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Fecal microbiota transplantation: History, procedure and regulatory considerations 粪便微生物群移植:历史、程序和监管注意事项。
IF 2.7 3区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2023-11-07 DOI: 10.1016/j.lpm.2023.104204
Thanush D , M.P. Venkatesh

Fecal microbiota transplantation (FMT) is a medical treatment which involves the transfer of feces from a healthy donor to a recipient to restore the balance of gut microbiota and improve clinical outcomes. FMT has gained recognition in recent years due to its effectiveness in treating recurrent Clostridioides difficile infections (rCDI) and other gastrointestinal disorders. Additionally, it has been studied as an intervention for some other conditions, like inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). This review covers regulatory considerations related to FMT, including the current state of FMT regulation and the need for further research to fully understand the safety and efficacy of this treatment. For transplantation of fecal microbiota, the Food and Drug Administration (FDA) classifies the treatment as an investigational new drug (IND), which typically requires physicians and scientists to submit an IND application. Ethical issues surrounding FMT, including the necessity of informed consent from donors and recipients and the potential transmission of infectious agents, are also discussed. Overall, FMT has the potential to offer significant therapeutic benefits, but it also raises regulatory and ethical considerations that require careful consideration. Further research is necessary to fully comprehend risks and benefits of FMT and to develop guidelines for its use in clinical practice.

粪便微生物群移植(FMT)是一种医学治疗方法,包括将粪便从健康供体转移到受体,以恢复肠道微生物群的平衡并改善临床结果。近年来,FMT因其在治疗复发性艰难梭菌感染(rCDI)和其他胃肠道疾病方面的有效性而获得认可。此外,它还被研究为其他一些疾病的干预措施,如炎症性肠病(IBD)和肠易激综合征(IBS)。这篇综述涵盖了与FMT相关的监管考虑,包括FMT监管的现状以及进一步研究的必要性,以充分了解这种治疗的安全性和有效性。对于粪便微生物群的移植,美国食品药品监督管理局(FDA)将该疗法归类为研究性新药(IND),通常需要医生和科学家提交IND申请。还讨论了围绕FMT的伦理问题,包括捐赠者和接受者知情同意的必要性以及传染源的潜在传播。总的来说,FMT有可能提供显著的治疗益处,但它也提出了需要仔细考虑的监管和伦理考虑。有必要进行进一步的研究,以充分了解FMT的风险和益处,并制定其在临床实践中的使用指南。
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引用次数: 0
Sickle cell disease and pregnancy 镰状细胞病与妊娠。
IF 2.7 3区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2023-11-07 DOI: 10.1016/j.lpm.2023.104203
Julie Carrara , Anoosha Habibi , Alexandra Benachi , Geoffrey Cheminet

Pregnancy is a particularly risky period in the life of patients with sickle cell disease (SCD). Physiological changes during pregnancy increase the risk of vaso-occlusive crises (VOC), acute chest syndrome, venous thromboembolic events, and infections. This concerns haemoglobin (Hb) S/C and S/β+-thalassaemia patients as much than S/S or S/β0-thalassaemia patients. SCD also increases the risk of obstetrical complications, such as preeclampsia, in utero foetal death, preterm delivery mostly induced, and intrauterine growth restriction. Thus, pregnancy should be planned and closely monitored by a multidisciplinary team involving obstetricians and sickle cell disease specialists. Before pregnancy, the parents should also be informed about the risk of transmission of this autosomal recessive disease, and the father should therefore be prescribed haemoglobin electrophoresis. Treatments have to be revised when planning pregnancy: hydroxyurea (HU) should be stopped as soon as pregnancy is suspected or confirmed. Preventive blood transfusion is not systematic, but is recommended in the case of a pre-existing transfusion program prior to pregnancy, severe pre-existing organ damage, severe obstetric history, and severe or repeated crises during follow-up, especially in patients taking HU before. Despite the risks of prematurity, systematic administration of corticosteroids for foetal lung maturation is not recommended due to the risk of maternal vaso-occlusive event. Although more frequent, due to obstetrical and maternal complications, caesarean section is not systematic, in the absence of maternal contraindications. It is advisable not to exceed the term of 39 weeks of amenorrhoea. Post-partum follow-up is recommended, particularly because of the risk of thromboembolism.

在镰状细胞病(SCD)患者的生命中,怀孕是一个特别危险的时期。妊娠期间的生理变化会增加血管闭塞危象(VOC)、急性胸部综合征、静脉血栓栓塞事件和感染的风险。这涉及血红蛋白(Hb)S/C和S/β+-地中海贫血患者,与S/S或S/β0-地中海贫血患者一样多。SCD还增加了产科并发症的风险,如先兆子痫、宫内胎儿死亡、主要是诱导早产和宫内生长受限。因此,应由产科医生和镰状细胞病专家组成的多学科团队计划并密切监测妊娠情况。怀孕前,还应告知父母这种常染色体隐性遗传疾病的传播风险,因此应给父亲开血红蛋白电泳处方。计划怀孕时必须修改治疗方法:一旦怀疑或确认怀孕,应立即停止使用羟基脲(HU)。预防性输血不是系统性的,但建议在怀孕前已有输血计划、已有严重器官损伤、有严重产科病史以及随访期间出现严重或反复危机的情况下进行,尤其是在之前服用HU的患者中。尽管存在早产风险,但由于母体血管闭塞事件的风险,不建议系统给予皮质类固醇用于胎儿肺成熟。尽管剖腹产更常见,但由于产科和产妇并发症,在没有产妇禁忌症的情况下,剖腹产不是系统性的。建议不要超过39周的闭经期。建议产后随访,特别是因为存在血栓栓塞的风险。
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引用次数: 0
End-stage heart failure: The future of heart transplant and artificial heart 终末期心力衰竭:心脏移植和人工心脏的未来。
IF 2.7 3区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2023-10-26 DOI: 10.1016/j.lpm.2023.104191
Karl Bounader , Erwan Flécher

In the last decades, outcomes significantly improved for both heart transplantation and LVAD. Heart transplantation remains the gold standard for the treatment of end stage heart failure and will remain for many years to come. The most relevant limitations are the lack of grafts and the effects of long-term immunosuppressive therapy that involve infectious, cancerous and metabolic complications despite advances in immunosuppression management. Mechanical circulatory support has an irreplaceable role in the treatment of end-staged heart failure, as bridge to transplant or as definitive implantation in non-transplant candidates. Although clinical results do not overcome those of HTx, improvement in the new generation of devices may help to reach the equipoise between the two therapies.

This review will go through the evolution, current status and perspectives of both therapeutics.

在过去的几十年里,心脏移植和LVAD的结果都显著改善。心脏移植仍然是治疗末期心力衰竭的黄金标准,并将持续多年。最相关的限制是缺乏移植物和长期免疫抑制治疗的效果,尽管免疫抑制管理取得了进展,但这些治疗涉及感染、癌症和代谢并发症。机械循环支持在治疗终末期心力衰竭方面具有不可替代的作用,可以作为移植的桥梁或非移植候选者的最终植入物。尽管临床结果并不能克服HTx,但新一代设备的改进可能有助于达到两种疗法之间的平衡。这篇综述将介绍这两种疗法的发展、现状和前景。
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引用次数: 0
Electrical therapies in heart failure: Evolving technologies and indications 心力衰竭的电疗法:不断发展的技术和适应症。
IF 2.7 3区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2023-10-26 DOI: 10.1016/j.lpm.2023.104192
Cecilia Linde

Device therapy for heart failure has rapidly evolved over 2 decades. The knowledge of indications, assessment lead and device technology has expanded to include CRT, leadless pacing and conduction system pacing such as His bundle and left bundle branch area pacing. But there is still a lack of evidence for these new technologies as well as for common indications such as atrial fibrillation and upgrading from a previous device. The role of personalized medicine will become increasingly important when selecting candidates for CRT, primary preventive ICD  ablation procedures and emerging new devices such as cardiac contractility modulation (CCM). Rapidity of therapy is associated with outcome which will be a challenge. If properly implemented devices and drugs will have a large positive affect of HF outcomes.

心力衰竭的设备治疗在20多年的时间里迅速发展。适应症、评估导线和设备技术的知识已经扩展到包括CRT、无导线起搏和传导系统起搏,如希氏束和左束分支区域起搏。但对于这些新技术以及心房颤动和从以前的设备升级等常见适应症,仍然缺乏证据。在选择CRT、初级预防性ICD消融程序和开发心脏收缩性调节(CCM)等新设备的候选者时,个性化药物的作用将变得越来越重要。治疗的快速性与结果相关,这将是一个挑战。如果正确使用设备和药物,将对HF的输出产生巨大的积极影响。
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引用次数: 0
Heart failure with preserved ejection fraction: New challenges and new hopes 保留射血分数的心力衰竭:新的挑战和新的希望:心力衰竭管理和治疗的创新。
IF 2.7 3区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2023-10-22 DOI: 10.1016/j.lpm.2023.104185
Damien Logeart

Heart failure (HF) is a major public health problem affecting millions of adults worldwide. HF with preserved ejection fraction, i.e. > 50 %, (HFpEF) accounts for more than half of all HF cases, and its incidence and prevalence are increasing with the aging of the population and the growing prevalence of metabolic disorders such as obesity, diabetes and hypertension. Diagnosis of HFpEF requires a combination of numerous echocardiographic parameters and also results of natriuretic peptide assays, to which may be added the need for a stress test. HFpEF is characterized by complex, interrelated pathophysiological mechanisms, which must be understood. This complexity probably accounts for the lack of evidence-based medicine compared with HF with reduced EF. Nevertheless, significant progress has been made recently, with a high level of evidence obtained for the SGLT2 inhibitor class on the one hand, and promising data with new drugs targeting more specifically certain mechanisms such as obesity and inflammation on the other.

心力衰竭(HF)是影响全球数百万成年人的主要公共卫生问题。射血分数保持不变的HF(HFpEF)占所有HF病例的一半以上,其发病率和患病率随着人口老龄化和肥胖、糖尿病和高血压等代谢紊乱患病率的增加而增加。HFpEF的诊断需要结合多种超声心动图参数和钠尿肽测定结果,除此之外可能还需要进行压力测试。HFpEF具有复杂、相互关联的病理生理机制,这一点必须加以理解。与EF降低的HF相比,这种复杂性可能是缺乏循证医学的原因。尽管如此,最近还是取得了重大进展,一方面获得了SGLT2抑制剂类的高水平证据,另一方面也获得了针对肥胖和炎症等特定机制的新药的有希望的数据。
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引用次数: 0
New insights in acute heart failure 急性心力衰竭的新见解。
IF 2.7 3区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2023-10-21 DOI: 10.1016/j.lpm.2023.104184
Ayu Asakage , Alexandre Mebazaa , Benjamin Deniau

Acute heart failure (AHF) is a clinical complex disease and a worldwide issue due to its inconsistent diagnosis and poor prognosis. The cornerstone of pathophysiology of AHF is systemic venous congestion, which is led by the underlying structural and functional cardiac condition. Systemic venous congestion is a major target for AHF management because it causes symptoms and organs dysfunction, and is associated with poor prognosis. The mainstay of decongestive therapy is diuresis with intravenous loop diuretics combined with other diuretics including thiazides when necessary, and non-invasive ventilation. The presence of unresolved congestion at discharge can lead heart failure related rehospitalization, and careful follow-up is required especially during “vulnerable phase”, several months after discharge. The updated recommendation for management of AHF has been provided by latest guidelines from European Society of Cardiology and American Heart Association/American College of Cardiology/Heart Failure Society of America. Several large studies have currently demonstrated the benefits of guideline-directed oral medical therapies, and trials are ongoing on medication such as selective sodium-glucose transport proteins 2 inhibitors and protocols for congestive therapy. This review aimed to summarize the latest insights in AHF, based primarily on the most recent guidelines and large randomized controlled trials.

急性心力衰竭(AHF)是一种临床复杂疾病,由于其诊断不一致和预后不良而成为世界性问题。AHF病理生理学的基石是全身静脉充血,这是由潜在的结构和功能性心脏状况引起的。系统性静脉充血是AHF治疗的主要目标,因为它会导致症状和器官功能障碍,并与不良预后有关。缓解充血的主要治疗方法是静脉循环利尿剂与其他利尿剂联合利尿,必要时包括噻嗪类药物,以及无创通气。出院时未解决的充血可能导致心力衰竭相关的再次住院,需要仔细随访,尤其是在出院后几个月的“脆弱期”。欧洲心脏病学会和美国心脏协会/美国心脏病学院/美国心力衰竭协会的最新指南提供了AHF管理的最新建议。目前,几项大型研究已经证明了指南指导的口服药物治疗的益处,并且正在进行药物试验,如选择性钠-葡萄糖转运蛋白2抑制剂和充血性治疗方案。本综述旨在总结AHF的最新见解,主要基于最新指南和大型随机对照试验。
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引用次数: 0
Facing the Evidences with Type 2 Diabetes: Contemporary Challenges 面对2型糖尿病的证据:当代挑战。
IF 2.7 3区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2023-10-05 DOI: 10.1016/j.lpm.2023.104179
Michel Marre
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引用次数: 0
Severity of kidney involvement as predictor of death, severe heart failure and renal events in patients with type 2 diabetes: data from a prospective cohort 肾脏受累的严重程度作为2型糖尿病患者死亡、严重心力衰竭和肾脏事件的预测因素:来自前瞻性队列的数据。
IF 2.7 3区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2023-10-04 DOI: 10.1016/j.lpm.2023.104177
Samy Hadjadj , Pierre Jean Saulnier , Bertrand Cariou , SURDIAGENE study investigators

Type 2 diabetes is associated with an increased risk for end-stage renal disease and heart failure, contributing to premature death. All these 3 events are inter-related, suggesting common risk factors and/or pathophysiological pathways.

The SURDIAGENE (SUrvie Rénale DIAbète et GENEtique) cohort is a single centre hospital-based cohort of persons living with type 2 diabetes, recruiting participants at Poitiers university hospital, France, from 2002 to 2011 with further follow-up till 2015.

Here, we describe the cumulative prevalence of hard renal events (sustained doubling of serum creatinine and/or renal replacement therapy), heart failure leading to hospitalization (HFH) and all-cause death, according to the KDIGO classification, which considers CKD stages according to CKD EPI equation [1], [2], [3], [4], [5] and albuminuria (A1, A2, A3) according to albumin/creatinine ratio with thresholds at 30 and 300 mg/g. We considered 1450 participants with KDIGO stage available at baseline.

Considering a cumulated follow-up duration of 10667 patient.years with 100 renal events, 247 HFH and 527 deaths, our study showed that the more severe the KDIGO stage, the higher the incidence rate not only for renal event, but also for HFH and for all-cause death. For instance, in CKD1A1 and CKD4A3 the incidence rates for hard renal events, HFH and death were 0.98 and 140.70, 4.46 and 107.09, 13.64 and 156.56 per 1000 patient.years, respectively. Interestingly, the incidence of renal event was lower than the incidence of all-cause death in all KDIGO stages, at variance with the data from recent renal outcome trials on SGLT2 inhibitors and finerenone.

We conclude that KDIGO stages should be considered for renal but also for HFH risk classification. The analysis of the respective incidence of renal events and deaths in observational studies and RCTs deserves further evaluation in type 2 diabetes.

2型糖尿病与终末期肾病和心力衰竭的风险增加有关,导致过早死亡。所有这3个事件都是相互关联的,提示共同的危险因素和/或病理生理途径。SURDIAGENE(SUrvie Rénale DIAbète et GENEtique)队列是一个以2型糖尿病患者为基础的单中心医院队列,从2002年到2011年在法国普瓦捷大学医院招募参与者,并进一步随访到2015年。在这里,我们描述了根据KDIGO分类的硬肾事件(血清肌酐持续翻倍和/或肾脏替代治疗)、导致住院的心力衰竭(HFH)和全因死亡的累积患病率,根据CKD EPI方程[1-5]考虑CKD分期,根据白蛋白/肌酐比值考虑白蛋白尿(A1、A2、A3),阈值为30和300mg/g。我们在基线时考虑了1450名KDIGO阶段的参与者。考虑到10667名患者的累计随访时间,100例肾事件、247例HFH和527例死亡,我们的研究表明,KDIGO阶段越严重,不仅肾事件的发生率越高,HFH和全因死亡的发生率也越高。例如,在CKD1A1和CKD4A3中,硬肾事件、HFH和死亡的发生率分别为0.98和140.70、4.46和107.09、13.64和156.56/1000名患者年。有趣的是,在所有KDIGO阶段,肾事件的发生率都低于全因死亡的发生率,这与最近SGLT2抑制剂和芬瑞酮的肾结果试验数据不一致。我们得出的结论是,肾脏和HFH风险分类应考虑KDIGO分期。在2型糖尿病的观察性研究和随机对照试验中对肾脏事件和死亡的各自发生率的分析值得进一步评估。
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引用次数: 1
Clinical Trials with reno-vascular end points in patients with diabetes: Changing the scenario over the past 20 years 糖尿病患者雷诺血管终点的临床试验:过去20年中的变化。
IF 2.7 3区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2023-09-30 DOI: 10.1016/j.lpm.2023.104178
Tomasz J. Block , Mark E. Cooper

Major clinical advances over the last 25 years in the area of diabetic kidney disease (DKD) have been confirmed in large seminal clinical trials. These findings add to the previously identified benefits resulting from intensive glucose and blood pressure control therapies. Furthermore, newer glucose lowering treatments such as SGLT2 inhibitors and GLP-1 agonists appear very promising and are likely to transform the management and outlook of DKD over the next decade. In addition, newer mineralocorticoid receptor antagonists and a recently reported trial with an endothelin receptor blocker also have the potential to change clinical practice.

在过去25年中,糖尿病肾病(DKD)领域的主要临床进展已在大型精液临床试验中得到证实。这些发现增加了先前确定的强化血糖和血压控制疗法的益处。此外,SGLT2抑制剂和GLP-1激动剂等新型降血糖治疗似乎非常有前景,并可能在未来十年改变DKD的管理和前景。此外,新的盐皮质激素受体拮抗剂和最近报道的内皮素受体阻滞剂试验也有可能改变临床实践。
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引用次数: 1
Diagnostic Criteria and Etiopathogenesis of Type 2 Diabetes and Its Complications: Lessons from the Pima Indians 2型糖尿病及其并发症的诊断标准和病因:来自皮马印第安人的经验教训。
IF 2.7 3区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2023-09-30 DOI: 10.1016/j.lpm.2023.104176
Helen C Looker , Douglas C Chang , Leslie J Baier , Robert L Hanson , Robert G Nelson

The Phoenix Epidemiology and Clinical Research Branch of the National Institute of Diabetes and Digestive and Kidney Diseases has conducted prospective studies of diabetes and its complications in the Pima Indians living in Arizona, USA for over 50 years. In this review we highlight areas in which these studies provided vital insights into the criteria used to diagnose type 2 diabetes, the pathophysiologic changes that accompany the development of type 2 diabetes, and the course and determinants of diabetes complications—focusing specifically on diabetic kidney disease. We include data from our longitudinal population-based study of diabetes and its complications, studies on the role of insulin resistance and insulin secretion in the pathophysiology of type 2 diabetes, and in-depth studies of diabetic kidney disease that include measures of glomerular function and research kidney biopsies. We also focus on the emerging health threat posed by youth-onset type 2 diabetes, which was first seen in the Pima Indians in the 1960s and is becoming an increasing issue worldwide.

美国国家糖尿病、消化和肾脏疾病研究所凤凰城流行病学和临床研究分院对居住在美国亚利桑那州的皮马印第安人的糖尿病及其并发症进行了50多年的前瞻性研究。在这篇综述中,我们强调了这些研究为诊断2型糖尿病的标准、伴随2型糖尿病发展的病理生理变化以及糖尿病并发症的过程和决定因素提供了重要见解的领域,特别是糖尿病肾病。我们纳入了糖尿病及其并发症的纵向人群研究数据,胰岛素抵抗和胰岛素分泌在2型糖尿病病理生理学中作用的研究,以及糖尿病肾病的深入研究,包括肾小球功能测量和肾活检研究。我们还关注年轻人发病的2型糖尿病对健康构成的新威胁,这种糖尿病于20世纪60年代首次出现在皮马印第安人身上,并正在成为世界范围内日益严重的问题。
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引用次数: 0
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