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Background: The recent advances in biotechnology and computer science have led to an ever-increasing availability of public biomedical data distributed in large databases worldwide. However, these data collections are far from being “big” enough and “standardized” so to be integrated, making impossible to fully exploit latest machine learning technologies for the analysis of data themselves. Hence, facing this huge flow of biomedical data is a challenging task for researchers and clinicians due to their complexity and high heterogeneity. An effective strategy to address this issue could be the building of a formal conceptual model, which in general allows the design of semantic tools to collect and explore data for a given pathology. This is the case of neurodegenerative diseases and the Alzheimer Disease (AD), in particular. The last years have witnessed the creation of specialized data collections such as the one maintained by the Alzheimer’s Disease Neuroimaging Initiative (ADNI), which contains the largest number of biomedical concepts in the field of AD. For this class of diseases Big Data and Deep Learning give hope for the discovery of new biomarkers for early diagnosis. Hence, a new way must be undertaken of collecting and managing biomedical data. Results: We developed a detailed ontology for clinical multidimensional datasets from the ADNI repository in order to simplify the data access, to obtain new diagnostic knowledge about Alzheimer’s disease and ease the task of harmonization. Conclusions: The semantic data base, populated by ADNI data will suggest new queries allowing machine learning techniques to be applied to any possible combination of data set. The conceptual model could be adopted by any center, so giving rise to new databases that, if made public available, will simplify data integration and multi center data collection projects.

Background and Aims Proteinuria selectivity index (PSI) predicts steroid responsiveness in minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). Rituximab, a monoclonal antibody targeting CD20, has increasingly recognized as a potential therapy of idiopathic podocytopathies, such as MCD and FSGS, although the mechanism of action is still unrecognized and randomized controlled studies are still lacking. Currently, no tools are available to predict responsiveness to RTX. We explored the role of PSI as a potential predictor of RTX responsiveness in MCD and FSGS. Method We analysed cases of biopsy-proven MCD and FSGS followed at one single centre, who received RTX therapy. Baseline data, including proteinuria and PSI, were collected. Proteinuria was considered selective with PSI (clearance of urinary IgG/transferrin ratio) 50%) and substantial improvement of clinical symptoms. Results RTX was administered to 14 patients with MCD and 16 patients with FSGS and, of them, PSI was available before treatment for 10 and 14 patients, respectively. Baseline characteristics of the patients are shown in Table 1. Among the 24 cases with available PSI, CR was reported in 12 and PR in 5, while 9 did not respond to RTX. All patients who achieved CR and PR had selective proteinuria at baseline, while all patients with PSI >0.20 did not respond to RTX (Figure 2). Median relapse-free survival was 25.4 months. Among responders, in 10 out of 19 patients (53%) the relapse occurred between 4 and 60 months from initial treatment. No potentially life-threatening adverse events have been observed. Conclusion Selective proteinuria before treatment can predict the response to RTX in adult patients with steroid-dependent and refractory forms of MCD and FSGS.

The recent technological advances have led to the availability of a huge amount of biomedical data, that are heterogeneous, complex, and distributed in biological databases. In particular, in neurodegenerative diseases area, last years have witnessed the increasing of specialized databases such as Alzheimer's Disease Neuroimaging Initiative (ADNI) [1], which covers psychometric tests, biospecimen, imaging, and laboratory results. Analyzing these data is a challenging task and machine learning (ML) may offer methods and tools for knowledge discovery from them. However, ADNI suffers from a scarce conceptualization behind the collected data, which prevents a fully intuitive access to the data themselves and a direct analysis through ML methods. This fact suggests that a better semantic description of the domain must be proposed. Therefore, in order to take advantage of this big data repository, we are working on two directions: 1) develop a detailed ontology to give a more conceptual organization to the data, to ease data access and interpretation, and to facilitate data integration approaches with other data sources; 2) apply logic data mining methodologies to extract knowledge and generate probabilistic diagnostic models from the ontology, in order to classify patients into disease categories.

Thrombotic microangiopathies (TMA) are a group of clinical conditions mainly characterized by low platelet count, hemolytic anemia and organ damage. TMA can be acquired or hereditary and classified...

The role of anti-human leukocyte antigens DQ region (HLA-DQ) in transplantation is historically less studied than HLA-DR and HLA class I regions, but several studies are demonstrating that anti HLA-DQ antibodies are among the most frequent anti HLA antibodies that develop after transplantation and can have great influence on the developing of humoral rejection and graft loss. In this article we review the gene structure and nomenclature of the HLA-DQ region, the role of anti HLA-DQ antibodies after and before transplantation and briefly the associations of particular HLA-DQ alleles and other diseases.

We compared retrospectively the level of hemoglobin and the percentage of patients with anemia among 59 kidney transplant recipients receiving everolimus, cyclosporine, and corticosteroids and 128 treated with cyclosporine, mycophenolic acid, and corticosteroids. We also compared age at the time of transplantation, sex and ferritine, serum creatinine, creatinine clearance, folic acid, cyanocobalamine levels, use od recombinant erythropoietin, mean corpuscolar volume at the last ambulatory control. Statistical analysis included Student t test, χ(2) test, and logistic regression. The analysis was performed using SPSS software. We observed no difference in terms of hemoglobin levels in patients treated with everolimus (12.9 ± 1.6 vs 12.7 ± 1.5 g/dL). Anemia (defined as hemoglobin 13 g/dL in men and12 g/dL in women, or need to use erythropoietin) was found in 49% and 45% of patients in the 2 groups respectively (P = .6). The other parameters evaluated were similar except for the mean corpuscular volume, which was significantly lower in the everolimus group. In the multivariate analysis only serum creatinine and estimated glomerular filtration rate influenced the level of hemoglobin. We observed no differences in terms of development of anemia in renal transplanted patients treated with everolimus-based regimen.

Background Interferon-beta (IFN-beta) is one of the most widely prescribed medications for relapsing-remitting multiple sclerosis (RRMS). IFN-related thrombotic microangiopathy (TMA) is a rare but severe complication, with a fulminant clinical onset and a possibly life-threatening outcome that may occur years after a well-tolerated treatment with IFN. Most patients evolve rapidly to advanced chronic kidney disease and eventually to renal failure. Methods We performed a retrospective analysis of TMA cases diagnosed and managed in our Nephrology Department from 2010 to 2015, and performed a literature review of IFN-beta-induced TMA. Results Three cases of TMA among patients treated with IFN-beta were identified who did not show any renal improvement following conventional therapy: IFN withdrawal and plasma exchange (PE, range 8–18) sessions. All of them responded favourably to eculizumab, with progressive clinical and renal improvement, allowing dialysis discontinuation, without recurrence of TMA during a long-term follow-up (range 1–5 years). Conclusions TMA is a recognized severe complication in RRMS patients treated with IFN-beta. Withdrawal of IFN and treatment with PE, steroids or rituximab did not improve the poor renal prognosis in our three patients and in all the previously described cases in the literature. In our experience, eculizumab had a strikingly favourable effect on renal recovery, suggesting a role of IFN-beta as a trigger in complement-mediated TMA. Neurologists and nephrologists should be vigilant to this complication to prevent possibly irreversible renal damage.

Observation that 1,25-Dihydroxyvitamin-D3 has an immunomodulatory effect on innate and adaptive immunity raises the possible effect on clinical graft outcome. Aim of this study was to evaluate the correlation of biopsy-proven acute rejection, CMV infection, BKV infection, with 1,25-Dihydroxyvitamin-D3 deficiency and the benefit of calcitriol supplementation before and during the transplantation. Risk factors and kidney graft function were also evaluated. All RTRs received induction therapy with basiliximab, cyclosporine, mycophenolic acid, and steroids. During the first year, the incidence of BPAR (4% vs 11%, P=.04), CMV infection (3% vs 9%, P=.04), and BKV infection (6% vs 19%, P=.04) was significantly lower in users compared to controls. By multivariate Cox regression analysis, 1,25-Dihydroxyvitamin-D3 deficiency and no calcitriol exposure were independent risk factors for BPAR (HR=4.30, P

In this retrospective study, we compared the outcome of renal transplanted patients who received everolimus (EVR) (C0: 8-12 ng/mL)+cyclosporine (CsA) (C2: 150-300 ng/mL)+steroids, vs those who received enteric-coated mycophenolate sodium (EC-MPS) (1,440 mg/d)+CsA (C2: 500-700 ng/mL)+steroids. Efficacy was evaluated at 5 years. We found a nonsignificant trend toward a better 5-year graft survival (81.2% vs 68.6%) and better graft function (estimated glomerular filtration rate 71.8±35.7 vs 60.0±26.2 mL/min, P=.114) in favor of the EVR group. In our experience, EVR with a very low dose of CsA was associated with a nonstatistical trend toward better renal function and graft survival compared to a standard regimen of CsA and EC-MPS.

The optimal timing of dialysis initiation is still unclear. We aimed to ascertain whether a strict clinical follow-up can postpone need for dialysis in chronic kidney disease (CKD) stage 5 patients. We reviewed records of all consecutive adult patients attending our conservative CKD stage 5 outpatient clinic from 2001 to 2010. Chronicity was defined as two consecutive estimated glomerular filtration rate (eGFR) measurements below 15 ml/min/1.73 m2. Characteristics of subjects, including comorbidities, were assessed at baseline; blood pressure and serum markers of uremia were assessed both at first and last visit. GFR was estimated by the 4-variable Modification of Diet in Renal Disease (MDRD) formula. In the 312 patients analyzed baseline eGFR was 9.7 ± 2.7 ml/min, which declined by 1.93 ± 4.56 ml/min after 15.6 ± 18.2 months. Age was inversely related to eGFR decline (r −0.27, p = 0.000). During conservative follow-up 55 subjects (18 %) died. In comparison with those eventually entering dialysis, deceased subjects were older and had a longer follow-up with no CKD progression. Multivariate analysis identified age, proteinuria and lower baseline K values as the only independent determinants of death. One hundred ninety-four subjects (66 %) started dialysis with an average eGFR of 6.1 ± 1.9 ml/min. During 35.8 ± 24.7 months of dialysis follow-up, 84 patients died. Multivariate analysis identified age as the main determinant of death (hazard ratio [HR] for every year 1.07, 95 % confidence interval [CI] 1.04–1.11, p 0.000). Patients starting dialysis with eGFR below the median, e.g.

Background There are limited published data concerning the effects of different immunosuppressive regimens on the development of polyomavirus (BKV) viremia. We examined the risk of developing BKV viremia in kidney transplant recipients receiving everolimus (EVR) or mycophenolic acid (MPA) as maintenance therapy. Methods We observationally analyzed 296 patients who underwent renal transplantation at our center between 2005 and 2010: 58 were treated with EVR and low-dose cyclosporine (LD-CyA) (group 1) and 238 with MPA and standard-dose CyA (group 2). All of the patients received induction therapy with basiliximab and maintenance steroids. BKV viremia (a whole-blood viral load of >850 copies/mL) was measured by means of real-time polymerase chain reaction at least once a month during a 12-month follow-up period. Results BKV viremia was detected in 57 patients (19%), five (9%) in group 1 and 52 (22%) in group 2. Kaplan–Meier analyses showed that freedom from BKV viremia was significantly more frequent in group 1. The mean time of onset of BKV viremia was about four months after transplantation in both groups. The median viral load was greater in group 2 (12.5 ± 6.1 vs. 2.5 ± 1.8 × 104 copies/mL; p = 0.01). After the onset of BKV viremia, graft function significantly declined in group 2: 11 patients developed polyomavirus-associated nephropathy (PVAN) and four presumptive PVAN; nine experienced an acute rejection after the discontinuation of MPA, and 11 (21%) lost their graft. There was no graft loss in group 1. Conclusion These findings suggest that in comparison with MPA and Cya, an EVR and LD-CyA regimen lowers the risk of BKV viremia after kidney transplantation and favorably alters outcomes.

Abstract 3879 Purpose. The use of early (interim) positron emission tomography (PET) restaging during front-line therapy in Hodgkin's lymphoma (HL) has considerably increased in clinical practice as an early recognition of treatment failure allows patients to be addressed to more intensive treatment regimens. Patients and Methods. Between June 1997 and June 2009, 304 newly-diagnosed Hodgkin's lymphoma patients (147 early-stage and 157 advanced-stage) were treated with the ABVD regimen at two Italian institutions. Patients underwent to a PET staging and restaging at baseline, after 2 cycles of therapy and at the end of the treatment. Results. 53 patients showed a positive interim PET and only 13/53 (24.5%) achieved a complete response (CR), whereas 251 patients showed a negative PET and 231/251 (92%) remained in CR. Comparison between interim PET-positive and interim PET-negative patients indicated a significant association between PET findings and 9-year progression-free survival (p=0.0000) and 9-year overall survival (p=0.0000), with a median follow-up of 31 months. Among the early-stage patients, 19 had a positive interim PET and only 4 (21%) achieved a CR; among the 128 negative interim PET patients, 122 (97.6%) obtained a CR. In the advanced-stage subset, 34 patients showed a persistently positive PET (with only 9/34, 26.4% in CR), whereas 123 showed a negative interim PET, with 109 (88.6%) remaining in CR. Conclusions. Our results confirm the role of early PET as a significant step forward for the management of both early and advanced-stage HL patients, offering the potential for an immediate switch to high-dose treatments, if required. Disclosures: No relevant conflicts of interest to declare.