Epstein-Barr virus (EBV) reactivation after allogeneic hematopoietic cell transplantation (allo-HCT) is one of the major concerns that may lead to fatal EBV diseases. However, updated data are needed ...because of the remarkable evolution of the HCT protocol and donor selection. We conducted a retrospective study that enrolled 890 allo-HCT recipients. Independent risk factors for EBV reactivation were use of antithymocyte globulin, haploidentical donor, and the presence of chronic graft-versus-host disease. The cumulative incidence of EBV reactivation was 2.9%, 11.7%, 27.3%, and 41.9% for patients with 0, 1, 2, and 3 risk factors, respectively (P < 0.001). Posttransplant lymphoproliferative disorders (PTLDs) occurred in seven patients. EBV reactivation was associated with inferior survival in recipients who survived more than 2 years post-HCT (P < 0.001) but might time-dependently benefit those patients with malignancies by decreasing relapse incidence (P = 0.046). A decreased relapse incidence was observed 1 year after HCT for recipients at first or second remission (P = 0.042) and in the first year post-HCT for recipients with advanced diseases (P = 0.032). We concluded that with current management, PTLDs were efficiently controlled, but EBV reactivation still had a multifactorial impact on transplant outcomes. Multicenter prospective studies are warranted to validate these findings.
We endeavor to develop a novel deep learning architecture tailored specifically for the analysis and classification of tongue features, including color, shape, and coating. Unlike conventional ...methods based on architectures like VGG or ResNet, our proposed method aims to address the challenges arising from their extensive size, thereby mitigating the overfitting problem. Through this research, we aim to contribute to the advancement of techniques in tongue feature recognition, ultimately leading to more precise diagnoses and better patient rehabilitation in Traditional Chinese Medicine (TCM).
In this study, we introduce TGANet (Tongue Feature Attention Network) to enhance model performance. TGANet utilizes the initial five convolutional blocks of pre-trained VGG16 as the backbone and integrates an attention mechanism into this backbone. The integration of the attention mechanism aims to mimic human cognitive attention, emphasizing model weights on pivotal regions of the image. During the learning process, the allocation of attention weights facilitates the interpretation of causal relationships in the model's decision-making.
Experimental results demonstrate that TGANet outperforms baseline models, including VGG16, ResNet18, and TSC-WNet, in terms of accuracy, precision, F1 score, and AUC metrics. Additionally, TGANet provides a more intuitive and meaningful understanding of tongue feature classification models through the visualization of attention weights.
In conclusion, TGANet presents an effective approach to tongue feature classification, addressing challenges associated with model size and overfitting. By leveraging the attention mechanism and pre-trained VGG16 backbone, TGANet achieves superior performance metrics and enhances the interpretability of the model's decision-making process. The visualization of attention weights contributes to a more intuitive understanding of the classification process, making TGANet a promising tool in tongue diagnosis and rehabilitation.
The clinical outcome of Philadelphia chromosome-negative B cell acute lymphoblastic leukemia (Ph-neg B-ALL) varies considerably from one person to another after clinical treatment due to lack of ...targeted therapies and leukemia's heterogeneity. Ferroptosis is a recently discovered programmed cell death strongly correlated with cancers. Nevertheless, few related studies have reported its significance in acute lymphoblastic leukemia.
Herein, we collected clinical data of 80 Ph-neg B-ALL patients diagnosed in our center and performed RNA-seq with their initial bone marrow fluid samples. Throughout unsupervised machine learning K-means clustering with 24 ferroptosis related genes (FRGs), the clustered patients were parted into three variant risk groups and were performed with bioinformatics analysis.
As a result, we discovered significant heterogeneity of both immune microenvironment and genomic variance. Furthermore, the immune check point inhibitors response and potential implementation of Sorafenib in Ph-neg B-ALL was also analyzed in our cohort. Lastly, one prognostic model based on 8 FRGs was developed to evaluate the risk of Ph-neg B-ALL patients.
Jointly, our study proved the crucial role of ferroptosis in Ph-neg B-ALL and Sorafenib is likely to improve the survival of high-risk Ph-neg B-ALL patients.
Genetic diagnostic methods for evaluation of chimerism after HSCT, such as STR-PCR and XY-FISH, have limited sensitivity. When donor chimerism is in the micro range (< 1%), deviations in the accuracy ...of assessment are the most significant disadvantage of these common methods. We developed a highly sensitive method that applies SNPs based on NGS in order to explore the value of donor cell microchimerism in microtransplantation (MST). This improved SNP-NGS approach has higher sensitivity (0.01–0.05%) and only requires a small amount of DNA (8–200 ng). We retrospectively analyzed the clinical data of 48 patients with AML who received HLA-mismatched stem cell MST at our center to assess the impact of microchimerism on clinical prognosis. Patients whose duration of microchimerism was > 10.5 months (median) had a relapse rate of 26.1%, and had better 5-year LFS and OS (73.4% and 82.6%). In contrast, patients whose duration of microchimerism was < 10.5 months had a higher relapse rate (69.6%), and their 5-year LFS and OS were 30.4% and 43.5%. In conclusion, duration of donor chimerism is highly valuable for assessment of survival and prognosis in patients with AML who have received HLA-mismatched stem cell MST, especially the intermediate-risk group.
Among 4,780 consecutive adult acute lymphoblastic/myeloblastic leukemia patients, we identified 117 (2.4%) patients with mixed-phenotype acute leukemia fulfilling WHO 2008 criteria; these were ...classified as: Blymphoid+ myeloid (n=64), T-lymphoid+myeloid (n=38), B+T-lymphoid (n=14) and trilineage (n=1). Of 92 patients karyotyped, 59 were abnormal and were classified as: complex (22 of 92), t(9;22)(q34;q11) (14 of 92), monosomy 7 (7 of 92), polysomy 21 (7 of 92), t(v;11q23) (4 of 92), t(10;11)(p15;q21) (3 of 92), while STIL-TAL1 fusion was detected in one (T+My) patient. After investigating common acute leukemia-related mutations in 17 genes, 12 of 31 (39%) patients were found to have at least one mutation, classified with: IKZF1 deletion (4 of 31), and EZH2 (3 of 31), ASXL1 (3 of 31), ETV6 (2 of 31), NOTCH1 (1 of 31), and TET2 (1 of 31) mutations. Array-CGH revealed genomic deletions of CDKN2A (4 of 12), IKZF1 (3 of 12), MEF2C (2 of 12), BTG1 (2 of 12), together with BCOR, EBF1, K-RAS, LEF1, MBNL1, PBX3, and RUNX1 (one of 12 each). Our results indicate that mixed-phenotype acute leukemia is a complex entity with heterogeneous clinical, immunophenotypic, cytogenetic, and molecular genetic features.
Posaconazole (PCZ) is used prophylactically to prevent invasive fungal infections (IFIs) in patients with hematological malignancies.
To evaluate the cut-off serum concentration of PCZ for successful ...IFI prophylaxis in Chinese subjects.
A total of 74 patients treated with induction chemotherapy (
= 10) and allogeneic hematopoietic stem cell transplantation (HSCT) (
= 64), who received PCZ prophylactically as an oral suspension for >7 days, were included in the study. Clinical, radiological, microbiological culture results, and treatment responses were analyzed and drug concentration assays performed.
The overall incidence of possible, probable, and proven IFIs was 13.5% (10/74), with five patients in the chemotherapy group and five in the HSCT group. The PCZ serum concentration in most patients (54/63) was in the range of 0.25-1.0 μg/ml, and this concentration range was significantly associated with the success rate of PCZ prophylaxis. A cut-off value of 0.47 μg/ml can be considered as an evaluation index for PCZ prophylaxis. Taking a proton pump inhibitor (PPI) would reduce the PCZ blood concentration, but not affect the IFD breakthrough point. PCZ treatment for hematopoietic malignancy or HSCT patients with a serum concentration of PCZ < 0.47 μg/ml were risk factors for PCZ prophylaxis of IFIs, determined by univariable and multivariable regression analyses.
The serum concentration of PCZ was related to the incidence of IFIs and a serum concentration of >0.47 μg/ml is highly recommended to avoid IFIs after chemotherapy or HSCT.
Chinese Clinical Trial Registry: ChiCTR1900026294.
The purpose of the present work was to determine the incidence and clinical implications of somatic EZH2 mutations in 714 patients with de novo acute myelogenous leukemia by sequencing the entire ...coding region. EZH2 mutations were identified in 13/714 (1.8%) of AML patients were found to be more common in males (P = 0.033). The presence of EZH2 mutations was significantly associated with lower blast percentage (21-30%) in bone marrow (P<0.0001) and -7/del(7q) (P = 0.025). There were no differences in the incidence of mutation in 13 genes, ASXL1, CBL, c-KIT, DNMT3A, FLT3, IDH1, IDH2, MLL, NPM1, NRAS, RUNX1, TET2, and WT1, between patients with and without EZH2 mutations. No difference in complete remission, event-free survival, or overall survival was observed between patients with and without EZH2 mutation (P>0.05). Overall, these results showed EZH2 mutation in de novo acute myeloid leukemia as a recurrent genetic abnormality to be associated with lower blast percentage in BM and -7/del(7q).
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