Mediterranean Journal of Hematology and Infectious Diseases最新文献

Sickle cell disease (SCD) is a genetic disease of public health concern. Adult patients face various disease-related complications, which affect their quality of life (QoL). Few studies have examined relationships between these events and health-related (HR) QoL. We conducted a study of 240 adults with SCD seen in steady state at a routine clinic visit over one year. Two self-administered questionnaires were used to determine patients' HRQoL: the sickle cell self-efficacy scale (SCSES) comprising 9 specific items and the unspecific SF-36 scoring system comprising 8 subscales, which construct the physical component summary (PCS) and the mental component summary (MCS). Factors impacting HRQoL were established using univariate and multivariate regression analyses. Participants had a median age of 28 years (Sex ratio male/female 0.61; 68% SS genotype). Most of them had experienced more than one SCD-related complication and more than one affected organ system. A good correlation was established between the SCD-specific and the unspecific scoring systems (p < 0.0001). Using the SF-36 scoring system, energy/fatigue, general health, and pain subscales showed the lowest median scores (50, 45, and 56.5, respectively), while physical functioning had the highest median score (75). In univariate and multivariate analyses, hospitalization for SCD complications occurring during the last year preceding QoL evaluation was the main feature impacting HRQoL (p < 0.001). Good compliance to hydroxyurea (HU) therapy was associated with higher SCSES (p = 0.04) and higher emotional role functioning (p = 0.03) scores. The recent occurrence of severe SCD complications mainly influenced HRQoL. Our study suggests that a more effective treatment through better compliance with HU therapy would provide benefit in terms of QoL.

Syphilis, a sexually transmitted infection caused by Treponema pallidum (T. pallidum), is re-emerging globally. Recent epidemiological data show a rising incidence, particularly among men who have sex with men (MSM). Known as 'the great mimic' for its broad clinical spectrum, secondary syphilis classically presents with a maculopapular rash involving the trunk and extremities. However, it can also present with atypical cutaneous manifestations, especially in immunocompromised patients. This aspect may contribute to delayed diagnosis and treatment. Starting from a clinical case, we will conduct a literature review on syphilis/HIV coinfection, with a particular focus on the broad spectrum of cutaneous manifestations and the key differential diagnoses involved. We report the case of a 60-year-old male living with HIV who presented with non-pruritic, polymorphic skin lesions sparing the palms and soles. The patient had a prior history of treated latent syphilis. Initial diagnostic workup excluded common differentials, including monkeypox and fungal infections. Serologic testing confirmed active syphilis with a reactive Rapid Plasma Reagin (RPR) titer of 1:32, skin biopsy showed dense plasma cell-rich infiltrate, and immunohistochemistry was positive for T. pallidum. Despite negative cerebrospinal fluid findings, neurological symptoms prompted treatment with intravenous penicillin G, and the symptoms resolved with treatment. This case underscores the importance of considering syphilis in the differential diagnosis of atypical dermatologic presentations, given its increasing prevalence and potential for severe systemic involvement.

Background: Thalassemia is an inherited blood disorder characterized by abnormal hemoglobin production, leading to chronic anemia. Patients, particularly those who are transfusion-dependent, face a heightened risk of infections due to disease-related factors like anemia and treatment-related complications such as iron overload and splenectomy. This study explores the factors contributing to infections in thalassemia patients to improve management strategies.

Methods: A retrospective analysis was conducted on 303 patients with thalassemia at a tertiary care center from 2007 to 2022. Data were collected on demographics, transfusion dependency, splenectomy status, ferritin levels, vaccination history, and culture results. Logistic regression analysis was used to identify infection risk factors, with significance set at p-value < 0.05.

Results: Out of 303 patients, 72 (23.8%) experienced culture-positive infections, with Escherichia coli being the most isolated pathogen. Patients with infections had significantly higher ferritin levels and were less likely to be on chelation therapy. Chelation therapy was significantly associated with a reduced risk of infection (OR 0.18, p < 0.001). Higher serum albumin levels were also associated with lower odds of infection (OR 0.92, p < 0.001). Mortality was significantly higher among patients with positive cultures compared to those without (22% vs. 3%, p < 0.001).

Conclusion: This study highlights the strong link between iron overload, chelation, and risk of infection in thalassemia patients. Effective management, including proper chelation therapy and monitoring ferritin levels, is critical for reducing infections and improving outcomes. Further studies are needed to confirm these findings and guide future management strategies.

Invasive fungal infections (IFIs) mostly affect immunocompromised hosts and are responsible for high rates of complications and mortality. Prevalence of IFIs has been reported between 7 and 15% and is evolving due to the introduction of new drugs in the prophylaxis of high-risk patients. Invasive candidiasis has become less frequent, while cases of aspergillosis are increasing. The most important risk factors for IFIs can be divided into 3 categories: those related to the hematological neoplasm, those related to the patient's lifestyle, and those dictated by the transplant characteristics. In high-risk patients, prophylaxis is driven by both local epidemiology and the timing of engraftment. During the pre-engraftment period, a wide spectrum of drugs can be chosen as antifungals, while in the post-engraftment period, posaconazole is recommended for patients presenting with GvHD who are undergoing immunosuppression. Regarding treatment, voriconazole is still the recommended drug for invasive aspergillosis, although adverse events, toxicity, and drug interactions are particularly relevant. In the management of IFIs, international guidelines recommend the best drugs for prophylaxis and treatment, but the future holds new molecules that are already demonstrating excellent efficacy and tolerability.

Background: Elderly patients with relapsed acute myeloid leukemia (AML) have limited treatment options and a poor prognosis. Venetoclax combined with azacitidine has shown promising activity in newly diagnosed or relapsed/refractory AML, but real-world data on older populations remain scarce. This study aimed to evaluate the efficacy, safety, and prognostic factors - including select blood biomarkers - of venetoclax plus azacitidine in elderly patients with relapsed AML.

Methods: We conducted a single-center retrospective review of patients aged ≥65 years diagnosed with relapsed AML who received venetoclax plus azacitidine between January 2018 and December 2022. Patient demographics, baseline disease characteristics, and treatment details were collected. Blood biomarkers, such as lactate dehydrogenase (LDH), C-reactive protein (CRP), and selected molecular markers (including FLT3-ITD and NPM1 mutations), were also assessed at baseline to evaluate their prognostic value. The primary endpoint was the overall response rate (ORR), defined as the sum of complete Remission (CR) and CR with incomplete hematologic recovery (CRi). Secondary endpoints included overall survival (OS), event-free survival (EFS), and safety. Prognostic factors were identified through univariate and multivariate analyses using Cox proportional hazards models. Survival curves were constructed via the Kaplan-Meier method.

Results: A total of 50 patients (median age, 72 years; range, 65-82) met the inclusion criteria. The ORR was 60% (40% CR and 20% CRi). The median OS was 9.2 months (95% CI: 6.8-11.5), and the median EFS was 6.0 months (95% CI: 4.2-8.3). Common Grade 3-4 adverse events included neutropenia (46%) and thrombocytopenia (32%). The 30-day treatment-related mortality rate was 4%. Elevated baseline LDH (≥ the upper limit of normal) was associated with reduced OS (p=0.03). Patients with high CRP levels and/or adverse molecular markers, such as FLT3-ITD positivity, also showed a trend toward poorer survival, which, however, did not reach statistical significance in the multivariate model. Multivariate analysis confirmed poor Eastern Cooperative Oncology Group (ECOG) performance status, baseline LDH level, and adverse cytogenetics as independent predictors of reduced OS.

Conclusion: Venetoclax combined with azacitidine demonstrated encouraging efficacy and manageable toxicity in this retrospective analysis of elderly patients with relapsed AML. Elevated LDH and adverse molecular/cytogenetic profiles were associated with worse outcomes. These findings highlight the importance of integrating blood biomarker assessment into routine evaluation and suggest venetoclax-based regimens may be a viable therapeutic option in older, relapsed AML populations. Prospective multicenter studies are warranted to confirm these results and refine patient selection.

Cuproptosis is a distinct modality of regulated cell death precipitated by an overload of intracellular copper, critically dependent on mitochondrial respiration. The underlying mechanism involves the direct interaction of copper ions with lipoylated components integral to the mitochondrial tricarboxylic acid (TCA) cycle. This binding event triggers the aggregation of these proteins, induces significant proteotoxic stress, and leads to the depletion of essential iron-sulfur cluster proteins, culminating in cell demise. Given that copper homeostasis is frequently dysregulated within cancer cells, rendering them potentially more susceptible to copper-induced toxicity, cuproptosis has rapidly become a focal point of oncological research. This systematic review meticulously analyzes and synthesizes findings from a curated collection of 45 research articles. It aims to provide a comprehensive description of the molecular intricacies of cuproptosis, explore its documented associations with a spectrum of solid tumors (including gastric, lung, liver, neuroblastoma, and ovarian cancers) and lymphoma, and examine its emerging connections with viral infections like COVID-19 and pseudorabies virus. The review elaborates on the reported prognostic significance of cuproptosis-related genes and associated pathways across various malignancies. Furthermore, it details the burgeoning therapeutic strategies designed to harness cuproptosis, encompassing the application of copper ionophores, the development of sophisticated nanomedicine platforms, and synergistic approaches that combine cuproptosis induction with immunotherapy, chemotherapy, or sonodynamic therapy. The potential clinical utility of cuproptosis-associated biomarkers for predicting patient prognosis and therapeutic response is discussed based on the evidence presented in the reviewed literature.

Bruton's tyrosine kinase inhibitors (BTKis) have reshaped the management of chronic lymphocytic leukemia (CLL). The first-generation BTKi ibrutinib demonstrated significant efficacy, leading to the development of second-generation agents (acalabrutinib, zanubrutinib) with improved selectivity and safety. However, resistance-most often driven by BTK mutations at the cysteine residue at position 481 (C481S)-remains a major therapeutic limitation. Noncovalent BTKis, such as pirtobrutinib, offer effective options for patients relapsing after covalent BTKi therapy. However, the emergence of novel resistance mutations continues to limit durable responses. As insights into the molecular basis of BTK resistance evolve, routine mutation testing is poised to become integral to personalized treatment in CLL. Future clinical trials are expected to adopt mutation-driven stratification to guide therapeutic sequencing. Ultimately, overcoming BTKi resistance will require innovative strategies, including BTK degraders, bispecific antibodies, and T cell-engaging immunotherapies.