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Trend in prevalence, associated risk factors, and longitudinal outcomes of sarcopenia in China: A national cohort study 中国肌肉疏松症的患病趋势、相关风险因素和纵向结果:全国队列研究。
IF 9 2区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-05-27 DOI: 10.1111/joim.13808
Weida Qiu, Anping Cai, Liwen Li, Yingqing Feng

Aims

To estimate the contemporary trend in the prevalence of sarcopenia and evaluate its risk factors and the longitudinal associations with multiple chronic conditions and mortality among Chinese middle-aged and older adults.

Methods

This was a nationwide, prospective cohort study using data from the China Health and Retirement Longitudinal Study. The definition of sarcopenia was based on the Asian Working Group for Sarcopenia 2019 algorithm. In the cross-sectional analysis, we estimated the trend in the weighted prevalence of sarcopenia from 2011 to 2015 and examined the associated risk factors for sarcopenia severity in 2011. In the longitudinal analysis, we assessed the longitudinal associations between sarcopenia and 14 chronic conditions and mortality during a 9-year follow-up.

Results

The weighted prevalence of sarcopenia remained consistently high in the overall population from 2011 (15.9%, 95% confidence intervals [CI]: 15.1, 16.6) to 2015 (15.0%, 95% CI: 14.3, 15.6; p for trend = 0.075). A range of risk factors were independently associated with the severity of sarcopenia, including older age, female sex, lower socioeconomic status, smoking status, malnutrition, and several chronic conditions. Possible sarcopenic and sarcopenic individuals had higher odds of several chronic conditions (i.e., heart disease, chronic lung disease, and memory-related disease) and increased risks of mortality (possible sarcopenia: odds ratios (OR): 1.66, 95% CI: 1.37, 2.00; sarcopenia: OR: 1.69, 95% CI: 1.36, 2.11) in 9 years of follow-up.

Conclusions

The prevalence of sarcopenia remained consistently high in the investigated population. Various risk factors were significantly associated with a higher prevalence of sarcopenia. Sarcopenic individuals had higher odds of several chronic conditions and increased risks of mortality, highlighting that the urgent need for dedicated efforts to improve the management of sarcopenic patients.

目的:估计当代中国中老年人肌肉疏松症患病率的趋势,评估其风险因素及其与多种慢性疾病和死亡率的纵向关系:这是一项全国性的前瞻性队列研究,使用的数据来自中国健康与退休纵向研究(China Health and Retirement Longitudinal Study)。对 "肌肉疏松症 "的定义基于亚洲 "肌肉疏松症工作组 "的 2019 年算法。在横断面分析中,我们估计了2011年至2015年肌肉疏松症加权患病率的变化趋势,并研究了2011年肌肉疏松症严重程度的相关风险因素。在纵向分析中,我们评估了9年随访期间肌肉疏松症与14种慢性疾病和死亡率之间的纵向关联:从 2011 年(15.9%,95% 置信区间 [CI]:15.1, 16.6)到 2015 年(15.0%,95% 置信区间:14.3, 15.6;趋势 p = 0.075),总体人群中肌肉疏松症的加权患病率一直居高不下。一系列风险因素与肌肉疏松症的严重程度有独立关联,包括年龄较大、女性、社会经济地位较低、吸烟状况、营养不良和几种慢性疾病。可能患有肌肉疏松症和肌肉疏松症的人患有几种慢性疾病(即心脏病、慢性肺病和记忆相关疾病)的几率更高,死亡风险也更高(可能患有肌肉疏松症:几率比(OR):1.66,95% CI:1.37,2.00;肌肉疏松症:OR:1.69,95% CI:1.37,2.00):结论:在调查人群中,肌肉疏松症的发病率一直居高不下。各种风险因素都与较高的肌肉疏松症患病率密切相关。肌肉疏松症患者罹患几种慢性疾病的几率更高,死亡风险也更高。
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引用次数: 0
MASLD and MASH at the crossroads of hepatology trials and cardiorenal metabolic trials MASLD 和 MASH 处于肝病试验和心肾代谢试验的十字路口。
IF 11.1 2区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-05-13 DOI: 10.1111/joim.13793
Faiez Zannad, Arun J. Sanyal, Javed Butler, João Pedro Ferreira, Nicolas Girerd, Veronica Miller, Ambarish Pandey, Chirag R. Parikh, Vlad Ratziu, Zobair M. Younossi, Stephen A. Harrison

Steatotic liver disease (SLD) is a worldwide public health problem, causing considerable morbidity and mortality. Patients with SLD are at increased risk for major adverse cardiovascular (CV) events, type 2 diabetes mellitus and chronic kidney disease. Conversely, patients with cardiometabolic conditions have a high prevalence of SLD. In addition to epidemiological evidence linking many of these conditions, there is evidence of shared pathophysiological processes. In December 2022, a unique multi-stakeholder, multi-specialty meeting, called MOSAIC (Metabolic multi Organ Science Accelerating Innovation in Clinical Trials) was convened to foster collaboration across metabolic, hepatology, nephrology and CV disorders. One of the goals of the meeting was to consider approaches to drug development that would speed regulatory approval of treatments for multiple disorders by combining liver and cardiorenal endpoints within a single study. Non-invasive tests, including biomarkers and imaging, are needed in hepatic and cardiorenal trials. They can be used as trial endpoints, to enrich trial populations, to diagnose and risk stratify patients and to assess treatment efficacy and safety. Although they are used in proof of concept and phase 2 trials, they are often not acceptable for regulatory approval of therapies. The challenge is defining the optimal combination of biomarkers, imaging and morbidity/mortality outcomes and ensuring that they are included in future trials while minimizing the burden on patients, trialists and trial sponsors. This paper provides an overview of some of the wide array of CV, liver and kidney measurements that were discussed at the MOSAIC meeting.

脂肪肝(SLD)是一个全球性的公共卫生问题,会导致相当高的发病率和死亡率。脂肪肝患者发生重大不良心血管(CV)事件、2 型糖尿病和慢性肾病的风险增加。相反,心血管代谢疾病患者的 SLD 患病率也很高。除了有流行病学证据表明这些疾病之间存在联系外,还有证据表明这些疾病具有共同的病理生理过程。2022 年 12 月,召开了一次名为 MOSAIC(代谢多器官科学加速临床试验创新)的独特的多利益相关者、多专业会议,以促进代谢、肝脏、肾脏和心血管疾病之间的合作。会议的目标之一是审议药物开发方法,通过在单项研究中结合肝脏和心肾终点,加快监管机构对多种疾病治疗方法的审批。肝脏和心肾试验需要非侵入性测试,包括生物标志物和成像。它们可用作试验终点、丰富试验人群、诊断和对患者进行风险分层,以及评估治疗效果和安全性。虽然它们可用于概念验证和二期试验,但通常不被监管机构批准用于治疗。目前面临的挑战是如何定义生物标记物、成像和发病率/死亡率结果的最佳组合,并确保将其纳入未来的试验中,同时最大限度地减轻患者、试验者和试验赞助商的负担。本文概述了在 MOSAIC 会议上讨论的一系列心血管、肝脏和肾脏测量方法。
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引用次数: 0
Platelets as an inter-player between hyperlipidaemia and atherosclerosis 血小板是高脂血症和动脉粥样硬化之间的相互作用者。
IF 11.1 2区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-05-05 DOI: 10.1111/joim.13794
Nailin Li

Platelet hyperreactivity and hyperlipidaemia contribute significantly to atherosclerosis. Thus, it is desirable to review the platelet–hyperlipidaemia interplay and its impact on atherogenesis. Native low-density lipoprotein (nLDL) and oxidized LDL (oxLDL) are the key proatherosclerotic components of hyperlipidaemia. nLDL binds to the platelet-specific LDL receptor (LDLR) ApoE-R2′, whereas oxLDL binds to the platelet-expressed scavenger receptor CD36, lectin-type oxidized LDLR 1 and scavenger receptor class A 1. Ligation of nLDL/oxLDL induces mild platelet activation and may prime platelets for other platelet agonists. Platelets, in turn, can modulate lipoprotein metabolisms. Platelets contribute to LDL oxidation by enhancing the production of reactive oxygen species and LDLR degradation via proprotein convertase subtilisin/kexin type 9 release. Platelet-released platelet factor 4 and transforming growth factor β modulate LDL uptake and foam cell formation. Thus, platelet dysfunction and hyperlipidaemia work in concert to aggravate atherogenesis. Hypolipidemic drugs modulate platelet function, whereas antiplatelet drugs influence lipid metabolism. The research prospects of the platelet–hyperlipidaemia interplay in atherosclerosis are also discussed.

血小板高反应性和高脂血症是动脉粥样硬化的重要原因。因此,有必要回顾一下血小板-高脂血症的相互作用及其对动脉粥样硬化的影响。原生低密度脂蛋白(nLDL)和氧化低密度脂蛋白(oxLDL)是高脂血症的主要促动脉粥样硬化成分。nLDL 与血小板特异性低密度脂蛋白受体(LDLR)ApoE-R2'结合,而 oxLDL 则与血小板表达的清道夫受体 CD36、凝集素型氧化 LDLR 1 和清道夫受体 A 类 1 结合。而血小板又能调节脂蛋白代谢。血小板通过释放 9 型枯草蛋白酶/kexin,促进活性氧的产生和低密度脂蛋白还原酶的降解,从而促进低密度脂蛋白的氧化。血小板释放的血小板因子 4 和转化生长因子 β 可调节低密度脂蛋白的吸收和泡沫细胞的形成。因此,血小板功能障碍和高脂血症共同加剧了动脉粥样硬化的发生。降血脂药物调节血小板功能,而抗血小板药物则影响脂质代谢。此外,还讨论了动脉粥样硬化中血小板-高脂血症相互作用的研究前景。
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引用次数: 0
High-throughput molecular assays for inclusion in personalised oncology trials – State-of-the-art and beyond 用于个性化肿瘤试验的高通量分子检测--最新技术及其他。
IF 11.1 2区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-05-02 DOI: 10.1111/joim.13785
Anders Edsjö, Hege G. Russnes, Janne Lehtiö, David Tamborero, Eivind Hovig, Albrecht Stenzinger, Richard Rosenquist, the PCM4EU consortium

In the last decades, the development of high-throughput molecular assays has revolutionised cancer diagnostics, paving the way for the concept of personalised cancer medicine. This progress has been driven by the introduction of such technologies through biomarker-driven oncology trials. In this review, strengths and limitations of various state-of-the-art sequencing technologies, including gene panel sequencing (DNA and RNA), whole-exome/whole-genome sequencing and whole-transcriptome sequencing, are explored, focusing on their ability to identify clinically relevant biomarkers with diagnostic, prognostic and/or predictive impact. This includes the need to assess complex biomarkers, for example microsatellite instability, tumour mutation burden and homologous recombination deficiency, to identify patients suitable for specific therapies, including immunotherapy. Furthermore, the crucial role of biomarker analysis and multidisciplinary molecular tumour boards in selecting patients for trial inclusion is discussed in relation to various trial concepts, including drug repurposing. Recognising that today's exploratory techniques will evolve into tomorrow's routine diagnostics and clinical study inclusion assays, the importance of emerging technologies for multimodal diagnostics, such as proteomics and in vivo drug sensitivity testing, is also discussed. In addition, key regulatory aspects and the importance of patient engagement in all phases of a clinical trial are described. Finally, we propose a set of recommendations for consideration when planning a new precision cancer medicine trial.

在过去的几十年里,高通量分子检测技术的发展彻底改变了癌症诊断,为个性化癌症医疗的概念铺平了道路。通过生物标记物驱动的肿瘤学试验引入此类技术推动了这一进展。在这篇综述中,探讨了各种最先进测序技术的优势和局限性,包括基因组测序(DNA 和 RNA)、全外显子组/全基因组测序和全转录组测序,重点关注它们识别具有诊断、预后和/或预测作用的临床相关生物标记物的能力。这包括需要评估复杂的生物标志物,如微卫星不稳定性、肿瘤突变负荷和同源重组缺陷,以确定适合特定疗法(包括免疫疗法)的患者。此外,还讨论了生物标志物分析和多学科分子肿瘤委员会在选择纳入试验的患者方面所起的关键作用,以及各种试验概念,包括药物再利用。我们认识到,今天的探索性技术将发展成为明天的常规诊断和临床研究纳入试验,因此还讨论了蛋白质组学和体内药物敏感性测试等多模式诊断新兴技术的重要性。此外,还介绍了临床试验各阶段的关键监管问题和患者参与的重要性。最后,我们提出了一系列建议,供规划新的精准癌症医学试验时参考。
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引用次数: 0
Epigenetic reprograming in myalgic encephalomyelitis/chronic fatigue syndrome: A narrative of latent viruses 肌痛性脑脊髓炎/慢性疲劳综合征的表观遗传学重编程:潜伏病毒的叙述
IF 11.1 2区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-05-01 DOI: 10.1111/joim.13792
Eirini Apostolou, Anders Rosén

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic disease presenting with severe fatigue, post-exertional malaise, and cognitive disturbances—among a spectrum of symptoms—that collectively render the patient housebound or bedbound. Epigenetic studies in ME/CFS collectively confirm alterations and/or malfunctions in cellular and organismal physiology associated with immune responses, cellular metabolism, cell death and proliferation, and neuronal and endothelial cell function. The sudden onset of ME/CFS follows a major stress factor that, in approximately 70% of cases, involves viral infection, and ME/CFS symptoms overlap with those of long COVID. Viruses primarily linked to ME/CFS pathology are the symbiotic herpesviruses, which follow a bivalent latent–lytic lifecycle. The complex interaction between viruses and hosts involves strategies from both sides: immune evasion and persistence by the viruses, and immune activation and viral clearance by the host. This dynamic interaction is imperative for herpesviruses that facilitate their persistence through epigenetic regulation of their own and the host genome. In the current article, we provide an overview of the epigenetic signatures demonstrated in ME/CFS and focus on the potential strategies that latent viruses—particularly Epstein–Barr virus—may employ in long-term epigenetic reprograming in ME/CFS. Epigenetic studies could aid in elucidating relevant biological pathways impacted in ME/CFS and reflect the physiological variations among the patients that stem from environmental triggers, including exogenous viruses and/or altered viral activity.

肌痛性脑脊髓炎/慢性疲劳综合征(ME/CFS)是一种慢性疾病,表现为严重疲劳、劳累后乏力和认知障碍等一系列症状,这些症状共同导致患者无法出门或卧床不起。对 ME/CFS 的表观遗传学研究共同证实,与免疫反应、细胞新陈代谢、细胞死亡和增殖、神经元和内皮细胞功能相关的细胞和机体生理学发生了改变和/或故障。ME/CFS是在一个主要的应激因素之后突然发生的,在大约70%的病例中涉及病毒感染,ME/CFS的症状与长期COVID的症状重叠。与 ME/CFS 病理有关的病毒主要是共生疱疹病毒,其生命周期为二价潜伏-裂解周期。病毒和宿主之间复杂的相互作用涉及双方的策略:病毒的免疫逃避和持续存在,以及宿主的免疫激活和病毒清除。疱疹病毒通过对自身和宿主基因组的表观遗传调控来促进其持续存在,这种动态的相互作用对于疱疹病毒来说是必不可少的。在这篇文章中,我们概述了在 ME/CFS 中显示的表观遗传特征,并重点探讨了潜伏病毒(尤其是 Epstein-Barr 病毒)在 ME/CFS 中长期表观遗传重编程过程中可能采用的潜在策略。表观遗传学研究有助于阐明影响 ME/CFS 的相关生物通路,并反映出患者因环境诱因(包括外源性病毒和/或病毒活性改变)而产生的生理差异。
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引用次数: 0
Effectiveness of integrated person-centered interventions for older people's care: Review of Swedish experiences and experts’ perspective 以人为本的老年人护理综合干预措施的有效性:瑞典经验回顾与专家观点。
IF 11.1 2区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-04-25 DOI: 10.1111/joim.13784
Mariam Kirvalidze, Anne-Marie Boström, Ann Liljas, Megan Doheny, Anne Hendry, Brendan McCormack, Laura Fratiglioni, Sulin Ali, Zahra Ebrahimi, Sölve Elmståhl, Maria Eriksdotter, Pascal Gläske, Lena-Karin Gustafsson, Åsa Hedberg Rundgren, Helena Hvitfeldt, Carin Lennartsson, Lena Marmstål Hammar, Gunnar H Nilsson, Peter Nilsson, Joakim Öhlén, Anna Sandgren, Annika Söderman, Karl Swedberg, Nicoline Vackerberg, Davide Liborio Vetrano, Helle Wijk, Janne Agerholm, Amaia Calderón-Larrañaga

Older adults have multiple medical and social care needs, requiring a shift toward an integrated person-centered model of care. Our objective was to describe and summarize Swedish experiences of integrated person-centered care by reviewing studies published between 2000 and 2023, and to identify the main challenges and scientific gaps through expert discussions. Seventy-three publications were identified by searching MEDLINE and contacting experts. Interventions were categorized using two World Health Organization frameworks: (1) Integrated Care for Older People (ICOPE), and (2) Integrated People-Centered Health Services (IPCHS). The included 73 publications were derived from 31 unique and heterogeneous interventions pertaining mainly to the micro- and meso-levels. Among publications measuring mortality, 15% were effective. Subjective health outcomes showed improvement in 24% of publications, morbidity outcomes in 42%, disability outcomes in 48%, and service utilization outcomes in 58%. Workshop discussions in Stockholm (Sweden), March 2023, were recorded, transcribed, and summarized. Experts emphasized: (1) lack of rigorous evaluation methods, (2) need for participatory designs, (3) scarcity of macro-level interventions, and (4) importance of transitioning from person- to people-centered integrated care. These challenges could explain the unexpected weak beneficial effects of the interventions on health outcomes, whereas service utilization outcomes were more positively impacted. Finally, we derived a list of recommendations, including the need to engage care organizations in interventions from their inception and to leverage researchers’ scientific expertise. Although this review provides a comprehensive snapshot of interventions in the context of Sweden, the findings offer transferable perspectives on the real-world challenges encountered in this field.

老年人有多种医疗和社会护理需求,需要向以人为本的综合护理模式转变。我们的目标是通过回顾 2000 年至 2023 年间发表的研究,描述并总结瑞典在以人为本的综合护理方面的经验,并通过专家讨论找出主要挑战和科学差距。通过搜索 MEDLINE 和联系专家,我们确定了 73 篇出版物。采用世界卫生组织的两个框架对干预措施进行了分类:(1)老年人综合护理(ICOPE)和(2)以人为本的综合健康服务(IPCHS)。收录的 73 篇出版物来自 31 种独特的、不同的干预措施,主要涉及微观和中观层面。在衡量死亡率的出版物中,15%是有效的。24%的出版物显示主观健康结果有所改善,42%的出版物显示发病结果有所改善,48%的出版物显示残疾结果有所改善,58%的出版物显示服务利用率有所改善。对 2023 年 3 月在斯德哥尔摩(瑞典)举行的研讨会讨论情况进行了记录、转录和总结。专家们强调:(1) 缺乏严格的评估方法,(2) 需要参与式设计,(3) 缺乏宏观层面的干预措施,(4) 必须从以人为本过渡到以人为本的综合护理。这些挑战可以解释为什么干预措施对健康结果的有益影响出乎意料地微弱,而对服务利用结果的影响则更为积极。最后,我们提出了一系列建议,包括需要让护理组织从一开始就参与干预,并充分利用研究人员的科学专业知识。虽然这篇综述提供了瑞典干预措施的全面概况,但研究结果为这一领域在现实世界中遇到的挑战提供了可借鉴的视角。
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引用次数: 0
Preoperative prediction of metastatic pheochromocytoma and paraganglioma using clinical, genetic, and biochemical markers: A cohort study 利用临床、遗传和生化标记对转移性嗜铬细胞瘤和副神经节瘤进行术前预测:一项队列研究。
IF 11.1 2区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-04-24 DOI: 10.1111/joim.13791
Seung Shin Park, Chang Ho Ahn, Seunghoo Lee, Woochang Lee, Won Woong Kim, Yu-Mi Lee, Su Jin Kim, Tae-Yon Sung, Kyu Eun Lee, Jung Hee Kim, Seung Hun Lee, Jung-Min Koh

Background

The prevalence of metastatic pheochromocytoma and paraganglioma (PPGL) is approximately 15%–20%. Although there are indicators to assess metastatic risks, none of them predict metastasis reliably. Therefore, we aimed to develop and validate a scoring system using clinical, genetic, and biochemical risk factors to preoperatively predict the metastatic risk of PPGL.

Methods

In the cross-sectional cohort (n = 180), clinical, genetic, and biochemical risk factors for metastasis were identified using multivariate logistic regression analysis, and a novel scoring system was developed. The scoring system was validated and compared with the age, size of tumor, extra-adrenal location, and secretory type (ASES) score in the longitudinal cohort (n = 114).

Results

In the cross-sectional cohort, pseudohypoxia group-related gene variants (SDHB, SDHD, or VHL), methoxytyramine >0.16 nmol/L, and tumor size >6.0 cm were independently associated with metastasis after multivariate logistic regression. Using them, the gene variant, methoxytyramine, and size of tumor (GMS) score were developed. In the longitudinal cohort, Harrell's concordance index of the GMS score (0.873, 95% confidence interval [CI]: 0.738–0.941) was higher than that of the ASES score (0.713, 95% CI: 0.567–0.814, p = 0.007). In the longitudinal cohort, a GMS score ≥2 was significantly associated with a higher risk of metastasis (hazard ratio = 25.07, 95% CI: 5.65–111.20). A GMS score ≥2 (p < 0.001), but not ASES score ≥2 (p = 0.090), was associated with shorter progression-free survival.

Conclusion

The GMS scoring system, which integrates gene variant, methoxytyramine level, and tumor size, provides a valuable preoperative approach to assess metastatic risk in PPGL.

背景转移性嗜铬细胞瘤和副神经节瘤(PPGL)的发病率约为 15%-20%。虽然有一些评估转移风险的指标,但它们都不能可靠地预测转移。方法在横断面队列(n = 180)中,使用多变量逻辑回归分析确定了转移的临床、遗传和生化风险因素,并建立了一个新的评分系统。结果在横断面队列中,假缺氧组相关基因变异(SDHB、SDHD或VHL)、甲氧基酪胺>0.16 nmol/L和肿瘤大小>6.0 cm与多变量逻辑回归后的转移独立相关。利用这些因素制定了基因变异、甲氧基酪胺和肿瘤大小(GMS)评分。在纵向队列中,GMS 评分的 Harrell 一致性指数(0.873,95% 置信区间 [CI]:0.738-0.941)高于 ASES 评分(0.713,95% CI:0.567-0.814,P = 0.007)。在纵向队列中,GMS评分≥2与较高的转移风险显著相关(危险比=25.07,95% CI:5.65-111.20)。结论GMS评分系统综合了基因变异、甲氧基酪胺水平和肿瘤大小,为评估PPGL的转移风险提供了一种有价值的术前方法。
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引用次数: 0
Early transfusion patterns improve the Molecular International Prognostic Scoring System (IPSS-M) prediction in myelodysplastic syndromes 早期输血模式可改善骨髓增生异常综合征的分子国际预后评分系统(IPSS-M)预测。
IF 11.1 2区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-04-23 DOI: 10.1111/joim.13790
Maria Creignou, Elsa Bernard, Alessandro Gasparini, Anna Tranberg, Gabriele Todisco, Pedro Luis Moura, Elisabeth Ejerblad, Lars Nilsson, Hege Garelius, Petar Antunovic, Fryderyk Lorenz, Bengt Rasmussen, Gunilla Walldin, Teresa Mortera-Blanco, Monika Jansson, Magnus Tobiasson, Chiara Elena, Jacqueline Ferrari, Anna Gallì, Sara Pozzi, Luca Malcovati, Gustaf Edgren, Michael J. Crowther, Martin Jädersten, Elli Papaemmanuil, Eva Hellström-Lindberg

Background

The Molecular International Prognostic Scoring System (IPSS-M) is the new gold standard for diagnostic outcome prediction in patients with myelodysplastic syndromes (MDS). This study was designed to assess the additive prognostic impact of dynamic transfusion parameters during early follow-up.

Methods

We retrieved complete transfusion data from 677 adult Swedish MDS patients included in the IPSS-M cohort. Time-dependent erythrocyte transfusion dependency (E-TD) was added to IPSS-M features and analyzed regarding overall survival and leukemic transformation (acute myeloid leukemia). A multistate Markov model was applied to assess the prognostic value of early changes in transfusion patterns.

Results

Specific clinical and genetic features were predicted for diagnostic and time-dependent transfusion patterns. Importantly, transfusion state both at diagnosis and within the first year strongly predicts outcomes in both lower (LR) and higher-risk (HR) MDSs. In multivariable analysis, 8-month landmark E-TD predicted shorter survival independently of IPSS-M (p < 0.001). A predictive model based on IPSS-M and 8-month landmark E-TD performed significantly better than a model including only IPSS-M. Similar trends were observed in an independent validation cohort (n = 218). Early transfusion patterns impacted both future transfusion requirements and outcomes in a multistate Markov model.

Conclusion

The transfusion requirement is a robust and available clinical parameter incorporating the effects of first-line management. In MDS, it provides dynamic risk information independently of diagnostic IPSS-M and, in particular, clinical guidance to LR MDS patients eligible for potentially curative therapeutic intervention.

背景分子国际预后评分系统(IPSS-M)是骨髓增生异常综合征(MDS)患者诊断结果预测的新金标准。本研究旨在评估早期随访期间动态输血参数对预后的附加影响。方法:我们检索了 IPSS-M 队列中 677 名瑞典成年 MDS 患者的完整输血数据。我们将时间依赖性红细胞输注依赖性(E-TD)添加到 IPSS-M 特征中,并对总生存期和白血病转化(急性髓性白血病)进行了分析。应用多态马尔可夫模型评估了输血模式早期变化的预后价值。结果 特定的临床和遗传特征可预测诊断和时间依赖性输血模式。重要的是,诊断时和第一年内的输血状态可有力预测低危(LR)和高危(HR)MDS 的预后。在多变量分析中,8 个月的标志性 E-TD 预测了较短的生存期,而与 IPSS-M 无关(p < 0.001)。基于 IPSS-M 和 8 个月地标 E-TD 的预测模型明显优于仅包含 IPSS-M 的模型。在一个独立的验证队列(n = 218)中也观察到了类似的趋势。在多态马尔可夫模型中,早期输血模式对未来输血需求和预后都有影响。在 MDS 中,它提供了独立于诊断性 IPSS-M 的动态风险信息,特别是为符合潜在治愈性治疗干预条件的 LR MDS 患者提供了临床指导。
{"title":"Early transfusion patterns improve the Molecular International Prognostic Scoring System (IPSS-M) prediction in myelodysplastic syndromes","authors":"Maria Creignou,&nbsp;Elsa Bernard,&nbsp;Alessandro Gasparini,&nbsp;Anna Tranberg,&nbsp;Gabriele Todisco,&nbsp;Pedro Luis Moura,&nbsp;Elisabeth Ejerblad,&nbsp;Lars Nilsson,&nbsp;Hege Garelius,&nbsp;Petar Antunovic,&nbsp;Fryderyk Lorenz,&nbsp;Bengt Rasmussen,&nbsp;Gunilla Walldin,&nbsp;Teresa Mortera-Blanco,&nbsp;Monika Jansson,&nbsp;Magnus Tobiasson,&nbsp;Chiara Elena,&nbsp;Jacqueline Ferrari,&nbsp;Anna Gallì,&nbsp;Sara Pozzi,&nbsp;Luca Malcovati,&nbsp;Gustaf Edgren,&nbsp;Michael J. Crowther,&nbsp;Martin Jädersten,&nbsp;Elli Papaemmanuil,&nbsp;Eva Hellström-Lindberg","doi":"10.1111/joim.13790","DOIUrl":"10.1111/joim.13790","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The Molecular International Prognostic Scoring System (IPSS-M) is the new gold standard for diagnostic outcome prediction in patients with myelodysplastic syndromes (MDS). This study was designed to assess the additive prognostic impact of dynamic transfusion parameters during early follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrieved complete transfusion data from 677 adult Swedish MDS patients included in the IPSS-M cohort. Time-dependent erythrocyte transfusion dependency (E-TD) was added to IPSS-M features and analyzed regarding overall survival and leukemic transformation (acute myeloid leukemia). A multistate Markov model was applied to assess the prognostic value of early changes in transfusion patterns.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Specific clinical and genetic features were predicted for diagnostic and time-dependent transfusion patterns. Importantly, transfusion state both at diagnosis and within the first year strongly predicts outcomes in both lower (LR) and higher-risk (HR) MDSs. In multivariable analysis, 8-month landmark E-TD predicted shorter survival independently of IPSS-M (<i>p</i> &lt; 0.001). A predictive model based on IPSS-M and 8-month landmark E-TD performed significantly better than a model including only IPSS-M. Similar trends were observed in an independent validation cohort (<i>n</i> = 218). Early transfusion patterns impacted both future transfusion requirements and outcomes in a multistate Markov model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The transfusion requirement is a robust and available clinical parameter incorporating the effects of first-line management. In MDS, it provides dynamic risk information independently of diagnostic IPSS-M and, in particular, clinical guidance to LR MDS patients eligible for potentially curative therapeutic intervention.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"296 1","pages":"53-67"},"PeriodicalIF":11.1,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.13790","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140672265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Gestational diabetes mellitus is associated with greater incidence of dementia during long-term post-partum follow-up 妊娠期糖尿病与产后长期随访期间痴呆症发病率升高有关
IF 11.1 2区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-04-17 DOI: 10.1111/joim.13787
Yang Zhang, Darui Gao, Ying Gao, Jing Li, Chenglong Li, Yang Pan, Yongqian Wang, Junqing Zhang, Fanfan Zheng, Wuxiang Xie

Background

The impact of gestational diabetes mellitus (GDM) on incident dementia is unknown. Our aim was to evaluate the relationship between GDM and all-cause dementia and the mediating effects of chronic diseases on this relationship.

Methods

This prospective cohort study included women from the UK Biobank who were grouped based on GDM history. Multivariate Cox proportional hazard models were used to explore the associations between GDM and dementia. We further analysed the mediating effects of chronic diseases on this relationship and the interactions of covariates.

Results

A total of 1292 women with and 204,171 women without a history of GDM were included. During a median follow-up period of 45 years after first birth, 2921 women were diagnosed with dementia. Women with a GDM history had a 67% increased risk of incident dementia (hazard ratio 1.67, 95% confidence interval: 1.03–2.69) compared with those without a GDM history. According to mediation analyses, type 2 diabetes, coronary heart disease, chronic kidney disease and comorbidities (diagnosed with any two of the three diseases) explained 34.5%, 8.4%, 5.2% and 18.8% of the mediating effect on the relationship. Subgroup analyses revealed that physical activity modified the association between GDM history and dementia (p for interaction = 0.030). Among physically inactive women, GDM was significantly associated with incident dementia; however, this association was not observed among physically active women.

Conclusions

A history of GDM was associated with a greater risk of incident dementia. Type 2 diabetes partially mediated this relationship. Strategies for dementia prevention might be considered for women with a history of GDM.

背景妊娠期糖尿病(GDM)对痴呆症的影响尚不清楚。我们的目的是评估 GDM 与全因痴呆之间的关系,以及慢性疾病对这一关系的中介作用。我们采用多变量 Cox 比例危险模型来探讨 GDM 与痴呆之间的关系。我们进一步分析了慢性疾病对这一关系的中介效应以及协变量的交互作用。结果 共纳入了 1292 名有 GDM 病史的妇女和 204171 名无 GDM 病史的妇女。在首次分娩后 45 年的中位随访期间,有 2921 名妇女被诊断患有痴呆症。与无 GDM 史的妇女相比,有 GDM 史的妇女患痴呆症的风险增加了 67%(危险比 1.67,95% 置信区间:1.03-2.69)。根据中介分析,2 型糖尿病、冠心病、慢性肾脏病和合并症(被诊断患有这三种疾病中的任何两种)对这一关系的中介效应分别占 34.5%、8.4%、5.2% 和 18.8%。分组分析表明,体育锻炼可改变 GDM 史与痴呆症之间的关系(交互作用 p = 0.030)。在缺乏体育锻炼的女性中,GDM 与痴呆症的发生显著相关;然而,在体育锻炼积极的女性中却没有观察到这种关联。2型糖尿病部分介导了这种关系。对于有 GDM 病史的女性,可以考虑采取预防痴呆症的策略。
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引用次数: 0
Reframing prediabetes: A call for better risk stratification and intervention 重塑糖尿病前期:呼吁更好地进行风险分层和干预
IF 11.1 2区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-04-12 DOI: 10.1111/joim.13786
Sun H. Kim

Prediabetes is an intermediate state of glucose homeostasis whereby plasma glucose concentrations are above normal but below the threshold of diagnosis for diabetes. Over the last several decades, criteria for prediabetes have changed as the cut points for normal glucose concentration and diagnosis of diabetes have shifted. Global consensus does not exist for prediabetes criteria; as a result, the clinical course and risk for type 2 diabetes vary. At present, we can identify individuals with prediabetes based on three glycemic tests (hemoglobin A1c, fasting plasma glucose, and 2-h plasma glucose during an oral glucose tolerance test). The majority of individuals diagnosed with prediabetes meet only one of these criteria. Meeting one, two, or all glycemic criteria changes risk for type 2 diabetes, but this information is not widely known and does not currently guide intervention strategies for individuals with prediabetes. This review summarizes current epidemiology, prognosis, and intervention strategies for individuals diagnosed with prediabetes and suggests a call for more precise risk stratification of individuals with prediabetes as elevated (one prediabetes criterion), high risk (two prediabetes criteria), and very high risk (three prediabetes criteria). In addition, the roles of oral glucose tolerance testing and continuous glucose monitoring in the diagnostic criteria for prediabetes need reassessment. Finally, we must reframe our goals for prediabetes and prioritize intensive interventions for those at high and very high risk for type 2 diabetes.

糖尿病前期是血糖平衡的中间状态,即血浆葡萄糖浓度高于正常值,但低于糖尿病诊断的临界值。在过去的几十年里,糖尿病前期的标准随着血糖浓度正常与糖尿病诊断临界点的变化而变化。对于糖尿病前期的标准,全球尚未达成共识;因此,临床病程和罹患 2 型糖尿病的风险也各不相同。目前,我们可以根据三种血糖检测方法(血红蛋白 A1c、空腹血浆葡萄糖和口服葡萄糖耐量试验中的 2 小时血浆葡萄糖)来确定糖尿病前期患者。大多数被诊断为糖尿病前期的患者只符合其中一个标准。符合一个、两个或所有血糖标准会改变罹患 2 型糖尿病的风险,但这一信息并不广为人知,目前也无法指导针对糖尿病前期患者的干预策略。这篇综述总结了目前的流行病学、预后和针对被诊断为糖尿病前期患者的干预策略,并建议对糖尿病前期患者进行更精确的风险分层,将其分为高危(符合一项糖尿病前期标准)、高危(符合两项糖尿病前期标准)和极高危(符合三项糖尿病前期标准)。此外,还需要重新评估口服葡萄糖耐量试验和持续葡萄糖监测在糖尿病前期诊断标准中的作用。最后,我们必须重新制定糖尿病前期的目标,优先考虑对那些高危和极高危 2 型糖尿病患者进行强化干预。
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引用次数: 0
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Journal of Internal Medicine
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