Intertwined depressive and cognitive trajectories and the risk of dementia and death in older adults:a competing risk analysis

Background Depressive symptoms and cognitive impairment often interact,rendering their associations controversial.To date,their joint trajectories and associations with dementia and death remain underexplored.Aims To explore the interactions between depressive symptoms and cognitive function,their developmental trajectories and the associations with all-cause dementia,Alzheimer’s disease(AD)and all-cause death in older adults.Methods Data were from the Health and Retirement Study.Depressive symptoms and cognitive function were measured using the 8-item Centre for Epidemiologic Studies Depression Scale and the Telephone Interview of Cognitive Status,respectively.All-cause dementia and AD were defined by self-reported or proxy-reported physician diagnoses.All-cause death was determined by interviews.The restricted cubic spline,group-based trajectory modelling and subdistribution hazard regression were used.Results Significant interactions between depressive symptoms and cognitive function in 2010 in their association with new-onset all-cause dementia and AD from 2010 to 2020 were found,especially in women(p for interaction<0.05).Independent trajectory analysis showed that emerging or high(vs no)depressive trajectories and poor or rapidly decreased cognitive trajectories(vs very good)from 1996 to 2010 were at significantly higher risk of subsequent all-cause dementia,AD and all-cause death.15 joint trajectories of depressive symptoms and cognitive function from 1996 to 2010 were determined,where rapidly decreased cognitive function was more common in those with no depressive symptoms.Compared with older adults with the trajectory of no depressive symptoms and very good cognitive function,those with the trajectory of no depressive symptoms but rapidly decreased cognitive function were much more likely to develop new-onset all-cause dementia and death,with subdistribution hazard ratios(95%confidence intervals)of 4.47(2.99 to 6.67)and 1.84(1.43 to 2.36),especially in women.Conclusions To effectively mitigate the risk of dementia and death,it is crucial to acknowledge the importance of preventing cognitive decline in older adults without depressive symptoms,particularly in women.

Audits of Death in HIV-Infected Children and Adolescents Followed up in the Pediatric Department of the Regional Teaching Hospital of Borgou/Alibori from 2005 to 2020

Introduction: Human immunodeficiency virus (HIV) is a major public health problem with high morbidity and mortality among children. The objective of this work was to audit the deaths of children and adolescents with HIV infection followed up in the pediatric department of the Regional Teaching Hospital of Borgou/Alibori (CHUDB/A) the from 2005 to 2020. Patients and Method: This was a retrospective and descriptive study conducted in the pediatric department of CHUD/B-A in Parakou. All children with HIV infection who died from January 1, 2005 to August 31, 2020 were included. Data collection was carried out in three stages: a phase of medical records processing, a phase of community survey and a phase of death audits. The variables studied were sociodemographic, clinical, biological, therapeutic and evolutionary. Results: Over the study period, the data of 464 infected children were recorded, including 92 deaths, representing a case fatality rate of 19.83%. Severe acute malnutrition (69.23%), gastro-intestinal tract infections (43.58%) and serious opportunistic pulmonary infections (24.36% pulmonary tuberculosis and 19.23% pneumocystis) were the main causes of death. The main dysfunctions found were: the delayed diagnosis of HIV infection (79.35%), the absence or delay in consultation when the child’s clinical condition deteriorates (32.61% and 47.83%), delayed initiation of antiretroviral treatment (42.39%) and non-adherence to treatment (38.04%). Non-adherence to treatment was predominant in adolescents (90.49%). Conclusion: Specific interventions for early detection, adequate nutritional care, psychosocial support for adolescents and mothers of children are necessary to reduce mortality due to HIV among children and adolescents.

Effects of Maternal Death on Children Living in the Sagnarigu Municipality

Introduction: The greatest effect of maternal mortality is renowned in children aged 2 - 5 months whose mothers had died. Children whose mothers died due to maternal complications were likely to record a higher mortality in infancy compared to children of surviving mothers. Motherless children mostly suffer a lot due to lack of day-to-day care, isolation, lack of motivation as well as economic cost associated with mother’s death. Thus, the purpose of this study was to ascertain the lives of children whose mothers passed away during childbirth at the Sagnarigu Municipality. Methods: This quantitative cross-sectional study was carried out at the Sagnarigu Municipal. The study recruited 297 respondents. To assess the effects of maternal death on the lives of children, families that experienced maternal death were assessed. The number of pregnancies experienced by the deceased woman, pregnancy-related complaints experienced, determinants of maternal death, number of children alive, and their standard of living were assessed with the aid of a structured questionnaire. Results: The data showed that negligence, illiteracy, poor road access, poverty, ignorance, delays in recognizing the problem, delays in making appropriate decisions, delays in the health facility, delays in giving the appropriate treatments, and traditional beliefs were some of the factors that led to maternal death in the Sagnarigu Municipality. Conclusion: The study concluded that determinants of maternal death in the Sagnarigu Municipal included the following;negligence, illiteracy, poverty, and delays in recognizing the problem. The study findings also demonstrated that the effects of maternal death on children are diverse and cut across different areas of a child’s life including livelihood sustenance, healthcare, education, and emotional and psychological development.

Epidemiological Aspects of Stillbirth and Neonatal Deaths in the Delivery Room at the Libreville Mother-Child University Hospital from 2019 to 2022

Introduction: Stillbirths are estimated at 2 million each year, of which more than 40% occur during labour. Our objective was to study the epidemiological aspects of stillbirth and neonatal deaths in the delivery room in our health facility. Patients and methods: Prospective, descriptive and analytical study, conducted at the Jeanne Ebori Foundation Mother-Child University Hospital over 4 years (January 2019-December 2022). All neonatal deaths in the delivery room or foetal death in utero, were included. Results: Among the 18,346 deliveries performed, 512 newborns were declared dead in the delivery room (27.9‰ live births), divided into in utero foetal death (19.0‰) and immediate neonatal death (8.9‰). The mean age was 34.3 weeks of amenorrhea. The rate of preterm birth was 60.4%. The sex ratio was 1.1. The average weight was 2186.6. The main causes were vascular (46.1%), foetal (20.2%), adnexal (17.1%) and asphyxia per partum (16.6%). Foetal causes were more likely to result in IUFD than other causes (OR = 6.4 [2.4 - 15.7], p < 0.001). After birth, partum asphyxia was more likely to lead to death before 15 minutes of life than other causes (OR = 11 [6.1 - 18.9], p Conclusion: The causes of stillbirth and early neonatal mortality are dominated by maternal vascular pathologies. However, the proportion of childbirth-related causes remains worrying. Better monitoring of pregnancy and labour will minimize this prevalence in our hospital.

Effect of the Implementation of Emonc in the Reduction of Maternal Deaths in the Department of Collines from 2018 to 2022

Background: Maternal and neonatal mortality remains a public health problem in Benin. Each year, approximately 1500 maternal deaths and more than 12,000 newborn deaths are recorded there. In order to correct the situation, strategies such as the implementation of Emergency Obstetric and Neonatal Care (EmONC) were initiated. Objective: Determine the rates of maternal deaths in EmONC centers in the Collines department from 2018 to 2022. Framework and Methods: The study took place in Benin precisely in the Collines department. This was a descriptive cross-sectional study. Data collection was carried out during the first two weeks of January 2023 and covered data from the 09 Basic Emergency Obstetric and Neonatal Care centers (BEMONC) and the Obstetric and Neonatal Care centers of Complete Emergency (CEmONC) of the Collines department from 2018 to 2022. An estimate of the ratios of maternal deaths occurring at the level of the EmONC centers of the Collines department from 2018-2022 was carried out followed by constructive suggestions. Results: During the five years (2018 to 2022), the Collines department recorded 42,582 live births with 148 maternal deaths, i.e. a ratio of 348 maternal deaths per 100,000 live births. Between 2018 and 2022, the highest maternal death ratio was recorded in 2019, i.e. 425 maternal deaths per 100,000 live births for all EmONC centers and 607 maternal deaths per 100,000 live births in EmONC centers. The highest maternal death ratio at the BEmONC center level was recorded in 2020, i.e. 129 maternal deaths per 100,000 births. Conclusion: These results suggest that despite the implementation of EmONC in the Collines department, maternal deaths have not decreased. To improve these outcomes for a reduction in maternal deaths, urgent action must be taken.

Epidemiology of Maternal Deaths from 2017 to 2022 in the Obstetrics and Gynaecology Department of the University Hospital of Tengandogo, Burkina Faso

Background: Although maternal mortality is declining in most countries, it remains a significant public health problem worldwide, with high rates, particularly in developing and insecure countries like ours. Objective: To study the epidemiological factors and factors associated with the occurrence of maternal death in the Gynecology-Obstetrics Department of University Hospital of Tengandogo. Method: It was a retrospective case-control study with a descriptive and analytical purpose over a period of 6 years from January 1, 2017 to December 31, 2022. Cases were women with maternal deaths during the study period. Data processing and analysis were performed using Stata version 13 software. Univariate and multivariate analyses were performed with Stata version 13 software, and logistic regression modeling was used to estimate crude and adjusted odds ratios (OR), their 95% confidence intervals (CI), and the threshold for statistical significance was set at a p value < 0.05. Results: A total of 372 patients were included in the study, including 146 cases of maternal death. The in-hospital maternal mortality rate was 1933 deaths per 100,000 live births. The average age was 28.5 years. 58.9% of patients lived in rural areas. Married patients accounted for 88.7% of cases. The average parity was 3. Direct obstetrical causes were the main causes of death, accounting for 72.6%. They were dominated by post-partum hemorrhage (24.2%), puerperal infection (18.6%), pre-eclampsia/eclampsia (16.1%) and retroplacental hematoma (8.9%). Chronic anemia (12.9%) was the main indirect obstetric cause. Risk factors associated with maternal death were primiparity (OR for paucigravida and multigravida at 0.05;P = 0.001);ambulance transport (OR for patients referred and brought in by personal vehicle = 0.3, p < 0.001) and vaginal delivery (OR for cesarean deliveries = 0.4, p < 0.001). Conclusion: To reduce maternal mortality in Burkina Faso, strategies such as educating women about danger signs during pregnancy and promoting women’s education can be adopted.

Review of Maternal Deaths over 3 and a Half Years at the Kara University Hospital Center, Northern Togo: About 65 Cases

Objective: To analyze maternal deaths, identify causes and dysfunctions leading to these deaths in order to contribute to the implementation of strategies to reduce maternal mortality at CHU Kara. Method: Cross-sectional descriptive study involving 65 cases of maternal deaths recorded at CHU-Kara from January 1, 2018 to June 30, 2021. Results: Our study focused on 65 cases of maternal deaths recorded at the maternity ward of CHU-Kara. The average age was 30 years, with a range of 15 to 45 years. They were mostly housewives (52.3%), uneducated (38.5%), multiparous (41.5%), and referred (86.2%). The causes were mainly direct obstetric causes (81.54%), with preeclampsia and its complications (28.30%) and immediate postpartum hemorrhage (20.75%) being the most common. However, uterine rupture (20.5%) and post-abortion sepsis (16.4%) were the most lethal etiologies. Delayed evacuation (46.43%), inadequate transportation (91%), and insufficient prenatal care (72.31%) were the dysfunctions before referral. Within the CHU Kara, delays in management (58.46%), unavailability of blood and labile products (18%), and insufficient monitoring were the dysfunctions identified. Ninety-five point four percent (95.4%) of the deaths were preventable. Conclusion: The magnitude of intrahospital maternal deaths, the various dysfunctions observed in the occurrence of maternal deaths before referral/evacuation and within the hospital highlight the importance of effectively implementing recommendations from audits in the fight against maternal mortality. The majority of the deaths were preventable (95.38%).

The Impact of Finerenone on Changes in Pulse Wave Velocity, Arterial Pressure and Heart Related Deaths in Hemodialysis Patients—Study Perspective

The description in the abstract lacks clear logic and a comprehensive summary of this study, so please revise and improve it according to the design theme and main content of this study, and describe it in the order of (research background), purpose/aim, method, results and conclusions. The introduction of the abstract and preface is rather lengthy, but the summary of the whole study and the presentation of the research background are not perfect (mainly because the logic of the context is not clear and orderly), so it will appear a bit messy. Hope to be able to modify (this has been mentioned in the preliminary opinion). Cardiovascular events (CVE) pose a significant threat to individuals with end-stage renal disease (ESRD), yet these patients are often excluded from cardiovascular clinical trials, leaving prognostic factors associated with CVE in ESRD patients largely unexplored. Recent human studies have demonstrated elevated circulating aldosterone levels in ESRD patients, correlating with left ventricular hypertrophy. Additionally, animal models have shown improvements in uremic cardiomyopathy with spironolactone therapy, prompting interest in assessing the efficacy of spironolactone or eplerenone in reducing mortality and improving cardiovascular function in dialysis patients. Clinicians have historically been cautious about prescribing mineralocorticoid receptor antagonists (MRAs) to congestive heart failure patients with chronic kidney disease (CKD) due to hyperkalemia risk. However, the emergence of finerenone, a novel MR antagonist with a favorable safety profile and lower hyperkalemia risk, has renewed interest in MRA therapy in this population. Heart disease, including coronary artery disease, hypertension, and left ventricular failure, is alarmingly prevalent in dialysis patients, contributing significantly to elevated mortality rates compared to the general population. Arterial stiffness, as indicated by pulse wave velocity (PWV), progressively worsens with advancing CKD stages, peaking in severity among ESRD patients undergoing dialysis. High PWV serves as a crucial risk stratification tool in ESRD. Elevated NT-proBNP and BNP levels in ESRD patients are well-documented, with significant associations observed between baseline peptide concentrations and cardiovascular morbidity and mortality. By incorporating finerenone into our study, we aim to investigate its potential benefits in reducing arterial stiffness, lowering blood pressure, and ultimately mitigating heart-related mortality among hemodialysis patients. This study holds substantial implications for hypertension and cardiovascular risk management in this vulnerable patient population. Eligible participants must have been on chronic hemodialysis for at least three months, with ACE inhibitors or angiotensin receptor blockers included in their therapy at maximum tolerable doses. Serum potassium levels 5.7 mmol/L, left ventricular ejection fraction 50%, and PWV higher than age-estimated values are also prerequisites for study entry. Randomized allocation will be conducted using a permuted block design, stratified by center, with allocation communicated via signed study forms during initial examinations. All steps of this research will be conducted in accordance with the principles of the Helsinki Declaration.

Immunomodulatory and chemopreventive effects of resveratrol on the digestive system cancers

Resveratrol(RSV),the primary polyphenol found in grapes,has been revealed to have anti-inflammatory properties by reducing the capacity of the peripheral blood mononuclear cells to produce pro-inflammatory cytokines,including IL-1β,IL-6,IL-1ra and TNFα.Considering the close association between chronic inflammation and cancer development,RSV’s immunomodulatory properties are one way by which the polyphenol may inhibit cancer initiation,proliferation,neovascularization,and migration.Resveratrol influences the generation of microtumor environment which is one of the key factors in cancer progress.In addition to immunomodulation,RSV inhibits cancer development by expressing anti-oxidant effects,causing cell cycle arrest,stimulating the function of certain enzymes,and activating cell signaling pathways.The end outcome is one of the various forms of cell death,including apoptosis,pyroptosis,necroptosis,and more,as it has been observed in vitro.RSV has been shown to act against cancer in practically every organ,while its effects on colon cancer have been documented more frequently.It is remarkable that longer-term clinical studies that may have established the potential for this natural substance to serve as a therapeutic adjuvant to traditional anti-cancer medications were not prompted by the encouraging outcomes seen with cancer cells treated with non-toxic doses of resveratrol.The current review aims to assess the recent findings about the immunological and anti-cancer characteristics of RSV,with a particular emphasis on cancers of the digestive tract,as a challenge for future clinical research that may contribute to the better prognosis of cancer.

Leveraging diverse cell-death patterns to predict the clinical outcome of immune checkpoint therapy in lung adenocarcinoma:Based on muti-omics analysis and vitro assay

Advanced LUAD shows limited response to treatment including immune therapy.With the development of sequencing omics,it is urgent to combine high-throughput multi-omics data to identify new immune checkpoint therapeutic response markers.Using GSE72094(n=386)and GSE31210(n=226)gene expression profile data in the GEO database,we identified genes associated with lung adenocarcinoma(LUAD)death using tools such as“edgeR”and“maftools”and visualized the characteristics of these genes using the“circlize”R package.We constructed a prognostic model based on death-related genes and optimized the model using LASSO-Cox regression methods.By calculating the cell death index(CDI)of each individual,we divided LUAD patients into high and low CDI groups and examined the relationship between CDI and overall survival time by principal component analysis(PCA)and Kaplan-Meier analysis.We also used the“ConsensusClusterPlus”tool for unsupervised clustering of LUAD subtypes based on model genes.In addition,we collected data on the expression of immunomodulatory genes and model genes for each cohort and performed tumor microenvironment analyses.We also used the TIDE algorithm to predict immunotherapy responses in the CDI cohort.Finally,we studied the effect of PRKCD on the proliferation and migration of LUAD cells through cell culture experiments.The study utilized the TCGA-LUAD cohort(n=493)and identified 2,901 genes that are differentially expressed in patients with LUAD.Through KEGG and GO enrichment analysis,these genes were found to be involved in a wide range of biological pathways.The study also used univariate Cox regression models and LASSO regression analyses to identify 17 candidate genes that were best associated with mortality prognostic risk scores.By comparing the overall survival(OS)outcomes of patients with different CDI values,it was found that increased CDI levels were significantly associated with lower OS rates.In addition,the study used unsupervised cluster analysis to divide 115 LUAD patients into two distinct clusters with significant differences in OS timing.Finally,a prognostic indicator called CDI was established and its feasibility as an independent prognostic indicator was evaluated by Cox proportional risk regression analysis.The immunotherapy efficacy was more sensitive in the group with high expression of programmed cell death models.Relationship between programmed cell death(PCD)signature models and drug reactivity.After evaluating the median inhibitory concentration(IC50)of various drugs in LUAD samples,statistically significant differences in IC50 values were found in cohorts with high and low CDI status.Specifically,Gefitinib and Lapatinib had higher IC50 values in the high-CDI cohort,while Olaparib,Oxaliplatin,SB216763,and Axitinib had lower values.These results suggest that individuals with high CDI levels are sensitive to tyrosine kinase inhibitors and may be resistant to conventional chemotherapy.Therefore,this study constructed a gene model that can evaluate patient immunotherapy by using programmed cell death-related genes based on muti-omics.The CDI index composed of these programmed cell death-related genes reveals the heterogeneity of lung adenocarcinoma tumors and serves as a prognostic indicator for patients.

Risk of cardiovascular death in patients with hepatocellular carcinoma based on the Fine-Gray model

BACKGROUND Hepatocellular carcinoma(HCC)is one of the most common types of cancers worldwide,ranking fifth among men and seventh among women,resulting in more than 7 million deaths annually.With the development of medical tech-nology,the 5-year survival rate of HCC patients can be increased to 70%.How-ever,HCC patients are often at increased risk of cardiovascular disease(CVD)death due to exposure to potentially cardiotoxic treatments compared with non-HCC patients.Moreover,CVD and cancer have become major disease burdens worldwide.Thus,further research is needed to lessen the risk of CVD death in HCC patient survivors.METHODS This study was conducted on the basis of the Surveillance,Epidemiology,and End Results database and included HCC patients with a diagnosis period from 2010 to 2015.The independent risk factors were identified using the Fine-Gray model.A nomograph was constructed to predict the CVM in HCC patients.The nomograph performance was measured using Harrell’s concordance index(C-index),calibration curve,receiver operating characteristic(ROC)curve,and area under the ROC curve(AUC)value.Moreover,the net benefit was estimated via decision curve analysis(DCA).RESULTS The study included 21545 HCC patients,of whom 619 died of CVD.Age(<60)[1.981(1.573-2.496),P<0.001],marital status(married)[unmarried:1.370(1.076-1.745),P=0.011],alpha fetoprotein(normal)[0.778(0.640-0.946),P=0.012],tumor size(≤2 cm)[(2,5]cm:1.420(1.060-1.903),P=0.019;>5 cm:2.090(1.543-2.830),P<0.001],surgery(no)[0.376(0.297-0.476),P<0.001],and chemotherapy(none/unknown)[0.578(0.472-0.709),P<0.001]were independent risk factors for CVD death in HCC patients.The discrimination and calibration of the nomograph were better.The C-index values for the training and validation sets were 0.736 and 0.665,respectively.The AUC values of the ROC curves at 2,4,and 6 years were 0.702,0.725,0.740 in the training set and 0.697,0.710,0.744 in the validation set,respectively.The calibration curves showed that the predicted probab-ilities of the CVM prediction model in the training set vs the validation set were largely consistent with the actual probabilities.DCA demonstrated that the prediction model has a high net benefit.CONCLUSION Risk factors for CVD death in HCC patients were investigated for the first time.The nomograph served as an important reference tool for relevant clinical management decisions.

Prognostic characterization of copper death-related immune checkpoint genes and analysis of immunologic and pharmacologic therapy in bladder cancer

Objective:Copper death-induced tumor cell death and immune checkpoint blockade therapy are highly selective.Combining their advantages and understanding their characteristics in bladder cancer is very important for the development of new targeted therapy.The identification of bladder cancer by screening the characteristic genes of copper death-related immune checkpoints provide a theoretical basis for the selection of adjuvant treatment options and the application of new targets.Methods:The expression samples of normal bladder tissue and bladder cancer were obtained from TCGA and GEO databases,and 13 cop-per death genes and 79 immune checkpoint genes were extracted from previous studies.The mRNA expression of prognostic genes was verified by qPCR.The copper death-related immune checkpoint genes were screened by correlation analysis to construct a prognostic model,and the differences in the efficacy of immunotherapy and chemotherapy between the high-risk group and the low-risk group were evaluated.Results:A prognostic model consisting of BTNL9,CD160,TNFRSF14 and TNFRSF18 was constructed.Its reliable predictive ability was proved in both databases,and qPCR showed that the expression levels of the four genes were significantly different between the normal group and the cancer cell group.The effect of immunotherapy in the lowrisk group was better than that in the high-risk group.Patients in the high-risk group had better chemotherapy efficacy.Conclusion:The copper death-related immune checkpoint gene model can accurately predict the prognosis of patients.Drug and immune analysis provide a basis for clinical treatment,and the discovery of potential targets provides a new solution for clinical decision-making.

Roles of the tumor microenvironment in the resistance to programmed cell death protein 1 inhibitors in patients with gastric cancer

Despite the continuous developments and advancements in the treatment of gastric cancer(GC),which is one of the most prevalent types of cancer in China,the overall survival is still poor for most patients with advanced GC.In recent years,with the progress in tumor immunology research,attention has shifted toward immunotherapy as a therapeutic approach for GC.Programmed cell death protein 1(PD-1)inhibitors,as novel immunosuppressive medications,have been widely utilized in the treatment of GC.However,many patients are still resistant to PD-1 inhibitors and experience recurrence in the advanced stages of PD-1 immunotherapy.To reduce the occurrence of drug resistance and recurrence in GC patients receiving PD-1 immunotherapy,to maximize the clinical activity of immunosuppressive drugs,and to elicit a lasting immune response,it is essential to research the tumor microenvironment mechanisms leading to PD-1 inhibitor resistance in GC patients.This article reviews the progress in studying the factors influencing the resistance to PD-1 inhibitors in the GC tumor microenvironment,aiming to provide insights and a basis for reducing resistance to PD-1 inhibitors for GC patients in the future.

Establishment of human cerebral organoid systems to model early neural development and assess the central neurotoxicity of environmental toxins

Human brain development is a complex process,and animal models often have significant limitations.To address this,researchers have developed pluripotent stem cell-derived three-dimensional structures,known as brain-like organoids,to more accurately model early human brain development and disease.To enable more consistent and intuitive reproduction of early brain development,in this study,we incorporated forebrain organoid culture technology into the traditional unguided method of brain organoid culture.This involved embedding organoids in matrigel for only 7 days during the rapid expansion phase of the neural epithelium and then removing them from the matrigel for further cultivation,resulting in a new type of human brain organoid system.This cerebral organoid system replicated the temporospatial characteristics of early human brain development,including neuroepithelium derivation,neural progenitor cell production and maintenance,neuron differentiation and migration,and cortical layer patterning and formation,providing more consistent and reproducible organoids for developmental modeling and toxicology testing.As a proof of concept,we applied the heavy metal cadmium to this newly improved organoid system to test whether it could be used to evaluate the neurotoxicity of environmental toxins.Brain organoids exposed to cadmium for 7 or 14 days manifested severe damage and abnormalities in their neurodevelopmental patterns,including bursts of cortical cell death and premature differentiation.Cadmium exposure caused progressive depletion of neural progenitor cells and loss of organoid integrity,accompanied by compensatory cell proliferation at ectopic locations.The convenience,flexibility,and controllability of this newly developed organoid platform make it a powerful and affordable alternative to animal models for use in neurodevelopmental,neurological,and neurotoxicological studies.

Elucidating the molecular basis of ATP-induced cell death in breast cancer: Construction of a robust prognostic model

BACKGROUND Breast cancer is a multifaceted and formidable disease with profound public health implications.Cell demise mechanisms play a pivotal role in breast cancer pathogenesis,with ATP-triggered cell death attracting mounting interest for its unique specificity and potential therapeutic pertinence.AIM To investigate the impact of ATP-induced cell death(AICD)on breast cancer,enhancing our understanding of its mechanism.METHODS The foundational genes orchestrating AICD mechanisms were extracted from the literature,underpinning the establishment of a prognostic model.Simultaneously,a microRNA(miRNA)prognostic model was constructed that mirrored the gene-based prognostic model.Distinctions between high-and low-risk cohorts within mRNA and miRNA characteristic models were scrutinized,with the aim of delineating common influence mechanisms,substantiated through enrichment analysis and immune infiltration assessment.RESULTS The mRNA prognostic model in this study encompassed four specific mRNAs:P2X purinoceptor 4,pannexin 1,caspase 7,and cyclin 2.The miRNA prognostic model integrated four pivotal miRNAs:hsa-miR-615-3p,hsa-miR-519b-3p,hsa-miR-342-3p,and hsa-miR-324-3p.B cells,CD4+T cells,CD8+T cells,endothelial cells,and macrophages exhibited inverse correlations with risk scores across all breast cancer subtypes.Furthermore,Kyoto Encyclopedia of Genes and Genomes analysis revealed that genes differentially expressed in response to mRNA risk scores significantly enriched 25 signaling pathways,while miRNA risk scores significantly enriched 29 signaling pathways,with 16 pathways being jointly enriched.CONCLUSION Of paramount significance,distinct mRNA and miRNA signature models were devised tailored to AICD,both potentially autonomous prognostic factors.This study's elucidation of the molecular underpinnings of AICD in breast cancer enhances the arsenal of potential therapeutic tools,offering an unparalleled window for innovative interventions.Essentially,this paper reveals the hitherto enigmatic link between AICD and breast cancer,potentially leading to revolutionary progress in personalized oncology.

Efficacy of chemotherapy containing bevacizumab in patients with metastatic colorectal cancer according to programmed cell death ligand 1

BACKGROUND Bevacizumab,an anti-vascular endothelial growth factor(VEGF)monoclonal antibody,inhibits angiogenesis and reduces tumor growth.Serum VEGF-C,lactate dehydrogenase,and inflammatory markers have been reported as predictive markers related to bevacizumab treatment.Programmed cell death ligand 1(PD-L1)could act upon VEGF receptor 2 to induce cancer cell angiogenesis and metastasis.AIM To investigate the efficacy of bevacizumab-containing chemotherapy in patients with metastatic colorectal cancer(CRC)according to the expression of PD-L1.METHODS This analysis included CRC patients who received bevacizumab plus FOLFOX or FOLFIRI as first-line therapy between June 24,2014 and February 28,2022,at Samsung Medical Center(Seoul,South Korea).Analysis of patient data included evaluation of PD-L1 expression by the combined positive score(CPS).We analyzed the efficacy of bevacizumab according to PD-L1 expression status in patients with CRC.RESULTS A total of 124 patients was included in this analysis.Almost all patients were treated with bevacizumab plus FOLFIRI or FOLFOX as the first-line chemotherapy.While 77%of patients received FOLFOX,23%received FOLFIRI as backbone first-line chemotherapy.The numbers of patients with a PD-L1 CPS of 1 or more,5 or more,or 10 or more were 105(85%),64(52%),and 32(26%),respectively.The results showed no significant difference in progression-free survival(PFS)and overall survival(OS)with bevacizumab treatment between patients with PDL1 CPS less than 1 and those with PD-L1 CPS of 1 or more(PD-L1<1%vs PD-L1≥1%;PFS:P=0.93,OS:P=0.33),between patients with PD-L1 CPS less than 5 and of 5 or more(PD-L1<5%vs PD-L1≥5%;PFS:P=0.409,OS:P=0.746),and between patients with PD-L1 CPS less than 10 and of 10 or more(PD-L1<10%vs PD-L1≥10%;PFS:P=0.529,OS:P=0.568).CONCLUSION Chemotherapy containing bevacizumab can be considered as first-line therapy in metastatic CRC irrespective of PD-L1 expression.

Risk scores for allograft failure: Are they still useful in liver recipients from donation after circulatory death?

BACKGROUND Liver grafts from donation after circulatory death(DCD)are associated with a higher risk of early graft dysfunction,determined by the warm ischemia and cold ischemia times.It is essential to have precise criteria to identify this complication in order to guide therapeutic strategies.AIM To validate different graft and recipient survival scores in patients undergoing liver transplantation(LT)with DCD grafts.METHODS A retrospective and observational unicentric study was conducted on 65 LT patients with grafts obtained from controlled DCD donors from November 2013 to November 2022.The United Kingdom(UK)risk score,early allograft dysfunction(EAD)Olthoff score,and model for early allograft function(MEAF)score were used to evaluate the risk of graft and recipient survival post-transplant.For survival analysis purposes,we used the Kaplan-Meier method,and the differences between subgroups were compared using the log-rank(Mantel-Cox)test.RESULTS Sixty-five patients were included in the study.The UK risk score did not demonstrate predictive capacity for recipient or graft survival.However,in donors aged over 70 years old(18.4%),it significantly predicted graft survival(P<0.05).According to Kaplan-Meier survival curves,graft survival rates at 6 months,2 years,and 5 years in the futility group dramatically decreased to 50%compared to the other groups(log-rank 8.806,P<0.05).The EAD Olthoff and MEAF scores did not demonstrate predictive capacity for recipient or graft survival.Based on Kaplan-Meier survival curves,patients with a MEAF score≥7 had a lower graft survival rate at 6 months,2 years,and 5 years compared to patients with a lower MEAF score(log-rank 4.667,P<0.05).CONCLUSION In our series,both UK DCD risk score and MEAF score showed predictive capability for graft survival.

Effectiveness and tolerability of programmed cell death protein-1 inhibitor+chemotherapy compared to chemotherapy for upper gastrointestinal tract cancers

BACKGROUND The combination of programmed cell death protein-1(PD-1)inhibitor and che-motherapy is approved as a standard first-or second-line treatment in patients with advanced oesophageal or gastric cancer.However,it is unclear whether this combination is superior to chemotherapy alone.AIM To assess the comparative effectiveness and tolerability of combining PD-1 inhibitors with chemotherapy vs chemotherapy alone in patients with advanced gastric cancer,gastroesophageal junction(GEJ)cancer,or oesophageal carcinoma.METHODS We searched the PubMed and Embase databases for studies that compared the efficacy and tolerance of PD-1 inhibitors in combination with chemotherapy vs chemotherapy alone in patients with advanced oesophageal or gastric cancer.We employed either random or fixed models to analyze the outcomes of each clinical trial,en-compassing data on overall survival(OS),progression-free survival(PFS),objective response rate,and adverse events(AEs).RESULTS Nine phase 3 clinical trials(7016 advanced oesophageal and gastric cancer patients)met the inclusion criteria.Our meta-analysis demonstrated that the pooled PD-1 inhibitor+chemotherapy group had a significantly longer OS than the chemotherapy-alone group[hazard ratio(HR)=0.76,95%confidence interval(CI):0.71-0.81];the pooled PFS result was consistent with that of OS(HR=0.67,95%CI:0.61-0.74).The count of patients achieving an objective response in the PD-1 inhibitor+chemotherapy group surpassed that of the chemotherapy-alone group[odds ratio(OR)=1.86,95%CI:1.59-2.18].AE incidence was also higher in the combination-therapy group than in the chemotherapy-alone group,regardless of whether≥grade 3 only(OR=1.30,95%CI:1.07-1.57)or all AE grades(OR=1.88,95%CI:1.39-2.54)were examined.We performed a subgroup analysis based on the programmed death-ligand 1(PD-L1)combined positive score(CPS)and noted extended OS and PFS durations within the CPS≥1,CPS≥5,and CPS≥10 subgroups of the PD-1 inhibitor+chemotherapy group.CONCLUSION In contrast to chemotherapy alone,the combination of PD-1 inhibitor and chemotherapy appears to present a more favorable option for initial or subsequent treatment in patients with gastric cancer,GEJ tumor,or oesophageal cancer.This holds true particularly for individuals with PD-L1 CPS scores of≥5 and≥10.

Analysis of the Necessity and Modalities of Imparting Death Education to Medical Students Undergoing Training in Oncology Departments

Patients with advanced-stage tumors may experience various psychological problems that can have a significant impact on the effectiveness of cancer treatment and the quality of their survival.Therefore,it is crucial for oncologists to prioritize addressing the psychological issues that patients encounter throughout the diagnosis and treatment process.As future frontline healthcare professionals,oncology medical students should receive education on end-of-life care early on in their training.This will enable them to develop a profound appreciation for the value of life,deliver improved medical services,and contribute to the humanization of medicine.Furthermore,they will be able to provide terminal patients and their families with effective professional guidance,assisting patients in finding peaceful endings with minimal pain and helping families come to terms with the inevitable realities they face.Moreover,this education can effectively enhance their sense of responsibility toward life and cultivate a positive and optimistic attitude toward their own lives.

Normothermic regional perfusion mobile teams in controlled donation after circulatory death pathway: Evidence and peculiarities

To facilitate the implementation of controlled donation after circulatory death(cDCD)programs even in hospitals not equipped with a local Extracorporeal Membrane Oxygenation(ECMO)team(Spokes),some countries and Italian Regions have launched a local cDCD network with a ECMO mobile team who move from Hub hospitals to Spokes for normothermic regional perfusion(NRP)implantation in the setting of a cDCD pathway.While ECMO teams have been clearly defined by the Extracorporeal Life Support Organization,regarding composition,responsibilities and training programs,no clear,widely accepted indications are to date available for NRP teams.Although existing NRP mobile networks were developed due to the urgent need to increase the number of cDCDs,there is now the necessity for transplantation medicine to identify the peculiarities and responsibility of a NRP team for all those centers launching a cDCD pathway.Thus,in the present manuscript we summarized the character-istics of an ECMO mobile team,highlighting similarities and differences with the NRP mobile team.We also assessed existing evidence on NRP teams with the goal of identifying the characteristic and essential features of an NRP mobile team for a cDCD program,especially for those centers who are starting the program.Differences were identified between the mobile ECMO team and NRP mobile team.The common essential feature for both mobile teams is high skills and experience to reduce complications and,in the case of cDCD,to reduce the total warm ischemic time.Dedicated training programs should be developed for the launch of de novo NRP teams.