European Journal of Haematology最新文献

{"title":"Targeting the Immune Microenvironment in Chronic Lymphocytic Leukemia: An Evolving Therapeutic Strategy","authors":"Clement Chung,&nbsp;David Doan","doi":"10.1111/ejh.14408","DOIUrl":"10.1111/ejh.14408","url":null,"abstract":"<p>Although small molecule inhibitors that target the aberrant signaling pathways and molecular defects of chronic lymphocytic leukemia (CLL) result in improved survival benefits vs. traditional chemoimmunotherapy or chemotherapy, treatment resistance may result later, reflecting the intrinsic tumor heterogeneity, persistence of the leukemic clone, and presence of the tumor microenvironment, which supports the survival of the disease clone. Patients with CLL have immune-related abnormalities in T lymphocyte subset composition, immune synapse formation, and other immune dysregulations. Cellular interactions between the disease clone and its microenvironment provide therapeutic opportunities to target these tumor pathogenesis pathways, potentially improving the patient's immune functions and clinical outcomes of targeted therapies. At present, despite the lack of response of immune checkpoint inhibitors in CLL, they showed promising efficacy in patients with Richter transformation. Together with CD19-targeted chimeric antigen receptor–modified T cell (CAR-T) therapy, novel bispecific antibodies and other immunotherapies are being investigated to improve survival outcomes for patients with relapsed or refractory (R/R) CLL, as exemplified by epcoritamab, a bispecific antibody that recently demonstrated initial efficacy in R/R CLL and in patients in high-risk CLL subgroups, including those with <i>TP53</i> aberrations and unmutated genes that encode immunoglobulin variable heavy chain region (<i>IGHV</i>). Furthermore, to address the immune escape of cancer cells and issues that impact the durability of single-targeted T cell-redirected therapies, novel strategies such as trispecific antibodies and combination therapies are being investigated to increase tumor specificity or immune cell activation. In summary, there is emerging evidence that immunotherapies may counteract the immunosuppressive microenvironment of CLL, improve clinical responses, decrease the risk of infection, and overcome treatment resistance.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 6","pages":"953-972"},"PeriodicalIF":2.3,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejh.14408","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Impact of Continuous Dasatinib Administration on the Prognosis of Patients With BCR::ABL1 Acute Lymphoblastic Leukemia: Result of the Prospective MRD2014 Study Conducted by Fukuoka Blood and Marrow Transplantation Group (FBMTG)","authors":"Koji Nagafuji,&nbsp;Yoshikiyo Ito,&nbsp;Toshihiro Miyamoto,&nbsp;Tetsuya Eto,&nbsp;Tomohiko Kamimura,&nbsp;Koji Kato,&nbsp;Yasuhiko Miyazaki,&nbsp;Atsuhi Wake,&nbsp;Kentaro Kohno,&nbsp;Ken Takase,&nbsp;Yutaka Imamura,&nbsp;Naoyuki Uchida,&nbsp;Kazuki Tanimoto,&nbsp;Noriaki Kawano,&nbsp;Toshiro Kurokawa,&nbsp;Yukio Kondo,&nbsp;Tomoaki Fujisaki,&nbsp;Junichi Tsukada,&nbsp;Koji Yonemoto,&nbsp;Koichi Akashi","doi":"10.1111/ejh.14407","DOIUrl":"10.1111/ejh.14407","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To assess the efficacy of continuous dasatinib in improving outcomes for adult patients with <i>BCR::ABL1</i> ALL.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The prospective, multicenter ALL/MRD2014 trial introduced a modified protocol compared to the MRD2008 trial, incorporating continuous dasatinib use and reduced chemotherapy intensity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among the 164 adult ALL patients enrolled (2014–2019), 61 were Philadelphia-positive (Ph+) (median age 50 years; 38 males, 23 females). Post-induction, 96.7% achieved complete remission (CR). The 3-year event-free survival (EFS) and overall survival (OS) were 51% and 76%, respectively. Patients undergoing allo-HSCT in CR1 had improved outcomes, with a 3-year EFS of 64% and OS of 87%. MRD-negative patients before transplantation exhibited superior survival (EFS: 71% vs. 29%; OS: 94% vs. 57%). Comparison with the MRD2008 trial revealed similar outcomes, with the MRD2014 trial achieving a 3-year EFS of 51% and OS of 76% vs. 52% and 84% in MRD2008. Although not statistically significant, the MRD2014 trial showed trends of increased relapse (CIR: 39% vs. 26%, <i>p</i> = 0.305) and reduced non-relapse mortality (NRM: 10% vs. 21%, <i>p</i> = 0.181).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The ALL/MRD2014 trial underscores the importance of MRD status and allo-HSCT in Ph+ ALL. Continuous dasatinib-based regimens offer favorable outcomes in MRD-negative patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>This study was registered with the UMIN Clinical Trials Registry (UMIN-CTR), number UMIN000012382</p>\u0000 </section>\u0000 </div>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 6","pages":"1001-1010"},"PeriodicalIF":2.3,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Further Reflections on 6-MP Adherence and Habit Strength: The Impact of Dose Adjustment Complexity and Caregiver Burden","authors":"Jiamin Lu,&nbsp;Hui Wu,&nbsp;Wei Wei","doi":"10.1111/ejh.14406","DOIUrl":"10.1111/ejh.14406","url":null,"abstract":"","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 6","pages":"1055-1056"},"PeriodicalIF":2.3,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Strategies for Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia in Adult Patients: Optimizing the Use of Monoclonal Antibodies","authors":"Antonella Bruzzese,&nbsp;Enrica Antonia Martino,&nbsp;Caterina Labanca,&nbsp;Giulio Caridà,&nbsp;Francesco Mendicino,&nbsp;Eugenio Lucia,&nbsp;Virginia Olivito,&nbsp;Noemi Puccio,&nbsp;Antonino Neri,&nbsp;Fortunato Morabito,&nbsp;Ernesto Vigna,&nbsp;Massimo Gentile","doi":"10.1111/ejh.14405","DOIUrl":"10.1111/ejh.14405","url":null,"abstract":"<p>The treatment landscape for relapsed or refractory acute lymphoblastic leukemia (RR ALL) has evolved significantly with the introduction of monoclonal antibodies such as blinatumomab and inotuzumab ozogamicin. These agents have demonstrated remarkable efficacy, achieving high response rates and minimal residual disease (MRD) negativity. However, the optimal selection, sequencing, and integration of monoclonal antibodies and other modalities like standard chemotherapy or chimeric antigen receptor T-cell therapy remain areas of active investigation. The absence of direct comparative studies has led to reliance on indirect analyses, which provide conflicting results regarding the relative benefits of inotuzumab and blinatumomab. While inotuzumab is preferred in high-disease-burden settings due to its cytoreductive capabilities, blinatumomab shows superior performance in low-disease-burden settings by leveraging preserved T-cell function. Sequential and combination approaches, such as induction with inotuzumab followed by blinatumomab consolidation, may optimize outcomes, particularly for patients undergoing subsequent allogeneic stem cell transplantation (alloSCT). The interval between inotuzumab and alloSCT is critical to mitigate the risk of veno-occlusive disease (VOD). Despite these advances, the prognosis for patients with high-risk genetic lesions, such as TP53 mutations, remains poor, underscoring the need for innovative therapeutic strategies. As monoclonal antibodies increasingly move into frontline therapy, their role in relapse settings must be redefined. Future research should focus on unraveling the molecular underpinnings of resistance and refining treatment paradigms to improve survival and quality of life for patients with RR ALL.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 6","pages":"938-952"},"PeriodicalIF":2.3,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejh.14405","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Mutations Driving Aplastic Anemia: A Focus on Key Allelic Changes","authors":"Fabiana Burceaga,&nbsp;Ayline Cárdenas,&nbsp;Jessica Ortega,&nbsp;Eduardo Galván","doi":"10.1111/ejh.14399","DOIUrl":"10.1111/ejh.14399","url":null,"abstract":"<p>Aplastic Anemia (AA) is a rare blood disorder where the bone marrow fails, leading to pancytopenia. Most of the time it is idiopathic; however, it can also be caused by drugs, radiation, infections, or genetic issues. Recent molecular research has revealed that specific mutations in the Human Leukocyte Antigen (HLA) genes play a pivotal role in AA's pathogenesis, clinical presentation, and therapeutic response. Notably, mutations in the HLA have emerged as crucial in the disease's molecular pathway. These mutations interfere with HLA coding. Specifically, cytotoxic CD8+ T cells become aberrantly activated and undergo clonal expansion that continues to attack the hematopoietic stem cells (HSCs). Advances in genetic screening allow the detection of these specific mutations, enabling a more personalized treatment approach, considering immunosuppressive therapies (IST) or bone marrow transplantation. This review is based on the role of the most common HLA genotype (HLA-B*40:02 and HLA-B*14:02) and somatic mutations (TERT, TERC, ASXL1, and DNMT3A) in contributing to immune dysregulation and the clinical presentation of AA according to the severity, treatment response, and prognosis depending on the mutation presented.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 6","pages":"914-923"},"PeriodicalIF":2.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejh.14399","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TP53-Mutated Acute Myeloid Leukemia: Review of Treatment and Challenges","authors":"Bipin Ghimire,&nbsp;Markie Zimmer,&nbsp;Vijayalakshmi Donthireddy","doi":"10.1111/ejh.14404","DOIUrl":"10.1111/ejh.14404","url":null,"abstract":"<p>Patients with acute myeloid leukemia (AML) harboring mutations in <i>TP53</i> (<i>TP53</i>-MT) have poor responses to current therapies and unfavorable prognoses. Despite the recognition of variant <i>TP53</i> as an adverse feature of AML, an optimal treatment regimen has not yet been established, underlining a critical need for new, more effective therapeutic combinations and novel treatments. We present the case of a patient with <i>TP53</i>-MT AML and marked myelodysplasia who developed primary refractory disease after induction therapy with the intensive chemotherapy regimen of liposomal daunorubicin and cytarabine. Our patient's optimal response to second induction chemotherapy with FLAG-Ida prompted an exploration of established and investigational treatment regimens for this specific high-risk AML subtype. Therefore, we performed a comprehensive literature review of findings from studies exploring AML therapies, focusing on outcomes for patients with <i>TP53</i>-MT AML. The summary provided here reveals the complexity of defining the therapeutic responses of patients with the heterogeneous <i>TP53</i>-MT genetic background and the challenges in treating this high-risk form of AML. Future work must continue to investigate novel therapies and combinations to improve patient outcomes in this vulnerable population.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 6","pages":"924-937"},"PeriodicalIF":2.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejh.14404","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improved Outcomes of Myeloma Cast Nephropathy in Newly Diagnosed Multiple Myeloma With Modern Anti-Myeloma Therapies","authors":"Michael Sang Hughes,&nbsp;Metodi Balev,&nbsp;Jai Radhakrishnan,&nbsp;Divaya Bhutani,&nbsp;Markus Mapara,&nbsp;Suzanne Lentzsch,&nbsp;Rajshekhar Chakraborty","doi":"10.1111/ejh.14403","DOIUrl":"10.1111/ejh.14403","url":null,"abstract":"<div>\u0000 \u0000 <p>Myeloma cast nephropathy (MCN) is a driver of renal failure in newly diagnosed multiple myeloma (NDMM) and has been historically associated with increased early mortality. Since patients with moderate to severe renal insufficiency are typically excluded from trials, we performed a retrospective study to characterize modern-era outcomes in MCN. We reviewed 274 consecutive NDMM patients from 2017 to 2023 at an academic center and identified 46 patients (16.8%) with MCN. Among them, 96% had received bortezomib and 67% anti-CD38⁺ monoclonal antibody in frontline therapy. As per the International Myeloma Working Group criteria, the renal overall response rate was 76.1% (35/46), and the renal complete response (CR) rate was 32.6% (15/46) at 6 months. Overall survival (OS) at 6 months did not differ between MCN (100%) and controls (98.2%). At a median follow-up of ~3 years, the mean MCN OS was within 7 months of control (<i>p</i> = 0.039) by equivalence testing. Most involved free light chain (iFLC) and proteinuria reduction occurred within 1 month of treatment (83.1%, 3.9 g/d, respectively). In summary, we report excellent 6-month renal recovery without early mortality in MCN patients with modern anti-myeloma therapies. Prospective studies focused on MCN are urgently needed to further improve the renal CR rate.</p>\u0000 </div>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 6","pages":"990-1000"},"PeriodicalIF":2.3,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Case-Driven Multi-Omics Analysis for Longitudinal Ibrutinib Response Evaluation of Patients With Chronic Lymphocytic Leukemia","authors":"Sólja Remisdóttir Veyhe,&nbsp;Marcus Høy Hansen,&nbsp;Oriane Cédile,&nbsp;Michael Boe Møller,&nbsp;Mie Kiszka Nielsen,&nbsp;Mads Thomassen,&nbsp;Karen Juul-Jensen,&nbsp;Henrik Frederiksen,&nbsp;Karen Dybkær,&nbsp;Charlotte Guldborg Nyvold","doi":"10.1111/ejh.14397","DOIUrl":"10.1111/ejh.14397","url":null,"abstract":"<p>Patients with chronic lymphocytic leukemia (CLL) undergoing ibrutinib treatment often experience incomplete response, yet the molecular level underlying clonal inertia remains to be explored. We investigated the molecular and clinical dynamics of CLL during 16 months of ibrutinib monotherapy by analyzing blood samples from two patients who continued having CLL cells in the peripheral blood during treatment. At diagnosis, the clonal burden within the B cell compartment was found to be 55% (pt1) and 86% (pt2) for the dominant clones. At 16 months following treatment these clones still constituted 66% and 89%, respectively. Utilizing multi-omic methodologies at the DNA and RNA levels, including single-cell transcriptomics, we aimed to establish a comprehensive framework for multi-omics analysis for longitudinal ibrutinib response evaluation. The presented study revealed genomically stable disease during ibrutinib treatment, but with intensified expression of genes involved in pathways related to apoptosis, cellular stress response, and canonical NF-κB signaling from diagnosis to 16 months of treatment.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 6","pages":"973-981"},"PeriodicalIF":2.3,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejh.14397","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Measurable Residual Disease in UBTF-TD Adult Acute Myeloid Leukemia","authors":"Helena Castellet,&nbsp;Guillermo Ramil,&nbsp;Maite Carricondo,&nbsp;Guadalupe Oñate,&nbsp;Ana Garrido,&nbsp;Alícia Artigas,&nbsp;Marta Pratcorona,&nbsp;Olga Salamero,&nbsp;Albert Cortés-Bullich,&nbsp;Susana Vives,&nbsp;Mar Tormo,&nbsp;Martí Mascaró,&nbsp;David Gallardo,&nbsp;Josep Maria Marti Tutusaus,&nbsp;Antonio Garcia,&nbsp;Jorge Sierra,&nbsp;Jordi Esteve,&nbsp;Josep Nomdedéu,&nbsp;the CETLAM group","doi":"10.1111/ejh.14402","DOIUrl":"10.1111/ejh.14402","url":null,"abstract":"","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 6","pages":"1052-1054"},"PeriodicalIF":2.3,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outcomes of Melflufen Treatment in Patients With Relapsed/Refractory Multiple Myeloma","authors":"Shahrier Hossain,&nbsp;Clifton Mo,&nbsp;Sarah Patches,&nbsp;Houry Leblebjian,&nbsp;Kathryn Goodrich,&nbsp;Eileen Regan,&nbsp;Kathleen O'Neill,&nbsp;Kim Noonan,&nbsp;Paul G. Richardson,&nbsp;Jacob Laubach","doi":"10.1111/ejh.14398","DOIUrl":"10.1111/ejh.14398","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Melphalan flufenamide (melflufen) plus dexamethasone is fully approved in Europe for patients with relapsed/refractory multiple myeloma (RRMM) with ≥ 3 prior lines of therapy. We analyzed the efficacy and safety of melflufen in the real-world setting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this retrospective analysis, we examined baseline features, efficacy, and safety outcomes with melflufen plus dexamethasone in a cohort of 12 patients with heavily pre-treated RRMM at the Dana-Farber Cancer Institute, USA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients had received a median of 5.5 prior lines of therapy. Three patients (25%) had extramedullary disease, three (25%) cytogenetically high-risk features, and five (42%) had received prior autologous stem cell transplantation. The overall response rate was 55% (complete response: three [27%], very good partial response: one [9%], partial response: two [18%] patients). Five patients (42%) had stable disease; one was non-evaluable. Adverse events (AEs) were mostly hematologic and proved manageable; two patients had Grade 2 infections. Reasons for melflufen discontinuation were progressive disease (42%), drug withdrawal from the United States market (33%), AEs (17%), and sudden death (8%) unrelated to treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Consistent with clinical trial data, melflufen had an expected safety profile with manageable toxicity and clinically meaningful efficacy in patients with RRMM treated in the real-world setting.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 6","pages":"982-989"},"PeriodicalIF":2.3,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejh.14398","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}