Transfusional approach in multi-ethnic Sickle Cell patients: real-world practice data from a Multicenter survey in Italy

Sickle cell disease (SCD) is a worldwide distributed hereditary red cell disorder characterized by recurrent acute vaso-occlusive crises (VOCs and anemia). Gold standard treatments are hydroxycarbamide (HC) and/or different red blood cell (RBC) transfusion regimens to limit disease progression. Here, we report a retrospective study on 1,579 SCD patients (median age 23 years; 802 males/777 females), referring to 34 comprehensive Italian centers for hemoglobinopathies. Although we observed a similar proportion of Caucasian (47.9%) and African (48.7%) patients, Italian SCD patients clustered into two distinct overall groups: children of African descent and adults of Caucasian descent. We found a subset of SCD patients requiring more intensive therapy with a combination of HC plus chronic transfusion regimen, due to partial failure of HC treatment alone in preventing or reducing sickle cell-related acute manifestations. Notably, we observed a higher use of acute transfusion approaches for SCD patients of African descent when compared to Caucasian subjects. This might be related to (i) age of starting HC treatment; (ii) patients' low social status; (iii) patients' limited access to family practitioners; or (iv) discrimination. In our cohort, alloimmunization was documented in 135 patients (8.5%) and was more common in Caucasians (10.3%) than in Africans (6.6%). Alloimmunization was similar in male and female and more frequent in adults than in children. Our study reinforces the importance of donor-recipient exact matching for ABO, Rhesus, and Kell antigen systems for RBC compatibility as a winning strategy to avoid or limit alloimmunization events that negatively impact the clinical management of SCD-related severe complications

Italian patients with hemoglobinopathies exhibit a 5-fold increase in age-standardized lethality due to SARS-CoV-2 infection.

Since the beginning of the COVID-19 pandemic, concerns have been expressed worldwide for patients with hemoglobinopathies and their vulnerability to SARS-CoV-2 infection. Data from Lebanon confirmed a role of underlying comorbidities on COVID-19 severity, but no deaths among a cohort of thalassemia patients.1 Patients with sickle cell disease (SCD) displayed a broad range of severity after SARS-CoV-2 infection, spanning from a favorable outcome unless pre-existing comorbidities (UK cohort)2 to high case mortality in US.3 History of pain, heart, lung, and renal comorbidities was identified as risk factors of worse COVID-19 outcomes by the US SECURE-SCD Registry.4 While Italy experienced a death rate in the general population among the highest in the world, preliminary data from the first wave of the pandemic showed a lower than expected number of infected thalassemia patients (updated up to April 10, 2020), likely due to earlier and more vigilant self-isolation compared to the general population.

Long-Term Outcomes with Subcutaneous C1-Inhibitor Replacement Therapy for Prevention of Hereditary Angioedema Attacks

Background For the prevention of attacks of hereditary angioedema (HAE), the efficacy and safety of subcutaneous human C1-esterase inhibitor (C1-INH[SC]; HAEGARDA, CSL Behring) was established in the 16-week Clinical Study for Optimal Management of Preventing Angioedema with Low-Volume Subcutaneous C1-Inhibitor Replacement Therapy (COMPACT). Objective To assess the long-term safety, occurrence of angioedema attacks, and use of rescue medication with C1-INH(SC). Methods Open-label, randomized, parallel-arm extension of COMPACT across 11 countries. Patients with frequent angioedema attacks, either study treatment-naive or who had completed COMPACT, were randomly assigned (1:1) to 40 IU/kg or 60 IU/kg C1-INH(SC) twice per week, with conditional uptitration to optimize prophylaxis (ClinicalTrials.gov registration no. NCT02316353). Results A total of 126 patients with a monthly attack rate of 4.3 in 3 months before entry in COMPACT were enrolled and treated for a mean of 1.5 years; 44 patients (34.9%) had more than 2 years of exposure. Mean steady-state C1-INH functional activity increased to 66.6% with 60 IU/kg. Incidence of adverse events was low and similar in both dose groups (11.3 and 8.5 events per patient-year for 40 IU/kg and 60 IU/kg, respectively). For 40 IU/kg and 60 IU/kg, median annualized attack rates were 1.3 and 1.0, respectively, and median rescue medication use was 0.2 and 0.0 times per year, respectively. Of 23 patients receiving 60 IU/kg for more than 2 years, 19 (83%) were attack-free during months 25 to 30 of treatment. Conclusions In patients with frequent HAE attacks, long-term replacement therapy with C1-INH(SC) is safe and exhibits a substantial and sustained prophylactic effect, with the vast majority of patients becoming free from debilitating disease symptoms

Gli appalti verdi nel codice dei contratti pubblici

Il saggio affronta il tema della conformazione del mercato delle commesse pubbliche alle esigenze di sostenibilità ambientale. All’analisi relativa all’evoluzione della considerazione degli aspetti ambientali nella legislazione e nella giurisprudenza comunitarie e nazionali in tema di contratti pubblici, con particolare attenzione agli strumenti a tal fine adottati in seno al nuovo codice di cui al d.lgs. n. 50/2016, segue una riflessione conclusiva che mette in luce le contraddizioni ed i potenziali rischi della sempre maggiore complessità contrattuale – necessitata proprio dalle istanze ambientaliste – sugli stessi obbiettivi di ecoefficienza

I criteri di aggiudicazione

Il contributo tratta dei criteri di aggiudicazione nel Codice dei Contratti Pubblici, in particolare del criterio del prezzo più basso e dell'offerta economicamente più vantaggiosa

Feedback effects of growth hormone on growth hormone-releasing hormone and somatostatin are not evident in aged rats

In 8- and 20-month-old male rats, treated or not with growth hormone (GH) for 4 days, simultaneous evaluation of hypothalamic GH-releasing hormone (GHRH) and somatostatin (SS) gene expression, GH secretion from anterior pituitaries (APs) in vitro (basal and GHRH-stimulated) and plasma IGF-I levels was performed. Twenty-month-old rats showed decreased GHRH mRNA levels, decreased GH secretion from APs in vitro (not responsive to GHRH stimulation) and reduced plasma IGF-I levels as compared to younger counterparts. SS mRNA levels were only slightly reduced in the hypothalamus of aged rats. Short-term administration of biosynthetic human GH (125 microgram/rat, twice daily, IP) to 8-month-old rats abolished the in vitro GHRH-stimulated GH release from APs and altered GH regulatory neuropeptides gene expression, i.e., reducing GHRH mRNA levels and increasing SS mRNA levels. In 20-month-old rats, hGH administration increased plasma IGF-I levels but did not change significantly GHRH and SS gene expression. These data indicate that the feedback effects exerted by circulating GH on GHRH and SS neurons, while evident in adult rats, are not detectable in aged rats