Presse Medicale最新文献

英文中文

Bispecific antibody and chimeric antigen receptor (CAR) modified T-cell in the treatment of multiple myeloma: Where do we stand today? 双特异性抗体和嵌合抗原受体（CAR）修饰的t细胞治疗多发性骨髓瘤：我们今天的进展如何？

IF 3.2 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

Presse Medicale

Pub Date : 2024-12-09 DOI: 10.1016/j.lpm.2024.104265

Xiang Zhou, K Martin Kortuem, Leo Rasche, Hermann Einsele

Although the prognosis of patients with multiple myeloma (MM) has been significantly improved by the introduction of proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies, MM is still considered an incurable disease in the vast majority of the patients. In recent years, T-cell based immunotherapy represents a novel treatment strategy for relapsed/refractory (RR) MM. So far, chimeric antigen receptor (CAR) modified T-cells and bispecific T-cell engaging antibodies (bsAb) have shown promising anti-MM efficacy and manageable safety profile within clinical trials, and B-cell maturation antigen (BCMA) is the most commonly used immune target for T-cell based immunotherapies in MM. To date, several CAR T-cell and bsAb products have already been approved for the treatment of RRMM, leading to a paradigm shift in the MM therapy and providing a potential curative option. In this review, we provide a summary of mechanisms of action, immune targets, selected clinical data, resistance mechanisms and therapy sequencing of CAR T-cell and bsAb in MM.

尽管通过引入蛋白酶体抑制剂、免疫调节药物和单克隆抗体，多发性骨髓瘤（MM）患者的预后得到了显著改善，但在绝大多数患者中，MM仍被认为是一种不治之症。近年来，基于t细胞的免疫治疗代表了复发/难治性（RR） MM的一种新的治疗策略。到目前为止，嵌合抗原受体（CAR）修饰的t细胞和双特异性t细胞结合抗体（bsAb）在临床试验中显示出有希望的抗MM疗效和可管理的安全性，b细胞成熟抗原（BCMA）是基于t细胞的MM免疫治疗中最常用的免疫靶点。一些CAR - t细胞和bsAb产品已经被批准用于治疗RRMM，导致MM治疗的范式转变，并提供了一种潜在的治疗选择。本文综述了CAR - t细胞和bsAb在MM中的作用机制、免疫靶点、临床数据、耐药机制和治疗序列。

引用次数: 0

Preventative and curative treatment of venous thromboembolic disease in cancer patients 癌症患者静脉血栓栓塞性疾病的预防和治疗。

IF 3.2 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

Presse Medicale

Pub Date : 2024-09-07 DOI: 10.1016/j.lpm.2024.104242

Marc Carrier , Laurent Bertoletti , Philippe Girard , Sylvie Laporte , Isabelle Mahé

Cancer-associated venous thromboembolism (CAT) is common in patients with cancer and associated with significant morbidity and mortality. The incidence of CAT continues to rise, complicating patient care and burdening healthcare systems. Patients with cancer experiencing VTE face poorer prognoses, making prevention and effective management imperative. This narrative review synthesizes evidence on thromboprophylaxis in ambulatory patients with cancer receiving systemic therapy and acute treatment strategies for CAT. Risk assessment models (e.g., Khorana score) aid in identifying high-risk patients who may benefit from thromboprophylaxis. Pharmacological thromboprophylaxis with low molecular weight heparins (LMWHs) and direct oral anticoagulants (DOACs) has been shown to reduce the risk of CAT without significantly increasing the risk of bleeding complications. However, implementation of risk-based strategies remains limited in clinical practice. For acute CAT management, LMWHs have been the standard of care, but DOACs are increasingly favored due to their convenience and efficacy. However, challenges persist, including bleeding risks and drug interactions. Emerging therapies targeting Factor XI inhibitors present promising alternatives, potentially addressing current limitations in anticoagulation management for CAT.

癌症相关静脉血栓栓塞症（CAT）在癌症患者中很常见，并与严重的发病率和死亡率相关。癌症相关静脉血栓栓塞（CAT）的发病率持续上升，使患者护理变得更加复杂，也加重了医疗保健系统的负担。发生 VTE 的癌症患者预后较差，因此预防和有效管理势在必行。这篇叙述性综述综合了接受系统治疗的非卧床癌症患者血栓预防措施和 CAT 急性治疗策略的相关证据。风险评估模型（如霍拉纳评分）有助于识别可能受益于血栓预防的高危患者。使用低分子量肝素（LMWHs）直接口服抗凝剂（DOACs）进行药物血栓预防已被证明可降低 CAT 的风险，同时不会显著增加出血并发症的风险。然而，基于风险的策略在临床实践中的实施仍然有限。在急性 CAT 的治疗中，LMWHs 一直是治疗标准，但 DOACs 因其方便和有效而越来越受到青睐。然而，挑战依然存在，包括出血风险和药物相互作用。以因子 XI 抑制剂为靶点的新兴疗法是很有前景的替代疗法，有可能解决目前 CAT 抗凝治疗的局限性。

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引用次数: 0

Impact of thrombophilia on venous thromboembolism management 血栓性疾病对静脉血栓栓塞治疗的影响。

IF 3.2 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

Presse Medicale

Pub Date : 2024-09-06 DOI: 10.1016/j.lpm.2024.104247

Joseph Emmerich , Stéphane Zuily , Isabelle Gouin-Thibault , Pierre-Emmanuel Morange , Francis Couturaud , Menno Huisman

Hypercoagulable states, also called thrombophilia, can either be congenital or acquired. Congenital thrombophilia, associated mainly with venous thrombosis, is either secondary to coagulation-inhibitor deficiencies, i.e., antithrombin, protein C and Protein S, or gain of function mutations, i.e., factor V Leiden and prothrombin G20210A mutations. Despite the relative frequency of these two mutations, they have not been associated with venous thrombosis recurrence. Most prevalent thrombophilia have a limited impact and usually does not change indications for duration of antithrombotic treatment or prophylaxis compared to decisions based on clinical factors. However, rare inherited thrombophilia such as antithrombin deficiency could justify a long-term anticoagulation. The main acquired thrombophilia, the Antiphospholipid syndrome (APS), is associated with both arterial and venous thrombosis. Its impact on patient management is significant: choice of the anticoagulant (DOAC vs. warfarin), duration of anticoagulation, screening of any organ involvement and systemic autoimmune disease, introduction of immunosuppressive therapy.

高凝状态又称血栓性疾病，可以是先天性的，也可以是后天获得的。先天性血栓性疾病主要与静脉血栓形成有关，继发于凝血抑制剂缺乏（即抗凝血酶、蛋白 C 和蛋白 S）或功能增益突变（即因子 V Leiden 和凝血酶原 G20210A 突变）。尽管这两种突变相对频繁，但它们与静脉血栓复发并无关联。大多数流行性血栓性疾病的影响有限，与根据临床因素做出的决定相比，通常不会改变抗血栓治疗或预防的适应症。然而，罕见的遗传性血栓性疾病，如抗凝血酶缺乏症，可能需要长期抗凝治疗。抗磷脂综合征（APS）是主要的后天性血栓性疾病，与动脉和静脉血栓都有关联。抗磷脂综合征对患者管理的影响很大：抗凝药物的选择（DOAC 与华法林）、抗凝时间的长短、任何器官受累和系统性自身免疫疾病的筛查、免疫抑制疗法的引入。

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引用次数: 0

Elderly patients with venous thromboembolism: Insights from the RIETE registry 静脉血栓栓塞症老年患者：RIETE 登记的启示。

IF 3.2 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

Presse Medicale

Pub Date : 2024-09-06 DOI: 10.1016/j.lpm.2024.104246

Patrick Mismetti , Laurent Bertoletti , Isabelle Gouin , Joseph Emmerich , Manuel Monreal

Venous thromboembolism (VTE) presents a notable healthcare burden, particularly among the elderly, who experience increased risks and more severe complications. This review aims to use the extensive data from the RIETE registry, a comprehensive database on consecutive patients with VTE. We examine the clinical features, therapeutic approaches, and patient outcomes of VTE in elderly patients, compared to younger patients, offering a comprehensive understanding of management challenges and emphasizing the need for strategies that accommodate the unique challenges of this population.

静脉血栓栓塞症（VTE）给医疗保健带来了显著的负担，尤其是老年人，他们面临的风险更高，并发症也更严重。本综述旨在利用 RIETE 登记处的大量数据，这是一个关于连续 VTE 患者的综合数据库。与年轻患者相比，我们研究了老年 VTE 患者的临床特征、治疗方法和患者预后，从而全面了解管理方面的挑战，并强调需要制定能应对这一人群独特挑战的策略。

引用次数: 0

A tribute to Guy Meyer 向盖伊-迈耶致敬

IF 3.2 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

Presse Medicale

Pub Date : 2024-09-01 DOI: 10.1016/j.lpm.2024.104244

Francis Couturaud, Philippe Girard, on behalf of the authors and FCRIN INNOVTE members

引用次数: 0

Risk stratification of acute pulmonary embolism 急性肺栓塞的预后。

IF 3.2 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

Presse Medicale

Pub Date : 2024-09-01 DOI: 10.1016/j.lpm.2024.104243

Pierre-Marie Roy , Olivier Sanchez , Menno Huisman , David Jimenez

Risk stratification of patients with acute pulmonary embolism (PE) assists with the selection of appropriate initial therapy and treatment setting. Patients with acute symptomatic PE that present with arterial hypotension or shock have a high risk of death, and treatment guidelines recommend strong consideration of reperfusion in this setting. For haemodynamically stable patients with PE, the combination of a negative clinical prognostic score and the absence of computed tomography-assessed right ventricle enlargement may accurately identify those at low-risk of short-term complications after the diagnosis of PE, and such patients might benefit from an abbreviated hospital stay or outpatient therapy. Some evidence suggests that the accumulation of factors indicating worse outcomes from PE on standard anticoagulation identifies the more severe stable patients with acute PE who might benefit from intensive monitoring and recanalization procedures, particularly if haemodynamic deterioration occurs. Current risk classifications have several shortcomings that might adversely affect clinical and healthcare decisions. Ongoing initiatives aim to address many of those shortcomings, and will hopefully help optimize risk stratification algorithms and treatment strategies.

对急性肺栓塞（PE）患者进行风险分层有助于选择适当的初始疗法和治疗环境。出现动脉低血压或休克的急性无症状肺栓塞患者死亡风险很高，治疗指南建议在这种情况下应重点考虑再灌注治疗。对于血流动力学稳定的 PE 患者，如果临床预后评分为阴性，且没有计算机断层扫描评估的右心室扩大，则可准确识别出那些在确诊 PE 后短期并发症风险较低的患者，这些患者可能会从缩短住院时间或门诊治疗中获益。一些证据表明，在标准抗凝治疗的情况下，显示 PE 后果较差的因素的累积可识别出病情较严重的稳定型急性 PE 患者，这些患者可能会从强化监测和再通程序中获益，尤其是在血流动力学恶化的情况下。目前的风险分类存在一些缺陷，可能会对临床和医疗决策产生不利影响。正在进行的计划旨在解决其中的许多缺陷，并有望帮助优化风险分层算法和治疗策略。

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引用次数: 0

Duration of anticoagulation of venous thromboembolism 静脉血栓栓塞抗凝治疗的持续时间。

IF 3.2 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

Presse Medicale

Pub Date : 2024-09-01 DOI: 10.1016/j.lpm.2024.104245

Francis Couturaud , Nicolas Meneveau , Marie Antoinette Sevestre , Pierre-Emmanuel Morange , David Jimenez

Venous thromboembolism (VTE) is a common, serious condition that requires anticoagulation for at least three months to prevent recurrence and long-term complications. After this initial period, the decision to continue or stop anticoagulation depends on the balance between the risk of recurrent VTE and the risk of bleeding. Established guidelines suggest short-term anticoagulation for VTE caused by transient factors and indefinite anticoagulation for recurrent or cancer-associated VTE. However, for a first unprovoked VTE, decision-making remains challenging. Current predictive scores for recurrence and bleeding are not sufficiently reliable, and the safety and efficacy of reduced-dose anticoagulation remain unclear. In the future, precision and patient-centred medicine may improve treatment decisions in this area.

静脉血栓栓塞症（VTE）是一种常见的严重疾病，需要至少三个月的抗凝治疗，以防止复发和长期并发症。在这一初始阶段之后，是否继续或停止抗凝取决于复发 VTE 的风险和出血风险之间的平衡。既定指南建议，对于由短暂性因素引起的 VTE，应进行短期抗凝治疗；对于复发性或癌症相关性 VTE，则应进行无限期抗凝治疗。然而，对于首次发生的无诱因 VTE，决策仍具有挑战性。目前的复发和出血预测评分不够可靠，减量抗凝的安全性和有效性仍不明确。未来，精准医学和以患者为中心的医学可能会改善这方面的治疗决策。

引用次数: 0

Advancing the management of acute intermediate-high-risk pulmonary embolism: The enduring legacy of Professor Guy Meyer 推进急性中高危肺栓塞的治疗：盖伊-迈耶教授的不朽遗产。

IF 3.2 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

Presse Medicale

Pub Date : 2024-09-01 DOI: 10.1016/j.lpm.2024.104248

Stavros V. Konstantinides , Olivier Sanchez , Samuel Z. Goldhaber , Nicolas Meneveau

Only few years after the first report on diagnosing acute pulmonary embolism (PE) with pulmonary angiography, studies began to investigate the effectiveness and safety of thrombolytic therapy for achieving early reperfusion. In 1992, Guy Meyer demonstrated the fast improvement of pulmonary haemodynamics after alteplase administration; this drug has remained the mainstay of thrombolysis for PE over almost 35 years. In the meantime, algorithms for PE risk stratification continued to evolve. The landmark Pulmonary Embolism International Thrombolysis (PEITHO) trial, led by Guy Meyer, demonstrated the clinical efficacy of thrombolysis for intermediate-risk PE, albeit at a relatively high risk of major, particularly intracranial bleeding. Today, systemic thrombolysis plays an only minor role in the real-world treatment of acute PE in the United States and Europe, but major trials are underway to test safer reperfusion regimens. Of those, the PEITHO-3 study, conceived by Guy Meyer and other European and North American experts, is an ongoing randomised, placebo-controlled, double-blind, multinational academic trial. The primary objective is to assess the efficacy of reduced-dose intravenous thrombolytic therapy against the background of heparin anticoagulation in patients with intermediate-high-risk PE. In parallel, trials with similar design are testing the efficacy and safety of catheter-directed local thrombolysis or mechanical thrombectomy. Increasingly, focus is being placed on long-term functional and patient-reported outcomes, including quality of life indicators, as well as on the utilization of health care resources. The pioneering work of Guy Meyer will thus continue to have a major impact on the management of PE for years to come.

在首次报道通过肺血管造影诊断急性肺栓塞（PE）后仅几年，就开始研究溶栓疗法实现早期再灌注的有效性和安全性。1992 年，盖伊-迈耶（Guy Meyer）展示了阿替普酶用药后肺血流动力学的快速改善；近 35 年来，这种药物一直是 PE 溶栓治疗的主要药物。与此同时，PE 风险分层的算法也在不断发展。盖-迈耶领导的具有里程碑意义的肺栓塞国际溶栓（PEITHO）试验证明了溶栓治疗中危 PE 的临床疗效，尽管大出血尤其是颅内出血的风险相对较高。如今，在美国和欧洲，全身溶栓治疗在急性 PE 的实际治疗中只发挥了微不足道的作用，但测试更安全再灌注方案的大型试验正在进行中。其中，PEITHO-3 研究是由盖伊-迈耶（Guy Meyer）及其他欧洲和北美专家构想的，是一项正在进行中的随机、安慰剂对照、双盲、跨国学术试验。其主要目的是评估在肝素抗凝的背景下，减少剂量静脉溶栓疗法对中高风险 PE 患者的疗效。与此同时，设计类似的试验也在测试导管引导局部溶栓或机械血栓切除术的有效性和安全性。人们越来越关注长期功能和患者报告的结果，包括生活质量指标，以及医疗资源的利用情况。因此，盖伊-迈耶的开创性工作将在未来几年继续对 PE 的治疗产生重大影响。

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引用次数: 0

Diagnostic management of acute pulmonary embolism 急性肺栓塞的诊断治疗。

IF 3.2 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

Presse Medicale

Pub Date : 2024-09-01 DOI: 10.1016/j.lpm.2024.104241

M.V. Huisman , C. Tromeur , G. le Gal , P.Y. Le Roux , M. Righini

Straightforward, accurate diagnostic management in patients presenting with clinically suspected pulmonary embolism (PE) is essential, since starting anticoagulant treatment may give important adverse effects of bleeding, while false exclusion of the disease may lead to recurrent VTE, with associated morbidity and mortality. In the past three decades, considerable improvement in the diagnostic management of PE has been made. Computed tomography pulmonary angiography (CTPA) has largely replaced conventional pulmonary angiography and ventilation-perfusion lung scanning as the imaging methods of choice. Several diagnostic algorithms, all able to minimize the need for radiological imaging have been developed and validated. Lastly, within the diagnostic algorithms, varying d-dimer cut-off levels have successfully been introduced to further downsize the need for radiological imaging.

对临床疑似肺栓塞（PE）患者进行直接、准确的诊断治疗至关重要，因为开始抗凝治疗可能会导致出血等严重不良后果，而错误排除疾病可能会导致 VTE 复发，并带来相关的发病率和死亡率。在过去的三十年中，PE 的诊断治疗有了很大的改进。计算机断层扫描肺血管造影术（CTPA）已在很大程度上取代了传统的肺血管造影术和肺通气灌注扫描，成为首选的成像方法。目前已开发并验证了几种诊断算法，它们都能最大限度地减少对放射成像的需求。最后，在这些诊断算法中，还成功引入了不同的 D-二聚体截断水平，以进一步减少对放射成像的需求。

引用次数: 0

Painful forms of diabetic neuropathy 疼痛型糖尿病神经病变。

IF 2.7 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

Presse Medicale

Pub Date : 2024-04-23 DOI: 10.1016/j.lpm.2024.104236

Bernard Bauduceau, Lyse Bordier

Diabetic neuropathy is a frequent and severe degenerative complication of diabetes. The diagnosis is easily performed in painful symptomatic patients. Sensitivity disorders responsible for numbness, tingling, and loss of feeling are part and parcel of diabetic foot syndrome and require investigation in view of preventing trophic ulcers. To date, there exists no specific treatment for diabetic neuropathy possibly preventable by careful control of metabolic disorder. Effective management of diabetic patients would make it possible to limit the dramatic consequences of diabetic neuropathy while at the same time acting on other complications.

糖尿病神经病变是一种常见的严重退行性糖尿病并发症。有疼痛症状的患者很容易被诊断出来。导致麻木、刺痛和感觉丧失的敏感性失调是糖尿病足综合征的重要组成部分，需要进行检查以预防营养性溃疡。迄今为止，还没有治疗糖尿病神经病变的特效药，但只要认真控制代谢紊乱，是可以预防的。对糖尿病患者进行有效的管理将有可能限制糖尿病神经病变的严重后果，同时对其他并发症起到作用。

引用次数: 0

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