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Histone deacetylase inhibitors (HDACi) had emerged as promising drugs in leukaemia, but their toxicity due to lack of specificity limited their use. Therefore, there is a need to elucidate the role of HDACs in specific settings. The study of HDAC expression in childhood leukaemia could help to choose more specific HDACi for selected candidates in a personalized approach. We analysed HDAC1-11, SIRT1, SIRT7, MEF2C and MEF2D mRNA expression in 211 paediatric patients diagnosed with acute leukaemia. There was a global overexpression of HDACs, while specific HDACs correlated with clinical and biological features, and some even predicted outcome. Thus, some HDAC and MEF2C profiles probably reflected the lineage and the maturation of the blasts and some profiles identified specific oncogenic pathways active in the leukaemic cells. Specifically, we identified a distinctive signature for patients with KMT2A (MLL) rearrangement, with high HDAC9 and MEF2D expression, regardless of age, KMT2A partner and lineage. Moreover, we observed an adverse prognostic value of HDAC9 overexpression, regardless of KMT2A rearrangement. Our results provide useful knowledge on the complex picture of HDAC expression in childhood leukaemia and support the directed use of specific HDACi to selected paediatric patients with acute leukaemia.

Recent studies have questioned the role of unidirectional airflow ventilation system in reducing surgical site infection (SSI) in prosthetic implant surgery. The aim of the ISChIA study ("Infezioni del Sito Chirurgico in Interventi di Artroprotesi" which means "Surgical site infections in arthroplasty surgery") was to evaluate, as a contribution to this debate, the association between heating, ventilation and air conditioning systems, microbial air contamination and surgical site infection in hip and knee arthroplasty.The study was performed from March 2010 to February 2012 in 14 hospitals, for a total of 28 operating theatres: 16 were equipped with vertical unidirectional airflow ventilation (U-OTs), 6 with mixed airflow ventilation (M-OTs), 6 with turbulent airflow ventilation (T-OTs). Microbial air contamination in the operating theatre was evaluated by means of passive (Index of Microbial Air contamination, IMA) and active (Colony Forming Units per cubic metre, cfu/m3) sampling. SSI surveillance was carried out according to the Hospitals in Europe Link for Infection Control through Surveillance protocol.A total of 1,285 elective prosthesis procedures (61.1% hip and 38.9% knee) were included in the study. The results showed a wide variability of the air microbial contamination in operating theatres equipped with unidirectional airflow. The recommended values of ≤2 IMA and ≤10 cfu/m3 were exceeded, respectively, by 58.9% and 46.4% of samples from U-OTs and by 87.6% and 100% of samples from M-OTs. No significant difference was observed between SSI cumulative incidence in surgical procedures performed in U-OTs compared with those performed in T-OTs. A lower risk of SSI, even though not statistically significant, was shown in surgical procedures performed in U-OTs with a microbial air contamination within the recommended values (≤2 IMA and ≤10 cfu/m3) compared with those performed in U-OTs where these limits were exceeded, and compared with those performed in T-OTs with microbial air contamination within the recommended values for this type of OTs (≤25 IMA, ≤180 cfu/m3.ISChIA study did not show a protective effect of unidirectional airflow compared with turbulent airflow in arthroplasty surgery. However, the frequent exceeding of recommended air microbial contamination values in OTs equipped with unidirectional airflow, and the lower SSI risk in surgical procedures performed in compliant U-OTs compared with those performed in non-compliant U-OTs and with those performed in compliant T-OTs, suggest the need of further studies, which should consider air microbial contamination and other aspects of SSI prevention that may negate the potential benefits of the ventilation system; differences in intrinsic and extrinsic risk factors, medical treatment and surgical technique are also to be considered. Training interventions aimed at improving the behaviour of operators are essential.

FLT3 abnormalities are negative prognostic markers in acute leukemia. Infant leukemias are a subgroup with frequent MLL (KMT2A) rearrangements, FLT3 overexpression and high sensitivity to cytarabine, but dismal prognosis. Cytarabine is transported into cells by Human Equilibrative Nucleoside Transporter-1 (hENT1, SLC29A1), but the mechanisms that regulate hENT1 in acute leukemia have been scarcely studied.We explored the expression and functional link between FLT3 and main cytarabine transporters in 50 pediatric patients diagnosed with acute lymphoblastic leukemia and MLL rearrangement (ALL-MLL+) and other subtypes of leukemia, and in leukemia cell lines.A significant positive correlation was found between FLT3 and hENT1 expression in patients. Cytarabine uptake into cells was mediated mainly by hENT1, hENT2 and hCNT1. hENT1-mediated uptake of cytarabine was transiently abolished by the FLT3 inhibitor PKC412, and this effect was associated with decreased hENT1 mRNA and protein levels. Noticeably, the cytotoxicity of cytarabine was lower when cells were first exposed to FLT3 inhibitors (PKC412 or AC220), probably due to decreased hENT1 activity, but we observed a higher cytotoxic effect if FLT3 inhibitors were administered after cytarabine.FLT3 regulates hENT1 activity and thereby affects cytarabine cytotoxicity. The sequence of administration of cytarabine and FLT3 inhibitors is important to maintain their efficacy.

The Perioperative Antibiotic Prophylaxis (PAP) contributes considerably to the total amount of antibiotics used in hospitals and has been shown to be associated with increase in antibiotic resistance and healthcare costs. The level of compliance with the national guidelines of current practices of PAP for elective hip and knee prosthesis procedures in a network of Italian hospitals (the multicentre Surgical Site Infection surveillance project GISIO-ISChIA), has been evaluated.Compliance of the current prophylactic antibiotic practices with the published national guidelines was assessed for each included operative procedure, considering indication, timing of administration, prescribed antimicrobial agent and total duration of prophylaxis.A total of 14 hospitals and 1285 surgical procedures were included. 99.4% of patients received antimicrobial prophylaxis pre-operatively and 73.0% of patients received PAP within the recommended time period (within 60 minutes before incision). The rate of compliance with discontinuation of PAP within 24 hours after initiation of surgery was 70.2%. Taking into account all doses administered, the antibiotic was chosen appropriately in 57.7% of patients. PAP was performed appropriately, in accordance with national guidelines, in 43.6% of surgical operations.Given the increasing number of replacement procedures in Italy and in Europe, the gap between the evidence-based guidelines and practice must be appropriately addressed in order to improve PAP practices.

Objective. To evaluate potential associations of vascular endothelial growth factor (VEGF) gene polymorphisms with Behçet's disease (BD) and disease expression. Methods. Case patients were 122 consecutive Italian patients with BD followed at the Rheumatology, Ophthalmology, and Neurology Units in Bologna, Ferrara, Milano, Palermo, Potenza, Prato, Reggio Emilia, and Trento over a 3-year period (1997-99) and who satisfied the International Study Group criteria for BD. Also selected as a control group were 200 healthy age and sex matched blood donors. All patients with BD and controls were genotyped by polymerase chain reaction and allele-specific oligonucleotide techniques for +936 C/T (rs3025039) and -634 C/G (rs2010963) mutations and for an 18 base pair (bp) insertion/deletion (I/D) polymorphism at -2549 of the the VEGF promoter region. In vitro release of VEGF by peripheral blood mononuclear cells (PBMC) was investigated by ELISA in healthy controls homozygous for the polymorphisms studied. Results. The carriage rates of the alleles I and -634C were significantly more frequent in patients with BD than in healthy controls [p corr = 0.036, OR 1.8 (95% CI 1.1-2.9) and p corr = 0.05, OR 1.8 (95% CI 1.1-3.0), respectively]. While the distribution of allele +936T was similar in patients with BD and healthy controls, its frequency was significantly higher in BD patients with posterior uveitis/retinal vasculitis than in those without (p = 0.022, OR 2.4, 95% CI 1.1-5.0). Lipopolysaccharide-stimulated VEGF production from PBMC of healthy subjects was higher in II homozygous than in DD homozygous. Conclusion. Our data indicate that carriers of -634C and I alleles are associated with susceptibility to developing BD.

Intercellular adhesion molecule 1 (ICAM-1) is strongly expressed in vascular endothelial cells and perivascular inflammatory infiltrates in immunopathologic studies of Behçet's disease (BD) lesions. ICAM-1 genes may contribute to the inflammatory events responsible for the vessel damage in BD. We examined potential associations of ICAM-1 gene polymorphisms with BD susceptibility.Case patients were 74 consecutive Italian patients with BD who were followed at the Bologna, Ferrara, Milano, Potenza, Prato, Reggio Emilia, and Trento rheumatology, ophthalmology, and neurology units over a 3 year period (1997-99) who satisfied the International Study Group criteria for BD; 228 healthy Italian blood donors from the same geographic areas were selected as control groups. All BD patients and controls were genotyped by polymerase chain reaction and allele-specific oligonucleotide techniques for ICAM-1 polymorphisms at codon 241 (exon 4) and codon 469 (exon 6).The frequency of R241 was significantly higher in BD patients than in controls (20.3% vs 5.7%; p = 0.001, pcorr = 0.002, OR 4.2, 95% CI 1.9-9.3). The distribution of E/K 469 genotype was similar in patients and controls. Comparing patients with different clinical features, we found only a trend to higher frequency of R241 in patients with articular manifestations (21.4% vs 12.5%; p = 0.08).Our findings show that G/R 241 polymorphism of ICAM-1 is associated with BD susceptibility.

To evaluate the distribution of the MHC class I chain related gene A transmembrane (MICA-TM) alleles in Italian patients with Behçet's disease (BD), and to investigate the relative contribution of MICA alleles and HLA-B51 in the susceptibility and specific clinical features of BD.A total of 69 consecutive Italian patients who satisfied the International Study Group criteria for BD were followed at rheumatology, ophthalmology, and neurology units during a 3 year period (1997-99). We selected 130 healthy subjects from the same geographic areas as controls. All patients and controls were examined for MICA microsatellite polymorphisms using polymerase chain reaction. Serological HLA class B51 typing was performed by a standard microlymphocytotoxicity technique.A strong association with HLA-B51 was observed in patients with BD (OR 5.7, 95% CI 2.8-11.3). The MICA-TM allele A6, in linkage disequilibrium with HLA-B51, was only slightly increased in patients compared to controls (60.9% vs 50.8%; p = NS). No significant associations between HLA-B51 or MICA-TM alleles and clinical subgroups, particularly central nervous system or eye involvement, were found.HLA-B51 is the most important susceptibility gene in BD. Association with MICA-A6, when it exists, is secondary to the strong linkage disequilibrium with HLA-B51.

Widespread use of poliovirus vaccines has lead to a dramatic decline on the incidence of paralytic poliomyelitis in the Western Hemisphere. In Italy, the use of live attenuated vaccine (OPV) has lead to virtual eradication of poliomyelitis. However, wild poliovirus is still endemic in some less developed countries, and there is still a risk of importation of wild-virus poliomyelitis as result of immigration from these areas. Therefore, a serologic study of the immunologic status to poliovirus was carried out in 242 immigrants from less developed countries in the Veneto Region (North-East Italy). The overall prevalence of serum neutralizing antibodies was 98.3 percent for poliovirus type 1, 99.6 percent for type 2, and 95.9 percent for type 3. The modal titres were 1:128 (21.1 percent), 1:512 (26.4 percent), and 1:32 (22.3 percent) for poliovirus type 1, type 2, and type 3, respectively. No subject was simultaneously lacking neutralizing antibodies to all three polioviruses. The mean duration of stay in Italy before testing was 1.53 years (range 1 month to 7 years). These results show a good level of the immunity status, similar to those found in the Veneto general population. Although the risk of paralytic poliomyelitis in our population is very low, seronegative immigrants originating from areas of high endemicity could reintroduce wild poliovirus. It is therefore important to maintain a careful surveillance system on the importation of wild poliovirus and to plan vaccination programs for unprotected immigrants.

Objective. To determine the type and frequency of clinical features of Behcets disease in a population of Italian patients. Methods. We retrospectively v studied 137 Italian patients (76 males and 61 females, age at onset 29.6 +/- 12.2 [mean +/-SD] Years) seen consecutively in nine different referral centers. The duration of follow-up (it study entry was 10.9 +/- 8.2 years. Virtually all patients fulfilled the classification criteria developed by the International Study Group for Behcets disease. The clinical manifestations of the patients were recorded by the attending physicians using specifically designed forms. \ Results. The most frequent manifestations at disease onset were oral (78.3%) and genital aphthae (29.2%) followed by inflammatory ocular involvement (20%) and arthritis (14.2%). The commonest (>50% of cases) manifestations observed throughout the disease course were oral aphthae (99.3%),genital aphthae (62.8%), various cutaneous lesions including erythema nodosum (81.8%), and inflammatory ocular disease (60.6%). Panuveitis and posterior uveitis/retinitis occurred more frequently in males compared with females (28.9% versus 11.5% aid 57.9% versus 36.1%, respectively; p

To analyze potential associations of Glu-Asp298 polymorphism in exon 7 and 4 a/b polymorphism in intron 4 of the endothelial nitric oxide synthase (eNOS) gene with susceptibility for Behçet's disease (BD).Seventy-three consecutive Italian patients who satisfied the International Study Group criteria for BD and 135 healthy blood donor controls from the same geographic area were genotyped by polymerase chain reaction and allele-specific oligonucleotide techniques for eNOS polymorphisms in exon 7 and in intron 4.The distribution of the Glu-Asp298 genotype differed significantly between BD patients and controls (p(corr) = 0.00009). Allele Asp298 was significantly more frequent in BD patients than in controls (p(corr) = 0.0006, OR 2.1, 95% CI 1.5-3.3). The distribution of 4 a/b genotype was similar in patients and controls.Our findings show that Glu-Asp298 polymorphism of eNOS gene is associated with BD susceptibility.