Francesca Binda

Direct‐acting antivirals in hepatitis C virus (HCV)‐infected and HCV/HIV‐coinfected patients: real‐life safety and efficacy

Clinical trials of all‐oral direct‐acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection reported high response rates in HCV/HIV coinfection, similar to those obtained in HCV monoinfection. We evaluated the safety and efficacy of these regimens in a clinical practice setting.

Imatinib and ruxolitinib association: first experience in two patients

We report the first case of 2 patients with a previous diagnosis of post-polycythemic (PV) myelofibrosis who developed chronic myeloid leukemia (CML) seven years later, both treated with an association of a tyrosine-kinase inhibitor (imatinib) and a JAK1/JAK2 inhibitor (ruxolitinib). In 1992, a 46-

Low-dose alemtuzumab-associated immune thrombocytopenia in chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is frequently complicated during its course by autoimmune disorders (from 2 to 12% of cases), such as autoimmune hemolytic anemia (AIHA) and immune thrombocytopenic purpura (ITP). In particular, ITP has been reported in about 2–5% of CLL population. Recently, Cuker et al. reported the occurrence of ITP in 6/216 patients with relapsing-remitting multiple sclerosis in a phase 2 clinical trial of annual alemtuzumab. Alemtuzumab is an anti-CD52 monoclonal antibody used in CLL both as first-line treatment and in relapsed/refractory patients. We evaluated a cohort of 64 consecutive patients affected by relapsed-refractory CLL treated with low-dose alemtuzumab and we observed a incidence of ITP higher than predicted. Our data, associated with the report of Cuker et al., seem to suggest an important role of alemtuzumab in the pathogenesis of ITP which could be related to its induced dysregulation of T-lymphocyte activity.

Developing core elements and checklist items for global hospital antimicrobial stewardship programmes: a consensus approach

OBJECTIVES With increasing global interest in hospital antimicrobial stewardship (AMS) programmes, there is a strong demand for core elements of AMS to be clearly defined on the basis of principles of effectiveness and affordability. To date, efforts to identify such core elements have been limited to Europe, Australia, and North America. The aim of this study was to develop a set of core elements and their related checklist items for AMS programmes that should be present in all hospitals worldwide, regardless of resource availability. METHODS A literature review was performed by searching Medline and relevant websites to retrieve a list of core elements and items that could have global relevance. These core elements and items were evaluated by an international group of AMS experts using a structured modified Delphi consensus procedure, using two-phased online in-depth questionnaires. RESULTS The literature review identified seven core elements and their related 29 checklist items from 48 references. Fifteen experts from 13 countries in six continents participated in the consensus procedure. Ultimately, all seven core elements were retained, as well as 28 of the initial checklist items plus one that was newly suggested, all with ≥80% agreement; 20 elements and items were rephrased. CONCLUSIONS This consensus on core elements for hospital AMS programmes is relevant to both high- and low-to-middle-income countries and could facilitate the development of national AMS stewardship guidelines and adoption by healthcare settings worldwide.

HIV-1 A1 Subtype Epidemic in Italy Originated from Africa and Eastern Europe and Shows a High Frequency of Transmission Chains Involving Intravenous Drug Users

Background Subtype A accounts for only 12% of HIV-1 infections worldwide but predominates in Russia and Former Soviet Union countries of Eastern Europe. After an early propagation via heterosexual contacts, this variant spread explosively among intravenous drug users. A distinct A1 variant predominates in Greece and Albania, which penetrated directly from Africa. Clade A1 accounts for 12.5% of non-B subtypes in Italy, being the most frequent after F1 subtype. Aim Aim of this study was to investigate the circulation of A1 subtype in Italy and trace its origin and diffusion through phylogenetic and phylodynamic approaches. Results The phylogenetic analysis of 113 A1 pol sequences included in the Italian ARCA database, indicated that 71 patients (62.8%) clustered within 5 clades. A higher probability to be detected in clusters was found for patients from Eastern Europe and Italy (88.9% and 60.4%, respectively) compared to those from Africa (20%) (p < .001). Higher proportions of clustering sequences were found in intravenous drug users with respect to heterosexuals (85.7% vs. 59.3%, p = .056) and in women with respect to men (81.4% vs. 53.2%, p < .006). Subtype A1 dated phylogeny indicated an East African origin around 1961. Phylogeographical reconstruction highlighted 3 significant groups. One involved East European and some Italian variants, the second encompassed some Italian and African strains, the latter included the majority of viruses carried by African and Italian subjects and all viral sequences from Albania and Greece. Conclusions Subtype A1 originated in Central Africa and spread among East European countries in 1982. It entered Italy through three introduction events: directly from East Africa, from Albania and Greece, and from the area encompassing Moldavia and Ukraine. As in previously documented A1 epidemics of East European countries, HIV-1 A1 subtype spread in Italy in part through intravenous drug users. However, Eastern European women contributed to the penetration of such variant, probably through sex work.

Local and global spatio-temporal dynamics of HIV-1 subtype F1.

Previous studies have attempted to explore the origin of the F1 subtype, but the precise origin of the Romanian and South American F1 variants remains controversial. As the F1 subtype is the most frequent non‐B variant among Europeans residing in Italy, the aim of this study was to estimate its phylogeography in order to reconstruct its origin and route of dispersion. The phylogeographical analyses, which were made using the Bayesian Markov Chain Monte Carlo approach and BEAST software, revealed two significant clades: the first included all of the Romanian strains together with a few Italian and four African isolates; the second encompassed all of the South American sequences and the large majority of Italian variants. By putting the African reference sequences into two discrete groups based on specific countries, phylogeographic analysis indicated that the F1 epidemic originated in Cameroon/Democratic Republic of Congo in the early 1940s, and was exported to South America 10 years later. Subsequently, the F1 virus spread to Angola and, from there, was exported to Romania in the early 1960s. It reached Italy in the 1970s from South America and Romania. The South American and Romanian variants of F1 have different African countries of origin and different temporal spreads. The South American variant seems to be characterized by multiple introduction events, whereas the Romanian strain probably spread as a result of a single entry. Two different pathways from South America and Romania led the F1 variant to Italy in the 1970s. J. Med. Virol. 86:186–192, 2014.

Short course of bortezomib in anemic patients with relapsed cold agglutinin disease. A phase II prospective GIMEMA study

TO THE EDITOR: Cold agglutinin disease (CAD) is a chronic hemolytic disorder caused by anti–red blood cell immunoglobulin M (IgM) autoantibodies most often monoclonal with k light-chain restriction.[1][1],[2][2] The autoantibody reacts at temperatures lower than the body temperature, causing

Paroxysmal Nocturnal Hemoglobinuria (Pnh): Brain Mri Ischemic Lesions In Neurologically Asymtomatic Patients

This study investigated for the first time brain ischemic involvement in 19 consecutive neurologically asymptomatic PNH patients by non-enhanced cerebral MRI, and by intracranial arterial and venous angio-MRI. Eleven cases (58%, 7 aged <65) showed pathological findings: 9 white matter (WM) abnormalities related to chronic ischemic small vessel disease, 2 a focal abnormality >5 mm, and 5 cases a score >4 by the age-related white matter changes (ARWMC) scale. Compared with age and sex-matched controls (1:2 ratio), patients showed an increased frequency of periventricular WM vascular degeneration (32% versus 5.2%, p = 0.04) and of severe lesions (ARWMC scale score >4) (26% versus 2.6%, p = 0.05), and a higher overall ARWMC scale score (3.5 ± 1.07 versus 2.0 ± 0.8, mean ± SD, p < 0.0001). Notably, vascular abnormalities suspected for prior partial venous thrombosis, were observed in PNH cases only. MRI lesions were not related to blood counts, hemolytic markers, clone size, disease duration, and therapy with eculizumab. Neurological examination was unremarkable in all patients but one (Parkinson disease). Psychiatric assessment revealed a case of generalized anxiety disorder, 1 bipolar disorder type 2, and 1 adjustment disorder. In conclusion, brain MRI may be useful at diagnosis and during the course of the disease to explore subclinical neurological involvement.

Renal function in HIV/HBV co-infected and HBV mono-infected patients on a long-term treatment with tenofovir in real life setting

The human immunodeficiency virus (HIV)/hepatitis B virus (HBV) co‐infection is likely to be associated with an increased risk of kidney disease, due to the additional factors that may affect renal function in the HIV population. We aimed to evaluate renal toxicity in HIV/HBV and HBV mono‐infected patients on long‐term therapy with tenofovir (TDF) and to explore the association of polymorphisms in ATP‐binding cassette (ABCC)2, ABCC4, ABCC10 with the development of renal dysfunction. From September 2006 to November 2014, 44 HIV/HBV co‐infected and 34 HBV mono‐infected patients were commenced on TDF. Data of renal safety were retrospectively collected and analyzed. ABCC2, ABCC4 and ABCC10 genotypes were identified by real‐time PCR. Over 60 months of observation, there was a significant increase in mean creatinine levels from baseline (P<.01) that was not significantly different between the two study groups. Moreover, a significant decline in estimated glomerular filtration rate (eGFR) was observed from baseline (P<.01), and it was significantly greater in HBV mono‐infected than co‐infected patients (P=.03). The distribution of ABCC2, ABCC4 and ABCC10 genotypes among a subgroup of 34 patients did not show significant association with eGFR decline <90 mL/min per 1.73 m2. Although our findings showed a statistically significant decrease in eGFR with long‐term use of TDF, its clinical impact seems to be modest. The role of genetic factors to identify patients at greater risk for developing tenofovir‐induced renal toxicity needs to be further investigated.

Unconventional T-cells in Chronic Hepatitis B Patients on Long-Term Suppressive Therapy with Tenofovir followed by a Peg-IFN Add-On Strategy: a randomized study

HBV eradication in chronic hepatitis B (CHB) subjects is rarely achieved with either nucleos(t)ide analogues (NA) or pegylated interferon (Peg‐IFN), which both have a limited effect in restoring immune responses. Thirty CHB subjects on long‐term treatment with tenofovir (TDF) and HBV suppression were enrolled and randomized 1:2 to either receive Peg‐IFN‐α‐2a add‐on therapy or continue TDF alone. We studied γδ T and iNKT frequency and function (by flow cytometry) at baseline, at 12 weeks and 12 weeks after the end of treatment. A higher reduction in qHBsAg occurred in the add‐on group compared with the NA group at W12 (P = .016) and at W24 (P = .012). A decline of qHBsAg ≥0.5 log10 at week 24 occurred in 4 of 10 patients in the add‐on arm and 1 of 20 in the NA arm, respectively (P = .03). HBsAg loss was seen in 20% of subjects in the add‐on group and in none of the NA group. Compared to HBV negative, CHB on TDF showed lower frequency of iNKT (P = .03) and γδ T cells (P = .03) as well as fewer γδ T cells expressing Vδ2 T‐cell receptors (P = .005). No changes in unconventional T‐cell frequency and function were shown in both add‐on and NA patients nor were differences detected between the two treatment groups. We report persistent impairment of unconventional T cells in CHB. Despite a greater qHBsAg decline of add‐on patients, our data failed to detect any effect of Peg‐IFN treatment on unconventional T cells.