BACKGROUND The cardiovascular hazards of total homocysteine(tHcy)are long known.In addition,despite the acknow-ledgment on the importance of low ankle-brachial index(ABI)(<0.9),borderline ABI(0.91-0.99)was once com...BACKGROUND The cardiovascular hazards of total homocysteine(tHcy)are long known.In addition,despite the acknow-ledgment on the importance of low ankle-brachial index(ABI)(<0.9),borderline ABI(0.91-0.99)was once commonly overlooked.This study aims to explore the independent and joint effect of tHcy level and borderline ABI on all-cause death in hypertensive population.METHODS This study included 10,538 participants from China H-type Hypertension Registry Study.ABI was described into two groups:normal ABI(1.00-1.40)and borderline ABI.tHcy level was also divided into two groups:<15.02 and≥15.02μmo/L.Four groups were analyzed,using COX proportional hazard regression model,separately and pairwise to observe the independ-ent and joint effect on all-cause death.RESULTS A total of 126(1.2%)deaths were observed in the 1.7 years follow-up time.Borderline ABI has a higher predicted risk of death than normal ABI(HR=1.87,95%CI:1.17-3.00)after adjusting for potential covariates.Compare with tHcy level<15.02μmo/L(low tHcy),those with tHcy≥15.02μmo/L(high tHcy)had higher risk to event outcome(HR=1.99,95%CI:1.30-3.05).According to the cumulative hazard curve,group with borderline ABI and high tHcy level has significantly higher altitude and larger increasing rate over follow-up period compare to other groups.Among those with borderline ABI,participants with high tHcy had higher death risk than those with low tHcy,nevertheless,no significant different between borderline and normal ABI among those with low tHcy levels.CONCLUSIONS Borderline ABI and tHcy level both have independent predictive value on all-cause death.The combined group of borderline ABI and high tHcy has highest risk factor of outcomes,which suggested the mutual additive value of border-line ABI and tHcy.More attention should be given to the importance of borderline ABI in hypertensive population,especially with elevated tHcy level.展开更多
Objective: To determine the impact of pulmonary hypertension (PH) on maintenance hemodialysis (MHD) patients' cardiovascular events and all-cause mortality. Methods: We included 90 MHD patients, divided into group...Objective: To determine the impact of pulmonary hypertension (PH) on maintenance hemodialysis (MHD) patients' cardiovascular events and all-cause mortality. Methods: We included 90 MHD patients, divided into group with PH and group without PH. All patients had been followed up for 4 years, and the primary endpoints were all cause mortality and cardiovascular events. We compared the clinical data and the endpoint events between the two groups. Results: We found PH in 37 patients (41.11%). The incidence of previous cardiovascular disease in group with PH was significantly higher than that in group without PH (χ2=2.034, P < 0.05). The left atrial diameter in group with PH was significantly higher than that in group without PH (t = 7.265, P < 0.01). Logistic regression analysis revealed that previous cardiovascular disease and left atrial diameter were the independent determinants of PH. The rate of new cardiovascular events in group with PH(59.5%) was significantly higher than that in group without PH(34%) (χ2=9.203, P < 0.05). The associated variables of cardiovascular events were:systolic pulmonary arterial pressure, age, history cardiovascular disease, hs-CRP, ejection fraction, left ventricular diastolic dysfunction. In a multivariate model, the PH maintained its independent association. The mortality rate in group with PH (48.6%) was significantly higher than that in group without PH (26.4%) (χ2=5.049, P <0.05). In the Cox survival analysis, we found an association between mortality and systolic pulmonary arterial pressure, age, previous cardiovascular disease, Alb, ejection fraction. In a multivariate model the PH remains as independent predictor of mortality. Conclusion:Pulmonary hypertension is common in HD patients and a valuable predictor of mortality and cardiovascular events.展开更多
BACKGROUND Left ventricular hypertrophy(LVH)is prevalent in obese individuals.Besides,both of LVH and obesity is as-sociated with subclinical LV dysfunction.The study aims to investigate the interplay between body fat...BACKGROUND Left ventricular hypertrophy(LVH)is prevalent in obese individuals.Besides,both of LVH and obesity is as-sociated with subclinical LV dysfunction.The study aims to investigate the interplay between body fat and LVH in relation to all-cause death in patients with coronary artery disease(CAD).METHODS In this retrospective cohort study,a total of 2243 patients with angiographically proven CAD were included.Body fat and LV mass were calculated using established formulas.Patients were grouped according to body fat percentage and pres-ence or absence of LVH.Cox-proportional hazard models were used to observe the interaction effect of body fat and LVH on all-cause death.RESULTS Of 2243 patients enrolled,560(25%)had a higher body fat percentage,and 1045(46.6%)had LVH.After a median follow-up of 2.2 years,the cumulative mortality rate was 8.2%in the group with higher body fat and LVH,2.5%in those with lower body fat and no LVH,5.4%in those with higher body fat and no LVH,and 7.8%in those with lower body fat and LVH(log-rank P<0.001).There was a statistically significant interaction between body fat percentage and LVH(P interaction was 0.003).After correcting for confounding factors,patients with higher body fat and LVH had the highest risk of all-cause death(HR=3.49,95%CI:1.40-8.69,P=0.007)compared with those with lower body fat and no LVH;in contrast,patients with higher body fat and no LVH had no statistically significant difference in risk of death compared with those with lower body fat and no LVH(HR=2.03,95%CI:0.70-5.92,P=0.195).CONCLUSION A higher body fat percentage was associated with a different risk of all-cause death in patients with CAD,strat-ified by coexistence of LVH or not.Higher body fat was significantly associated with a greater risk of mortality among patients with LVH but not among those without LVH.展开更多
BACKGROUND Numerous observational studies have documented a correlation between inflammatory bowel disease(IBD)and an increased risk of dementia.However,the causality of their associations remains elusive.AIM To asses...BACKGROUND Numerous observational studies have documented a correlation between inflammatory bowel disease(IBD)and an increased risk of dementia.However,the causality of their associations remains elusive.AIM To assess the causal relationship between IBD and the occurrence of all-cause dementia using the two-sample Mendelian randomization(MR)method.METHODS Genetic variants extracted from the large genome-wide association study(GWAS)for IBD(the International IBD Genetics Consortium,n=34652)were used to identify the causal link between IBD and dementia(FinnGen,n=306102).The results of the study were validated via another IBD GWAS(United Kingdom Biobank,n=463372).Moreover,MR egger intercept,MR pleiotropy residual sum and outlier,and Cochran's Q test were employed to evaluate pleiotropy and heterogeneity.Finally,multiple MR methods were performed to estimate the effects of genetically predicted IBD on dementia,with the inverse variance weighted approach adopted as the primary analysis.RESULTS The results of the pleiotropy and heterogeneity tests revealed an absence of significant pleiotropic effects or heterogeneity across all genetic variants in outcome GWAS.No evidence of a causal effect between IBD and the risk of dementia was identified in the inverse variance weighted[odds ratio(OR)=0.980,95%CI:0.942-1.020,P value=0.325],weighted median(OR=0.964,95%CI:0.914-1.017,P value=0.180),and MR-Egger(OR=0.963,95%CI:0.867-1.070,P value=0.492)approaches.Consistent results were observed in validation analyses.Reverse MR analysis also showed no effect of dementia on the development of IBD.Furthermore,MR analysis suggested that IBD and its subtypes did not causally affect allcause dementia and its four subtypes,including dementia in Alzheimer's disease,vascular dementia,dementia in other diseases classified elsewhere,and unspecified dementia.CONCLUSION Taken together,our MR study signaled that IBD and its subentities were not genetically associated with all-cause dementia or its subtypes.Further large prospective studies are warranted to elucidate the impact of intestinal inflammation on the development of dementia.展开更多
BACKGROUND The measurement of triceps skinfold(TSF)thickness serves as a noninvasive metric for evaluating subcutaneous fat distribution.Despite its clinical utility,the TSF thickness trajectories and their correlatio...BACKGROUND The measurement of triceps skinfold(TSF)thickness serves as a noninvasive metric for evaluating subcutaneous fat distribution.Despite its clinical utility,the TSF thickness trajectories and their correlation with overall mortality have not been thoroughly investigated.AIM To explore TSF thickness trajectories of Chinese adults and to examine their associations with all-cause mortality.METHODS This study encompassed a cohort of 14747 adults sourced from the China Health and Nutrition Survey.Latent class trajectory modeling was employed to identify distinct trajectories of TSF thickness.Subjects were classified into subgroups reflective of their respective TSF thickness trajectory.We utilized multivariate Cox regression analyses and mediation examinations to explore the link between TSF thickness trajectory and overall mortality,including contributory factors.RESULTS Upon adjustment for multiple confounding factors,we discerned that males in the‘Class 2:Thin-stable’and‘Class 3:Thin-moderate’TSF thickness trajectories exhibited a markedly reduced risk of mortality from all causes in comparison to the‘Class 1:Extremely thin’subgroup.In the mediation analyses,the Geriatric Nutritional Risk Index was found to be a partial intermediary in the relationship between TSF thickness trajectories and mortality.For females,a lower TSF thickness pattern was significantly predictive of elevated all-cause mortality risk exclusively within the non-elderly cohort.CONCLUSION In males and non-elderly females,lower TSF thickness trajectories are significantly predictive of heightened mortality risk,independent of single-point TSF thickness,body mass index,and waist circumference.展开更多
BACKGROUND Proton pump inhibitors(PPIs)are widely used,including among cancer patients,to manage gastroesophageal reflux and other gastric acid-related disorders.Recent evidence suggests associations between long-term...BACKGROUND Proton pump inhibitors(PPIs)are widely used,including among cancer patients,to manage gastroesophageal reflux and other gastric acid-related disorders.Recent evidence suggests associations between long-term PPI use and higher risks for various adverse health outcomes,including greater mortality.AIM To investigate the association between PPI use and all-cause mortality among cancer patients by a comprehensive analysis after adjustment for various confounders and a robust methodological approach to minimize bias.METHODS This retrospective cohort study used data from the TriNetX research network,with electronic health records from multiple healthcare organizations.The study employed a new-user,active comparator design,which compared newly treated PPI users with non-users and newly treated histamine2 receptor antagonists(H2RA)users among adult cancer patients.Newly prescribed PPIs(esomeprazole,lansoprazole,omeprazole,pantoprazole,or rabeprazole)users were compared to non-users or newly prescribed H2RAs(cimetidine,famotidine,nizatidine,or ranitidine)users.The primary outcome was all-cause mortality.Each patient in the main group was matched to a patient in the control group using 1:1 propensity score matching to reduce confounding effects.Multivariable Cox regression models were used to estimate hazard ratios(HRs)and 95% confidence interval(CI).RESULTS During the follow-up period(median 5.4±1.8 years for PPI users and 6.5±1.0 years for non-users),PPI users demonstrated a higher all-cause mortality rate than non-users after 1 year,2 years,and at the end of follow up(HRs:2.34-2.72).Compared with H2RA users,PPI users demonstrated a higher rate of all-cause mortality HR:1.51(95%CI:1.41-1.69).Similar results were observed across sensitivity analyses by excluding deaths from the first 9 months and 1-year post-exposure,confirming the robustness of these findings.In a sensitivity analysis,we analyzed all-cause mortality outcomes between former PPI users and individuals who have never used PPIs,providing insights into the long-term effects of past PPI use.In addition,at 1-year follow-up,the analysis revealed a significant difference in mortality rates between former PPI users and non-users(HR:1.84;95%CI:1.82-1.96).CONCLUSION PPI use among cancer patients was associated with a higher risk of all-cause mortality compared to non-users or H2RA users.These findings emphasize the need for cautious use of PPIs in cancer patients and suggest that alternative treatments should be considered when clinically feasible.However,further studies are needed to corroborate our findings,given the significant adverse outcomes in cancer patients.展开更多
BACKGROUND: We aimed to investigate whether the pressure injury risk mediates the association of left ventricular ejection fraction(LVEF) with all-cause death in patients with acute myocardial infarction(AMI) aged 80 ...BACKGROUND: We aimed to investigate whether the pressure injury risk mediates the association of left ventricular ejection fraction(LVEF) with all-cause death in patients with acute myocardial infarction(AMI) aged 80 years or older.METHODS: This retrospective cohort study included 677 patients with AMI aged 80 years or older from a tertiary-level hospital. Pressure injury risk was assessed using the Braden scale at admission, and three risk groups(low/minimal, intermediate, high) were defined according to the overall score of six different variables. LVEF was measured during the index hospitalization for AMI. All-cause death after hospital discharge was the primary outcome.RESULTS: Over a median follow-up period of 1,176 d(interquartile range [IQR], 722–1,900 d), 226(33.4%) patients died. Multivariate Cox regression analysis showed that reduced LVEF was associated with an increased risk of all-cause death only in the high-risk group of pressure injury(adjusted hazard ratios [HR]=1.81, 95% confidence interval [CI]: 1.03–3.20;P=0.040), but not in the low/minimal-(adjusted HR=1.29, 95%CI: 0.80–2.11;P=0.299) or intermediate-risk groups(adjusted HR=1.14, 95%CI: 0.65–2.02;P=0.651). Significant interactions were detected between pressure injury risk and LVEF(adjusted P=0.003). The cubic spline with hazard ratio plot revealed a distinct shaped curve relation between LVEF and all-cause death among different pressure injury risk groups.CONCLUSIONS: In older patients with AMI, the risk of pressure injury mediated the association between LVEF and all-cause death. The classification of older patients for both therapy and prognosis assessment appears to be improved by the incorporation of pressure injury risk assessment into AMI care management.展开更多
Background Post myocardial infarction (post-MI) patients with low left ventricular ejection fraction (LVEF) have been candidates for an implantable cardioverter-defibrillator (ICD) since the Multicenter Automati...Background Post myocardial infarction (post-MI) patients with low left ventricular ejection fraction (LVEF) have been candidates for an implantable cardioverter-defibrillator (ICD) since the Multicenter Automatic Defibrillator Implantation Trail Ⅱ (MADIT Ⅱ). However, due to the high costs of ICDs, widespread usage has not been accepted. Therefore, further risk stratification for post-MI patients with low LVEF may aid in the selection of patients that will benefit most from ICD treatment. Methods Four hundred and seventeen post-MI patients with low LVEF (≤35%) were enrolled in the study. All the patients received standard examination and proper treatment and were followed up to observe the all-cause death rate and sudden cardiac death (SCD) rate. Then COX proportional-hazards regression model was used to investigate the clinical factors which affect the all-cause death rate and SCD rate. Results Of 55 patients who died during (32±24) months of follow-up, 37 (67%) died suddenly. After adjusting for baseline clinical characteristics, multivariate COX proportional-hazards regression model identified the following variables associated with death from all causes: New York Heart Association (NYHA) heart failure class ≥Ⅲ (Hazard ratio: 2.361), LVEF ≤20% (Hazard ratio: 2.514), sustained ventricular tachycardia (Hazard ratio: 6.453), and age 〉70 years (Hazard ratio: 3.116). The presence of sustained ventricular tachycardia (Hazard ratio: 6.491) and age ≥70 years (Hazard ratio: 2.694) were specifically associated with SCD. Conclusions In the post-MI patients with low LVEF, factors as LVEF ≤20%, age ≥70 years, presence of ventricular tachycardia, and NYHA heart failure class ≥111 predict an adverse outcome. The presence of sustained ventricular tachycardia and age ≥70 years was associated with occurrence of SCD in these patients.展开更多
Purpose:To examine the joint associations between meeting guidelines for physical activity(PA)and sleep duration and all-cause mortality risk among adults.Methods:Participants were adults(n=282,473)aged 18-84 years wh...Purpose:To examine the joint associations between meeting guidelines for physical activity(PA)and sleep duration and all-cause mortality risk among adults.Methods:Participants were adults(n=282,473)aged 18-84 years who participated in the 2004-2014 U.S.National Health Interview Survey.Mortality status was ascertained using the National Death Index through December 2015.Self-reported PA(Active:meeting both aerobic(AER)and muscle-strengthening(MSA)guidelines,AER only(AER),MSA only(MSA),or not meeting either AER or MSA(Inactive))and sleep duration(Short,recommended(Rec),or Long)were classified according to guidelines,and 12 PA-sleep categories were derived.Adjusted hazard ratios and 95%confidence intervals(95%CIs)for all-cause mortality risk were estimated using Cox proportional hazards regression models.Results:A total of 282,473 participants(55%females)were included;18,793 deaths(6.7%)occurred over an average follow-up of 5.4 years.Relative to the Active-Rec group,all other PA-sleep groups were associated with increased mortality risk except for the Active-Short group(hazard ratio=1.08;95%CI:0.92-1.26).The combination of long sleep with either MSA or Inactive appeared to be synergistic.For a given sleep duration,mortality risk progressively increased among participants classified as AER,MSA,and Inactive.Within each activity level,the mortality risk was greatest among adults with long sleep.Conclusion:Relative to adults meeting guidelines for both PA and sleep duration,adults who failed to meet guidelines for both AER and muscle strengthening PA and who also failed to meet sleep duration guidelines had elevated all-cause mortality risks.These results support interventions targeting both PA and sleep duration to reduce mortality risk.展开更多
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 a...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.展开更多
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 thera...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.展开更多
Tumor vaccines are a promising avenue in cancer immunotherapy.Despite the progress in targeting specific immune epitopes,tumor cells lacking these epitopes can evade the treatment.Here,we aimed to construct an efficie...Tumor vaccines are a promising avenue in cancer immunotherapy.Despite the progress in targeting specific immune epitopes,tumor cells lacking these epitopes can evade the treatment.Here,we aimed to construct an efficient in situ tumor vaccine called Vac-SM,utilizing shikonin(SKN)to induce immunogenic cell death(ICD)and Mycobacterium smegmatis as an immune adjuvant to enhance in situ tumor vaccine efficacy.SKN showed a dose-dependent and time-dependent cytotoxic effect on the tumor cell line and induced ICD in tumor cells as evidenced by the CCK-8 assay and the detection of the expression of relevant indicators,respectively.Compared with the control group,the in situ Vac-SM injection in mouse subcutaneous metastatic tumors significantly inhibited tumor growth and distant tumor metastasis,while also improving survival rates.Mycobacterium smegmatis effectively induced maturation and activation of bone marrow-derived dendritic cells(DCs),and in vivo tumor-draining lymph nodes showed an increased maturation of DCs and a higher proportion of effector memory T-cell subsets with the Vac-SM treatment,based on flow cytometry analysis results.Collectively,the Vac-SM vaccine effectively induces ICD,improves antigen presentation by DCs,activates a specific systemic antitumor T-cell immune response,exhibits a favorable safety profile,and holds the promise for clinical translation for local tumor immunotherapy.展开更多
BACKGROUND The Khorana risk score(KRS)has poor predictive value for cancer-associated thrombosis in a single tumor type but is associated with early all-cause mortality from cancer.Evidence for the association between...BACKGROUND The Khorana risk score(KRS)has poor predictive value for cancer-associated thrombosis in a single tumor type but is associated with early all-cause mortality from cancer.Evidence for the association between KRS and all-cause mortality in Japanese patients with gastric and colorectal cancer is limited.AIM To investigate whether KRS was independently related to all-cause mortality in Japanese patients with gastric and colorectal cancer after adjusting for other covariates and to shed light on its temporal validity.METHODS Data from Dryad database were used in this study.Patients in the Gastroen-terology Department of Sapporo General Hospital,Sapporo,Japan,were enrolled.The starting and ending dates of the enrollment were January 1,2008 and January 5,2015,respectively.The cutoff date for follow-up was May 31,2016.The inde-pendent and dependent(target)variables were the baseline measured using the KRS and final all-cause mortality,respectively.The KRS was categorized into three groups:Low-risk group(=0 score),intermediate-risk group(1-2 score),and high-risk group(≥3 score).RESULTS Men and patients with Eastern Cooperative Oncology Group Performance Status(ECOG PS)≥2 displayed a higher 2-year risk of death than women and those with ECOG PS 0-1 in the intermediate/high risk group for KRS.The higher the score,the higher the risk of early death;however,the relevance of this independent prediction decreased with longer survival.The overall survival of each patient was recorded via real-world follow-up and retrospective observations,and this study yielded the overall relationship between KRS and all-cause mortality.CONCLUSION The prechemotherapy baseline of KRS was independently associated with all-cause mortality within 2 years;however,this independent predictive relationship weakened as survival time increased.展开更多
BACKGROUND In recent years,immune checkpoint inhibitors(ICIs)have demonstrated remarkable efficacy across diverse malignancies.Notably,in patients with advanced gastric cancer,the use of programmed death 1(PD-1)blocka...BACKGROUND In recent years,immune checkpoint inhibitors(ICIs)have demonstrated remarkable efficacy across diverse malignancies.Notably,in patients with advanced gastric cancer,the use of programmed death 1(PD-1)blockade has significantly prolonged overall survival,marking a pivotal advancement comparable to the impact of Herceptin over the past two decades.While the therapeutic benefits of ICIs are evident,the increasing use of immunotherapy has led to an increase in immune-related adverse events.CASE SUMMARY This article presents the case of a patient with advanced gastric cancer and chronic plaque psoriasis.Following sintilimab therapy,the patient developed severe rashes accompanied by cytokine release syndrome(CRS).Fortunately,effective management was achieved through the administration of glucocorticoid,tocilizumab,and acitretin,which resulted in favorable outcomes.CONCLUSION Glucocorticoid and tocilizumab therapy was effective in managing CRS after PD-1 blockade therapy for gastric cancer in a patient with chronic plaque psoriasis.展开更多
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 ...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.展开更多
Severe trauma is one of the main causes of premature death,posing a significant challenge to public health systems.[1]At present,there is a lack of universally accepted guidelines for rapid detection of life-threateni...Severe trauma is one of the main causes of premature death,posing a significant challenge to public health systems.[1]At present,there is a lack of universally accepted guidelines for rapid detection of life-threatening severe trauma,[2]and the accuracy of existing prognostic models in predicting early death is limited.[3,4]Severe non-brain-injured trauma(SNT)patients account for approximately 70%of all trauma-related deaths.Moreover,there is a lack of studies on early death in SNT patients.[5]This study aims to identify risk factors associated with early death(≤72 h post-admission)in SNT patients.展开更多
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 ...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.展开更多
Objective: Liver cancer is a major health concern globally and in China. This analysis investigated deaths and disability-adjusted life years(DALYs) with respect to etiologies and risk factors for liver cancer in Chin...Objective: Liver cancer is a major health concern globally and in China. This analysis investigated deaths and disability-adjusted life years(DALYs) with respect to etiologies and risk factors for liver cancer in China and worldwide.Methods: Global and China-specific data were collected on liver cancer deaths, DALYs, and age-standardized rates(ASRs) from the Global Burden of Disease Study 2019 database. Liver cancer etiologies were classified into five groups and risk factors were categorized into three levels. Each proportion of liver cancer burden was calculated in different geographic regions. The joinpoint regression model were used to assess the trends from 1990±2019.Results: Liver cancer accounted for 484,577 deaths worldwide in 2019 with an ASR of 5.9 per 100,000 population. China had an elevated liver cancer death ASR in 2019 and males had an ASR 1.7 times the global rate. The global ASR for DALYs peaked at 75±79 years of age but peaked earlier in China. Hepatitis B virus was the prominent etiology globally(39.5%) and in China(62.5%), followed by hepatitis C virus and alcohol consumption. In high sociodemographic index countries, non-alcoholic steatohepatitis has gained an increasing contribution as an etiologic factor. The liver cancer burden due to various etiologies has decreased globally in both genders. However, metabolic risk factors, particularly obesity, have had a growing contribution to the liver cancer burden, especially among males.Conclusions: Despite an overall decreasing trend in the liver cancer burden in China and worldwide, there has been a rising contribution from metabolic risk factors, highlighting the importance of implementing targeted prevention and control strategies that address regional and gender disparities.展开更多
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 H...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.展开更多
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 mortal...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.展开更多
基金funded by the Key R&D ProjectsJiangxi [20203BBGL73173]+4 种基金the National Natural Science Foundation of China [81960074]Project of Jiangxi Provincial Health Commission [202130440]5511 Science and Technology Innovation Talent Project of Jiangxi Province (CN)[20165BCD41005]Jiangxi Provincial Natural Science Foundation[20212ACB206019]the Second Affiliated Hospital of Nanchang University[2016YNQN12034, 2019YNLZ12010, IIT-I-2021-002, 2021YNFY2024]
文摘BACKGROUND The cardiovascular hazards of total homocysteine(tHcy)are long known.In addition,despite the acknow-ledgment on the importance of low ankle-brachial index(ABI)(<0.9),borderline ABI(0.91-0.99)was once commonly overlooked.This study aims to explore the independent and joint effect of tHcy level and borderline ABI on all-cause death in hypertensive population.METHODS This study included 10,538 participants from China H-type Hypertension Registry Study.ABI was described into two groups:normal ABI(1.00-1.40)and borderline ABI.tHcy level was also divided into two groups:<15.02 and≥15.02μmo/L.Four groups were analyzed,using COX proportional hazard regression model,separately and pairwise to observe the independ-ent and joint effect on all-cause death.RESULTS A total of 126(1.2%)deaths were observed in the 1.7 years follow-up time.Borderline ABI has a higher predicted risk of death than normal ABI(HR=1.87,95%CI:1.17-3.00)after adjusting for potential covariates.Compare with tHcy level<15.02μmo/L(low tHcy),those with tHcy≥15.02μmo/L(high tHcy)had higher risk to event outcome(HR=1.99,95%CI:1.30-3.05).According to the cumulative hazard curve,group with borderline ABI and high tHcy level has significantly higher altitude and larger increasing rate over follow-up period compare to other groups.Among those with borderline ABI,participants with high tHcy had higher death risk than those with low tHcy,nevertheless,no significant different between borderline and normal ABI among those with low tHcy levels.CONCLUSIONS Borderline ABI and tHcy level both have independent predictive value on all-cause death.The combined group of borderline ABI and high tHcy has highest risk factor of outcomes,which suggested the mutual additive value of border-line ABI and tHcy.More attention should be given to the importance of borderline ABI in hypertensive population,especially with elevated tHcy level.
基金1.Special Funds Provided for the Basic Scientific Research Operating Expenses of Central Universities2.Nanjing Medical Science and Technology Development Project+2 种基金3.Youth Science Foundation Project of National Natural Science Foundation of China.Project No:1.0214143802062.YKK150563.81500537.
文摘Objective: To determine the impact of pulmonary hypertension (PH) on maintenance hemodialysis (MHD) patients' cardiovascular events and all-cause mortality. Methods: We included 90 MHD patients, divided into group with PH and group without PH. All patients had been followed up for 4 years, and the primary endpoints were all cause mortality and cardiovascular events. We compared the clinical data and the endpoint events between the two groups. Results: We found PH in 37 patients (41.11%). The incidence of previous cardiovascular disease in group with PH was significantly higher than that in group without PH (χ2=2.034, P < 0.05). The left atrial diameter in group with PH was significantly higher than that in group without PH (t = 7.265, P < 0.01). Logistic regression analysis revealed that previous cardiovascular disease and left atrial diameter were the independent determinants of PH. The rate of new cardiovascular events in group with PH(59.5%) was significantly higher than that in group without PH(34%) (χ2=9.203, P < 0.05). The associated variables of cardiovascular events were:systolic pulmonary arterial pressure, age, history cardiovascular disease, hs-CRP, ejection fraction, left ventricular diastolic dysfunction. In a multivariate model, the PH maintained its independent association. The mortality rate in group with PH (48.6%) was significantly higher than that in group without PH (26.4%) (χ2=5.049, P <0.05). In the Cox survival analysis, we found an association between mortality and systolic pulmonary arterial pressure, age, previous cardiovascular disease, Alb, ejection fraction. In a multivariate model the PH remains as independent predictor of mortality. Conclusion:Pulmonary hypertension is common in HD patients and a valuable predictor of mortality and cardiovascular events.
基金the Key Research and Development Projects of Science&Technology Department of Sichuan Province(2019YFS0351)。
文摘BACKGROUND Left ventricular hypertrophy(LVH)is prevalent in obese individuals.Besides,both of LVH and obesity is as-sociated with subclinical LV dysfunction.The study aims to investigate the interplay between body fat and LVH in relation to all-cause death in patients with coronary artery disease(CAD).METHODS In this retrospective cohort study,a total of 2243 patients with angiographically proven CAD were included.Body fat and LV mass were calculated using established formulas.Patients were grouped according to body fat percentage and pres-ence or absence of LVH.Cox-proportional hazard models were used to observe the interaction effect of body fat and LVH on all-cause death.RESULTS Of 2243 patients enrolled,560(25%)had a higher body fat percentage,and 1045(46.6%)had LVH.After a median follow-up of 2.2 years,the cumulative mortality rate was 8.2%in the group with higher body fat and LVH,2.5%in those with lower body fat and no LVH,5.4%in those with higher body fat and no LVH,and 7.8%in those with lower body fat and LVH(log-rank P<0.001).There was a statistically significant interaction between body fat percentage and LVH(P interaction was 0.003).After correcting for confounding factors,patients with higher body fat and LVH had the highest risk of all-cause death(HR=3.49,95%CI:1.40-8.69,P=0.007)compared with those with lower body fat and no LVH;in contrast,patients with higher body fat and no LVH had no statistically significant difference in risk of death compared with those with lower body fat and no LVH(HR=2.03,95%CI:0.70-5.92,P=0.195).CONCLUSION A higher body fat percentage was associated with a different risk of all-cause death in patients with CAD,strat-ified by coexistence of LVH or not.Higher body fat was significantly associated with a greater risk of mortality among patients with LVH but not among those without LVH.
文摘BACKGROUND Numerous observational studies have documented a correlation between inflammatory bowel disease(IBD)and an increased risk of dementia.However,the causality of their associations remains elusive.AIM To assess the causal relationship between IBD and the occurrence of all-cause dementia using the two-sample Mendelian randomization(MR)method.METHODS Genetic variants extracted from the large genome-wide association study(GWAS)for IBD(the International IBD Genetics Consortium,n=34652)were used to identify the causal link between IBD and dementia(FinnGen,n=306102).The results of the study were validated via another IBD GWAS(United Kingdom Biobank,n=463372).Moreover,MR egger intercept,MR pleiotropy residual sum and outlier,and Cochran's Q test were employed to evaluate pleiotropy and heterogeneity.Finally,multiple MR methods were performed to estimate the effects of genetically predicted IBD on dementia,with the inverse variance weighted approach adopted as the primary analysis.RESULTS The results of the pleiotropy and heterogeneity tests revealed an absence of significant pleiotropic effects or heterogeneity across all genetic variants in outcome GWAS.No evidence of a causal effect between IBD and the risk of dementia was identified in the inverse variance weighted[odds ratio(OR)=0.980,95%CI:0.942-1.020,P value=0.325],weighted median(OR=0.964,95%CI:0.914-1.017,P value=0.180),and MR-Egger(OR=0.963,95%CI:0.867-1.070,P value=0.492)approaches.Consistent results were observed in validation analyses.Reverse MR analysis also showed no effect of dementia on the development of IBD.Furthermore,MR analysis suggested that IBD and its subtypes did not causally affect allcause dementia and its four subtypes,including dementia in Alzheimer's disease,vascular dementia,dementia in other diseases classified elsewhere,and unspecified dementia.CONCLUSION Taken together,our MR study signaled that IBD and its subentities were not genetically associated with all-cause dementia or its subtypes.Further large prospective studies are warranted to elucidate the impact of intestinal inflammation on the development of dementia.
基金Supported by National High Level Hospital Clinical Research Funding,No.2022-PUMCH-B-015CAMS Innovation Fund for Medical Sciences,No.2021-1-12M-002+1 种基金CAMS Innovation Fund for Medical Sciences,No.2023-I2M-C&T-B-043Beijing Municipal Natural Science Foundation,No.M22014.
文摘BACKGROUND The measurement of triceps skinfold(TSF)thickness serves as a noninvasive metric for evaluating subcutaneous fat distribution.Despite its clinical utility,the TSF thickness trajectories and their correlation with overall mortality have not been thoroughly investigated.AIM To explore TSF thickness trajectories of Chinese adults and to examine their associations with all-cause mortality.METHODS This study encompassed a cohort of 14747 adults sourced from the China Health and Nutrition Survey.Latent class trajectory modeling was employed to identify distinct trajectories of TSF thickness.Subjects were classified into subgroups reflective of their respective TSF thickness trajectory.We utilized multivariate Cox regression analyses and mediation examinations to explore the link between TSF thickness trajectory and overall mortality,including contributory factors.RESULTS Upon adjustment for multiple confounding factors,we discerned that males in the‘Class 2:Thin-stable’and‘Class 3:Thin-moderate’TSF thickness trajectories exhibited a markedly reduced risk of mortality from all causes in comparison to the‘Class 1:Extremely thin’subgroup.In the mediation analyses,the Geriatric Nutritional Risk Index was found to be a partial intermediary in the relationship between TSF thickness trajectories and mortality.For females,a lower TSF thickness pattern was significantly predictive of elevated all-cause mortality risk exclusively within the non-elderly cohort.CONCLUSION In males and non-elderly females,lower TSF thickness trajectories are significantly predictive of heightened mortality risk,independent of single-point TSF thickness,body mass index,and waist circumference.
文摘BACKGROUND Proton pump inhibitors(PPIs)are widely used,including among cancer patients,to manage gastroesophageal reflux and other gastric acid-related disorders.Recent evidence suggests associations between long-term PPI use and higher risks for various adverse health outcomes,including greater mortality.AIM To investigate the association between PPI use and all-cause mortality among cancer patients by a comprehensive analysis after adjustment for various confounders and a robust methodological approach to minimize bias.METHODS This retrospective cohort study used data from the TriNetX research network,with electronic health records from multiple healthcare organizations.The study employed a new-user,active comparator design,which compared newly treated PPI users with non-users and newly treated histamine2 receptor antagonists(H2RA)users among adult cancer patients.Newly prescribed PPIs(esomeprazole,lansoprazole,omeprazole,pantoprazole,or rabeprazole)users were compared to non-users or newly prescribed H2RAs(cimetidine,famotidine,nizatidine,or ranitidine)users.The primary outcome was all-cause mortality.Each patient in the main group was matched to a patient in the control group using 1:1 propensity score matching to reduce confounding effects.Multivariable Cox regression models were used to estimate hazard ratios(HRs)and 95% confidence interval(CI).RESULTS During the follow-up period(median 5.4±1.8 years for PPI users and 6.5±1.0 years for non-users),PPI users demonstrated a higher all-cause mortality rate than non-users after 1 year,2 years,and at the end of follow up(HRs:2.34-2.72).Compared with H2RA users,PPI users demonstrated a higher rate of all-cause mortality HR:1.51(95%CI:1.41-1.69).Similar results were observed across sensitivity analyses by excluding deaths from the first 9 months and 1-year post-exposure,confirming the robustness of these findings.In a sensitivity analysis,we analyzed all-cause mortality outcomes between former PPI users and individuals who have never used PPIs,providing insights into the long-term effects of past PPI use.In addition,at 1-year follow-up,the analysis revealed a significant difference in mortality rates between former PPI users and non-users(HR:1.84;95%CI:1.82-1.96).CONCLUSION PPI use among cancer patients was associated with a higher risk of all-cause mortality compared to non-users or H2RA users.These findings emphasize the need for cautious use of PPIs in cancer patients and suggest that alternative treatments should be considered when clinically feasible.However,further studies are needed to corroborate our findings,given the significant adverse outcomes in cancer patients.
基金This work was supported by the Key Research and Development Projects of Science&Technology Department of Sichuan Province(2019YFS0351).
文摘BACKGROUND: We aimed to investigate whether the pressure injury risk mediates the association of left ventricular ejection fraction(LVEF) with all-cause death in patients with acute myocardial infarction(AMI) aged 80 years or older.METHODS: This retrospective cohort study included 677 patients with AMI aged 80 years or older from a tertiary-level hospital. Pressure injury risk was assessed using the Braden scale at admission, and three risk groups(low/minimal, intermediate, high) were defined according to the overall score of six different variables. LVEF was measured during the index hospitalization for AMI. All-cause death after hospital discharge was the primary outcome.RESULTS: Over a median follow-up period of 1,176 d(interquartile range [IQR], 722–1,900 d), 226(33.4%) patients died. Multivariate Cox regression analysis showed that reduced LVEF was associated with an increased risk of all-cause death only in the high-risk group of pressure injury(adjusted hazard ratios [HR]=1.81, 95% confidence interval [CI]: 1.03–3.20;P=0.040), but not in the low/minimal-(adjusted HR=1.29, 95%CI: 0.80–2.11;P=0.299) or intermediate-risk groups(adjusted HR=1.14, 95%CI: 0.65–2.02;P=0.651). Significant interactions were detected between pressure injury risk and LVEF(adjusted P=0.003). The cubic spline with hazard ratio plot revealed a distinct shaped curve relation between LVEF and all-cause death among different pressure injury risk groups.CONCLUSIONS: In older patients with AMI, the risk of pressure injury mediated the association between LVEF and all-cause death. The classification of older patients for both therapy and prognosis assessment appears to be improved by the incorporation of pressure injury risk assessment into AMI care management.
文摘Background Post myocardial infarction (post-MI) patients with low left ventricular ejection fraction (LVEF) have been candidates for an implantable cardioverter-defibrillator (ICD) since the Multicenter Automatic Defibrillator Implantation Trail Ⅱ (MADIT Ⅱ). However, due to the high costs of ICDs, widespread usage has not been accepted. Therefore, further risk stratification for post-MI patients with low LVEF may aid in the selection of patients that will benefit most from ICD treatment. Methods Four hundred and seventeen post-MI patients with low LVEF (≤35%) were enrolled in the study. All the patients received standard examination and proper treatment and were followed up to observe the all-cause death rate and sudden cardiac death (SCD) rate. Then COX proportional-hazards regression model was used to investigate the clinical factors which affect the all-cause death rate and SCD rate. Results Of 55 patients who died during (32±24) months of follow-up, 37 (67%) died suddenly. After adjusting for baseline clinical characteristics, multivariate COX proportional-hazards regression model identified the following variables associated with death from all causes: New York Heart Association (NYHA) heart failure class ≥Ⅲ (Hazard ratio: 2.361), LVEF ≤20% (Hazard ratio: 2.514), sustained ventricular tachycardia (Hazard ratio: 6.453), and age 〉70 years (Hazard ratio: 3.116). The presence of sustained ventricular tachycardia (Hazard ratio: 6.491) and age ≥70 years (Hazard ratio: 2.694) were specifically associated with SCD. Conclusions In the post-MI patients with low LVEF, factors as LVEF ≤20%, age ≥70 years, presence of ventricular tachycardia, and NYHA heart failure class ≥111 predict an adverse outcome. The presence of sustained ventricular tachycardia and age ≥70 years was associated with occurrence of SCD in these patients.
基金MJD is supported by a Career Development Fellowship(APP1141606)from the National Health and Medical Research Council.
文摘Purpose:To examine the joint associations between meeting guidelines for physical activity(PA)and sleep duration and all-cause mortality risk among adults.Methods:Participants were adults(n=282,473)aged 18-84 years who participated in the 2004-2014 U.S.National Health Interview Survey.Mortality status was ascertained using the National Death Index through December 2015.Self-reported PA(Active:meeting both aerobic(AER)and muscle-strengthening(MSA)guidelines,AER only(AER),MSA only(MSA),or not meeting either AER or MSA(Inactive))and sleep duration(Short,recommended(Rec),or Long)were classified according to guidelines,and 12 PA-sleep categories were derived.Adjusted hazard ratios and 95%confidence intervals(95%CIs)for all-cause mortality risk were estimated using Cox proportional hazards regression models.Results:A total of 282,473 participants(55%females)were included;18,793 deaths(6.7%)occurred over an average follow-up of 5.4 years.Relative to the Active-Rec group,all other PA-sleep groups were associated with increased mortality risk except for the Active-Short group(hazard ratio=1.08;95%CI:0.92-1.26).The combination of long sleep with either MSA or Inactive appeared to be synergistic.For a given sleep duration,mortality risk progressively increased among participants classified as AER,MSA,and Inactive.Within each activity level,the mortality risk was greatest among adults with long sleep.Conclusion:Relative to adults meeting guidelines for both PA and sleep duration,adults who failed to meet guidelines for both AER and muscle strengthening PA and who also failed to meet sleep duration guidelines had elevated all-cause mortality risks.These results support interventions targeting both PA and sleep duration to reduce mortality risk.
文摘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.
基金the financial support received from the Michael J.Fox Foundation through the Target Advancement Program Grant Award (Grant No.MJFF-000649) (to HK)。
文摘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.
基金supported by grants from the Natural Science Foundation of Huai'an Science and Technology Bureau(Grant No.HAB202312)the Science and Technology Development Fund of the Affiliated Hospital of Xuzhou Medical University(Grant No.XYFY2021018).
文摘Tumor vaccines are a promising avenue in cancer immunotherapy.Despite the progress in targeting specific immune epitopes,tumor cells lacking these epitopes can evade the treatment.Here,we aimed to construct an efficient in situ tumor vaccine called Vac-SM,utilizing shikonin(SKN)to induce immunogenic cell death(ICD)and Mycobacterium smegmatis as an immune adjuvant to enhance in situ tumor vaccine efficacy.SKN showed a dose-dependent and time-dependent cytotoxic effect on the tumor cell line and induced ICD in tumor cells as evidenced by the CCK-8 assay and the detection of the expression of relevant indicators,respectively.Compared with the control group,the in situ Vac-SM injection in mouse subcutaneous metastatic tumors significantly inhibited tumor growth and distant tumor metastasis,while also improving survival rates.Mycobacterium smegmatis effectively induced maturation and activation of bone marrow-derived dendritic cells(DCs),and in vivo tumor-draining lymph nodes showed an increased maturation of DCs and a higher proportion of effector memory T-cell subsets with the Vac-SM treatment,based on flow cytometry analysis results.Collectively,the Vac-SM vaccine effectively induces ICD,improves antigen presentation by DCs,activates a specific systemic antitumor T-cell immune response,exhibits a favorable safety profile,and holds the promise for clinical translation for local tumor immunotherapy.
文摘BACKGROUND The Khorana risk score(KRS)has poor predictive value for cancer-associated thrombosis in a single tumor type but is associated with early all-cause mortality from cancer.Evidence for the association between KRS and all-cause mortality in Japanese patients with gastric and colorectal cancer is limited.AIM To investigate whether KRS was independently related to all-cause mortality in Japanese patients with gastric and colorectal cancer after adjusting for other covariates and to shed light on its temporal validity.METHODS Data from Dryad database were used in this study.Patients in the Gastroen-terology Department of Sapporo General Hospital,Sapporo,Japan,were enrolled.The starting and ending dates of the enrollment were January 1,2008 and January 5,2015,respectively.The cutoff date for follow-up was May 31,2016.The inde-pendent and dependent(target)variables were the baseline measured using the KRS and final all-cause mortality,respectively.The KRS was categorized into three groups:Low-risk group(=0 score),intermediate-risk group(1-2 score),and high-risk group(≥3 score).RESULTS Men and patients with Eastern Cooperative Oncology Group Performance Status(ECOG PS)≥2 displayed a higher 2-year risk of death than women and those with ECOG PS 0-1 in the intermediate/high risk group for KRS.The higher the score,the higher the risk of early death;however,the relevance of this independent prediction decreased with longer survival.The overall survival of each patient was recorded via real-world follow-up and retrospective observations,and this study yielded the overall relationship between KRS and all-cause mortality.CONCLUSION The prechemotherapy baseline of KRS was independently associated with all-cause mortality within 2 years;however,this independent predictive relationship weakened as survival time increased.
基金Supported by Shaoxing Health Science and Technology Program,No.2022SY016,No.2022KY010.
文摘BACKGROUND In recent years,immune checkpoint inhibitors(ICIs)have demonstrated remarkable efficacy across diverse malignancies.Notably,in patients with advanced gastric cancer,the use of programmed death 1(PD-1)blockade has significantly prolonged overall survival,marking a pivotal advancement comparable to the impact of Herceptin over the past two decades.While the therapeutic benefits of ICIs are evident,the increasing use of immunotherapy has led to an increase in immune-related adverse events.CASE SUMMARY This article presents the case of a patient with advanced gastric cancer and chronic plaque psoriasis.Following sintilimab therapy,the patient developed severe rashes accompanied by cytokine release syndrome(CRS).Fortunately,effective management was achieved through the administration of glucocorticoid,tocilizumab,and acitretin,which resulted in favorable outcomes.CONCLUSION Glucocorticoid and tocilizumab therapy was effective in managing CRS after PD-1 blockade therapy for gastric cancer in a patient with chronic plaque psoriasis.
文摘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.
基金supported by Suzhou Gusu Health Talents Scientifi c Research Project(GSWS2021017)Scientific Pre-research Fund of the Second Affiliated Hospital of Soochow University(SDFEYQN2007).
文摘Severe trauma is one of the main causes of premature death,posing a significant challenge to public health systems.[1]At present,there is a lack of universally accepted guidelines for rapid detection of life-threatening severe trauma,[2]and the accuracy of existing prognostic models in predicting early death is limited.[3,4]Severe non-brain-injured trauma(SNT)patients account for approximately 70%of all trauma-related deaths.Moreover,there is a lack of studies on early death in SNT patients.[5]This study aims to identify risk factors associated with early death(≤72 h post-admission)in SNT patients.
基金This study is funded by the Major Project of the National Social Science Fund of China(21&ZD187).
文摘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.
基金supported by the Capital’s Funds for Health Improvement and Research (Grant No. 2024-1G-4023)。
文摘Objective: Liver cancer is a major health concern globally and in China. This analysis investigated deaths and disability-adjusted life years(DALYs) with respect to etiologies and risk factors for liver cancer in China and worldwide.Methods: Global and China-specific data were collected on liver cancer deaths, DALYs, and age-standardized rates(ASRs) from the Global Burden of Disease Study 2019 database. Liver cancer etiologies were classified into five groups and risk factors were categorized into three levels. Each proportion of liver cancer burden was calculated in different geographic regions. The joinpoint regression model were used to assess the trends from 1990±2019.Results: Liver cancer accounted for 484,577 deaths worldwide in 2019 with an ASR of 5.9 per 100,000 population. China had an elevated liver cancer death ASR in 2019 and males had an ASR 1.7 times the global rate. The global ASR for DALYs peaked at 75±79 years of age but peaked earlier in China. Hepatitis B virus was the prominent etiology globally(39.5%) and in China(62.5%), followed by hepatitis C virus and alcohol consumption. In high sociodemographic index countries, non-alcoholic steatohepatitis has gained an increasing contribution as an etiologic factor. The liver cancer burden due to various etiologies has decreased globally in both genders. However, metabolic risk factors, particularly obesity, have had a growing contribution to the liver cancer burden, especially among males.Conclusions: Despite an overall decreasing trend in the liver cancer burden in China and worldwide, there has been a rising contribution from metabolic risk factors, highlighting the importance of implementing targeted prevention and control strategies that address regional and gender disparities.
文摘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.
文摘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.