Mediterranean Journal of Hematology and Infectious Diseases最新文献

Background: Ubiquitination affects cancer progression by regulating both tumor-suppressing and tumor-promoting proteins in cancer. The current study sought to evaluate the role of TNF receptor-associated factor 6 (TRAF6) in the malignant proliferation of the human NK/T cell lymphoma cell line HANK1.

Methods: TRAF6 and MST1 expression levels in HANK1, KHYG-1, and SNK-6 cells were determined by RT-qPCR and Western blot analysis, followed by transfection of si-TRAF6 into HANK1 cells. Cell viability and proliferation were assessed by cell-counting kit-8 and 5-Ethynyl-2'-deoxyuridine (EdU) assays, and proliferating cell nuclear antigen (PCNA) expression levels in cells were determined by Western blot analysis. After that, cells were treated with MG132, followed by analysis of the binding of TRAF6 to macrophage stimulating 1 (MST1) via co-immunoprecipitation and the ubiquitination level of MST1 via the ubiquitination assay. The functional rescue experiment was performed with si-MST1 and si-TRAF6 in cells.

Results: TRAF6 was upregulated in HANK1 cells. Inhibition of TRAF6 reduced cell viability and the number of EdU-positive cells, and downregulated PCNA expression. TRAF6 binds to MST1 to promote ubiquitination-mediated degradation of MST1. After MG132 treatment, the ubiquitination level of MST1 declined. Silencing MST1 abolished the inhibition of TRAF6 on malignant proliferation of HANK1 cells.

Conclusion: TRAF6 was upregulated in HANK1 cells and bound to MST1 to promote ubiquitination-mediated degradation of MST1, consequently facilitating the malignant proliferation of HANK1 cells.

Thromboembolic and hemorrhagic complications are significant causes of morbidity and mortality in patients with acute leukemias (AL). While AL is characterized by a complex hemostatic imbalance, conventional coagulation tests and platelet counts offer limited predictive value for bleeding and thrombotic events. Global coagulation assays (GCAs), such as the Thrombin Generation Assay (TGA), provide a more comprehensive assessment of coagulation potential and may offer improved risk stratification. This prospective, single-center pilot study aimed to explore the utility of TGA in newly diagnosed adult patients with AL. Between February 2022 and September 2024, 111 patients were enrolled at the Department of Translational and Precision Medicine, Sapienza University of Rome. Baseline clinical and laboratory data, including TGA parameters, were collected, and patients were monitored for thrombotic events until death or last follow-up. TGA values at diagnosis displayed wide inter-individual and inter-subtype variability. With a median follow-up of 8.28 months, 8 (7.2%) thrombotic events were reported. No statistically significant association was found between baseline TGA parameters and the development of thrombotic events (p > 0.05). These findings suggest that a single TGA measurement at diagnosis may not predict thrombotic risk in AL patients. Future studies incorporating longitudinal TGA assessments and additional hemostatic evaluations, such as platelet function analysis, may help refine risk prediction for both thrombotic and hemorrhagic complications in this high-risk population.

Background: Acquired immunodeficiency syndrome (AIDS) caused by human immunodeficiency virus (HIV) remains a serious public health problem. Opportunistic infections and malignancies are the more frequent causes of hospitalization. We investigated hospitalized people with HIV (PWH) over the past 12 years to determine the types and changing trends of the disease presentation in a large tertiary academic centre in Eastern China.

Methods: We evaluated a total of 2,140 hospitalized PWH from January 2010 to December 2021. Demographic, clinical, and laboratory data, as well as opportunistic infections, malignancies, and in-hospital outcomes, were collected and analyzed.

Results: Over time, the incidence of opportunistic infections has declined. Conversely, the incidence of malignancies has increased, with non-AIDS-defining cancers (NADCs) occurring more frequently than ADCs. Notably, in 2020-2021, the incidence of NADCs surpassed that of opportunistic infections, marking a novel shift in the disease spectrum. The overall in-hospital mortality rate was 8.1%, and in-hospital mortality gradually decreased over time. Opportunistic infections, malignancies, and CD4⁺ T cell count were independent predictors of in-hospital mortality.

Conclusion: Our study provided a comprehensive description of the disease characteristics of PWH in eastern China over the past 12 years. The disease spectrum of PWH has undergone tremendous changes over time, highlighting the necessity of early HIV diagnosis and broader access to optimal treatment and management strategies.

Background: Post-treatment lung destruction (LD) impairs quality of life in pulmonary tuberculosis (TB) survivors, yet early risk-stratification tools are lacking. We aimed to develop and internally validate a clinical-laboratory nomogram to predict LD at completion of standard anti-TB therapy.

Methods: In this retrospective cohort, we enrolled 205 treatment-naïve adults with pulmonary TB from April 2021 to April 2025. LD was defined on follow-up chest CT as extensive fibrosis, bronchiectasis with volume loss, or parenchymal destruction. Twenty-two baseline demographic, clinical, laboratory, and imaging variables were screened. Least absolute shrinkage and selection operator (LASSO; 10-fold cross-validation) was used for variable selection, followed by Akaike information criterion (AIC)-guided stepwise multivariable logistic regression. Model performance was compared with random forest (RF) and support vector machine (SVM) classifiers. Discrimination (area under the receiver-operating characteristic curve, AUC), calibration (bootstrap-corrected curve; Brier score), and clinical utility (decision-curve analysis, DCA) were assessed; internal validation used 1,000-sample bootstrap resampling.

Results: LD occurred in 61/205 patients (29.8%). Nine predictors-silicosis, drug resistance, symptom-to-treatment delay, lymphocyte count, C-reactive protein, aspartate aminotransferase, γ-glutamyl transferase, albumin, and baseline atelectasis/cavity-composed the final model. The nomogram showed excellent discrimination (AUC = 0.93, 95% CI 0.897-0.971; optimism-corrected AUC = 0.93) and good calibration (Brier = 0.13). Across 10-40% risk thresholds, DCA indicated a higher net benefit than treat-all or treat-none strategies. Logistic regression slightly outperformed RF (AUC = 0.91) and SVM (AUC = 0.92) while retaining interpretability.

Conclusions: An inexpensive, easily applicable nomogram integrating routine clinical and laboratory indices accurately predicts post-treatment LD in TB patients. The tool can support personalized follow-up and timely interventions, warranting external validation in multicenter prospective cohorts.

Objectives: The primary objective was to evaluate the risk of developing glucose dysregulation and diabetes mellitus over 10 years among transfusion-dependent β-thalassemia (β-TDT) patients with varying levels of fasting plasma glucose (FPG) within the normoglycemic range. The secondary objective was to identify which baseline variables were associated with a higher risk of developing abnormal fasting glucose levels in the future.

Setting: This retrospective observational study included β-TDT patients followed from January 2014 to January 2025 in three thalassemia centers: Tehran and Shiraz in Iran, and Ferrara in Italy.

Patients and results: A total of 238 β-TDT patients (age range: 10-41.9 years; 96 males and 142 females) were included in the study. Patients were categorized into three subgroups according to their fasting glycemic status during the 10 year follow-up [Group A: 93/238 β-TDT patients (39.1%) with persistent normal FPG according to the American Diabetes Association (ADA) criteria; Group B: 67/238 patients (28.1%) developed persistent impaired fasting glucose (IFG), and Group C: 78/238 patients (32.8%) developed thalassemia-related diabetes mellitus (Th-RDM)]. To determine the optimal cutoff for the risk of progressing to impaired fasting glucose (IFG) and Th-RDM at 10-year follow-up, ROC curve analyses and respective areas under the curve were analyzed. The FPG cutoff value for optimal specificity and sensitivity was established at 87.5 mg/dL. Almost all (76/78) patients who developed Th-RDM (97.4%) were diagnosed in Shiraz. At the diagnosis of Th-RDM, the multivariate linear regression model documented an association of FPG with serum ferritin level (t-stat: 2.9873; P: 0.0041) but not with the other investigated variables: age, gender, body mass index, pre-transfusional hemoglobin level, oral iron chelating agents, serum ferritin, history of splenectomy and positive family history for T1 DM and T2 DM reported at baseline. These results reinforce the main role of chronic iron burden in the etiopathogenesis of Th-RDM in β-TDT patients.

Conclusions: FPG levels at the upper end of the normal range (defined as < 100 mg/dL) in β-TDT patients with severe iron overload are associated with a significantly increased risk for developing either IFG or Th-RDM over a 10-year observational period. The identification of an FPG cutoff (87.5 mg/dL), above which the risk for future dysglycemia increases significantly, could be useful in the routine practice, urging clinicians to intensify iron chelation and monitor these patients more closely.

Background: Polatuzumab vedotin combined with rituximab, cyclophosphamide, doxorubicin, and prednisolone (PRCHP) is a new standard first-line therapy; however, patients aged >80 years were excluded from the POLARIX trial. This single-center, retrospective study evaluated the efficacy and safety of dose-attenuated PRCHP compared with those of dose-attenuated RCHOP in very elderly patients.

Methods: A total of 63 participants aged 80 years or older were treated with PRCHP, and 76 were treated with RCHOP. Propensity score matching (PSM) was performed to adjust for baseline differences in Ann Arbor stage, international prognosis index, and frailty score.

Results: After a 1:1 PSM matching, 59 patient pairs were selected (median age: 84 years). Patients were classified as fit (n= 9, 15%), unfit (n= 21, 36%), or frail (n= 29, 49%) based on their frailty scores. The overall response rate, complete response rate, overall survival, and progression-free survival (PFS) at 12 months were comparable between the dose-attenuated PRCHP and RCHOP groups. In patients with frailty, the 12-month PFS was comparable (50.9% vs. 53.7%); however, in non-frail patients, the PFS was higher in the dose-attenuated PRCHP group than that in the RCHOP group (80.8% vs. 60.1%, p=0.04). Safety profile of grade 3/4 adverse events was similar for both groups; however, peripheral neuropathy was prominent in the RCHOP group (p=0.06).

Conclusion: Despite limitations-including the retrospective design, single-center setting, small sample size, and heterogeneous dose modifications-this study suggests that dose-attenuated PRCHP offers comparable efficacy and safety to dose-attenuated RCHOP in patients aged >80 years. PFS may be prolonged in non-frail patients receiving PRCHP, with a potentially lower risk of peripheral neuropathy.