Survivals after liver transplantation for hepatocellular carcinoma:Granular data for a better allocation process?

To the Editor:A large international study has been recently published focusing on the combination of morphological aspects and alpha-fetoprotein(AFP)as predictors of survival in patients with hepatocellular cancer(HCC)treated with liver transplantation(LT)[1].As a matter of fact,morphology and biology represent the two sides of the same

Incidence,Risk Factors,and Prognosis of Patients with Hepatocellular Carcinoma and Brain Metastases

Objective Brain metastases significantly impact the clinical course of patients with hepatocellular carcinoma(HCC).This study aimed to examine the age-related incidence,demographics,and survival of patients with HCC and brain metastases.Methods Data of HCC patients from 2010 to 2015 in the Surveillance,Epidemiology,and End Results(SEER)Registry were screened for the presence of brain metastases.They were stratified by age and ethnicity.Multivariable logistic and Cox regression analyses were used to identify factors associated with brain metastases and those with overall survival(OS)and liver cancer-specific survival(CSS),respectively.Results A total of 141 HCC patients presenting with brain metastases were identified,accounting for 0.35% of all HCC patients and 2.37% of patients with metastatic disease.Among all HCC patients,the incidence rate was the highest among patients aged 30-49 years old(0.47%).Ethnicity was not associated with the presence of brain metastases at the time of HCC diagnosis.However,African-American patients presented with a significantly lower disease-specific survival[median time:1 month;interquartile range(IQR):0-3.0 months].Initial lung or bone metastasis was independently associated with an increased risk of the presence of brain metastases[odds ratio(OR):12.62,95% confidence interval(CI):8.40-18.97]but was not associated with a worse OS or CSS among those with brain metastases.Conclusion This study identified the age-related incidence and risk factors of brain metastases in HCC patients.These results may contribute to the consideration of brain screening among patients with initial metastatic HCC with lung or bone metastases,and influence the counseling of this patient population regarding their prognosis.

Production traits and fertility of reciprocal hybrids between Argopecten irradians irradians and A.i.concentricus

The two bay scallop subspecies,Argopecten irradians irradians(NN)and A.i.concentricus(SS),are fast growing and major cultured bivalves in China.However,their relatively small sizes and decreasing production traits caused by long-term inbreeding have been major concerns to the industry in the last two decades.Hybridization between the two bay scallop subspecies may provide a new approach to breed a new variety with superior production traits for the industry.For this end,in this study,we hybridized the two bay scallop subspecies in order to obtain a new strain that incorporates the genes of both subspecies.No significant difference was found in fertilization rate,hatching rate and metamorphosis rate between the purebred and crossbred cohorts(NN♀×SS♂,denoted as NS;SS♀×NN♂,denoted as SN).Both mating strategy(intra-vs.inter-population crosses)and egg origin had significant effects on growth and survival at the larval stage.Heterosis was observed in the crossbred and was more pronounced in older stages.Genetic diversity of the reciprocal hybrids,especially that of SN,was increased compared with the purebred cohorts.Almost all hybrids were completely fertile and able to reproduce by selffertilization or by backcrossing with either parent.Apparently,male sterile individuals whose gonads were fully occupied by the ovary part at mature stage were found in the hybrids for the first time.The hybrids,especially SN,may provide precious germplasm resources for the production of ternary hybrids with the Peruvian scallop,A.purpuratus.

Evaluating the influence of sarcopenia and myosteatosis on clinical outcomes in gastric cancer patients undergoing immune checkpoint inhibitor

BACKGROUND The development and progression of gastric cancer(GC)are closely linked to the nutritional status of patients.Although immunotherapy has been demonstrated to be clinically effective,the relationships of sarcopenia and myosteatosis with the use of immune checkpoint inhibitors(ICIs)in patients with gastric cancer remain to be characterized.METHODS We performed a retrospective study of patients who were undergoing immuno-therapy for GC.For the evaluation of sarcopenia,the optimal cut-off value for the skeletal muscle index was established using receiver operating characteristic analysis of data obtained from pre-treatment computed tomography images at the L3 vertebral level.Myosteatosis was defined using the mean skeletal muscle density(SMD),with a threshold value of<41 Hounsfield units(HU)for patients with a body mass index(BMI)<25 kg/m^(2)and<33 HU for those with a BMI≥25 kg/m^(2).The log-rank test was used to compare progression-free survival(PFS)and overall survival(OS),and a Cox proportional hazard model was used to identify prognostic factors.Nomograms were developed to predict the PFS and OS of patients on the basis of the results of multivariate analyses.RESULTS We studied 115 patients who were undergoing ICI therapy for GC,of whom 27.4%had sarcopenia and 29.8%had myosteatosis.Patients with sarcopenia or myosteatosis had significantly shorter PFS and OS than those without these conditions.Furthermore,both sarcopenia and myosteatosis were found to be independent predictors of PFS and OS in patients with GC administering an ICI.The prediction models created for PFS and OS were associated with C-indexes of 0.758 and 0.781,respectively.CONCLUSION The presence of sarcopenia or myosteatosis is a reliable predictor of the clinical outcomes of patients with GC who are undergoing treatment with an ICI.

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.

Predictive value of preoperative routine examination for the prognosis of patients with pT2N0M0 or pT3N0M0 colorectal cancer

BACKGROUND In recent years,the incidence of colorectal cancer(CRC)has been increasing.With the popularization of endoscopic technology,a number of early CRC has been diagnosed.However,despite current treatment methods,some patients with early CRC still experience postoperative recurrence and metastasis.AIM To search for indicators associated with early CRC recurrence and metastasis to identify high-risk populations.METHODS A total of 513 patients with pT2N0M0 or pT3N0M0 CRC were retrospectively enrolled in this study.Results of blood routine test,liver and kidney function tests and tumor markers were collected before surgery.Patients were followed up through disease-specific database and telephone interviews.Tumor recurrence,metastasis or death were used as the end point of study to find the risk factors and predictive value related to early CRC recurrence and metastasis.RESULTS We comprehensively compared the predictive value of preoperative blood routine,blood biochemistry and tumor markers for disease-free survival(DFS)and overall survival(OS)of CRC.Cox multivariate analysis demonstrated that low platelet count was significantly associated with poor DFS[hazard ratio(HR)=0.995,95% confidence interval(CI):0.991-0.999,P=0.015],while serum carcinoembryonic antigen(CEA)level(HR=1.008,95%CI:1.001-1.016,P=0.027)and serum total cholesterol level(HR=1.538,95%CI:1.026-2.305,P=0.037)were independent risk factors for OS.The cutoff value of serum CEA level for predicting OS was 2.74 ng/mL.Although the OS of CRC patients with serum CEA higher than the cutoff value was worse than those with lower CEA level,the difference between the two groups was not statistically significant(P=0.075).CONCLUSION For patients with T2N0M0 or T3N0M0 CRC,preoperative platelet count was a protective factor for DFS,while serum CEA level was an independent risk factor for OS.Given that these measures are easier to detect and more acceptable to patients,they may have broader applications.

Time trends and outcomes of gastrostomy placement in a Swedish national cohort over two decades

BACKGROUND Percutaneous endoscopic gastrostomy(PEG)and laparoscopically inserted gastrostomy have become the gold standard for adult patients and children,respectively,requiring long-term enteral nutrition support.Procedure-related mortality is a rare event,often reported to be zero in smaller studies.National data on 30-d mortality and long-term survival rates after gastrostomy placement are scarce in the literature.AIM To study the use of gastrostomies in Sweden from 1998-2019 and to analyze procedure-related mortality and short-term(<30 d)and long-term survival.METHODS In this retrospective,population-based cohort study,individuals that had received a gastrostomy between 1998-2019 in Sweden were included.Individuals were identified in the Swedish National Patient Register,and survival analysis was possible by cross-referencing the Swedish Death Register.The cohort was divided into three age groups:Children(0-18 years);adults(19-64 years);and elderly(≥65 years).Kaplan-Meier with log-rank test and Cox regression were used for survival analysis.RESULTS In total 48682 individuals(52%males,average age 60.9±25.3 years)were identified.The cohort consisted of 12.0%children,29.5%adults,and 58.5%elderly.An increased use of gastrostomies was observed during the study period,from 13.7/100000 to 22.3/100000 individuals(P<0.001).The use of PEG more than doubled(about 800 to 1800/year),with a corresponding decrease in open gastrostomy(about 700 to 340/year).Laparoscopic gastrostomy increased more than ten-fold(about 20 to 240/year).Overall,PEG,open gastrostomy,and laparoscopic gastrostomy constituted 70.0%(n=34060),23.3%(n=11336),and 4.9%(n=2404),respectively.Procedure-related mortality was 0.1%(n=44)overall(PEG:0.05%,open:0.24%,laparoscopic:0.04%).The overall 30-d mortality rate was 10.0%(PEG:9.8%,open:12.4%,laparoscopic:1.7%)and decreased from 11.6%in 1998-2009 vs 8.5%in 2010-2019(P<0.001).One-year and ten-year survival rates for children,adults,and elderly were 93.7%,67.5%,and 42.1%and 79.9%,39.2%,and 6.8%,respectively.The most common causes of death were malignancies and cardiovascular and respiratory diseases.CONCLUSION The annual use of gastrostomies in Sweden increased during the study period,with a shift towards more minimally invasive procedures.Although procedure-related death was rare,the overall 30-d mortality rate was high(10%).To overcome this,we believe that patient selection should be improved.

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.

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.

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.

Association of tumor budding with clinicopathological features and prognostic value in stage III-IV colorectal cancer

BACKGROUND Tumor budding(TB)has emerged as a promising independent prognostic biomarker in colorectal cancer(CRC).The prognostic role of TB has been extensively studied and currently affects clinical decision making in patients with stage I and II CRC.However,existing prognostic studies on TB in stage III CRC have been confined to small retrospective cohort studies.Consequently,this study investigated the correlation among TB categories,clinicopathological features,and prognosis in stage III-IV CRC to further enhance the precision and individualization of treatment through refined prognostic risk stratification.AIM To analyze the relationship between TB categories and clinicopathological characteristics and assess their prognostic value in stage III-IV CRC to further refine the prognostic risk stratification of stage III-IV CRC.METHODS The clinical data of 547 CRC patients were collected for this retrospective study.Infiltration at the front edge of the tumor buds was counted according to the 2016 International Tumor Budding Consensus Conference guidelines.RESULTS Multivariate Cox proportional hazards regression analysis demonstrated that chemotherapy(P=0.004),clinical stage IV(P<0.001),≥4 regional lymph node metastases(P=0.004),left-sided colonic cancer(P=0.040),and Bd 2-3(P=0.002)were independent prognostic factors in patients with stage III-IV CRC.Moreover,the density of tumor infiltrating lymphocytes was higher in Bd 1 than in Bd 2-3,both in the tumor stroma and its invasive margin.CONCLUSION TB has an independent predictive prognostic value in patients with stage III-IV CRC.It is recommended to complete the TB report of stage III-IV CRC cases in the standardized pathological report to further refine risk stratification.

Identifying and validating MMP family members(MMP2,MMP9,MMP12,and MMP16)as therapeutic targets and biomarkers in kidney renal clear cell carcinoma(KIRC)

Kidney Renal Clear Cell Carcinoma(KIRC)is a malignant tumor that carries a substantial risk of morbidity and mortality.The MMP family assumes a crucial role in tumor invasion and metastasis.This study aimed to uncover the mechanistic relevance of the MMP gene family as a therapeutic target and diagnostic biomarker in Kidney Renal Clear Cell Carcinoma(KIRC)through a comprehensive approach encompassing both computational and molecular analyses.STRING,Cytoscape,UALCAN,GEPIA,OncoDB,HPA,cBioPortal,GSEA,TIMER,ENCORI,DrugBank,targeted bisulfite sequencing(bisulfite-seq),conventional PCR,Sanger sequencing,and RT-qPCR based analyses were used in the present study to analyze MMP gene family members to accurately determine a few hub genes that can be utilized as both therapeutic targets and diagnostic biomarkers for KIRC.By performing STRING and Cytohubba analyses of the 24 MMP gene family members,MMP2(matrix metallopeptidase 2),MMP9(matrix metallopeptidase 9),MMP12(matrix metallopeptidase 12),and MMP16(matrix metallopeptidase 16)genes were denoted as hub genes having highest degree scores.After analyzing MMP2,MMP9,MMP12,and MMP16 via various TCGA databases and RT-qPCR technique across clinical samples and KIRC cell lines,interestingly,all these hub genes were found significantly overexpressed at mRNA and protein levels in KIRC samples relative to controls.The notable effect of the up-regulated MMP2,MMP9,MMP12,and MMP16 was also documented on the overall survival(OS)of the KIRC patients.Moreover,targeted bisulfite-sequencing(bisulfite-seq)analysis revealed that promoter hypomethylation pattern was associated with up-regulation of hub genes(MMP2,MMP9,MMP12,and MMP16).In addition to this,hub genes were involved in various diverse oncogenic pathways.The MMP gene family members(MMP2,MMP9,MMP12,and MMP16)may serve as therapeutic targets and prognostic biomarkers in KIRC.

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

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

Computed tomography-based radiomics to predict early recurrence of hepatocellular carcinoma post-hepatectomy in patients background on cirrhosis

BACKGROUND The prognosis for hepatocellular carcinoma(HCC)in the presence of cirrhosis is unfavourable,primarily attributable to the high incidence of recurrence.AIM To develop a machine learning model for predicting early recurrence(ER)of posthepatectomy HCC in patients with cirrhosis and to stratify patients’overall survival(OS)based on the predicted risk of recurrence.METHODS In this retrospective study,214 HCC patients with cirrhosis who underwent curative hepatectomy were examined.Radiomics feature selection was conducted using the least absolute shrinkage and selection operator and recursive feature elimination methods.Clinical-radiologic features were selected through univariate and multivariate logistic regression analyses.Five machine learning methods were used for model comparison,aiming to identify the optimal model.The model’s performance was evaluated using the receiver operating characteristic curve[area under the curve(AUC)],calibration,and decision curve analysis.Additionally,the Kaplan-Meier(K-M)curve was used to evaluate the stratification effect of the model on patient OS.RESULTS Within this study,the most effective predictive performance for ER of post-hepatectomy HCC in the background of cirrhosis was demonstrated by a model that integrated radiomics features and clinical-radiologic features.In the training cohort,this model attained an AUC of 0.844,while in the validation cohort,it achieved a value of 0.790.The K-M curves illustrated that the combined model not only facilitated risk stratification but also exhibited significant discriminatory ability concerning patients’OS.CONCLUSION The combined model,integrating both radiomics and clinical-radiologic characteristics,exhibited excellent performance in HCC with cirrhosis.The K-M curves assessing OS revealed statistically significant differences.

Assessing recent recurrence after hepatectomy for hepatitis Brelated hepatocellular carcinoma by a predictive model based on sarcopenia

BACKGROUND Sarcopenia may be associated with hepatocellular carcinoma(HCC)following hepatectomy.But traditional single clinical variables are still insufficient to predict recurrence.We still lack effective prediction models for recent recurrence(time to recurrence<2 years)after hepatectomy for HCC.AIM To establish an interventable prediction model to estimate recurrence-free survival(RFS)after hepatectomy for HCC based on sarcopenia.METHODS We retrospectively analyzed 283 hepatitis B-related HCC patients who underwent curative hepatectomy for the first time,and the skeletal muscle index at the third lumbar spine was measured by preoperative computed tomography.94 of these patients were enrolled for external validation.Cox multivariate analysis was per-formed to identify the risk factors of postoperative recurrence in training cohort.A nomogram model was developed to predict the RFS of HCC patients,and its predictive performance was validated.The predictive efficacy of this model was evaluated using the receiver operating characteristic curve.RESULTS Multivariate analysis showed that sarcopenia[Hazard ratio(HR)=1.767,95%CI:1.166-2.678,P<0.05],alpha-fetoprotein≥40 ng/mL(HR=1.984,95%CI:1.307-3.011,P<0.05),the maximum diameter of tumor>5 cm(HR=2.222,95%CI:1.285-3.842,P<0.05),and hepatitis B virus DNA level≥2000 IU/mL(HR=2.1,95%CI:1.407-3.135,P<0.05)were independent risk factors associated with postoperative recurrence of HCC.Based on the sarcopenia to assess the RFS model of hepatectomy with hepatitis B-related liver cancer disease(SAMD)was established combined with other the above risk factors.The area under the curve of the SAMD model was 0.782(95%CI:0.705-0.858)in the training cohort(sensitivity 81%,specificity 63%)and 0.773(95%CI:0.707-0.838)in the validation cohort.Besides,a SAMD score≥110 was better to distinguish the high-risk group of postoperative recurrence of HCC.CONCLUSION Sarcopenia is associated with recent recurrence after hepatectomy for hepatitis B-related HCC.A nutritional status-based prediction model is first established for postoperative recurrence of hepatitis B-related HCC,which is superior to other models and contributes to prognosis prediction.

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.

Growth of RB Population in the Conversion Phase of Chlamydia Life Cycle

Upon infecting a host cell,the reticulate body(RB)form of the Chlamydia bacteria simply proliferates by binary fission for an extended period.Available data show only RB units in the infected cells 20 hours post infection(hpi),spanning nearly half way through the development cycle.With data collected every 4 hpi,conversion to the elementary body(EB)form begins abruptly at a rapid rate sometime around 24 hpi.By modeling proliferation and conversion as simple birth and death processes,it has been shown that the optimal strategy for maximizing the total(mean)EB population at host cell lysis time is a bang-bang control qualitatively replicating the observed conversion activities.However,the simple birth and death model for the RB proliferation and conversion to EB deviates in a significant way from the available data on the evolution of the RB population after the onset of RB-to-EB conversion.By working with a more refined model that takes into account a small size threshold eligibility requirement for conversion noted in the available data,we succeed in removing the deficiency of the previous models on the evolution of the RB population without affecting the optimal bang-bang conversion strategy.

Predictive value of red blood cell distribution width and hematocrit for short-term outcomes and prognosis in colorectal cancer patients undergoing radical surgery

BACKGROUND Previous studies have reported that low hematocrit levels indicate poor survival in patients with ovarian cancer and cervical cancer,the prognostic value of hematocrit for colorectal cancer(CRC)patients has not been determined.The prognostic value of red blood cell distribution width(RDW)for CRC patients was controversial.AIM To investigate the impact of RDW and hematocrit on the short-term outcomes and long-term prognosis of CRC patients who underwent radical surgery.METHODS Patients who were diagnosed with CRC and underwent radical CRC resection between January 2011 and January 2020 at a single clinical center were included.The short-term outcomes,overall survival(OS)and disease-free survival(DFS)were compared among the different groups.Cox analysis was also conducted to identify independent risk factors for OS and DFS.RESULTS There were 4258 CRC patients who underwent radical surgery included in our study.A total of 1573 patients were in the lower RDW group and 2685 patients were in the higher RDW group.There were 2166 and 2092 patients in the higher hematocrit group and lower hematocrit group,respectively.Patients in the higher RDW group had more intraoperative blood loss(P<0.01)and more overall complications(P<0.01)than did those in the lower RDW group.Similarly,patients in the lower hematocrit group had more intraoperative blood loss(P=0.012),longer hospital stay(P=0.016)and overall complications(P<0.01)than did those in the higher hematocrit group.The higher RDW group had a worse OS and DFS than did the lower RDW group for tumor node metastasis(TNM)stage I(OS,P<0.05;DFS,P=0.001)and stage II(OS,P=0.004;DFS,P=0.01)than the lower RDW group;the lower hematocrit group had worse OS and DFS for TNM stage II(OS,P<0.05;DFS,P=0.001)and stage III(OS,P=0.001;DFS,P=0.001)than did the higher hematocrit group.Preoperative hematocrit was an independent risk factor for OS[P=0.017,hazard ratio(HR)=1.256,95%confidence interval(CI):1.041-1.515]and DFS(P=0.035,HR=1.194,95%CI:1.013-1.408).CONCLUSION A higher preoperative RDW and lower hematocrit were associated with more postoperative complications.However,only hematocrit was an independent risk factor for OS and DFS in CRC patients who underwent radical surgery,while RDW was not.

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.