Individualized therapy

个体化治疗
  • 文章类型: Journal Article
    这篇叙述性综述提供了对泌乳素瘤的简洁探索,最常见的垂体腺瘤,专注于其流行病学,临床表现,和治疗干预措施。从其患病率和病因的概述开始,本综述探讨了泌乳素腺瘤的性别分布和家族性关联.临床表现,包括内分泌干扰,生殖健康问题,和代谢紊乱,被检查,强调它们对荷尔蒙调节和心血管健康的影响。然后叙述通过药物治疗,手术干预,和放射治疗,突出它们的功效,副作用,和长期管理挑战。讨论了减轻副作用和优化治疗结果的策略,强调多学科合作在泌乳素瘤管理中的重要性。这篇综述是为医疗保健专业人员和研究人员提供的简明而全面的资源,提供对催乳素瘤的临床复杂性和治疗细微差别的见解,以指导最佳的患者护理策略。
    This narrative review provides a succinct exploration of prolactinoma, the most common pituitary adenoma, focusing on its epidemiology, clinical manifestations, and therapeutic interventions. Beginning with an overview of its prevalence and aetiology, the review delves into the gender distribution and familial associations of prolactinoma. Clinical presentations, including endocrine disruptions, reproductive health issues, and metabolic disturbances, are examined, emphasizing their impact on hormonal regulation and cardiovascular health. The narrative then navigates through pharmacological treatments, surgical interventions, and radiation therapy, highlighting their efficacy, side effects, and long-term management challenges. Strategies to mitigate side effects and optimize treatment outcomes are discussed, emphasizing the importance of multidisciplinary collaboration in prolactinoma management. This review is a concise yet comprehensive resource for healthcare professionals and researchers, providing insights into prolactinoma\'s clinical complexities and therapeutic nuances to guide optimal patient care strategies.
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  • 文章类型: Journal Article
    细胞片技术(CST)主要用于修复目的的组织工程。我们的初步研究表明,使用CST建立的体内前列腺癌模型优于传统的细胞悬浮方法。然而,CST用于膀胱癌细胞的潜力尚未被研究.在这项研究中,我们研究了两种膀胱癌细胞系的能力,T24和5637,形成细胞片。我们发现T24细胞成功形成细胞片。然后我们进行染色以评估完整性,特定标记,和T24细胞片的增殖特性。我们的研究结果表明,膀胱癌细胞片可以建立,为体内和体外膀胱癌研究以及患者个性化药物选择提供了有价值的工具。
    Cell sheet technology (CST) has primarily been applied in tissue engineering for repair purposes. Our preliminary research indicates that an in vivo prostate cancer model established using CST outperforms traditional cell suspension methods. However, the potential for CST to be used with bladder cancer cells has not yet been explored. In this study, we investigated the ability of two bladder cancer cell lines, T24 and 5637, to form cell sheets. We found that T24 cells successfully formed cell sheets. We then performed staining to evaluate the integrity, specific markers, and proliferation characteristics of the T24 cell sheets. Our findings demonstrate that bladder cancer cell sheets can be established, providing a valuable tool for both in vivo and in vitro bladder cancer studies and for personalized drug selection for patients.
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  • 文章类型: Journal Article
    与其他人群相比,印度2型糖尿病(T2DM)的患病率很高,具有独特的临床特征。尽管糖尿病治疗取得了进展,印度仍有相当数量的患者血糖控制不良和并发症.二肽基肽酶-4(DPP-4)抑制剂由于其良好的疗效和耐受性而仍然是T2DM治疗的重要组成部分。鉴于目前的情况,有必要重新审视DPP-4抑制剂在印度患者T2DM治疗中的作用.这份共识文件旨在从印度的角度为DPP-4抑制剂在T2DM管理中的应用提供指导。由100名专家组成的共识小组在广泛的文献回顾和讨论的基础上提出了建议。专家组强调了及时控制血糖的重要性,联合治疗,并针对T2DM的潜在病理生理学。本文对DPP-4抑制剂与二甲双胍和/或钠-葡萄糖转运蛋白-2抑制剂的组合进行了合理化,考虑到它们的互补作用机制。本文为临床医生在使用DPP-4抑制剂的印度人群中优化T2DM的管理提供了有价值的见解,并提出了选择基于DPP-4抑制剂的疗法的算法。
    India has a high prevalence of type 2 diabetes mellitus (T2DM) with unique clinical characteristics compared to other populations. Despite advancements in diabetes therapy, a significant number of patients in India still experience poor glycemic control and complications. Dipeptidyl peptidase-4 (DPP-4) inhibitors continue to be an important component of T2DM treatment due to their favorable efficacy and tolerability profile. Given the current scenario, there is a need to revisit the role of DPP-4 inhibitors in T2DM management in Indian patients. This consensus paper aims to provide guidance on the utilization of DPP-4 inhibitors in T2DM management from an Indian perspective. A consensus group of 100 experts developed recommendations based on an extensive literature review and discussions. The expert group emphasized the importance of timely glycemic control, combination therapy, and targeting the underlying pathophysiology of T2DM. The combinations of DPP-4 inhibitors with metformin and/or sodium-glucose transport protein-2 inhibitors are rationalized in this paper, considering their complementary mechanisms of action. This paper provides valuable insights for clinicians in optimizing the management of T2DM in the Indian population with the use of DPP-4 inhibitors and proposes an algorithm for selecting DPP-4 inhibitor-based therapies.
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  • 文章类型: Journal Article
    重复经颅磁刺激(rTMS)是帕金森病(PD)的一种有效的非侵入性神经调节技术。然而,rTMS的疗效在个体之间差异很大。本研究旨在探讨PD患者对rTMS反应的相关因素。
    我们回顾性分析了70例特发性PD患者的反应,这些患者连续14天接受rTMS,以开放标记(n=31)或随机,双盲,安慰剂对照试验(RCT)(n=39)。采用帕金森病联合评定量表第三部分(UPDRSIII)对PD患者的运动症状进行评估。根据以前的研究,UPDRSIII分为六个症状群:轴向功能障碍,静止性震颤,刚性,影响左右四肢的运动迟缓,和姿势震颤。随后,分析了rTMS对不同运动症状群和临床预测因子的疗效。
    治疗14天后,在开放标签试验和RCT中,只有UPDRSIII总评分和刚性评分得到改善.多元线性回归分析结果表明,基线刚性评分(β=0.37,p=0.047)和RMT(β=0.30,P=0.02)正预测UPDRSIII的改善。基线刚度评分(β=0.55,P<0.0001)被确定为预测刚度改善的独立因素。
    这项研究表明,经过14天的治疗,UPDRSIII总评分和僵硬度得到了显着改善,基线刚性评分和RMT被确定为治疗反应的预测因子,强调个性化治疗的必要性。
    UNASSIGNED: Repetitive transcranial magnetic stimulation (rTMS) is an effective noninvasive neuromodulation technique for Parkinson\'s disease (PD). However, the efficacy of rTMS varies widely between individuals. This study aimed to investigate the factors related to the response to rTMS in PD patients.
    UNASSIGNED: We retrospectively analyzed the response of 70 idiopathic PD patients who underwent rTMS for 14 consecutive days targeting the supplementary motor area (SMA) in either an open-label trail (n = 31) or a randomized, double-blind, placebo-controlled trial (RCT) (n = 39). The motor symptoms of PD patients were assessed by the United Parkinson\'s Disease Rating Scale Part III (UPDRSIII). Based on previous studies, the UPDRSIII were divided into six symptom clusters: axial dysfunction, resting tremor, rigidity, bradykinesia affecting right and left extremities, and postural tremor. Subsequently, the efficacy of rTMS to different motor symptom clusters and clinical predictors were analyzed in these two trails.
    UNASSIGNED: After 14 days of treatment, only the total UPDRSIII scores and rigidity scores improved in both the open-label trial and the RCT. The results of multiple linear regression analysis indicated that baseline rigidity scores (β = 0.37, p = 0.047) and RMT (β = 0.30, P = 0.02) positively predicted the improvement of UPDRSIII. The baseline rigidity score (β = 0.55, P < 0.0001) was identified as an independent factor to predict the improvement of rigidity.
    UNASSIGNED: This study demonstrated significant improvements in total UPDRSIII scores and rigidity after 14-day treatment, with baseline rigidity scores and RMT identified as predictors of treatment response, underscoring the need for individualized therapy.
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  • 文章类型: Journal Article
    本研究旨在评估新兴血清学标志物的预测能力,血清HBVRNA和HBcrAg,对于HBeAg阳性慢性乙型肝炎(CHB)儿童的HBeAg血清转换。在2021年4月至2022年9月期间入住湖南省儿童医院肝病中心并接受恩替卡韦和干扰素-α联合治疗的未治疗HBeAg阳性CHB儿童被招募。在基线和治疗的第12、24和48周测量血清HBVRNA和HBcrAg。我们的研究表明,血清HBVRNA(HR=0.71,95%CI:0.56-0.91,p=0.006),HBcrAg(HR=0.60,95%CI:0.43-0.84,p=0.003),和HBsAg(HR=0.49,95CI:0.36-0.69,p<0.001)在第12周是HBeAg血清转换的独立预测因子。ROC曲线分析表明,第36周的血清HBVRNA下降值(ΔHBVRNA)和第12周的HBcrAg下降值(ΔHBcrAg)(AUC=0.871,p=0.003和AUC=0.810,p=0.003)可以有效地预测HBeAg血清转换。此外,确定了最佳临界值,第36周时ΔHBVRNA>3.759log10拷贝/mL或第12周时ΔHBcrAg>0.350log10U/mL的儿童更有可能实现HBeAg血清转换。血清HBVRNA和HBcrAg为儿童CHB的治疗提供了新的见解。在治疗期间早期评估血清HBVRNA和HBcrAg可以帮助临床决策并优化个性化治疗方法。
    This study aimed to assess the predictive capacity of emerging serological markers, serum HBV RNA and HBcrAg, for HBeAg seroconversion in children with HBeAg-positive chronic hepatitis B (CHB). Treatment-naïve HBeAg-positive CHB children who admitted to the Liver Disease Center of Hunan Children\'s Hospital between April 2021 and September 2022 and received treatment with the combined entecavir and interferon-alpha treatment were recruited. Serum HBV RNA and HBcrAg were measured at baseline and Weeks 12, 24, and 48 of treatment. Our study showed that serum HBV RNA (HR = 0.71, 95% CI: 0.56-0.91, p = 0.006), HBcrAg (HR = 0.60, 95% CI: 0.43-0.84, p = 0.003), and HBsAg (HR = 0.49, 95%CI: 0.36-0.69, p < 0.001) at Week 12 were independent predictors of HBeAg seroconversion. ROC curve analysis presented that serum HBV RNA decline value (ΔHBV RNA) at Week 36 and HBcrAg decline value (ΔHBcrAg) at Week 12 (AUC = 0.871, p = 0.003 and AUC = 0.810, p = 0.003, respectively) could effectively predict HBeAg seroconversion. Furthermore, the optimal critical values were determined and the children with ΔHBV RNA > 3.759 log10 copies/mL at Week 36 or ΔHBcrAg >0.350 log10 U/mL at Week 12 more likely to achieve HBeAg seroconversion. The serum HBV RNA and HBcrAg provide new insights into the treatment of CHB in children. Early assessment of serum HBV RNA and HBcrAg during treatment can assist clinical decision-making and optimize individualized therapeutic approaches.
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  • 文章类型: Journal Article
    背景:使用elexa-/teza-/ivacaftor(ETI)进行高效CFTR调节剂治疗可改善肺部预后,汗液氯化物,囊性纤维化(CF)患者的体重指数(BMI)和生活质量。据报道,CFTR调节剂对脂溶性维生素和微量营养素的吸收有所改善,但缺乏有关ETI治疗的数据。
    方法:这项单中心回顾性研究评估了一秒用力呼气量(FEV-1),汗液氯化物,BMI,转氨酶(AST,ALT),胆红素,维生素A,D,E,符合ETI条件的儿童和成人的锌和硒。在ETI开始之前和之后一年内评估参数。
    结果:58例患者(中位年龄m=28岁,SD±11.6年,包括51.7%的女性14<18岁)。ETI后FEV-1和汗液氯化物明显改善。BMI或AST没有变化。ETI4周后ALT显著升高,但在进一步的过程中恢复至正常水平。ETI后胆红素水平仍然升高。维生素A在ETI后12个月显著升高。没有发现维生素D的变化,E,锌和硒。
    结论:这项研究增加了证据,证明ETI后可以发现一些脂溶性维生素水平的改善。没有发现微量营养素方面的变化。建议进行个性化随访和补充。
    BACKGROUND: Highly-effective CFTR-modulator therapy with elexa-/teza-/ivacaftor (ETI) has led to improvements in pulmonary outcomes, sweat chloride, body mass index (BMI) and quality of life in people with cystic fibrosis (CF). Improved uptake of fat-soluble vitamins and micronutrients has been reported for CFTR-modulators but data regarding ETI therapy is lacking.
    METHODS: This single-center retrospective study evaluated forced expiratory volume in one second (FEV-1), sweat chloride, BMI, transaminases (AST, ALT), bilirubin, vitamins A, D, E, zinc and selenium in children and adults eligible for ETI. Parameters were assessed before and up to one year after initiation of ETI.
    RESULTS: 58 patients (median age m = 28 years, SD ± 11.6 years, 51.7% female14 < 18 years old) were included. FEV-1 and sweat chloride improved significantly after ETI. There were no changes in BMI or AST. ALT was increased significantly after 4 weeks of ETI but returned to normal levels in further course. Bilirubin levels remained elevated after ETI. Vitamin A was significantly higher 12 months after ETI. No changes were found for vitamins D, E, zinc and selenium.
    CONCLUSIONS: This study adds to the evidence that improvements of some fat-soluble vitamin levels can be found after ETI. No changes regarding micronutrients were noted. Individualized follow-up and supplementation are recommended.
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  • 文章类型: Journal Article
    在新冠肺炎大流行期间人气上升,维生素D3目前令人印象深刻,这要归功于众多针对其与人体稳态相互作用的研究。同时,在补充建议方面有一个高峰。一些研究集中在自身免疫性疾病和营养缺乏之间的联系,尤其是维生素D3。由于针对儿童(0-18岁之间的患者)的专门文献远远不等于以成人为中心的分支的信息多样性,这篇综述旨在介绍微生物和营养平衡与儿童系统性红斑狼疮(pSLE)活动之间的关系。理想的实际目的在于更好地理解和充分,受影响者的个性化管理,以降低发病率。摘要的中心是建立维生素D缺乏症在小儿红斑狼疮的发展和演变中的影响。我们将讨论与维生素D3在狼疮的病理生理级联中所起的影响的两个实体相关的方面,而且当缺乏过度补充(维生素D过多症)时,毒性的风险及其影响也是如此。我们将讨论维生素D缺乏症与免疫功能调节的关系,炎症过程的增强,氧化应激的增加,认知大脑区域的灌注,SLE的季节性发病率及其严重程度。最后,我们回顾当前的知识,大流行后,关于维生素缺乏症D-pSLE的关系。
    Having increased popularity during the Covid-19 pandemic, vitamin D3 is currently impressing thanks to the numerous researches aimed at its interactions with the body\'s homeostasis. At the same time, there is a peak in terms of recommendations for supplementation with it. Some of the studies focus on the link between autoimmune diseases and nutritional deficiencies, especially vitamin D3. Since the specialized literature aimed at children (patients between 0-18 years old) is far from equal to the informational diversity of the adult-centered branch, this review aims to bring up to date the relationship between the microbial and nutritional balance and the activity of pediatric systemic lupus erythematosus (pSLE). The desired practical purpose resides in a better understanding and an adequate, individualized management of the affected persons to reduce morbidity. The center of the summary is to establish the impact of hypovitaminosis D in the development and evolution of pediatric lupus erythematosus. We will address aspects related to the two entities of the impact played by vitamin D3 in the pathophysiological cascade of lupus, but also the risk of toxicity and its effects when the deficiency is over supplemented (hypervitaminosis D). We will debate the relationship of hypovitaminosis D with the modulation of immune function, the potentiation of inflammatory processes, the increase of oxidative stress, the perfusion of cognitive brain areas, the seasonal incidence of SLE and its severity. Finally, we review current knowledge, post-pandemic, regarding the hypovitaminosis D - pSLE relationship.
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  • 文章类型: Journal Article
    这项研究调查了免疫和上皮间质转化(EMT)相关基因和非编码RNA在神经胶质瘤发展和诊断中的关键作用,鉴于与这种普遍的CNS恶性肿瘤相关的具有挑战性的5年生存率。神经胶质瘤患者的临床和RNA数据从CGGA数据库中精心收集,EMT相关基因来自dbEMT2.0,而免疫相关基因来自MSigDB。采用共识集群,鉴定了新的分子亚组。随后的分析,包括估计,TIMER,和MCP计数器,提供了对肿瘤微环境(TIME)和免疫状态的见解。功能研究,拥抱GO,KEGG,GSVA,和GSEA分析,揭示了控制这些分子亚群的潜在机制。利用LASSO算法和多元Cox回归,我们构建了一个预后风险模型.该研究揭示了两个不同的分子亚群,具有明显不同的生存结果。更有利的预后与低免疫评分有关,肿瘤纯度高,和丰富的非编码RNA差异表达的免疫浸润细胞,包括miRNA。功能分析揭示了这些亚组之间差异表达基因和非编码RNA中免疫和EMT相关途径的富集。GSVA和GSEA分析提示EMT异常状态可能导致神经胶质瘤相关免疫紊乱。风险模型,以OS-EMT-ICI基因为中心,在准确预测神经胶质瘤生存率方面显示出希望。此外,将风险模型与临床特征整合在一起的列线图显示了神经胶质瘤患者预后预测的显著准确性.总之,OS-EMT-ICI基因和非编码RNA表达成为与免疫微环境失调密切相关的有价值的指标。为OBMRC框架内的神经胶质瘤患者提供精确预后预测的可靠工具。
    This study investigates the crucial role of immune- and epithelial-mesenchymal transition (EMT)-associated genes and non-coding RNAs in glioma development and diagnosis, given the challenging 5-year survival rates associated with this prevalent CNS malignant tumor. Clinical and RNA data from glioma patients were meticulously gathered from CGGA databases, and EMT-related genes were sourced from dbEMT2.0, while immune-related genes were obtained from MSigDB. Employing consensus clustering, novel molecular subgroups were identified. Subsequent analyses, including ESTIMATE, TIMER, and MCP counter, provided insights into the tumor microenvironment (TIME) and immune status. Functional studies, embracing GO, KEGG, GSVA, and GSEA analyses, unraveled the underlying mechanisms governing these molecular subgroups. Utilizing the LASSO algorithm and multivariate Cox regression, a prognostic risk model was crafted. The study unveiled two distinct molecular subgroups with significantly disparate survival outcomes. A more favorable prognosis was linked to low immune scores, high tumor purity, and an abundance of immune infiltrating cells with differential expression of non-coding RNAs, including miRNAs. Functional analyses illuminated enrichment of immune- and EMT-associated pathways in differentially expressed genes and non-coding RNAs between these subgroups. GSVA and GSEA analyses hinted at abnormal EMT status potentially contributing to glioma-associated immune disorders. The risk model, centered on OS-EMT-ICI genes, exhibited promise in accurately predicting survival in glioma. Additionally, a nomogram integrating the risk model with clinical characteristics demonstrated notable accuracy in prognostic predictions for glioma patients. In conclusion, OS-EMT-ICI gene and non-coding RNA expression emerges as a valuable indicator intricately linked to immune microenvironment dysregulation, offering a robust tool for precise prognosis prediction in glioma patients within the OBMRC framework.
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  • 文章类型: Journal Article
    在寿命稳步增长的时代,老年人的神经退行性疾病提出了重大的治疗和社会经济挑战。适当平衡的饮食和微生物组多样性作为神经变性治疗干预的目标越来越受到关注。微生物群可能会影响认知功能,神经元的生存和死亡,在帕金森病(PD)中发现了肠道菌群失调。色氨酸(Trp),必需氨基酸,被微生物群降解,并拥有许多具有免疫和神经调节特性的化合物。这篇广泛的叙述性综述提供了支持微生物群概念的数据,Trp-犬尿氨酸(KYN)途径和芳香烃受体(AhRs)形成参与PD的三联体。受干扰的肠-脑轴允许促炎分子和α-突触核蛋白的双向扩散,这可能有助于疾病的发展/进展。我们建议犬尿氨酸和AhR配体的外周水平与肠道中的Trp代谢密切相关,应与微生物群的组成一起研究。这种方法可以清楚地描绘PD患者的亚群,表现为微生物群-Trp-KYN-脑三联症,谁将受益于Trp代谢的改变。微生物组分析,Trp-KYN通路代谢产物和AhR信号可能揭示肠道窘迫的机制,并为早期PD的诊断和治疗提供新的靶点。基于明确定义的食物方案的组合的治疗干预措施,Trp和益生菌似乎有潜在的益处,需要进一步的实验和临床研究。
    In the era of a steadily increasing lifespan, neurodegenerative diseases among the elderly present a significant therapeutic and socio-economic challenge. A properly balanced diet and microbiome diversity have been receiving increasing attention as targets for therapeutic interventions in neurodegeneration. Microbiota may affect cognitive function, neuronal survival and death, and gut dysbiosis was identified in Parkinson\'s disease (PD). Tryptophan (Trp), an essential amino acid, is degraded by microbiota and hosts numerous compounds with immune- and neuromodulating properties. This broad narrative review presents data supporting the concept that microbiota, the Trp-kynurenine (KYN) pathway and aryl hydrocarbon receptors (AhRs) form a triad involved in PD. A disturbed gut-brain axis allows the bidirectional spread of pro-inflammatory molecules and α-synuclein, which may contribute to the development/progression of the disease. We suggest that the peripheral levels of kynurenines and AhR ligands are strongly linked to the Trp metabolism in the gut and should be studied together with the composition of the microbiota. Such an approach can clearly delineate the sub-populations of PD patients manifesting with a disturbed microbiota-Trp-KYN-brain triad, who would benefit from modifications in the Trp metabolism. Analyses of the microbiome, Trp-KYN pathway metabolites and AhR signaling may shed light on the mechanisms of intestinal distress and identify new targets for the diagnosis and treatment in early-stage PD. Therapeutic interventions based on the combination of a well-defined food regimen, Trp and probiotics seem of potential benefit and require further experimental and clinical research.
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  • 文章类型: Journal Article
    糖尿病肾病(DN)是糖尿病中一种显著的微血管并发症,与心肾血管疾病相关的复杂分子途径和机制。长期高血糖通过代谢异常诱导肾内皮功能障碍和损伤,炎症,和氧化应激,从而损害血液动力学。同时,纤维化和硬化改变加剧肾小球和肾小管损伤。在宏观层面,肾微脉管系统和体循环之间的相互交流建立了推动疾病进展的恶性循环。目前的管理方法强调严格控制血糖水平和血压,与肾素-血管紧张素系统阻断赋予肾脏保护。新型抗糖尿病药物表现出肾脏保护作用,可能通过内皮调制介导。尽管如此,新兴疗法为提高患者预后和减轻疾病负担提供了新的途径.基于精度的方法,加上解决全球血管风险的全面战略,将是减轻与糖尿病相关的心肾负担的关键。
    Diabetic nephropathy (DN) represents a significant microvascular complication in diabetes, entailing intricate molecular pathways and mechanisms associated with cardiorenal vascular diseases. Prolonged hyperglycemia induces renal endothelial dysfunction and damage via metabolic abnormalities, inflammation, and oxidative stress, thereby compromising hemodynamics. Concurrently, fibrotic and sclerotic alterations exacerbate glomerular and tubular injuries. At a macro level, reciprocal communication between the renal microvasculature and systemic circulation establishes a pernicious cycle propelling disease progression. The current management approach emphasizes rigorous control of glycemic levels and blood pressure, with renin-angiotensin system blockade conferring renoprotection. Novel antidiabetic agents exhibit renoprotective effects, potentially mediated through endothelial modulation. Nonetheless, emerging therapies present novel avenues for enhancing patient outcomes and alleviating the disease burden. A precision-based approach, coupled with a comprehensive strategy addressing global vascular risk, will be pivotal in mitigating the cardiorenal burden associated with diabetes.
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