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Cystic Fibrosis Modulator Therapies. 囊性纤维化调节剂疗法。
IF 10.5 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-01-27 DOI: 10.1146/annurev-med-042921-021447
Shijing Jia, Jennifer L Taylor-Cousar

Cystic fibrosis (CF) is an inherited multisystemic disease that can cause progressive bronchiectasis, pancreatic endocrine and exocrine insufficiency, distal intestinal obstruction syndrome, liver dysfunction, and other disorders. Traditional therapies focused on the treatment or prevention of damage to each organ system with incremental modalities such as nebulized medications for the lungs, insulin for diabetes, and supplementation with pancreatic enzymes. However, the advent of highly effective modulator therapies that target specific cystic fibrosis transmembrane conductance regulator protein malformations resulting from individual genetic mutations has transformed the lives and prognosis for persons with CF.

囊性纤维化(CF)是一种遗传性多系统疾病,可导致进行性支气管扩张、胰腺内分泌和外分泌功能不全、远端肠梗阻综合征、肝功能障碍等疾病。传统的治疗方法侧重于治疗或预防对每个器官系统的损害,如肺部的雾化药物,糖尿病的胰岛素和补充胰酶。然而,针对由个体基因突变引起的特异性囊性纤维化跨膜传导调节蛋白畸形的高效调节疗法的出现改变了CF患者的生活和预后。
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引用次数: 10
Post-COVID-19 Condition. Post-COVID-19条件。
IF 10.5 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-01-27 DOI: 10.1146/annurev-med-043021-030635
Ani Nalbandian, Amar D Desai, Elaine Y Wan

An estimated 10-15% of those infected with SARS-CoV-2 may have post-COVID-19 condition. Common lingering signs and symptoms include shortness of breath, fatigue, high heart rate, and memory and cognitive dysfunction even several months after infection, often impacting survivors' quality of life. The prevalence and duration of individual symptoms remain difficult to ascertain due to the lack of standardized research methods across various studies and limited patient follow-up in clinical studies. Nonetheless, data indicate post-COVID-19 condition may occur independent of acuity of initial infection, hospitalization status, age, or pre-existing comorbidities. Risk factors may include female sex and underlying respiratory or psychiatric disease. Supportive therapies to mitigate symptoms remain the mainstay of treatment. Reassuringly, most patients experience a reduction in symptoms by 1 year. The use of a universal case definition and shared research methods will allow for further clarity regarding the pervasiveness of this entity and its long-term health consequences.

据估计,10-15%的SARS-CoV-2感染者可能会出现covid -19后症状。常见的持续体征和症状包括呼吸急促、疲劳、心率高、记忆和认知功能障碍,甚至在感染后几个月也会出现,这通常会影响幸存者的生活质量。由于各种研究缺乏标准化的研究方法以及临床研究中患者随访有限,个体症状的患病率和持续时间仍然难以确定。尽管如此,数据表明,covid -19后疾病的发生可能与初始感染的急性程度、住院情况、年龄或先前存在的合并症无关。危险因素可能包括女性和潜在的呼吸或精神疾病。缓解症状的支持性疗法仍然是主要的治疗方法。令人放心的是,大多数患者的症状减轻了1年。采用普遍的案例定义和共同的研究方法,将有助于进一步明确这一实体的普遍性及其对健康的长期影响。
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引用次数: 62
Diverse Approaches to Gene Therapy of Sickle Cell Disease. 镰状细胞病基因治疗的多种方法。
IF 10.5 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-01-27 Epub Date: 2022-09-06 DOI: 10.1146/annurev-med-042921-021707
Shanna L White, Kevyn Hart, Donald B Kohn

Sickle cell disease (SCD) results from a single base pair change in the sixth codon of the β-globin chain of hemoglobin, which promotes aggregation of deoxyhemoglobin, increasing rigidity of red blood cells and causing vaso-occlusive and hemolytic complications. Allogeneic transplant of hematopoietic stem cells (HSCs) can eliminate SCD manifestations but is limited by absence of well-matched donors and immune complications. Gene therapy with transplantation of autologous HSCs that are gene-modified may provide similar benefits without the immune complications. Much progress has been made, and patients are realizing significant clinical improvements in multiple trials using different approaches with lentiviral vector-mediated gene addition to inhibit hemoglobin aggregation. Gene editing approaches are under development to provide additional therapeutic opportunities. Gene therapy for SCD has advanced from an attractive concept to clinical reality.

镰状细胞病(SCD)源于血红蛋白β-球蛋白链第六密码子中一个碱基对的改变,这种改变会促进脱氧血红蛋白的聚集,增加红细胞的硬度,引起血管闭塞和溶血并发症。异体造血干细胞(HSCs)移植可以消除 SCD 的表现,但受限于缺乏匹配的供体和免疫并发症。通过移植经过基因修饰的自体造血干细胞进行基因治疗,可能会带来类似的益处,但不会出现免疫并发症。目前已经取得了很大进展,在使用慢病毒载体介导的基因添加抑制血红蛋白聚集的不同方法进行的多项试验中,患者的临床症状得到了明显改善。目前正在开发基因编辑方法,以提供更多的治疗机会。针对 SCD 的基因疗法已经从一个极具吸引力的概念发展成为临床现实。
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引用次数: 0
SGLT2 Inhibitors: The Sweet Success for Kidneys. SGLT2抑制剂:肾脏的甜蜜成功。
IF 10.5 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-01-27 DOI: 10.1146/annurev-med-042921-102135
Atit Dharia, Abid Khan, Vikas S Sridhar, David Z I Cherney

Sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitors) were originally developed as antidiabetic agents, with cardiovascular (CV) outcome trials demonstrating improved CV outcomes in patients with type 2 diabetes mellitus (T2D). Secondary analyses of CV outcome trials and later dedicated kidney outcome trials consistently reported improved kidney-related outcomes independent of T2D status and across a range of kidney function and albuminuria. Importantly, SGLT2 inhibitors are generally safe and well tolerated, with clinical trials and real-world analyses demonstrating a decrease in the risk of acute kidney injury. The kidney protective effects of SGLT2 inhibitors generally extend across different members of the class, possibly on the basis of hemodynamic, metabolic, anti-inflammatory, and antifibrotic mechanisms. In this review, we summarize the effects of SGLT2 inhibitors on kidney outcomes in diverse patient populations.

钠-葡萄糖共转运蛋白-2抑制剂(SGLT2抑制剂)最初是作为抗糖尿病药物开发的,心血管(CV)结局试验表明,2型糖尿病(T2D)患者的CV结局得到改善。对CV结果试验和后来专门的肾脏结果试验的二次分析一致报告了独立于T2D状态和一系列肾功能和蛋白尿的肾脏相关结果的改善。重要的是,SGLT2抑制剂通常是安全且耐受性良好的,临床试验和实际分析表明急性肾损伤的风险降低。SGLT2抑制剂的肾脏保护作用通常延伸到该类别的不同成员,可能基于血流动力学、代谢、抗炎和抗纤维化机制。在这篇综述中,我们总结了SGLT2抑制剂对不同患者群体肾脏结局的影响。
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引用次数: 4
Hepcidin and Iron in Health and Disease. Hepcidin和铁在健康和疾病中的作用。
IF 10.5 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-01-27 DOI: 10.1146/annurev-med-043021-032816
Elizabeta Nemeth, Tomas Ganz

Hepcidin, the iron-regulatory hormone, determines plasma iron concentrations and total body iron content. Hepcidin, secreted by hepatocytes, functions by controlling the activity of the cellular iron exporter ferroportin, which delivers iron to plasma from intestinal iron absorption and from iron stores. Hepcidin concentration in plasma is increased by iron loading and inflammation and is suppressed by erythropoietic stimulation and during pregnancy. Hepcidin deficiency causes iron overload in hemochromatosis and anemias with ineffective erythropoiesis. Hepcidin excess causes iron-restrictive anemias including anemia of inflammation. The development of hepcidin diagnostics and therapeutic agonists and antagonists should improve the treatment of iron disorders.

铁调节激素Hepcidin决定血浆铁浓度和全身铁含量。Hepcidin由肝细胞分泌,其功能是控制细胞铁出口国铁转运蛋白的活性,铁转运蛋白将铁从肠道铁吸收和铁储存中输送到血浆中。血浆中Hepcidin浓度因铁负荷和炎症而升高,并在促红细胞生成和妊娠期间受到抑制。Hepcidin缺乏症导致血色素沉着症和贫血伴无效的红细胞生成。Hepcidin过量会导致铁限制性贫血,包括炎症性贫血。hepcidin诊断和治疗激动剂和拮抗剂的发展应改善铁疾病的治疗。
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引用次数: 29
FGFR2 Inhibition in Cholangiocarcinoma. FGFR2在胆管癌中的抑制作用
IF 10.5 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-01-27 DOI: 10.1146/annurev-med-042921-024707
Arndt Vogel, Oreste Segatto, Albrecht Stenzinger, Anna Saborowski

Biliary tract cancer (BTC) is the second most common primary liver cancer after hepatocellular carcinoma and accounts for 2% of cancer-related deaths. BTCs are classified according to their anatomical origin into intrahepatic (iCCA), perihilar, or distal cholangiocarcinoma, as well as gall bladder carcinoma. While the mutational profiles in these anatomical BTC subtypes overlap to a large extent, iCCA is notable for the high frequency of IDH1/2 mutations (10-22%) and the nearly exclusive occurrence of FGFR2 fusions in 10-15% of patients. In recent years, FGFR2 fusions have become one of the most promising targets for precision oncology targeting BTC, with FGFR inhibitors already approved in Europe and the United States for patients with advanced, pretreated iCCA. While the therapeutic potential of nonfusion alterations is still under debate, it is expected that the field of FGFR2-directed therapies will be subject to rapid further evolution and optimization. The scope of this review is to provide an overview of oncogenic FGFR signaling in iCCA cells and highlight the pathophysiology, diagnostic testing strategies, and therapeutic promises and challenges associated with FGFR2-altered iCCA.

胆道癌(BTC)是仅次于肝细胞癌的第二大常见原发性肝癌,占癌症相关死亡人数的2%。btc根据其解剖学起源分为肝内(iCCA)、门周或远端胆管癌以及胆囊癌。虽然这些解剖型BTC亚型的突变谱在很大程度上重叠,但iCCA值得注意的是IDH1/2突变的高频率(10-22%)和10-15%患者中几乎只发生FGFR2融合。近年来,FGFR2融合已成为靶向BTC的精准肿瘤学最有希望的靶点之一,FGFR抑制剂已在欧洲和美国被批准用于晚期、预处理的iCCA患者。虽然不融合改变的治疗潜力仍在争论中,但预计fgfr2定向治疗领域将受到快速进一步发展和优化的影响。本综述的范围是提供iCCA细胞中致癌性FGFR信号的概述,并强调与fgfr2改变的iCCA相关的病理生理学、诊断测试策略、治疗前景和挑战。
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引用次数: 6
Valvular Heart Disease: New Concepts in Pathophysiology and Therapeutic Approaches. 瓣膜性心脏病:病理生理学和治疗方法的新概念。
IF 10.5 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-01-27 DOI: 10.1146/annurev-med-042921-122533
Mackram F Eleid, Vuyisile T Nkomo, Sorin V Pislaru, Bernard J Gersh

This review discusses recent advancements in the field of valvular heart disease. Topics covered include recognition of the impact of atrial fibrillation on development and assessment of valvular disease, strategies for global prevention of rheumatic heart disease, understanding and management of secondary mitral regurgitation, the updated classification of bicuspid aortic valve disease, recognition of heightened cardiovascular risk associated with moderate aortic stenosis, and a growing armamentarium of transcatheter therapies.

本文综述了瓣膜性心脏病领域的最新进展。涵盖的主题包括认识到心房颤动对瓣膜疾病的发展和评估的影响,全球预防风湿性心脏病的策略,了解和管理继发性二尖瓣反流,二尖瓣疾病的最新分类,认识到与中度主动脉狭窄相关的心血管风险增加,以及越来越多的经导管治疗方法。
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引用次数: 1
Use of Race in Kidney Function Estimation: Lessons Learned and the Path Toward Health Justice. 种族在肾功能评估中的应用:经验教训与健康公正之路。
IF 10.5 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-01-27 DOI: 10.1146/annurev-med-042921-124419
Dinushika Mohottige, Opeyemi Olabisi, L Ebony Boulware

In 2020, the nephrology community formally interrogated long-standing race-based clinical algorithms used in the field, including the kidney function estimation equations. A comprehensive understanding of the history of kidney function estimation and racial essentialism is necessary to understand underpinnings of the incorporation of a Black race coefficient into prior equations. We provide a review of this history, as well as the considerations used to develop race-free equations that are a guidepost for a more equity-oriented, scientifically rigorous future for kidney function estimation and other clinical algorithms and processes in which race may be embedded as a variable.

2020年,肾脏病学界正式质疑该领域长期使用的基于种族的临床算法,包括肾功能估计方程。全面了解肾功能估计和种族本质主义的历史对于理解将黑人种族系数纳入先前方程的基础是必要的。我们对这段历史进行了回顾,并对用于开发无种族方程的考虑进行了回顾,这些方程为未来更加公平、科学严谨的肾功能估计和其他临床算法和过程提供了指导,其中种族可能作为一个变量嵌入。
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引用次数: 1
Origins of Racial and Ethnic Bias in Pulmonary Technologies. 肺技术中种族和民族偏见的起源。
IF 10.5 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-01-27 DOI: 10.1146/annurev-med-043021-024004
Michael W Sjoding, Sardar Ansari, Thomas S Valley

Understanding how biases originate in medical technologies and developing safeguards to identify, mitigate, and remove their harms are essential to ensuring equal performance in all individuals. Drawing upon examples from pulmonary medicine, this article describes how bias can be introduced in the physical aspects of the technology design, via unrepresentative data, or by conflation of biological with social determinants of health. It then can be perpetuated by inadequate evaluation and regulatory standards. Research demonstrates that pulse oximeters perform differently depending on patient race and ethnicity. Pulmonary function testing and algorithms used to predict healthcare needs are two additional examples of medical technologies with racial and ethnic biases that may perpetuate health disparities.

了解偏见是如何在医疗技术中产生的,并制定识别、减轻和消除其危害的保障措施,对于确保所有人的平等表现至关重要。本文以肺部医学为例,描述了如何通过不具代表性的数据,或通过将健康的生物决定因素与社会决定因素合并,在技术设计的物理方面引入偏见。然后,不充分的评估和监管标准可能会使其永久化。研究表明,脉搏血氧仪的表现因患者的种族而异。肺功能测试和用于预测医疗保健需求的算法是另外两个带有种族和民族偏见的医疗技术的例子,这些偏见可能使健康差距永久化。
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引用次数: 4
COVID-19 and Kidney Disease. COVID-19和肾脏疾病。
IF 10.5 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-01-27 DOI: 10.1146/annurev-med-042420-104753
Maureen Brogan, Michael J Ross

COVID-19 can cause acute kidney injury and may cause or exacerbate chronic kidney diseases, including glomerular diseases. SARS-CoV-2 infection of kidney cells has been reported, but it remains unclear if viral infection of kidney cells causes disease. The most important causes of kidney injury in patients with COVID-19 include impaired renal perfusion and immune dysregulation. Chronic kidney disease, especially kidney failure with kidney replacement therapy and kidney transplant, is associated with markedly increased COVID-19 mortality. Persons with severe kidney disease have been excluded from most clinical trials of COVID-19 therapies, so therapeutic approaches must be extrapolated from studies of patients without kidney disease. Some medications used to treat COVID-19 should be avoided or used at reduced dosages in patients with severe kidney disease and in kidney transplant recipients. Additional research is needed to determine the optimal strategies to prevent and treat COVID-19 in patients with kidney disease.

COVID-19可导致急性肾损伤,并可能导致或加重慢性肾脏疾病,包括肾小球疾病。SARS-CoV-2感染肾细胞已有报道,但目前尚不清楚病毒感染肾细胞是否会导致疾病。COVID-19患者肾损伤的最重要原因包括肾灌注受损和免疫失调。慢性肾脏疾病,特别是肾替代治疗和肾移植后的肾衰竭,与COVID-19死亡率显著增加相关。患有严重肾脏疾病的人被排除在大多数COVID-19治疗的临床试验之外,因此治疗方法必须从没有肾脏疾病的患者的研究中推断出来。一些用于治疗COVID-19的药物应避免使用,或在严重肾脏疾病患者和肾移植接受者中减少剂量。需要进一步的研究来确定预防和治疗肾脏疾病患者COVID-19的最佳策略。
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引用次数: 2
期刊
Annual review of medicine
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