Current Research in Translational Medicine最新文献

英文中文

Multidimensional evaluation of CMV-specific T Cells: enhancing therapy through transcriptional insights cmv特异性T细胞的多维评估：通过转录的见解增强治疗

IF 3.2 4区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Current Research in Translational Medicine

Pub Date : 2025-07-01 Epub Date: 2025-04-29 DOI: 10.1016/j.retram.2025.103517

Changchang Sun , Mingli Xu , Min Yan , Meiying Shen , Xiaojian Han , Hongbin Zhang , Chao Hu , Yingming Wang , Wang Wang , Aishun Jin , Yingying Wang

Adoptive immunotherapy with CMV-specific T cells (CMV-VSTs) has shown favorable efficacy and minimal adverse effects in clinical settings, serving as prophylaxis, preemptive and/or curative treatment for the restoration of CMV-specific immunity in patients after allogeneic hematopoietic stem cell transplantation. The establishment of a CMV-VST bank enables the prompt use of CMV-VSTs as off-the-shelf therapeutics. CMV-VSTs can be generated through cell culture or immunomagnetic selection based on IFN-γ secretion or multimer technology. In this study, we investigated the feasibility of generating CMV-VSTs via cell expansion after IFN-γ based immunomagnetic isolation, with the goal of establishing a good-quality, cost-effective local production approach. We also assessed the value of incorporating transcriptomic analysis into the current T cell evaluation framework. Our results demonstrate that good-quality CMV-VSTs can be produced using either autologous feeder cells or feeder cells from the rapid expansion protocol (REP), in combination with cytokines such as IL-2 or IL-7/IL-15. Phenotypic and functional analyses confirmed the consistent quality of the final T cell products and showed no significant differences across the various combinations of feeder cells and cytokines. However, transcriptomic analysis highlighted the advantages of using IL-7/IL-15 and autologous feeder cells. Collectively, our findings offer new insights into future strategies for the manufacturing of antigen-specific T cells and underscore the importance of comprehensive, multidimensional assessment in T cell-based immunotherapies.

cmv特异性T细胞（CMV-VSTs）过继免疫治疗在临床环境中显示出良好的疗效和最小的不良反应，可作为异基因造血干细胞移植后患者cmv特异性免疫恢复的预防、先发制人和/或治疗性治疗。CMV-VST库的建立使CMV-VST能够作为现成的治疗药物迅速使用。CMV-VSTs可以通过细胞培养或基于IFN-γ分泌或多重技术的免疫磁选择产生。在本研究中，我们研究了基于IFN-γ的免疫磁分离后通过细胞扩增产生CMV-VSTs的可行性，目的是建立一种高质量、高成本效益的本地生产方法。我们还评估了将转录组学分析纳入当前T细胞评估框架的价值。我们的研究结果表明，高质量的CMV-VSTs可以使用自体供体细胞或快速扩增方案（REP）的供体细胞，结合IL-2或IL-7/IL-15等细胞因子产生。表型和功能分析证实了最终T细胞产物的一致质量，并且在不同的饲养细胞和细胞因子组合中没有显着差异。然而，转录组学分析强调了使用IL-7/IL-15和自体饲养细胞的优势。总的来说，我们的发现为抗原特异性T细胞制造的未来策略提供了新的见解，并强调了在基于T细胞的免疫疗法中全面、多维评估的重要性。

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引用次数: 0

Acute-onset chronic inflammatory demyelinating polyneuropathy in a 23-year-old male exacerbated by an asymptomatic COVID-19 infection 一名23岁男性因无症状COVID-19感染而加重的急性发作慢性炎症性脱髓鞘多神经病变

IF 3.2 4区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Current Research in Translational Medicine

Pub Date : 2025-07-01 Epub Date: 2025-03-31 DOI: 10.1016/j.retram.2025.103511

Sawsan Ismail , Aiman Abo Al shamat , Ali Ghalion , Hanafi Alyman Hannouf , Tamim Alsuliman , Kanaan Al-Tameemi

引用次数: 0

The vaso-occlusive pain crisis in sickle cell patients: A focus on pathogenesis 镰状细胞病患者的血管闭塞性疼痛危机：发病机制的焦点

IF 3.2 4区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Current Research in Translational Medicine

Pub Date : 2025-07-01 Epub Date: 2025-03-29 DOI: 10.1016/j.retram.2025.103512

Fatemeh Javaherforoosh Zadeh , Azadeh Fateh , Hamed Saffari , Mohammadtaghi Khodadadi , Mohammadamin Eslami Samarian , Nasim Nikoubakht , Fatemeh Dadgar , Vahid Goodarzi

Vaso-occlusive pain crisis (VOC) is recognized as a prominent complication of sickle cell disease, accompanied by debilitating pain and serious consequences for patients, making it the primary cause of visits to hospital emergency departments. In the etiology of VOC, the intricate interaction of endothelial cells, hypoxia, inflammation, and the coagulation system is pivotal. Hemoglobin S polymerization under hypoxic conditions leads to the formation of rigid and adhesive red blood cells that interact with vascular endothelial cells and other blood cells, causing occlusion and subsequent inflammation. Hemolysis of red blood cells results in anemia and heightened inflammation, whereas oxidative stress and involvement of the coagulation system further complicate matters. In this review, we strive to examine the pathophysiology of VOC from these mentioned aspects by consolidating findings from various studies, as a comprehensive understanding of the causes of VOC is essential for the development of targeted therapeutic interventions and the prevention and management of pain, ultimately improving the quality of life for patients.

血管闭塞性疼痛危像（VOC）被认为是镰状细胞病的一个重要并发症，伴随着使患者衰弱的疼痛和严重后果，使其成为医院急诊科就诊的主要原因。在VOC的病因学中，内皮细胞、缺氧、炎症和凝血系统的复杂相互作用是关键。缺氧条件下的血红蛋白S聚合导致形成刚性和黏附的红细胞，与血管内皮细胞和其他血细胞相互作用，引起闭塞和随后的炎症。红细胞溶血导致贫血和炎症加剧，而氧化应激和凝血系统的参与使问题进一步复杂化。在这篇综述中，我们通过整合各种研究结果，努力从上述方面检查VOC的病理生理，因为全面了解VOC的原因对于制定有针对性的治疗干预措施和预防和管理疼痛至关重要，最终提高患者的生活质量。

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引用次数: 0

Pneumonia definition in allogeneic hematopoietic cell transplant recipients: Update and challenges in 2024. Recommendations from the EBMT Infectious Diseases Working Party and Practice Harmonization and Guidelines committee 同种异体造血细胞移植受者的肺炎定义：2024年的更新和挑战。EBMT传染病工作组和实践协调与指南委员会的建议

IF 3.2 4区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Current Research in Translational Medicine

Pub Date : 2025-07-01 Epub Date: 2025-03-20 DOI: 10.1016/j.retram.2025.103509

Dionysios Neofytos , Paul E. Verweij , Dina Averbuch , Malgorzata Mikulska , Jan Styczynski , José Luis Piñana , Simone Cesaro , Isabel Sanchez-Ortega , Raffaella Greco , Francesco Onida , Ibrahim Yakoub-Agha , Per Ljungman , Camara Rafael de la , Anne Bergeron

To optimize and homogenize data on infectious diseases complications, the Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation (IDWP EBMT) participated in the 2023 EBMT international workshop focusing on the standardization of the definition of specific infections, including respiratory infections [1]. This is pertinent considering that a new software for data collection, including data on post-transplant infectious disease complications, was launched in 2023 and which will remain the main tool for future epidemiological studies. In this report, we briefly discuss our proposals for pneumonia definition, predominately focusing on bacterial and fungal pneumonias. We specifically address definitions of pneumonia diagnosis, infection onset date, resolution, recurrence, and breakthrough infection, and the challenges we encountered as a group to accurately define pneumonia in hematopoietic cell transplant (HCT) recipients (Table 1). Infections with community acquired respiratory viruses and adenovirus are discussed in a separate report [1]. Definitions on CMV pneumonia have been previously described and recently updated and hence not discussed in this paper [2,3].

为了优化和统一传染病并发症的数据，欧洲血液和骨髓移植学会（IDWP EBMT）传染病工作组参加了2023年EBMT国际研讨会，重点是标准化特定感染的定义，包括呼吸道感染[1]。考虑到用于收集数据（包括移植后传染病并发症数据）的新软件于2023年启动，这将是相关的，该软件仍将是未来流行病学研究的主要工具。在本报告中，我们简要讨论了我们对肺炎定义的建议，主要集中在细菌性和真菌性肺炎上。我们特别讨论了肺炎诊断、感染发病日期、消退、复发和突破性感染的定义，以及我们作为一个小组在准确定义造血细胞移植（HCT）受者肺炎时遇到的挑战（表1）。社区获得性呼吸道病毒和腺病毒感染在另一份报告bbb中进行了讨论。CMV肺炎的定义此前已有描述，最近也有更新，因此本文未讨论[2,3]。

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引用次数: 0

Allogeneic hematopoietic stem cell transplantation in 18 patients with atypical inherited bone marrow failure syndromes: Efficacy and long-term outcomes 异基因造血干细胞移植治疗18例非典型遗传性骨髓衰竭综合征的疗效和长期预后

IF 3.2 4区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Current Research in Translational Medicine

Pub Date : 2025-07-01 Epub Date: 2025-05-21 DOI: 10.1016/j.retram.2025.103519

Yimin Wang, Jing Wang, Qianqian Xiao, Xiaolin Yu, Xiaochen Song, Wenjun Li, Lei Deng, Yixi Hou, Fang Zhou

引用次数: 0

VEXAS associated acute disseminated Encephalo-Myelitis (ADEM)-like syndrome: A case report and review of the literature VEXAS相关急性播散性脑脊髓炎（ADEM）样综合征：1例报告及文献回顾

IF 3.2 4区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Current Research in Translational Medicine

Pub Date : 2025-07-01 Epub Date: 2025-03-09 DOI: 10.1016/j.retram.2025.103505

Gregorio Maria Bergonzi , Corrado Campochiaro , Alessandro Tomelleri , Anna Del Poggio , Raffaello Bonacchi , Laura Ferré , Giulia Furnari , Costanza Piccolo , Gianluca Scorpio , Fabio Ciceri , Lorenzo Dagna , Massimo Filippi , Elisa Diral

引用次数: 0

A complex clinical presentation of ultra-high risk acute promyelocytic leukemia: A case report and insights on management 超高危险急性早幼粒细胞白血病的复杂临床表现：一例报告及治疗见解

IF 3.2 4区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Current Research in Translational Medicine

Pub Date : 2025-07-01 Epub Date: 2025-03-18 DOI: 10.1016/j.retram.2025.103506

Lucrezia De Marchi , Giovangiacinto Paterno , Kristian Taka , Laura Giannì , Giulia Colafranceschi , Tiziana Ottone , Manuela Rizzo , Mariadomenica Divona , Raffaele Palmieri , Francesco Buccisano , Luca Maurillo , Maria Ilaria Del Principe , Maria Teresa Voso , Carmelo Gurnari , Adriano Venditti

引用次数: 0

Organ transplantation in Africa: Confronting socioeconomic, cultural, and infrastructural hurdles 非洲的器官移植：面对社会经济、文化和基础设施障碍

IF 3.2 4区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Current Research in Translational Medicine

Pub Date : 2025-07-01 Epub Date: 2025-04-28 DOI: 10.1016/j.retram.2025.103516

David B. Olawade , Aderonke Odetayo , Sheila Marinze , Eghosasere Egbon , Viviane Chinwah

Background

Organ transplantation is a critical procedure offering life-saving treatment for patients with end-stage organ failure. In Africa, however, the accessibility and development of organ transplantation are severely hampered by numerous barriers. Socioeconomic disparities, inadequate healthcare infrastructure, legal and ethical gaps, cultural resistance, and the dual burden of infectious and non-communicable diseases are among the significant challenges faced. This review aims to comprehensively explore these barriers and propose actionable strategies to address them.

Method

A narrative review was conducted by searching electronic databases, including PubMed, Google Scholar, Scopus, and JSTOR. The review prioritized studies addressing the challenges of organ transplantation in Africa, focusing on socioeconomic factors, healthcare infrastructure, cultural beliefs, legal frameworks, and the impact of infectious and non-communicable diseases. Studies offering solutions tailored to the African context were also included.

Results

The review identified several key obstacles, including high costs of transplantation, a limited number of transplant centers, and a critical shortage of skilled healthcare professionals. Cultural beliefs and widespread misconceptions impede organ donation acceptance. Additionally, infectious and non-communicable diseases complicate the transplantation process and outcomes. Weak legal frameworks exacerbate the risks of organ trafficking and unethical practices, while low public awareness further undermines efforts to enhance organ donation rates.

Conclusion

Addressing these multifaceted challenges necessitates a comprehensive approach. Strengthening healthcare infrastructure, enhancing capacity-building programs, developing robust legal and ethical frameworks, and implementing targeted public education campaigns are critical for improving organ transplantation in Africa.

器官移植是终末期器官衰竭患者救命治疗的重要手段。然而，在非洲，器官移植的可及性和发展受到许多障碍的严重阻碍。社会经济差距、保健基础设施不足、法律和道德差距、文化阻力以及传染病和非传染性疾病的双重负担是面临的重大挑战。本综述旨在全面探讨这些障碍，并提出解决这些障碍的可行策略。方法通过检索PubMed、谷歌Scholar、Scopus、JSTOR等电子数据库进行综述。审查将解决非洲器官移植挑战的研究列为优先事项，重点是社会经济因素、保健基础设施、文化信仰、法律框架以及传染病和非传染性疾病的影响。提供适合非洲情况的解决办法的研究也列入其中。结果该综述确定了几个主要障碍，包括移植费用高、移植中心数量有限以及熟练的医疗保健专业人员严重短缺。文化信仰和普遍的误解阻碍了器官捐赠的接受。此外，传染病和非传染性疾病使移植过程和结果复杂化。薄弱的法律框架加剧了器官贩运和不道德做法的风险，而公众意识低下进一步破坏了提高器官捐献率的努力。应对这些多方面的挑战需要采取综合措施。加强医疗基础设施、加强能力建设项目、制定健全的法律和道德框架以及实施有针对性的公共教育运动，对于改善非洲的器官移植至关重要。

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引用次数: 0

Optimizing CAR-T cell function in solid tumor microenvironment: insights from culture media additives 优化CAR-T细胞在实体肿瘤微环境中的功能：来自培养基添加剂的见解。

IF 3.2 4区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Current Research in Translational Medicine

Pub Date : 2025-04-01 Epub Date: 2024-12-31 DOI: 10.1016/j.retram.2024.103491

Wenwen Chen, Luxia Xu, Zhigang Guo, Muya Zhou

Cancer remains one of the most pressing health challenges worldwide. Recently, chimeric antigen receptor (CAR)-T cell therapy has emerged as a promising approach for treating hematological cancers. However, the translation of CAR-T cell therapy to solid tumors faces formidable obstacles, notably the immunosuppressive tumor microenvironment. Within solid tumors, CAR-T cells encounter a hostile milieu that promotes exhaustion and diminishes their long-term effectiveness against cancer cells. Optimizing the manufacturing process is paramount to ensuring the efficacy of CAR-T cell therapy in solid tumors. A critical aspect of this optimization lies in refining the composition of cell culture media. By supplementing basic culture media with specific additives, researchers aim to improve the behavior and functionality of CAR-T cells, thereby enhancing their therapeutic potential. This review delves into the culture media additives that have been investigated or show promise in modulating CAR-T cell phenotypes and enhancing their anti-tumor efficacy. We explore various types of additives and their mechanisms of action to mitigate exhaustion and augment persistence within the challenging solid tumor microenvironment. By shedding light on the latest advancements in culture media optimization for CAR-T cell therapy, this review aims to provide insights into novel strategies for overcoming the hurdles posed by solid tumors. Ultimately, these insights hold the potential to enhance the effectiveness of CAR-T cell therapy and improve outcomes for cancer patients.

癌症仍然是全世界最紧迫的健康挑战之一。最近，嵌合抗原受体(CAR)-T细胞疗法已成为治疗血液病的一种很有前途的方法。然而，将CAR-T细胞疗法转化为实体肿瘤面临着巨大的障碍，特别是免疫抑制肿瘤微环境。在实体肿瘤中，CAR-T细胞会遇到一个不利的环境，这种环境会促进细胞衰竭，降低它们对抗癌细胞的长期有效性。优化制造工艺对于确保CAR-T细胞治疗实体瘤的疗效至关重要。这种优化的一个关键方面在于改进细胞培养基的组成。通过在基础培养基中添加特定的添加剂，研究人员旨在改善CAR-T细胞的行为和功能，从而增强其治疗潜力。本文综述了已研究或有望调节CAR-T细胞表型和增强其抗肿瘤功效的培养基添加剂。我们探索了各种类型的添加剂及其作用机制，以减轻消耗和增强具有挑战性的实体肿瘤微环境中的持久性。通过揭示CAR-T细胞治疗培养基优化的最新进展，本综述旨在为克服实体瘤带来的障碍提供新的策略。最终，这些见解有可能提高CAR-T细胞治疗的有效性，改善癌症患者的预后。

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引用次数: 0

Denutrition status prevails over a standard AML risk assessment in older adults 在老年人中，营养不良状况比标准AML风险评估更重要

IF 3.2 4区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Current Research in Translational Medicine

Pub Date : 2025-04-01 Epub Date: 2025-02-06 DOI: 10.1016/j.retram.2025.103500

Laura Simon , Alexis Caulier , Céline Berthon , Thomas Boyer , Véronique Harrivel , Magalie Joris , Isabelle Leduc , Nicolas Duployez , Claude Preudhomme , Jean-Pierre Marolleau , Delphine Lebon

Older adults with acute myeloid leukemia (AML) have a poor prognosis because frailty and the characteristics of the disease limit the use of intensive chemotherapy (ICT). Treatment with 5-azacitidine (5-AZA) or low-dose cytarabine (Cytarabine) (LDAC) – with or without venetoclax – is currently recommended in this setting. However, we lack real-life data on response rates and treatment outcomes.

We conducted a retrospective, multicenter registry study of 279 older adults with AML (median [interquartile range (IQR)] age: 76 [70–81]) having undergone first-line treatment with LDAC (n = 87) or 5-AZA (n = 192) between 2009 and 2019 (i.e. mainly before the venetoclax era) in a university medical center in France. The complete remission rate was 27.3 % overall. After a median follow-up period of 6.9 months, the median [IQR] overall survival (OS) time was shorter in the LDAC group (4.8 months [2.13–14.41]) than in the 5-AZA group (8.9 months [3.2–13.5]; p = 0.046). Ultimately, however, the OS rates were similar in the LDAC and 5-AZA groups (hazard ratio [HR]: 95 % confidence interval [CI]: 1.37 [0.92–2.04], p = 0.12).

None of the conventional markers with prognostic value in younger patients receiving ICT (such as those in the European LeukemiaNet classification) appeared to predict the outcome in our population of older patients. Albumin <30 g/L was the only factor that predicted day-30 mortality and OS (adjusted odds ratio [95 %CI]: 6.25 [2.08 – 20.0]; p < 0.001; adjusted HR [95 %CI]: 0.65 [0.44–0.96]; p = 0.030).

老年人急性髓性白血病（AML）预后较差，因为虚弱和疾病的特点限制了强化化疗（ICT）的使用。在这种情况下，目前推荐使用5-阿扎胞苷（5-AZA）或低剂量阿糖胞苷（阿糖胞苷）（LDAC）联合或不联合venetoclax治疗。然而，我们缺乏关于反应率和治疗结果的真实数据。我们对2009年至2019年（即主要在venetoclax时代之前）在法国一所大学医学中心接受LDAC （n = 87）或5-AZA （n = 192）一线治疗的279名老年AML患者（中位[四分位数范围（IQR）]年龄：76[70-81]）进行了一项回顾性、多中心注册研究。总体完全缓解率为27.3%。中位随访期为6.9个月后，LDAC组的中位总生存期（IQR）（4.8个月[2.13-14.41]）短于5-AZA组（8.9个月[3.2-13.5]）；P = 0.046)。然而，最终，LDAC组和5-AZA组的OS率相似（风险比[HR]: 95%可信区间[CI]: 1.37 [0.92-2.04], p = 0.12）。在接受ICT治疗的年轻患者中，没有一种具有预后价值的传统标志物（如欧洲白血病网分类）能够预测老年患者的预后。白蛋白30 g/L是预测第30天死亡率和总生存率的唯一因素(校正比值比[95% CI]: 6.25 [2.08 - 20.0]；p & lt;0.001;校正后HR [95% CI]: 0.65 [0.44-0.96]；P = 0.030)。

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