Long-term treatment with deferiprone enhances left ventricular ejection function when compared to deferoxamine in patients with thalassemia major

Transfusion and iron chelation treatment have significantly reduced morbidity and improved survival of patients with thalassemia major. However, cardiac disease continues to be the most common cause of death. We report the left-ventricular ejection fraction, determined by echocardiography, in one hundred sixtyeight patients with thalassemia major followed for at least 5 years who received continuous monotherapy with deferoxamine (N = 108) or deferiprone (N = 60). The statistical analysis, using the generalized estimating equations model, indicated that the group treated with deferiprone had a significantly better left-ventricular ejection fraction than did those treated with deferoxamine (coefficient 0.97; 95% CI 0.37; 1.6, p = 0.002). The heart may be particularly sensitive to iron-induced mitochondrial damage because of the large number of mitochondria and its low level of antioxidants. Deferiprone, because of its lower molecular weight, might cross into heart mitochondria more efficiently, improving their activity and, thereby, myocardial cell function. Our findings indicate that the long-term administration of deferiprone significantly enhances left-ventricular function over time in comparison with deferoxamine treatment. However, because of limitations related to the design of this study, these findings should be confirmed in a prospective, randomized clinical trial

Serial echocardiographic left ventricular ejection fraction measurements: a tool for detecting thalassemia major patients at risk of cardiac death

Cardiac damage remains a major cause of mortality among patients with thalassemia major. The detection of a lower cardiac magnetic resonance T2* (CMR-T2*) signal has been suggested as a powerful predictor of the subsequent development of heart failure. However, the lack of worldwide availability of CMR-T2* facilities prevents its widespread use for follow-up evaluations of cardiac function in thalassemia major patients, warranting the need to assess the utility of other possible procedures.In this setting,the determination of left ventricular ejection fraction (LVEF)offers an accurate and reproducible method for heart function evaluation. These findings suggest a reduction in LVEF≥7%, over time, determined by 2-D echocardiography, may be considered a strong predictive tool for the detection of thalassemia major patients with increased risk of cardiac death. The reduction of LVEF≥7% had higher (84.76%) predictive value. Finally, Kaplan–Meier survival curves of thalassemia major patients with LVEF≥7% showed a statistically significant decreased probability of survival for heart disease (p=0.0022). However, because of limitations related to the study design, such findings should be confirmed in a large long-term prospective clinical trial

Re-irradiation with carbon ion radiotherapy for pelvic rectal cancer recurrences in patients previously irradiated to the pelvis

Background/Aim: Re-irradiation of locally recurrent rectal cancer poses challenges due to the proximity of critical organs, such as the bowel. This study aimed at evaluating the safety and efficacy of re-irradiation with Carbon Ion Radiotherapy (CIRT) in rectal cancer patients with local recurrence. Patients and Methods: Between 2014 and 2018, 14 patients were treated at the National Center of Oncological Hadrontherapy (CNAO Foundation) with CIRT for locally recurrent rectal cancer. Results: All patients concluded the treatment. No G≥3 acute/late reaction nor pelvic infections were observed. The 1-year and 2-year local control rates were, 78% and 52%, respectively, and relapse occurred close to the bowel in 6 patients. The 1-year and 2-year overall survival rates were 100% and 76.2% each; while the 1-year and 2-year metastasis free survival rates were 64.3% and 43%. Conclusion: CIRT as re-irradiation for locally recurrent rectal cancer emerges as a safe and valid treatment with an acceptable rate of morbidity of surrounding healthy tissue

Scaling of the buckling transition of ridges in thin sheets

When a thin elastic sheet crumples, the elastic energy condenses into a network of folding lines and point vertices. These folds and vertices have elastic energy densities much greater than the surrounding areas, and most of the work required to crumple the sheet is consumed in breaking the folding lines or ``ridges''. To understand crumpling it is then necessary to understand the strength of ridges. In this work, we consider the buckling of a single ridge under the action of inward forcing applied at its ends. We demonstrate a simple scaling relation for the response of the ridge to the force prior to buckling. We also show that the buckling instability depends only on the ratio of strain along the ridge to curvature across it. Numerically, we find for a wide range of boundary conditions that ridges buckle when our forcing has increased their elastic energy by 20% over their resting state value. We also observe a correlation between neighbor interactions and the location of initial buckling. Analytic arguments and numerical simulations are employed to prove these results. Implications for the strength of ridges as structural elements are discussed.Comment: 42 pages, latex, doctoral dissertation, to be submitted to Phys Rev

Distribution of killer cell immunoglobulin-like receptors genes in the Italian Caucasian population

BACKGROUND: Killer cell immunoglobulin-like receptors (KIRs) are a family of inhibitory and activatory receptors that are expressed by most natural killer (NK) cells. The KIR gene family is polymorphic: genomic diversity is achieved through differences in gene content and allelic polymorphism. The number of KIR loci has been reported to vary among individuals, resulting in different KIR haplotypes. In this study we report the genotypic structure of KIRs in 217 unrelated healthy Italian individuals from 22 immunogenetics laboratories, located in the northern, central and southern regions of Italy. METHODS: Two hundred and seventeen DNA samples were studied by a low resolution PCR-SSP kit designed to identify all KIR genes. RESULTS: All 17 KIR genes were observed in the population with different frequencies than other Caucasian and non-Caucasian populations; framework genes KIR3DL3, KIR3DP1, KIR2DL4 and KIR3DL2 were present in all individuals. Sixty-five different profiles were found in this Italian population study. Haplotype A remains the most prevalent and genotype 1, with a frequency of 28.5%, is the most commonly observed in the Italian population. CONCLUSION: The Italian Caucasian population shows polymorphism of the KIR gene family like other Caucasian and non-Caucasian populations. Although 64 genotypes have been observed, genotype 1 remains the most frequent as already observed in other populations. Such knowledge of the KIR gene distribution in populations is very useful in the study of associations with diseases and in selection of donors for haploidentical bone marrow transplantation

Retrospective multicenter study on ‘real life’ experience on the use of two different hexavalent vaccines in 5 local health authorities of the sicilian region from 2016 to 2019

Background and Objective: Hexavalent vaccination (HV) is a priority for protecting infants against six potentially deadly infectious diseases. In Italy, Europe and recently in the U.S. there are three commercially authorised vaccines. HV is currently used in a primary immunisation regimen with three doses (3-5-11 months). A retrospective clinical study was conducted in Sicily, Italys fourth-most populated region (10% of national population and 9% of all newborns), in order to evaluate real life data on HV during 2016-2019. Methods: Data on the completion of the administration of HV, on interchangeability between the two vaccines that alternated between 2016 and 2019 (Infarix Hexa ®- Vaxelis ®), on use above the established age and on co-administration with Rotavirus and Pneumococcus vaccines were investiganted in five Local Health Unit of the Sicilian Region. Scientific coordination was in charge to the Clinical Epidemiology Unit of the University Hospital (UH) of Palermo, through a questionnaire approved by the ethics committee of the same UH. Results: Data collected from the LHUs of Agrigento, Catania, Palermo, Ragusa and Trapani, constituting 72.5% of the Sicilian population, showed an average of 91.5% completion of the HV cycle at 24 months of age. The average age of administration gradually increased in children who switched between the two vaccines compared to those who completed the vaccination cycle with the same product. Interchangeability with one or two doses of hexavalent was documented in 17.8% (2018) and 16% (2019) of infants. Co-administration was 93% with the 13-valent conjugate anti-pneumococcal vaccine and 70% with the anti-rotavirus vaccine. Conclusions: This retrospective analysis could contribute to demonstrate safety and sustainability of the interchangeability between different types of the same HV, helping Public Health Authorities to manage potential disruptions due to missed routine immunization opportunities pandemic-related or change of vaccines due to National or Regional tender