surviving,caspase-3,AQP1与妊娠晚期羊水过少相关性研究

目的:探讨Survivin、caspase-3及水通道蛋白1(Aquaporin 1,AQP1)与妊娠晚期羊水过少中的作用及相关性,为妊娠晚期羊水过少的临床治疗提供新的思路。方法:收集32例选择性剖宫产羊水过少临床病例以及30羊水正常的胎膜组织样本,采用免疫组织化学SP法检测Survivin、caspase-3及AQP1,并对其强度行定量分析。结果:羊水过少患者胎膜组织Survivin、AQP1的表达均低于羊水正常组,而caspase-3表达高于正常组。Survivin与caspase-3表达呈负相关,与AQP1表达呈正相关,caspase-3与AQP1表达呈负相关。结论:妊娠晚期羊水过少可能与Survivin表达减少,caspase-3表达增加引起胎膜组织细胞过度凋亡,AQP1下调,羊水的跨膜运输异常有关。

Surviving by Dying:A Paradox of Life On Mark Twain' s Is He Living,or is He Dead

Is He Living,or Is He Dead is a splendid sample of Twain' s bitter satire.By focusing on textual analysis of the story,this thesis is trying to illustrate "surviving by dying",such a paradox of life implied by Mark Twain,and to reveal the tragic nature masked by the humorous satire in the story.

A Surviving Patient with Record High Creatinine

Creatinine is a product of muscle protein breakdown cleared by the kidneys at a constant rate. The glomerular filtration rate is estimated based on serum creatinine. There is no definitive level of serum creatinine which is itself incompatible with human survival. We present the highest serum creatinine associated with survival based on a thorough review of the literature. A 34-year-old male patient with baseline serum creatinine of 1.2 mg/dl presented our emergency department with a six week history of new onset of uremic symptoms. His past medical history was unremarkable. On exam, he was in no distress. His BMI was 28. His exam was significant only for elevated blood pressure and asterixis. His peak serum creatinine was 53.9 mg/dl. The patient subsequently required maintenance hemodialysis and later changed to long-term peritoneal dialysis. To our knowledge, based on a thorough review of the literature using PubMed, Cochrane Database and the United States Renal Data System (USRDS), this is the highest level of serum creatinine ever reported. We conclude that serum creatinine itself is non-lethal. It is more likely that other electrolyte and retained metabolic abnormalities of renal failure frequently cause symptoms or death before creatinine toxicity, if such a level exists, creatinine has reached.

Implementing surviving sepsis campaign bundles in China： a prospective cohort study

Background Surviving sepsis campaign （SSC） bundles have been demonstrated to significantly improve survival in sepsis and septic shock patients worldwide. Compliance with these protocols and resultant mortality in sepsis patients was investigated in intensive care units （ICUs） in China. Methods Adult patients with severe sepsis or septic shock treated from September 2007 to October 2008 in 11 ICUs of Chinese teaching hospitals were included. The primary outcome was compliance with resuscitation and management bundles. Secondary outcomes included individual bundle protocol impact and the effects of the completed bundle protocol number on 28-day mortality. Results Overall compliance during 6-hr resuscitation and 24-hour management bundles were 5.5% and 17.4%, respectively, and 28-day mortality was 33.0%. Compliance with protocols for blood cultures before antibiotics （42.2%）, central venous pressure 〉8 mmHg （65.9%）, central venous oxygen saturation 〉70% （25.0%）, and optimized glucose control （82.1%）, were significantly associated with decreased 28-day mortality （P 〈0.05）. When adjusted for age, acute organ dysfunction, and APACHE II score, compliance with the blood culture before antibiotics protocol produced the most significant decrease in 28-day mortality （OR, 0.33; 95% CI, 0.16-0.70; P=0.004）. Compliance with z5 protocols in the 6-hour resuscitation bundle was also associated with lower 28-day mortality in septic shock patients （OR, 0.17; 95% CI, 0.06-0.54; P = 0.001）. Conclusions Compliance with resuscitation and management bundles is generally poor in China; however, when applied, 6-hour resuscitation bundle are associated with significant reductions in 28-day mortality for sepsis patients.

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.

The impact of alpha-fetoprotein(AFP),child-turcotte-pugh(CTP)score and disease staging on the survival of hepatocellular carcinoma(HCC)patients:a retrospective cohort from single oncology center

Background:Hepatocellular carcinoma(HCC)is the most common cause of cancer-related death in Saudi Arabia.Our study aimed to investigate the patterns of HCC and the effect of TNM staging,Alfa-fetoprotein(AFP),and Child-Turcotte Pugh(CTP)on patients’overall survival(OS).Methods:A retrospective analysis was conducted on 43 HCC patients at a single oncology center in Saudi Arabia from 2015 to 2020.All patients had to fulfill one of the following criteria:(a)a liver lesion reported as definitive HCC on dynamic imaging and/or(b)a biopsy-confirmed diagnosis.Results:The mean patient age of all HCC cases was 66.8 with a male-to-female ratio of 3.3:1.All patients were stratified into two groups:viral HCC(n=22,51%)and non-viral HCC(n=21,49%).Among viral-HCC patients,55%were due to HBV and 45%due to HCV.Cirrhosis was diagnosed in 79%of cases.Age and sex did not significantly statistically differ in OS among viral and non-viral HCC patients(p-value>0.05).About 65%of patients had tumor size>5 cm during the diagnosis,with a significant statistical difference in OS(p-value=0.027).AFP was>400 ng/ml in 45%of the patients.There was a statistically significant difference in the OS in terms of AFP levels(p-value=0.021).A statistically significant difference was also observed between the CTP score and OS(p-value=0.02).CTP class B had the longest survival.BSC was the most common treatment provided to HCC patients followed by sorafenib therapy.There was a significant statistical difference in OS among viral and non-viral HCC patients(p-value=0.008).Conclusions:The most common predictors for OS were the underlying cause of HCC,AFP,and tumor size.Being having non-viral etiology,a tumor size>5 cm,an AFP>400 ng/mL,and a CTP score class C were all negatively associated with OS.

Insights into spinal muscular atrophy from molecular biomarkers

Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle weakness.It is one of the most common genetic causes of mortality among infants aged less than 2 years.Biomarker research is currently receiving more attention,and new candidate biomarkers are constantly being discovered.This review initially discusses the evaluation methods commonly used in clinical practice while briefly outlining their respective pros and cons.We also describe recent advancements in research and the clinical significance of molecular biomarkers for spinal muscular atrophy,which are classified as either specific or non-specific biomarkers.This review provides new insights into the pathogenesis of spinal muscular atrophy,the mechanism of biomarkers in response to drug-modified therapies,the selection of biomarker candidates,and would promote the development of future research.Furthermore,the successful utilization of biomarkers may facilitate the implementation of gene-targeting treatments for patients with spinal muscular atrophy.

Development of a nomogram for overall survival in patients with esophageal carcinoma:A prospective cohort study in China

BACKGROUND Esophageal carcinoma(EC)presents a significant public health issue in China,with its prognosis impacted by myriad factors.The creation of a reliable prog-nostic model for the overall survival(OS)of EC patients promises to greatly advance the customization of treatment approaches.AIM To create a more systematic and practical model that incorporates clinically significant indicators to support decision-making in clinical settings.METHODS This study utilized data from a prospective longitudinal cohort of 3127 EC patients treated at Chongqing University Cancer Hospital between January 1,2018,and December 12,2020.Utilizing the least absolute shrinkage and selection operator regression alongside multivariate Cox regression analyses helped pinpoint pertinent variables for constructing the model.Its efficacy was assessed by concordance index(C-index),area under the receiver operating characteristic curve(AUC),calibration curves,and decision curve analysis(DCA).RESULTS Nine variables were determined to be significant predictors of OS in EC patients:Body mass index(BMI),Karnofsky performance status,TNM stage,surgery,radiotherapy,chemotherapy,immunotherapy,platelet-to-lymphocyte ratio,and albumin-to-globulin ratio(ALB/GLB).The model demonstrated a C-index of 0.715(95%CI:0.701-0.729)in the training cohort and 0.711(95%CI:0.689-0.732)in the validation cohort.In the training cohort,AUCs for 1-year,3-year,and 5-year OS predictions were 0.773,0.787,and 0.750,respectively;in the validation cohort,they were 0.772,0.768,and 0.723,respectively,illustrating the model's precision.Calibration curves and DCA verified the model's predictive accuracy and net benefit.CONCLUSION A novel prognostic model for determining the OS of EC patients was successfully developed and validated to help clinicians in devising individualized treatment schemes for EC patients.

Netrin-1 signaling pathway mechanisms in neurodegenerative diseases

Netrin-1 and its receptors play crucial roles in inducing axonal growth and neuronal migration during neuronal development.Their profound impacts then extend into adulthood to encompass the maintenance of neuronal survival and synaptic function.Increasing amounts of evidence highlight several key points:(1)Diminished Netrin-1 levels exacerbate pathological progression in animal models of Alzheimer’s disease and Parkinson’s disease,and potentially,similar alterations occur in humans.(2)Genetic mutations of Netrin-1 receptors increase an individuals’susceptibility to neurodegenerative disorders.(3)Therapeutic approaches targeting Netrin-1 and its receptors offer the benefits of enhancing memory and motor function.(4)Netrin-1 and its receptors show genetic and epigenetic alterations in a variety of cancers.These findings provide compelling evidence that Netrin-1 and its receptors are crucial targets in neurodegenerative diseases.Through a comprehensive review of Netrin-1 signaling pathways,our objective is to uncover potential therapeutic avenues for neurodegenerative disorders.

Trends of alkaline phosphatase to prealbumin ratio in patients with hepatitis B linked to hepatocellular carcinoma development

BACKGROUND Chronic hepatitis B often progresses silently toward hepatocellular carcinoma(HCC),a leading cause of mortality worldwide.Early detection of HCC is crucial,yet challenging.AIM To investigate the role of dynamic changes in alkaline phosphatase to prealbumin ratio(APR)in hepatitis B progression to HCC.METHODS Data from 4843 patients with hepatitis B(January 2015 to January 2024)were analyzed.HCC incidence rates in males and females were compared using the log-rank test.Data were evaluated using Kaplan–Meier analysis.The Linear Mixed-Effects Model was applied to track the fluctuation of APR levels over time.Furthermore,Joint Modeling of Longitudinal and Survival data was employed to investigate the temporal relationship between APR and HCC risk.RESULTS The incidence of HCC was higher in males.To ensure the model’s normality assumption,this study applied a logarithmic transformation to APR,yielding ratio.Ratio levels were higher in females(t=5.26,P<0.01).A 1-unit increase in ratio correlated with a 2.005-fold higher risk of HCC in males(95%CI:1.653-2.431)and a 2.273-fold higher risk in females(95%CI:1.620-3.190).CONCLUSION Males are more prone to HCC,while females have higher APR levels.Despite no baseline APR link,rising APR indicates a higher HCC risk.

Nomogram for overall survival in ampullary adenocarcinoma using the surveillance,epidemiology,and end results database and external validation

BACKGROUND Ampullary adenocarcinoma is a rare malignant tumor of the gastrointestinal tract.Currently,only a few cases have been reported,resulting in limited information on survival.AIM To develop a dynamic nomogram using internal and external validation to predict survival in patients with ampullary adenocarcinoma.METHODS Data were sourced from the surveillance,epidemiology,and end results stat database.The patients in the database were randomized in a 7:3 ratio into training and validation groups.Using Cox regression univariate and multivariate analyses in the training group,we identified independent risk factors for overall survival and cancer-specific survival to develop the nomogram.The nomogram was validated with a cohort of patients from the First Affiliated Hospital of the Army Medical University.RESULTS For overall and cancer-specific survival,12(sex,age,race,lymph node ratio,tumor size,chemotherapy,surgical modality,T stage,tumor differentiation,brain metastasis,lung metastasis,and extension)and 6(age;surveillance,epidemiology,and end results stage;lymph node ratio;chemotherapy;surgical modality;and tumor differentiation)independent risk factors,respectively,were incorporated into the nomogram.The area under the curve values at 1,3,and 5 years,respectively,were 0.807,0.842,and 0.826 for overall survival and 0.816,0.835,and 0.841 for cancer-specific survival.The internal and external validation cohorts indicated good consistency of the nomogram.CONCLUSION The dynamic nomogram offers robust predictive efficacy for the overall and cancer-specific survival of ampullary adenocarcinoma.

Hepatocellular carcinoma recurrence after liver transplant:An Australian single-centre study

BACKGROUND Hepatocellular carcinoma(HCC)is a leading cause of cancer-related deaths worldwide.Liver transplantation(LT)offers the most effective treatment.HCC recurrence is the strongest risk factor that decreases post-LT survival in patients transplanted for HCC.The rate of HCC recurrence is generally reported as 8%-20%in the literature.Many predictors of HCC have already been researched,however,to our knowledge there are no published studies on this topic using Australian data.AIM To determine the rate and identify predictors of HCC recurrence in a contemporary Western Australian LT cohort.METHODS We performed a retrospective cohort study of all liver transplants in patients with HCC at Sir Charles Gairdner Hospital between 2006 and 2021.Data was collected from various health record databases and included recipient demographics,serum biochemistry,radiology,operation notes,explant histopathology and details of recurrence.Overall survival of HCC patients post-LT,stratified for recurrence,was calculated by Kaplan Meier analysis.Univariate and multivariate Cox regression was used to determine predictors of HCC recurrence post-LT.RESULTS Between 1/1/2006 and 12/31/2021,119 patients were transplanted with HCC.8.4%of subjects developed recurrent HCC after LT with median follow-up time of 5.4 years.The median time to recurrence was 2.9 years±0.75 years.When comparing baseline characteristics,a greater proportion of subjects with recurrence had common characteristics on explant histopathology,including>3 viable nodules(P=0.001),vascular invasion(P=0.003)and poorly differentiated HCC(P=0.03).Unadjusted survival curves showed lower 1-year,3-year,5-year and 10-year survival rates in subjects with HCC recurrence compared to those without HCC recurrence(90%vs 92%,70%vs 88%,42%vs 80%,14%vs 76%,respectively;log rank P<0.001).CONCLUSION HCC recurrence was low at 8.4%in this contemporary Australian cohort,however it significantly impacted post-LT survival.Further studies are required to confirm predictors of recurrence and improve recipient outcomes.

Surviving rate of graphs and Firefighter Problem

The Firefighter Problem on a graph can be viewed as a simplified model of the spread of contagion,fire,rumor,computer virus,etc.The fire breaks out at one or more vertices in a graph at the first round,and the firefighter chooses some vertices to protect.The fire spreads to all non-protected neighbors at the beginning of each time-step.The process stops when the fire can no longer spread.The Firefighter Problem has attracted considerable attention since it was introduced in 1995.In this paper we provide a survey on recent research progress of this field,including algorithms and complexity,Firefighter Problem for special graphs(finite and infinite)and digraphs,surviving rate and burning number of graphs.We also collect some open problems and possible research subjects.

Unusual Ovarian Cancer Relapse Managed by Nivolumab in a Long-term Surviving Patient with PD-L1 Mutation

INTRODUCTION This report describes a case of ovarian cancer recurrent as sternal and costal metastasis long after initial treatment. The whole-exome sequencing suggested programmed death-ligand I （PD-L1） mutation. The patient responded well to nivolumab, an anti-PD-1 monoclonal antibody. We discuss the case and review the literature.

GATIS score for predicting the prognosis of rectal neuroendocrine neoplasms:A Chinese multicenter study of 12-year experience

BACKGROUND There is currently a shortage of accurate,efficient,and precise predictive instruments for rectal neuroendocrine neoplasms(NENs).AIM To develop a predictive model for individuals with rectal NENs(R-NENs)using data from a large cohort.METHODS Data from patients with primary R-NENs were retrospectively collected from 17 large-scale referral medical centers in China.Random forest and Cox proportional hazard models were used to identify the risk factors for overall survival and progression-free survival,and two nomograms were constructed.RESULTS A total of 1408 patients with R-NENs were included.Tumor grade,T stage,tumor size,age,and a prognostic nutritional index were important risk factors for prognosis.The GATIS score was calculated based on these five indicators.For overall survival prediction,the respective C-indexes in the training set were 0.915(95%confidence interval:0.866-0.964)for overall survival prediction and 0.908(95%confidence interval:0.872-0.944)for progression-free survival prediction.According to decision curve analysis,net benefit of the GATIS score was higher than that of a single factor.The time-dependent area under the receiver operating characteristic curve showed that the predictive power of the GATIS score was higher than that of the TNM stage and pathological grade at all time periods.CONCLUSION The GATIS score had a good predictive effect on the prognosis of patients with R-NENs,with efficacy superior to that of the World Health Organization grade and TNM stage.

Cellular preconditioning and mesenchymal stem cell ferroptosis

In this editorial,we comment on the article published in the recent issue of the World Journal of Stem Cells.They focus on stem cell preconditioning to prevent ferroptosis by modulating the cystathionineγ-lyase/hydrogen sulfide(H_(2)S)pathway as a novel approach to treat vascular disorders,particularly pulmonary hypertension.Preconditioned stem cells are gaining popularity in regenerative medicine due to their unique ability to survive by resisting the harsh,unfavorable microenvironment of the injured tissue.They also secrete various paracrine factors against apoptosis,necrosis,and ferroptosis to enhance cell survival.Ferroptosis,a regulated form of cell death characterized by iron accumulation and oxidative stress,has been implicated in various pathologies encompassing dege-nerative disorders to cancer.The lipid peroxidation cascade initiates and sustains ferroptosis,generating many reactive oxygen species that attack and damage multiple cellular structures.Understanding these intertwined mechanisms provi-des significant insights into developing therapeutic modalities for ferroptosis-related diseases.This editorial primarily discusses stem cell preconditioning in modulating ferroptosis,focusing on the cystathionase gamma/H_(2)S ferroptosis pathway.Ferroptosis presents a significant challenge in mesenchymal stem cell(MSC)-based therapies;hence,the emerging role of H_(2)S/cystathionase gamma/H_(2) S signaling in abrogating ferroptosis provides a novel option for therapeutic intervention.Further research into understanding the precise mechanisms of H_(2)S-mediated cytoprotection against ferroptosis is warranted to enhance the thera-peutic potential of MSCs in clinical settings,particularly vascular disorders.

Priming mesenchymal stem cells to develop “super stem cells”

The stem cell pre-treatment approaches at cellular and sub-cellular levels encompass physical manipulation of stem cells to growth factor treatment,genetic manipulation,and chemical and pharmacological treatment,each strategy having advantages and limitations.Most of these pre-treatment protocols are non-combinative.This editorial is a continuum of Li et al’s published article and Wan et al’s editorial focusing on the significance of pre-treatment strategies to enhance their stemness,immunoregulatory,and immunosuppressive properties.They have elaborated on the intricacies of the combinative pre-treatment protocol using pro-inflammatory cytokines and hypoxia.Applying a well-defined multi-pronged combinatorial strategy of mesenchymal stem cells(MSCs),pre-treatment based on the mechanistic understanding is expected to develop“Super MSCs”,which will create a transformative shift in MSC-based therapies in clinical settings,potentially revolutionizing the field.Once optimized,the standardized protocols may be used with slight modifications to pre-treat different stem cells to develop“super stem cells”with augmented stemness,functionality,and reparability for diverse clinical applications with better outcomes.

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.

Impact of preoperative inflammatory and nutritional markers on the prognosis of patients with peritoneal metastasis of colorectal cancer

BACKGROUND Identifying patients with peritoneal metastasis(PMs)of colorectal cancer(CRC)who will benefit from cytoreductive surgery and hyperthermic intraperitoneal chemotherapy is crucial before surgery.Inflammatory and nutritional indicators play essential roles in cancer development and metastasis.AIM To investigate the association of preoperative inflammatory and nutritional markers with prognosis in patients with CRC-PM.METHODS We included 133 patients diagnosed with CRC-PM between July 2012 and July 2018.Patients’demographics,overall survival(OS),and preoperative inflammatory and nutritional markers were evaluated.The Kaplan-Meier method and log-rank test were used to estimate differences.RESULTS Of the 133 patients,94(70.6%)had normal hemoglobin(Hb)and 54(40.6%)had a high neutrophil-to-lymphocyte ratio(NLR).The median OS(mOS)was significantly lower for patients with high NLR(7.9 months)than for those with low NLR(25.4 months;P=0.002).Similarly,patients with normal Hb had a longer mOS(18.5 months)than those with low Hb(6.3 months;P<0.001).Multivariate analysis identified age,carbohydrate antigen 199 levels,NLR,Hb,and peritoneal cancer index as independent predictors of OS.Based on these findings,a nomogram was constructed,which demonstrated a good capacity for prediction,with a C-index of 0.715(95%confidence interval:0.684-0.740).Furthermore,the 1-and 2-year survival calibration plots showed good agreement between predicted and actual OS rates.The areas under the curve for the 1-and 2-year survival predictions of the nomogram were 0.6238 and 0.6234,respectively.CONCLUSION High NLR and low Hb were identified as independent predictive risk factors for poor prognosis in patients with CRC-PM.The established nomogram demonstrated high accuracy in predicting OS for patients with CRC-PM,indicating its potential as a valuable prognostic tool for this patient population.

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.