Mediterranean Journal of Hematology and Infectious Diseases最新文献

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.

Background: Hepatitis B virus (HBV) infection leads to liver fibrosis. Although liver biopsy remains the gold standard for diagnosis, its invasive nature limits routine application. Serum interleukin-34 (IL-34), which plays a role in macrophage activation and fibrogenesis, and shear wave elastography (SWE), a non-invasive method for measuring liver stiffness, represent potential diagnostic alternatives. This study compared the accuracy of IL-34 and SWE with liver biopsy findings in treatment-naive patients with chronic hepatitis B (CHB).

Material and methods: Between 2021 and 2022, 392 treatment-naive patients with CHB who were evaluated for liver biopsy were screened, and 105 eligible patients were prospectively enrolled in the study. Liver fibrosis was assessed by concurrently comparing SWE and IL-34 levels with histopathological biopsy findings.

Results: Of the 105 included patients (55% male; mean age 42.97 years), median IL-34 levels were significantly higher in those with fibrosis ≥2 than in patients with fibrosis 0-1 (10.70 vs. 6.20 pg/mL, p<0.001). ROC analysis identified optimal cut-off values of 8.1 pg/mL for IL-34 (AUC=0.955, sensitivity=88.2%, specificity=86.4%) and 8.18 kPa for SWE (AUC=0.939, sensitivity=100%, specificity=87.5%) for predicting significant fibrosis.

Conclusion: IL-34 and SWE exhibit high diagnostic performance as non-invasive methods for assessing liver fibrosis in CHB patients. The integration of these approaches into clinical practice may significantly reduce the need for biopsy and, due to their repeatability and lower cost, provide substantial advantages in patient management. This study is limited by its single-center design and the small number of cases with advanced fibrosis, which may affect its generalizability. Larger multicenter studies are warranted to validate these findings.

Plasma cell leukemia (PCL) is a rare and aggressive form of multiple myeloma (MM), characterized by the presence of malignant plasma cells in the peripheral blood. Until 2021, PCL was defined as plasmacytosis comprising at least 20% of the differential white blood cell count in peripheral blood. (CPCs). PCL was found in 2-4% of newly diagnosed MM cases. It can also develop from a preexisting, usually end-stage, MM, known as secondary PCL (sPCL), which exhibits distinct biological and clinical features. Both primary plasma cell leukemia (pPCL) and secondary plasma cell leukemia (sPCL) are very rare presentations of MM. According to the International Myeloma Working Group, plasma cell leukemia is generally diagnosed when the percentage of CPCs in peripheral blood exceeds 5%. PCL has a more aggressive clinical presentation than MM, involving more severe cytopenia, hypercalcemia, and renal failure. Higher tumor burden and proliferation activity in PCL are reflected by elevated levels of B2- B2-microglobulin and lactate dehydrogenase (LDH). Extramedullary localization at diagnosis is more common in pPCL and sPCL than in MM. Conversely, osteolytic lesions are less frequent in pPCL. The immunophenotype of PCL expresses the common MM markers, CD38 and CD138, but exhibits a more immature phenotype than MM. Molecularly, PCL lacks a specific marker but shows a markedly lower frequency of hyperploidy and significantly increased gains of chromosome 1 and translocations t(14;16) or t(14;20). Additionally, it has also been reported that the t(11;14) translocation occurs more frequently and is associated with a better prognosis. The recent therapy of PCL is similar to that of other high-grade myelomas, taking advantage of anti-proteasome, like bortezomib, an immunomodulator, like lenalidomide, and dexamethasone triplet + anti-CD38 antibody and/or cyclophosphamide, and hematopoietic stem cell transplantation. However, the results are not as good as in the other forms of myeloma.

Background: This study aimed to explore the role of SLC22A4 (encoding the organic cation transporter OCTN1) in acute myeloid leukaemia (AML) prognosis and therapy. Methods: RNA-sequencing data from 151 TCGA-AML samples and six Gene Expression Omnibus datasets (62 normal bone marrow and 520 AML samples) were analysed. Weighted gene co-expression network analysis identified immune-related gene modules. Differential expression analysis, survival analysis (Kaplan-Meier, Cox regression), methylation profiling, immune infiltration (xCell, EPIC), and drug sensitivity correlations were performed. Statistical methods included Wilcoxon rank-sum tests, ROC curves, and LASSO regression.

Results: SLC22A4 expression was significantly decreased in AML compared with normal samples. The high-expression group was associated with a better prognosis than the low-expression group. Gene set enrichment analysis revealed enrichment in metabolic transport, immune, and tumour-related pathways. SLC22A4 expression was negatively correlated with immune cells, and methylation of SLC22A4 was significantly negatively correlated with expression. Moreover, it was predicted that 5 miRNAs could regulate SLC22A4 expression. Drug-sensitivity analysis showed positive correlations with cyclobenzaprine, hydrochloride, SGX-523, and simvastatin, and negative correlations with fluorouracil, abexinostat, EMD-534085, hypothemycin, tamoxifen, and sunitinib.

Conclusion: SLC22A4 may be useful as a potent molecular-targeted agent in AML.

Iron is required for several vital biological processes in all human cells. In mammals, a considerable number of proteins are involved in iron metabolism and utilize iron in many essential cellular processes, such as oxygen transport, mitochondrial respiration, gene regulation, and DNA synthesis or repair. Iron metabolism is a complex system finely regulated at both systemic and cellular levels. It involves the development of specialized mechanisms for iron absorption, transport, recycling, storage, and export, and protection against toxic compounds that can be generated during iron redox cycling in the presence of oxygen. The erythropoietic compartment consumes the majority of iron to support the high demand for hemoglobin synthesis. A tightly regulated system enables efficient iron uptake by erythroid cells and its subsequent processing for the synthesis of large amounts of heme, which is then incorporated into hemoglobin. A bidirectional regulatory system between erythropoiesis and iron metabolism ensures precise coordination between the two processes. This regulation is often disrupted in various anemic conditions.