Cause Of Death Research Articles

Transition towards cancer mortality predominance over cardiovascular disease mortality in Brazil, 2000–2019: a population-based study

Cardiovascular disease (CVD) and cancer are the first and second leading causes of death in Brazil and worldwide. However, an ongoing epidemiological transition in which cancer surpasses CVD has been observed in many high and middle-income countries. In this study, we provided a nationwide analysis of the transition towards cancer mortality predominance over CVD mortality in Brazil. We leveraged data from 5570 municipalities using the Mortality Information System and classified the causes of death using ICD-10 codes. Age-standardized CVD and cancer mortality rates were calculated annually between 2000 and 2019. Mortality rate ratios (MRRs=CVD rates divided by cancer rates) described the predominance of cancer or CVD mortality across municipalities and states. Choropleth maps displayed state-specific MRRs and the transition in the predominant cause of death over time. From 2000 to 2019, CVD mortality rates declined in 25 out of 27 states, whereas cancer mortality increased in 15 states, indicating a shift towards cancer predominance. While in 2000 cancer mortality was lower than CVD in all states and only exceeded the latter in 7% of the municipalities, by 2019 the gap narrowed considerably, with 13% of municipalities displaying higher cancer mortality rates vs CVD mortality rates. Additionally, higher household income correlated with higher mortality from cancer vs CVD. An ongoing epidemiological transition in which cancer mortality surpasses CVD mortality is occurring in Brazil, particularly in municipalities with higher household incomes. Our findings may provide important information for policymakers and public health practitioners in Brazil. National Council for Scientific and Technological Development (CNPq).

Donor Characteristics and Outcomes of Pediatric Heart Transplantation in South Korea.

Heart transplantation is often limited by the availability of transplantable donor heart and understanding of donor aspects that would influence transplant outcomes becomes important. In this study, donor characteristics and their impact on the outcomes of pediatric heart transplantations performed in South Korea were investigated. We reviewed the medical records of patients less than 18 years old who received heart transplantation between 2002 and 2022 in three tertiary hospitals located in South Korea. A total of 139 cases were enrolled. One-year mortality was 10.4% and total mortality was 33.8%. Forty-nine recipients (35.3%) showed biopsy-proven rejections and 20 (14.4%) showed cardiac allograft vasculopathy during mean follow-up of 6.4 ± 4.9 years. Six recipients (4.5%) showed left ventricle ejection fraction of less than 55% post-transplantation. The mean age of the donors was 23.0 ± 15.4 years. The most common cause of death of the donors was unspecified illness (46.4%). Donors with a history of diabetes, hypertension, smoking, and alcohol consumption were 0%, 3.1%, 32.1%, and 34.4%, respectively. Mean total ischemic time was 191.6 ± 72.7 min, while total ischemic time was over 4 h in 37 patients (26.6%). There were no significant relationship between donor factors and survival. However, donor's history of drinking or cardiopulmonary resuscitation was significantly associated with acute rejection and donor's age with cardiac allograft vasculopathy. Donor factors did not show significant impact on post-transplant survival but some factors were predictive of post-transplant rejection and cardiac allograft vasculopathy.

Patterns of medicine use in the year prior to death by suicide: an Australian population-based case series study

Prescribed medicines are commonly used to treat mental health conditions but are also often implicated in suicide death by poisoning. This was a descriptive study quantifying changes in dispensing and initiation of antidepressants, benzodiazepines, and antipsychotics in the year prior to death by suicide. In this Australian population-based case series, we used national coronial data linked with dispensing claims for all people ≥10 years who died by suicide (2013-2019). Our primary outcome was change in aggregate weekly medicine dispensing the year before death, quantified using piecewise linear regression stratified by cause of death (medicine poisoning vs other causes). Our secondary outcome was change in medicine initiation rates. This study was performed between June 2021 and July2023. Our study included 14,207 people (24% female, median age 44 years). In the year prior to death, we observed higher rates of nervous system medicine use in people who died by medicine poisoning compared with those that did not: antidepressants (62.4% vs 42.9%), benzodiazepines (51.4% vs 29.0%), antipsychotics (25.6% vs 17.1%), opioids (43.8% vs 23.4%). For benzodiazepines, among people who died by medicine poisoning the slope (rate of increase) changed from 0.18 (95% CI-0.01, 0.37) to 4.12 (95% CI 0.98, 7.26) dispensings per 1000 people per week at 8 weeks prior to death. Among people who died of other causes, the slope changed from 0.18 (95% CI 0.14, 0.22) to 2.41 (95% CI 1.90, 2.91) also at 8 weeks prior to death. For antidepressants, among people who died of medicine poisoning we observed no change in the slope. Among people who died of other causes, the slope increased from 0.18 (95% CI 0.09, 0.28) to 1.68 (95% CI 1.20, 2.15) at 14 weeks prior to death. Dispensing of antidepressants and benzodiazepines increased more rapidly closer to date of death, regardless of medicine involvement in death. This suggests these changes may reflect worsening symptoms or increased help seeking and that the method of death by suicide may be due to greater means access. However, findings need to be interpreted with caution as our analyses were performed on aggregate data and may not reflect person-level changes. This study is funded by a grant from the Australian National Health and Medical Research Council (NHMRC) and the Translational Australian Clinical Toxicology Research (TACT) Group.

The anthraquinone derivative KA-4s reduces energy metabolism and enhances the sensitivity of ovarian cancer cells to cisplatin.

Ovarian cancer is the leading cause of death from female gynecological cancers. Cisplatin (DDP)is a first-line drug for ovarian cancer treatment. Due to DDP resistance, there is an urgent need for novel therapeutic drugs with improved antitumor activity. AMPK-mediated metabolic regulatory pathways are related to tumor drug resistance. Our study aimed to determine the relationship between reversing DDP resistance with the anthraquinone derivative KA-4s and regulating AMPK energy metabolism in ovarian cancer. The results showed that KA-4s inhibited the proliferation of ovarian cancer cells. The combination of KA-4s with DDP effectively promoted drug-resistant ovarian cancer cell apoptosis and inhibited cell migration and invasion. Moreover, KA-4s decreased the intracellular ATP level and increased the calcium ion level, leading to AMPK phosphorylation. Further studies suggested that the AMPK signaling pathway may be involved in the mechanism through which KA-4s reduce drug resistance. KA-4s inhibited mitochondrial respiration and glycolysis; downregulated the glucose metabolism-related proteins GLUT1 and GLUT4; the lipid metabolism-related proteins SREBP1 and SCD1; and the drug resistance-related proteins P-gp, MRP1, and LRP. The inhibitory effect of KA-4s on GLUT1 was confirmed by the application of the GLUT1 inhibitor BAY-876. KA-4s combined with DDP significantly increased the expression of p-AMPKand reduced the expression of P-gp. In a xenograft model of ovarian cancer, treatment with KA-4s combined with DDP reduced energy metabolism and drug resistance, inducing tumor apoptosis. Consequently, KA-4s might be evaluated as a new agent for enhancing the chemotherapeutic efficacy of treatment for ovarian cancer.

A cohort analysis of familial partial lipodystrophy from two Mediterranean countries.

To assess the disease burden of familial partial lipodystrophy (FPLD) caused by LMNA (FPLD2) and PPARG (FPLD3) variants to augment the knowledge of these rare disorders characterized by selective fat loss and metabolic complications. An observational longitudinal study, including 157 patients (FPLD2: 139 patients, mean age 46 ± 17 years, 70% women; FPLD3: 18 patients, mean age: 44 ± 17 years, 78% women) from 66 independent families in two countries (83 from Turkey and 74 from Spain), was conducted. Patients were diagnosed at a mean age of 39 ± 19 years, 20 ± 16 years after the first clinical signs appeared. Men reported symptoms later than women. Symptom onset was earlier in FPLD2. Fat loss was less prominent in FPLD3. In total, 92 subjects (59%) had diabetes (age at diagnosis: 34 ± 1 years). Retinopathy was more commonly detected in FPLD3 (P < .05). Severe hypertriglyceridaemia was more frequent among patients with FPLD3 (44% vs. 17%, P = .01). Hepatic steatosis was detected in 100 subjects (66%) (age at diagnosis: 36 ± 2 years). Coronary artery disease developed in 26 patients (17%) and 17 (11%) suffered from a myocardial infarction. Turkish patients had a lower body mass index, a higher prevalence of hepatic steatosis, greater triglyceride levels and a tendency towards a higher prevalence of coronary artery disease. A total of 17 patients died, with a mean time to death of 75 ± 3 years, which was shorter in the Turkish cohort (68 ± 2 vs. 83 ± 4 years, P = .01). Cardiovascular events were a major cause of death. Our analysis highlights severe organ complications in patients with FPLD, showing differences between genotypes and Mediterranean countries. FPLD3 presents a milder phenotype than FPLD2, but with comparable or even greater severity of metabolic disturbances.

Low-dose sufentanil does not affect tolerance to LBNP-induced central hypovolemia or blood pressure responses during a cold pressor test.

Hemorrhage is a leading cause of death in the prehospital setting. Since trauma-induced pain often accompanies a hemorrhagic insult, the administered pain medication must not interfere with critical autonomic regulation of arterial blood pressure and vital organ perfusion. The purpose of this study was to test two unrelated hypotheses: 1) sublingual sufentanil (Dsuvia) impairs tolerance to progressive central hypovolemia and 2) sublingual sufentanil attenuates pain sensation and the accompanying cardiovascular responses to a noxious stimulus. Twenty-nine adults participated in this double-blinded, randomized, crossover, placebo-controlled trial. After sublingual administration of sufentanil (30 μg) or placebo, participants completed a progressive lower-body negative pressure (LBNP) challenge to tolerance (aim 1). After a recovery period, participants completed a cold pressor test (CPT; aim 2). Addressing the first aim, tolerance to LBNP was not different between trials (P = 0.495). Decreases in systolic blood pressure from baseline to the end of LBNP also did not differ between trials (time P < 0.001, trial P = 0.477, interaction P = 0.587). Finally, increases in heart rate from baseline to the end of LBNP did not differ between trials (time P < 0.001, trial P = 0.626, interaction P = 0.424). Addressing the second aim, sufentanil attenuated perceived pain (P < 0.001) in response to the CPT, though the magnitude of the change in mean blood pressure during the CPT (P = 0.078) was not different between trials. These data demonstrate that sublingual sufentanil does not impair tolerance to progressive central hypovolemia. Additionally, sublingual sufentanil attenuates perceived pain, but not the accompanying mean blood pressure responses to the CPT.NEW & NOTEWORTHY Addressing two unique aims, we observed that sublingual sufentanil administration does not impair tolerance or cardiovascular responses to lower-body negative pressure (LBNP)-induced progressive central hypovolemia. Second, despite pain perception being reduced, sublingual sufentanil did not attenuate mean blood pressure responses to a cold pressor test (CPT).

Mortality following admission to the paediatric intensive care unit: A Swedish longitudinal cohort study.

This study aimed to compare outcomes post-admission to a Swedish paediatric intensive care unit (PICU) in children with complex chronic conditions (CCC) and without CCC. In this observational registry-based study, consecutive admissions to the Astrid Lindgren Children's Hospital PICU from 1 January 2008 to 31 December 2016 were analysed. Data on demographics, predicted death rates (PDR), admission diagnoses and causes of death were collected. Mortality was recorded up to 15 years after admission and compared between groups. Patients with CCC constituted 64.6% (n = 3026) of PICU admissions and 83.5% (n = 111) of PICU deaths. The crude mortality rate in PICU was 2.84% overall. CCC-patients were 2.83 times more likely to die in PICU compared to non-CCC (OR 2.83; 95% CI: 1.78-4.49). Mortality increased in the CCC-cohort up to 5 years after PICU discharge, while non-CCC patients generally survived if they survived in PICU. Of the patients who died in PICU, the median PDR was 22.9% for CCC-patients and 66.5% in the non-CCC cohort. Children with CCC accounted for most admissions and deaths in PICU. Despite lower severity of illness scores upon admission, CCC patients were nearly three times more likely to die in PICU compared to non-CCC patients.

Redox Imbalance and Cardiovascular Pathogenesis: Exploring the Therapeutic Potential of Phytochemicals

Abstract: The intriguing role of the oxidation system in cardiovascular disease lies in its contribution to chronic and acute increases in intracellular reactive oxygen species (ROS), driving the progression of cardiovascular diseases (CVDs). ROS, produced as by-products of oxidative physiological and metabolic events, act as mediators in various signaling pathways contributing to cardiovascular pathology. The delicate equilibrium between the production of free radicals and antioxidant defense shifts in favor of the former, resulting in redox imbalance and extensive cellular damage. Among CVDs, coronary artery disease (CAD) remains as the leading cause of death globally. Understanding the significance of oxidative damage in the dysfunction of endothelial cells, atherosclerosis, and other pathogenic events and pathways is crucial for preventing and managing CVD. Consequently, it is imperative to comprehend the mechanism/s underlying the pathogenic alterations of CVD due to oxidative damage to develop effective prevention strategies. Many studies have reported bioactive phytochemical/s as potential therapies against CVDs, modulating ROS generation, controlling the CVD-related inflammatory mediators and protecting the vascular system. Therefore, this review provides an update for understanding how the phytoconstituents exhibit preventive roles in oxidative stress-related CVD, thus improving the quality of life of people. This study conducted a thorough literature search on CVD, oxidative imbalance, and phytoconstituents. The search was performed using multiple search engines and the main keywords, and only English publications until June 2023 were included. However, there is a need for more research and clinical trials to fully elucidate the efficacy and safety of these phytochemicals for managing the disease.

Role of mesenchymal stem cells in sepsis and their therapeutic potential in sepsis‑associated myopathy (Review).

Sepsis‑induced myopathy (SIM) is one of the leading causes of death in critically ill patients. SIM mainly involves the respiratory and skeletal muscles of patients, resulting in an increased risk of lung infection, aggravated respiratory failure, and prolonged mechanical ventilation and hospital stay. SIM is also an independent risk factor associated with increased mortality in critically ill patients. At present, no effective treatment for SIM has yet been established. However, mesenchymal stem cells (MSCs) have emerged as a promising therapeutic approach and have been utilized in the treatment of various clinical conditions. A significant body of basic and clinical research supports the efficacy of MSCs in managing sepsis and muscle‑related diseases. This literature review aims to explore the relationship between MSCs and sepsis, as well as their impact on skeletal muscle‑associated diseases. Additionally, the present review discusses the potential mechanisms and therapeutic benefits of MSCs in the context of SIM.

Comparative Cardiovascular Risks of Radical Prostatectomy and External Beam Radiation Therapy in Early-Stage Prostate Cancer: A Comprehensive Retrospective Analysis.

The risk of cardiac disease mortality has recently become a focal point of concern within the medical community for patients with prostate cancer (PCa). Given that radical prostatectomy (RP) and external beam radiation therapy (EBRT) are the main treatment modalities for localized PCa, their specific impact on cardiovascular-specific mortality (CSM) remains unclear. This study explored the specific effects of RP and EBRT on CSM risk to guide clinical treatment decisions. Data from patients aged 45-74years, who were diagnosed with T1-2N0M0 stage PCa from the SEER database (2010-2015), were used. Multivariate statistical methods, including propensity score matching (PSM), competing risk regression, COX regression analysis, and Fine-Gray testing, were applied to assess the impact of RP and EBRT on CSM risk. Among 146,082 T1-2 stage PCa patients, cardiac disease emerged as the primary cause of death, surpassing PCa itself. Multifactorial COX regression and competing risk regression analyses indicated that local treatments do not increase CSM risk. Further analysis revealed a significant increase in CSM risk for patients undergoing only EBRT compared with those undergoing only RP (hazard ratio [HR] = 2.71, 95% confidence interval [CI] 1.96-3.74, P < 0.001), with subsequent PSM adjustment, further confirming a significantly reduced risk in the RP treatment group (HR 0.23, 95% CI 0.13-0.40, P < 0.001). T1-2 stage PCa patients face a significant risk of CSM, with RP offering a potential advantage over EBRT in reducing this risk. These findings encourage clinicians to comprehensively consider the potential impact on cardiac health when formulating treatment plans, providing crucial guidance for optimizing treatment strategies.

Histology-Tailored Approach to Soft Tissue Sarcoma.

Soft tissue sarcomas are a diverse and heterogeneous group of cancers of mesenchymal origin. Each histological type of soft tissue sarcoma has unique clinical particularities, which makes them challenging to diagnose and treat. Multidisciplinary management of these rare diseases is thus key for improved survival. The role of surgery has been well established, and it represents the cornerstone curative treatment for soft tissue sarcomas. To date, local recurrence is the leading cause of death in low-grade sarcomas located at critical sites, and distant metastasis in high-grade sarcomas, regardless of the site of origin. Management must be tailored to each individual histologic type. We describe the most common types of extremity, trunk, abdominal, and retroperitoneal soft tissue sarcoma along with characteristics to consider for optimized management.

Spatiotemporal patterns and surveillance artifacts in maternal mortality in the United States: a population-based study

Reports of high and rising maternal mortality ratios (MMR) in the United States have caused serious concern. We examined spatiotemporal patterns in cause-specific MMRs, in order to obtain insights into the cause for the increase. The study included all maternal deaths recorded by the Centers for Disease Control and Prevention from 1999 to 2021. Changes in overall and cause-specific MMRs were quantified nationally; in low-vs high-MMR states (i.e., MMRs <20 vs≥26 per 100,000 live births in 2018-2021); and in California vs Texas (populous states with low vs high MMRs). Cause-specific MMRs included those due to unambiguous causes (e.g., selected obstetric causes such as pre-eclampsia/eclampsia) and less-specific/potentially incidental causes (e.g., "other specified pregnancy-related conditions", chronic hypertension, and malignant neoplasms). MMRs increased from 9.60 (n=1543) in 1999-2002 to 23.5 (n=3478) per 100,000 live births in 2018-2021. The temporal increase in MMRs was smaller in low-MMR states (from 7.82 to 14.1 per 100,000 live births) compared with high-MMR states (from 11.1 to 31.4 per 100,000 live births). MMRs due to selected obstetric causes decreased to a similar extent in low-vs high-MMR states, whereas the increase in MMRs from less-specific/potentially incidental causes was smaller in low- vs high-MMR states (MMR ratio (RR) 5.57, 95% CI 4.28, 7.25 vs 7.07, 95% CI 5.91, 8.46), and in California vs Texas (RR 1.67, 95% CI 1.03, 2.69 vs 10.8, 95% CI 6.55, 17.7). The change in malignant neoplasm-associated MMRs was smaller in California vs Texas (RR 1.21, 95% CI 0.08, 19.3 vs 91.2, 95% CI 89.2, 94.8). MMRs from less-specific/potentially incidental causes increased in all race/ethnicity groups. Spatiotemporal patterns of cause-specific MMRs, including similar reductions in unambiguous obstetric causes of death and variable increases in less-specific/potentially incidental causes, suggest misclassified maternal deaths and overestimated maternal mortality in some US states. This work received no funding.

Burden of Ischemic Heart Diseases among US States from 1990-2019.

Ischemic Heart Disease (IHD) is a leading cause of global mortality, including in the United States. Understanding the burden of IHD in the United States is crucial for informed decision-making and targeted interventions aimed at reducing morbidity and mortality associated with this leading cause of death. This study aimed to understand the burden of IHD, identify gender disparities and risk factors, explore the relationship between socioeconomic growth and IHD, and analyze risk factor distribution across the states of the United States. This study utilized data from the Global Burden of Diseases Study 2019, which provided comprehensive information on IHD from 1990 to 2019. Data related to IHD from these years were extracted using a query tool from the Institute for Health Metrics and Evaluation (IHME) website. The study assessed the relationship between IHD and socioeconomic development using the Socio-demographic Index (SDI) and measured the overall impact of IHD using Disability-adjusted Life Years (DALYs), considering premature death and disability. Additionally, the study analyzed the burden of IHD attributed to six main risk factors. Data analysis involved comparing prevalence, mortality, SDI, DALYs, attributable burden, and risk estimation among the states. Between 1990 and 2019, there was an improvement in socioeconomic development in all states. Age-standardized rates of disease burden for IHD decreased by 50% [ASDR 3278.3 to 1629.4 (95% UI: 1539.9-1712.3) per 100,000] with the most significant decline observed in Minnesota. Males had higher burden rates than females in all states, and the southeast region had the highest mortality rates. The prevalence of IHD showed a declining trend, with approximately 8.9 million cases (95% UI: 8.0 million to 9.8 million) in 2019, representing a 37.1% decrease in the Age-standardized Prevalence Rate (ASPR) from 1990. Metabolic risks were the leading contributors to the disease burden, accounting for 50% of cases, with Mississippi having the highest attributable risk. Arkansas had the highest attributable risk for high cholesterol and smoking. Conversely, Minnesota had the lowest burden of IHD among all the states. This study highlights variations in the burden of IHD across US states and emphasizes the need for tailored prevention programs to address specific risk factors and gender differences. Understanding the trend in IHD may inform policymakers and healthcare professionals in effectively allocating resources to reduce the burden of IHD and improve national health outcomes.

Research trends on forensic entomology for five decades worldwide

Forensic entomology, the study of insects and arthropods in criminal investigations, is crucial for estimating postmortem intervals, determining changes in corpse positioning, and identifying causes of death. This study analyzes global research trends in forensic entomology using data from the Scopus database spanning 1970 to 2024, with data visualized through VOSviewer. A total of 2,261 articles were identified, with an average productivity of 42 papers per year. The leading countries in forensic entomology research are the United States (n = 444), Brazil (n = 266), China (n = 198), the United Kingdom (n = 194), and Germany (n = 156). Current hot topics in the field include pupae, feeding behavior, beetles, and genetics. These findings underscore the ongoing interest and advancements in forensic entomology, highlighting its significance and diverse applications in criminal investigations.

Trends in Driving Under the Influence of Alcohol and Cannabis Among Young Adults in Washington State From Before to During the COVID-19 Pandemic.

Objectives. To examine trends in young adult self-reported driving under the influence of alcohol (DUI-A), cannabis (DUI-C), and simultaneous alcohol and cannabis use (DUI-AC) in a state with legalized nonmedical cannabis use from before to during the COVID-19 pandemic. Methods. We used logistic regression and annual statewide data from the Washington Young Adult Health Survey to assess DUI behaviors from 2016 to 2021. Results. Both prepandemic yearly changes in prevalence and deviations from those trends during the pandemic years were small and not statistically significant. However, prevalence estimates were alarming: 12.0% of participants reported DUI-A, 12.5% reported DUI-C, and 2.7% reported DUI-AC. Exploratory moderation analyses indicated a relative increase in DUI-A during 2020 among 4-year college students relative to young adults not attending 4-year colleges. Conclusions. Young adults in Washington State continued to engage in risky DUI behaviors during the pandemic. College students may have increased their likelihood of DUI-A during COVID-19. Public Health Implications. Young adults, for whom vehicle crashes remain a leading cause of death, showed little change in DUI behaviors during the COVID-19 pandemic. There is continued need for young adult DUI prevention efforts. (Am J Public Health. 2024;114(S8):S698-S701. https://doi.org/10.2105/AJPH.2024.307767).

Evaluation of a Novel Mechanical Compression Device.

Venous thromboembolism (VTE) is a leading preventable cause of death in hospitalized patients. Current intermittent pneumatic compression (IPC) devices used to provide external mechanical compression for VTE prevention are associated with a multitude of clinical challenges that often result in subtherapeutic use. A comparative study was conducted of the real-world clinical use of a novel mechanical compression device (MCD) and a current IPC device. The purpose of this quality improvement project was to compare use of the novel MCD and the standard IPC device on three clinical inpatient hospital units. Comparisons were based on the following patient outcome measures: evaluation of wear time, adherence to optimal wear time, evaluation of both patient comfort and device satisfaction, and perceived impact on mobility goals. Nurses' satisfaction with the clinical usability for mobility was also measured. This project used a pre-post design. A convenience sample of 89 surgical patients on the three clinical study units and 63 nursing staff members were recruited for the study. Data were collected using electronic health records, MCD data records, patient surveys, and nursing staff surveys. Data were analyzed using descriptive statistics and independent sample t tests. In the preintervention period, data were collected using the current IPC device. Nursing staff were then trained on use of the MCD. In the postintervention period, the MCDs were used in place of the IPC devices. MCD patients had significantly longer (P ≤ 0.001) wear time (mean, 19.3 hours/day) compared with IPC patients (mean, 12.9 hours/day). MCD patients also reported significantly better sleep (P = 0.04), fewer problems with sweaty legs (P ≤ 0.001), and improved assistance with mobility goals (P ≤ 0.001) than IPC patients. Nursing staff reported significantly improved accuracy of mobility documentation (P ≤ 0.001) with the MCD, but no differences in their perception of patient satisfaction with meeting mobility goals. Use of the MCD device for VTE prophylaxis resulted in actual and perceived improvements from the perspective of both patients and nurses. While these results provide initial data in support of a potentially promising system, more research is needed.

Mitochondrial elongation confers protection against doxorubicin-induced cardiotoxicity

Doxorubicin (DOX)-induced cardiac damage remains a leading cause of death amongst cancer survivors. DOX-induced cardiotoxicity (DIC) is mediated by disturbed mitochondrial dynamics, but it remains debated that the mechanisms by which DOX disrupted equilibrium between mitochondrial fission and fusion. In the present study, we observed DOX induced mitochondrial elongation in multiple cardiovascular cell lines. Mechanically, DOX not only downregulated the mitochondrial fusion proteins including Mitofusin 1/2 (MFN1/2) and Optic atrophy 1 (OPA1), but also induced lower motility of dynamin-related protein 1(Drp1) and its phosphorylation on 637 serine, which could inhibit mitochondrial fission. Interestingly, DOX failed to induce mitochondrial elongation in cardiomyocytes co-treated with protein kinase A (PKA) inhibitor H89 or expressing phosphodeficient Drp1-S637A variants. Besides, carbonyl cyanide 3-chlorophenylhydrazone (CCCP) was able to blocked the mitochondrial elongation induced by DOX treatment, which could be phenocopied by OPA1 knockdown. Therefore, we speculated that DOX inhibited both mitochondrial fission and fusion simultaneously, yet enabled mitochondrial fusion dominate the mitochondrial dynamics, resulting in mitochondrial elongation as the main manifestation. Notably, blocking mitochondrial elongation by inhibiting Drp1-S637 phosphorylation or OPA1 knockdown aggravated DOX-induced cardiomyocytes death. Based on these results, we propose a novel mechanistic model that DOX-induced mitochondrial elongation is attributed to the equilibrium disturbance of mitochondrial dynamics, which serves as an adaptive response and confers protection against DIC.

Collaborative Forensic Autopsy Documentation and Supervised Report Generation Using a Hybrid Mixed-Reality Environment and Generative AI.

Forensic investigation is a complex procedure involving experts working together to establish cause of death and report findings to legal authorities. While new technologies are being developed to provide better post-mortem imaging capabilities-including mixed-reality (MR) tools to support 3D visualisation of such data-these tools do not integrate seamlessly into their existing collaborative workflow and report authoring process, requiring extra steps, e.g. to extract imagery from the MR tool and combine with physical autopsy findings for inclusion in the report. Therefore, in this work we design and evaluate a new forensic autopsy report generation workflow and present a novel documentation system using hybrid mixed-reality approaches to integrate visualisation, voice and hand interaction, as well as collaboration and procedure recording. Our preliminary findings indicate that this approach has the potential to improve data management, aid reviewability, and thus, achieve more robust standards. Further, it potentially streamlines report generation and minimise dependency on external tools and assistance, reducing autopsy time and related costs. This system also offers significant potential for education. A free copy of this paper and all supplemental materials are available at https://osf.io/ygfzx.

Ten-Year Outcome After Supracricoid Partial Laryngectomy in cT3M0 Laryngeal Squamous Cell Carcinoma-A STROBE Analysis.

The aim of this study was to document 10-year outcomes after supracricoid partial laryngectomy (SCPL) in selected cT3M0 laryngeal squamous cell carcinoma (SCC) patients. This real-life retrospective observational study analyzed an inception cohort of 168 patients with isolated, untreated, selected cT3M0 laryngeal SCC, that were consecutively managed by SCPL during the period 1973-2013, and followed up until death or for a minimum of 10 years in 92% of cases at a single French academic and tertiary referral care center. Prior induction chemotherapy, arytenoid cartilage removal, level II-IV neck dissection, and postoperative radiation therapy were performed on 148, 77, 136, and 27 patients, respectively. The main objective was to determine 10-year actuarial local control and laryngeal preservation estimates. Secondary objectives included 10-year actuarial survival and cause-of-death analysis, and assessment of correlations between endpoints and clinical variables. The significance threshold was set at p < 0.005. Ten-year actuarial local control, laryngeal preservation, and survival estimates were 90%, 85%, and 52%, respectively. Salvage treatment resulted in an overall 99% local control rate. Metachronous second primary cancer, intercurrent disease without evidence of SCC, SCPL-related death, and uncontrolled local recurrence accounted for 31%, 26%, 7%, and 2% of causes of death. On univariate analysis, overall local recurrence and laryngeal preservation rates varied significantly, from 5% to 54% and 90% to 46% when resection margins were R0 and R1, respectively. The present study highlighted successful 10-year outcomes after SCPL, providing further evidence in favor of its integration into the conservative armamentarium for endolaryngeal cT3 SCC. 4 Laryngoscope, 134:4557-4563, 2024.

Pediatric Trauma - A Silent Epidemic.

Trauma is the leading cause of preventable deaths in children all over the world. In the majority of cases, children are innocent victims of road traffic accidents. They suffer from both short-term and long-term impacts of trauma. Deaths from road traffic accidents can be prevented by adopting simple road safety measures and the use of protective equipment. Worldwide programs have been initiated to curb this ever-rising menace; however, the success of these programs depends on their outreach and acceptance among the population in general. Golden hours in trauma management is the initial hour post-trauma, the success of resuscitation depends on the appropriate management of pediatric trauma victims in hospitals dedicated to the management of pediatric trauma victims. The current review highlights the epidemiology, pattern of injury, road safety measures, and global health initiatives for the prevention of accident-related injury in children. The shortcomings of this review are as follows- Firstly pediatric trauma is an exhaustive topic, it is impossible to cover all aspects of pediatric trauma. Thus, the review might have missed some important aspects of pediatric trauma. Secondly, the concept of a pediatric trauma registry is nonexistent in almost all developing countries; hence a true picture of pediatric trauma epidemiology and injury patterns is missing. Thirdly not much work has been done on pediatric trauma in developing countries leading to insufficient data from these countries.