Eculizumab treatment: stochastic occurrence of C3 binding to individual PNH erythrocytes

C5 blockade by eculizumab prevents complement-mediated intravascular hemolysis in paroxysmal nocturnal hemoglobinuria (PNH). However, C3-bound PNH red blood cells (RBCs), arising in almost all treated patients, may undergo extravascular hemolysis reducing clinical benefits. Despite the uniform deficiency of CD55 and of CD59, there are always two distinct populations of PNH RBCs, with (C3+) and without (C3-) C3 binding

Identification and molecular characterization of a novel 55 kb deletion recurrent in Southern Italy: the Italian (G) γ((A) γδβ)°-thalassemia

OBJECTIVES: To characterize the molecular basis of a β-thalassemia defect in subjects with mild microcytosis associated with normal Hb A2 and increased levels of Hb F. METHODS: Six subjects from 3 apparently unrelated families from Campania (Southern Italy) have been investigated by using DNA restriction analysis, Inverse PCR, cloning, sequencing, Multiplex ligation-dependent probe amplification (MLPA), quantitative Real Time PCR, gap-PCR. RESULTS: We have identified a novel 55 kb β-globin gene cluster deletion in three unrelated families: the Italian (G) γ((A) γδβ)°-thalassemia. This deletion removes most of β-globin cluster. The 5' breakpoint was within the (A) γ-globin exon 2 and the 3' breakpoint was within a 160 bp palindrome: the breakpoint-flanking regions present a micro-homology (5'-TGGG-3') that, together with the palindromic structure, may have contributed to the recombination. CONCLUSIONS: Large deletions of β-globin gene cluster are usually found in single families. Here we report about the novel Italian (G) γ((A) γδβ)°-thalassemia we have found in three families. Twenty years ago the characterization of the first family was challenging, whereas that of the other families has taken advantage of nowadays techniques. The relatively high frequency of this novel deletion in Southern Italy suggests that it should be tested, together with the Sicilian (δβ)°-thalassemia, in Italian and Mediterranean families with microcytosis, normal Hb A2 and increased Hb F levels

Ischemic stroke. Clinical pathway impact

Purpose: A clinical pathway for patients with acute ischemic stroke was implemented in 2014 by one Italian teaching hospital multidisciplinary team. The purpose of this paper is to determine whether this clinical pathway had a positive effect on patient management by comparing performance data. Design/methodology/approach: Volume, process and outcome indicators were analyzed in a pre-post retrospective observational study. Patients’ (admitted in 2013 and 2015) medical records with International Classification of Diseases, ICD-9 code 433.x (precerebral artery occlusion and stenosis), 434.x (cerebral artery occlusion) and 435.x (transient cerebral ischemia) and registered correctly according to hospital guidelines were included. Findings: An increase context-sensitive in-patient numbers with more severe cerebrovascular events and an increase in patient transfers from the Stroke to Neurology Unit within three days (70 percent, p=0.25) were noted. Clinical pathway implementation led to an increase in patient flow from the Emergency Department to dedicated specialized wards such as the Stroke and Neurology Unit (23.7 percent, p<0.001). Results revealed no statistically significant decrease in readmission rates within 30 days (5.7 percent, p=0.85) and no statistically significant differences in 30-day mortality. Research limitations/implications: The pre-post retrospective observational study design was considered suitable to evaluate likely changes in patient flow after clinical pathway implementation, even though this design comes with limitations, describing only associations between exposure and outcome. Originality/value: Clinical pathway implementation showed an overall positive effect on patient management and service efficiency owing to the standardized application in time-dependent protocols and multidisciplinary/integrated care implementation, which improved all phases in acute ischemic stroke care