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Purpose The aim of this study was to evaluate the effect of different clinical covariates on tacrolimus dose requirements in adult kidney transplant patients with a specific focus on drug interactions. Patients Tacrolimus dosing requirement, normalized by drug levels and expressed as the concentration/dose (C/D) ratio as a surrogate index of tacrolimus bioavailability, was employed to identify four categories of tacrolimus dosing requirement, namely, very high, high, small, and very-small, in very fast, fast, slow, and very slow metabolizers, respectively. Steroid weight-based doses were analyzed instead of fixed doses, and genetic analysis of cytochrome P450 (CYP) 3A5*1/*3 and multi-drug resistance 1 ( MDR1 ) C3435T and C1236T polymorphisms were performed Results Multivariate analysis on 450 adult transplant patients identified six risk factors for being slow metabolizers and therefore requiring small tacrolimus doses: male sex (OR  1.615, p = 0.020); age >60 years (OR 2.456, p = 0.0005); body mass index ≥25 (OR 1.546, p = 0.046), hepatitis C virus positivity (OR 2.800, p = 0.0004); low steroid dose <0.06 mg/kg (OR 3.101, p  < 0.0001). Patients with a small tacrolimus requirement were at increased risk for multiple infections (OR  1.533, p = 0.0008) and higher systolic blood pressure (OR  1.385, p = 0.022) and showed a significant association with the CYP3A5*3/*3 genotype adjusted by MDR1 polymorphisms C3435T and C1236T (OR 8.104, p = 0.0001). Conclusions Our results demonstrate the importance of the interaction among genetic and clinical factors in conditioning tacrolimus disposition, with corticosteroid weight-based dose being the only modifiable risk factor for tacrolimus requirement. As the tacrolimus dosing requirement increases with increasing tacrolimus clearance through concomitant steroid use, undesirable changes in tacrolimus levels may occur when steroid doses are tapered, predominantly in slow metabolizers. This often neglected drug interaction has to be monitored to optimize tacrolimus exposure in kidney transplant patients.

Objective Several studies have shown the presence of anti-IFI16 antibodies in systemic lupus erythematosus (SLE), Sjögren Syndrome (SjS), systemic sclerosis (SSc) and other autoimmune diseases. However, the significance of anti-IFI16 antibodies in SLE has not been fully characterized. The aim of this study was to investigate associations between anti-IFI16 antibodies and clinical and serologic parameters of SLE. Methods An enzyme-linked immunosorbent assay (ELISA) kit was used to measure anti-IFI16 antibodies in the sera of 168 SLE patients, 46 patients with any type of primary glomerulonephritis (GN) and 182 healthy controls (HCs). Associations between anti-IFI16 antibodies and clinical and serologic parameters of SLE were statistically evaluated using both univariate and multivariate analysis. Results Significantly higher anti-IFI16 titres were observed in SLE patients compared to both non-SLE GN and HCs (median levels: 270.1 U/ml vs 132.1 U/ml, p = 0.001, and 52.9 U/ml, p < 0.0001, respectively). With cut-off levels corresponding to the 95th percentile of the control population (113 U/ml), 63% of the SLE patients tested positive for anti-IFI16 autoantibodies, compared to just 24% of patients with primary non-SLE GN and 5% of HCs. The presence of anti-IFI16 antibodies inversely correlated with proteinuria (univariate analysis) and C3 hypocomplementaemia (univariate and multivariate analyses). Conclusions The inverse correlations observed between anti-IFI16 positivity, proteinuria and C3 hypocomplementaemia suggest that anti-IFI16 antibodies do not contribute to renal inflammation in SLE; indeed they may even prevent complement consumption. Anti-IFI16 antibodies hold the potential to serve as a new biomarker of disease activity in SLE.

BackgroundGrowth Arrest-Specific 6 (Gas6) and its receptor MERTK have been involved in the regulation of inflammation and apoptosis.ObjectivesWe evaluated if an impairment of Gas6/MERTK signalling system could be associated with Systemic Lupus Erythematosus (SLE) disease activity and, specifically, with kidney involvement.MethodsGas6 and the soluble, cleaved form of MERTK (sMER) plasma concentration were measured in 59 SLE patients and in 46 healthy controls. Clinical and laboratory data were collected.ResultsSLE patients had significantly higher plasma sMER concentrations (10,40 ng/ml [IQR 7,92–13,83] vs 2,65 ng/ml [2,38–3,23]) while healthy subjects showed only slightly higher plasma Gas6 concentrations than patients (22,8 ng/ml [IQR 19,2–24,7] vs 14,7 ng/ml [11,8–20,5]). Moreover, only sMER, but not Gas6, was significantly different being higher in SLE patients with renal involvement (11,3ng/mL [9,7–13,9ng/mL] vs 7,8 ng/mL [6,2–12,2ng/mL]). At univariate analysis sMER concentration was related to clinical and laboratory indexes of disease activity as SLEDAI, haemoglobin, ESR, proteinuria and creatinine plasma concentration but, at multiple regression analysis only 24 h urine protein concentration fitted the model (R=0,9751 F11,314; p<0,002).ConclusionsAn increased sMER concentration can be detected in SLE patients, particularly those who showed renal involvement. Interestingly sMER is directly related to the degree of proteinuria, This observation suggests an increased cleavage of MERTK; on this basis an impairment of MERTK-mediated apoptotic bodies clearance could be supposed.Disclosure of InterestNone declared

The aim of the present study was to explore the correlations between Spirituality/Mysticism/Psychoticism symptoms and suicidality in young adult survivors of the L'Aquila earthquake. The sample included 475 subjects recruited among high school seniors who had experienced the April 6, 2009, earthquake. Assessments included: Trauma and Loss Spectrum–Self Report and Mood Spectrum–Self Report (MOODS-SR). Mysticism/Spirituality dimension and suicidality were evaluated by means of some specific items of the MOOD-SR. The Spirituality/Mysticism/Psychoticism MOODS-SR factor score was significantly higher among subjects with PTSD diagnosis with respect to those without. Similarly, subjects with suicidal ideation, as well as those who committed a suicide attempt, reported significantly higher scores than those without.

Introduction We examined the construct of psychosis using the self-report instrument CAPE (Community Assessment of Psychic Experiences) in a sample of 1,323 students. Materials and Methods Taxometric analysis was carried out using Taxometric Programs for the R Computing Environment. The MAXCOV CCFI was 0.34, indicating a dimensional latent structure. All other taxometric analysis yielded very similar results indicative of dimensional structure. Conclusion In this study, using powerful analytic techniques designed expressly for the purpose, i.e. taxometric analysis, the latent construct of psychosis in a sample of young students appeared to be consistent with a dimensional, non-taxonic latent structure.

Polyomavirus BK (BKV) reactivation can occur in immunodeficient patients. Few studies on BKV infection in patients with systemic lupus erytematosus (SLE) nephritis are available. Aim of this study was to analyse the prevalence of BKV infection by quantifying viral load and to investigate the association with clinical and histological parameters indicating duration, type and activity of SLE. BKV-DNA was evaluated by polymerase chain reaction in serum (sBKV) and urine (uBKV) specimens from 40 patients with SLE nephritis and 29 healthy controls. Renal function, urinary activity, clinical index of SLE activity [SLE Disease Activity Index (SLEDAI) score], CD4+/CD8+ ratio, histological classes and duration of SLE nephritis were compared according to the BKV-DNA-positivity. sBKV was present in 15% of SLE patients and in 13.8% of controls; uBKV in 32% of SLE patients and in 17.2% of controls. There was no significant difference in terms of kidney function, urinary activity, SLEDAI score, presence of anti-dsDNA antibodies, CD4+/CD8+ ratio and BKV viremia and/viruria, as well as there was no significant correlation between SLEDAI score, anti-dsDNA antibodies titers and median viral load. Duration of nephropathy tended to be shorter in patients with BKV viremia and/or viruria; proteinuria/creatininuria ratio tended to be higher in patients with positive sBKV and uBKV. BKV-DNA-positivity tended to be more frequent in patients treated with an immunosuppressive agent versus those on steroid treatment. Reactivation of BKV infection can occur in patients with SLE, although prevalence data do not significantly differ from those obtained in the control group. The trend toward an association between BKV infection and degree of proteinuria and less duration of SLE nephritis could indicate a major susceptibility to develop BKV infection in more active phases of the disease. The role of BKV reactivation in terms of clinical parameters and histological pattern, as well as the role of therapeutic protocols in the onset of BKV reactivation and, conversely, the therapeutic implication of BKV reactivation in SLE patients remain to be defined and should be addressed in further studies on a larger number of patients. Lupus (2007) 16, 881—886.

We report the clinical and genetic study of a primary hyperoxaluria type I (PH1) family with two sisters homozygous for p.Gly170Arg who are still asymptomatic at age 29 and 35, and two brothers, also homozygous for the same mutation, who are affected since age 27 and 30. The clear sex difference observed in this family and in others reported in the literature fits well with the prevalence of males over females in the Italian registry. In the KO model of PH1, only male mice develop renal stones, suggesting that the sex difference may affect both oxalate production and stone formation. A likely mechanism is the sex-related expression of glycolate oxidase shown in experimental animals. The stable isotope method recently developed by Huidekoper and van Woerden for in vivo assessment of the endogenous oxalate production could help to clarify the issue in humans.