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The document discusses the impact of adding rituximab to the treatment of adults with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive B-ALL). A retrospective analysis involving five tertiary care centers in Mexico found that adding rituximab to the standard chemotherapy regimen with a tyrosine-kinase inhibitor (TKI) was associated with higher odds of reaching a 3-month complete molecular response (MR4) and a benefit in mortality. The study suggests that adding rituximab to the treatment regimen for Ph-positive B-ALL patients may lead to more profound responses and a dose-dependent benefit in relapse and mortality without increasing toxicity. [Extracted from the article]

In the United States (US) and worldwide alcohol is a major contributor to premature mortality and morbidity. We explored US trends in alcohol related mortality from 1999 to 2020 overall and by age, gender, race, and region Publicly available US Centers for Disease Control and Prevention (CDC) Wide-ranging Online Data for Epidemiologic Research (WONDER) and the underlying cause of death file from CDC WONDER using ICD-10 codes. In 1999, there were 19,356 alcohol-related deaths, a mortality rate of 10.7 per 100,000. By 2020, deaths increased to 48,870 or 21.6 per 100,000. Overall, the mortality rate ratio (MRR) was significantly increased by about 2.0-fold. There were significant increases in all 10-year age groups with the largest 3.8-fold in those 25 to 34. Women experienced a 2.5-fold increase; Asians and Pacific Islanders had the largest increase of 2.4-fold; and the Midwest showed the largest regional increase of 2.5-fold. During the last 20 years there have been significant increases of about 2-fold in US alcohol-related mortality. Clinical challenges are increased by interrelationships of risk factors, especially overweight and obesity, and diabetes, alcohol, overweight and obesity all cause liver damage which may be additive and lead to earlier onset of alcohol related mortality. In addition, health providers should also consider demographic shifts and regional differences. Targeted interventions by health care providers may reduce this increasing US epidemic of alcohol related mortality. These data also generate many hypotheses testable in analytic studies designed a priori to do so. [ABSTRACT FROM AUTHOR]

Introduction: Pathogenic variants in STXBP1 cause a spectrum of disorders mainly consisting of developmental and epileptic encephalopathy (DEE), often featuring drug-resistant epilepsy. An increased mortality risk occurs in individuals with drug-resistant epilepsy and DEE, with sudden unexpected death in epilepsy (SUDEP) often the major cause of death. This study aimed to identify the rate and causes of mortality in STXBP1-related disorders. Methods: Through an international call, we analyzed data on individuals with STXBP1 pathogenic variants, who passed away from causes related to their disease. Results: We estimated a mortality rate of 3.2% (31/966), based on the STXBP1 Foundation and the STXBP1 Global Connect registry. In total, we analyzed data on 40 individuals (23 males) harboring pathogenic STXBP1 variants, collected from different centers worldwide. They died at a median age of 13 years (range: 11 months—46 years). The most common cause of death was SUDEP (36%), followed by pulmonary infections and respiratory complications (33%). The incidence of SUDEP peaked in mid-childhood, while non-SUDEP causes were more frequent in early childhood or adulthood (p = 0.006). In the most severe phenotypes, death was related to non-SUDEP causes (p = 0.018). Conclusion: We found a mortality rate in STXBP1-related disorders similar to other DEEs, with an early age at death and SUDEP as well as pulmonary infections as the main cause of death. These findings assist in prognostic evaluation and genetic counseling for the families. They help to define the mortality risk of STXBP1-related disorders and implement preventative strategies. [ABSTRACT FROM AUTHOR]

BACKGROUND: Declining cardiovascular mortality rates have been well-documented, yet temporal trends of sudden cardiac death (SCD) in young individuals remain unclear. We provide contemporary nationwide estimates of the temporal trends of SCD in young individuals (1–35 years of age) from 2000 through 2019 and correlate these trends to changes in out-of-hospital cardiac arrest (OHCA) patterns, rates of inherited cardiac diseases, and implantations of implantable cardioverter defibrillators (ICD). METHODS: All individuals between 1 and 35 years of age living in Denmark from 2000 through 2019 were included, with annual re-evaluation of the at-risk population in regard to age. Adjudication of SCD cases relied on multiple sources, including death certificates, medical files, and autopsy reports. Information on OHCA, diagnostic rates, and ICD implantations were captured from nationwide administrative registries. Annual incidence rates of SCD were calculated, and temporal trends in SCD incidence were computed as percentage change annualized. Trends in OHCA survival and characteristics, diagnostic rates of inherited cardiac diseases, and ICD implantations were assessed. RESULTS: During the 20-year study period (47.5 million person-years), 1057 SCDs were identified (median age, 29 years; 69% male). The overall incidence of SCD was 2.2 per 100 000 person-years and declined by 3.31% (95% CI, 2.42–4.20) annually, corresponding to a 49% (95% CI, 38.7–57.6) reduction during the study. Rates of witnessed SCD declined markedly (percentage change annualized −7.03% [95% CI, −8.57 to −5.48]), but we observed no changes in the rate of unwitnessed SCD (percentage change annualized −0.09% [95% CI, −1.48 to 1.31]). Therefore, the proportion of unwitnessed SCD increased by 79% (P <0.001). Survival after OHCA in young individuals (1 to 35 years of age) increased from 3.9% to 28%, mainly because of increased bystander cardiopulmonary resuscitation and defibrillation rates. Diagnostic rates of inherited cardiac diseases increased 10-fold (incidence rate ratio, 10.4 [95% CI, 8.46–12.90]) and the ICD implantation rate increased 2-fold (incidence rate ratio, 1.97 [95% CI, 1.51–2.60]). CONCLUSIONS: SCD incidence rates in young individuals declined by 49% over the past 2 decades. The decline was paralleled by improved survival of OHCA, higher diagnostic rates of inherited cardiac diseases, and higher ICD implantation rates. However, rates of unwitnessed SCD were unchanged, which calls for new perspectives in preventive strategies. [ABSTRACT FROM AUTHOR]

Background: Research on mortality outcomes and non-cancer-related causes of death in patients with malignant brain tumors remains limited. This study aims to identify the prevalence of non-cancer-related causes of death after brain cancer (BC) diagnosis. Methods: Data of patients diagnosed with BC in the USA between 2000 and 2019 from the Surveillance, Epidemiology, and End Results (SEER) database were retrieved and analyzed. Standardized mortality ratios (SMRs) were calculated for all the reported causes of death. Results: A total of 59,663 deaths were reported during the follow-up period. The highest number of fatalities (34,677) occurred within the first year following BC diagnosis. BC-attributable deaths were the leading cause of mortality (55,482; 93%), followed by non-cancer deaths (3888; 6.5%). BC patients had an increased risk of non-cancer attributable deaths (SMR = 6.12; 95% CI 5.93–6.31) including heart diseases (N = 938; SMR = 5.3; 95% CI 4.96–5.65), cerebrovascular diseases (N = 453; SMR = 13.17; 95% CI 11.98–14.44), accidents and adverse effects (N = 227; SMR = 2.97; 95% CI 2.6–3.39), and septicemia (N = 155; SMR = 13.39; 95% CI 11.36–15.67). Conclusion: Compared to the general population, BC patients had a statistically significant higher risk of death from most of the reported causes. [ABSTRACT FROM AUTHOR]

The document is a letter to the editor published in the journal Leukemia & Lymphoma, discussing a retrospective study on primary bone lymphoma at the Princess Margaret Cancer Center in Toronto, Canada. The study focused on clinical characteristics, disease outcomes, and treatment options for primary bone lymphoma, a rare subtype of lymphoma affecting bone tissue. The study found that combined modality treatment with radiotherapy and chemotherapy containing rituximab is the preferred option, with favorable outcomes reported in terms of overall survival rates. The study also highlighted the importance of incorporating rituximab in treatment regimens for primary bone lymphoma. [Extracted from the article]

The European Heart Journal article discusses various sex-specific risk factors related to cardiovascular disease. It explores topics such as the cardiovascular safety of assisted reproductive technology, risk prediction models for cardiovascular disease in the Asia-Pacific region, the impact of a Mediterranean diet on atherosclerosis, and the association between adverse pregnancy outcomes and cardiovascular risk. Additionally, the article examines the timing of coffee consumption and its potential effects on mortality. The research presented in the article aims to challenge conventional perspectives and provide valuable insights into the prevention and management of cardiovascular diseases. [Extracted from the article]

The document titled "High burden and poor outcomes of myelodysplastic neoplasms (MDS) in the real-world: a 10-year audit of three Australian hospitals" published in Leukemia & Lymphoma highlights the challenges faced by patients with MDS in Australia. The study conducted at three hospitals in Melbourne from 2010 to 2020 revealed that MDS patients, especially those with high-risk MDS, have a high healthcare burden and poor outcomes. Treatment options are limited, with hypomethylating agents being the standard of care for higher-risk patients, and allogeneic hematopoietic stem cell transplantation being the only curative therapy. The study emphasizes the need for further research to improve outcomes for MDS patients. [Extracted from the article]

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease marked by systemic inflammation and immune dysregulation, leading to a higher risk of all-cause mortality. The Pan-Immune Inflammation Value (PIV), a novel biomarker capturing immune-inflammatory activity, has shown prognostic value in various diseases. However, its role in predicting outcomes in RA patients remains largely unexplored. Objectives: This study aimed to evaluate the association between PIV and all-cause mortality in RA patients, investigate nonlinear relationships, and identify threshold effects. Methods: Data from the 1999–2018 National Health and Nutrition Examination Survey (NHANES) were used, including 1,882 RA patients. PIV was calculated as (neutrophil count×platelet count×monocyte count)/lymphocyte count and categorized into quartiles (Q1–Q4). Multivariable Cox proportional hazards models were applied to assess the relationship between PIV and mortality, with results expressed as hazard ratios (HRs) and 95% confidence intervals (CIs). Restricted cubic splines (RCS) explored nonlinear trends, and segmented Cox regression identified threshold effects. Kaplan-Meier survival curves and subgroup analyses validated the findings and assessed potential modifiers. Results: Elevated PIV levels were strongly associated with increased all-cause mortality. Compared to Q1, adjusted HRs for Q2, Q3, and Q4 were 1.60 (95% CI: 1.01–2.53, P = 0.047), 1.70 (95% CI: 1.10–2.63, P = 0.016), and 2.12 (95% CI: 1.33–3.37, P = 0.002), respectively (P for trend < 0.001). RCS analysis revealed a nonlinear relationship with a threshold at PIV = 302. Below this threshold, increasing PIV was associated with higher mortality risk (HR = 1.67, 95% CI: 1.07–2.61, P = 0.024). Conversely, above the threshold, further increases in PIV were linked to reduced mortality risk (HR = 0.98, 95% CI: 0.97–0.99, P = 0.026). Kaplan-Meier survival curves showed a clear decline in survival probability with increasing PIV quartiles (P < 0.001). Subgroup analyses confirmed consistent findings, with a notable interaction observed in diabetic patients (P for interaction = 0.002). Conclusions: PIV is a significant and independent predictor of all-cause mortality in RA patients, characterized by a nonlinear association and a distinct threshold effect. These findings highlight the potential of PIV as a pragmatic biomarker for stratifying mortality risk and informing personalized treatment strategies in RA. [ABSTRACT FROM AUTHOR]

The European Heart Journal article sheds new light on sex-related risk factors and frailty in cardiovascular disease. It discusses the challenges in diagnosing and treating type 2 myocardial infarction, as well as the outcomes of percutaneous vs. surgical revascularization in patients with non-ST-segment elevation myocardial infarction. Additionally, the article explores sex-related differences in aortic aneurysms and the association between pregnancy and aortic events, highlighting the need for personalized care and inclusion of frail patients in cardiovascular trials. The research findings aim to inform clinical practice and future research directions in cardiovascular medicine. [Extracted from the article]

Background: Traumatic Brain Injury (TBI) is a critical public health issue in the United States, contributing significantly to morbidity, mortality, and healthcare costs. Accounting for a substantial proportion of injury-related deaths and disabilities, TBI impacts a wide demographic, with particularly high incidence rates among young and elderly populations. Despite earlier declines, recent years have seen an uptick in TBI-related fatalities. This study aimed to evaluate the patterns and geographical disparities in mortality related to TBI among the adult population in the United States. Methods: We examined the death certificates sourced from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database to identify adults in whom TBI was documented as an underlying or contributing cause of death between 1999 and 2020. Age-adjusted mortality rates (AAMRs) per 100,000 individuals and annual percent change (APC) were computed and stratified based on year, gender, race/ethnicity, and geographic region. Results: Between 1999 and 2020, 1,026,185 TBI-related deaths occurred among adults aged ≥ 25 years. The AAMR remained stable from 22.2 in 1999 to 22.3 in 2007, followed by an insignificant decline to 21.5 in 2010, and a steeper significant subsequent increase to 24.6 in 2020. Men had consistently higher AAMR than women from 1999 (men: 35.6; women: 11.1) to 2020 (men: 38.8; women: 11.9). The 85 + years age group had the highest AAMR 118.5 trailed by 75–84-year age group at 53.2. American Indian or Alaska Native adults had the highest AAMR (31.9) followed by White (24.4). South had the highest AAMR (25.3), followed by West (22.7). Non-metropolitan areas consistently had higher mortality rates compared to metropolitan areas. Conclusions: Following a brief period of stability in TBI-related mortality from 1999 to 2010, there has been a subsequent increase of 1.3% per year in mortality till 2020. Notable geographic and demographic disparities persist, underscoring the need for further research and precise health policy interventions to better understand and address these differences. [ABSTRACT FROM AUTHOR]

Objective: In this study, we develop a new formula for predicting all-cause mortality in an ethnicity/region-specific cohort of antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Methods: We included 290 Korean patients with AAV in this study and retrospectively reviewed their medical records regarding clinical data at diagnosis and during follow-up. We introduce a new index, called the NFPM value after the initials of New Formula for Predicting Mortality, which we derived using the independent predictors of all-cause mortality obtained in the multivariable Cox proportional hazard analysis. The cut-offs of the parameters for mortality were determined using the highest or lowest tertile of each parameter according to its positive or negative association with all-cause mortality, respectively. Results: The median age was 60.0 years and 35.9% were male patients. Of the 290 patients, 39 died during follow-up (13.4%). In the multivariable Cox analysis, male sex, the five-factor score (FFS), and serum albumin were independent predictors of all-cause mortality. A new formula was developed as follows: NFPM = male sex (yes = 1 or no = 0) + FFS ≥ 2.0 (yes = 1 or no = 0) + serum albumin ≤ 3.2 mg/dL (yes = 1 or no = 0). We demonstrated that patients with a NFPM value ≥ 2 seemed to have an increased risk for all-cause mortality compared to those with a NFPM value < 2. Conclusions: This study demonstrated that it could be clinically useful and significant to develop a new formula to predict all-cause mortality using independent predictors in each different ethnicity/region-specific cohort of AAV. [ABSTRACT FROM AUTHOR]

Background: Among non-communicable disorders (NCDs), stroke remains the second leading cause of death and the third leading cause of death and disability combined (as expressed by disability-adjusted life-years lost—DALYs) in the world. Aims: The study was aimed to estimate global, regional and nationa burden of stroke and its risk factors from 1990 to 2021. Methods: Finding presented in this paper were derived mainly from the Global Burden of Disease 2021 Study on stroke burden published in The Lancet Neurology 2024:23:973-1003. Results: The estimated global cost of stroke is over US$890 billion (0.66% of the global GDP). From 1990 to 2021, the burden (in terms of the absolute number of cases) increased substantially (70.0% increase in incident strokes, 44.0% deaths from stroke, 86.0% prevalent strokes, and 32% DALYs), with the bulk of the global stroke burden (87.0% of deaths and 89.0% of DALYs) residing in lower-income and lower-middle-income countries (LMICs). Stroke attributable to metabolic risks constituted 69.0% of all strokes, environmental risks constituted 37.0%, and behavioral risks constituted 35.0%. Conclusion: This World Stroke Organization (WSO) Global Stroke Fact Sheet 2025 provides the most updated information that can be used to inform communication with all internal and external stakeholders; all statistics have been reviewed and approved for use by the WSO Executive Committee and leaders from the Global Burden of Disease research group. [ABSTRACT FROM AUTHOR]

The article from the JNCI: Journal of the National Cancer Institute discusses the evolving landscape of clinical trial design for early-stage breast cancer (eBC) and the impact on patient outcomes. It highlights the shift in focus towards high-risk disease populations and the need for tailored treatments based on individualized risk factors beyond stage. The study emphasizes the importance of engaging patients in evidence-based dialogue about their risk of recurrence and the potential benefits of new treatments, aiming to improve survival and quality of life for all patients with eBC. [Extracted from the article]

Background Approximately 40 000 individuals die from metastatic breast cancer each year. We examined what fractions of annual breast cancer–specific death are due to stage I, II, III, and IV disease and if these proportions changed over time. Methods We used data from Surveillance, Epidemiology, and End Results Program covering 1975-2017. After filtering for female sex at birth, 1 primary tumor type, surgery, American Joint Committee on Cancer Staging Manual (6th edition) stage above 0, no bilateral cancer, and survival data available, the final analysis included 972 763 patients. Temporal trends were assessed using a linear model and analysis of variance test. Results The contribution of stage I and II cancers to breast cancer–specific death increased statistically significantly from 16.2% to 23.1% and from 30.7% to 39.5%, respectively, between 2000 and 2017. The contribution of stages III and IV cancers decreased from 36.4% to 30.3% and from 16.7% to 7.1%, respectively. In 2000, 0.92%, 4.0%, and 10.7% breast cancer–specific deaths were due to T1a, T1b, and T1c node-negative cancers, respectively, which increased significantly to 1.9%, 5.8%, and 14.7% by 2017. These temporal trends were similar for hormone receptor–positive and hormone receptor–negative cancers. The contribution of breast cancer–specific death to all-cause mortality declined from 23.9% to 16.6% for stage I and from 47.7% to 36.9% for stage II cancers by 2017. Conclusions Patients with stage I and II breast cancers have excellent prognosis, yet these cancers account for more than 60% of current breast cancer–specific death because of their large absolute numbers. To further reduce breast cancer death, strategies are needed to identify and treat patients with stage I and II disease who remain at risk for recurrence. [ABSTRACT FROM AUTHOR]

The "Proceedings of the 2024 Autumn Meeting of the Society of British Neurological Surgeons" document delves into various neurosurgical topics, including incidental meningiomas, whole genome sequencing for gliomas, and brain metastases management. It highlights the importance of continuity of care in the neuro-oncology unit and discusses barriers to its implementation, such as rota issues. The study on brain and CNS tumor incidence patterns reveals higher rates among males, with the highest rates in males aged 50-64, indicating a rising trend over the last 17 years. Further research is needed to identify risk factors and develop prevention strategies for these tumors. [Extracted from the article]

Survivors of head and neck squamous cell carcinoma face excess mortality from multiple causes. However, impact and patterns of all-cause mortality remains unknown in oral cancer patients. The aim of this study was to analyse these patterns in long-term survivors. We retrospectively studied clinically node-negative (cN0) oral cancer patients primarily surgically treated at tertiary cancer center. A total of 152 patients were identified. Median follow-up of our cohort was 59 months. A total of 76 patients died. Thirty-four (22.4%) patients died from primary tumor recurrence and 42 (27.6%) patients died from competing causes. The most common competing causes of death were: cardiovascular disease (n = 18; 42.9%), followed by second primary cancer (SPC) (n = 11; 26.2%). Lung cancer accounted for 54.5% (6 of 11) of SPC associated deaths. Patients with cN0 oral cancer treated with up-front surgery are potentially highly curable for index cancer but face significant risks of mortality from causes other than disease recurrence. Nearly one-third of these patients died from competing causes of death which are major cause of mortality after the fourth year of follow-up period. This study highlights the importance of adjusted follow-up strategies addressing this population specific risks. [ABSTRACT FROM AUTHOR]

The "Acta Cardiologica" abstract presents various studies on heart conditions in athletes, left bundle branch pacing, atrial fibrillation, implantable loop recorders, cryoballoon ablation, antidiabetic drugs' effects on cardiac fibroblasts, anthracycline-induced cardiotoxicity, coronary microvascular dysfunction, and macrophages in heart failure. These studies aim to enhance understanding and treatment of heart diseases in diverse populations. Results from a stress-measurement tool intervention in hospital workers showed reduced burnout sensitivity, improved work motivation, and decreased perceived stress levels, with positive impacts on well-being and work-life balance. The BE.REAL registry study in Belgium demonstrated the effectiveness and safety of inclisiran in reducing LDL-C levels in atherosclerotic cardiovascular disease patients, highlighting promising outcomes for this patient population. [Extracted from the article]

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The article discusses the importance of strengthening general practice to improve longevity and reduce health inequalities. It highlights the role of general practice in providing comprehensive care for the whole population, from prevention to long-term management of chronic conditions. The text emphasizes the impact of social determinants on mortality rates and the need for national policies to address inequalities. It also explores the mechanisms through which general practice contributes to improving longevity, focusing on factors such as funding, staffing, access, clinical generalism, and relationship continuity. [Extracted from the article]

AbstractBackgroundObjectivesMethodsResultsConclusionsMultidrug-resistant bacteria (MDR) represent a significant global health concern and vary in specific settings. Spain reported several annual deaths attributed to MDR bacteria, mainly carbapenemase-producing Enterobacterales.We aimed to characterise the incidence and temporal trends of MDR bacterial infections or colonisations reported within the province of Granada (data from five hospitals), and to investigate factors linked to clinical vulnerability.We conducted an observational retrospective study (2014–2022) using the Andalusian Epidemiological Surveillance System. We employed descriptive, bivariate analyses and geographical mapping. Multivariable logistic regression models were adjusted to identify factors associated with (1) carbapenemase-production and (2) in-hospital mortality.We included 1482 patients. The main microorganisms identified were Klebsiella spp., Escherichia spp. and Acinetobacter baumannii. Carbapenemases were detected in 23% of cases, and were associated with higher in-hospital mortality rates (OR: 1.92; 95% confidence interval (95% CI): 1.31–2.81) and male sex (OR: 1.50; 95% CI: 1.01–2.23). The overall in-hospital mortality rate was estimated at 18.1%. Infections caused by A. baumannii (OR: 2.11; 95% CI: 1.41–3.13) or carbapenemase-producing Klebsiella pneumoniae (OR: 2.11; 95% CI: 1.28–3.45) were associated with increased mortality.These findings contribute to our understanding of the characteristics associated with carbapenemase-producing and early mortality resulting from MDR bacteria. This study offers insights into the factors associated with clinical vulnerability, which may improve future preventive measures. [ABSTRACT FROM AUTHOR]

Background: Beagles are a popular companion animal dog breed and are generally stated to be a healthy breed. This VetCompass study aimed to report the demography, common disorders and mortality of Beagles under primary veterinary care in the UK. Anonymised clinical records within VetCompass were followed over time to extract disorder and mortality data during 2019 on Beagles under primary veterinary care in the UK. Results: Beagles comprised 19,906 (0.88%) of the 2,250,417 dogs in the study population. Annual proportional birth rates showed an increasing breed popularity from 0.41% of all dogs born in 2005 and peaking at 1.06% in 2012, followed by a decrease to 0.90% in 2019. The median adult bodyweight was 18.19 kg (IQR 15.68–21.07). From a random sample of Beagles (3,729/19,906, 18.73%), the most diagnosed disorders were obesity (24.27%, 95% CI: 22.89–25.65), periodontal disease (17.78%, 95% CI: 16.55–19.01), overgrown nail(s) (11.61%, 95% CI: 10.58–12.64), otitis externa (11.18%, 95% CI: 10.17–12.19) and anal sac impaction (10.59%, 95% CI 9.60-11.58). Once disorders were grouped by pathology, the most common group-level disorders were obesity (24.27%, 95% CI: 22.89–25.65), dental disorders (21.48%, 95% CI: 20.16–22.80), ear disorders (13.62%, 95% CI: 12.52–14.72), claw/nail disorders (13.14%, 95% CI: 12.06–14.22) and anal sac disorders (11.10%, 95% CI: 10.09–12.11). The median age at death was 11.28 years (IQR 9.32–13.08) for 322 deaths recorded during the study period. The most common causes of death at group level were neoplasia (19.26%, 95% CI: 14.76–23.75), mass (13.18%, 95% CI: 9.32–17.03), poor quality of life (12.84%, 95% CI: 9.03–16.65), and brain disorders (6.76%, 95% CI: 3.90–9.62). Conclusions: Their disorder profile suggests the Beagle breed should not be considered to have an extreme conformation. Owners and veterinary teams should put special emphasis on care related to bodyweight control and dental hygiene in Beagles. Their median age at death of 11.70 years suggests reasonable overall health but neoplasia is a common biomedical cause of death in Beagles. Plain English summary: The Beagle is a scenthound originally created to hunt hare but that is now more commonly kept as a companion dog breed. The Beagle is promoted as a generally healthy dog but there is limited published evidence of the health of the subset of the breed that is owned outside of laboratory research. This VetCompass study aimed to report on the demography, common disorders and mortality of Beagles under primary veterinary care in the UK. VetCompass collects anonymised veterinary clinical records for research on canine health. Beagles comprised 0.88% of the 2,250,417 dogs in the current study under veterinary care during 2019 in the UK. The average adult bodyweight of Beagles was 18.19 kg. Male Beagles were on average over 3 kg heavier than female Beagles (19.70 kg vs. 16.59 kg). From a random sample of 3,729 Beagles whose clinical records were examined in more detail, the most common disorders diagnosed were obesity (24.27% of all Beagles affected in 2019), dental disease (17.78%), overgrown nail(s) (11.61%), ear infection (11.18%) and anal sac impaction (10.59%). From 322 dogs that died during the study, the average age at death was 11.28 years. Females outlived males by almost a year (11.70 years vs. 10.75 years). The most common general causes of death were cancer (19.26%,), lumps (13.18%), poor quality of life (12.84%) and brain disorders (6.76%). These results confirm the Beagle as a generally healthy breed, with a lifespan and disorder profile similar to dogs overall. However, owners and veterinary teams should put special emphasis on care related to bodyweight control and dental hygiene in Beagles. [ABSTRACT FROM AUTHOR]

Key Points: Question: Is early aortic valve intervention superior to guideline-directed conservative management in asymptomatic patients with severe aortic stenosis and myocardial fibrosis? Findings: In this multicenter randomized clinical trial of 224 patients with asymptomatic severe aortic stenosis and myocardial fibrosis, there was no significant difference in the primary composite end point of all-cause death or unplanned aortic stenosis–related hospitalization in patients randomized to receive early intervention vs patients randomized to receive guideline-directed conservative management: 18% vs 23%. Meaning: Among patients with asymptomatic severe aortic stenosis and myocardial fibrosis, early aortic valve intervention did not improve clinical outcomes compared with guideline-directed conservative management. Importance: Development of myocardial fibrosis in patients with aortic stenosis precedes left ventricular decompensation and is associated with an adverse long-term prognosis. Objective: To investigate whether early valve intervention reduced the incidence of all-cause death or unplanned aortic stenosis–related hospitalization in asymptomatic patients with severe aortic stenosis and myocardial fibrosis. Design, Setting, and Participants: This prospective, randomized, open-label, masked end point trial was conducted between August 2017 and October 2022 at 24 cardiac centers across the UK and Australia. Asymptomatic patients with severe aortic stenosis and myocardial fibrosis were included. The final date of follow-up was July 26, 2024 Intervention: Early valve intervention with transcatheter or surgical aortic valve replacement or guideline-directed conservative management. Main Outcomes and Measures: The primary outcome was a composite of all-cause death or unplanned aortic stenosis–related hospitalization in a time-to-first-event intention-to-treat analysis. There were 9 secondary outcomes, including the components of the primary outcome and symptom status at 12 months. Results: The trial enrolled 224 eligible patients (mean [SD] age, 73 [9] years; 63 women [28%]; mean [SD] aortic valve peak velocity of 4.3 [0.5] m/s) of the originally planned sample size of 356 patients. The primary end point occurred in 20 of 113 patients (18%) in the early intervention group and 25 of 111 patients (23%) in the guideline-directed conservative management group (hazard ratio, 0.79 [95% CI, 0.44-1.43]; P =.44; between-group difference, −4.82% [95% CI, −15.31% to 5.66%]). Of 9 prespecified secondary end points, 7 showed no significant difference. All-cause death occurred in 16 of 113 patients (14%) in the early intervention group and 14 of 111 (13%) in the guideline-directed group (hazard ratio, 1.22 [95% CI, 0.59-2.51]) and unplanned aortic stenosis hospitalization occurred in 7 of 113 patients (6%) and 19 of 111 patients (17%), respectively (hazard ratio, 0.37 [95% CI, 0.16-0.88]). Early intervention was associated with a lower 12-month rate of New York Heart Association class II-IV symptoms than guideline-directed conservative management (21 [19.7%] vs 39 [37.9%]; odds ratio, 0.37 [95% CI, 0.20-0.70]). Conclusions and Relevance: In asymptomatic patients with severe aortic stenosis and myocardial fibrosis, early aortic valve intervention had no demonstrable effect on all-cause death or unplanned aortic stenosis–related hospitalization. The trial had a wide 95% CI around the primary end point, with further research needed to confirm these findings. Trial Registration: ClinicalTrials.gov Identifier: NCT03094143 This randomized clinical trial examines whether early valve intervention will reduce the incidence of all-cause death or unplanned aortic stenosis–related hospitalization in asymptomatic patients with severe aortic stenosis and myocardial fibrosis. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) is the leading cause of death worldwide with mortality rates in women currently exceeding those in men. To date, evidence is widely lacking for unique female determinants of CVD. However, strong associations with psychological stress, obesity or elevated inflammatory biomarkers with adverse cardiovascular outcomes in women have been identified in various studies. Interestingly, amygdalar metabolic activity, a central neural structure involved in emotional stress processing, has proven to be an independent predictor of major adverse cardiovascular events (MACE). Moreover, upregulated amygdalar metabolism was directly linked to myocardial injury in women, but not in men. This newly suggested sex-dependent brain-heart interrelation was further supported by the discovery that bone marrow activity, a surrogate parameter of inflammation, represents a potential bridging link between amygdalar activity and cardiovascular pathology by fueling inflammatory processes that promote atherosclerotic disease. Such malignant cascade of events might account, at least in part, for the excess female mortality seen in women with coronary artery disease and calls for sex-specific research toward pharmacologic or behavioral modulators to improve cardiovascular outcomes, particularly in women. This mini review summarizes recent advances in cardiovascular sex-specific medicine, thereby focusing on the interplay between the limbic system, autonomic regulation and inflammatory biomarkers, which may help to tailor CVD management toward the female cardiovascular phenotype. [ABSTRACT FROM AUTHOR]

Background: Ischemic stroke is the second leading cause of death and the third leading cause of combined disability and mortality globally. While reperfusion therapies play a critical role in the management of acute ischemic stroke (AIS), their applicability is limited, leaving many patients with significant neurological deficits and poor prognoses. Neuroprotective agents have garnered attention for their potential as adjunct therapies; however, their relative efficacy remains unclear. This study utilized a network meta-analysis (NMA) to systematically compare the efficacy of neuroprotective agents in improving neurological function and prognosis in stroke patients. Methods: This study adhered to PRISMA guidelines and the Cochrane Handbook for systematic reviews. Randomized controlled trials (RCTs) were identified through comprehensive searches of the PubMed, Embase, and Cochrane Library databases. Two independent reviewers conducted the selection process, data extraction, and quality assessment. Outcomes included 90-day modified Rankin Scale (90d-mRS), change of National Institutes of Health Stroke Scale score from baseline to 90-day/14-day/7-day (90d/14d/7d-NIHSS) and 90-day/14-day Barthel Index (90d/14d-BI). Data analyses were performed using RevMan 5.4 and Stata 14.0. Results: A total of 42 RCTs involving 12,210 participants were included in this analysis. The interventions assessed included Cerebrolysin, Citicoline, Edaravone, Edaravone Dextranol, Human urinary kallidinogenase, Minocycline, Nerinetide, Butylphthalide, Vinpocetine, and Control. The NMA results demonstrated that NBP ranked highest for the 90d-mRS, 90d-NIHSS, 14d-NIHSS, and 14d-BI outcomes. Edaravone was found to be the most effective intervention for the 7d-NIHSS and 90d-BI outcomes. Conclusion: The findings of this study indicate that different neuroprotective agents exhibit distinct advantages at specific stages of recovery. NBP showed outstanding performance in improving 90d-mRS and 90d-NIHSS, underscoring its potential in long-term rehabilitation. Edaravone demonstrated significant superiority in 7d-NIHSS scores, highlighting its role in early neuroprotection. These results provide valuable insights for individualized clinical treatment. To further validate the efficacy and safety of neuroprotective agents, future studies should involve larger sample sizes and conduct multicenter, large-scale randomized controlled trials. Systematic review registration: https://www.crd.york.ac.uk/prospero/display%5frecord.php?RecordID=601346 , identifier CRD42024601346. [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]

Background: The detection of unexpected findings (UF) during CT scans of patients undergoing TAVR is frequent; however, it is unclear whether such findings have a clinical impact on the TAVR pathway. Methods: We conducted a retrospective, single-center observational study enrolling patients who were candidates for TAVR. All enrolled patients underwent a CT scan before valve implantation. The primary outcome of this study was all-cause mortality, while the secondary outcome was to determine whether the diagnosis of clinically relevant UF on CT scans results in a significant delay in the TAVR procedure. Results: A total of 284 patients were enrolled. Clinically relevant UF were identified in 15% of the patients, with the most common types being pulmonary masses or nodules. During the follow-up period, 83 patients (29.2%) died. The prognosis was worsened by chronic kidney disease (HR 1.76, p = 0.03) and left ventricular dilatation (HR 1.74, p = 0.04), while the diagnosis of clinically relevant UF did not impact all-cause mortality (p = 0.38). No statistically significant differences were found in the delay from the diagnosis of severe aortic stenosis to TAVR between patients with and without clinically relevant UF (p = 0.07), although patients with clinically relevant UF experienced a median delay of approximately 37 days in the TAVR procedure. Conclusions: The presence of clinically relevant UF on preoperative CT scans does not affect all-cause mortality but shows a trend toward increasing the time from diagnosis to the procedure in patients with severe aortic stenosis undergoing TAVR. Further studies are required to confirm these findings in larger patient cohorts. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an emerging global health concern, and it is not only the keystone precursor of eventual liver-related morbidity, but it also places patients at considerably higher cardiovascular risk, which is still a leading cause of death in these patients. The most important common underlying pathophysiological mechanisms in these diseases are primarily related to insulin resistance, chronic inflammation and oxidative stress. The presence of MASLD with cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) elevates the risk for poor outcomes, thus this review highlights a method to the therapeutic approaches. Given the intertwined nature of MASLD, T2DM, and CVD, there is an urgent need for therapeutic strategies that address all three conditions. Although lifestyle changes are important as treatment, medication plays a crucial role in managing hyperglycemia, enhancing liver function and lowering cardiovascular risk. The onset and progression of MASLD should be addressed through a multifaceted therapeutic approach, targeting inflammatory, immune, metabolic, oxidative stress, hormonal and gutaxis pathways, alongside the treatment strategies for T2DM. In this review, we discuss the effects of antidiabetic drugs with an impact on both liver outcomes and cardiovascular risk in patients affected by MASLD, T2DM and CDV. [ABSTRACT FROM AUTHOR]

Background: During the last few years, significant pathophysiological differences between heart failure (HF) patients with "normal" ejection fraction (EF) (50% to 64%) and those with supra-normal EF (≥65%) have been highlighted. However, these distinct EF phenotypes have been poorly investigated in elderly patients aged ≥70 y. Accordingly, the present study aimed at assessing the clinical and echocardiographic characteristics of a retrospective cohort of elderly HFpEF patients (aged ≥ 70 y), categorized on the basis of "normal" EF (50 to 64%) or "supra-normal" EF (≥65%). Methods: All patients aged ≥ 70 y that were discharged from our Institution with a first diagnosis of HF with preserved EF (HFpEF) between January 2020 and March 2021 entered the study. All patients underwent clinical evaluation, blood tests, and transthoracic echocardiography. The primary endpoint was "all-cause mortality", while the secondary one was the composite "all-cause mortality or rehospitalization for all causes" over a mid-term follow-up. Results: A total of 200 HFpEF patients (86.4 ± 6.6 y, 70% females) were retrospectively evaluated. The "normal" EF group (n = 99) and the "supra-normal" EF one (n = 101) were separately analyzed. Compared to patients with "normal" EF, those with "supra-normal" EF were older, with greater comorbidity burden, and moderate-to-severe frailty status. The mean follow-up duration was 3.6 ± 0.3 y. During follow-up, 79 patients died, and 73 were rehospitalized. In the multivariate Cox regression analysis, age (HR 1.09, 95% CI 1.03–1.16, p = 0.002), EF (HR 1.08, 95% CI 1.03–1.14, p = 0.004), tricuspid annular plane systolic excursion (TAPSE)/systolic pulmonary artery pressure (sPAP) ratio (HR 0.14, 95% CI 0.03–0.61, p = 0.009), and infectious disease occurring during the baseline stay (HR 7.23, 95% CI 2.41–21.6, p < 0.001) were independently associated with the primary endpoint in the whole study population. EF (HR 1.04, 95% CI 1.01–1.07, p = 0.02) also predicted the secondary endpoint. EF ≥65% was the best cut-off to predict both endpoints. Conclusions: "Supra-normal" EF (≥65%) at hospital admission is independently associated with all-cause mortality and rehospitalization for all causes in elderly HFpEF patients over a mid-term follow-up. [ABSTRACT FROM AUTHOR]

Acute lymphoblastic leukemia (ALL) is a malignant condition of lymphoid progenitor cells that primarily affects the pediatric population, but also adults. The 5-year survival rate is 90% in children and approximately 40% in adults, with survival increasing through the use of peripheral stem cell allotransplantation (SCT). The relapse rate after stem cell transplantation (SCT) in adult acute lymphoblastic leukemia (ALL) patients ranges from 35% to 45%, making relapse a major cause of death in this population. Background: We present an atypical case of late testicular involvement in ALL in a 50-year-old man diagnosed with ALL pro-T in remission post-chemotherapy (GMALL 2003 protocol) and allogeneic stem cell transplantation (alloSCT) from a related donor. Methods: This case describes a 50-year-old male with ALL pro-T who experienced three rare extramedullary relapses post-chemotherapy and alloSCT. Five years after remission, he had a unilateral testicular relapse confirmed by immunophenotyping of spermatic fluid. Results: Despite no bone marrow involvement, he was treated with chemotherapy, intrathecal therapy, and bilateral testicular radiotherapy. He later relapsed in the orbit, controlled by radiotherapy, followed by a third relapse in the heart and colon. Conclusions: This case highlights the unusual sites and consecutive nature of extramedullary relapses in adult ALL. [ABSTRACT FROM AUTHOR]

Background/Objectives: Stroke is a leading cause of mortality and disability worldwide, ranking as the second most common cause of death and the third in disability-adjusted life-years lost. Ischaemic stroke, which constitutes the majority of cases, poses significant public health and economic challenges. This study evaluates trends in ischaemic stroke hospitalisations in Italy from 2008 to 2022, focusing on differences before and after the COVID-19 pandemic. Methods: We analysed ischaemic stroke hospitalisations among individuals admitted through emergency services using Italian hospital discharge records from 2008 to 2022. Poisson Inverse Gaussian regression was employed to assess hospitalisation trends, accounting for age, sex, and geographic variations. Results: Among 1,689,844 ischaemic stroke hospitalisations, there was a marked age-related increase, particularly among individuals aged 74 and older, with males consistently showing higher rates. Hospitalisation trends demonstrated a 20% reduction over 15 years, suggesting improvements in stroke prevention and treatment. However, there was a slight increase in rates during the COVID-19 period, despite the overall declining trend, highlighting the potential healthcare challenges experienced during the pandemic. Multivariable analysis confirmed age and male sex as significant risk factors. Conclusions: This study underscores the age-related increase in stroke hospitalisation rates, emphasising the need for targeted prevention strategies for elderly populations. The overall reduction in stroke hospitalisation rates reflects advancements made in healthcare, although the impact of COVID-19 on access to stroke care is evident. Future policies must address the pandemic's effects on stroke care continuity and prioritise interventions tailored to age and sex. [ABSTRACT FROM AUTHOR]

The letter to the editor published in Leukemia & Lymphoma discusses the diagnostic yield of routine magnetic resonance imaging (MRI) of the central nervous system in high-risk systemic diffuse large B-cell lymphoma patients with negative cerebrospinal fluid analyses. The study found that CNS-MRI may be avoided in these patients, as the incidence of synchronous central nervous system involvement was low. The research suggests that CNS-MRI has low utility for neurologically asymptomatic patients with negative CSF analyses, and clinical evaluation of neurological symptoms may guide the need for additional imaging. [Extracted from the article]

The article "Assessing the Economic Value of Statins: A Comparison of Branded and Generic Options in India" published in the Journal of Cardiovascular Disease Research discusses the economic implications of statins in treating cardiovascular diseases in India. The study compares the cost variations between branded and generic statins, highlighting significant price differences that may impact patient compliance and healthcare systems. The research emphasizes the importance of including more hypolipidemic drugs under the Drug Price Control Order to reduce cost disparities and promote the use of cost-effective generic options. The study findings suggest that promoting generics can enhance treatment adherence and improve overall health outcomes, contributing to the goal of achieving universal health coverage. [Extracted from the article]

The article explores the use of Mechanical Thrombectomy (MT) for acute ischemic stroke caused by large vessel occlusions, aiming to restore blood flow and minimize brain damage. Studies show that MT within six hours of symptom onset can significantly improve patient outcomes. The text covers differential diagnosis, diagnostic studies, pharmacologic and non-pharmacologic therapies, and management strategies for acute ischemic stroke, emphasizing the importance of early recognition and personalized intervention strategies for various patient populations. Complications of MT, post-thrombectomy care, and the use of ASPECTS scores and the modified Rankin Scale in treatment decisions are also discussed, highlighting the need for rapid identification and treatment to optimize outcomes. [Extracted from the article]

Upper respiratory infections (URIs) are the leading cause of acute disease incidence worldwide and contribute to a substantial health-care burden. Although acute otitis media is a common complication of URIs, the combined global burden of URIs and otitis media has not been studied comprehensively. We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 to explore the fatal and non-fatal burden of the two diseases across all age groups, including a granular analysis of children younger than 5 years, in 204 countries and territories from 1990 to 2021. Mortality due to URIs and otitis media was estimated with use of vital registration and sample-based vital registration data, which are used as inputs to the Cause of Death Ensemble model to separately model URIs and otitis media mortality by age and sex. Morbidity was modelled with a Bayesian meta-regression tool using data from published studies identified via systematic reviews, population-based survey data, and cause-specific URI and otitis media mortality estimates. Additionally, we assessed and compared the burden of otitis media as it relates to URIs and examined the collective burden and contributing risk factors of both diseases. The global number of new episodes of URIs was 12·8 billion (95% uncertainty interval 11·4 to 14·5) for all ages across males and females in 2021. The global all-age incidence rate of URIs decreased by 10·1% (–12·0 to –8·1) from 1990 to 2019. From 2019 to 2021, the global all-age incidence rate fell by 0·5% (–0·8 to –0·1). Globally, the incidence rate of URIs was 162 484·8 per 100 000 population (144 834·0 to 183 289·4) in 2021, a decrease of 10·5% (–12·4 to –8·4) from 1990, when the incidence rate was 181 552·5 per 100 000 population (160 827·4 to 206 214·7). The highest incidence rates of URIs were seen in children younger than 2 years in 2021, and the largest number of episodes was in children aged 5–9 years. The number of new episodes of otitis media globally for all ages was 391 million (292 to 525) in 2021. The global incidence rate of otitis media was 4958·9 per 100 000 (3705·4 to 6658·6) in 2021, a decrease of 16·3% (–18·1 to –14·0) from 1990, when the incidence rate was 5925·5 per 100 000 (4371·8 to 8097·9). The incidence rate of otitis media in 2021 was highest in children younger than 2 years, and the largest number of episodes was in children aged 2–4 years. The mortality rate of URIs in 2021 was 0·2 per 100 000 (0·1 to 0·5), a decrease of 64·2% (–84·6 to –43·4) from 1990, when the mortality rate was 0·7 per 100 000 (0·2 to 1·1). In both 1990 and 2021, the mortality rate of otitis media was less than 0·1 per 100 000. Together, the combined burden accounted for by URIs and otitis media in 2021 was 6·86 million (4·24 to 10·4) years lived with disability and 8·16 million (4·99 to 12·0) disability-adjusted life-years (DALYs) for all ages across males and females. Globally, the all-age DALY rate of URIs and otitis media combined in 2021 was 103 per 100 000 (63 to 152). Infants aged 1–5 months had the highest combined DALY rate in 2021 (647 per 100 000 [189 to 1412]), followed by early neonates (aged 0–6 days; 582 per 100 000 [176 to 1297]) and late neonates (aged 7–24 days; 482 per 100 000 [161 to 1052]). The findings of this study highlight the widespread burden posed by URIs and otitis media across all age groups and both sexes. There is a continued need for surveillance, prevention, and management to better understand and reduce the burden associated with URIs and otitis media, and research is needed to assess their impacts on individuals, communities, economies, and health-care systems worldwide. Bill & Melinda Gates Foundation. [ABSTRACT FROM AUTHOR]

Background Understanding mortality among travellers is essential for mitigating risks and enhancing travel safety. However, limited evidence exists on severe illnesses and injuries leading to death among travellers, particularly in low- and middle-income countries and remote regions. Methods We conducted a retrospective census study using country-level observational data from death certificates of travellers of seven South American countries (Argentina, Brazil, Chile, Colombia, Ecuador, Peru and Uruguay) from 2017 to 2021. Causes of death were evaluated using ICD-10 codes, categorized into non-communicable diseases (NCDs), communicable diseases and injuries. We quantified causes of death by demographic characteristics (e.g. age, sex) and geographical variables. Chi-square tests were used to assess differences between categories. We calculated crude mortality rates and incidence rate ratios (IRRs) per country's subregions. Results A total of 17 245 deaths were reported. NCDs (55%) were the most common cause of death, followed by communicable diseases (23.4%) and injuries (18.1%). NCD-associated deaths increased after age 55 years and were highest among ≥85 years. Communicable diseases were more common at younger age (<20 years). Injury-associated deaths were more common in men (79.9%) and 25–29-year-olds (17.1%). Most deaths (68.2%) could have been avoided by prevention or treatment. Mortality risk was higher among travellers in bordering regions between countries. In Roraima (Brazil) and Norte de Santander (Colombia), locations bordering Venezuela, the death IRR was 863 and 60, respectively. These countries' reference mortality rates in those regions were much lower. More than 80% of the deaths in these border regions of Brazil and Colombia involved Venezuelan citizens. Conclusion The study identified risk factors and high-risk locations for deaths among travellers in seven countries of South America. Our findings underscore the need for specific health interventions tailored to traveller demographics and destination to optimize prevention of avoidable deaths in South America. [ABSTRACT FROM AUTHOR]