A systematic review of progenitor survival and maturation in Parkinsonian models

Stem cell-based brain repair is a promising emergent therapy for Parkinson's disease based on years of foundational research using human fetal donors as a cell source.Unlike current therapeutic options for patients,this approach has the potential to provide longterm stem cell–derived reconstruction and restoration of the dopaminergic input to denervated regions of the brain allowing for restoration of certain functions to patients.The ultimate clinical success of stem cell–derived brain repair will depend on both the safety and efficacy of the approach and the latter is dependent on the ability of the transplanted cells to survive and differentiate into functional dopaminergic neurons in the Parkinsonian brain.Because the pre-clinical literature suggests that there is considerable variability in survival and differentiation between studies,the aim of this systematic review was to assess these parameters in human stem cell-derived dopaminergic progenitor transplant studies in animal models of Parkinson's disease.A defined systematic search of the PubMed database was completed to identify relevant studies published up to March 2024.After screening,76 articles were included in the analysis from which 178 separate transplant studies were identified.From these,graft survival could be assessed in 52 studies and differentiation in 129 studies.Overall,we found that graft survival ranged from<1% to 500% of cells transplanted,with a median of 51%of transplanted cells surviving in the brain;while dopaminergic differentiation of the cells ranged from 0% to 46% of cells transplanted with a median of 3%.This systematic review suggests that there is considerable scope for improvement in the differentiation of stem cell-derived dopaminergic progenitors to maximize the therapeutic potential of this approach for patients.

Cancer survival analysis on population-based cancer registry data in Zhejiang Province,China(2018-2019)

Objective:This is a comprehensive overview of long-term cancer survival in Zhejiang Province,China.Hybrid analysis,a combination of cohort and period analysis,has been proposed to derive up-to-date cancer survival estimates.Using this approach,we aimed to timely and accurately analyze the 5-year relative survival(RS)and net survival(NS)in cancer registries of Zhejiang Province,China.Methods:A total of 255,725 new cancer cases diagnosed during 2013-2017 were included in 14 cancer registries in Zhejiang Province,China,with a follow-up on vital status until the end of 2019.The hybrid analysis was used to calculate the 5-year RS and 5-year NS during 2018-2019 for overall and stratifications by sex,cancer type,region,and age at diagnosis.Results:During 2018-2019,the age-standardized 5-year RS and NS for overall cancer in Zhejiang was 47.5%and 48.6%,respectively.The age-standardized 5-year RS for cancers of women(55.4%)was higher than that of men(40.0%),and the rate of urban areas(49.7%)was higher than that of rural areas(43.1%).The 5-year RS declined along with age,from 84.4%for ages<45 years to 23.7%for ages>74 years.Our results of the RS and NS showed the similar trend and no significant difference.The top five cancers with top age-standardized 5-year RS were thyroid cancer(96.0%),breast cancer(84.3%),testicular cancer(79.9%),prostate cancer(77.2%),and bladder cancer(70.6%),and the five cancers with the lowest age-standardized 5-year RS were pancreatic cancer(6.0%),liver cancer(15.6%),gallbladder cancer(17.1%),esophageal cancer(22.7%),and leukemia(31.0%).Conclusions:We reported the most up-to-date 5-year cancer RS and NS in Zhejiang Province,China for the first time,and found that the 5-year survival for cancer patients in Zhejiang during 2018-2019 was relatively high.The population-based cancer registries are recognized as key policy tools that can be used to evaluate both the impact of cancer prevention strategies and the effectiveness of health systems.

Application of Survival Quilts for prognosis prediction of gastrectomy patients based on the Surveillance,Epidemiology,and End Results database and China National Cancer Center Gastric Cancer database

Objective:Accurate prognosis prediction is critical for individualized-therapy making of gastric cancer patients.We aimed to develop and test 6-month,1-,2-,3-,5-,and 10-year overall survival(OS)and cancer-specific survival(CSS)prediction models for gastric cancer patients following gastrectomy.Methods:We derived and tested Survival Quilts,a machine learning-based model,to develop 6-month,1-,2-,3-,5-,and 10-year OS and CSS prediction models.Gastrectomy patients in the development set(n=20,583)and the internal validation set(n=5,106)were recruited from the Surveillance,Epidemiology,and End Re-sults(SEER)database,while those in the external validation set(n=6,352)were recruited from the China National Cancer Center Gastric Cancer(NCCGC)database.Furthermore,we selected gastrectomy patients with-out neoadjuvant therapy as a subgroup to train and test the prognostic models in order to keep the accuracy of tumor-node-metastasis(TNM)stage.Prognostic performances of these OS and CSS models were assessed using the Concordance Index(C-index)and area under the curve(AUC)values.Results:The machine learning model had a consistently high accuracy in predicting 6-month,1-,2-,3-,5-,and 10-year OS in the SEER development set(C-index=0.861,0.832,0.789,0.766,0.740,and 0.709;AUC=0.784,0.828,0.840,0.849,0.869,and 0.902,respectively),SEER validation set(C-index=0.782,0.739,0.712,0.698,0.681,and 0.660;AUC=0.751,0.772,0.767,0.762,0.766,and 0.787,respectively),and NCCGC set(C-index=0.691,0.756,0.751,0.737,0.722,and 0.701;AUC=0.769,0.788,0.790,0.790,0.787,and 0.788,respectively).The model was able to predict 6-month,1-,2-,3-,5-,and 10-year CSS in the SEER development set(C-index=0.879,0.858,0.820,0.802,0.784,and 0.774;AUC=0.756,0.827,0.852,0.863,0.874,and 0.884,respectively)and SEER validation set(C-index=0.790,0.763,0.741,0.729,0.718,and 0.708;AUC=0.706,0.758,0.767,0.766,0.766,and 0.764,respectively).In multivariate analysis,the high-risk group with risk score output by 5-year OS model was proved to be a strong survival predictor both in the SEER development set(hazard ratio[HR]=14.59,95%confidence interval[CI]:1.872-2.774,P<0.001),SEER validation set(HR=2.28,95%CI:13.089-16.293,P<0.001),and NCCGC set(HR=1.98,95%CI:1.617-2.437,P<0.001).We further explored the prognostic value of risk score resulted 5-year CSS model of gastrectomy patients,and found that high-risk group remained as an independent CSS factor in the SEER development set(HR=12.81,95%CI:11.568-14.194,P<0.001)and SEER validation set(HR=1.61,95%CI:1.338-1.935,P<0.001).Conclusion:Survival Quilts could allow accurate prediction of 6-month,1-,2-,3-,5-,and 10-year OS and CSS in gastric cancer patients following gastrectomy.

Retrospective Analysis of Radiofrequency Ablation in Patients with Small Solitary Hepatocellular Carcinoma:Survival Outcomes and Development of a Machine Learning Prognostic Model

Background and Objective The effectiveness of radiofrequency ablation(RFA)in improving long-term survival outcomes for patients with a solitary hepatocellular carcinoma(HCC)measuring 5 cm or less remains uncertain.This study was designed to elucidate the impact of RFA therapy on the survival outcomes of these patients and to construct a prognostic model for patients following RFA.Methods This study was performed using the Surveillance,Epidemiology,and End Results(SEER)database from 2004 to 2017,focusing on patients diagnosed with a solitary HCC lesion≤5 cm in size.We compared the overall survival(OS)and cancer-specific survival(CSS)rates of these patients with those of patients who received hepatectomy,radiotherapy,or chemotherapy or who were part of a blank control group.To enhance the reliability of our findings,we employed stabilized inverse probability treatment weighting(sIPTW)and stratified analyses.Additionally,we conducted a Cox regression analysis to identify prognostic factors.XGBoost models were developed to predict 1-,3-,and 5-year CSS.The XGBoost models were evaluated via receiver operating characteristic(ROC)curves,calibration plots,decision curve analysis(DCA)curves and so on.Results Regardless of whether the data were unadjusted or adjusted for the use of sIPTWs,the 5-year OS(46.7%)and CSS(58.9%)rates were greater in the RFA group than in the radiotherapy(27.1%/35.8%),chemotherapy(32.9%/43.7%),and blank control(18.6%/30.7%)groups,but these rates were lower than those in the hepatectomy group(69.4%/78.9%).Stratified analysis based on age and cirrhosis status revealed that RFA and hepatectomy yielded similar OS and CSS outcomes for patients with cirrhosis aged over 65 years.Age,race,marital status,grade,cirrhosis status,tumor size,and AFP level were selected to construct the XGBoost models based on the training cohort.The areas under the curve(AUCs)for 1,3,and 5 years in the validation cohort were 0.88,0.81,and 0.79,respectively.Calibration plots further demonstrated the consistency between the predicted and actual values in both the training and validation cohorts.Conclusion RFA can improve the survival of patients diagnosed with a solitary HCC lesion≤5 cm.In certain clinical scenarios,RFA achieves survival outcomes comparable to those of hepatectomy.The XGBoost models developed in this study performed admirably in predicting the CSS of patients with solitary HCC tumors smaller than 5 cm following RFA.

Mid-term survival of the Optimys short stem: A prospective case series of 500 patients

BACKGROUND In recent years,there has been an increase in the number of total hip arthroplasty procedures in the younger patient population.This active group has higher expectations of their prosthesis in comparison to the older population,and there is a greater physical demand for the prosthesis.Short femoral stems were in-troduced to retain proximal bone stock and joint biomechanics and became more common to implant in this specific population.Currently,the long-term survival and functional outcomes of various short stems are still being investigated in different clinics.AIM To determine the 5-year survival of the Optimys hip stem.METHODS This was a prospective multicenter cohort study of 500 patients conducted in two hospitals in the Netherlands.All patients received the Optimys short stem(Mathys Ltd,Bettlach,Switzerland).The primary outcome measure was survival of the hip stem,with revision as the endpoint.The secondary outcome measurements included patient-reported outcome measures(PROMs).Kaplan-Meier analysis was used to calculate the 5-year survival rate.Log-minus-log transformation was performed to calculate the 95%confidence interval(95%CI).Mixed model analyses were performed to assess the course of the PROMs during the 1st 2 years after surgery.Analyses were modeled separately for the 1st and 2nd years to calculate the yearly change in PROMs during both follow-up periods with accompanying 95%CIs.RESULTS The mean age of the total 500 patients was 62.3 years(standard deviation:10.6)and 202 were male(40%).At a median follow-up of 5.5 years(interquartile range:4.5-6.7),7 patients were deceased and 6 revisions were registered,for infection(n=3),subsidence(n=2)and malposition(n=1).This resulted in an overall 5-year survival of 98.8%(95%CI:97.3-99.5).If infection was left out as reason for revision,a stem survival of 99.4%(95%CI:98.1-99.8)was seen.Baseline questionnaires were completed by 471 patients(94%),317 patients(63%)completed the 1-year follow-up questionnaires and 233 patients(47%)completed the 2-year follow-up.Both outcome measures significantly improved across all domains in the 1st year after the operation(P<0.03 for all domains).In the 2nd year after surgery,no significant changes were observed in any domain in comparison to the 1-year follow-up.CONCLUSION The Optimys stem has a 5-year survival of 98.8%.Patient-reported outcome measures increased significantly in the 1st postoperative year with stabilization at the 2-year follow-up.

Retrospective cohort study on the postoperative survival rate enhancement of patients with colorectal cancer using three traditional Chinese medicine formulations:evidence from 1,361 cases

Background:Prior studies have affirmed the safety and effectiveness of traditional Chinese medicine in treating colorectal cancer patients.However,definitive evidence regarding whether traditional Chinese medicine can significantly enhance the survival of colorectal cancer patients remains elusive.This study seeks to provide conclusive insights by examining the postoperative administration of Xihuang capsules,Pingxiao capsules,and Zilongjin tablets and its impact on the 5-year overall survival(OS)and disease-free survival(DFS)rates among colorectal cancer patients.Methods:A retrospective study was conducted,involving 1,361 patients selected from the medical center.This retrospective study was carried out at a medical center in Tianjin,China.We assessed differences in postoperative OS and DFS between the control group and the medication group using Kaplan–Meier survival analysis and Cox proportional hazards modeling.Additionally,propensity score matching was used to mitigate imbalances in baseline characteristics among patients.Results:Before propensity score matching,Xihuang capsules could prolong the 5-year OS(79.9%vs.81.4%,P=0.0480)and 5-year DFS(74.9%vs.79.5%,P=0.0046)of patients after surgery.Similar conclusions were obtained after propensity score matching:OS(74.8%vs.78.3%,P=0.0084),DFS(72.7%vs.78.9%,P=0.008).Patients taking Pingxiao capsules showed improved 5-year OS(77.2%vs.84.0%,P=0.0383)and 5-year DFS(69.9%vs.80.0%,P=0.0157)after propensity score matching.Patients taking Zilongjin tablets showed improvement in the 2-year OS(84.2%vs.93.1%,P=0.0390)and 1-year DFS(88.2%vs.92.0%,P=0.0320)after propensity score matching.Conclusion:Xihuang capsules and Pingxiao capsules significantly improved the 5-year OS and DFS of patients with colorectal cancer after surgery.Zilongjin tablets showed improvement in the 2-year OS and 1-year DFS after surgery for patients.

Development of a new Cox model for predicting long-term survival in hepatitis cirrhosis patients underwent transjugular intrahepatic portosystemic shunts

BACKGROUND Transjugular intrahepatic portosystemic shunt(TIPS)placement is a procedure that can effectively treat complications of portal hypertension,such as variceal bleeding and refractory ascites.However,there have been no specific studies on predicting long-term survival after TIPS placement.AIM To establish a model to predict long-term survival in patients with hepatitis cirrhosis after TIPS.METHODS A retrospective analysis was conducted on a cohort of 224 patients who un-derwent TIPS implantation.Through univariate and multivariate Cox regression analyses,various factors were examined for their ability to predict survival at 6 years after TIPS.Consequently,a composite score was formulated,encompassing the indication,shunt reasonability,portal venous pressure gradient(PPG)after TIPS,percentage decrease in portal venous pressure(PVP),indocyanine green retention rate at 15 min(ICGR15)and total bilirubin(Tbil)level.Furthermore,the performance of the newly developed Cox(NDC)model was evaluated in an in-ternal validation cohort and compared with that of a series of existing models.RESULTS The indication(variceal bleeding or ascites),shunt reasonability(reasonable or unreasonable),ICGR15,post-operative PPG,percentage of PVP decrease and Tbil were found to be independent factors affecting long-term survival after TIPS placement.The NDC model incorporated these parameters and successfully identified patients at high risk,exhibiting a notably elevated mortality rate following the TIPS procedure,as observed in both the training and validation cohorts.Additionally,in terms of predicting the long-term survival rate,the performance of the NDC model was significantly better than that of the other four models[Child-Pugh,model for end-stage liver disease(MELD),MELD-sodium and the Freiburg index of post-TIPS survival].CONCLUSION The NDC model can accurately predict long-term survival after the TIPS procedure in patients with hepatitis cirrhosis,help identify high-risk patients and guide follow-up management after TIPS implantation.

Cancer survival statistics in China 2019-2021:a multicenter,population-based study

Background:A milestone goal of the Healthy China Program(2019-2030)is to achieve 5-year cancer survival at 43.3%for all cancers combined by 2022.To assess the progress towards this target,we analyzed the updated survival for all cancers combined and 25 specific cancer types in China from 2019 to 2021.Methods:We conducted standardized data collection and quality control for cancer registries across 32 provincial-level regions in China,and included 6,410,940 newly diagnosed cancer patients from 281 cancer registries during 2008-2019,with follow-up data on vital status available until December 2021.We estimated the age-standardized 5-year relative survival overall and by site,age group,and period of diagnosis using the International Cancer Survival Standard Weights,and quantified the survival changes to assess the progress in cancer control.Results:In 2019-2021,the age-standardized 5-year relative survival for all cancers combined was 43.7%(95%confidence interval[CI],43.6-43.7).The 5-year relative survival varied by cancer type,ranging from 8.5%(95%CI,8.2-8.7)for pancreatic cancer to 92.9%(95%CI,92.4-93.3)for thyroid cancer.Eight cancers had 5-year survival of over 60%,including cancers of the thyroid,breast,testis,bladder,prostate,kidney,uterus,and cervix.The 5-year relative survival was generally lower in males than in females.From 2008 to 2021,we observed significant survival improvements for cancers of the lung,prostate,bone,uterus,breast,cervix,nasopharynx,larynx,and bladder.The most significant improvement was in lung cancer.Conclusions:Progress in cancer control was evident in China.This highlights the importance of a comprehensive approach to control and prevent cancer.

Annual variation of adult survival of a south-temperate House Wren population in Argentina

Identifying factors affecting the survival of individuals is essential for understanding the evolution of life-history traits and population dynamics.Despite numerous studies on this subject in north-temperate environments,there is a lack of equivalent studies at similar latitudes in the south.Here,we used a 14-year dataset of capture,banding,and resighting to estimate the annual variation in the apparent adult survival probability of a south-temperate population of House Wrens(Troglodytes aedon bonariae).We evaluated temporal variation in sur-vival and the effect of environmental(climatic)and demographic variables(adult abundance,total number of fledglings produced during each breeding season)on survival estimators.We found that the probability of adult survival decreased as the abundance of breeding adults increased.This density-dependent effect could be related to the resident lifestyle of southern House Wrens,which could determine an intense competition for territories and resources that ultimately would affect their survival.

Multiple myeloma survival in New South Wales, Australia, by treatment era to 2020

Objective: Australia has relatively high multiple myeloma(MM) incidence and mortality rates. Advancements in MM treatment over recent decades have driven improvements in MM survival in high-income countries;however, reporting in Australia is limited. We investigated temporal trends in population-wide MM survival across 3 periods of treatment advancements in New South Wales(NSW), Australia.Methods: Individuals with an MM diagnosis in the NSW Cancer Registry between 1985 and 2015 with vital follow-up to 2020, were categorized into 3 previously defined treatment eras according to their diagnosis date(1985±1995, chemotherapy only;1996±2007, autologous stem cell transplantation;and 2008±2015, novel agents including proteasome inhibitors and immunomodulatory drugs). Both relative survival and cause-specific survival according to Fine and Gray's competing risks cumulative incidence function were calculated by treatment era and age at diagnosis.Results: Overall, 11,591 individuals were included in the study, with a median age of 70 years at diagnosis. Five-year relative survival improved over the 36-year(1985±2020) study period(31.0% in 1985±1995;41.9% in 1996±2007;and 56.1% in 2008±2015). For individuals diagnosed before 70 years of age, the 5-year relative survival nearly doubled, from 36.5% in 1985±1995 to 68.5% in 2008±2015. Improvements for those > 70 years of age were less pronounced between 1985±1995 and 1996±2007;however, significant improvements were observed for those diagnosed in 2008±2015. Similar overall and age-specific patterns were observed for causespecific survival. After adjustment for gender and age at diagnosis, treatment era was strongly associated with both relative and cause-specific survival(P < 0.0001).Conclusions: Survival of individuals with MM is improving in Australia with treatment advances. However, older age groups continue to experience poor survival outcomes with only modest improvements over time. Given the increasing prevalence of MM in Australia, the effects of MM treatment on quality of life, particularly in older age, warrant further attention.

Transcriptome Analysis of Heterosis in Survival in the Hybrid Progenies of‘Haida No.1’and Orange-Shelled Lines of the Pacific Oyster Crassostrea gigas

Heterosis has been exploited to enhance the yield and adaptability in various shellfish species;however,the molecular basis of it remains unclear.The Pacific oyster Crassostrea gigas is one of the most economically important aquaculture species,and its productive traits can be improved by hybridization.Here,an intraspecific cross between orange shell(O,10th generation)and‘Haida No.1’(H,13th generation)of C.gigas was performed to assess the heterosis of survival trait.Survival rates of hybrid family(OH)and inbred families(HH and OO)were compared at larval stage,and eyed-pediveliger larvae of three families were subjected to transcriptome analysis.The analysis results of best-parent heterosis and mid-parent heterosis showed that the hybrid family exhi-bited a high heterosis in survival relative to the parental families.The OH-M(OH vs.OO)and OH-P(OH vs.HH)had 425 and 512 dif-ferentially expressed genes(DEGs),respectively.Functional enrichment analysis of these DEGs revealed that the significantly enrich-ed genes function in virion binding,C-type lectin receptor signaling pathway,cellular defense response and other immune-related pro-cesses,which involves perlucin-like protein,CD209 antigen-like protein,ZNFX1,caspase-3 and acan genes.These differentially ex-pressed genes in OH-M and OH-P,together with the immune-related processes mentioned above may play an important role in the larval survival of C.gigas.In addition,three genes(CYP450,fucolectin and perlucin-like)are associated with the orange shell and low survival of maternal oyster OO.These findings provide support for the application of hybrid with superior survival and will facilitate the understanding of heterosis formation in the Pacific oyster.

Treatment patterns and survival outcomes in patients with nonmetastatic early-onset pancreatic cancer

BACKGROUND The incidence of patients with early-onset pancreatic cancer(EOPC;age≤50 years at diagnosis)is on the rise,placing a heavy burden on individuals,families,and society.The role of combination therapy including surgery,radiotherapy,and chemotherapy in non-metastatic EOPC is not well-defined.AIM To investigate the treatment patterns and survival outcomes in patients with non-metastatic EOPC.METHODS A total of 277 patients with non-metastatic EOPC who were treated at our institution between 2017 and 2021 were investigated retrospectively.Overall survival(OS),disease-free survival,and progression-free survival were estimated using the Kaplan-Meier method.Univariate and multivariate analyses with the Cox proportional hazards model were used to identify prognostic factors.RESULTS With a median follow-up time of 34.6 months,the 1-year,2-year,and 3-year OS rates for the entire cohort were 84.3%,51.5%,and 27.6%,respectively.The median OS of patients with localized disease who received surgery alone and adjuvant therapy(AT)were 21.2 months and 28.8 months,respectively(P=0.007).The median OS of patients with locally advanced disease who received radiotherapy-based combination therapy(RCT),surgery after neoadjuvant therapy(NAT),and chemotherapy were 28.5 months,25.6 months,and 14.0 months,respectively(P=0.002).The median OS after regional recurrence were 16.0 months,13.4 months,and 8.9 months in the RCT,chemotherapy,and supportive therapy groups,respectively(P=0.035).Multivariate analysis demonstrated that carbohydrate antigen 19-9 level,pathological grade,T-stage,N-stage,and resection were independent prognostic factors for non-metastatic EOPC.CONCLUSION AT improves postoperative survival in localized patients.Surgery after NAT and RCT are the preferred therapeutic options for patients with locally advanced EOPC.

Survival outcomes in early-onset oesophageal adenocarcinoma patients:A systematic review and meta-analyses

BACKGROUND The incidence of oesophageal adenocarcinoma(OAC)has been reported to be increasing in many countries.Alongside this trend,an increase in incidence of early-onset OAC,defined as OAC in adults aged under 50 years,has been observed.It is unclear whether survival outcomes for early-onset OAC patients differ from older age groups.AIM To investigate survival outcomes in early-onset OAC patients.METHODS Ovid Medline and Embase were searched from inception to January 2022 for relevant studies relating to early-onset OAC and survival outcomes.Results regarding the overall five-year survival and risk of death of younger and older patients with OAC were extracted and pooled using meta-analyses to produce pooled estimates and 95%CIs where possible.RESULTS Eleven studies which compared survival of early-onset OAC,defined as age at diagnosis of<50 years,with older patients were included.A narrative review of median and mean survival demonstrated conflicting results,with studies showing early-onset OAC patients having both better and worse outcomes compared to older age groups.A meta-analysis of five-year survival demonstrated similar outcomes across age groups,with 22%-25%of patients in the young,middle and older age groups alive after five years.A meta-analysis of four studies demon-strated that early-onset OAC patients did not have a significantly increased risk of death compared to middle-aged patients(hazard ratio 1.12,95%CI:0.85-1.47).INTRODUCTION There is concern that the incidence of oesophageal adenocarcinoma(OAC)in patients under 50,described as early-onset OAC,is increasing.However,data regarding survival of younger patients with OAC is sparse.Globally,while increasing age remains a major non-modifiable risk factor for cancer,the incidence of early-onset cancers,largely accepted to be in adults aged under 50 years,is increasing[1].This includes an observed increase in the incidence of gastrointestinal malignancies such as colorectal,oesophageal,gastric and hepatobiliary cancers[2-4].Despite oesophageal squamous cell carcinoma(OSCC)being more common globally(88%of cases)[5],a striking increase in oesophageal OAC incidence has been reported in developed countries,such as the United States and Europe[6,7].Worryingly,the United Kingdom has the highest incidence of OAC cases in the world[8].In addition to the increase in OAC,an increase in incidence of early-onset OAC,defined as OAC in adults aged under 50 years,has been observed[9,10].A population-based cohort in the Netherlands,consisting of 59584 patients,demonstrated the incidence of early-onset OAC to have tripled from 1989 to 2018,while OSCC cases declined in this age group[7].OAC usually develops in the lower third of the oesophagus and the gastro-oesophageal junction,with risk factors including obesity and gastro-oesophageal reflux disease[11].A poor prognosis is observed,with the overall five-year survival rate for oesophageal cancer between 15%-20%,even with treatment[12,13].These low survival rates are likely due to a combination of late diagnosis,intrinsic resistance to systemic therapy and the limited efficacy of surgical resection.Younger patients tend to present at a more advanced stage at diagnosis compared to those diagnosed later in life.A single centre,retrospective study found that 33.3%of patients in the younger age category(<50 years old)presented with stage IV OAC,compared to the 20.6%of the oldest age category(>70 years old)[14].Another population-based study in the Netherlands observed that OAC patients under 50 years old also presented with distant metastasis more often in comparison to older patients(50.5%vs 44.7%),and that tumour differentiation also varied between age groups[15].Reports of survival estimates in patients with early-onset OAC compared with older patients have resulted in contrasting findings to date.Some studies report that due to the advanced stage and aggressiveness of the tumours seen that the prognosis of these patients is almost always worse than their older counterparts[16].In contrast,another study found that the overall survival,as well as stage-specific survival was higher in those who were younger[17].A Dutch study which included only resectable cases found no difference in 5-year disease specific survival[18].Given the conflicting evidence to date,the aim of this systematic review was to investigate survival in OAC patients according to age at diagnosis.A protocol was composed,and the reporting of this systematic review designed,using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines[19].The protocol included:The review question,search strategy,inclusion criteria,type of quality assessment,the strategy for data analysis,and the‘population,intervention,comparator,and outcome’criteria.These are expanded below.

Options and survival benefits of conversion therapy for unresectable hepatocellular carcinoma

In the study by Wu et al,patients with unresectable hepatocellular carcinoma were subjected to transarterial chemoembolization(TACE)as a conversion therapy in order to render their tumors suitable for resection.A nomogram was devised and shown to be effective in predicting the survival of these patients.Generalization of the results,however,is questionable since the study subjects consisted of patients who had resection after TACE while excluding patients with the same disease but not suitable for TACE.Immunotherapy can be considered to be an option for conversion therapy.However,markers for determining responses to a conversion therapy and for guiding the decision between TACE and sequential immunotherapy have been lacking.The question of whether effective conversion therapy can truly enhance overall survival remains unanswered.

The impact of chemotherapy-naïve open radical cystectomy delay and perioperative transfusion on the recurrence-free survival: A perioperative parameters-based nomogram

Objective: To develop and internally validate a nomogram to predict recurrence-free survival (RFS) including the time to radical cystectomy (RC) and perioperative blood transfusion (PBT) as potential predictors.Methods: Patients who underwent open RC and ileal conduit between January 1996 to December 2016 were split into developing (n=948) and validating (n=237) cohorts. The time to radical cystectomy (TTC) was defined as the interval between the onset of symptoms and RC. The regression coefficients of the independent predictors obtained by Cox regression were used to construct the nomogram. Discrimination, validation, and clinical usefulness in the validation cohort were assessed by the area under the curve, the calibration plot, and decision curve analysis.Results: In the developing dataset, the 1-, 5-, and 10-year RFS were 83.0%, 47.2%, and 44.4%, respectively. On multivariate analysis, independent predictors were TTC (hazards ratio [HR] 1.07, 95% confidence interval [CI] 1.05-1.08, p<0.001), PBT (one unit: HR 1.40, 95% CI 1.03-1.90, p=0.03;two or more units: HR 1.72, 95% CI 1.29-2.29, p<0.001), bilateral hydronephrosis (HR 1.54, 95% CI 1.21-1.97, p<0.001), squamous cell carcinoma (HR 0.60, 95% CI 0.45-0.81, p=0.001), pT3-T4 (HR 1.77, 95% CI 1.41-2.22, p<0.001), lymph node status (HR 1.53, 95% CI 1.21-1.95, p<0.001), and lymphovascular invasion (HR 1.28, 95% CI 1.01-1.62, p=0.044). The areas under the curve in the validation dataset were 79.3%, 69.6%, and 76.2%, for 1-, 5-, and 10-year RFS, respectively. Calibration plots showed considerable correspondence between predicted and actual survival probabilities. The decision curve analysis revealed a better net benefit of the nomogram.Conclusion: A nomogram with good discrimination, validation, and clinical utility was constructed utilizing TTC and PBT in addition to standard pathological criteria.

Survival Analysis of Patients Undergoing Intraoperative Contrast-enhanced Ultrasound in the Surgical Treatment of Malignant Glioma

Objective:Complete resection of malignant gliomas is often challenging.Our previous study indicated that intraoperative contrast-enhanced ultrasound(ICEUS)could aid in the detection of residual tumor remnants and the total removal of brain lesions.This study aimed to investigate the survival rates of patients undergoing resection with or without the use of ICEUS and to assess the impact of ICEUS on the prognosis of patients with malignant glioma.Methods:A total of 64 patients diagnosed with malignant glioma(WHO grade HI and IV)who underwent surgery between 2012 and 2018 were included.Among them,29 patients received ICEUS.The effects of ICEUS on overall survival(OS)and progression-free survival(PFS)of patients were evaluated.A quantitative analysis was performed to compare ICEUS parameters between gliomas and the surrounding tissues.Results:The ICEUS group showed better survival rates both in OS and PFS than the control group.The univariate analysis revealed that age,pathology and ICEUS were significant prognostic factors for PFS,with only age being a significant prognostic factor for OS.In multivariate analysis,age and ICEUS were significant prognostic factors for both OS and PFS.The quantitative analysis showed that the intensity and transit time of microbubbles reaching the tumors were significantly different from those of microbubbles reaching the surrounding tissue.Conclusion:ICEUS facilitates the identification of residual tumors.Age and ICEUS are prognostic factors for malignant glioma surgery,and use of ICEUS offers a better prognosis for patients with malignant glioma.

Extreme Responses of An Integrated System with A Semi-Submersible Wind Turbine and Four Torus-Shaped Wave Energy Converters in Different Survival Modes

Offshore wind power is a kind of important clean renewable energy and has attracted increasing attention due to the rapid consumption of non-renewable energy.To reduce the high cost of energy,a possible try is to utilize the combination of wind and wave energy considering their natural correlation.A combined concept consisting of a semi-submersible wind turbine and four torus-shaped wave energy converters was proposed and numerically studied under normal operating conditions.However,the dynamic behavior of the integrated system under extreme sea conditions has not been studied yet.In the present work,extreme responses of the integrated system under two different survival modes are evaluated.Fully coupled time-domain simulations with consideration of interactions between the semi-submersible wind turbine and the torus-shaped wave energy converters are performed to investigate dynamic responses of the integrated system,including mooring tensions,tower bending moments,end stop forces,and contact forces at the Column-Torus interface.It is found that the addition of four tori will reduce the mean motions of the yaw,pitch and surge.When the tori are locked at the still water line,the whole integrated system is more suitable for the survival modes.

Long-Term Survival Trend of Gynecological Cancer:A Systematic Review of Population-Based Cancer Registration Data

Gynecological cancer significantly affect the health of women.This review aimed to describe the global patterns and trends in the survival of patients with gynecological cancers.We searched PubMed,Embase,Web of Science,SinoMed,and SEER for survival analyses of cancer registration data of cervical,endometrial,and ovarian cancers published between 1980 and 2022.Globally,the highest 5-year observed survival rate for cervical cancer was 76.5% in Anshan,Liaoning,China(2008-2017).The 5-year observed survival rates of endometrial and ovarian cancers were higher in Finland(1995-1999,82.5%)and Singapore(1988-1992,62.0%).The 5-year relative survival rate of cervical cancer patients was higher in Haining,Zhejiang,China(2011-2014,85.8%).Korea ranked first at 89.0% and 64.5% for endometrial and ovarian cancers,respectively.Survival rates have improved for cervical,endometrial,and ovarian cancers.Patients aged≥75 years and those with advancedstage disease had the worst 5-year survival rates.Survival rates were better for squamous cell carcinoma in cervical cancer,for endometrial carcinoma and mucinous adenocarcinoma in endometrial cancer,and for germ cell and sex-cord stromal tumors in ovarian cancer.Over the past four decades,the survival rates of gynecological cancers have increased globally,with notable increases in cervical and endometrial cancers.Survival rates are higher in developed countries,with a slow-growing trend.Future studies should focus on improving survival,especially in ovarian cancer patients.

Bayesian network-based survival prediction model for patients having undergone post-transjugular intrahepatic portosystemic shunt for portal hypertension

BACKGROUND Portal hypertension(PHT),primarily induced by cirrhosis,manifests severe symptoms impacting patient survival.Although transjugular intrahepatic portosystemic shunt(TIPS)is a critical intervention for managing PHT,it carries risks like hepatic encephalopathy,thus affecting patient survival prognosis.To our knowledge,existing prognostic models for post-TIPS survival in patients with PHT fail to account for the interplay among and collective impact of various prognostic factors on outcomes.Consequently,the development of an innovative modeling approach is essential to address this limitation.AIM To develop and validate a Bayesian network(BN)-based survival prediction model for patients with cirrhosis-induced PHT having undergone TIPS.METHODS The clinical data of 393 patients with cirrhosis-induced PHT who underwent TIPS surgery at the Second Affiliated Hospital of Chongqing Medical University between January 2015 and May 2022 were retrospectively analyzed.Variables were selected using Cox and least absolute shrinkage and selection operator regression methods,and a BN-based model was established and evaluated to predict survival in patients having undergone TIPS surgery for PHT.RESULTS Variable selection revealed the following as key factors impacting survival:age,ascites,hypertension,indications for TIPS,postoperative portal vein pressure(post-PVP),aspartate aminotransferase,alkaline phosphatase,total bilirubin,prealbumin,the Child-Pugh grade,and the model for end-stage liver disease(MELD)score.Based on the above-mentioned variables,a BN-based 2-year survival prognostic prediction model was constructed,which identified the following factors to be directly linked to the survival time:age,ascites,indications for TIPS,concurrent hypertension,post-PVP,the Child-Pugh grade,and the MELD score.The Bayesian information criterion was 3589.04,and 10-fold cross-validation indicated an average log-likelihood loss of 5.55 with a standard deviation of 0.16.The model’s accuracy,precision,recall,and F1 score were 0.90,0.92,0.97,and 0.95 respectively,with the area under the receiver operating characteristic curve being 0.72.CONCLUSION This study successfully developed a BN-based survival prediction model with good predictive capabilities.It offers valuable insights for treatment strategies and prognostic evaluations in patients having undergone TIPS surgery for PHT.

Key Genes Involved in the Beneficial Mechanism of Hyperbaric Oxygen for Glioblastoma and Predictive Indicators of Hyperbaric Oxygen Prolonging Survival in Glioblastoma Patients

Objective The prognosis of glioblastoma is poor,and therapy-resistance is largely attributed to intratumor hypoxia.Hyperbaric oxygen(HBO)effectively alleviates hypoxia.However,the sole role of HBO in glioblastoma remains controversial.We previously reported that HBO can promote apoptosis,shorten protrusions,and delay growth of glioblastoma,but the molecular mechanism is unclear.We aimed to test candidate genes in HBO-exposed glioblastoma cells and to analyze their correlation with the survival of glioblastoma patients.Methods Glioblastoma cell lines exposed to repetitive HBO or normobaric air(NBA)were collected for RNA isolation and microarray data analysis.GO analysis,KEGG pathway analysis and survival analysis of the differentially expressed genes(DEGs)were performed.Results HBO not only inhibited hypoxia-inducing genes including CA9,FGF11,PPFIA4,TCAF2 and SLC2A12,but also regulated vascularization by downregulating the expression of COL1A1,COL8A1,COL12A1,RHOJ and FILIP1L,ultimately attenuated hypoxic microenvironment of glioblastoma.HBO attenuated inflammatory microenvironment by reducing the expression of NLRP2,CARD8,MYD88 and CD180.HBO prevented metastasis by downregulating the expression of NTM,CXCL12,CXCL13,CXCR4,CXCR5,CDC42,IGFBP3,IGFBP5,GPC6,MMP19,ADAMTS1,EFEMP1,PTBP3,NF1 and PDCD1.HBO upregulated the expression of BAK1,PPIF,DDIT3,TP53I11 and FAS,whereas downregulated the expression of MDM4 and SIVA1,thus promoting apoptosis.HBO upregulated the expression of CDC25A,MCM2,PCNA,RFC33,DSCC1 and CDC14A,whereas downregulated the expression of ASNS,CDK6,CDKN1B,PTBP3 and MAD2L1,thus inhibiting cell cycle progression.Among these DEGs,17 indicator-genes of HBO prolonging survival were detected.Conclusions HBO is beneficial for glioblastoma.Glioblastoma patients with these predictive indicators may prolong survival with HBO therapy.These potential therapeutic targets especially COL1A1,ADAMTS1 and PTBP3 deserve further validation.