ANCA-negative EGPA: only eosinophils without vasculitis? Insights from anti-T2 biologics

The pathogenic role of p-ANCA in eosinophilic granulomatosis with polyangiitis (EGPA) is a long-standing matter of debate. In this work, we report our real-life experience with EGPA patients, treated with biologics targeting type 2 (T2)-eosinophilic inflammation (Mepolizumab, Benralizumab, Dupilumab). Interestingly, we observed EGPA extrarespiratory relapses only in p-ANCA-positive patients (2/5 cutaneous vasculitis, 3/5 constitutional symptoms), with new rise of p-ANCA and normal eosinophil blood count. Notably, revising our cohort with the new ACR 2022 criteria, these five patients were the only ones to satisfy the entry criterion of vasculitis' defined diagnosis at disease onset. These observations may suggest that biologics, selectively turning off T2 inflammation, may have unmasked p-ANCA exclusive role in the pathogenesis of vasculitis in EGPA. Therefore, we raise the question whether EGPA vasculitis exists only in p-ANCA-positive patients, and whether p-ANCA-negative disease is "only eosinophils without vasculitis"

Low-dose Oral Imatinib in the treatment of systemic sclerosis interstitial lung disease unresponsive to cyclophosphamide. A phase II pilot study

none16noFraticelli P, Gabrielli B; Pomponio, G; Valentini, G; Bosello, S; Riboldi, P; Gerosa, M; Faggioli, P; Giacomelli, R; Del Papa, N; Gerli, R; Lunardi, C; Bombardieri, S; Malorni, W; Corvetta, A; Moroncini, G; Gabrielli, A.Fraticelli P, Gabrielli B; Pomponio, G; Valentini, G; Bosello, S; Riboldi, P; Gerosa, M; Faggioli, P; Giacomelli, R; Del Papa, N; Gerli, R; Lunardi, C; Bombardieri, S; Malorni, W; Corvetta, A; Moroncini, Gianluca; Gabrielli, Armand

Safety and Efficacy of Subcutaneous Rituximab in Previously Untreated Patients with CD20+ Diffuse Large B-Cell Lymphoma or Follicular Lymphoma: Results from an Italian Phase IIIb Study

Subcutaneous (SC) rituximab may be beneficial in terms of convenience and tolerability, with potentially fewer and less severe administration-related reactions (ARRs) compared to the intravenous (IV) form. This report presents the results of a phase IIIb study conducted in Italy. The study included adult patients with CD20+ DLBCL or FL having received at least one full dose of IV RTX 375 mg/m2 during induction or maintenance. Patients on induction received ≥4 cycles of RTX SC 1400 mg plus standard chemotherapy and FL patients on maintenance received ≥6 cycles of RTX SC. Overall, 159 patients (73 DLBCL, 86 FL) were enrolled: 103 (54 DLBCL, 49 FL) completed induction and 42 patients with FL completed 12 maintenance cycles. ARRs were reported in 10 patients (6.3%), 3 (4.2%) with DLBCL and 7 (8.1%) with FL, all of mild severity, and resolved without dose delay/discontinuation. Treatment-emergent adverse events (TEAEs) and serious adverse events occurred in 41 (25.9%) and 14 patients (8.9%), respectively. Two patients with DLBCL had fatal events: Klebsiella infection (related to rituximab) and septic shock (related to chemotherapy). Neutropenia (14 patients, 8.9%) was the most common treatment-related TEAE. Two patients with DLBCL (2.8%) and 6 with FL (7.0%) discontinued rituximab due to TEAEs. 65.2% and 69.7% of patients with DLBCL and 67.9% and 73.6% of patients with FL had complete response (CR) and CR unconfirmed, respectively. The median time to events (EFS, PFS, and OS) was not estimable due to the low rate of events. At a median follow-up of 29.5 and 47.8 months in patients with DLBCL and FL, respectively, EFS, PFS, and OS were 70.8%, 70.8%, and 80.6% in patients with DLBCL and 77.9%, 77.9%, and 95.3% in patients with FL, respectively. The switch from IV to SC rituximab in patients with DLBCL and FL was associated with low risk of ARRs and satisfactory response in both groups. This trial was registered with NCT01987505

The interplay among psychopathology, personal resources, context-related factors and real-life functioning in schizophrenia: stability in relationships after 4 years and differences in network structure between recovered and non-recovered patients

Improving real-life functioning is the main goal of the most advanced integrated treatment programs in people with schizophrenia. The Italian Network for Research on Psychoses previously explored, by using network analysis, the interplay among illness-related variables, personal resources, context-related factors and real-life functioning in a large sample of patients with schizophrenia. The same research network has now completed a 4-year follow-up of the original sample. In the present study, we used network analysis to test whether the pattern of relationships among all variables investigated at baseline was similar at follow-up. In addition, we compared the network structure of patients who were classified as recovered at follow-up versus those who did not recover. Six hundred eighteen subjects recruited at baseline could be assessed in the follow-up study. The network structure did not change significantly from baseline to follow-up, and the overall strength of the connections among variables increased slightly, but not significantly. Functional capacity and everyday life skills had a high betweenness and closeness in the network at follow-up, as they had at baseline, while psychopathological variables remained more peripheral. The network structure and connectivity of non-recovered patients were similar to those observed in the whole sample, but very different from those in recovered subjects, in which we found few connections only. These data strongly suggest that tightly coupled symptoms/dysfunctions tend to maintain each other's activation, contributing to poor outcome in schizophrenia. Early and integrated treatment plans, targeting variables with high centrality, might prevent the emergence of self-reinforcing networks of symptoms and dysfunctions in people with schizophrenia

The interplay among psychopathology, personal resources, context-related factors and real-life functioning in schizophrenia: stability in relationships after 4 years and differences in network structure between recovered and non-recovered patients

Improving real-life functioning is the main goal of the most advanced integrated treatment programs in people with schizophrenia. The Italian Network for Research on Psychoses previously explored, by using network analysis, the interplay among illness-related variables, personal resources, context-related factors and real-life functioning in a large sample of patients with schizophrenia. The same research network has now completed a 4-year follow-up of the original sample. In the present study, we used network analysis to test whether the pattern of relationships among all variables investigated at baseline was similar at follow-up. In addition, we compared the network structure of patients who were classified as recovered at follow-up versus those who did not recover. Six hundred eighteen subjects recruited at baseline could be assessed in the follow-up study. The network structure did not change significantly from baseline to follow-up, and the overall strength of the connections among variables increased slightly, but not significantly. Functional capacity and everyday life skills had a high betweenness and closeness in the network at follow-up, as they had at baseline, while psychopathological variables remained more peripheral. The network structure and connectivity of non-recovered patients were similar to those observed in the whole sample, but very different from those in recovered subjects, in which we found few connections only. These data strongly suggest that tightly coupled symptoms/dysfunctions tend to maintain each other's activation, contributing to poor outcome in schizophrenia. Early and integrated treatment plans, targeting variables with high centrality, might prevent the emergence of self-reinforcing networks of symptoms and dysfunctions in people with schizophrenia

Mepolizumab for Eosinophilic Granulomatosis With Polyangiitis: A European Multicenter Observational Study.

OBJECTIVE: Mepolizumab proved to be an efficacious treatment for eosinophilic granulomatosis with polyangiitis (EGPA) at a dose of 300 mg every 4 weeks in the randomized, controlled MIRRA trial. In a few recently reported studies, successful real-life experiences with the approved dose for treating severe eosinophilic asthma (100 mg every 4 weeks) were observed. We undertook this study to assess the effectiveness and safety of mepolizumab 100 mg every 4 weeks and 300 mg every 4 weeks in a large European EGPA cohort. METHODS: We included all patients with EGPA treated with mepolizumab at the recruiting centers in 2015-2020. Treatment response was evaluated from 3 months to 24 months after initiation of mepolizumab. Complete response to treatment was defined as no disease activity (Birmingham Vasculitis Activity Score [BVAS] = 0) and a prednisolone or prednisone dose (or equivalent) of ≤4 mg/day. Respiratory outcomes included asthma and ear, nose, and throat (ENT) exacerbations. RESULTS: Two hundred three patients, of whom 191 received a stable dose of mepolizumab (158 received 100 mg every 4 weeks and 33 received 300 mg every 4 weeks) were included. Twenty-five patients (12.3%) had a complete response to treatment at 3 months. Complete response rates increased to 30.4% and 35.7% at 12 months and 24 months, respectively, and rates were comparable between mepolizumab 100 mg every 4 weeks and 300 mg every 4 weeks. Mepolizumab led to a significant reduction in BVAS score, prednisone dose, and eosinophil counts from 3 months to 24 months, with no significant differences observed between 100 mg every 4 weeks and 300 mg every 4 weeks. Eighty-two patients (40.4%) experienced asthma exacerbations (57 of 158 [36%] who received 100 mg every 4 weeks; 17 of 33 [52%] who received 300 mg every 4 weeks), and 31 patients (15.3%) experienced ENT exacerbations. Forty-four patients (21.7%) experienced adverse events (AEs), most of which were nonserious AEs (38 of 44). CONCLUSION: Mepolizumab at both 100 mg every 4 weeks and 300 mg every 4 weeks is effective for the treatment of EGPA. The 2 doses should be compared in the setting of a controlled trial

Partnership tecnologiche e strategie aziendali

Le partnership tecnologiche, sforzi inter-organizzativi finalizzati alla R&S, rappresentano uno dei fronti \u2018pi\uf9 caldi\u2019 dell\u2019azione aziendale contemporanea (Hagedoorn, 2002), ma non \ue8 ancora del tutto chiaro se le dinamiche attivate nell\u2019ambito di tali connessioni siano strettamente limitate agli aspetti tecnologici o possano avere ricadute sui processi di formulazione delle strategie. L\u2019esperienza del Gruppo Loccioni, media impresa italiana che opera come system integrator, mostra come l\u2019allargamento dei circuiti di divisione del lavoro cognitivo (Rullani, 1997) implicato dalla costituzione di partnership in R&S, produca un apprendimento organizzativo che genera un progressivo miglioramento della capacit\ue0 di envisioning, a sua volta riflessa nella componente emergente delle strategie (Mintzberg, 1994) e nel conseguente ingresso in ambienti fino ad allora considerati \u2018lontani\u2019 dal management aziendale

A morphometric sexing approach for the Ring-necked Parakeet Psittacula krameri in Italy.

Only one fact is certain when sexing the Ring-necked Parakeet visually: adult males have a rosecoloured ring and a black bib that is fully developed by their third year. Sexually immature males (those <3 years old) and females are considered impossible to separate without using biometric measures, some additional to those in previous literature. While the biometrics of males and females overlap broadly in value, males tend to be slightly larger than females in all measurements. We tested the possibility of sexing individuals of this species using a series of biometric measurements. A total of 97 parakeets were captured and measured in 2016–17. Measurements of wing length, tail length, bill length, height and thickness, tarsus length, mass, third-primary length and number of yellow underwing coverts were recorded for these individuals. In addition, photographs of the head and wing were taken. Feather samples were taken from all individuals for DNA extraction and 45 of these birds (26 females and 19 males) have been sexed. The measurements from these known-sex individuals were pooled with the measurements for adult males and a logistic regression of the known sexes was performed to verify whether the mean value of the biometric variables was statistically different between females and males. We found that it is possible to separate the sexes using morphological measures of wing, tail, bill length and thickness, tarsus and the number of yellow underwing cover

From the Mailing List of the Italian Society of Nephrology: use of isolation rooms for HBV-positive patients in dialysis[PART TWO]

In the course of recent months, on the mailing list of the Italian Society of Nephrology (ML-SIN), a message asking for opinions on preventative measures for HBsAg patients has stimulated an extensive debate, in particular on the use of separate dialysis rooms. The discussion evidenced significant differences in the procedures adopted, not only between dialysis units, but also in regional health systems' directives. This emphasizes the necessity in dealing carefully with this problem, taking into account the scientific evidence of the infectious risk and epidemiological profile of hepatitis B virus (HBV) in dialysis patients. Moreover, potential solutions must be considered in terms of their effective cost benefit ratio. To complete the previous article, which examined the question from the viewpoint of an expert nephrologist, this issue of the review dedicated to the ML-SIN reports the opinion of an infectious diseases specialist, identified for its scientific contribution to this specific discussion