Risk-score

风险评分
  • 文章类型: Journal Article
    GeRi评分对120天死亡率的验证,老年儿科医生术前就诊的影响,并根据结果进行手术时机。该评分对120天死亡率具有预测价值。在24小时内手术或术前老年就诊均未发现优势。
    目标:许多工具可以预测髋部骨折患者的死亡率,但是它们包括许多变量,需要耗时的评估,而且很难计算。GeRi评分提供了一种快速的术前评估方法。这项研究的目的是验证120天随访中的分数,并确定老年病学家术前就诊和手术时机对患者预后的影响。
    方法:对2017年至2021年的AltersTraumaRegisterDGU®进行了回顾性分析,包括所有股骨近端骨折.患者被分为低,moderate-,和基于GeRi评分的高危人群。死亡率采用logistic回归分析。为了确定手术时间和术前访视的影响,使用精确的GeRi-Score进行匹配,术前步行能力,骨折类型,还有手术时间.
    结果:该研究包括38,570名患者,分为12,673个低风险,18,338中等风险,和7559名高风险患者。中等风险组的死亡风险是低风险组的三倍(OR3.19(95%CI2.68-3.79;p<0.001)),而高危组的死亡风险几乎是低危组的8倍(OR7.82(95%CI6.51-9.93;p<0.001)).在所有组的前24小时内,手术均未发现优势。术前老年就诊和死亡率之间存在相关性,表明中度和高危人群的内部死亡率增加。
    结论:GeRi评分对120天死亡率具有预测价值。在24小时内没有发现手术的优势。分析没有证明术前老年就诊的益处,但是需要更多的数据。
    A validation of the GeRi-Score on 120-day mortality, the impact of a pre-operative visit by a geriatrician, and timing of surgery on the outcome was conducted. The score has predictive value for 120-day mortality. No advantage was found for surgery within 24 h or a preoperative geriatric visit.
    OBJECTIVE: Numerous tools predict mortality among patients with hip fractures, but they include many variables, require time-consuming assessment, and are difficult to calculate. The GeRi-Score provides a quick method of pre-operative assessment. The aim of this study is to validate the score in the 120-day follow-up and determine the impact of a pre-operative visit by a geriatrician and timing of surgery on the patient outcome.
    METHODS: A retrospective analysis of the AltersTraumaRegister DGU® from 2017 to 2021 was conducted, including all proximal femur fractures. The patients were divided into low-, moderate-, and high-risk groups based on the GeRi-Score. Mortality was analyzed using logistic regression. To determine the influence of the time to surgery and the preoperative visit by a geriatrician, matching was performed using the exact GeRi-Score, preoperative walking ability, type of fracture, and the time to surgery.
    RESULTS: The study included 38,570 patients, divided into 12,673 low-risk, 18,338 moderate-risk, and 7,559 high-risk patients. The moderate-risk group had three times the mortality risk of the low-risk group (OR 3.19 (95% CI 2.68-3.79; p<0.001)), while the high-risk group had almost eight times the mortality risk than the low-risk group (OR 7.82 (95% CI 6.51-9.93; p<0.001)). No advantage was found for surgery within the first 24 h across all groups. There was a correlation of a preoperative geriatric visit and mortality showing an increase in the moderate and high-risk group on in-house mortality.
    CONCLUSIONS: The GeRi-Score has predictive value for 120-day mortality. No advantage was found for surgery within 24 h. The analysis did not demonstrate a benefit of the preoperative geriatric visit, but more data are needed.
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  • 文章类型: Journal Article
    背景:免疫检查点抑制剂(ICI)与危及生命的心肌炎有关,但越来越多地认识到轻度表现。导致ICI-心肌炎的相同自身免疫过程可以表现为并发全身性肌炎,肌无力样综合征,和呼吸肌衰竭。缺乏这种“心肌毒性”的预后因素。
    方法:多中心注册中心回顾性收集了2014-2023年期间17个国家的数据。多变量cox回归模型(风险比(HR),[95%置信区间])用于确定主要复合结局的危险因素:严重心律失常,心力衰竭,呼吸肌衰竭,和/或心肌毒性相关死亡。协变量包括人口统计学,合并症,心肌肌肉症状,诊断,和治疗。使用时间依赖性协变量,并估算缺失数据。得出并外部验证了基于点的预后风险评分。
    结果:在748例患者中(67%为男性,年龄23-94),主要复合结局的30天发生率,心肌毒性死亡,总死亡率为33%,13%,分别为17%。通过多变量分析,主要复合结局与活动性胸腺瘤相关(HR=3.60[1.93-6.72]),心肌肉症状的存在(HR=2.60[1.58-4.28]),出现心电图时低QRS电压(HR≤0.5mV与>1mV=2.08[1.31-3.30]),左心室射血分数(LVEF)<50%(HR=1.78[1.22-2.60]),和肌钙蛋白升高增量(HR=1.86[1.44-2.39],2.99[1.91-4.65],4.80[2.54-9.08],高于参考上限20倍、200倍和2000倍,分别)。使用这些参数制定的预后风险评分显示出良好的表现;30天主要结局发生率从3.9%(风险评分=0)逐渐增加到81.3%(风险评分=4)。该风险评分在两个独立的法国和美国队列中进行了外部验证。在外部法国队列中前瞻性地使用该风险评分,以识别在没有免疫抑制的情况下管理的低风险患者,这些患者没有心脏-肌肉毒性事件。
    结论:ICI-心肌炎可表现为高发病率和高死亡率。心肌炎的严重程度与肌钙蛋白的大小有关,胸腺瘤,低QRS电压,沮丧的LVEF,和心肌症状.包含这些特征的风险评分表现良好。
    UNASSIGNED: Immune-checkpoint inhibitors (ICI) are associated with life-threatening myocarditis but milder presentations are increasingly recognized. The same autoimmune process that causes ICI-myocarditis can manifest concurrent generalized myositis, myasthenia-like syndrome, and respiratory muscle failure. Prognostic factors for this \"cardiomyotoxicity\" are lacking.
    UNASSIGNED: A multicenter registry collected data retrospectively from 17 countries between 2014-2023. A multivariable cox regression model (hazard-ratio(HR), [95%confidence-interval]) was used to determine risk factors for the primary composite outcome: severe arrhythmia, heart failure, respiratory muscle failure, and/or cardiomyotoxicity-related death. Covariates included demographics, comorbidities, cardio-muscular symptoms, diagnostics, and treatments. Time-dependent covariates were used and missing data were imputed. A point-based prognostic risk score was derived and externally validated.
    UNASSIGNED: In 748 patients (67% male, age 23-94), 30-days incidence of the primary composite outcome, cardiomyotoxic death, and overall death were 33%, 13%, and 17% respectively. By multivariable analysis, the primary composite outcome was associated with active thymoma (HR=3.60[1.93-6.72]), presence of cardio-muscular symptoms (HR=2.60 [1.58-4.28]), low QRS-voltage on presenting electrocardiogram (HR for ≤0.5mV versus >1mV=2.08[1.31-3.30]), left ventricular ejection fraction (LVEF) <50% (HR=1.78[1.22-2.60]), and incremental troponin elevation (HR=1.86 [1.44-2.39], 2.99[1.91-4.65], 4.80[2.54-9.08], for 20, 200 and 2000-fold above upper reference limit, respectively). A prognostic risk score developed using these parameters showed good performance; 30-days primary outcome incidence increased gradually from 3.9%(risk-score=0) to 81.3%(risk-score≥4). This risk-score was externally validated in two independent French and US cohorts. This risk score was used prospectively in the external French cohort to identify low risk patients who were managed with no immunosuppression resulting in no cardio-myotoxic events.
    UNASSIGNED: ICI-myocarditis can manifest with high morbidity and mortality. Myocarditis severity is associated with magnitude of troponin, thymoma, low-QRS voltage, depressed LVEF, and cardio-muscular symptoms. A risk-score incorporating these features performed well.
    UNASSIGNED: NCT04294771 and NCT05454527.
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  • 文章类型: Journal Article
    背景:晚期患者受益于早期的姑息治疗。然而,这并不总是发生。该项目评估了已经可用的风险评分,护理评估需求(CAN)评分,将能够在退伍军人健康管理局(VHA)住院后30天内确定死亡风险最大的患者。
    方法:本回顾性分析的队列包括所有年龄在18岁以上且最近有CAN评分的VA急性患者。CAN评分是自动计算的VA风险评分,用于确定是否可以预测急性护理入院后的死亡风险。进行单因素logistic回归以获得入院后30天内的死亡概率,根据他们的CAN得分。
    结果:从2019年1月1日至2019年12月31日评估了298,467例患者记录。入院30天后有6%的死亡率,入院后1年内死亡率为17%。平均CAN评分为65(SD:29)。平均而言,CAN评分每增加一次,死亡概率就会增加7%.CAN评分为90的患者入院后30天死亡率为10%。
    结论:现成的风险评分,根据EHR数据自动计算,能够在急性护理环境中识别30天死亡率高的患者。下一步将是评估如何利用CAN评分来改善高危住院退伍军人的临终关怀。
    BACKGROUND: Terminally ill patients benefit from earlier engagement in palliative care. However, this does not always occur. This project assessed if an already available risk score, the Care Assessment Needs (CAN) score, would be able to identify patients at greatest risk for mortality within 30 days of hospital admission within the Veterans Health Administration (VHA).
    METHODS: The cohort of this retrospective analysis included all VA acute are patients over 18 years of age with a recent CAN score. The CAN score is an automatically calculated VA risk score that was repurposed to determine if it could predict risk of mortality after acute care admission. Univariate logistic regression was performed to obtain the probability of mortality within 30 days of admission, based on their CAN score.
    RESULTS: 298,467 patient records were assessed from January 1, 2019, to December 31, 2019. There was 6% mortality after 30 days of admissions, and 17% mortality within 1-year post-admission. Mean CAN score was 65 (SD: 29). On average, each incremental increase in the CAN score increased the probability of mortality by 7%. Patients with a CAN score of 90 had a 10% probability of 30-day post-admission mortality.
    CONCLUSIONS: A readily available risk score, automatically calculated from EHR data, was able to identify patients at high risk for 30-day mortality in the acute care setting. Next steps will be to assess how the CAN score can be utilized to in improve end of life care for high-risk hospitalized Veterans.
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  • 文章类型: Journal Article
    BACKGROUND: The hepatocellular carcinoma (HCC) incident rate is gradually increasing yearly despite all the research and efforts taken by scientific communities and governing bodies. Approximately 90% of all liver cancer cases belong to HCC. Usually, HCC patients approach the treatment in the late stages of this malignancy which becomes the primary cause of high mortality rate. The knowledge about molecular pathogenesis of HCC is limited and needs more attention from researchers to identify the driver genes and miRNAs, which causes to translate this information into clinical practice. Therefore, the key regulators identification of miRNA-mRNA regulatory network is essential to identify HCC-associated genes.
    METHODS: We extracted microRNA (miRNA) and messenger RNA (mRNA) expression datasets of normal and tumor HCC patient samples from UCSC Xena followed by identifying differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs). Univariate and multivariate cox-proportional hazard models were utilized to identify DEMs having significant association with overall survival (OS). Kaplan-Meier (KM) plotter was used to validate the presence of prognostic DEMs. A risk-score model was used to evaluate the effectiveness of KM-plotter validated DEMs combination on risk of samples. Target DEGs of prognostic miRNAs were identified via sources such as miRTargetLink and miRWalk followed by their validation in an external microarray cohort and enrichment analysis.
    RESULTS: 562 DEGs and 388 DEMs were identified followed by seven prognostic miRNAs (i.e., miR-19a, miR-19b, miR-30d-5p, miR-424-5p, miR-3677-5p, miR-3913-5p, miR-7705) post univariate, multivariate, risk-score model evaluation and KM-plotter analyses. ANLN, MRO, CPEB3 were their targets and were also validated in GSE84005 dataset.
    CONCLUSIONS: The findings of this study decipher that most significant miRNAs and their identified target genes have association with apoptosis, inflammation, cell cycle regulation and cancer-related pathways, which appear to contribute to HCC pathogenesis and therefore, the discovery of new targets.
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  • 文章类型: Journal Article
    目的:肝癌是一种预后不良的常见病。本研究的目的是从单细胞RNA中识别基于恶性细胞受体配体基因的亚群,这可能导致肝癌患者的定制免疫疗法。
    方法:基于scRNA-seq数据,我们鉴定了与预后相关的受体-配体基因,并通过单变量Cox回归和共识聚类将患者分为分子亚型.进行LASSO回归以构建预后模型,这在TCGA和ICGC数据集中得到了验证。使用ssGSEA分析免疫浸润和免疫治疗反应的预测,估计,潮汐,和TRS分数计算。最后,细胞系中关键基因和蛋白质水平的qPCR和蛋白质印迹验证。
    结果:使用16基因表达水平的风险模型预测肝癌患者的预后。RiskScore与肿瘤临床特征和免疫功能显著相关,结合临床病理特征进行生存预测。SRXN1在肝癌细胞和正常肝细胞中的表达差异。
    结论:我们的研究利用单细胞分析来研究恶性细胞与其他细胞类型之间的通讯,基于恶性细胞受体配体基因识别分子亚型,为个性化免疫治疗和预后预测模型的开发提供新的见解。
    Liver cancer is a prevalent disease with a dismal prognosis. The aim of the research is to identify subgroups based on malignant cell receptor ligand gene from single-cell RNA, which might lead to customized immunotherapy for patients with liver cancer.
    Based on scRNA-seq data, we identified the receptor-ligand genes associated with prognosis and classify patients into molecular subtypes by univariate Cox regression and consensus clustering. LASSO regression was performed to construct a prognostic model, which was validated in TCGA and ICGC datasets. Immune infiltration and prediction of immunotherapy response were analyzed using ssGSEA, ESTIMATE, TIDE, and TRS score calculation. Finally, qPCR and Western blot validation of key genes and protein levels in cell lines.
    A risk model using 16-gene expression levels predicted liver cancer patients\' prognosis. The RiskScore associated significantly with tumor clinical characteristics and immunity, integrated with clinicopathological features for survival prediction. Differential expression of SRXN1 was verified in hepatocellular carcinoma and normal liver cells.
    Our study utilizes single-cell analysis to investigate the communication between malignant cells and other cell types, identifying molecular subtypes based on malignant cell receptor ligand genes, offering new insights for the development of personalized immunotherapy and prognostic prediction models.
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  • 文章类型: Journal Article
    背景:这项研究的目的是为进行冠状动脉旁路移植术(CABG)的患者开发一种新的针对印度人群的风险预测评分(NH评分),并将其与胸外科医师协会(STS)评分和EuroSCOREII进行比较。
    方法:对2015年至2021年接受CABG的成年患者(n=6703)的基线特征进行分析,并分为训练数据(2015-2020年;n=5561)和验证数据(2020-2021年;n=1142)。CatBoost算法被训练来预测风险评分(NH评分),并通过Precision-RecallCurve和F1Score在验证集上测试性能。通过Brier评分测量模型校准,预期校准误差和最大校准误差。
    结果:所有结局的NH评分均优于STS和EuroSCOREII。对于死亡率,NH评分的PRAUC为(0.463[95%置信区间[CI],0.28-0.64])相比,STS评分为0.113[95%CI,0.04-0.22],EuroSCOREII评分为0.146[95%CI,0.06-0.31](p0.0001)。在发病率方面,NH评分优于STS评分(0.43[95%CI,0.33-0.50])。(0.229[95%CI,0.18-0.3,p<0.0001)。观察到的NH评分与预测的比率优于STS评分,与EuroSCOREII相似。与STS评分相比,NH评分在预测长期通气风险方面也更准确。
    结论:NH评分与STS评分和EuroSCOREII在印度人群中接受CABG患者的风险预测模型方面的表现相比,有了极好的改善。它保证对更大的数据集进行进一步验证。
    BACKGROUND: The aim of this study was to develop a new risk prediction score (NH Score) for patients undergoing coronary artery bypass grafting (CABG) specific to the Indian population and compare it to the Society of Thoracic Surgeon (STS) Score and the EuroSCORE II.
    METHODS: The baseline features of adult patients who underwent CABG between the years 2015 and 2021 (n = 6703) were taken and split into training data (2015-2020; n = 5561) and validation data (2020-2021; n = 1142). The CatBoost algorithm was trained to predict risk scores (NH score), and the performance was tested on the validation set by Precision-Recall Curve and F1 Score. Model calibration was measured by the Brier Score, Expected Calibration Error and Maximum Calibration Error.
    RESULTS: The NH score outperformed both the STS and EuroSCORE II for all outcomes. For mortality, the PR AUC for NH Score was (0.463 [95% confidence interval [CI], 0.28-0.64]) compared to 0.113 [95% CI, 0.04-0.22] for the STS score and 0.146 [95% CI, 0.06-0.31] for the EuroSCORE II (p ≪ 0.0001). With respect to morbidity NH Score was superior to the STS score (0.43 [95% CI, 0.33-0.50]) vs. (0.229 [95% CI, 0.18-0.3, p < 0.0001). The observed to the predicted ratio for NH score was superior to the STS Score and similar to EuroSCORE II. NH Score was also more accurate at predicting the risk of prolonged ventilation compared to the STS Score.
    CONCLUSIONS: NH score shows an excellent improvement over the performance of STS score and EuroSCORE II for modelling risk predictions for patients undergoing CABG in Indian population. It warrants further validation for larger datasets.
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  • 文章类型: Journal Article
    炎症是大多数恶性肿瘤的重要致病因子。了解炎症和癌症发展的潜在机制至关重要,从而制定和发展抗癌治疗策略。然而,在NSCLC中,炎症相关基因表征以及预后和化疗或免疫治疗的风险模型构建仍不清楚.
    从癌症基因组图谱(TCGA)数据库下载总共1014个具有RNA序列结果的肺癌样品。患者队列随机分为训练和测试队列,和200个炎症相关的基因是基于以前发表的数据进行筛选。进行了基于差异表达基因(DEGs)的共识聚类以及富集和免疫功能分析。建立预后预测模型,并基于该模型进行化疗和免疫治疗敏感性分析。最后,使用H1299和HCC827细胞测试KRT6A敲低后的米托蒽醌和奥沙尔铂敏感性。
    我们从NSCLC数据集中鉴定了炎症相关基因,建立了基于聚类炎症相关基因的预后预测标志,为区分预后不良的高危NSCLC病例奠定了一定的基础。列线图提供了1-的AUC值,3-,验证队列的5年总生存率分别为0.831,0.853和0.86.Moover,根据NSCLC患者的不同风险组,对免疫治疗或化疗的不同敏感性进行了分类,提供了有力的临床参考。最后,在H1299和HCC827细胞中靶向对米托蒽醌和奥沙利铂敏感的KRT6A。
    炎症相关基因风险评分是NSCLC潜在的化疗和免疫治疗生物标志物,针对非小细胞肺癌中米托蒽醌和奥沙利铂敏感的KRT6A。强调炎症相关基因可以为区分预后不良的高危NSCLC病例奠定一定的基础。基于炎症相关基因的风险评分与CD274、TGFBR1和TGFB1表达呈正相关。在H1299和HCC827细胞中靶向对米托蒽醌和奥沙利铂敏感的KRT6A。
    Inflammation is an important pathogenic factor of most malignant tumors. It is essential to understand mechanism underlying inflammation and cancer development, so as to formulate and develop anti-cancer treatment strategies. However, inflammatory-related gene characterization as well as risk model construction in prognosis and response chemotherapy or immunotherapy in NSCLC are still remain unclear.
    A total of 1014 lung cancer samples with RNA-seqencing results were download from The Cancer Genome Atlas (TCGA) database. The patient cohort was randomized as a training and test cohorts, and 200 inflammatory-related genes were selected based on previously published data. Consensus clustering and Enrichment and immune function analyses base on Differential expression genes (DEGs) were performed. Prognosis Prediction Model were Constructed and Chemotherapy and immunotherapy sensitivity base on this model were performed. At last, H1299 and HCC827 cells were used to tested the mitoxantrone and oxal iplatin sensitivity after KRT6A knockdown.
    We identified the inflammatory-related genes from NSCLC datasets to build one prognosis prediction signature based on cluster inflammatory-related genes to lay a certain foundation for distinguishing high-risk NSCLC cases with dismal prognostic outcome. The nomogram provides the AUC values for 1-, 3-, and 5-year overall survival were 0.831, 0.853, and 0.86 in validation cohort. Morover, different sensitivity of immunotherapy or chemotherapy also were classified base on the different risk groups in NSCLC patients, which provided potent clinical reference. At last, targeting KRT6A sensitive to mitoxantrone and oxaliplatin in H1299 and HCC827 cells.
    Inflammatory-related gene risk-score is the potential chemotherapeutic and immunotherapeutic biomarker for NSCLC, and targeting KRT6A sensitive to mitoxantrone and oxaliplatin in NSCLC.HighlightsInflammatory-related genes can lay a certain foundation for distinguishing high-risk NSCLC cases with dismal prognostic outcome.Risk-score base on inflammatory-related genes is positive correlated with CD274, TGFBR1 and TGFB1 expression.Targeting KRT6A sensitive to mitoxantrone and oxaliplatin in H1299 and HCC827 cells.
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  • 文章类型: Journal Article
    这项研究开发了一种易于使用的死亡率预测工具,显示出可接受的歧视,没有明显的不适合。GeRi评分能够预测死亡率,并且可以区分轻度,中、高危人群。因此,GeRi评分可能有可能分配医疗护理的强度.
    目的:有几种预测髋部骨折患者死亡率的工具,但是所有这些都由大量的变量组成,需要耗时的评估和/或难以计算。这项研究的目的是开发和验证一个易于使用的分数,这主要取决于常规数据。
    方法:来自老年创伤注册中心的患者被分为发展组和验证组。使用Logistic回归模型来建立内部死亡率模型并获得得分。使用Akaike信息标准(AIC)和似然比检验比较候选模型。使用曲线下面积(AUC)和Hosmer-Lemeshow检验测试模型的质量。
    结果:纳入38,570例患者,几乎相等地分布到开发和验证数据集。最终模型的AUC为0.727(95%CI0.711-0.742),与基本模型相比,AIC显著降低了偏差,Hosmer-Lemeshow检验显示没有明显的拟合缺失(p=0.07)。GeRi-Score预测内部死亡率为5.3%,而不是在开发数据集中观察到的死亡率为5.3%,而死亡率为5.4%。5.7%在验证数据集中。GeRi评分能够区分轻度,中、高危人群。
    结论:GeRi-Score是一种易于使用的死亡率预测工具,具有可接受的区分度,并且没有明显的拟合缺失。GeRi评分可能具有在髋部骨折手术中分配围手术期医疗护理强度的潜力,并且可以在质量管理计划中用作基准工具。
    This study developed an easy-to-use mortality prediction tool, which showed an acceptable discrimination and no significant lack of fit. The GeRi-Score was able to predict mortality and could distinguish between mild, moderate and high risk groups. Therefore, the GeRi-Score might have the potential to distribute the intensity of medical care.
    OBJECTIVE: Several mortality-predicting tools for hip fracture patients are available, but all consist of a high number of variables, require a time-consuming evaluation and/or are difficult to calculate. The aim of this study was to develop and validate an easy-to-use score, which depends mostly on routine data.
    METHODS: Patients from the Registry for Geriatric Trauma were divided into a development and a validation group. Logistic regression models were used to build a model for in-house mortality and to obtain a score. Candidate models were compared using Akaike information criteria (AIC) and likelihood ratio tests. The quality of the model was tested using the area under the curve (AUC) and the Hosmer-Lemeshow test.
    RESULTS: 38,570 patients were included, almost equal distributed to the development and to the validation dataset. The AUC was 0.727 (95% CI 0.711 - 0.742) for the final model, AIC resulted in a significant reduction in deviance compared to the basic model, and the Hosmer-Lemeshow test showed no significant lack of fit (p = 0.07). The GeRi-Score predicted an in-house mortality of 5.3% vs. 5.3% observed mortality in the development dataset and 5.4% vs. 5.7% in the validation dataset. The GeRi-Score was able to distinguish between mild, moderate and high risk groups.
    CONCLUSIONS: The GeRi-Score is an easy-to-use mortality-predicting tool with an acceptable discrimination and no significant lack of fit. The GeRi-Score might have the potential to distribute the intensity of perioperative medical care in hip fracture surgery and can be used in quality management programs as benchmark tool.
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  • 文章类型: Journal Article
    准确预测早期结直肠癌(CRC)的复发和临床结果的必要性对于确定可能从辅助化疗中受益的患者至关重要。这里,我们开发并验证了一种基于基因的风险评分算法,用于根据转移相关蛋白分泌的改变对早期疾病患者进行分层和个性化治疗.对具有不同遗传背景的高转移性和低转移性CRC细胞系的分泌组的定量无标记蛋白质组学分析揭示了153种差异分泌的蛋白质(倍数变化>5)。在转录组水平上验证了分泌组中的这些变化。从119个上调的蛋白质开始,由IGFBP3、CD109、LTBP1、PSAP、在顺序发现后识别出BMP1和NPC2,培训,并在四个不同的队列中进行验证。该签名用于开发风险评分算法,命名为SEC6,用于患者分层。SEC6风险评分成分在预后不良的CRC亚型中显示出较高的表达:共有分子亚型4(CMS4),CRIS-B,像茎一样。签名的高表达也与显示dMMR的患者有关,CIMP+状态,和BRAF突变。此外,SEC6标记与较低的总生存率相关,无进展间隔,以及II期和III期患者的疾病特异性生存率。基于SEC6的风险分层表明,5-FU治疗对低风险患者有益,而只有积极治疗(FOLFOX和FOLFIRI)对II期和III期的高危患者有益处.总之,这种新的风险评分证明了分泌区室作为具有高预后和化疗预测能力的生物标志物的可靠来源的价值。提供了一个潜在的新工具,用于定制患者护理决策。
    The necessity to accurately predict recurrence and clinical outcome in early stage colorectal cancer (CRC) is critical to identify those patients who may benefit from adjuvant chemotherapy. Here, we developed and validated a gene-based risk-score algorithm for patient stratification and personalised treatment in early stage disease based on alterations in the secretion of metastasis-related proteins. A quantitative label-free proteomic analysis of the secretome of highly and poorly metastatic CRC cell lines with different genetic backgrounds revealed 153 differentially secreted proteins (fold-change >5). These changes in the secretome were validated at the transcriptomic level. Starting from 119 up-regulated proteins, a six-gene/protein-based prognostic signature composed of IGFBP3, CD109, LTBP1, PSAP, BMP1, and NPC2 was identified after sequential discovery, training, and validation in four different cohorts. This signature was used to develop a risk-score algorithm, named SEC6, for patient stratification. SEC6 risk-score components showed higher expression in the poor prognosis CRC subtypes: consensus molecular subtype 4 (CMS4), CRIS-B, and stem-like. High expression of the signature was also associated with patients showing dMMR, CIMP+ status, and BRAF mutations. In addition, the SEC6 signature was associated with lower overall survival, progression-free interval, and disease-specific survival in stage II and III patients. SEC6-based risk stratification indicated that 5-FU treatment was beneficial for low-risk patients, whereas only aggressive treatments (FOLFOX and FOLFIRI) provided benefits to high-risk patients in stages II and III. In summary, this novel risk-score demonstrates the value of the secretome compartment as a reliable source for the retrieval of biomarkers with high prognostic and chemotherapy-predictive capacity, providing a potential new tool for tailoring decision-making in patient care.
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  • 文章类型: Journal Article
    背景:大约90%的肝癌相关死亡是由肝细胞癌(HCC)引起的。N7-甲基鸟苷(m7G)修饰与各种疾病的生物学过程和调节有关。据我们所知,其在HCC发病机制和预后中的作用尚未得到彻底研究。目的:鉴定N7-甲基鸟苷(m7G)在HCC中相关的预后生物标志物。此外,我们还研究了m7G相关预后基因标记与HCC免疫浸润的相关性.方法:将TCGA数据集用作训练和GEO数据集“GSE76427”,以验证结果。使用R统计软件版本4.1.2进行统计分析。结果:功能富集分析确定了一些与HCC相关的发病机制。我们确定了3个m7G相关基因(CDK1,ANO1和PDGFRA)作为HCC的预后生物标志物。从这3个预后m7G相关基因计算风险评分,其显示在训练和验证数据集中,高风险组比低风险组具有显著较差的预后。在预测列线图中,风险评分对3年和5年总生存率的预测优于整个队列中的理想模型。此外,免疫检查点基因如CTLA4,HAVCR2,LAG3和TIGT在高危组中的表达明显更高,化疗敏感性分析显示高危组对索拉非尼治疗有反应.结论:3个m7G基因相关特征模型可作为HCC预后的生物标志物,指导免疫治疗和化疗反应。需要对这种生物标志物模型进行未来的临床研究以验证其临床意义。
    Background: About 90% of liver cancer-related deaths are caused by hepatocellular carcinoma (HCC). N7-methylguanosine (m7G) modification is associated with the biological process and regulation of various diseases. To the best of our knowledge, its role in the pathogenesis and prognosis of HCC has not been thoroughly investigated. Aim: To identify N7-methylguanosine (m7G) related prognostic biomarkers in HCC. Furthermore, we also studied the association of m7G-related prognostic gene signature with immune infiltration in HCC. Methods: The TCGA datasets were used as a training and GEO dataset \"GSE76427\" for validation of the results. Statistical analyses were performed using the R statistical software version 4.1.2. Results: Functional enrichment analysis identified some pathogenesis related to HCC. We identified 3 m7G-related genes (CDK1, ANO1, and PDGFRA) as prognostic biomarkers for HCC. A risk score was calculated from these 3 prognostic m7G-related genes which showed the high-risk group had a significantly poorer prognosis than the low-risk group in both training and validation datasets. The 3- and 5-years overall survival was predicted better with the risk score than the ideal model in the entire cohort in the predictive nomogram. Furthermore, immune checkpoint genes like CTLA4, HAVCR2, LAG3, and TIGT were expressed significantly higher in the high-risk group and the chemotherapy sensitivity analysis showed that the high-risk groups were responsive to sorafenib treatment. Conclusion: These 3 m7G genes related signature model can be used as prognostic biomarkers in HCC and a guide for immunotherapy and chemotherapy response. Future clinical study on this biomarker model is required to verify its clinical implications.
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