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Most patients with hereditary or chronic acquired anemias are dependent on regular red cell transfusions. Untreated iron overload from transfusions is responsible for morbidity and mortality in patients with thalassemia major. However, clinical consequences of parenchymal iron overload have been reported not only in thalassemia major but also in patients with myelodysplastic syndrome. The current standard in iron chelation therapy is deferoxamine mesylate (Desferal®). Deferasirox is the first oral iron chelator approved in the Europe Union for use in patients with transfusional iron overload with different diseases. The aim of this review is to examine the properties and management of Deferasirox.

The primary objective of this study was to evaluate the health-related quality of life (HRQOL) in lower-risk, transfusion-dependent patients with myelodysplastic syndromes (MDS) treated with deferasirox. A secondary objective was to investigate the relationship between HRQOL, serum ferritin levels and transfusion dependency. This was a prospective multicentre study enrolling 159 patients, of whom 152 received at least one dose of deferasirox. HRQOL was assessed with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) at baseline and then at 3, 6, 9 and 12 months. Primary analysis was performed estimating mean HRQOL scores over time by a linear mixed model on selected scales. The median age of treated patients was 72 years (range 24-87 years). No statistically significant changes over time were found in mean scores for global health status/quality of life (p=0.564), physical functioning (p=0.409) and fatigue (p=0.471) scales. Also, no significant changes were found for constipation (p=0.292), diarrhoea (p=0.815) and nausea and vomiting (p=0.643). Serum ferritin levels were not associated with HRQOL outcomes. A higher patient-reported baseline pain severity was an independent predictive factor of an earlier achievement of transfusion independence with a HR of 1.032 (99% CI 1.004 to 1.060; p=0.003). HRQOL of transfusion-dependent patients with MDS receiving deferasirox therapy remains stable over time. HRQOL assessment might also provide important predictive information on treatment outcomes. NCT00469560.

Background To evaluate the capability of basal and one-month differed white blood cells (WBC), neutrophil, lymphocyte and platelet values and their ratios (neutrophils-to-lymphocytes ratio, NLR, and platelets-to-lymphocytes ratio, PLR) in predicting the response to i mmune checkpoint inhibitors (ICI) in metastatic melanoma (MM). Methods We performed a retrospective study of 272 BRAF wild-type MM patients treated with first line ICI. Bivariable analysis was used to correlate patient/tumor characteristics with clinical outcomes. Variations between time 1 and time 0 (Δ) of blood parameters were also calculated and dichotomized using cut-off values assessed by ROC curve. Results At baseline, higher neutrophils and NLR negatively correlated with PFS, OS and disease control rate (DCR). Higher PLR was also associated with worse OS. In multivariable analysis, neutrophils (p = 0.003), WBC (p = 0.069) and LDH (p = 0.07) maintained their impact on PFS, while OS was affected by LDH (p < 0.001), neutrophils (p < 0.001) and PLR (p = 0.022), while DCR by LDH (p = 0.03) and neutrophils (p = 0.004). In the longitudinal analysis, PFS negatively correlated with higher Δplatelets (p = 0.039), ΔWBC (p < 0.001), and Δneutrophils (p = 0.020), and with lower Δlymphocytes (p < 0.001). Moreover, higher ΔNLR and ΔPLR identified patients with worse PFS, OS and DCR. In the multivariable model, only ΔNLR influenced PFS (p = 0.004), while OS resulted affected by higher ΔWBC (p < 0.001) and lower Δlymphocytes (p = 0.038). Higher ΔWBC also affected the DCR (p = 0.003). When clustering patients in 4 categories using basal LDH and ΔNLR, normal LDH/lower ΔNLR showed a higher PFS than high LDH/higher ΔNLR (20 vs 5 months). Moreover, normal LDH/higher Δlymphocytes had a higher OS than high LDH/lower Δlymphocytes (50 vs. 10 months). Conclusions Baseline and early variations of blood cells, together with basal LDH, strongly predict the efficacy of ICI in MM. Our findings propose simple, inexpensive biomarkers for a better selection of patient treatments. Prospective multicenter studies are warranted to confirm these data.

Ravulizumab is a second-generation C5i engineered from eculizumab to achieve immediate, complete, and sustained inhibition of terminal complement activity in PNH. The REACTION observational cohort study describes the effectiveness and tolerability of ravulizumab in Italian patients who were previously treated with eculizumab. Eighty-one PNH patients were enrolled in this study. The primary endpoint was the percentage change in lactate dehydrogenase (LDH) from baseline to the end of observation (52 weeks follow-up). Among secondary endpoints, transfusion avoidance, breakthrough hemolysis (BTH) and patients’ quality of life (QoL) were evaluated. The median (25–75 percentiles) percentage change in LDH at 52 weeks follow-up was -2.6 (-11.5–13.4) U/L, with 92.3% of the patients presenting LDH within or < 1.5 × upper limit of normal (ULN). Overall, 20 (25.0%) patients required transfusion during the eculizumab period and 15 (18.8%) during the ravulizumab. Seven BTH events were observed, 5 during eculizumab period and 2 (triggered by other medical conditions) during ravulizumab, suggesting the reduction of pharmacokinetic BTH during ravulizumab treatment. EORTC-QLQ-C30 and FACIT-Fatigue scores were similar to the general population, and patients’ preference indicated ravulizumab as the favorite treatment. The REACTION study confirmed the effectiveness of ravulizumab in maintaining stable disease and hemolysis control in the real-world setting. Clinical trial registration. NCT05274633, 02-Mar-2022.

Background/Objectives: Androgen deprivation therapy (ADT) is the mainstay of prostate cancer treatment, especially in advanced disease. In particular, the gonadotropin-releasing hormone agonists (aGnRH) reduce the production of gonadotropin and, therefore, of testosterone. In about 10% of patients, the non-pulsatile stimulation of GnRH receptor initially causes a surge in LH and testosterone, defined as the “flare-up phenomenon”, leading to increased bone pain, spinal cord compression, bladder outlet obstruction and cardiovascular issues. To mitigate this effect, combining a first-generation antiandrogen agent (FGA) with aGnRH is recommended. However, second-generation anti-androgens, such as apalutamide, bind selectively and irreversibly to the androgen receptor (AR), exhibiting a more efficient inhibition of the AR pathway. Methods: This is a descriptive retrospective study of 27 patients (pts) with mHSPC, treated at a single center (“Santa Maria delle Grazie” Hospital in Pozzuoli, ASL Napoli 2 Nord, Italy) between June 2022 and April 2024. Patients received apalutamide monotherapy for 14 days followed by continuous combination with aGnRH plus apalutamide. Serum PSA and testosterone levels were measured at baseline, at day 14 (after 13 days of apalutamide monotherapy), at day 28 (after an additional 15 days of apalutamide plus a aGnRH), and at day 60. Results: PSA levels decreased from a mean of 45.2 (±63.1) ng/mL at baseline to a mean of 12.6 (±23.4) ng/mL at day 14 and to 3.3 ng/mL (±6.0) at day 28 of treatment. After 14 days of apalutamide monotherapy, 21 patients (77.8%) achieved a >50% PSA reduction and 4 (14.8%) a >90% PSA reduction. The number of patients with undetectable PSA was one (3.7%) at day 14, two (7.4%) at day 28, and nine (33.3%) at day 60. The mean serum testosterone levels were 6.56 (±4.46) ng/mL at baseline, 6.58 (±4.42) ng/mL at day 14, and 2.40 (± 3.38) ng/mL at day 28. No significant difference in PSA and testosterone level reduction during treatment emerged between subgroups of patients with low- vs. high-volume disease. Conclusions: Apalutamide alone is a viable option for mitigating the flare-up phenomenon, avoiding first generation anti-androgen therapy, and it can achieve rapid and deep biochemical control.

Background Qualitative and quantitative research investigating determinants of adherence to clinical guidelines (GLs) on surgical antibiotic prophylaxis (SAP) are scarce. We conducted a mixed-method study aimed at investigating barriers and at describing attitudes of healthcare professionals (HCPs) regarding SAP in three Italian children’s hospitals. Methods The study comprised two sequential phases: 1) collection of qualitative data through focus groups; 2) conduction of a survey on HCPs attitudes towards SAP. Focus groups were carried out in each hospital with a theoretical convenience sample of 10–15 HCPs. Categorical analysis was conducted. Emerging categories and additional topics derived by literature search were used to develop the survey questionnaire, which included 13 questions expressed through a 4-point Likert scale. Members of surgical teams were invited by e-mail to fill in the questionnaire. We summed up the points assigned to each 4-point Likert scale response and calculated a cumulative score expressing overall concordance to expected HCPs attitudes on SAP. We conducted univariate and multivariate analysis to evaluate the relationship among characteristics of respondents and concordance with expected attitudes. Results The main categories identified in the qualitative phase included determinants of general adherence to GLs (e.g., relevance of clinical judgment), individual determinants (e.g., poor knowledge on hospital data) and organizational/structural determinants (e.g., patient flows). A total of 357 HCPs participated in the survey (response rate: 82.1%). Among respondents, 75% reported that SAP should be performed with first or second-generation cephalosporins, 44% that 2–3 days of antibiotic administration are useful as a precaution after surgery, 32% that SAP is needed for all surgical procedures. At multivariate analysis, professional category (physicians vs nurses; OR: 3.31; 95%CI: 1.88–5.82), and hospital (hospital 1 and 2 vs hospital 3; ORs: 2.79, 95%CI: 1.22–6.36; 2.40, 95%CI: 1.30–4.43, respectively) were significantly and independently associated with higher concordance with expected attitudes on SAP. Conclusions Results from this study were useful to identify obstacles to appropriate SAP use in children. In our setting, findings support that a quality-improvement intervention should take into account local contexts, with development of hospital policies, education on SAP recommendations, and dissemination of data on adherence to recommendations.

Purpose The use of surgical antibiotic prophylaxis (SAP) in children is poorly characterized. Our aim was to evaluate the effectiveness of a quality improvement (QI) intervention targeting SAP in children, by means of a multicenter prospective intervention study, with a before and after design. Methods We prospectively investigated elective surgical procedures performed in children <18 years, prior to the QI intervention, after the intervention and at 9-month follow-up. The primary outcomes were adherence to SAP indications and SAP appropriateness, defined considering antibiotic choice, timing of first dose and duration of administration. We compared SAP adherence and appropriateness prior the QI intervention, to the post-intervention and the follow-up. We considered patient and procedure characteristics as covariates in two logistic regression models to assess the effect of the QI intervention on SAP adherence and appropriateness. Results We collected information on 2383 procedures (pre-intervention: 784; post-intervention: 790; follow-up: 809). The QI intervention had a significant impact on the adherence to SAP indications (86.6% in the post-intervention, compared to 82.0% prior to the intervention; p  < 0.05), and on its appropriateness (35.7% compared to 19.9%; p  < 0.01). The impact of the intervention on SAP appropriateness was maintained at follow-up (38.3%; p  < 0.01 compared to pre-intervention). All components of SAP appropriateness significantly improved after the intervention and at follow-up. The logistic regression analyses confirmed the effect of intervention in improving adherence to SAP indications and appropriateness. Conclusions Following the QI intervention, there was a significant improvement in quality of SAP in pediatric surgery, though more efforts are needed to increase SAP appropriateness.