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Pharmacological therapy for stable chronic obstructive pulmonary disease 稳定期慢性阻塞性肺疾病的药物治疗
Q1 Medicine Pub Date : 2023-04-05 DOI: 10.1002/cdt3.65
Ruirui Duan, Baicun Li, Ting Yang

In recent years, emphasis has shifted from preventing and treating chronic obstructive pulmonary disease (COPD) to early prevention, early treatment, and disease stabilization, with the main goal of improving patients’ quality of life and reducing the frequency of acute exacerbations. This review summarizes pharmacological therapies for stable COPD.

近年来,慢性阻塞性肺疾病(COPD)的重点已从预防和治疗转向早期预防、早期治疗和疾病稳定,主要目标是提高患者的生活质量和减少急性加重的频率。本文综述了稳定型COPD的药物治疗方法。
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引用次数: 1
Interactions between the lung microbiome and host immunity in chronic obstructive pulmonary disease 慢性阻塞性肺疾病中肺微生物组与宿主免疫的相互作用
Q1 Medicine Pub Date : 2023-04-03 DOI: 10.1002/cdt3.66
Yixing Zhu, De Chang

Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory disease and the third leading cause of death worldwide. Developments in next-generation sequencing technology have improved microbiome analysis, which is increasingly recognized as an important component of disease management. Similar to the gut, the lung is a biosphere containing billions of microbial communities. The lung microbiome plays an important role in regulating and maintaining the host immune system. The microbiome composition, metabolites of microorganisms, and the interactions between the lung microbiome and the host immunity profoundly affect the occurrence, development, treatment, and prognosis of COPD. In this review, we drew comparisons between the lung microbiome of healthy individuals and that of patients with COPD. Furthermore, we summarize the intrinsic interactions between the host and the overall lung microbiome, focusing on the underlying mechanisms linking the microbiome to the host innate and adaptive immune response pathways. Finally, we discuss the possibility of using the microbiome as a biomarker to determine the stage and prognosis of COPD and the feasibility of developing a novel, safe, and effective therapeutic target.

慢性阻塞性肺疾病(COPD)是一种常见的慢性呼吸系统疾病,也是全球第三大死亡原因。新一代测序技术的发展改善了微生物组分析,这越来越被认为是疾病管理的重要组成部分。与肠道类似,肺是一个包含数十亿微生物群落的生物圈。肺微生物组在调节和维持宿主免疫系统中起着重要作用。微生物组组成、微生物代谢物以及肺部微生物组与宿主免疫的相互作用深刻影响COPD的发生、发展、治疗和预后。在这篇综述中,我们比较了健康个体和COPD患者的肺微生物组。此外,我们总结了宿主与整体肺部微生物组之间的内在相互作用,重点关注微生物组与宿主先天和适应性免疫反应途径之间的潜在机制。最后,我们讨论了利用微生物组作为生物标志物来确定COPD的分期和预后的可能性,以及开发一种新的、安全的、有效的治疗靶点的可行性。
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引用次数: 0
Alignment of human aquaporin 4 and ß-amyloid proteins may indicate involvement of ß-amyloid in brain water homeostasis and prevention of brain edema 人类水通道蛋白4和ß-淀粉样蛋白的排列可能表明ß-淀粉样蛋白参与脑水稳态和预防脑水肿
Q1 Medicine Pub Date : 2023-03-29 DOI: 10.1002/cdt3.64
Steven Lehrer, Peter H. Rheinstein

The amyloid hypothesis states that the buildup of ß-amyloid in the brain is the main factor for Alzheimer's disease (AD) pathogenesis. An imbalance between ß-amyloid production and ß-amyloid clearance causes the advanced stages of the disease, including the development of neurofibrillary tangles containing tau protein.1

Many medications that aim to reduce ß-amyloid in AD are not clinically effective. FDA has approved aducanumab, one of four anti-ß-amyloid antibodies that have been demonstrated to mediate the removal of amyloid plaque from the brains of AD patients. FDA accepted the decrease of amyloid plaque as a surrogate endpoint for aducanumab. But there is intense disagreement over the justification for approval and the scope of the clinical benefit provided by antiamyloid antibodies.2

One side effect of the antibodies is brain edema, effusion, and hemorrhages, so called amyloid-related imaging abnormalities (ARIA). ARIA occurs in aged squirrel monkeys as well as in humans.3

Lecanemab, an antiamyloid monoclonal antibody, was associated with edema or effusions in 12.4% of subjects, including three fatal brain hemorrhages; the placebo group had 1.7% brain edema.4-9 In the case of donanemab, another anti-amyloid monoclonal antibody, if edema or effusion occurred with the first three doses of the drug, the dosage was not increased.10

A serious clinical condition, brain edema is defined by a pathological swelling of the brain tissue brought on by an increase in the water content of the brain. In humans11 and in a mouse model, APOE isoform affects neurological prognosis following intracerebral hemorrhage. Poor functional outcome and more cerebral edema are linked to APOE4.12 Three SNPs of the ABCC8 gene, rs2283261, rs3819521, and rs2283258, are significantly associated with brain edema, measured by increased intracranial pressure and CT imaging. Haptoglobin type, Hp2 versus Hp1, may also influence brain edema.13

Aquaporins, a family of water channel proteins that have been found in animals, may provide an explanation for AD brain edema. Aquaporin-4 (AQP4), the most significant form of aquaporin in the central nervous system, mediates water homeostasis in healthy and pathological settings, such as severe brain injury.13, 14

Because brain edema has occurred during clinical trials of most anti-amyloid antibodies, we hypothesize that ß-amyloid might be an important element in brain water homeostasis. Removing ß-amyloid could cause brain edema and bleeding in some AD patients. To investigate this idea, we analyzed structures of aquaporin-4 and ß-amyloid from the RCSB protein data bank.

To help identify the brain regions where anti-amyloid antibodies may act, we used the Allen Brain Atlas and the H

淀粉样蛋白假说认为ß-淀粉样蛋白在大脑中的积聚是阿尔茨海默病(AD)发病的主要因素。ß-淀粉样蛋白产生和ß-淀粉样蛋白清除之间的不平衡导致疾病的晚期,包括含有tau蛋白的神经原纤维缠结的发展。许多旨在减少AD中ß-淀粉样蛋白的药物在临床上并不有效。FDA已经批准了aducanumab,这是四种抗-ß-淀粉样蛋白抗体之一,已被证明可以介导AD患者大脑中淀粉样蛋白斑块的清除。FDA接受淀粉样斑块的减少作为aducanumab的替代终点。但是对于批准的理由和抗淀粉样蛋白抗体提供的临床益处的范围存在激烈的分歧。抗体的一个副作用是脑水肿、积液和出血,即所谓的淀粉样蛋白相关成像异常(ARIA)。ARIA不仅发生在人类身上,也发生在年老的松鼠猴身上。3Lecanemab,一种抗淀粉样蛋白单克隆抗体,在12.4%的受试者中与水肿或积液相关,包括3例致命性脑出血;安慰剂组脑水肿率为1.7%。4-9在另一种抗淀粉样蛋白单克隆抗体donanemab的情况下,如果前三次剂量的药物出现水肿或积液,则不增加剂量。脑水肿是一种严重的临床状况,是由大脑含水量增加引起的脑组织的病理性肿胀。在人类和小鼠模型中,APOE亚型影响脑出血后的神经预后。ABCC8基因的三个snp rs2283261、rs3819521和rs2283258与脑水肿显著相关,通过颅内压升高和CT成像测量。触珠蛋白类型,Hp2与Hp1,也可能影响脑水肿。水通道蛋白是一种在动物体内发现的水通道蛋白家族,它可能是AD脑水肿的一种解释。水通道蛋白-4 (AQP4)是中枢神经系统中最重要的水通道蛋白形式,在健康和病理环境中介导水稳态,如严重脑损伤。13,14因为在大多数抗淀粉样蛋白抗体的临床试验中都发生过脑水肿,我们假设ß-淀粉样蛋白可能是脑水稳态的一个重要因素。去除ß-淀粉样蛋白会导致一些AD患者脑水肿和出血。为了研究这一观点,我们分析了RCSB蛋白质数据库中的水通道蛋白-4和ß-淀粉样蛋白的结构。为了帮助确定抗淀粉样蛋白抗体可能起作用的大脑区域,我们使用Allen brain Atlas和Human Protein Atlas来检测大脑中AQP4和APP(淀粉样蛋白前体蛋白)RNA的表达。15,16在PYMOL v 2.5.0软件上使用Super命令对两个蛋白序列进行Super比对。Super进行序列无关的基于结构的动态规划对齐(与align命令不同),然后进行一系列的优化循环,旨在通过消除具有高相对可变性的配对来改善拟合。对于序列相似度较低的蛋白质,Super命令比align命令更可靠。AQP4表达(Allen Brain Atlas)如图1所示。AQP4 RNA在多种脑区广泛而强烈地表达,包括AD发病的海马和海马旁区。图2为AQP4 RNA表达示意图。AQP4 RNA在人类和小鼠的多种脑区中都有强烈和广泛的表达(未显示)。供体为24岁男性黑人或非裔美国人(Allen Brain Atlas)。淀粉样蛋白前体蛋白(APP) RNA表达见图3。与AQP4一样,APP在整个大脑中强烈表达(Human Protein Atlas)。Pymol对29个排列的水通道蛋白-4和ß-淀粉样蛋白原子进行了5次循环计算,21个原子的原子位置的最终均方根偏差(RMSD)为0.300 Å(图4)。Pymol自动确定要计算的最佳循环数。RMSD值越低,表明验证的对准精度越高。RMSD值为1 Å或更小表示非常好的对齐。两个排列的分子水通道蛋白-4和ß-淀粉样蛋白如图5所示。21原子排列非常好。箭头表示水通道蛋白4外显子3上覆盖缬氨酸162的ß-淀粉样蛋白的异亮氨酸77。比对是比较相关蛋白质序列的有力方法。它们可以用来记录关于匹配序列的各种信息,例如共享的结构功能或共同的进化祖先。在过去的几十年里,蛋白质序列比对分析已经成为生物信息学分析研究的一个重要阶段。利用序列比对建立了大量蛋白质家族信息的蛋白质数据库。 我们的分析表明AQP4和ß-淀粉样蛋白可能具有共同的功能,包括维持脑水稳态和预防脑水肿。AQP4和APP在脑内表达的相似性(图2和3)支持了这一结论。最广泛的中枢神经系统水通道AQP4,常见于星形细胞端足。AQP4 RNA在人和小鼠的多种脑区均有广泛而强烈的表达。此外,整个小鼠大脑表现出显著的AQP4强度和星形胶质细胞端足的广泛免疫标记,这种模式代表了脉管系统和毛细血管壁。AQP4变异可能是AD血管源性水肿的危险因素。血管源性水肿是血管内皮细胞紧密连接破裂的直接结果,是由于血脑屏障完整性的破坏而产生的。由于来自脉管系统的液体和蛋白质穿透间隙,脑细胞外腔增大。血管源性水肿导致颅内压升高,脑血流量减少,脑疝,最终死亡。血管源性水肿可发生于外伤、动脉高血压、肿瘤释放的血管活性物质或内皮损伤物质,如花生四烯酸、兴奋性神经递质、类二十烷酸、缓激肽、组胺和自由基。血管源性水肿是抗淀粉样AD药物的常见副作用,可能是淀粉样蛋白从大脑中被清除的信号。一项AQP4外显子4的研究未发现突变。但在另一项研究中,在对363名创伤性脑损伤患者的临床、神经成像和遗传数据进行检查的研究中,在AQP4基因区域检测到7个标签单核苷酸多态性(snp)。标签SNP是位于基因组高度连锁不平衡区域的SNP,是单倍型SNP的一部分。两个标签snp, rs3763043,与精神分裂症相关,21和rs3875089,与脑出血相关,22与创伤性脑损伤后6个月评估的不良临床结果有关。23我们发现AQP4与ß-淀粉样蛋白密切相关,这可能表明ß-淀粉样蛋白与AQP4一样,在维持脑水稳态和预防脑水肿方面可能很重要。ß-淀粉样蛋白结构在哺乳动物进化过程中一直高度保守,表明一种或多种重要功能。例如,ß-amyloid具有抗菌作用,可能是对单纯疱疹型1.24的一种遗传防御。本研究的结果有两个值得注意的意义:(1)在抗淀粉样蛋白AD治疗前筛选AQP4多态性snp rs3763043、rs3875089和APOE4异构体,可以识别脑水肿出血高危患者。筛选ABCC8多态性和触珠蛋白形式也可能有价值。(2)在儿童中进行相同的筛查可以发现在某些运动中增加的创伤性脑损伤易感性:足球,曲棍球,篮球和棒球。APOE2、APOE4、AQP4和抗淀粉样蛋白抗体并不是AD血管源性水肿的唯一相关物质。治疗阿尔茨海默病的药物avagacestat是一种小分子γ -分泌酶抑制剂,可以降低ß-淀粉样蛋白水平,但也会引起血管源性水肿此外,在未接受任何治疗的AD患者中也发现无症状血管源性水肿因此,局灶性、局限性血管源性水肿可能是AD病理过程的一部分。由于APOE和ABCC8基因与脑水肿相关,因此评估这些蛋白结构与AQP4的对齐和其他相似之处是值得的。我们得出结论,ß-淀粉样蛋白可能参与脑水稳态和防止血管源性脑水肿。从AD患者体内去除ß-淀粉样蛋白可促进血管源性脑水肿和出血。筛选AQP4和ABCC8多态性、APOE2和APOE4亚型以及接触珠蛋白形式可以识别抗淀粉样蛋白治疗后脑水肿和出血的高危患者。进一步的研究是必要的。预印本发布https://doi.org/10.21203/rs.3.rs-2350250/v1Dr。Steven Lehrer和Peter H. Rhein
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引用次数: 0
Application of wearable devices for monitoring cardiometabolic dysfunction under the exposome paradigm 可穿戴设备在暴露模式下监测心脏代谢功能障碍的应用
Q1 Medicine Pub Date : 2023-03-23 DOI: 10.1002/cdt3.67
Haodong Zhang, Lingming Hu, Pai Zheng, Guang Jia

Environmental factors, including chemical/physical pollutants, as well as lifestyle and psychological factors, contribute greatly to the pathways leading to cardiometabolic diseases with a heavy disease burden and economic loss. The concept of exposomes provides a novel paradigm for combining all exposure characteristics to evaluate disease risk. A solution-like exposome requires technological support to provide continuous data to monitor vital signs and detect abnormal fluctuations. Wearable devices allow people to conveniently monitor signals during their daily routines. These new technologies empower users to more actively prevent and manage cardiometabolic disease by reviewing risk factors of the disease, especially lifestyle factors, such as sleeping time, screen time, and mental health condition. Devices with multiple sensors can monitor electrocardiography data, oxygen saturation, intraocular pressure, respiratory rate, and heart rate to enhance the exposome study and provide precise suggestions for disease prevention and management.

环境因素,包括化学/物理污染物,以及生活方式和心理因素,在导致心脏代谢疾病的途径中发挥了重要作用,造成了沉重的疾病负担和经济损失。暴露体的概念为综合所有暴露特征来评估疾病风险提供了一个新的范例。类似解决方案的exposure需要技术支持,以提供连续的数据,以监测生命体征和检测异常波动。可穿戴设备让人们在日常生活中方便地监控信号。这些新技术使用户能够通过审查疾病的风险因素,特别是生活方式因素,如睡眠时间、屏幕时间和精神健康状况,更积极地预防和管理心脏代谢疾病。多传感器设备可监测心电图、血氧饱和度、眼压、呼吸频率、心率等数据,加强暴露研究,为疾病预防和管理提供精准建议。
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引用次数: 1
Guide for Authors 作者指南
Q1 Medicine Pub Date : 2023-03-13 DOI: 10.1002/cdt3.61
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引用次数: 0
Trend analysis of noncommunicable diseases and their risk factors in Afghanistan 阿富汗非传染性疾病及其危险因素趋势分析
Q1 Medicine Pub Date : 2023-03-07 DOI: 10.1002/cdt3.62
Narges Neyazi, Ali Mohammad Mosadeghrad, Maryam Tajvar, Najibullah Safi

Background

Afghanistan is suffering from 40-year chronic conflicts, displacement, and demolition of its infrastructure. Afghanistan mortality survey 2010 shows nearly 46% of all deaths in the country were attributed to noncommunicable diseases (NCDs). In this study, we aimed to understand the differences in mortality and premature death due to NCDs by sex and the trend for the next 8 years.

Methods

We applied trend analysis using the secondary data from the Institute for Health Metrics and Evaluation, Global Burden of Diseases 2019. The information on NCD mortality, NCD deaths attributed to its risk factors, NCD percent of total years lived with disability (YLDs) attribution to each risk factor extracted from this database from 2008 to 2019. We investigated the trend from 2008 to 2019 for the mentioned factors and then forecast their trends until 2030.

Results

Our study shows that Afghanistan has had an increasing death number due to NCDs from 2008 to 2019 (50% for both sexes) and this will reach nearly 54% by 2030. Currently, half of NCDs deaths are premature in Afghanistan. The mortality rate and prevalence of risk factors are higher among women. More than 70% of YLDs will be due to NCDs in Afghanistan till 2030. Five risk factors including high systolic blood pressure (28.3%), high body mass index (23.4%), high blood glucose (20.6%), high low-density lipoprotein cholesterol (16.3%), and smoking (12.3%) will have the highest contribution to NCDs death in 2030, respectively.

Conclusions

In general, our study indicates that without any specific intervention to address NCDs in Afghanistan, not only the Sustainable Development Goal target for NCDs will not be met, but an increase in almost all risk factors prevalence, as well as NCD mortality, will be seen in Afghanistan.

阿富汗正遭受40年的长期冲突、流离失所和基础设施的破坏。2010年阿富汗死亡率调查显示,该国近46%的死亡是由非传染性疾病造成的。在这项研究中,我们旨在了解非传染性疾病死亡率和过早死亡的性别差异以及未来8年的趋势。方法利用2019年全球疾病负担卫生计量与评估研究所的二手数据进行趋势分析。从该数据库中提取的2008年至2019年非传染性疾病死亡率、非传染性疾病风险因素导致的非传染性疾病死亡、归因于每种风险因素的非传染性疾病占残疾总生存年数(YLDs)的百分比等信息。我们从2008年到2019年调查了上述因素的趋势,然后预测了它们到2030年的趋势。我们的研究表明,从2008年到2019年,阿富汗因非传染性疾病导致的死亡人数不断增加(男女均为50%),到2030年,这一数字将达到近54%。目前,阿富汗一半的非传染性疾病死亡是过早死亡。妇女的死亡率和危险因素的流行率较高。到2030年,阿富汗70%以上的死亡将是由非传染性疾病造成的。到2030年,包括高收缩压(28.3%)、高体重指数(23.4%)、高血糖(20.6%)、高低密度脂蛋白胆固醇(16.3%)和吸烟(12.3%)在内的5个危险因素将分别对非传染性疾病死亡的贡献最大。总的来说,我们的研究表明,如果没有任何具体的干预措施来解决阿富汗的非传染性疾病问题,不仅可持续发展目标的非传染性疾病目标将无法实现,而且阿富汗几乎所有风险因素的患病率以及非传染性疾病死亡率都将增加。
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引用次数: 1
Obesity in children and adolescents: Overview of the diagnosis and management 儿童和青少年肥胖:诊断和管理综述
Q1 Medicine Pub Date : 2023-03-07 DOI: 10.1002/cdt3.58
Joanna Y. L. Tung, Grace W. K. Poon, Juan Du, Kenneth K. Y. Wong

Childhood obesity is one of the biggest public health challenges globally. It is associated with various adverse health consequences throughout life. Prevention and early intervention represent the most reasonable and cost-effective approaches. Considerable progress has been achieved in the management of obesity in children and adolescents; yet, implementation in the real world remains a challenge. This article aimed to present an overview of the diagnosis and management of obesity in children and adolescents.

儿童肥胖是全球最大的公共卫生挑战之一。它与一生中各种不利的健康后果有关。预防和早期干预是最合理和最具成本效益的方法。在管理儿童和青少年肥胖方面取得了相当大的进展;然而,在现实世界中实现仍然是一个挑战。本文旨在介绍儿童和青少年肥胖的诊断和管理概况。
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引用次数: 0
Associations between diagnosis with stroke, comorbidities, and activity of daily living among older adults in the United States 美国老年人中风诊断、合并症和日常生活活动之间的关系
Q1 Medicine Pub Date : 2023-02-21 DOI: 10.1002/cdt3.60
Suebsarn Ruksakulpiwat, Wendie Zhou, Lalipat Phianhasin, Chitchanok Benjasirisan, Saeideh Salehizadeh, Limin Wang, Joachim G. Voss

Background

Stroke is the leading cause of mortality. This study aimed to investigate the association between stroke, comorbidities, and activity of daily living (ADL) among older adults in the United States.

Methods

Participants were 1165 older adults aged 60 and older from two waves (2016 and 2018) of the Health and Retirement Study who had a stroke. Descriptive statistics were used to describe demographic information and comorbidities. Logistic regressions and multiple regression analyses were used to determine associations between stroke, comorbidities, and ADL.

Results

The mean age was 75.32 ± 9.5 years, and 55.6% were female. An adjusted analysis shows that older stroke adults living with diabetes as comorbidity are significantly associated with difficulty in dressing, walking, bedding, and toileting. Moreover, depression was significantly associated with difficulty in dressing, walking, bathing, eating, and bedding. At the same time, heart conditions and hypertension as comorbidity were rarely associated with difficulty in ADL. After adjusting for age and sex, heart condition and depression are significantly associated with seeing a doctor for stroke (odds ratio [OR]: 0.66; 95% confidence interval [CI]: 0.49–0.91; p = 0.01) and stroke therapy (OR: 0.46; 95% CI: 0.25–0.84; p = 0.01). Finally, stroke problem (unstandardized β [B] = 0.58, p = 0.017) and stroke therapy (B = 1.42, p < 0.001) significantly predict a lower level of independence.

Conclusion

This study could benefit healthcare professionals in developing further interventions to improve older stroke adults' lives, especially those with a high level of dependence.

中风是导致死亡的主要原因。本研究旨在调查美国老年人中风、合并症和日常生活活动(ADL)之间的关系。方法:参与者为1165名60岁及以上的老年人,来自健康与退休研究的两波(2016年和2018年)卒中患者。描述性统计用于描述人口统计信息和合并症。使用逻辑回归和多元回归分析来确定卒中、合并症和ADL之间的关系。结果平均年龄75.32±9.5岁,女性占55.6%。一项调整后的分析显示,患有糖尿病的老年中风成年人与穿衣、行走、床上用品和如厕困难显著相关。此外,抑郁症与穿衣、走路、洗澡、吃饭和床上用品困难密切相关。同时,心脏病和高血压作为合并症很少与ADL困难相关。在调整了年龄和性别后,心脏病和抑郁症与中风就诊显著相关(优势比[OR]: 0.66;95%置信区间[CI]: 0.49-0.91;p = 0.01)和脑卒中治疗(OR: 0.46;95% ci: 0.25-0.84;p = 0.01)。最后,卒中问题(未标准化β [B] = 0.58, p = 0.017)和卒中治疗(B = 1.42, p < 0.001)显著预测较低的独立性水平。结论本研究有助于医疗保健专业人员制定进一步的干预措施,以改善老年中风患者的生活,特别是那些高度依赖中风患者的生活。
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引用次数: 1
Pharmacotherapy treatment patterns at hospital discharge and clinical outcomes among patients with heart failure with reduced ejection fraction 心力衰竭伴射血分数降低患者出院时的药物治疗模式和临床结果
Q1 Medicine Pub Date : 2023-02-08 DOI: 10.1002/cdt3.59
Yuttana Wongsalap, Duangkamon Poolpun, Konrapee Keawhai, Napusson Kitpluem, Parichat Pansiri, Siriluck Malaimat, Vichai Senthong, Kirati Kengkla

Background

This study aimed to assess the prescribing patterns of evidence-based pharmacotherapy and their association with clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF) in Thailand.

Methods

A retrospective cohort study of patients with HFrEF was conducted. Treatment with a β-blocker and renin–angiotensin system inhibitors (RASIs) with or without mineralocorticoid receptor antagonists (MRAs) at discharge was regarded as guideline-directed medical therapy (GDMT). All others were considered non-GDMT. The primary endpoint was the composite of all-cause mortality or heart failure (HF) rehospitalization. Inverse-probability-treatment-weighted adjusted Cox proportional hazard models were used to examine the treatment effects.

Results

In total, 653 patients with HFrEF (mean age 64.1 ± 14.3 years; 55.9% male) were included. GDMT with β-blockers and RASIs with or without MRAs was prescribed at a rate of 35.4%. During a median of 1-year follow-up, 167 patients (27.5%) had a composite event, 81 patients (13.3%) had all-cause mortality, and 109 patients (18.0%) had HF rehospitalization. Patients treated with GDMT at discharge showed significantly lower rates of the primary endpoint (adjusted hazard ratio [HR] 0.63; 95% CI 0.44–0.89; p = 0.009) compared with patients who did not receive GDMT. The use of GDMT was also associated with a significantly lower risk of all-cause mortality (adjusted HR 0.59; 95% CI 0.36–0.98; p = 0.045) and HF rehospitalization (adjusted HR 0.65; 95% CI 0.43–0.96; p = 0.031).

Conclusions

For HFrEF treatment, GDMT initiation at hospital discharge was associated with a significantly reduced risk of all-cause mortality and HF rehospitalization. Nevertheless, prescribing GDMT remains underused, and it could be encouraged to improve HF outcomes in real-world settings.

本研究旨在评估泰国心力衰竭伴射血分数降低(HFrEF)患者循证药物治疗的处方模式及其与临床结局的关系。方法对HFrEF患者进行回顾性队列研究。出院时使用β受体阻滞剂和肾素-血管紧张素系统抑制剂(RASIs)联合或不联合矿皮质激素受体拮抗剂(MRAs)进行治疗被视为指南导向药物治疗(GDMT)。所有其他的都被认为是非gdmt。主要终点是全因死亡率或心力衰竭(HF)再住院的综合。采用反概率处理加权校正Cox比例风险模型检验处理效果。结果共653例HFrEF患者(平均年龄64.1±14.3岁;55.9%为男性)。GDMT联合β受体阻滞剂和RASIs合并或不合并MRAs的处方率为35.4%。在中位1年的随访期间,167例患者(27.5%)出现复合事件,81例患者(13.3%)出现全因死亡,109例患者(18.0%)再次住院。出院时接受GDMT治疗的患者主要终点发生率显著降低(校正风险比[HR] 0.63;95% ci 0.44-0.89;p = 0.009),与未接受GDMT的患者相比。GDMT的使用还与全因死亡风险显著降低相关(调整后HR 0.59;95% ci 0.36-0.98;p = 0.045)和HF再住院(调整后HR 0.65;95% ci 0.43-0.96;p = 0.031)。结论:对于HF治疗,出院时开始GDMT与全因死亡率和HF再住院的风险显著降低相关。然而,处方GDMT仍未得到充分利用,可以鼓励在现实环境中改善心衰结果。
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引用次数: 0
High-fat-diet induced obesity and diabetes mellitus in Th1 and Th2 biased mice strains: A brief overview and hypothesis 高脂饮食诱导Th1和Th2偏倚小鼠品系肥胖和糖尿病:简要概述和假设
Q1 Medicine Pub Date : 2023-02-08 DOI: 10.1002/cdt3.57
Prakash Somi Sankaran

Obesity and diabetes mellitus are common metabolic diseases prevalent worldwide. Mice are commonly used to study the pathogenesis of these two conditions. Obesity and diabetes mellitus are induced by administering a high-fat diet in many studies although other diet-induced models are also used. Several factors may influence the outcome of the studies done to study diet-induced obesity in mice. The immune system plays a crucial role in the susceptibility of mice to develop obesity and metabolic disease. In this article, the reasons for differences in susceptibility to develop obesity and diabetes mellitus in mice in response to high-fat-diet feeding and the influence of immunological bias of the mice strain used in studies are evaluated. Mice strains that induce proinflammatory and Th1-type immune responses are found to be susceptible to high-fat-diet-induced obesity. A few studies which directly compared the effect of a high-fat diet on obesity and diabetic phenotype in Th1- and Th2-biased mice strains were briefly analyzed. Based on the observations, it is proposed that the liver and adipose tissue may respond differently to high-fat-diet feeding regimens in Th1- and Th2-biased mice strains. For instance, in Th1-biased mice, adipose tissue fat content was high both in the baseline as well as in response to a high-fat diet whereas in the liver, it was found to be less. It can be inferred that the immune responses to diet-induced models may provide insights into the pathogenesis of obesity and diabetes mellitus.

肥胖和糖尿病是世界范围内常见的代谢性疾病。通常用小鼠来研究这两种疾病的发病机制。在许多研究中,肥胖和糖尿病是由高脂肪饮食引起的,尽管其他饮食诱导模型也被使用。有几个因素可能会影响研究小鼠饮食引起的肥胖的结果。免疫系统在小鼠肥胖和代谢疾病的易感性中起着至关重要的作用。本文评价了高脂喂养小鼠对肥胖和糖尿病易感性差异的原因,以及研究中所用小鼠品系免疫偏倚的影响。诱导促炎和th1型免疫反应的小鼠品系被发现易受高脂肪饮食诱导的肥胖的影响。本文简要分析了几项直接比较高脂肪饮食对Th1-和th2偏倚小鼠品系肥胖和糖尿病表型影响的研究。基于这些观察,我们提出Th1-和th2偏向小鼠品系的肝脏和脂肪组织可能对高脂肪饮食喂养方案有不同的反应。例如,在th1偏向的小鼠中,脂肪组织脂肪含量在基线和对高脂肪饮食的反应中都很高,而在肝脏中,它被发现较少。由此可以推断,饮食诱导模型的免疫应答可能为肥胖和糖尿病的发病机制提供新的见解。
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引用次数: 1
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Chronic Diseases and Translational Medicine
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