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Background: Recent statistics highlight cardiovascular diseases (CVD) as a major global cause of death. This review examines the methodological approaches and the main results of independent, stratified, and joint association of sedentary time (ST) and physical activity (PA) on CVD outcomes. Methods: We searched PubMed, Embase, Web of Science, and Scopus for prospective cohorts that examined the independent, stratified, or joint associations of ST and PA with CVD outcomes. Independent associations were defined as analyses mutually adjusted for PA and ST. Stratified associations were considered when there was a reference group in each stratum of PA or ST, and joint associations were defined by a single reference group for all other combined categories of ST and PA levels. Results: Of 45 articles, 69% explored independent association of ST or PA on CVD outcomes, while 31% using a stratified/joint approach. Most studies used self-reports for ST and PA and focused on CVD mortality. Mutually adjusted analyses identified ST positively and PA inversely associated to CVD outcomes. Stratified studies showed higher ST's pronounced impact on CVD for lower PA levels. High PA mitigated but did not eliminate ST's negative impact. Joint analyses revealed highest CVD risk in those with both high ST and low PA, and elevated risk in various intermediate combinations. Conclusions: Employing independent, stratified, and joint association approaches can yield distinct and complementary public health messages aimed at promoting cardiovascular health. Recommendations should aim to not only to encourage boosting PA levels, but also, concurrently decrease ST. [ABSTRACT FROM AUTHOR]

To investigate how frailty modifies the association of sitting time with all-cause and cardiovascular mortality in Chilean adults. This prospective study included 2,604 participants aged ≥35 from the Chilean National Health Survey 2009–2010. Sitting time was self-reported, while frailty was assessed using a 36-item Frailty Index. Sitting time was categorized as low, medium, and high. Cox proportional hazard models were used to estimate the risk of mortality stratified for the sitting time categories. Over a median follow-up of 8.9 years, 311 participants died, 28% of them due to cardiovascular events. Frail people with prolonged sitting time were at higher risk of all-cause and cardiovascular mortality (hazard ratio 3.13; 95% confidence interval [2.06, 4.71] and hazard ratio 2.41; 95% confidence interval [1.50, 3.64], respectively). The observed risk was higher in women than men. Public health and individual strategies should be implemented to decrease sitting time across the population, with special attention on frail people. [ABSTRACT FROM AUTHOR]

Age-adjusted mortality rates (AAMR) for cardiovascular diseases (CVD) increased in 2020 and 2021, and provisional data indicated an increase in 2022, resulting in substantial excess CVD deaths during the COVID-19 pandemic. Updated estimates using final data for 2022 are needed. The National Vital Statistics System's final Multiple Cause of Death files were analyzed in 2024 to calculate AAMR from 2010 to 2022 and excess deaths from 2020 to 2022 for U.S. adults aged ≥35 years, with CVD as the underlying cause of death. The CVD AAMR among adults aged ≥35 years in 2022 was 434.6 deaths per 100,000 (95% CI=433.8, 435.5), which was lower than in 2021 (451.8 deaths per 100,000; 95% CI=450.9, 452.7). The most recent year with a similarly high CVD AAMR as in 2022 was 2012 (434.7 deaths per 100,000 population, 95% CI=433.8, 435.7). The CVD AAMR for 2022 calculated using provisional data overestimated the AAMR calculated using final data by 4.6% (95% CI=4.3%, 4.9%) or 19.9 (95% CI=18.6, 21.2) deaths per 100,000 population. From 2020 to 2022, an estimated 190,661 (95% CI=158,139, 223,325) excess CVD deaths occurred. In 2022, the CVD AAMR among adults aged ≥35 years did not increase, but rather declined from a peak in 2021, signaling improvements in adverse mortality trends that began in 2020, amid the COVID-19 pandemic. However, the 2022 CVD AAMR remains higher than observed before the COVID-19 pandemic, indicating an ongoing need for CVD prevention, detection, and management. [ABSTRACT FROM AUTHOR]

The article discusses the crucial task of maternal mortality review committees (MMRC) to identify factors beyond biomedical factors in cases of maternal deaths as of February 2025. Topics covered include investigating if the death was related to pregnancy and, if so, how it was related, and the impact of anti-abortion legislation that becomes political when MMRC funding is not guaranteed. Also noted are disputes on how maternal death numbers are counted.

Background: Medical assistance in dying (MAiD) was legalized in Canada following the Carter v. Canada ruling of 2015. In spite of legalization, the ethics of MAiD remain contentious. The bioethical literature has attempted to differentiate MAiD from withdrawing life-sustaining treatment (WLT) in an effort to examine the nature of the moral difference between the two. However, this research has often neglected the firsthand experiences of the clinicians involved in these procedures. By asking physicians if they perceive the major bioethical accounts as clinically useful, we seek to distinguish between aspects of the contemporary bioethical landscape which are useful at the bedside and those which are divorced from the realities faced by clinicians. Methods: We applied a qualitative descriptive approach to explore physicians' experiences and bioethical distinctions in providing MAiD and WLT. Results: Semi-structured interviews were conducted with 21 physicians, and the transcripts were thematically analyzed to identify common patterns and divergences in their perspectives. Three core themes were found: (1) consensus on MAiD's moral equivalence with WLT despite differences between the practice, (2) discord regarding the use of the term 'killing', and (3) disjuncture between bioethical debates and practice. Theme 1 comprised of three sub-themes: (1.1) no moral difference between MAiD and WLT, (1.2) physician versus underlying medical condition as cause of death, and (1.3) relief of suffering. Conclusions: In order to have practical utility for clinical practice, it is essential for bioethicists to engage in dialogue with patients and their medical providers pursuing MAiD or WLT. Theoretical debates that are divorced from the realities of terminal illness do not assist physicians with navigating the ethical terrain of ending a patient's life. This research captures meaningful accounts regarding MAiD and WLT that is rooted in the lived experience of the providers of these services in order for bioethical debates to have substantive impact in clinical practice and in legislation surrounding future health policies. [ABSTRACT FROM AUTHOR]

Aims Sex-specific low flow was recently defined as stroke volume index (SVi) ≤ 40 mL/m² in men and ≤32 mL/m² in women. We tested the prognostic association of these cut-offs in patients with aortic stenosis (AS) with concordantly and discordantly graded AS [concordantly graded AS by energy loss (CGASEL) and discordantly graded AS by energy loss (DGASEL)] based on pressure recovery adjusted aortic valve area [energy loss (EL)]. Methods and results Data from 1351 patients with asymptomatic AS, peak jet velocity <4 m/s, and preserved left ventricular ejection fraction enrolled in the Simvastatin and Ezetimibe in Aortic Stenosis study were used. DGASEL was defined as EL <1.0 cm² with mean aortic gradient <40 mmHg and CGASEL as EL ≥1.0 cm² with mean aortic gradient <40 mmHg. Patients were further grouped into normal and low flow. The outcome was combined all-cause death and hospitalization for heart failure (HF). CGASEL with normal/low flow was present in 915/253 patients, and DGASEL with normal/low flow was present in 57/126 patients. During a median follow-up of 4.3 years, event-free survival was lower in patients with DGASEL irrespective of flow compared to CGASEL with normal flow (P < 0.05). In Cox regression analysis, DGASEL with normal or low flow were both associated with increased risk of all-cause death and hospitalization for HF after adjustment for age, sex, heart rate, randomized study treatment, hypertension, aortic valve replacement, and aortic valve calcification (P < 0.05). No survival difference was found between patients with normal vs. low flow within groups of DGASEL or CGASEL. Conclusion Identification of low flow by the proposed sex-specific thresholds of SVi needs more prognostic validation before application in clinical practice. ClinicalTrials.gov identifier NCT00092677. [ABSTRACT FROM AUTHOR]

Statistics from reputable sources, including the World Health Organization (WHO), demonstrate that cancer is a leading cause of death globally, accounting for millions of deaths each year. When it comes to the early identification of cancer, machine learning (ML) is crucial. To analyze complex data and identify minute patterns that may indicate the presence of cancer, it employs robust computational approaches. Improving patient outcomes relies on early cancer detection since it paves the way for faster treatment and intervention, which might lead to better prognoses and higher survival rates. To choose features, this study intends to build an ML-based ensemble model utilizing ant colony optimization (ACO) and ant lion optimization (ALO). Next, ML classifiers are used as the initial predictions' basis learners. The last forecast is the result of combining two ensemble methods: voting and averaging classifiers. Four distinct cancer microarray datasets are used to assess the approach. With an accuracy of 99.08% on the Lung cancer dataset, the voting ensemble classifier outperforms the others, according to the empirical analysis. [ABSTRACT FROM AUTHOR]

Background: Marathon training and running have many beneficial effects on human health and physical fitness; however, they also pose risks. To date, no comprehensive review regarding both the benefits and risks of marathon running on different organ systems has been published. Main Body: The aim of this review was to provide a comprehensive review of the benefits and risks of marathon training and racing on different organ systems. A predefined search strategy including keywords (e.g., marathon, cardiovascular system, etc.) and free text search was used. Articles covering running regardless of sex, age, performance level, and event type (e.g., road races, mountain marathons) were considered, whereas articles examining only cycling, triathlon, stress-tests or other sports were excluded. In total, we found 1021 articles in PubMed, Scopus, and Google Scholar, of which 329 studies were included in this review. Overall, marathon training offers several benefits for different organ systems and reduces all-cause mortality. As such, it improves cardiovascular risk factors, leads to favorable cardiac adaptations, enhances lung function, and improves quality of life in chronic kidney disease patients. It also enhances gastrointestinal mobility and reduces the risk of specific tumors such as colorectal cancer and hepatocellular carcinoma. Marathon training enhances bone health and skeletal muscle metabolism. It further positively affects hematopoiesis and cytotoxic abilities of natural killer cells, and may act neuroprotective on a long-term basis. After a marathon, changes in biomarkers suggesting pathological events in certain organ systems such as cardiovascular, renal, gastrointestinal, liver, hematological, immune, musculoskeletal, central nervous, and endocrine systems can often be observed. Mostly, these changes are limited to 1–3 days post-race and usually normalize within a week. Moreover, marathon running poses the risk of serious adverse events such as sudden cardiac death or acute liver failure. Concerning lung function, a decrease after a marathon race was observed. Acute kidney injury, as well as electrolyte imbalances, are relatively common amongst marathon finishers. Many runners complain of gastrointestinal symptoms during or after long-distance running. Many runners suffer from running-related musculoskeletal injuries often impairing performance. A marathon is often accompanied by an acute inflammatory response with transient immunosuppression, making runners susceptible to infections. Also, hormonal alterations such as increased cortisol levels or decreased testosterone levels immediately after a race are observed. Disturbances in sleep patterns are commonly found in marathon runners leading up to or directly after the race. Conclusion: All in all, marathon training is generally safe for human health and individual organ systems. Considering the high popularity of marathon running, these findings supply athletes, coaches, sports scientists, and sports medicine practitioners with practical applications. Further large-scale studies examining long-term effects on the cardiovascular, renal, and other system are needed. Key Points: Marathon training and racing affects several organ systems in a positive and negative way. The most common problems during or after a marathon are acute kidney injury, gastrointestinal distress, running-related injuries, and upper respiratory tract infections. Generally, marathon training is safe for different organ systems and its positive effects outweigh any potential harms [ABSTRACT FROM AUTHOR]

Background: Since comorbid conditions are frequently present in chronic obstructive pulmonary disease (COPD) and affect outcome, a composite scoring system to quantify comorbidity might be helpful in assessing mortality risk. Methods: We tested the hypothesis that the Charlson Comorbidity Index (CCI) score at the time of an outpatient medical clinic encounter for COPD predicts all-cause mortality. Cox Proportional Hazards analyses were used in 200 randomly selected patients to relate CCI scores to all-cause mortality out to 5 years. Results: Mean age was 62 ± 10 years, 56% were female, FEV1 was 62%, CCI was 3.08 ± 2.30, and 30% had a CCI ≥ 4, indicating 3 or more comorbid conditions. All-cause mortality was 8.5% and 20% at 3 and 5 years, respectively. In univariate testing, the CCI score and hospitalizations predicted mortality, but FEV1 did not. In multivariable testing, which included covariates of age, sex, socioeconomic status, race, FEV1 percent-predicted, and all-cause hospitalizations in the preceding year, CCI expressed as a continuous variable strongly predicted mortality: hazard ratio (HR) 1.38 for each unit increase in the score (p < 0.0001). While 1 or 2 comorbid conditions were not significantly related to mortality, 3 or more comorbid conditions (compared to none) strongly predicted mortality: HR 9.80, 95% CI 3.80 to 25.00. Conclusion: Comorbidity, assessed with the CCI, is strongly predictive of mortality in outpatients with a clinical diagnosis of COPD, and this relationship appears to be non-linear. This instrument may be useful in determining prognosis in this population. [ABSTRACT FROM AUTHOR]

Anticoagulation therapy is a critical component of post-transcatheter aortic valve implantation (TAVI) management, aimed at reducing the risk of thromboembolic events and mortality. This review examines the efficacy of continuous versus interrupted anticoagulation strategies in TAVI patients, focusing on mortality, stroke rates, and composite events. A literature review was conducted, analyzing recent studies that evaluate the impact of different anticoagulation regimens on clinical outcomes in TAVI patients. Key outcomes assessed include all-cause mortality, thromboembolic events, and major cardiovascular complications within 30 days and up to one year post-procedure. The review identifies a trend favoring continuous anticoagulation, particularly with direct-acting oral anticoagulants (DOACs), which was associated with lower mortality rates and reduced stroke incidence in high-risk patients. However, findings were inconsistent across studies, with some reporting no significant differences in outcomes between continuous and interrupted strategies. Additionally, the review highlights the need to balance the benefits of thromboembolic prevention with the increased risk of bleeding and vascular complications associated with continuous therapy. The findings show the importance of individualized anticoagulation strategies tailored to patient risk profiles. Clinicians should weigh the potential benefits of continuous anticoagulation against the risks, particularly in high-risk populations. Ongoing research is essential to refine anticoagulation protocols in TAVI patients, enhancing both safety and efficacy in clinical practice. [ABSTRACT FROM AUTHOR]

Mummification refers to a process of desiccation with loss of up to 60–70% of the body weight. It may be unintentional when a body is exposed to dry heat, extreme cold or to reduced amounts of air, or it may be intentional from embalming or drying. To evaluate mummification in a contemporary medicolegal situation selected Pathology Files at Forensic Science SA (FSSA), Adelaide, Australia, were searched from 2004 to 2023 for autopsy cases where bodies had been described as completely mummified. Twenty-one cases were identified (out of a total of 2872 cases - <1%) consisting of 17 males and 4 females (M:F = 4:1) with an age range of 27 to 95 years (average 62 years). The estimated post mortem intervals ranged from 2 to 16 weeks (average 5 weeks) with 16 cases (76%) occurring during the warmer months. Nineteen bodies (91%) were found inside home addresses Causes of death were determined in only seven cases (33%) (3 drug toxicity; 3 cardiovascular disease and 1 hypothermia). Thus, the most typical case involved a socially isolated older male during summer at his home address. Changes to the body after mummification, with distortion and loss of tissues and organs, present challenges to forensic practitioners who may have difficulties in determining the time, cause and manner of death. [ABSTRACT FROM AUTHOR]

Background: Little is known about mortality from four disorder combinations: fully attributable to alcohol or tobacco, partly attributable to both alcohol and tobacco, to tobacco only, to alcohol only. Aim: To analyze whether residents who had disclosed risky alcohol drinking or daily tobacco smoking had a shorter time to death than non-risky drinkers and never daily smokers twenty years later according to the disorder combinations. Methods: A random adult general population sample (4,075 study participants) of a northern German area had been interviewed in the years 1996–1997. Vital status and death certificate data were gathered 2017–2018. The data analysis included estimates of alcohol- or tobacco-attributable mortality using all conditions given in the death certificate and alternatively the underlying cause of death only. Results: Among 573 deaths, 71.9–94.1% had any alcohol- or tobacco-attributable disorder depending on the estimate. Risky alcohol consumption and daily tobacco smoking at baseline were related to disorders in the death certificate according to the combinations. Deaths with an alcohol- and tobacco-attributable disorder were related to risky alcohol consumption (subhazard ratio 1.57; 95% confidence interval 1.25–1.98) and to daily tobacco smoking at baseline (subhazard ratio 1.85; 95% confidence interval 1.42–2.41). Conclusion: First, more than 70% of the deceased persons had one or more alcohol- or tobacco-attributable disorders. This finding suggests that total mortality seems to be the suitable outcome if potential effects of alcohol or tobacco consumption in a general population are to be estimated. Second, the relations of risky alcohol consumption and tobacco smoking with time to death speak in favor of the validity of alcohol- and of tobacco-attributable disorders in death certificates and of considering both alcohol consumption and tobacco smoking if attributable deaths are to be estimated. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular disease (CVD), a non-communicable condition, stands as the primary cause of death globally. This study seeks to evaluate the predictive power of atherogenic indices, which are recognized for their influence on CVD, alongside a newly developed index encompassing all three principal risk factors for CVD, referred to as the triglyceride-total cholesterol-body weight index (TCBI). The primary outcomes evaluated include both the incidence and mortality rates associated with CVD. Methods: A prospective cohort study was conducted on Mashhad stroke and heart atherosclerotic disorder (MASHAD) study data, involving 9704 healthy participants. Baseline variables were measured, and TCBI, Atherogenic Index of Plasma (AIP), Atherogenic Coefficient (AC), Castelli risk index I and II (CRI-I & II) were calculated using specific formulas. Results: Following a 10-year follow-up period, a significant positive relationship was observed between TCBI (HR: 1.078, 95% CI: 1.012–1.15), CRI-I (HR: 1.16, 95% CI: 1.007–1.337), and CRI-II (HR: 1.199, 95% CI: 1.001–1.437) with CVD mortality. However, no significant relationship was identified between TCBI and atherogenic indices related to CVD incidence, and neither AIP nor AC was associated with CVD mortality. Conclusion: In conclusion, TCBI, in contrast to AC and AIP, was linked to increased CVD mortality. However, the more substantial predictive capabilities of CRI-I and CRI-II compared to TCBI emphasize the importance of traditional atherogenic indices for accurate risk assessment. These findings underscore the necessity of enhancing the TCBI formula to improve its effectiveness in assessing CVD risk. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) is one of the most prevalent neurodegenerative disorders among older adults, yet its long-term impact on mortality within population-based cohorts remains insufficiently characterized. This study leverages data from the Neurological Disorders in Central Spain (NEDICES) cohort to provide a comprehensive 23-year mortality analysis in a Spanish population. Methods: In this prospective cohort study, 5278 individuals aged 65 years and older were evaluated across two waves: baseline (1994–1995) and follow-up (1997–1998). At baseline, 81 prevalent PD cases were identified, while 30 incident cases, likely in the premotor phase at baseline, were detected during follow-up. Mortality was tracked over 23 years, and Cox proportional hazard models were employed to estimate hazard ratios (HRs) for mortality, adjusting for relevant demographic and clinical variables. Results: Fifty-three individuals from the cohort in the reference group (without PD) were excluded due to unreliable mortality data. Among 111 PD cases, 109 (98.2%) died during follow-up compared to 4440 (86.8%) of 5114 without the disease. PD was associated with a significantly increased mortality risk (adjusted HR = 1.62; 95% confidence interval [CI] = 1.31–2.01). Patients with both PD and dementia had an even higher risk (HR = 2.19; 95% CI = 1.24–3.89). Early-onset PD (<65 years) showed heightened mortality risk (HR = 2.11; 95% CI = 1.22–3.64). Cardiovascular and cerebrovascular diseases were the leading causes of death in both PD and non-PD participants. PD was significantly more often listed as the primary cause of death in PD patients compared to the reference group (14.7% vs. 0.4%, p < 0.001). Conclusions: PD significantly increases mortality risk over 23 years, particularly among those with early onset and dementia. These findings underscore the importance of a multidisciplinary approach to PD care, targeting both motor and non-motor symptoms to enhance long-term outcomes. [ABSTRACT FROM AUTHOR]

Few studies have prospectively examined whether adverse childhood experiences contribute to suicide or substance-related mortality. Moreover, children are often exposed to multiple adversities making it critical to identify which clusters of adversities are most harmful for these outcomes. Accordingly, we investigated risk for suicide and substance-related mortality based on the number and clusters of adversities children were exposed to. Identifying information from 49,853 offspring born between 1959 and 1966 to participants in the Collaborative Perinatal Project was linked to the National Death Index to determine vital status by the end of 2016. We examined associations of the total number of adversities and five clusters of adversity (Low Adversity, Parental Harshness & Neglect, Family Instability, Poverty & Crowded Housing, Poverty & Parental Separation) with suicide and substance-related mortality. Of the 45,207 participants in the analysis sample, 267 died by suicide and 338 by substance use. Participants who experienced Family Instability had a higher risk of dying by suicide (hazard ratio [HR] = 1.92, 95% CI: 1.32, 2.79) and substance use (HR = 1.50, 95% CI: 1.02, 2.19). Participants who experienced Poverty & Parental Separation were at higher risk of dying by substance use (HR = 1.85, 95% CI: 1.40, 2.45). Adversities with documented harm including physical and sexual abuse were not assessed in the study. Childhood adversity is associated with multiple types of self-injury mortality, suggesting shared etiology of risk for suicide and substance-related mortality. Research on interventions that target shared pathways linking childhood vulnerability to multiple causes of death may help reduce the long-term impact of adversities. • The study includes 45,207 offspring of participants enrolled in the CPP and followed through middle adulthood. • This is the first study to examine clusters and cumulative adversity and risk of death by suicide and substance use. • Childhood adversity is associated with both suicide and substance-related mortality. • Findings support overlap in the etiology of risk for suicide and substance-related mortality. • It is important to prevent childhood adversities and to improve interventions designed to reduce their long-term harms. [ABSTRACT FROM AUTHOR]

The present study analyzed the impact of age on the causes of death (CODs) in patients with nasopharyngeal carcinoma (NPC) undergoing chemoradiotherapy (CRT) using machine learning approaches. A total of 2841 patients (1037 classified as older, ≥ 60 years and 1804 as younger, < 60 years) were enrolled. Variations in the CODs between the two age groups were analyzed before and after applying inverse probability of treatment weighting (IPTW). Additionally, seven different machine learning models were employed as predictive tools to identify key variables and assess the therapeutic outcomes in NPC patients receiving CRT. The younger group exhibited a significantly longer overall survival (OS) than the older group, both before the IPTW adjustment (140 vs. 50 months, P < 0.001) and after the adjustment (137 vs. 53 months, P < 0.001). After IPTW, the older group was associated with worse 5-, 10-, and 15-year cumulative incidences in terms of NPC-related deaths (30, 34, and 38% vs. 21, 27, and 30%; P < 0.001), cardiovascular disease (CVD; 4.1, 7.2, and 8.8% vs. 0.5, 1.8, and 3.0%; P < 0.001), and other causes (8.3, 17, and 24% vs. 4.1, 8.7, and 12%; P < 0.001). However, cumulative incidences of secondary malignant neoplasms were comparable between the two groups (P = 0.100). The random forest (RF) model demonstrated the highest concordance index of 0.701 among all models. Time-dependent variable importance plots indicated that age was the most influential factor affecting 3-, 5-, and 10-year survival, followed by metastasis and tumor stage. Younger patients had significantly longer OS than their older counterparts. Older patients had a higher likelihood of dying from non-NPC-related causes, particularly CVDs. The RF model showed the best predictive accuracy, identifying age as the most critical factor influencing OS in NPC patients undergoing CRT. [ABSTRACT FROM AUTHOR]

Introduction: Inclisiran is a novel drug that employs ribonucleic acid (RNA) interference to lower the levels of the proprotein convertase subtilisin/kexin type 9 (PCSK9) protein. It has demonstrated a significant reduction in LDL cholesterol levels compared to a placebo. We aim to comprehensively evaluate the safety of using Inclisiran in patients with dyslipidemia and ASCVD or an ASCVD risk equivalent. Methods: Four electronic databases, namely, Pubmed/MEDLINE, Web of Science, Embase, and ClinicalTrials.gov, were searched from inception to June 2024 to identify relevant randomized controlled trials (RCTs) comparing safety profiles of Inclisiran and the control group. The outcomes investigated were all-cause mortality, major adverse cardiovascular events (MACEs), injection-site adverse events, new-onset or worsening type 2 diabetes mellitus (T2DM), and nasopharyngitis. The effect estimates of outcomes were assessed using the risk ratio (RR) with a 95% confidence interval (CI). Random-effects meta-analysis was conducted using the restricted maximum likelihood method. Subgroup analysis was performed based on different dosing regimens. Results: The study included 7 RCTs, enrolling 4790 patients (age 63.8 ± 9.7 years, 33.2% females) who received Inclisiran. Compared to the control group, Inclisiran use did not yield a significant effect on all-cause mortality (RR, 0.92; 95% CI, 0.54 to 1.54; I2 = 0%), MACEs (RR, 0.98; 95% CI, 0.82 to 1.17; I2 = 0%), nasopharyngitis (RR, 1.10; 95% CI, 0.83 to 1.45; I2 = 0%), and T2DM (RR, 1.02; 95% CI, 0.85 to 1.21; I2 = 0%). However, Inclisiran use demonstrated a significant increase in injection-site adverse events (RR, 6.50; 95% CI, 3.20 to 13.20; I2 = 29%). Conclusions: Inclisiran use significantly increased injection-site reactions, with no increase in mortality, T2DM, or nasopharyngitis. It demonstrates a generally favorable safety profile, making it a promising option for lipid management in individuals at high cardiovascular risk, such as those with ASCVD or equivalent conditions. While it effectively improves dyslipidemia, decision-makers should be aware of an increased incidence of injection-site reactions, which, though typically mild, warrant consideration in clinical practice. Further trials are required to assess the safety of Inclisiran, particularly the association of the severity of injection-site adverse events over longer treatment durations. [ABSTRACT FROM AUTHOR]

Background: The objective of this research is to statistically assess the risk of cardiovascular mortality (CVM) between patients with small bowel adenocarcinoma (SBA) and the general population. Additionally, it aims to identify CVM-associated risk factors among individuals with SBA. Methods: Data obtained between 2000 and 2017 on SBA patients from the Surveillance, Epidemiology, and End Results (SEER) database were examined. Standardized mortality ratios (SMRs) and absolute excess risks (AERs) were obtained to compare CVM between patients and the general US population. To evaluate the cumulative mortality (CM) rate for all causes of death (COD), cumulative hazard curves were constructed. Two multivariate competing risk models were established to determine the independent predictors for CVM. Results: In the cohort of 5,175 SBA patients observed for 15,068.24 person-years, a total of 205 deaths were attributed to cardiovascular disease (CVD). The overall SMR of CVM was 1.41 (95% confidence interval (CI): 1.23–1.62, P < 0.05), whereas it reached 2.99 during the early stage of latency. Additionally, independent risk factors for CVM included age, marital status, calendar year of diagnosis, disease differentiation degree, SEER stage, and chemotherapy status. Conclusions: SBA patients exhibited a substantially elevated risk of developing CVM compared to the general US population. During the follow-up period, the CM rate for CVM continued to rise steadily. Timely identification of high-risk groups and effective interventions to safeguard cardiovascular health significantly improve patient prognosis. [ABSTRACT FROM AUTHOR]

The immune system plays a pivotal role in maintaining physiological homeostasis and influencing disease processes. Dysregulated immune responses drive chronic inflammation, which in turn results in a range of diseases that are among the leading causes of death globally. Traditional immune interventions, which aim to regulate either insufficient or excessive inflammation, frequently entail lifelong comorbidities and the risk of severe side effects. In this context, intrinsic immunomodulatory hydrogels, designed to precisely control the local immune microenvironment, have recently attracted increasing attention. In particular, these advanced hydrogels not only function as delivery mechanisms but also actively engage in immune modulation, optimizing interactions with the immune system for enhanced tissue repair, thereby providing a sophisticated strategy for managing chronic inflammation. In this tutorial review, we outline key elements of chronic inflammation and subsequently explore the strategic design principles of intrinsic immunomodulatory hydrogels based on these elements. Finally, we examine the challenges and prospects of such immunomodulatory hydrogels, which are expected to inspire further preclinical research and clinical translation in addressing chronic inflammation. [ABSTRACT FROM AUTHOR]

Determination of the causes of mortality in stranded marine mammals can contribute valuable information for conservation of wild populations, as well as contribute to risk assessments for different pathogens, hosts, and environmental conditions. This study examined necropsy reports for harbor (Phoca vitulina; n = 213) and gray (Halichoerus grypus; n = 40) seals stranded in Denmark in the period 2014 to 2021 to determine the causes of mortality where feasible. The likelihood that human interactions did or might have contributed to the mortality was also assessed. Infection with lungworms, heartworms, gastrointestinal roundworms, and influenza virus was tested for each seal in the data. Parasitic bronchopneumonia was the most common cause of death in both harbor (n = 68) and gray (n = 8) seals, and significantly more juveniles than adults died as a result of parasitic infections in the harbor seal cohort. Starvation was also a major cause of death in juvenile seals. Cause of death, death class (found dead, euthanized, or culled), and whether human interactions played a role in mortality did not vary significantly between the two species. Traumatic causes of death, resulting from confirmed or probable human interactions, were associated with adult and subadult seals of both species. Culling was the cause of death for 13.6% of harbor seals and 17.5% of gray seals. [ABSTRACT FROM AUTHOR]

Introduction: Abnormalities in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) are each associated with increased cardiovascular risk, after adjusting for non-lipid risk factors. However, whether and to what extent the association for each lipid measure is confounded by other lipid measures is less understood. Aim: This study aims to investigate the association of each lipid measure with cardiovascular and all-cause mortality while precluding the confounding caused by abnormalities in other lipid measures. Methods: The study utilized data from the third National Health and Nutrition Examination Survey (NHANES III, 1988–1994) and ten cycles of continuous NHANES (1999–2018). The study cohort included 23,761 participants who were 20 years or older, not pregnant, not receiving lipid-lowering treatment, and had complete data on all four lipid measures and mortality status. Participants were categorized into seven subgroups based on their lipid profiles. Kaplan-Meier survival curves and Cox proportional hazards models were used to examine the association between lipid abnormalities and mortality. Results: During a median follow-up of 140 months, 5,003 participants (14.1%) died, with 1,665 deaths (4.2%) attributable to cardiovascular causes. Compared with the reference group in which the four lipid measures were all normal, the subgroups with isolated high TC, two to three lipid abnormalities, and four lipid abnormalities were associated with increased risks for both cardiovascular and all-cause mortality in univariate analysis. However, only those with isolated high TC (for cardiovascular mortality, HR 1.52, 95% CI 1.13–2.06) and four lipid abnormalities (for all-cause mortality, HR 1.34, 95% CI 1.04–1.72) remained statistically significant after adjusting for non-lipid risk factors. Of note, compared with the reference group, the profile of non-lipid risk factors was apparently less favorable in the subgroup with two to three lipid abnormalities but similar (and some factors even more favorable) in the subgroup with isolated high TC. When the lipid measures were analyzed as continuous variables, a U-shaped relationship between HDL-C and mortality risk was observed for both cardiovascular and all-cause mortality, and very low LDL-C level was associated with increased mortality risk. No statistically significant association was found between TG levels and mortality risk. Conclusion: Isolated high TC, very low LDL-C, and concurrent abnormalities in all four lipid measures were associated with increased mortality risk, whereas isolated high TG was not. A U-shaped relationship may exist between HDL-C level and mortality. Overall, these findings underscore the need for integrated management of dyslipidemia that takes all four lipid measures as well as non-lipid cardiovascular risk factors into account, particularly for those with concurrent abnormalities in two or more lipid measures. [ABSTRACT FROM AUTHOR]

Simple Summary: Gastric cancer (GC) affects more than one million and is the fifth most frequently diagnosed cancer and the fourth leading cause of cancer death worldwide. Past studies have usually focused on a limited number of clinical or demographic factors to predict GC prognosis. In contrast, we used twenty-four features, including demographic, laboratory, clinical, and socio-economic information, to predict GC mortality. We investigated two case groups divided by cause of mortality (all-cause and disease-specific) with the construction of six machine learning (ML) models. In addition, the Shapley Additive Explanation (SHAP) method, an explainable artificial intelligence technique, was used. This approach allows us to identify and interpret the key features that have a significant impact on GC mortality. Key predictors of the mortality classification model included occurrence in other organs, age at diagnosis, AJCC7 stage, tumor size, CEA, smoking, and CA19-9. Accurate prediction of mortality and detection of risk factors for GC based on ML might provide opportunities for appropriate therapeutic interventions and decision-making. Background/Objectives: Gastric cancer is a leading cause of cancer-related mortality, particularly in East Asia, with a notable burden in Republic of Korea. This study aimed to construct and develop machine learning models for the prediction of gastric cancer mortality and the identification of risk factors. Methods: All data were acquired from the Korean Clinical Data Utilization for Research Excellence by multiple medical centers in South Korea. A total of 23,717 gastric cancer patients were divided into two groups by cause of mortality (all-cause of 2664 and disease-specific of 1620) and investigated. We used comprehensive data integrating clinical, pathological, lifestyle, and socio-economic factors. Cox proportional hazards analysis was conducted to estimate hazard ratios for mortality. Five machine learning models (random forest, gradient boosting machine, XGBoost, light GBM, and cat boosting) were developed to predict mortality. The models were interpreted by SHAP, one of the explainable AI techniques. Results: For all-cause mortality, the gradient-boosting machine learning model demonstrated the highest performance with an AUC-ROC of 0.795. For disease-specific mortality, the light GBM model outperformed others, achieving an AUC-ROC of 0.867. Significant predictors included the AJCC7 stage, tumor size, lymph node count, and lifestyle factors such as smoking, drinking, and diabetes. Conclusions: This study underscores the importance of integrating both clinical and lifestyle data to enhance mortality prediction accuracy in gastric cancer patients. The findings highlight the need for personalized treatment approaches in the Korean population and emphasize the role of demographic-specific data in predictive modeling. [ABSTRACT FROM AUTHOR]

Traumatic brain injuries (TBIs) are a leading cause of mortality and morbidity, particularly in forensic settings where determining the cause of death and timing of injury is critical. Glial fibrillary acidic protein (GFAP), a biomarker specific to astrocytes, has emerged as a valuable tool in post-mortem analyses of TBI. A PRISMA-based literature search included studies examining GFAP in human post-mortem samples such as brain tissue, cerebrospinal fluid (CSF), serum, and urine. The results highlight that GFAP levels correlate with the severity of brain injury, survival interval, and pathological processes such as astrocyte damage and blood–brain barrier disruption. Immunohistochemistry, ELISA, and molecular techniques were commonly employed for GFAP analysis, with notable variability in protocols and thresholds among studies. GFAP demonstrated high diagnostic accuracy in distinguishing TBI-related deaths from other causes, particularly when analyzed in CSF and serum. Furthermore, emerging evidence supports its role in complementing other biomarkers, such as S100B and NFL, to improve diagnostic precision. However, the review also identifies significant methodological heterogeneity and gaps in standardization, which limit the generalizability of findings. Future research should focus on establishing standardized protocols, exploring biomarker combinations, and utilizing advanced molecular tools to enhance the forensic application of GFAP. [ABSTRACT FROM AUTHOR]

Aims: The contribution of SARS‐CoV‐2 infection on lung damage and the effect of vaccination on either containing the number of deaths or mitigating lung damage has not been systematically investigated. Methods: Post‐mortem analysis was performed among consecutive in‐patients with COVID‐19 deceased in the Province of Trieste (2020–2022). The outcomes of the study were (i) rates of in‐hospital mortality, (ii) contribution of COVID‐19 to death, (iii) histological extent of lung injury and (iv) impact of vaccination. Results: A total of 1038 consecutive hospitalized patients who died with SARS‐CoV‐2 infection were autopsied and deep histological analysis of the lungs was performed in a randomly selected sample of 508 cases. Among them, SARS‐CoV‐2 infection was (a) the cause of death (n = 90), (b) contributing to death (n = 304) and (c) an accompanying feature (n = 114). The incidence of SARS‐CoV‐2 infection as the primary cause of mortality decreased over time (23.8% in 2020, 20.9% in 2021 and 7.9% in 2022). On multivariable analysis, vaccination (any dose) was independently associated with lower rates of death related to SARS‐CoV‐2 infection (HR.15, p <.001), after adjusting for other independent predictors. A total of 172 patients were vaccinated at least with two doses at the time of death: 93% triple‐vaccinated, 7% double‐vaccinated. On histological analysis, vaccinated patients had a greater frequency of pneumonia severity score 0 and 1 (20.3% vs. 5.4% and 20.9% vs. 7.7%, p <.001, respectively), and a substantially lower proportion of pneumonia severity score 3 (26.2% vs. 55.1%, p <.001) compared to unvaccinated patients. Conclusions: COVID‐19 vaccination has substantially reduced rates of death related to SARS‐CoV‐2 infection over time and may have the ability to mitigate lung damage. [ABSTRACT FROM AUTHOR]

Abdominal aortic aneurysms (AAAs) are an important cause of death. Small AAAs are surveyed with ultrasound (US) until a defined diameter threshold, often triggering a computer tomography scan and surgical repair. Nevertheless, 5%–10% of AAA ruptures are below threshold, and some large AAAs never rupture. AAA wall biomechanics may reveal vessel wall degradation with potential for patient-centred risk assessment. This clinical study investigated AAA vessel wall biomechanics and deformation patterns, including reproducibility. In 50 patients with AAA, 183 video clips were recorded by two sonographers. Prototype software extracted AAA vessel wall principal strain characteristics and patterns. Functional principal component analysis (FPCA) derived strain pattern statistics. Strain patterns demonstrated reduced AAA wall strains close to the spine. The strain pattern "topography" (i.e., curve phases or "peaks" and "valleys") had a 3.9 times lower variance than simple numeric assessment of strain amplitudes, which allowed for clustering in two groups with FPCA. A high mean reproducibility of these clusters of 87.6% was found. Median pulse pressure-normalised mean principal strain (PPPS) was 0.038%/mm Hg (interquartile range: 0.029–0.051%/mm Hg) with no correlation to AAA size (Spearman's ρ = 0.02, false discovery rate- p = 0.15). Inter-operator reproducibility of PPPS was poor (limits of agreement: ±0.031%/mm Hg). Strain patterns challenge previous numeric stiffness measures based on anterior-posterior-diameter and are reproducible for clustering. This study's PPPS aligned with prior findings, although clinical reproducibility was poor. In contrast, US-based strain patterns hold promising potential to enhance AAA risk assessment beyond traditional diameter-based metrics. [ABSTRACT FROM AUTHOR]

Previous research shows that large, densely populated urban areas have higher rates of child victimization that have persisted over time. However, few investigations have inquired about the processes that produce and sustain hot and cold spots of child victimization. As a result, the mechanisms that produce the observed spatial clustering of child victimization, and hence "why" harms against children tend to cluster in space, remains unknown. Does the likelihood of being a victim of violence in one location depend on a similar event happening in a nearby location within a specified timeframe? Rather, are child victims of violence more likely to reside in suboptimal neighborhood conditions? This paper aims to present an analytical and theoretical framework for distinguishing between these locational (point) processes to determine whether the empirical spatial patterns undergirding child victimization are more reflective of the "spread" via contagion (i.e., dependency) or whether they are produced by neighborhood structural inequality resulting from spatial heterogeneity. To detect spatial dependence, we applied the inhomogeneous K -function to Los Angeles Medical Examiner data on child homicide victim locations while controlling for regional differences in victimization events (i.e., heterogeneity). Our analysis found strong evidence of spatial clustering in child victimization at small spatial scales but inhibition at larger scales. We further found limited support for the spatiotemporal clustering of child victimization indicative of a contagion effect. Overall, our results support the role of neighborhood structural vulnerability in the underlying mechanisms producing patterns of child victimization across Los Angeles County. We conclude by discussing the policy implications for understanding this spatial patterning in geographical context and for developing effective and targeted preventive interventions. [ABSTRACT FROM AUTHOR]

Necrotizing enterocolitis (NEC) is one of the most common conditions requiring emergency surgery in the neonatal intensive care unit and is associated with a septic shock-like state contributing to multiorgan dysfunction. NEC affects 6 to 10% of very low-birth-weight infants and remains a leading cause of death. The occurrence of severe acute kidney injury (AKI) following surgical NEC is a harbinger of multiple morbidities. This review presents current evidence about the clinical impact of NEC-associated AKI on the clinical outcomes. Studies evaluating nephroprotective strategies to prevent AKI and its consequences are greatly needed to improve the postoperative recovery and clinical outcomes in neonates with NEC. Future observational studies and clinical trials in preterm infants with NEC prioritize measuring short-term (AKI) and longer term (chronic kidney disease) kidney outcomes. Key Points Severe AKI is common following surgical NEC. Severe AKI following NEC is associated with poor clinical outcomes. Studies evaluating nephroprotective strategies to prevent AKI and its consequences are needed. Impact Severe AKI (stage 2 and 3) occurs in 32.6% of neonates after NEC diagnosis and in 58.7% following surgical NEC diagnosis. NEC-associated AKI is associated with severe postoperative course, moderate-to-severe bronchopulmonary dysplasia, surgical complications, brain injury, and longer hospital stay in preterm infants. Severity of NEC-associated AKI can be utilized by bedside providers for the prognostication of clinical outcomes in preterm infants. [ABSTRACT FROM AUTHOR]

Objective: Understanding the local characteristics and statistics related to stillbirths may be the first step in a series of strategies associated with a reduction in stillbirth ratio. The aim of this study was to estimate the fetal mortality ratio and evaluate the investigation processes related to the causes of death, comparing the investigation according to the specific cause of death. Methods: A cross‐sectional study was retrospectively conducted in 10 tertiary obstetric care centers. Medical records of women with stillbirth managed between January 1, 2009 and December 31, 2018 were analyzed and classified, according to sociodemographic characteristics, and gestational and childbirth data, culminating in stillbirth. The stillbirth ratio and its causes were presented in proportions for the study period and individually for each health facility. Results: Cases of 3390 stillbirths were analyzed. The stillbirth ratio varied from 10.74/1000 live births (LBs) in 2009 to 9.31/1000 in 2018. "Intrauterine hypoxia and asphyxia" (ICD‐10 P20) and "unspecific causes of death" (ICD‐10 P95) represented 40.8% of the causes of death. Investigation for TORCHS and diabetes occurred in 90.8% and 61.4% of deaths, respectively. Placental and necroscopic tests were performed in 36.6% of the cases. Conclusion: The adoption of a rational and standardized investigation of stillbirth remains an unmet need; the use of additional tests and examinations are lacking, especially when unspecific causes are attributed. [ABSTRACT FROM AUTHOR]

Purpose Patients with acute decompensated heart failure (ADHF) present similarly to those with respiratory infections, which may lead to administration of unnecessary intravenous (IV) antibiotics. This study was conducted to assess outcomes in patients admitted for ADHF who received IV antibiotics vs those who did not. Methods This retrospective cohort study evaluated adults admitted with ADHF who received IV antibiotics for at least 48 hours or did not receive IV antibiotics. Patients with an active infection were excluded. The primary outcome was hospital length of stay in the unmatched cohort; secondary outcomes included 30-day readmission, all-cause mortality, amount of loop diuretic administered, total sodium and fluids received, Clostridioides difficile infection, IV antibiotic agents administered, and duration of therapy. Results The unmatched cohort included 38 patients who received IV antibiotics and 123 patients who did not receive IV antibiotics, while the matched cohort included 33 patients in each arm. In the unmatched and matched cohorts, patients receiving IV antibiotics had a longer median hospital length of stay (5 vs 3 days; P < 0.01 and 5 vs 4 days; P < 0.01) and received a greater median amount of total sodium (9.22 vs 0.28 g; P < 0.01 and 10.24 vs 0 g; P < 0.01) and median total volume from IV antibiotics and fluids (1,788 vs 50 mL; P < 0.01 and 1,825 vs 0 mL; P < 0.01). No significant differences were found for the other secondary outcomes. Ceftriaxone and azithromycin were the most frequently administered IV antibiotics, with a median duration of therapy of 4 days. Conclusion Use of IV antibiotics in patients with ADHF was associated with longer hospital length of stay and should be avoided in patients without evidence of infection. [ABSTRACT FROM AUTHOR]

Background & Aims: Hepatocellular carcinoma (HCC) is the third leading cause of cancer‐related death worldwide. Liver transplantation (LT) is a curative treatment option. We investigated survival outcomes based on recipient‐donor sex constellation (RDSC) following LT. Methods: We performed a European Liver Transplant Registry analysis, including patients from 1988 to December 2022. The cohort was split into four RDSC groups: female donor female recipient (FDFR), female donor male recipient (FDMR), male donor female recipient (MDFR) and male donor male recipient (MDMR). Survival analysis, including death with recurrence, was performed. Results: In 7601 LT for HCC with an overall median follow‐up of 22.6 months (5.8, 60.7), death was registered in 25.1% and, as primary cause of death, HCC tumour recurrence in 26.0%. There was no statistically significant difference on crude survival estimates among the different RDSC groups (log‐rank p = 0.66) with 10‐year overall survival (OS) of 54.5% in FDFR, 54.6% in FDMR, 59.1% in MDFR and 56.9% in MDMR. On multivariable analysis, RDSC showed a significant effect on OS (FDFR as reference): MDFR (aHR 0.72, p = 0.023). No significant difference was found for FDMR (aHR 0.98, p = 0.821) and MDMR (aHR 0.90, p= 0.288). Regarding overall registered causes of death, differences between RDSC groups were found in rejection (p = 0.017) and cardiovascular (p = 0.046) associated deaths. Conclusions: In female recipients undergoing LT for HCC, male donor grafts were associated with a 28% reduction of mortality compared to female donor grafts. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer‐related mortality worldwide, with its pathogenesis intricately linked to metabolic and immune dysregulation. This study aims to elucidate the molecular mechanisms underpinning HCC by analyzing metabolic and immune‐related pathways and constructing a prognostic risk model. Methods: We utilized data from The Cancer Genome Atlas (TCGA) to analyze genomic and clinical characteristics of HCC. Techniques such as single‐sample gene set enrichment analysis (ssGSEA), weighted gene coexpression network analysis (WGCNA), and gene set variation analysis (GSVA) were employed to explore the interplay between metabolic pathways, immune responses, and HCC progression. In addition, a prognostic risk model was developed using univariate Cox regression and LASSO regression analysis based on PPAR signaling and immune‐related genes. Results: Our ssGSEA results indicated a significant involvement of metabolism‐related pathways in HCC. The WGCNA identified key immune‐related genes, with particular modules correlating with macrophage activity. The prognostic model, comprising five key genes, effectively stratified patients into low‐ and high‐risk groups, with implications for overall survival (OS). Further analyses revealed the model's correlation with clinical characteristics and immune‐related indexes, suggesting its utility in predicting HCC progression. Conclusion: This study provides a comprehensive molecular portrait of HCC, emphasizing the role of metabolic reprogramming and immune responses. The prognostic model offers potential for personalized therapeutic strategies and improved clinical outcomes. Future research should focus on validating these findings and exploring the therapeutic potential of targeting metabolic and immune pathways in HCC. [ABSTRACT FROM AUTHOR]

Road traffic accidents (RTAs) are a major public health problem globally and cause deaths, disability, and significant economic costs. In Italy, there was an increased number of road accidents, deaths, and injuries in 2022 compared to 2021, although still below pre-pandemic levels. A retrospective observational study was performed on a case series of 53 consecutive fatal RTAs examined by the Section of Forensic Medicine of Verona. The case series was divided, according to the type of victims involved, into pedestrians, car drivers, car passengers, and motorcyclists. For each, the times and causes of death, the distribution of external and internal injuries, and toxicological data were analysed, and the results were compared with those in the literature. Although this is a preliminary study on a small case series and lacks statistical validation, so more cases are needed, the preliminary results seem to provide a useful tool for assessing injuries in complex fatal road accidents. [ABSTRACT FROM AUTHOR]

Currently, various tools aid in determining the cause of death and the circumstances surrounding it. Thanatochemistry is one such method that provides insights into the physiopathological mechanisms of death and the behavior of specific biomarkers in different body fluids postmortem. Certain biomarkers, characterized by their stability and specificity to vital tissues like the lungs, are associated with mechanisms contributing to death, such as acute pulmonary edema (APE). This study aims to analyze the behavior of midregional pro-adrenomedullin (MR-proADM) and cortisol levels, measured in pericardial fluid and femoral serum, in relation to the severity of APE, categorized according to specific criteria. Samples were collected from a total of 92 corpses (77 males, 15 females) with a mean age of 56.7 ± 15.2 years. The severity of APE associated with the deaths was classified into three groups: slight or absent (n = 7; 8.6%), medium or moderate (n = 16; 19.8%), and intense (n = 58;71.6%). The determination of MR-proADM and cortisol levels was conducted using ELISA kits and an Immunoassay Analyzer, respectively. Our results reveal a significant increase in MR-proADM concentration with the severity of APE. Furthermore, a correlation was established between cortisol and MR-proADM concentrations in both pericardial fluid and femoral serum samples. This indicates that the severity of APE influences the production of ADM, regardless of the specific underlying pathophysiological mechanisms. Cortisol values were also found to be higher in the intense APE group compared to the moderate group. This study contributes to our understanding of the relationship between MR-proADM and cortisol, and the severity of APE, shedding light on potential applications in postmortem investigations. [ABSTRACT FROM AUTHOR]

In forensic pathology, identifying causes of death in traumatic brain injuries (TBIs) devoid of observable signs presents a significant challenge. Post-mortem biochemistry plays a crucial role in forensic medicine, particularly in determining causes of death in TBIs that lack macroscopic or histopathological evidence. This study aimed to evaluate the utility of Neuron Specific Enolase (NSE) and S100 Calcium Binding Protein B (S100B) in post-mortem serum and cerebrospinal fluid (CSF) as markers for TBI. The relationship of these biochemical markers with survival time and post-mortem interval was also studied. The study sample consisted of 63 cases each from the TBI and the Non-TBI (NTBI) group. The NTBI group comprised of deaths due to mechanical asphyxia, myocardial infarction and isolated trunk trauma. While serum S100B and CSF NSE emerged as a promising marker for TBI, CSF S100B failed to differentiate TBI from the other causes of death. The absence of an association between the level of markers and survival time or post-mortem interval in TBIs highlights the limitations of these biomarkers in such contexts. This study underscores the potential of biochemical markers like serum S100B and CSF NSE in identifying TBI deaths, aiding forensic diagnoses where there are evidentiary limitations in traditional methods. Further research exploring additional markers and body fluids could enhance diagnostic precision in forensic neuropathology. [ABSTRACT FROM AUTHOR]

Sudden unexpected death in the young (SUDY) is defined as the rapid, unsuspected demise of an apparently healthy individual between the ages of one and 40 years. There is a gap in research pertaining to this population in a South African context. This retrospective study aimed to explore the burden, scope of post-mortem investigation, and risk factors of SUDY admissions to Salt River Mortuary (SRM) in Cape Town between 1 January 2010 and 31 December 2019. Medico-legal case files pertaining to SUDY cases from SRM were reviewed. SRM received a total of 34 601 admissions in the 10-year period; of which 1 997 (5.77%) were SUDY cases. Nearly two-thirds (62.59%) of the SUDY admissions were male. The leading cause of death was pneumonia (17.11%), and the most prevalent organ system implicated in cause of death was the pulmonary system (45.19%). At least 32.46% of SUDY cases were infectious-related, with varying degrees of confidence. A large proportion of cases had no history of acute or chronic illness (45.43%), and no family history of illness (56.66%). In total, 52 potential candidates were identified for a molecular autopsy, of which 47 have stored biological samples for future investigations. This study advocates for the routine performance of post-mortem ancillary microbiological and toxicological testing in cases of SUD, considering the large burden of infectious disease and substance abuse in South Africa. The retention of biological samples in undetermined or non-specific natural cases is also urged, to allow for cause of death determination on a molecular level. [ABSTRACT FROM AUTHOR]

Postmortem analysis of C-reactive protein (CRP) in autopsies has been extensively researched for its potential utility. This analysis could aid forensic pathologists in screening for and investigating the potential infectious or inflammatory causes of death, thereby guiding appropriate autopsy procedures. To assess the diagnostic accuracy of postmortem CRP analysis in autopsy settings, a thorough electronic literature search was conducted across databases such as PubMed, Scopus, Web of Science, and Cochrane Library. Two independent reviewers screened eligible studies, followed by a methodological quality assessment using the QUADAS-2 checklist. Utilising a random-effects model, hierarchical summary receiver operating characteristic (HSROC) curve analysis and bivariate model meta-analysis were performed to evaluate heterogeneity across studies. Of the 1286 studies initially identified, nine met the eligibility criteria for the final analysis. The pooled sensitivity of postmortem CRP analysis was 0.93 (95% CI, 0.76, 0.98), with a pooled specificity of 0.80 (95% CI, 0.71, 0.87). The prevalence across studies ranged from 0.23 to 0.68, with a median of 0.5. Moderate variability was observed in the heterogeneity assessment across the primary studies. In summary, the study findings indicate that postmortem serum CRP analysis demonstrates high diagnostic accuracy with moderate heterogeneity. Additionally, postmortem CRP testing may be useful as a screening tool in autopsy practice to rule out the likelihood of sepsis. [ABSTRACT FROM AUTHOR]

Suicide is one of the leading causes of death today, and among all mental illness, mood disorders account for one of the main risk factors. It is well known and proven that suicides are very common among people undergoing treatment and prescribed psychiatric medication. So far, however, there have only been a few studies dealing with this particular phenomenon. For this reason, autopsy patients who died by suicide, suffered from a mood disorder, and were known to be taking psychiatric medication at the time of death were selected for this study. The blood and urine samples taken during the autopsy underwent toxicological analysis and the results were compared with the prescribed therapy. A total of 22 people were included in the study: 12 presenting with depression and 10 with bipolar disorder. The toxicological analysis revealed that only 6 cases (27%) showed a qualitative match with the prescribed medication. In 5 cases (22.7%) the medication was only partially complied with and in 11 cases (50%) it was not complied with at all. Furthermore, even when medication was present, the value was often below the therapeutic range. Overall, more than 70% of the test subjects adhered to their medication only partially or not at all. Since treatment adherence is considered as a key factor in reducing the risk of suicide, this inevitably raises relevant clinical and forensic questions. Against this background, prospective monitoring of post-mortem medication levels in suicidal individuals and synergistic collaboration between clinicians and forensic pathologists could help to evaluate the effectiveness of specific medical interventions, highlight existing critical problems and develop new approaches to suicide prevention. [ABSTRACT FROM AUTHOR]

Certificates of medical evidence are often used to aid the court in assessing the cause and severity of a victim's injuries. In cases with significant blood loss, the question whether the bleeding itself was life-threatening sometimes arises. To answer this, the volume classification of hypovolemic shock described in ATLS® is commonly used as an aid, where a relative blood loss > 30% is considered life-threatening. In a recent study of deaths due to internal haemorrhage, many cases had a relative blood loss < 30%. However, many included cases had injuries which could presumably cause deaths via other mechanisms, making the interpretation uncertain. To resolve remaining ambiguity, we studied whether deaths due to isolated liver lacerations had a relative blood loss < 30%, a cause of death where the mechanism of death is presumably exsanguination only. Using the National Board of Forensic Medicine autopsy database, we identified all adult decedents, who had undergone a medico-legal autopsy 2001–2021 (n = 105 952), where liver laceration was registered as the underlying cause of death (n = 102). Cases where death resulted from a combination of also other injuries (n = 79), and cases that had received hospital care, were excluded (n = 4), leaving 19 cases. The proportion of internal haemorrhage to calculated total blood volume in these fatal pure exsanguinations ranged from 12 to 52%, with 63% of cases having a proportion < 30%. Our results lend further support to the claim that the volume classification of hypovolemic shock described in ATLS® is inappropriate for assessing the degree of life-threatening haemorrhage in medico-legal cases. [ABSTRACT FROM AUTHOR]

Protonitazene is a synthetic benzoimidazole opioid of the nitazenes class, developed in the 1950s as an effective analgesic, but never released in the market due to severe side effects and major risk of dependence. The laboratory was involved in the determination of the cause of death for 5 subjects deceased in a French department of the Indian Ocean. The 5 victims were male, aged between 20 and 35 years. The first 2 victims were found dead in their prison cell and the 3 other victims were found dead in a squat. Therefore, we have developed and validated a specific procedure to identify and quantify the drug in post mortem specimens using LC-MS/MS. The procedure involves extraction of 0.5 mL fluid at pH 9.5 with a mixture of organic solvents in presence of 20 ng fentanyl-d5 used as internal standard. Linearity of the method was verified from 0.1 to 20 ng/mL in both whole blood and urine (r2 = 0.9983 and 0.9993, respectively). The limit of detection was estimated at 0.05 ng/mL in each matrix. Protonitazene was identified at < LOQ to 0.8 ng/mL, 0.4 to 2.9 ng/mL and 3.0 to 8.0 ng/mL in femoral blood, urine and bile, respectively. Post mortem concentrations were very low, which is consistent with reported high toxicity of protonitazene. As nitazenes represent a growing threat to public health in various parts of the world, this method seems to be a good response to the challenges posed by the identification of this class of substances. [ABSTRACT FROM AUTHOR]

• Blocking excessive sTNF in the CNS after T9-SCI restores anti-viral immunity. • Inhibiting sTNF/TNFR1 activation on VGluT2+ not VGat+ INs prior to SCI in the throacic spinal cord improves anti-viral immunity in both male and female mice. • Inhibiting NF-κΒ activation on VGluT2+ not VGat+ INs prior to SCI in the thoracic spinal cord improves anti-viral immunity in both male and female mice. Spinal cord injury (SCI) is a devastating condition with 250,000 to 500,000 new cases globally each year. Respiratory infections, e.g., pneumonia and influenza are the leading cause of death after SCI. Unfortunately, there is a poor understanding of how altered neuro-immune communication impacts an individual's outcome to infection. In humans and rodents, SCI leads to maladaptive changes in the spinal-sympathetic reflex (SSR) circuit which is crucial to sympathetic function. The cause of the impaired immune function may be related to harmful neuroinflammation which is detrimental to homeostatic neuronal function, aberrant plasticity, and hyperexcitable circuits. Soluble tumor necrosis factor (sTNF) is a pro-inflammatory cytokine that is elevated in the CNS after SCI and remains elevated for several months after injury. By pharmacologically attenuating sTNF in the CNS after SCI we were able to demonstrate improved immune function. Furthermore, when we investigated the specific cellular population which may be involved in altered neuro-immune communication we reported that excessive TNFR1 activity on excitatory INs promotes immune dysfunction. Furthermore, this observation is NF-kβ dependent in VGluT2 + INs. Our data is the first report of a target within the CNS, TNFR1, that contributes to SCI-induced immune dysfunction after T9-SCI and is a potential avenue for future therapeutics. [ABSTRACT FROM AUTHOR]

Neuroticism is related to mental and physical health. This study examined whether neuroticism and its underlying components were associated with risk of all-cause and cause-specific mortality. Community-dwelling adults (N = 491,323) in the UK Biobank completed a neuroticism scale between 2006 and 2010. Vital status was tracked up to December 2022 via linkage with the UK National Health Service. Over 17 years of follow-up, 43,400 (8.8 %) participants died. Accounting for age, sex, and ethnicity, participants who scored 1 SD higher on neuroticism had a 10 % greater risk of dying (HR = 1.10, 95%CI = 1.09–1.11), an association that remained significant but was explained partly by socioeconomic status, health behaviors, and chronic conditions. Item-level analyses found that loneliness was the neuroticism item most predictive of mortality (HR = 1.46, 95%CI = 1.43–1.49), especially in males. Neuroticism and loneliness were more predictive of mortality among relatively younger adults and those with lower education. Among the causes of death, neuroticism and loneliness had the strongest association with deaths due to intentional self-harm, respiratory and digestive system diseases. Loneliness was assessed with a single item. The associations could be due to increases in neuroticism and loneliness approaching death. However, contrary to expectations from reverse causality, the associations were similar when excluding deaths within the first five or ten years of follow-up. Future research should examine whether findings from this high-income country replicate in middle- and lower-income communities. Loneliness was the component of neuroticism most strongly associated with premature mortality, including from intentional self-harm, respiratory, and digestive system causes of death. • Neuroticism was related to a higher risk of mortality in the large UK Biobank cohort. • Loneliness was the neuroticism item most strongly associated with premature mortality. • Neuroticism and loneliness had the strongest associations with intentional self-harm. • Associations were stronger among younger people and those without a college degree. [ABSTRACT FROM AUTHOR]

This study explores the association between serum chloride concentrations and all-cause mortality among patients in the Surgical Intensive Care Unit (SICU). Employing a retrospective cohort design, the study utilized data extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, specifically focusing on individuals admitted to the surgical/trauma ICUs. This dataset encompassed demographic profiles, laboratory findings, historical medical data, vital statistics, and variables pertinent to prognosis. Participants were divided into four groups based on their serum chloride concentrations. The primary outcomes assessed were mortality rates at 30, 90, and 180 days post-admission to the ICU. Analytical methods included Kaplan–Meier survival curves, Cox proportional hazards regression models, and Restricted Cubic Spline (RCS) analyses to delineate the relationship between serum chloride concentrations and patient outcomes. The study cohort comprised 10,996 patients, with observed mortality rates of 12.78% at 30 days, 17.14% at 90 days, and 20.32% at 180 days. Kaplan–Meier analyses revealed significant disparities in survival rates across the quartiles of serum chloride during the follow-up intervals (p < 0.001). The results from the multivariable Cox regression suggested a substantial inverse association between high serum chloride levels and decreased mortality at 30 days (hazard ratio [HR]: 0.96; 95%confidence interval [CI]: 0.95–0.97; P < 0.001), 90 days (HR: 0.97; 95% CI: 0.96–0.98; P < 0.001), and 180 days (HR: 0.97; 95% CI: 0.96–0.98; P < 0.001). Particularly, patients in the highest quartile of serum chloride faced significantly lower mortality risks compared to those in the lowest quartile (30 days HR = 0.65, 90 days HR = 0.71, 180 days HR = 0.69, P < 0.001). RCS analysis depicted an L-shaped curve demonstrating the dynamics between serum chloride concentrations and the risk of all-cause mortality across the 30-day, 90-day, and 180-day periods.Starting at a concentration of 104 mmol/L, a decrease in serum chloride levels was associated with an increased risk of mortality.These findings elucidate a marked nonlinear association between serum chloride levels and all-cause mortality in SICU patients, enhancing our comprehension of serum chloride's impact on clinical outcomes in this setting. [ABSTRACT FROM AUTHOR]

Non-communicable diseases (NCDs) such as cardiovascular diseases, respiratory diseases, and cancer represent a significant public health challenge in Argentina. This study aimed to estimate the burden of NCD mortality attributable to a high body mass index (BMI) in Argentina in 2018 and assess the associated economic costs. Comparative risk assessment modeling study. Potential impact fractions and preventable deaths were calculated under three counterfactual scenarios. Theoretical Minimum Risk Exposure Level (TMREL; mean BMI of 22.0 kg/m2), 1.0 kg/m2 reduction in BMI, and returned to 2005 BMI levels. The years of life lost (YLLs) and economic costs in terms of productivity loss were also estimated. In 2018, nearly two-thirds of Argentina's adult population were overweight or obese. In the TMREL scenario, 24 % of major NCD deaths and 20 % of all-cause deaths could have been prevented if the population had a mean BMI of 22 kg/m2. If a 1.0 kg/m2 reduction in BMI was achieved, 1.92 % of major NCD deaths and 3.48 % of all-cause deaths could have been avoided. Reducing the average BMI to the 2005 levels (25.8 kg/m2) could have prevented 6 % of major NCD deaths and 8.8 % of all-cause deaths. The economic costs associated with high BMI-related mortality were estimated to be 0.37 % and 0.62 % of Argentina's GDP for major NCDs and all-cause mortality, respectively. The burden of NCD mortality and associated economic costs attributable to high BMI in Argentina are substantial, highlighting the urgent need for multi-sectoral interventions to address the increasing prevalence of overweight and obesity. [ABSTRACT FROM AUTHOR]

Many countries have continued to experience a higher-than-expected number of deaths following the peaks in mortality observed in the first year of the Covid-19 pandemic. This review aims to identify the different explanations proposed for sustained higher-than-expected mortality beyond the first pandemic year. Scoping review. A systematic search of databases and grey literature sources was completed to identify English-language records proposing or investigating hypotheses for higher-than-expected mortality from April 2021 onwards in (sub)populations of high-income countries. Papers focused on survival following a diagnosis or intervention were excluded. Results were summarised narratively, and existing research prioritisation frameworks were adapted and applied to identify priorities for further research within a UK context. Seventy eligible papers were identified. Most were opinion pieces or simply presented trends; few included investigation of suggested hypotheses. Numerous explanations for higher-than-expected mortality were proposed, with hypotheses relating to direct Covid-19 mortality, sequalae of Covid-19 infection, the health service and wider impacts of the pandemic, and socioeconomic factors identified as highest-priority for further research. A critical understanding of the causes of higher-than-expected mortality is essential for achieving evidence-informed policy. This review proposes priorities for further research, although these are based on author opinion only and likely to vary by setting. We did not seek to clarify the potential interactions between the hypotheses identified, however, in the UK, it is likely that the wider impacts of the Covid-19 pandemic on socioeconomic conditions have exacerbated pre-existing austerity-related trends in stalling life expectancy. [ABSTRACT FROM AUTHOR]

Background: Approximately 1% of Sweden's 90 000 annual deaths were reported caused by poisoning. In this study, we aim to describe this poisoning population's characteristics, autopsy frequency and results of toxicology testing. Method: A national cohort study based on Swedish national registers. All deceased subjects older than 18 years with poisoning as the cause of death registered between 1 January 2000 and 31 December 2021 were included. Causes of death according to primary ICD‐10 code were analysed along with the substances found in forensic chemistry testing. Results: There were 27 057 poisonous deaths during the study periods 2 018 495 adult deaths. Subjects deceased due to poisoning had a median age of 53 years, and 18 838 (70%) were men. A private home was the most reported location of death (52%). In total, 23 260 (87%) did undergo some sort post‐mortem examination. Drugs (synthetic narcotics, opioids, heroin) caused 12 448 (46%) deaths, and alcohols explained 9056 cases (33%). Positive toxicological tests were found in 22 550 (83%) of the subjects. The most common separate substances were ethanol, zopiclone and nordazepam. Conclusion: Poisoning caused 1.3% of Swedish deaths. Men in their 50s were the most common victims, and their deaths were often cause by synthetic narcotics, other opioids or alcohol. The autopsy frequency was lower than expected for poisonous deaths. [ABSTRACT FROM AUTHOR]

ABSTRACT: Background: State Task Force National Tuberculosis Elimination Programme (STF-NTEP) wanted to ascertain the cause of death of tuberculosis (TB) patients was due to TB. Hence, this study was done to determine the cause of death among TB patients using verbal autopsy. Material and Method: The community-based cross-sectional study was conducted among the closest caregivers of the reported TB death cases using a verbal autopsy questionnaire. A list of TB deaths was extracted from Puducherry's State Tuberculosis Office (STO). The VA questionnaires were reviewed by two trained faculties and experts independently who were also asked to code the cause of death according to the International Classification of Diseases – 10th Revision. Data were analysed using the SPSS software receiver operator curve (ROC) curve and Cohen's kappa statistics with 95% confidence interval (CI) were applied to compare agreement between the raters. Results: Out of 307 TB deaths, 143 were contacted and the remaining were migrated, missing or not available. Among them 34.9% of the declared TB deaths are not due to TB. Cohen's kappa = 0.4; 95% CI: (0.858–0.985) showed moderate agreement between the raters. Experts' review was used as a reference standard to compare rater agreements. The Predictive accuracy of Rater 2 (area under the curve [AUC] −0.953; P value <0.001) was slightly higher than Rater 1 (AUC −0.942; P value <0.001). Conclusion: The findings of the study have clearly indicated that 34.9% of the declared TB deaths are not due to TB. [ABSTRACT FROM AUTHOR]

As novel psychoactive substances (NPSs) have continued to emerge over the past decade, NPS benzodiazepines have likewise increased in prevalence. They pose an evolving threat to public health and safety with regard to postmortem cases, particularly when used in combination with opioids. Bromazolam was first detected in Travis County, Texas, in April 2021. Given the recent onset of the fentanyl epidemic in this region, the international rise of bromazolam, and increased reports of "benzo-dope," a retrospective study was conducted to characterize bromazolam-positive deaths in Travis County and surrounding counties from 2021 to 2023. Bromazolam was identified in 112 deaths from 2021 to 2023, accounting for 1.57% of cases submitted for toxicology testing (n =  7129). During that interval, a 7.5-fold increase in postmortem bromazolam-related drug toxicities from 2021 (n  = 7) to 2023 (n  = 53) was observed. Fatalities primarily occurred in men in their early 30s. Postmortem concentrations ranged from 21 to 220 ng/mL, with mean (median) concentrations of 69.4 ± 48.4 (53.5) ng/mL. Polydrug use was present in 99% of bromazolam-positive deaths with co-occurrence with other drugs and drug classes widely varying over time. Bromazolam was attributed as the sole cause of death in one case with a postmortem blood concentration of 23 ng/mL. Polydrug use in bromazolam-related drug toxicities commonly involved fentanyl (82%), methamphetamine (41%), and cocaine (28%). Similarly, cases where bromazolam was an incidental finding and noncontributory to the cause of death often involved methamphetamine (38%), alprazolam (33%), and cocaine (33%). In light of the significant increase in fentanyl-related deaths in Travis County, the increasing prevalence of bromazolam accompanying fentanyl was particularly alarming due to the heightened risk of toxicity when used in combination. Identifying and evaluating bromazolam-related deaths clarify the impact of bromazolam on this population, promote awareness, and aid in identifying meaningful harm reduction strategies to decrease bromazolam-related morbidity and mortality. [ABSTRACT FROM AUTHOR]