Predictive preventive personalized medicine (PPPM / 3PM)

预防性个性化医疗 (PPPM / 3PM)
  • 文章类型: Journal Article
    由于共同危险因素的变化,癌症和中风的相互促进发生,如代谢途径和分子靶标,造成“恶性循环”。“癌症在缺血性卒中(IS)的发病机理中起着直接或间接的作用,以及在IS患者的治疗和临床管理中使用的反应性医疗方法,导致这些患者中与隐匿性癌症相关的临床挑战。缺乏可靠和简单的工具阻碍了预测的有效性,预防性,和个性化医疗(PPPM/3PM)方法。因此,我们进行了一项多中心研究,重点是多参数分析,以促进隐匿性癌症的早期诊断和癌症相关卒中的个性化治疗.
    对IS患者入院常规临床检查指标与电子病历进行回顾性整理。训练数据集包括136名患有并发癌症的IS患者,与对照组以1:1的比例匹配。通过逻辑回归和五种替代机器学习模型评估IS患者隐匿性癌症的风险。随后,选择预测效果最高的模型来创建列线图,它是临床实践中预测诊断的定量工具。内部验证采用了十倍的交叉验证,而外部验证涉及来自六个中心的239名IS患者。包括受试者工作特性(ROC)曲线的验证,校正曲线,决策曲线分析(DCA),并与先前研究的模型进行了比较。
    最终预测模型基于逻辑回归,并包含以下变量:缺血性病变区域,多个血管区域,高血压,D-二聚体,纤维蛋白原(FIB),和血红蛋白(Hb)。列线图的ROC曲线下面积(AUC)在训练数据集中为0.871,在外部测试数据集中为0.834。校准曲线和DCA都强调了列线图的强劲表现。
    列线图使住院IS患者能够进行早期隐匿性癌症诊断,并有助于准确识别IS的病因,而IS分层的推广使个性化治疗变得可行。基于IS患者常规临床检查指标的在线列线图为PPPM框架下的二级护理提供了具有成本效益的平台。
    在线版本包含补充材料,可在10.1007/s13167-024-00354-8获得。
    UNASSIGNED: The reciprocal promotion of cancer and stroke occurs due to changes in shared risk factors, such as metabolic pathways and molecular targets, creating a \"vicious cycle.\" Cancer plays a direct or indirect role in the pathogenesis of ischemic stroke (IS), along with the reactive medical approach used in the treatment and clinical management of IS patients, resulting in clinical challenges associated with occult cancer in these patients. The lack of reliable and simple tools hinders the effectiveness of the predictive, preventive, and personalized medicine (PPPM/3PM) approach. Therefore, we conducted a multicenter study that focused on multiparametric analysis to facilitate early diagnosis of occult cancer and personalized treatment for stroke associated with cancer.
    UNASSIGNED: Admission routine clinical examination indicators of IS patients were retrospectively collated from the electronic medical records. The training dataset comprised 136 IS patients with concurrent cancer, matched at a 1:1 ratio with a control group. The risk of occult cancer in IS patients was assessed through logistic regression and five alternative machine-learning models. Subsequently, select the model with the highest predictive efficacy to create a nomogram, which is a quantitative tool for predicting diagnosis in clinical practice. Internal validation employed a ten-fold cross-validation, while external validation involved 239 IS patients from six centers. Validation encompassed receiver operating characteristic (ROC) curves, calibration curves, decision curve analysis (DCA), and comparison with models from prior research.
    UNASSIGNED: The ultimate prediction model was based on logistic regression and incorporated the following variables: regions of ischemic lesions, multiple vascular territories, hypertension, D-dimer, fibrinogen (FIB), and hemoglobin (Hb). The area under the ROC curve (AUC) for the nomogram was 0.871 in the training dataset and 0.834 in the external test dataset. Both calibration curves and DCA underscored the nomogram\'s strong performance.
    UNASSIGNED: The nomogram enables early occult cancer diagnosis in hospitalized IS patients and helps to accurately identify the cause of IS, while the promotion of IS stratification makes personalized treatment feasible. The online nomogram based on routine clinical examination indicators of IS patients offered a cost-effective platform for secondary care in the framework of PPPM.
    UNASSIGNED: The online version contains supplementary material available at 10.1007/s13167-024-00354-8.
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  • 文章类型: Journal Article
    静脉内平滑肌瘤病(IVL)是一种罕见的内分泌相关肿瘤,具有血管内浸润的独特特征。这项研究旨在确定可靠的生物标志物,以在预测的背景下监督IVL的发展或复发,预防性,和个性化医疗(PPPM/3PM)。
    共招募60例,以检测IVL患者血清样本中的差异表达蛋白(DEPs)。这些病例包括复发性IVL,非复发性IVL,子宫肌瘤,和没有子宫肌瘤的健康个体,每个类别有15个案例。然后,加权基因共表达网络分析(WGCNA),套索惩罚Cox回归分析(Lasso),趋势聚类,和广义线性回归模型(GLM)用于筛选参与IVL进展的hub蛋白。
    首先,从2582种可识别蛋白中确定了93种差异表达蛋白(DEP),在IVL组中增加了54种蛋白质,剩下的蛋白质下降了。这些蛋白质富含对免疫环境的调节,主要通过激活B细胞的功能。在上述综合分析之后,建立了基于4种蛋白质(A0A5C2FUE5,A0A5C2GPQ1,A0A5C2GNC7和A0A5C2GBR3)的模型,以有效确定IVL病变进展的潜力.在这些蛋白质中,我们的结果表明,危险因素A0A5C2FUE5与IVL进展相关(OR=2.64).相反,A0A5C2GPQ1,A0A5C2GNC7和A0A5C2GBR3可能以保护性方式起作用并防止疾病发展(OR分别为0.32,0.60,0.53),多类接收机算子特征曲线分析进一步支持了这一点。
    基于整合的生物信息学分析最终鉴定了四种hub蛋白。这项研究通过3PM方法增强了这些新型生物标志物在预测IVL的预后或进展方面的有希望的应用。
    在线版本包含补充材料,可在10.1007/s13167-023-00338-0获得。
    UNASSIGNED: Intravenous leiomyomatosis (IVL) is a rare endocrine-associated tumor with unique characteristics of intravascular invasion. This study aimed to identify reliable biomarkers to supervise the development or recurrence of IVL in the context of predictive, preventive, and personalized medicine (PPPM/3PM).
    UNASSIGNED: A total of 60 cases were recruited to detect differentially expressed proteins (DEPs) in serum samples from IVL patients. These cases included those with recurrent IVL, non-recurrent IVL, uterine myoma, and healthy individuals without uterine myoma, with 15 cases in each category. Then, weighted gene co-expression network analysis (WGCNA), lasso-penalized Cox regression analysis (Lasso), trend clustering, and a generalized linear regression model (GLM) were utilized to screen the hub proteins involved in IVL progression.
    UNASSIGNED: First, 93 differentially expressed proteins (DEPs) were determined from 2582 recognizable proteins, with 54 proteins augmented in the IVL group, and the remaining proteins declined. These proteins were enriched in the modulation of the immune environment, mainly by activating the function of B cells. After the integrated analyses mentioned above, a model based on four proteins (A0A5C2FUE5, A0A5C2GPQ1, A0A5C2GNC7, and A0A5C2GBR3) was developed to efficiently determine the potential of IVL lesions to progress. Among these featured proteins, our results demonstrated that the risk factor A0A5C2FUE5 was associated with IVL progression (OR = 2.64). Conversely, A0A5C2GPQ1, A0A5C2GNC7, and A0A5C2GBR3 might act in a protective manner and prevent disease development (OR = 0.32, 0.60, 0.53, respectively), which was further supported by the multi-class receiver operator characteristic curve analysis.
    UNASSIGNED: Four hub proteins were eventually identified based on the integrated bioinformatics analyses. This study potentiates the promising application of these novel biomarkers to predict the prognosis or progression of IVL by a 3PM approach.
    UNASSIGNED: The online version contains supplementary material available at 10.1007/s13167-023-00338-0.
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  • 文章类型: Journal Article
    心血管健康(CVH)指标是否影响有或没有心血管疾病(CVDs)的寿命尚未得到很好的确定。本研究旨在调查无CVD事件参与者的CVH指标与预期寿命之间的关系。我们假设理想的CVH状态与预期寿命增加有关,并在预测框架内评估CVH状态作为长寿预防目标的效果,预防性,和个性化医疗(PPPM/3PM)。
    共有92,795名在开uan研究中的参与者接受了检查,然后随访到2020年。我们考虑了三个转变(从非CVD事件到偶发CVD事件,从非CVD事件到死亡率,从CVD事件到死亡率)。多状态寿命方法用于估计预期寿命。
    在13年的中位随访期间,12,541例(13.51%)死亡。与差的CVH相比,理想的CVH将CVD事件的发生率和无CVD事件的死亡率降低了约58%和27%,分别。与CVH指标较差的女性相比,在35岁时具有理想CVH的女性,无CVD事件的预期寿命延长了5.00(3.23-6.77)年。在男性中,理想的CVH与预期寿命延长6.74(5.55~7.93)年无CVD事件相关.
    理想的CVH状态与较低的过早死亡风险和较长的预期寿命相关,无论是普通人群还是心血管疾病患者,这是潜在的心血管疾病患者个性化医疗的经济有效的方法。我们的研究结果表明,促进更高的CVH评分或理想的CVH状态将导致减少CVD事件的负担和延长无病预期寿命。这为遵循PPPM/3PM概念的初级保健提供了准确的预测。
    在线版本包含补充材料,可在10.1007/s13167-023-00322-8获得。
    UNASSIGNED: Whether cardiovascular health (CVH) metrics impact longevity with and without cardiovascular diseases (CVDs) has not been well established. This study aimed to investigate the association between CVH metrics and life expectancy in participants free of CVD events. We hypothesized that ideal CVH status was associated with increased life expectancy and assessed the effect of CVH status as a prevention target of longevity in the framework of predictive, preventive, and personalized medicine (PPPM/3PM).
    UNASSIGNED: A total of 92,795 participants in the Kailuan study were examined and thereafter followed up until 2020. We considered three transitions (from non-CVD events to incident CVD events, from non-CVD events to mortality, and from CVD events to mortality). The multistate lifetable method was applied to estimate the life expectancy.
    UNASSIGNED: During a median follow-up of 13 years, 12,541 (13.51%) deaths occurred. Compared with poor CVH, ideal CVH attenuated the risk of incident CVD events and mortality without CVD events by approximately 58% and 27%, respectively. Women with ideal CVH at age 35 had a 5.00 (3.23-6.77) year longer life expectancy free of CVD events than did women with poor CVH metrics. Among men, ideal CVH was associated with a 6.74 (5.55-7.93) year longer life expectancy free of CVD events.
    UNASSIGNED: An ideal CVH status is associated with a lower risk of premature mortality and a longer life expectancy, either in the general population or in CVD patients, which are cost-effective ways for personalized medicine of potential CVD patients. Our findings suggest that the promotion of a higher CVH score or ideal CVH status would result in reduced burdens of CVD events and extended disease-free life expectancy, which offered an accurate prediction for primary care following the concept of PPPM/3PM.
    UNASSIGNED: The online version contains supplementary material available at 10.1007/s13167-023-00322-8.
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  • 文章类型: Journal Article
    UNASSIGNED: Ginseng, a traditional herbal medicine, has been used for thousands of years to treat various diseases including metabolic syndrome (MS). However, the underlying mechanism(s) of such beneficial actions of ginseng against MS is poorly understood. Emerging evidence indicates a close association of the host gut microbiota with MS. The present study was conducted to examine, whether the beneficial effects of Korean red ginseng (KRG) against MS could be influenced by gut microbial population and whether gut microbial profile could be considered a valuable biomarker for targeted treatment strategy for MS in compliance with the predictive, preventive, and personalized medicine (PPPM / 3PM).
    UNASSIGNED: This clinical study was a randomized, double-blind, placebo-controlled trial evaluating the effects of KRG treatment for 8 weeks on patients with MS. The anthropometric parameters, vital signs, metabolic biomarkers, and gut microbial composition through 16S rRNA gene sequencing were assessed at the baseline and endpoint. The impact of KRG was also evaluated after categorizing the subjects into responders and non-responders, as well as enterotypes 1 and 2 based on their gut microbial profile at the baseline.
    UNASSIGNED: Fifty out of 60 subjects who meet the MS criteria completed the trial without showing adverse reactions. The KRG treatment caused a significant decrease in systolic blood pressure (SBP). Microbial analysis revealed a decrease in Firmicutes, Proteobacteria, and an increase in Bacteroidetes in response to KRG. In patient stratification analysis, the responders showing marked improvement in the serum levels of lipid metabolic biomarkers TC and LDL due to the KRG treatment exhibited higher population of both the family Lachnospiraceae and order Clostridiales compared to the non-responders. The homeostasis model assessment-insulin resistance (HOMA-IR) and insulin level were decreased in enterotype 1 (Bacteroides-abundant group) and increased in enterotype 2 (prevotella-abundant group) following the KRG treatment.
    UNASSIGNED: In this study, the effects of KRG on the glucose metabolism in MS patients were influenced by the relative abundances of gut microbial population and differed according to the individual enterotype. Therefore, the analysis of enterotype categories is considered to be helpful in predicting the effectiveness of KRG on glucose homeostasis of MS patients individually. This will further help to decide on the appropriate treatment strategy for MS, in compliance with the perspective of PPPM.
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