BackgroundDementia contributes to morbidity and mortality in aging populations, with infectious diseases as frequent terminal events. In Brazil, data on causes of death in dementia and hospital-based end-of-life care are limited.ObjectiveTo describe causes of death, clinical characteristics, and pharmacological treatment patterns during the last month of life among patients with dementia hospitalized in a geriatric hospital in São Paulo, Brazil.MethodsThis retrospective observational study included all patients with clinically diagnosed dementia who died between 2015 and 2023 in a specialized geriatric hospital. Demographic, clinical, and pharmacological data were extracted from electronic medical records. Causes of death were classified using ICD-10 codes. Associations between dementia subtypes and infection-related deaths were evaluated using logistic regression adjusted for age, sex, and comorbidities. Statistical analyses were performed using R, with p < 0.05 considered significant.ResultsA total of 122 patients were included (mean age 83.6 ± 7.4 years; 61.5% female). Alzheimer's disease was the most frequent subtype (52.5%), followed by vascular (26.2%) and mixed dementia (21.3%). Infectious diseases accounted for 67.2% of deaths, mainly pneumonia (48.3%) and sepsis (18.9%). Antibiotics were prescribed in 76.2% of cases, and antipsychotics in 58.1%. Palliative care measures were documented in 41.0% of cases.ConclusionsInfectious diseases were the most frequent causes of death among hospitalized patients with dementia, with high antibiotic use and limited palliative care documentation. These findings indicate the need for integrated end-of-life protocols and improved recognition of palliative needs.
The historical development of the cell death concept is reviewed, with special attention to the origin of the terms necrosis, coagulation necrosis, autolysis, physiological cell death, programmed cell death, chromatolysis (the first name of apoptosis in 1914), karyorhexis, karyolysis, and cell suicide, of which there are three forms: by lysosomes, by free radicals, and by a genetic mechanism (apoptosis). Some of the typical features of apoptosis are discussed, such as budding (as opposed to blebbing and zeiosis) and the inflammatory response. For cell death not by apoptosis the most satisfactory term is accidental cell death. Necrosis is commonly used but it is not appropriate, because it does not indicate a form of cell death but refers to changes secondary to cell death by any mechanism, including apoptosis. Abundant data are available on one form of accidental cell death, namely ischemic cell death, which can be considered an entity of its own, caused by failure of the ionic pumps of the plasma membrane. Because ischemic cell death (in known models) is accompanied by swelling, the name oncosis is proposed for this condition. The term oncosis (derived from ónkos, meaning swelling) was proposed in 1910 by von Reckling-hausen precisely to mean cell death with swelling. Oncosis leads to necrosis with karyolysis and stands in contrast to apoptosis, which leads to necrosis with karyorhexis and cell shrinkage.
Donation after circulatory death (DCD) is an emerging heart transplantation (HT) strategy with improved waitlist and comparable post-transplant outcomes to donation after brain death (DBD) in adults. Pediatric DCD-HT is underutilized but gaining broader adoption. We assessed the impact of DCD listing on waitlist outcomes and graft survival in pediatric HT. We queried the OPTN (Organ Procurement and Transplantation Network)/UNOS (United Network for Organ Sharing) database for all pediatric primary isolated HT candidates between January 2021 and June 2024. Waitlist outcomes were compared by final listing type to account for crossovers. Offer dynamics were assessed by average interval between offers stratified by OPTN/UNOS status. Multivariable regression modeled offer frequency as a function of DCD listing. We compared 30-day survival between recipients of DCD and DBD organs. Among 2486 candidates, 86 were initially listed eligible for DCD and 2400 for DBD. DCD candidates had higher clinical acuity than DBD candidates. DCD listing was associated with significantly shorter intervals between offers across all statuses and increased offer rate by 134% (95% CI: 92%-186%). Waitlist outcomes did not differ significantly by final listing type. There was no difference in 30-day survival between DCD and DBD recipients. DCD listing in pediatric HT is associated with a shorter interval between offers and more frequent offers. Waitlist survival was similar between groups despite DCD candidates being sicker at listing. There was no difference in 30-day survival between DCD and DBD recipients. These findings suggest that broader adoption of pediatric DCD-HT can expand access to donor hearts without compromising early post-transplant outcomes.
In this study, we investigated fatal farm tractor-related injuries in Central Serbia over the 24-year period, focusing on the characteristics and mechanisms of injuries, causes of death, and key accident-causing and contributing factors for these fatalities. This epidemiological, analytical, retrospective, cross-sectional autopsy study included 1970 medicolegal deaths recorded between 2001 and 2024 within the territory of Central Serbia. During this period, 41 cases were reported as tractor-related fatalities. Blood alcohol concentration (BAC) was analyzed for all victims who died at the scene of the accidents, as well as those who survived <24 hours after the incident. Tractor rollovers were the leading mechanism of fatal injury, with the highest chance being for traumatic asphyxia as the cause of death. The second most common mechanism of injury was being run over by a tractor. The typical farm tractor driver, who is fatally injured in Central Serbia, is male, over 65 years old, with a mean BAC of 1.76±0.23‰. Rolling over is the most common mechanism of injury for farm tractor drivers.
US life expectancy declined after 2014 amid rising drug-poisoning and suicide mortality. We assessed whether recent, large statutory minimum-wage increases affected these outcomes. Using 2010-2019 National Vital Statistics System mortality data, we analyzed adults aged 25 and up and exploited cross-state adoption and differential exposure by education (no college versus at least some college) in a triple-differences framework. To address staggered adoption and treatment heterogeneity, we implemented a two-stage imputation estimator. We studied deaths per capita for poisonings, drug overdoses, opioid-related overdoses, and suicides. Twenty-six states (including Washington, D.C.) enacted statutory minimum wage increases while 25 did not. Pre-treatment placebo estimates show little evidence of systematic pre-existing trends that would confound the results. Average post-treatment mortality effects associated with minimum wage increases are generally small: poisonings -0.9% (95% CI -6.8%, +5.0%); suicides -1.0% (-7.5%, +5.5%); overdoses +0.5% (-5.2%, +6.2%); opioid-involved overdoses -2.8% (-10.2%, +4.6%). When restricting to states with 50% statutory hikes or higher, we reach similar conclusions. At magnitudes observed during 2010-2019, minimum-wage increases had, at most, modest effects on deaths of despair and are unlikely to meaningfully reduce drug overdose or suicide mortality in the medium term.
The purpose of the paper is to study the utilization profile of donor corneas with death-to-retrieval time (DRT) >12 h in the Indian population and to assess the safety of endothelial keratoplasty using such corneas. This retrospective study (Jan 2018-June 2023) analyzed eye bank records of donor corneas with DRT ≥12 h. The primary outcome assessed was the utilization rate across different keratoplasties. Secondary outcomes included records of endothelial cell density (ECD) of donor tissue. Records of outcomes of endothelial keratoplasty using such corneas in the form of postoperative recorded visual acuity, graft clarity, postoperative ECD, signs of graft infection, and failure were evaluated. Out of 333 donor corneas, 75.68% were suitable for transplantation, 21.3% were allocated for research, and 3% were unfit. Among transplantable corneas, 42.04% were used for optical penetrating keratoplasty (PK), 15.9% for Descemet stripping automated endothelial keratoplasty, 9.9% for therapeutic PK, 4.5% for deep anterior lamellar keratoplasty, 1.5% for patch grafts, 1.2% for tectonic PK, and 0.3% each in Descemet membrane endothelial keratoplasty and tuck in lamellar keratoplasty. Mean ECD for endothelial keratoplasty suitable corneas was 2633 ± 291 cells/mm². Minimum 6 months follow-up records of endothelial keratoplasty showed that 91% achieved best-corrected visual acuity ≥6/18 and ≥6/12 in 60%. The maximum follow-up period was 4 years. Mean ECD declined to 1857.02 ± 133.11 cells/mm² ( P < 0.0001). Graft rejection was recorded in 13.34%, elevated intraocular pressure in 18%, and graft infections in none. Properly screened corneas with DRT >12 h lead to successful endothelial keratoplasty outcomes. Traditional DRT limits should be re-evaluated, especially in regions with a shortage of donor cornea. Preservation quality, ECD, and preoperative assessment are critical.
The aim of this review is to explore self-injury mortality (SIM) for its utility and potential in capturing deaths due to a desire or indifference to ending one's life. Suicide deaths are underreported, and a high percentage of substance use disorder deaths are misclassified as "accidental" or "undetermined." The challenge is how to plan interventions when such deaths are inadequately ascertained? Shifting the focus from suicide to SIM unmasks a hidden global crisis. Globally over 727,000 suicide deaths are reported each year. However, if adjusted for estimated underreporting and substance use disorder deaths, the actual number of people driven by a desire to escape despair by bringing one's life to an end could be more than double this. A case is argued for construction of globally applicable composite measures of self-injury mortality (SIM). To respond intelligently to suicide and self-injury prevention opportunities requires that the etiology and natural history of underlying mental disorders are understood, so that effective interventions are implemented. This is illustrated for the following disorders: anorexia nervosa, schizophrenia, bipolar disorder, major depressive disorder, gambling disorder, and substance use disorder. The keys to reducing self-injury mortality as an outcome of mental and behavioral disorders remain timely clinical intervention by informed health professionals, and supportive families and communities. Policy and service interventions to address determinants and risk factors are equally important. The ultimate enabling agent for ensuring conditions for optimal mental health must be society itself, and how it prioritizes elements within the political economy.
BackgroundAlzheimer's disease (AD) among patients with metabolic syndrome-related conditions is a global threat, contributing significantly to escalating mortality and economic burden. They demonstrate analogous pathophysiologies and risk determinants, highlighting the necessity for addressing this critical issue.ObjectiveThis study analyzed demographic trends and disparities of AD with metabolic syndrome-related conditions among patients aged 75 and above from 1999 to 2020.MethodsThis study examined the death certificates sourced from the CDC-WONDER database from 1999 to 2020, to analyze age-adjusted mortality rates (AAMRs) per 100,000 population. The Joinpoint regression model was used to assess trends in overall demographics, geographic, and place-of-death variables.ResultsThere were 2,355,233 deaths documented with AD listed as the underlying cause of death among older adults (aged ≥75), out of which 444,488 deaths were related to metabolic syndrome-related conditions from 1999 to 2020. The AAMR rose substantially from 36.48 in 1999 to 157.93 in 2020. Women consistently had higher AAMRs than males (females: 107.79, males: 79.02). Non-Hispanic African Americans (121.65) showed the highest mortality rates among all racial groups. However, from 1999 to the early to mid-2000s, all races highlighted a sharp peak in mortality rates. Striking geographical disparities were noted, with Mississippi in the top 90th percentile and Massachusetts in the lower 10th percentile.ConclusionsThis study reveals the demographic and geographic variations in mortality rates, highlighting the modalities of interventions and the need for equitable healthcare access.
Medical assistance in dying (MAiD) has been available across Canada since 2016 for patients with amyotrophic lateral sclerosis (ALS). We aimed to characterize MAiD use, identify associated factors, and compare survival and location of death in a Canadian ALS cohort. We retrospectively reviewed patients with ALS followed at a Canadian multidisciplinary clinic who died between January 1, 2019 and December 31, 2024. Patient characteristics were described by MAiD status. Factors associated with MAiD utilization were evaluated using regression analyses, and survival and location of death were compared between patients who did and did not pursue MAiD. Of 255 patients (median age 67 years [IQR 60-75]; 42% female), 55 (21.6%) underwent MAiD. Percutaneous endoscopic gastrostomy (PEG) use was inversely associated with MAiD utilization (OR 0.34, 95% CI 0.15-0.78), whereas demographic and disease characteristics were not associated with MAiD. Survival from diagnosis to death was shorter among patients who underwent MAiD (median 12 vs 14 months; p = 0.019), with no difference from symptom onset. Death at home was more frequent with MAiD (62% vs 35%; p < 0.001). MAiD is a common end-of-life option in ALS, reflecting patient values and is associated with lower PEG use, shorter postdiagnosis survival, and more frequent death at home.
To examine early neurological deterioration (END) using different definitions according to the National Institutes of Health Stroke Scale (NIHSS) and Glasgow coma scale (GCS) scores for their ability to predict 90-day unfavorable functional outcomes in acute ischemic stroke (AIS) patients from the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). ENCHANTED was an international, multicenter, 2×2 quasi-factorial, prospective, randomized open trial of low-dose versus standard-dose intravenous alteplase, and intensive versus guideline-recommended blood pressure lowering in thrombolysis-eligible patients with AIS. Mild, moderate, and significant END_NIHSS were defined as an increase in the NIHSS score of ≥1, ≥2, and ≥4 points, respectively. Mild and moderate-significant END_GCS were defined as a decrease in the GCS score of ≥1 and ≥2 points, respectively. In all cases, END also included death within 24 hours. Any END was defined as an increase of ≥1 point in the NIHSS score, a decrease of ≥1 point in the GCS score, or death within 24 hours. Receiver operating characteristic curve analyses were used to assess the predictive performance of different definitions of END for death or major disability (modified Rankin scale scores 3-6) and all-cause mortality. Among the 4,434 AIS patients, END ranged from 7.9% to 23.0% depending on definition, with the highest frequency for 'any END'. The discriminative ability of any END was superior to mild END_NIHSS and mild END_GCS for predicting 90-day death or major disability (AUC 0.666 vs. 0.638 and 0.616; P<0.001) and all-cause mortality (AUC 0.722 vs. 0.692 and 0.720; P=0.001). Compared to patients without any END, those with any END had higher odds of 90-day death or major disability (OR 7.04, 95%CI 5.87-8.44) and all-cause mortality (OR 6.27, 95%CI 4.87-8.07). In thrombolysis-eligible AIS patients, a broad definition of END identifies more patients with underlying acute neurological deterioration and demonstrated the strongest discriminative ability for 90-day outcomes.
Left subclavian artery stenosis in patients requiring hemodialysis can cause coronary steal syndrome via the left internal thoracic artery (LITA) graft to the left anterior descending artery (LAD), potentially leading to graft failure. This study evaluated the influence of moderate left subclavian artery stenosis on long-term outcomes following LITA-LAD coronary artery bypass grafting. Among 1744 patients undergoing primary isolated coronary artery bypass grafting, 104 patients requiring hemodialysis with left upper limb arteriovenous fistulas and preoperative contrast-enhanced computed tomography were analyzed. Left subclavian artery stenosis was quantified as: (1-minimal lumen area/reference lumen area) × 100. Patients were grouped by stenosis severity: ≥50% (n = 25) versus <50% (n = 79). The primary end point was all-cause mortality; secondary end points included cardiac death and major adverse cardiac events (eg, heart failure admission, ischemic events, or cardiac death). Inverse probability of treatment weighting was used for covariate adjustment, and inverse probability of treatment weighting-adjusted Cox models estimated hazard ratios. Mean follow-up was 4.6 ± 3.1 years. In the inverse probability of treatment weighting cohort, 5-year survival was 62% versus 26% (nonstenosis vs stenosis; log-rank P < .001). Left subclavian artery stenosis was associated with higher risks of all-cause death (hazard ratio, 2.09; 95% CI, 1.39-3.15; P < .001) and cardiac death (hazard ratio, 3.68; 1.46-9.30; P = .006), but not with major adverse cardiac events. Moderate preoperative left subclavian artery stenosis was independently associated with increased long-term mortality and cardiac death after LITA-LAD coronary artery bypass graft in patients requiring hemodialysis. Routine preoperative subclavian imaging and consideration of revascularization or alternative inflow may be warranted.
Kidney transplantation outcomes have improved in the short term, but long-term graft survival gains have plateaued. Aging donors and recipients with increasing comorbidities may alter contemporary allograft outcomes. We retrospectively analyzed 2076 consecutive kidney transplants performed at a single Canadian center from 1969 to 2024, representing up to 50 y of complete follow-up. All-cause graft survival (ACGS) and death-censored graft survival were compared across 5 transplant eras using era-stratified Cox regression. The median recipient age increased significantly across the eras from 35 to 54 y (P < 0.01) and the donor age from 28 to 45 y (P < 0.01), paralleled by 3-5-fold increases in pretransplant diabetes and obesity. Death-censored graft survival improved through the early 2000s but has since plateaued, whereas ACGS declined in the modern era (2018-2024) compared with the 1998-2009 peak (P = 0.007). Death with function accounted for >60% of graft losses in recent years, with infectious deaths rising from 21% to 45% (P < 0.01). Increasing donor and recipient age, comorbidities, and delayed graft function independently predicted inferior survival. These findings reveal a reversal in ACGS gains in the contemporary era, highlighting the need for precision immunosuppression strategies tailored to the aging, comorbid transplant population.
BackgroundAlzheimer's disease and other dementias (ADODs) are increasing rapidly with population aging, yet region-specific projections for the Western Pacific remain limited.ObjectiveTo project ADOD disability-adjusted life-years (DALYs) and deaths in the Western Pacific to 2050 and evaluate how modifying key risk factors could inform policy and planning.MethodsUsing the Global Burden of Disease 2021 scenario framework, we modeled ADOD burden for 37 Western Pacific countries/areas (2023-2050), stratified by age and sex. Primary outcomes were all-age DALY and death rates per 100,000. Projections included a reference and four counterfactual scenarios. Uncertainty was estimated using 1000 Monte Carlo draws, summarized with 95% uncertainty intervals (UIs).ResultsRegional DALY rates rise from 777.6 (95% UI 375.5-1714.8) in 2023 to 1980.9 (964.7-4176.9) in 2050 (+154.7%), while death rates increase from 41.1 (10.5-110.2) to 119.7 (30.5-302.8) (+191.3%). Female rates exceed male rates throughout, widening absolute sex gaps. By 2050, ages 80-94 account for ∼62% of DALYs and ∼69% of deaths; ≥95 contribute ∼10% and ∼17%. Japan remains highest, while the Republic of Korea approaches comparable levels. China and Singapore show the steepest absolute increases. Scenario curves remain similar until the 2040s; small differences by 2050 reflect survival-driven cohort expansion at high-risk ages.ConclusionsDemographic aging will dominate Western Pacific dementia burden through mid-century. Prevention remains critical to delay onset, compress disability, and improve overall healthy aging, but demographic aging will still drive substantial growth in service needs. Health systems must scale dementia-capable primary care, long-term and palliative services, caregiver support, and gender-responsive planning.
Ferroptosis contributes to myocardial infarction (MI) pathogenesis. However, the role of nuclear receptor subfamily 1 group D member 2 (NR1D2) in MI-associated ferroptosis and its potential interaction with nuclear factor erythroid 2-related factor 2 (Nrf2) pathway remains unclear. We sought to determine whether NR1D2 regulates ferroptosis in MI through the Nrf2 pathway and to evaluate the therapeutic potential of NR1D2 knockdown. Bioinformatic analyses of GEO datasets identified NR1D2 as a key ferroptosis-related gene in MI. In vitro, NR1D2 expression was silenced in HL-1 cardiomyocytes subjected to hypoxia/reoxygenation (H/R) injury. Nrf2 inhibitor ML385 was used to verify pathway involvement. A mouse model of MI was established, and cardiac function was assessed following NR1D2 knockdown with or without ML385 co-treatment. NR1D2 expression was significantly upregulated in MI. Its knockdown in H/R-injured cardiomyocytes reduced cell death, inflammation, and ferroptosis, as indicated by decreased Fe²⁺ and malondialdehyde levels and elevated GSH/GSSG ratio. These protective effects were abolished by ML385, confirming Nrf2 dependence. Mechanistically, NR1D2 knockdown activated the Nrf2/HO-1 signaling axis, leading to the upregulation of downstream effectors glutathione peroxidase 4and SLC7A11. In MI mice, NR1D2 knockdown improved cardiac function (increased EF and FS), decreased infarct size, and inhibited ferroptosis-effects that were also negated by ML385. NR1D2 aggravates MI injury by suppressing the Nrf2 pathway and promoting ferroptosis. Targeting NR1D2 activates Nrf2 signaling and alleviates ferroptotic damage, revealing a novel regulatory mechanism and identifying NR1D2 as a promising therapeutic target for MI. A heart attack occurs when blood flow to the heart is blocked, causing heart muscle cells to die. We studied a specific type of cell death, ferroptosis, which is dependent on iron and worsens heart attack damage. Although ferroptosis is known to be important, how it is regulated remains unclear. Our data on heart attack identified NR1D2 as a protein that was significantly increased after a heart attack. To assess its importance, we reduced NR1D2 levels in isolated heart cells and in mice experiencing a heart attack. We discovered that lowering NR1D2 provided strong protection by reducing cell death and harmful inflammation and, crucially, preventing ferroptosis. We then sought to clarify the underlying mechanism. The protective effects of lowering NR1D2 were associated with activation of a well-known cellular defense pathway regulated by a protein called Nrf2. When we blocked the Nrf2 pathway, the benefits of reducing NR1D2 disappeared, confirming that NR1D2 acts by suppressing this natural protective system. In summary, our findings show that the NR1D2 protein aggravates heart attack injury by blocking the protective Nrf2 pathway and promoting ferroptosis. This suggests that therapies designed to target NR1D2 may offer a novel strategy to limit tissue damage and improve patient recovery after a heart attack.
In three studies, we tested whether icon arrays-which are a popular method of presenting risk information-can reduce predecisional information distortion that arises when early emerging preferences bias the evaluation of subsequently shown information. In Study 1, using traditional measures of information distortion, we found that risk-of-death information about two potential treatment options that was presented via icon arrays was distorted in favor of participants' leading alternative. The magnitude of distortion was similar to the level of distortion for other treatment information in the treatment scenario. Study 2 directly tested whether the presence versus absence of icon arrays when presenting risk information had any impact on levels of information distortion, this time using a dependent measure that targeted people's intuitive perceptions of risk. We found that the extent to which a 6% risk of death seemed riskier than a 3% risk of death was greater when the former risk was from a treatment option that was relatively undesired. This distortion was not significantly reduced by the presence of icon arrays. We replicated this pattern of results in a third study. These findings highlight the need for developing new tools and methods for presenting risk/likelihood information that can protect against the influence of predecisional information distortion. (PsycInfo Database Record (c) 2026 APA, all rights reserved).
Urolithiasis, a prevalent urological disorder, is associated with significant morbidity and economic burden. Despite the Global Burden of Disease (GBD) data, regional specificity for urolithiasis burden in North Africa and Middle East (NAME) remains limited. This study aims to fill this gap by analyzing the burden of urolithiasis in the NAME region from 1990 to 2021. Data from the GBD 2021 study were used to evaluate key health measures, including incidence, prevalence, mortality, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life years (DALYs). Age-standardized rates (ASRs) and absolute numbers were assessed across 21 NAME countries, stratified by sex, age, and sociodemographic index (SDI). Results were presented with 95% uncertainty intervals. In 2021, the overall incidence reached 5.3 million (95% uncertainty intervals: 4.2-6.8) cases, compared to 2.0 million (1.6-2.5) in 1990. Prevalence rose from about 76,000 (61,000-96,000) cases in 1990-201,000 (160,000-257,000) in 2021. The number of deaths increased considerably from 142.1 (79.8-194.5) to 394.2 (182.4-509.5), and the DALYs rose from 10,814.0 (7,970.0-13,932.3) to 25,213.3 (17,943.5-33,787.7) from 1990 to 2021. ASRs for all burden measures remained stable and females consistently exhibited lower rates compared to males. There was a positive correlation between SDI and rates of incidence, prevalence, and YLDs; however, deaths, YLLs, and DALYs exhibited no significant correlation with SDI. Urolithiasis imposes a growing health and economic burden in the NAME region, particularly among middle-aged populations and high-SDI countries. Targeted interventions and region-specific policies are crucial to address the rising disease burden effectively.
Long-term outcome after kidney transplantation remains limited due to high risks of cardiovascular, infectious and malignant premature death. Uremic solutes, such as urea and symmetric dimethylarginine (SDMA) are suggested to contribute to higher oxidative stress, chronic low-grade inflammation, and excess mortality. Therefore, we evaluated the associations of urea and SDMA with all-cause and cause-specific mortality in kidney transplant recipients. Baseline plasma SDMA was measured using liquid chromatography-mass spectrometry in kidney transplant recipients enrolled in the prospective TransplantLines Food and Nutrition Biobank and Cohort Study (Groningen, The Netherlands). We assessed prospective associations of SDMA with all-cause and cause-specific mortality using Cox regression. We included 628 adult kidney transplant recipients (56% male, age: 53±13 years, eGFR: 52±20 ml/min/1.73m2) at 5.4 [interquartile range: 1.8-12.0] years after transplantation. Median plasma urea was 9.6 [7.3, 13.4] mmol/L and plasma SDMA was 20 [15-25] µg/dL. In Cox regression analyses, both plasma urea (hazard ratio per doubling: 2.21, 95% CI: 2.22 to 2.85) and plasma SDMA (hazard ratio per doubling: 2.69, 95% CI: 1.95 to 3.70) were strongly associated with a higher risk of all-cause mortality. These associations remained for SDMA but not urea in a fully adjusted model and the observed associations were generally similar for all causes of death. Plasma urea and SDMA are both associated with a higher mortality risk in outpatient kidney transplant recipients. In a model including both urea and SDMA, only the association of SDMA with mortality remained.
Cervical cancer is the second leading cause of cancer-related death among women in Mexico, accounting for approximately 4,500 deaths annually. The Mexican Social Security Institute (IMSS), which provides mandatory social security and healthcare for formal-sector workers, currently relies on conventional cervical cytology for early detection. To explore alternatives, a workplace-based pilot program introducing human papillomavirus (HPV) self-sampling was implemented. This study compares the effectiveness and feasibility of HPV self-sampling with the existing cytology program, aiming to inform future screening strategies. A prospective analysis of the cost-saving impact was conducted from the IMSS institutional financing perspective, including healthcare program costs and IMSS-financed disability leave and pension payments. A two-module Markov model separately simulated clinical pathways for detection, diagnosis, and treatment under each screening strategy, and the natural progression of HPV infection and cervical intraepithelial neoplasia. Model inputs were derived from the HPV self-sampling pilot and complementary literature. Costs are reported in 2024 USD and both costs and outcomes are discounted at 3% annually. Both programs were evaluated by simulating a cohort of 100,000 women over a 10 year period. The HPV self-sampling strategy was less costly and more effective than cytology. In the modeled cohort, HPV screening prevented 812 cervical cancer cases at a total cost of 39.7 million USD, resulting in a cost of 48,896 USD per cancer case prevented. In contrast, the cytology program prevented 651 cases at a cost of 99.9 million USD, yielding 153,559 USD per case prevented. HPV self-sampling demonstrated a 61% increase in the detection of high-grade cervical lesions and was less costly and more effective than cytology. The reduction in disability leaves and associated social security expenditures further amplifies its economic value for an institution like IMSS. These findings highlight the potential benefits of increasing screening coverage and implementing workplace-based HPV screening.
Cancer remains one of the leading causes of morbidity and mortality worldwide, and its treatment is often compromised by tumor hypoxia, a condition associated with poor therapeutic outcomes. Hypoxia is particularly detrimental to oxygen-dependent therapies such as photodynamic therapy (PDT), which relies on the generation of reactive oxygen species and singlet oxygen to induce cancer cell death. Recently, biocompatible oxygen-generating systems, including photosynthetic microalgae, have emerged as promising alternatives capable of locally and continuously increasing oxygen levels under light exposure. In this context, this study investigates the impact of microalgae-mediated oxygen production on the chorioallantoic membrane (CAM) vascular network and its potential to enhance PDT efficacy. Recognizing the critical role of oxygen in PDT efficacy, we investigated whether Chlamydomonas reinhardtii, a photosynthetic microalga, could enhance treatment outcomes, using the CAM assay. Using methylene blue (MB) as the photosensitizer, three experimental groups were analyzed to assess vascular changes at a specific embryonic developmental day. PDT alone reduced vascular ramification by approximately 50%, whereas treatment with illuminated microalgae alone promoted an approximately 20% increase in vessel growth, indicating a pro-angiogenic effect. In contrast, the combination of PDT with oxygen-releasing microalgae produced a synergistic response. Specifically, the combined treatment using a reduced MB concentration achieved a ~ 50% reduction in vascularization, comparable to PDT alone but with a tenfold lower photosensitizer dose, corresponding to an order-of-magnitude increase in treatment efficiency. These findings suggest that microalgae-mediated oxygenation can significantly enhance PDT and support further exploration in mammalian in vivo models.