Hematology最新文献

Background: The red cell distribution width to albumin ratio (RAR) has emerged as a novel, easily calculated biomarker demonstrating prognostic value across various diseases. However, the relationship of RAR for all-cause mortality risk in critically ill patients with myelodysplastic syndromes (MDS) remains unclear.

Objectives: To explore the association between RAR and all-cause mortality in critically ill patients with MDS.

Methods: This retrospective cohort study utilized patient data from the MIMIC-IV database. The study population was patients with MDS admitted to ICU for the first time. The main outcome was all-cause mortality at 28-day, 90-day, and 365-day. The association between RAR and all-cause mortality was evaluated using Cox proportional hazards regression analysis. Restricted Cubic Spline (RCS) regression was employed to test for any non-linear relationship between RAR levels and the mortality risk.

Results: Patients in the high RAR group showed significantly worse survival rates across time points of 28-day, 90-day, and 365-day compared to the low RAR group (log-rank test, all P < 0.001). In the adjusted multivariable Cox regression model, elevated RAR as a continuous variable was significantly associated with an increased risk of all-cause mortality: 28-day (HR = 1.18; 95% CI: 1.08-1.29; P < 0.001), 90-day (HR = 1.18; 95% CI: 1.09-1.27; P < 0.001), and 365-day (HR = 1.17; 95% CI: 1.10-1.25; P < 0.001). RCS analysis confirmed a positive but non-linear association between increasing RAR levels and heightened mortality risk.

Conclusions: RAR, a readily available composite biomarker, is associated with all-cause mortality in critically ill patients with MDS.

Objectives: Several observational studies have suggested an association between sleep traits and leukaemia. This study aimed to determine the causal association between sleep traits and leukaemia using two-sample Mendelian Randomization (MR) analysis.

Methods: Publicly available databases were used to retrieve summary statistics from genome-wide association studies (GWAS) related to sleep traits (UK BioBank) and leukaemia (FinnGen database). Inverse Variance Weighted (IVW) method was utilized for the primary MR analysis. Subsequently, we conducted a reverse MR analysis. Sensitivity analyses and statistical power calculation validated the robustness of the research findings. The Steiger directionality test was employed to ascertain the direction of causality.

Results: Univariable MR identified nominal associations between chronotype and higher risk of acute lymphoblastic leukaemia (OR = 2.15, P = 0.014) and chronic myeloid leukaemia (OR = 1.27, P = 0.016), as well as between short sleep duration and lower lymphoid leukaemia risk (OR = 0.06, P = 0.035). However, none remained significant after FDR correction. Sensitivity analyses revealed no evidence of heterogeneity or horizontal pleiotropy. Adjusting for smoking and BMI in multivariable MR abolished all associations. Colocalization suggested shared genetic variants, but reverse MR indicated a significant effect only from acute lymphoblastic leukaemia to chronotype (P_FDR = 0.0017).

Conclusions: Our MR study found several nominal associations that sleep traits causally influence leukaemia subtypes. Nominal associations were not significant after multiple testing correction, attenuated by adjustment for smoking and BMI, and potentially affected by pleiotropy or reverse causation.

Background: B-cell acute lymphoblastic leukemia (B-ALL) is an aggressive hematological malignancy. Long non-coding RNAs (lncRNAs) play important roles in hematological diseases; nevertheless, their mechanistic contributions to B-ALL are still poorly defined.

Purpose: This study aimed to investigate the oncogenic role of HOTAIR and the regulatory mechanism underlying the progression of B-ALL via the HOTAIR/miR-326/IGF-1R axis.

Methods: The expression levels of HOTAIR and miR-326 were quantified by RT-qPCR in peripheral blood mononuclear cells (PBMCs) from B-ALL patients. CCK-8, EdU, and TUNEL assays were employed to evaluate cell viability, proliferation, and apoptosis, respectively. Dual-luciferase reporter assays were performed to verify molecular interactions, and Western blotting was performed to detect the activation of the PI3K/AKT signaling pathway.

Results: HOTAIR was prominently upregulated in patient-derived PBMCs, correlating with enhanced proliferation and suppressed apoptosis. Mechanistically, HOTAIR directly targeted miR-326 binding sites and regulated the expression of IGF-1R. Experiments affirmed that overexpression of miR-326 or knockdown of IGF-1R reversed the oncogenic effects induced by HOTAIR. Furthermore, silencing of HOTAIR decreased PI3K/AKT phosphorylation, indicating pathway dependence.

Conclusion: HOTAIR promotes the progression of B-ALL via the miR-326/IGF-1R axis and PI3K/AKT activation, suggesting its potential as a therapeutic target.

Background and objectives: The phase angle, which is associated with cellular health, has garnered increasing attention as a noninvasive and objective method for nutritional assessment. However, the association between malnutrition and phase angle in patients with acute myeloid leukemia remains unreported. Therefore, this study investigated this association in patients with acute myeloid leukemia and established a cut-off phase angle for identifying malnutrition.

Methods and study design: This cross-sectional study retrospectively analysed the data of 74 inpatients with acute myeloid leukemia (66.21% male; mean age, 52.68 ± 16.31 years). Nutritional status was assessed via the Patient-Generated Subjective Global Assessment (PG-SGA). Bioelectrical impedance analysis was employed to measure phase angles.

Results: The phase angle was negatively associated with malnutrition (B = -0.436; p < 0.001). Logistic regression analysis revealed that a low skeletal muscle index (SMI) (p = 0.016, OR = 5.021, 95% CI 1.347-18.716) and hemoglobin deficiency (p = 0.009, OR = 6.133, 95% CI 1.582-23.770) were risk factors for a low phase angle (PA) in acute myeloid leukemia inpatients. The area under the receiver operating characteristic (ROC) curve was 0.705. The cut-off phase angle for identifying malnutrition was 3.65° (sensitivity, 0.926; specificity, 0.553).

Conclusions: The phase angle may serve as a supplementary indicator of malnutrition in inpatients with acute myeloid leukemia, particularly when the Nutritional Risk Screening 2002 (NRS-2002) is not feasible. These findings may aid in the formulation of nutritional strategies for these patients.

Background: Hypoplastic myelodysplastic syndrome (hMDS) is an uncommon MDS subtype, accounting for approximately 10-15% of cases, characterized by bone marrow hypocellularity, severe cytopenias, and features of immune dysregulation. Its clinical course overlaps with aplastic anemia, yet optimal management for lower-risk patients remains undefined, particularly in Asian populations.

Methods: We retrospectively analyzed 48 patients with lower-risk hMDS (IPSS-R very low/low/intermediate) treated at Tianjin Medical University General Hospital from 2013 to 2021. Patients received cyclosporine A (CsA, n = 16), hypomethylating agents (HMAs, n = 10), low-dose HMAs (LD-HMAs, n = 11), or best supportive care (BSC, n = 11). Responses were assessed by modified IWG criteria, and survival was evaluated by Kaplan-Meier and Cox regression analyses.

Results: Median age was 61 years (range 16-84), with 60.4% male. Somatic mutations were present in 64.6%, and PNH clones in 29.2%. Six-month overall response rates were 75.0% for CsA, 70.0% for HMAs, 54.5% for LD-HMAs, and 36.4% for BSC (p = 0.220). CsA achieved significantly longer complete remission (median 75 months) and hematologic improvement durations (p < 0.05). Median overall survival (OS)/progression-free survival (PFS) for CsA were 78.0/76.0 months, compared with 17.0/6.8 for HMAs, 31.0/15.0 for LD-HMAs, and 36.0/15.0 for BSC (p < 0.01). HMAs were associated with increased grade 3-4 infections.

Conclusion: CsA provides superior response durability, survival outcomes, and safety compared with other approaches, supporting its use as first-line therapy in lower-risk hMDS. Integration of immune and molecular profiling may refine individualized treatment strategies.

Introduction: Blood is vital for life, but ensuring a safe and sufficient supply remains a public health challenge, particularly in low-resource settings. This study explores the knowledge, attitudes, practices, and factors influencing blood donation among pre-service teacher trainees at Finote Selam College of Education, Northwest Ethiopia.

Methods: A cross-sectional survey was conducted using proportionate sampling. Data were collected through questionnaires completed by the participants themselves and analyzed using SPSS version 27, with results presented in descriptive narratives and tables.

Results: Of 277 participants, 27.8% were male and 72.2% female. While 55.6% demonstrated adequate knowledge of blood donation and 42.2% had a positive attitude, only 28.2% had ever donated blood. Key factors influencing donation practices included knowledge, attitude, academic department, and religious affiliation.

Conclusion: Although participants had reasonable knowledge of blood donation, positive attitudes and actual donation rates were low. Department-specific awareness programs and regular donation drives, in partnership with health institutions, could enhance donation rates and foster social responsibility among future educators.

Objective: This review aims to summarize current progress in targeted therapy for acute myeloid leukemia (AML) with KMT2A rearrangement (KMT2Ar). This subtype of AML often shows resistance to chemotherapy and has a poor prognosis. The purpose is to emphasize potential therapeutic strategies and explore drugs currently under clinical development. Methods: We reviewed studies on the molecular characteristics of KMT2Ar AML and examined targeted drugs that can block key genetic and epigenetic mechanisms. Information on drug mechanisms, preclinical findings, and clinical trials was collected and analyzed.

Results: Several new agents targeting KMT2A-related pathways are being explored. Menin inhibitors show encouraging clinical activity, while other inhibitors, such as those targeting DOT1L, BET, and EZH2, have produced promising preclinical results. Early data suggest that combination therapy may be more effective in overcoming drug resistance than monotherapy.

Discussion: Providing a new therapeutic direction for the abnormal molecular networks in KMT2Ar AML offers a promising approach. However, most therapies are still in the early stages and clinical translation is limited. Further research is needed to improve the safety and long-term efficacy of the treatment.

Conclusion: There is an urgent need for effective targeted drugs for KMT2Ar AML. Continuous research and clinical trials will be key to improving patient prognosis and advancing precise treatment for this challenging leukemia subtype.

Objectives: To investigate the clinical significance of Fluorescence in situ hybridization (FISH) in detecting aberration of chromosome 5, 7, or 17 in newly diagnosed acute myeloid leukemia (AML) patients.

Methods: We retrospectively evaluated the clinical features and outcomes of 77 adult newly diagnosed AML patients with 5/5q, 7/7q, or 17/17p loss detected by either FISH or conventional karyotype.

Results: Among 77 patients, all (100%) were identified by FISH, while only 47 (61%) were positive with conventional karyotype. Patients with FISH-positive displayed similar age at onset, gender, WBC, and gene mutation spectrum with those identified by karyotype. In FISH-positive but karyotype-negative group, the 3-year OS and EFS were 28.9% and 23.9%, respectively, which were similar to 29.1% and 21% with FISH-positive and karyotype-positive (P = 0.59 and 0.48). When comparing the outcomes of patients with or without hematopoietic stem cell transplantation (HSCT), both groups of patients with and without HSCT showed similar outcomes. Patients underwent HSCT with 3-year OS at 76.2% in FISH and 64.3% in FISH-positive and karyotype-positive group (P = 0.66), while patients without HSCT had 3-year OS at 33.3% and 39% (P = 0.63), respectively.

Conclusion: Overall, patients with 5, 7, or 17 chromosomal abnormalities identified by either FISH or karyotype have similar clinical characteristics and outcomes. FISH could supplement to conventional karyotype for detecting aberration of chromosome 5, 7, or 17 in newly diagnosed AML.

Objectives: Prior research has highlighted immune cells' critical role in multiple myeloma (MM) pathogenesis, yet the causal relationships between them have remained obscure.

Methods: We utilized data from genome-wide association studies (GWAS) of European cohorts to conduct a Mendelian Randomization (MR) analysis, aiming to establish causal links between immune cell phenotypes and MM. We selected single nucleotide polymorphisms (SNPs) associated with immune cell traits at a suggestive significance threshold (P < 1 × 10^-5) to ensure sufficient instrumental variables, with F-statistics (>10) calculated to assess instrument strength. Multiple MR methods were applied to 731 immune phenotypes and MM.

Results: Eight immunophenotypes showed nominal associations with MM risk (P < 0.05). However, no associations survived the strict Bonferroni correction for multiple testing. Suggestive causal effects of MM on immunophenotypic traits are predominantly negative, implying that MM may impair the functionality of immune cells.

Discussion: This study uses GWAS data to elucidate the genetic impact of immune cells on the initiation and progression of MM. It presents genetic evidence suggesting that immune cells could alter MM risk based on a thorough genetic analysis. Bidirectional two-sample MR identified eight distinct immunophenotypes (encompassing four immune signatures: MFI, RC, AC, MP) with causal effects on MM.

Conclusion: Our study provides preliminary evidence for potential causal links between specific immune traits and MM risk. Independent replication in larger cohorts and functional validation are warranted given the nominal significance of these associations, which may inform future immunotherapeutic investigations. These findings contribute to a better understanding of the complex immune - MM interplay and may guide future investigations into immunotherapeutic approaches.

Objective: To explore the application efficacy of the UK Myeloma Alliance Risk Stratification (MRP) and the Simplified Frailty Index (FI) in patients with newly diagnosed multiple myeloma (NDMM).

Methods: 205 NDMM patients diagnosed in our hospital from 1 July 2014 to 1 July 2022; frailty was assessed using MRP and Simplified FI. The Fine-Gray competing risk model compared the cumulative incidence of early grade ≥3 infections. Kaplan-Meier method and the log-rank test were applied for analyzing OS and PFS. ROC curves, AUC values, and Youden's index were used to compare the predictive values for OS, PFS, and early grade ≥3 infections. P < 0.05 indicated statistical significance.

Results: The frail groups by MRP and the Simplified FI had significantly shorter OS (36 vs. 75 months and 38 vs. 76 months) and PFS (11 vs. 21 months and 11 vs. 23 months; P < 0.001) with increased mortality risk (HR: 2.51 and 2.12). One-year mortality was significantly higher in frail patients (P < 0.005). The common frail group showed the poorest outcomes, but without significant difference from individual frailty groups (P > 0.05). Frail patients by both showed higher rates of early grade ≥3 infections, but there was no statistically significant difference (50.6% vs. 37.9% and 45.76% vs. 41.78%, P > 0.05). Regarding predictive performance, both tools effectively predicted OS and PFS (all P < 0.05). For early infections, MRP was not predictive (P = 0.237) whereas FI was (P = 0.012), though their predictive performance did not differ significantly (P > 0.05).

Conclusion: Both MRP and FI are effective frailty assessment tools in NDMM patients. They significantly correlate with OS, PFS.