Prognostic Factors Related to In-hospital Death in Children with Biliary Atresia:Analysis of a Nationwide Inpatient Database

Background and Aims:Patients with biliary atresia(BA)are prone to hepatic decompensation,which might eventually lead to death.This study aimed to identify the possible risk factors affecting in-hospital death in BA patients in China.Methods:We collected data from the Hospital Quality Monitoring System,a national inpatient database.All patients aged up to 2 years old with a diagnosis of BA were included.The subjects were divided to three groups,including Kasai portoenterostomy(KP),liver transplantation(LT),and no surgery.Logistic regression with Firth’s method was performed to identify potential influencing variables associated with in-hospital death.Results:During the year 2013 to 2017,there were 14,038 pediatric admissions with a diagnosis of BA.The proportion of in-hospital death in pediatric BA admissions was 1.08%.Compared with patients under six months,there was a higher risk of in-hospital death for children aged six months to 1 year and 1–2 years old.Clinical signs,including cirrhosis,variceal bleeding,and hepatic encephalopathy,were significantly associated with the risk of in-hospital death.In no surgery group,compared to those in Beijing and Shanghai,BA patients admitted in other districts had a lower risk of in-hospital death(OR=0.39,95%CI:0.21,0.70).However,in the LT group,patients admitted in other districts had a higher risk of in-hospital death(OR=9.13,95%CI:3.99,20.87).Conclusions:In-hospital survival remains unsatisfactory for pediatric BA patients with severe complications.Furthermore,more resources and training for BA treatment,especially LT,are essential for districts with poor medical care in the future.

Risk factors analysis for in-hospital death of acute Stanford type B aortic dissection

Background Data is limited regarding the correlation between related factors and in-hospital death of Stan- ford type B acute aortic dissection （AAD）. Methods We registered consecutive Stanford type B AAD patients, who were in the Guangdong Cardiovascular Institute of Guangdong General Hospital from October 2010 to August 2011, and the onset day to admission day were less than or equal to 2 weeks. We collected in-hospital mortality, history of disease, laboratory parameters, some biochemical markers tests, treatment and so on, analyzed the relationship between risk factors and mortality. Results One hundred and five Stanford B AAD patients were enrolled, 9 patients died, accounting for 8.6%. There are 24 patients treated with medicine, and 4 cases finally died. Endovascular aortic repair （EVAR） 62 cases, 2 cases died. EVAR combined carotid artery bypass （CAB） 19 cases, and 3 cases died. Among the three treatments, there was no significant difference in statistics （P = 0.063）. Compared with the survivors, the death group had higher D-dimer （P = 0.016） and NT-proBNP （P = 0.014） level, and more patients with myocardial infarction （P = 0.007）, hypotension or shock （P = 0.019）, a- cute renal failure （P = 0.005）, nervous system related events （P 〈 0.001 ）. After adjusting for other predictors of in-hospital death, logistic regression analysis shows that the nervous system related events （odds ratio： 21.648; 95% CI： 1.228-381.704, P = 0.036 is the independent risk factor for death. Conclusions D-dimer, hypotension or shock, acute renal failure, nervous system related events are associated with hospitalization death of Stanford type B AAD patients, while nervous system related events is an independent risk factor for in-hospital death.

Without preprocedural aspirin, PCI carries higher risk of in-hospital death, stroke

Key points： Registry study looks at preprocedural aspirin use in more than 65,000 patients undergoing PCI Aspirin not given to 7%, with only a small minority having a documented contraindication In-hospital death, stroke risk both higher without aspirin

Development and validation of an emergency bloodstream infection score for predicting in-hospital mortality in patients with community-acquired bloodstream infections

BACKGROUND:Community-acquired bloodstream infections(CABSIs)are common in the emergency departments,and some progress to sepsis and even lead to death.However,limited information is available regarding the prediction of patients with high risk of death.METHODS:The Emergency Bloodstream Infection Score(EBS)for CABSIs was developed to visualize the output of a logistic regression model and was validated by the area under the curve(AUC).The Mortality in Emergency Department Sepsis(MEDS),Pitt Bacteremia Score(PBS),Sequential Organ Failure Assessment(SOFA),quick Sequential Organ Failure Assessment(qSOFA),Charlson Comorbidity Index(CCI),and McCabe–Jackson Comorbid Classification(MJCC)for patients with CABSIs were computed to compare them with EBS in terms of the AUC and decision curve analysis(DCA).The net reclassification improvement(NRI)index and integrated discrimination improvement(IDI)index were compared between the SOFA and EBS.RESULTS:A total of 547 patients with CABSIs were included.The AUC(0.853)of the EBS was larger than those of the MEDS,PBS,SOFA,and qSOFA(all P<0.001).The NRI index of EBS in predicting the in-hospital mortality of CABSIs patients was 0.368(P=0.04),and the IDI index was 0.079(P=0.03).DCA showed that when the threshold probability was<0.1,the net benefit of the EBS model was higher than those of the other models.CONCLUSION:The EBS prognostic models were better than the SOFA,qSOFA,MEDS,and PBS models in predicting the in-hospital mortality of patients with CABSIs.

Comparison of Child-Pugh, MELD, MELD-Na, and ALBI Scores in Predicting In-Hospital Mortality in Patients with HCC

Background & Objectives: Hepatocellular carcinoma (HCC) leads to high morbidity and mortality. Various models have been proposed for predicting the outcome of patients with HCC. We aim to compare the prognostic abilities of Child-Pugh, MELD, MELD-Na, and ALBI scores for predicting in-hospital mortality of HCC. Methods: We enrolled patients diagnosed with liver cirrhosis and HCC from May 2017 through May 2018. We further divided eligible patients into hepatitis B virus (HBV), patients without ascites, and patients with ascites subgroups. Areas under the characteristic curves (AUCs) were analyzed. Results: A total of 495 patients were included in the study. We collected data on patients at admission. A majority of patients were infected with HBV (91.5%). None of them were complicated with hepatic encephalopathy. Only 14.9% of patients presented with ascites. In the whole population, AUCs with 95% confidence interval (CI) of Child-Pugh, ALBI, MELD, and MELD-Na scores in predicting in-hospital mortality were 0.889 (95% CI: 0.858 - 0.915), 0.849 (95% CI: 0.814 - 0.879), 0.669 (95% CI: 0.626 - 0.711), and 0.721 (95% CI: 0.679 - 0.760), respectively. In the patients without ascites subgroup, Child-Pugh showed better discriminatory ability than ALBI score in predicting in-hospital mortality (P = 0.0002), while there were no significant differences among other comparisons. Conclusions: Child-Pugh and ALBI may be useful predictors for predicting in-hospital mortality in whole patients, in patients with HBV infection, and in patients without ascites. In HCC patients with ascites, MELD-Na may be effective for predicting in-hospital mortality.

Effect of internet multiple linkage mode-based extended care combined with in-hospital comfort care on colorectal cancer patients undergoing colostomy

BACKGROUND Patients with colorectal cancer may need postoperative nursing to improve prognosis,and conventional nursing is not effective.Clinical research is needed to explore nursing methods that can more effectively improve postoperative conditions on colorectal cancer patients undergoing colostomy.AIM To explore the effect of internet multiple linkage mode-based extended care combined with in-hospital comfort care on colorectal cancer patients undergoing colostomy.METHODS Data from 187 patients with colostomy treated in our hospital from May 2019 to March 2022 were collected and divided into three groups,A(n=62),B(n=62)and C(n=63),according to different intervention methods.Group A received internet multiple linkage mode-based extended care combined with in-hospital comfort care.Group B received internet multiple linkage mode-based extended care.Group C received usual care intervention.Complications were compared among the three groups.The stoma self-efficacy scale,Hamilton Anxiety Scale,RESULTS The complication rate of group A,B and C(16.13%,20.97%and 60.32%,respectively)was significantly different(all P<0.05).The incidence of complications in groups A and B was lower than that in group C,and there was no significant difference between groups A and B(P>0.05).After intervention,the scores of ostomy care,social contact,diet choice,confidence in maintaining vitality,confidence in self-care of ostomy,confidence in sexual life,confidence in sexual satisfaction and confidence in physical labor in the three groups were all higher than before intervention,and the scores of groups A and B were higher than those of group C,with statistical significance(P<0.05).The Hamilton Anxiety Scale and Hamilton Depression Scale scores of the three groups after intervention were lower than those before intervention.The scores of groups A and B were lower than those of group C,and the score of group A was lower than that of group B,all with statistical significance(all P<0.05).There was a statist-ically significant difference in cancer-induced fatigue among the three groups(P<0.05).After intervention,the scores of physical health,psychological health,social health and mental health of the three groups were lower than before the intervention.The scores of group A and B were lower than that of group C;and the score of group A was lower than that of group B,all with statistical significance(all P<0.05).CONCLUSION Internet multiple linkage mode-based extended care combined with in-hospital comfort care can effectively improve self-efficacy,bad mood,cancer-related fatigue and life quality of colorectal cancer patients undergoing colostomy.

A novel approach to Parkinson's disease treatment with a potentially dual-acting therapeutic agent that targetsα-synuclein aggregation and neuron death

Parkinson's disease(PD),a prevalent neurodegenerative disorder,is chara cterized by the loss of dopaminergic neurons and the aggregation ofα-synuclein protein into Lewy bodies.While the current standards of therapy have been successful in providing some symptom relief,they fail to address the underlying pathophysiology of PD and as a result,they have no effect on disease progression.

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.

Quercetin Alleviates Lipopolysaccharide-Induced Cardiac Inflammation via Inhibiting Autophagy and Programmed Cell Death

Objective The aim of this study is to explore the potential modulatory role of quercetin against Endotoxin or lipopolysaccharide(LPS)induced septic cardiac dysfunction.Methods Specific pathogen-free chicken embryos(n=120)were allocated untreated control,phosphate buffer solution(PBS)vehicle,PBS with ethanol vehicle,LPS(500 ng/egg),LPS with quercetin treatment(10,20,or 40 nmol/egg,respectively),Quercetin groups(10,20,or 40 nmol/egg).Fifteenday-old embryonated eggs were inoculated with abovementioned solutions via the allantoic cavity.At embryonic day 19,the hearts of the embryos were collected for histopathological examination,RNA extraction,real-time polymerase chain reaction,immunohistochemical investigations,and Western blotting.Results They demonstrated that the heart presented inflammatory responses after LPS induction.The LPS-induced higher mRNA expressions of inflammation-related factors(TLR4,TNFα,MYD88,NF-κB1,IFNγ,IL-1β,IL-8,IL-6,IL-10,p38,MMP3,and MMP9)were blocked by quercetin with three dosages.Quercetin significantly decreased immunopositivity to TLR4 and MMP9 in the treatment group when compared with the LPS group.Quercetin significantly decreased protein expressions of TLR4,IFNγ,MMP3,and MMP9 when compared with the LPS group.Quercetin treatment prevented LPS-induced increase in the mRNA expression of Claudin 1 and ZO-1,and significantly decreased protein expression of claudin 1 when compared with the LPS group.Quercetin significantly downregulated autophagyrelated gene expressions(PPARα,SGLT1,APOA4,AMPKα1,AMPKα2,ATG5,ATG7,Beclin-1,and LC3B)and programmed cell death(Fas,Bcl-2,CASP1,CASP12,CASP3,and RIPK1)after LPS induction.Quercetin significantly decreased immunopositivity to APOA4,AMPKα2,and LC3-II/LC3-I in the treatment group when compared with the LPS group.Quercetin significantly decreased protein expressions of AMPKα1,LC3-I,and LC3-II.Quercetin significantly decreased the protein expression to CASP1 and CASP3 by immunohistochemical investigation or Western blotting in treatment group when compared with LPS group.Conclusion Quercetin alleviates cardiac inflammation induced by LPS through modulating autophagy,programmed cell death,and myocardiocytes permeability.

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.

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.

Challenging situation of coronary artery anomaly associated with ischemia and/or risk of sudden death

Coronary artery anomaly is known as one of the causes of angina pectoris and sudden death and is an important clinical entity that cannot be overlooked.The incidence of coronary artery anomalies is as low as 1%-2%of the general population,even when the various types are combined.Coronary anomalies are practically challenging when the left and right coronary ostium are not found around their normal positions during coronary angiography with a catheter.If there is atherosclerotic stenosis of the coronary artery with an anomaly and percutaneous coronary intervention(PCI)is required,the suitability of the guiding catheter at the entrance and the adequate back up force of the guiding catheter are issues.The level of PCI risk itself should also be considered on a caseby-case basis.In this case,emission computed tomography in the R-1 subtype single coronary artery proved that ischemia occurred in an area where the coronary artery was not visible to the naked eye.Meticulous follow-up would be crucial,because sudden death may occur in single coronary arteries.To prevent atherosclerosis with full efforts is also important,as the authors indicated admirably.

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%).

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.

Assessment of programmed death-ligand 1 expression in primary tumors and paired lymph node metastases of gastric adenocarcinoma

BACKGROUND Anti-programmed death-1/programmed death-ligand 1(PD-1/PD-L1)immuno-therapy has demonstrated promising results on gastric cancer(GC).However,PD-L1 can express differently between metastatic sites and primary tumors(PT).AIM To compare PD-L1 status in PT and matched lymph node metastases(LNM)of GC patients and to determine the correlation between the PD-L1 status and clinicopathological characteristics.METHODS We retrospectively reviewed 284 GC patients who underwent D2-gastrectomy.PD-L1 was evaluated by immunohistochemistry(clone SP142)using the com-bined positive score.All PD-L1+PT staged as pN+were also tested for PD-L1 expression in their LNM.PD-L1(-)GC with pN+served as the comparison group.RESULTS Among 284 GC patients included,45 had PD-L1+PT and 24 of them had pN+.For comparison,44 PD-L1(-)cases with pN+were included(sample loss of 4 cases).Of the PD-L1+PT,54.2%(13/24 cases)were also PD-L1+in the LNM.Regarding PD-L1(-)PT,9.1%(4/44)had PD-L1+in the LNM.The agreement between PT and LNM had a kappa value of 0.483.Larger tumor size and moderate/severe peritumoral inflammatory response were associated with PD-L1 positivity in both sites.There was no statistical difference in overall survival for PT and LNM according to the PD-L1 status(P=0.166 and P=0.837,respectively).CONCLUSION Intra-patient heterogeneity in PD-L1 expression was observed between the PT and matched LNM.This disagreement in PD-L1 status may emphasize the importance of considering different tumor sites for analyses to select patients for immunotherapy.

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.

Efficacy and predictive factors of transarterial chemoembolization combined with lenvatinib plus programmed cell death protein-1 inhibition for unresectable hepatocellular carcinoma

BACKGROUND The efficacy and safety of transarterial chemoembolization(TACE)combined with lenvatinib plus programmed cell death protein-1(PD-1)for unresectable hepato-cellular carcinoma(HCC)have rarely been evaluated and it is unknown which factors are related to efficacy.AIM To evaluate the efficacy and independent predictive factors of TACE combined with lenvatinib plus PD-1 inhibitors for unresectable HCC.METHODS This study retrospectively enrolled patients with unresectable HCC who received TACE/lenvatinib/PD-1 treatment between March 2019 and April 2022.Overall survival(OS)and progression-free survival(PFS)were determined.The objective response rate(ORR)and disease control rate(DCR)were evaluated in accordance with the modified Response Evaluation Criteria in Solid Tumors.Additionally,the prognostic factors affecting the clinical outcome were assessed.RESULTS One hundred and two patients were enrolled with a median follow-up duration of 12.63 months.The median OS was 26.43 months(95%CI:17.00-35.87),and the median PFS was 10.07 months(95%CI:8.50-11.65).The ORR and DCR were 61.76%and 81.37%,respectively.The patients with Barcelona Clinic Liver Cancer Classification(BCLC)B stage,early neutrophil-to-lymphocyte ratio(NLR)response(decrease),or early alpha-fetoprotein(AFP)response(decrease>20%)had superior OS and PFS than their counterparts.CONCLUSION This study showed that TACE/lenvatinib/PD-1 treatment was well tolerated with encouraging efficacy in patients with unresectable HCC.The patients with BCLC B-stage disease with early NLR response(decrease)and early AFP response(decrease>20%)may achieve better clinical outcomes with this triple therapy.