic Pathology Services Mortuary.

Lysosomal trafficking markers covering PSAP, PGRN, SORT1 and LRP1 in body liquids and cerebral tissue as auxiliary indicative tool of traumatic brain injury.

To evaluate phenotypic progression in a large cohort of patients with arrhythmogenic cardiomyopathy (ACM) using cardiac magnetic resonance (CMR), and to assess the prognostic impact of baseline structural abnormalities and to investigate the impact of exercise performed after diagnosis. We retrospectively analysed individuals with a definitive diagnosis of ACM or identified as carriers of pathogenic or likely pathogenic (P/LP) ACM-related genetic variants, all of whom underwent at least one CMR. Longitudinal data on structural remodelling were available for a subset of patients with at least two CMRs. Patients were stratified into higher- and lower-exercise groups based on exercise performed after diagnosis. The primary composite endpoint included major ventricular arrhythmias (MVA), appropriate implantable cardioverter-defibrillator (ICD) interventions, sudden cardiac arrest, and sudden cardiac death. A total of 202 patients (mean age: 41.7 ± 16.4 years, 59% males) were included. Over a mean follow-up of 5.2 years, 32 patients (16%) reached the primary endpoint. Baseline myocardial fibrosis (MF) and reduced right ventricular ejection fraction independently predicted arrhythmic events [HR 4.9, (95% CI: 1.8-12.9), p < 0.001 and HR 2.6, (95% CI: 1.2-5.4), p = 0.002, respectively]. Among the 97 patients with at least 2 CMR scans, 32% developed de novo fibrosis, and 41% showed progression of MF. Patients with longer intervals between CMR scans demonstrated more pronounced structural remodelling, evidenced by greater increases in biventricular end-diastolic volumes and progressive declines in ventricular function. Significant left ventricular dilation was observed in the higher-exercise group, with an increase in indexed end-diastolic volumes. Carriers of PKP2 variants engaging in moderate-to-intense exercise exhibited a higher incidence of arrhythmic events. MF and right ventricular systolic dysfunction emerge as independent predictors of arrhythmic risk in ACM. Serial CMR assessments demonstrate that structural progression is common, supporting the concept that ACM represents a dynamic rather than a static disease process. Patients carrying PKP2 variants may exhibit heightened susceptibility to exercise-related arrhythmic risk.Arrhythmogenic cardiomyopathy (ACM) is a heart condition that can lead to dangerous arrhythmias and structural remodeling. In this study, we followed one of the largest groups of ACM patients with repeated cardiovascular magnetic resonance (CMR) scans to better understand how the disease evolves and how exercise after diagnosis affects outcomes.

Abstract We investigate the behaviors of (1 → 2) and (2 → 1) genuine tripartite EPR steering in generalized GHZ(GGHZ) states when observers undergo relativistic acceleration, and extend the analysis to network quantum steering in linear networks composed of two Bell states. Within the free Dirac field framework, our results demonstrate that both types of genuine tripartite steering and network steering exhibit monotonic degradation with increasing acceleration. In the single-accelerator scenario, all steering types persist even at infinite acceleration, while physically inaccessible (2 → 1) genuine steering emerges at high accelerations. Strikingly contrasting behavior is observed when two observers accelerate, where sudden death of steering occurs in all cases. Furthermore, we study the dynamical evolution of both genuine tripartite steering and network quantum steering in noninertial frames when one accelerated qubit undergoes decoherence. We reveal a hierarchy of sensitivity for both steering types to different decoherence noises in non-inertial frames, and find that genuine tripartite steering and network quantum steering are more sensitive to quantum decoherence effects than to the Unruh effect.

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease and a leading cause of heart failure and sudden cardiac death (SCD) in young adults. Given its complex pathophysiology, phenotypic diversity, and rapidly evolving therapeutic landscape, a structured and multidisciplinary approach to care is essential. This manuscript outlines a six-pillar framework to standardize and optimize evaluation and management of HCM. The proposed model organizes HCM care into six key domains. (i) Establishing the correct diagnosis, which requires differentiation between sarcomeric HCM and phenocopies such as amyloidosis, Fabry, or mitochondrial disease, using multimodal imaging and genetic testing. (ii) Establish presence of symptoms and of left ventricular outflow tract obstruction (LVOTO), which is central to symptom evaluation, prognostication, and treatment. Dynamic assessment with exercise echocardiography when required is essential to guide management, including pharmacotherapy or septal reduction therapy. (iii) Risk stratification for SCD integrates risk scores with adjunctive imaging data to support patient-centred implantable cardioverter defibrillator decisions. (iv) Genetic evaluation and family management enable cascade testing, early detection, and counselling. (v) Management of comorbidities-including atrial fibrillation, hypertension, obesity, and sleep-disordered breathing-is integral to holistic care and symptom control. (vi) Education and lifestyle guidance focus on safe sport participation, avoidance of dehydration and vasodilators, and reproductive counselling within a multidisciplinary setting.

Objectives: The identification of early warning biomarkers and associated molecular mechanisms of sudden cardiac death (SCD) caused by acute coronary syndrome (ACS) through the analysis of peripheral blood plasma extracellular vehicles (EVs) remains a significant gap in current knowledge. We aimed to screen for novel EV metabolic markers and validate their prediction ability thereby providing novel early diagnostic biomarkers for the risk of sudden death due to ACS; based on the premise that EVs mirror cellular metabolic stress, we hypothesized that specific EV metabolic signatures can predict SCD risk in ACS patients.. Methods: In this nested case-control study, plasma EVs from 18 non-ST-segment elevation ACS (NSTE-ACS), 21 ST-segment elevation myocardial infarction, 16 ACS-related SCD patients and 41 matched controls were isolated and characterized in accordance with the Minimal Information for Studies of Extracellular Vesicles 2018 guidelines. We performed a combined liquid chromatography-tandem mass spectrometry-based metabolomic and proteomic analysis of plasma EVs, conducted multi-omics integration for pathway and network analysis, and validated candidate biomarkers by enzyme-linked immunosorbent assay. ROC curve analysis and multivariate/univariate statistical methods were applied to evaluate the SCD risk predictive value of the identified markers. Results: We identified 27 differential metabolites associated with the progression of SCD in plasma EVs of ACS patients. The combined analysis suggested that glycolysis and the tricarboxylic acid cycle might be key metabolic pathways in SCD. Notably, EV-derived pyruvate and lactic dehydrogenase B (LDHB) levels were significantly elevated in SCD patients compared to controls ( P &lt;0.05), despite no differences in plasma concentrations, suggesting EV-derived pyruvate and LDHB as early biomarker to predict SCD in ACS patients. Integration of EV-derived pyruvate and LDHB with traditional biomarkers (creatine kinase isoenzyme, myoglobin [MYO]) improved SCD risk prediction (area under the curve [AUC] 0.786 for pyruvate + LDHB; AUC 0.9 when combined with creatine kinase isoenzyme), underscoring their potential for enhancing risk stratification. Conclusion: In this nested case-control study of ACS patients, multi-omics profiling of plasma EVs revealed altered distinct metabolic signatures in SCD cases, particularly the LDHB-pyruvate-spermine-spermidine network involoved in glycolysis and the tricarboxylic acid cycle. LDHB and pyruvate emerged as co-diagnostic biomarkers, enhancing predictive accuracy for cardiovascular events when combined with clinical indicators.

Left ventricular noncompaction (LVNC), an uncommon myocardial disorder, is pathologically defined by the presence of excessive trabecular meshwork and deep intertrabecular recesses within the ventricular chamber. Despite recognized genetic heterogeneity underlying LVNC pathogenesis, the molecular determinants remain incompletely elucidated. We recruited a multigenerational Chinese LVNC pedigree and systematically collected clinical data, comprehensive family histories, and peripheral blood samples from the proband and relatives for genetic investigation. The proband, diagnosed with LVNC by cardiac magnetic resonance, presented with classical morphological features of the disease and ultimately succumbed to sudden cardiac death. Next-generation sequencing identified compound heterozygous missense variants in the proband: LMNA(NM_001257374.1) c.232C>T (p.Arg78Trp) and MYH6(NM_002471.3) c.2677G>A (p.Val893Met). Segregation analysis of two asymptomatic younger family members - diagnosed with LVNC via cardiac magnetic resonance despite lacking obvious clinical symptoms - revealed heterozygosity for either LMNA c.232C>T (p.Arg78Trp) or the MYH6 c.2677G>A (p.Val893Met). Notably, mutation-negative relatives displayed neither clinical manifestations nor echocardiographic evidence of LVNC. These novel pathogenic variants have established the association between genotype and phenotype in familial LVNC, providing critical biomarkers for clinical genetic screening. Our findings have expanded the range of gene mutations associated with LVNC and further enhanced the understanding of the phenotypic characteristics of these mutations. Integrated genetic and cardiac magnetic resonance imaging analyses demonstrated that LMNA c.232C>T (p.Arg78Trp) and/or MYH6 c.2677G>A (p.Val893Met) variants were associated with LVNC.

ABSTRACT The heart's electrical function is known to adapt to physiological demands, but the mechanisms by which gravitational force may modulate conduction remain unexplored. Understanding this could reshape interpretations of cardiac electrical behavior in altered gravity, such as during long‐term spaceflight. Microgravity induces changes in cardiac morphology, fluid distribution, and autonomic regulation, linked to rhythm disturbances including QT prolongation and sudden cardiac death. Current explanations remain largely indirect, attributing electrical changes to haemodynamic or autonomic factors. Conventional ECG lacks the spatial resolution to determine whether gravity directly affects propagation. Here, we investigate whether gravitational loading directly alters cardiac conduction by examining posture‐driven shifts in gravitational vectors in a controlled ground‐based model. We developed a high‐density electrode array to perform localized body surface potential mapping, enabling the extraction of conduction‐sensitive propagation features. Using machine learning classification, we demonstrate that postural changes can be reliably detected based solely on these features, something not achievable with standard ECG metrics. These results suggest that cardiac conduction is not merely responding to systemic physiological feedback but is sensitive to changes in gravitational orientation through its effects on the spatial configuration of conductive myocardial tissue. This suggests a previously unrecognized mechanism by which gravity can directly influence cardiac electrophysiology. Our findings highlight a limitation in current cardiac monitoring systems, particularly in extreme environments such as space. By identifying gravity‐sensitive features of cardiac conduction, this work opens a path to new diagnostic tools and a deeper physiological understanding of the heart's adaptation to altered gravitational states.

Sudden unexpected death can occur even among patients with advanced cancer receiving hospice and palliative care. How bereaved families perceive this remains unclear. To investigate the prevalence of sudden unexpected death from bereaved family perspectives, the level of agreement with physician perspectives, and their association with bereaved families' mental health. We analyzed longitudinally linked data from a prospective cohort of advanced cancer patients in 23 palliative care units in Japan and a nationwide survey of bereaved families. Sudden unexpected death was assessed using previously reported definitions: (1) "surprise death" and (2) "rapid decline death," evaluated from both physician and bereaved family perspectives, and (3) "performance status-defined sudden death," evaluated only by physicians. Agreement among definitions was analyzed using kappa statistics. Bereaved families' mental health was evaluated using the Patient Health Questionnaire-9. Among 611 cases, "surprise death" and "rapid decline death" were more frequent from bereaved family (46.5% and 51.2%, respectively) than physician (8.2% and 16.5%, respectively) perspectives. Agreement between family and physician perspectives was low (κ = 0.04-0.14). The bereaved family-perceived "rapid decline death" was significantly correlated with depression (adjusted odds ratio = 1.75, p = 0.028), whereas physician-perceived sudden unexpected death showed no significant correlation. Compared with physicians' perspectives, bereaved family members perceive death to be sudden or unexpected more frequently and differently, and their perceptions are associated with postbereavement mental health. Further research is needed to explore strategies to improve communication and support families' psychological preparedness when a patient's death may be sudden and unexpected.

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of seizure-related deaths in people with epilepsy. Despite evidence that SUDEP counseling does not cause stress, improves treatment adherence, and empowers people with epilepsy and their caregivers, it remains underdiscussed. This study aimed to explore the in-depth perspectives of parents who have lost a child to SUDEP, focusing on their experiences, grief, and coping strategies, while factoring in their demographics, the clinical features of their deceased children, and their previous awareness of SUDEP, all aspects that have not been systematically investigated before. This qualitative phenomenological study involved in-depth semistructured interviews with 51 parents of 43 children who died of SUDEP. Transcripts were analyzed using immersion/crystallization qualitative methodology with Dedoose software, using an iterative consensus-building process. Thematic analysis revealed common perspectives, grief narratives, coping strategies, and perceived needs among parents after their child's SUDEP. Of the 51 participating parents (mean age 54.1 ± 9.4 years, 71% female), 27 reported being unaware of SUDEP before it occurred, whereas 24 reported previous awareness of it. These groups shared similar demographics and clinical characteristics. However, "unaware" parents expressed more intense trauma and prolonged maladaptive grief, characterized by guilt, extreme anger, and medical distrust. By contrast, "aware" parents described mitigated trauma, with less guilt- and anger-ridden grief, and reduced reliance on specialized support groups. Previous SUDEP awareness provided emotional preparation, buffering the devastating reality and fostering agency and acceptance. Another theme highlighted the struggles parents faced immediately after SUDEP, particularly with law enforcement and treating physicians. Unanimously, parents emphasized the paramount importance of counseling about the known relationship between epilepsy and SUDEP. Previous awareness of SUDEP (or lack thereof) has complex and far-reaching effects on the subsequent parental perceived trauma, grief, and coping processes. Furthermore, emergency responders, official personnel, and treating physicians may mishandle the aftermath of SUDEP. This study's findings strongly advocate for a paradigm shift in SUDEP-related practices across multiple disciplines, including legislation. Emphasis should be placed on increasing proactive SUDEP counseling to mitigate the traumatic effect and subsequent grieving process when SUDEP occurs.

A small ruminant flock of 19 Non-descript Goat and 9 Ramnad White Sheep were investigated for the complaint of anorexia, voiding of diarrhoeic watery faeces and sudden death of two lambs on previous day of presentation. Faecal samples were collected from the flock and subjected for routine parasitological examination. Microscopic examination of the faecal samples revealed mild to severe infection of Eimeria spp., Amphistome, Haemonchus contortus, Moniezia expansa and Trichuris spp. Mixed infection with 4 parasitic stages was observed in 6 (21.42%) animals, mixed infection with 3 parasitic stages in 8 (28.57%) animals, mixed infection with 2 parasitic stages in 12 (42.85%) animals were found. Eimeria spp. oocysts in faecal samples were further confirmed after sporulation using 2.5% potassium dichromate solution. Haemonchus contortus larvae were identified from faecal samples by culture using the jar method. Morphometry of oocysts, parasite eggs and larvae were also carried. Incidence of single parasite species infection was not recorded in this flock.

Desmoplakin (DSP) cardiomyopathy is an inherited condition caused by desmosome gene DSP mutation, resulting in arrhythmias, heart failure, and sudden cardiac death. Cardiac MRI typically presents with ring-like subepicardial late gadolinium enhancement which can be mistaken for myocarditis or fatty replacement.