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Bencardino K.,Niguarda Cancer Center | Mauri G.,Niguarda Cancer Center | Amatu A.,Niguarda Cancer Center | Tosi F.,Niguarda Cancer Center | And 9 more authors.
Clinical Colorectal Cancer | Year: 2016

Oxaliplatin immune-induced syndrome (OIIS) is an uncommon, potentially life-threatening, side effect associated with oxaliplatin-based chemotherapy. The present study reports 5 original cases of OIIS and systematically reviewed the available published cases. We retrospectively analyzed the clinical archives of the Niguarda Cancer Center from 2009 to 2015 and conducted a search for OIIS using the PubMed database, followed by deeper investigation of the references of the recorded studies. We pooled our series with other reported cases for systematic review in accordance with the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement using only English language as the selection criterion. A total of 61 OIIS cases were analyzed, the largest series reported to date. Of the 61 patients, 56 (91.8%) had received oxaliplatin for metastatic colorectal cancer. In 32 of the 61 patients (52.5%), OIIS was associated with grade 4 thrombocytopenia and in 4 (6.6%) with grade 4 anemia. OIIS was fatal in 4 patients. In 49 patients, oxaliplatin-induced immune system activation was tested using the Coombs test or by detection of antiplatelet antibodies and was positive in 87.7% of the patients. The average number of oxaliplatin cycles until the onset of OIIS was 16.7, and the number was significantly lower when oxaliplatin was administered as a rechallenge after a period of vacancy of treatment with this agent (4.6 cycles as rechallenge vs. 13.6 as first-time exposure; P < .00001). OIIS is triggered by cumulative administration of oxaliplatin, characteristically with a threefold earlier onset when the drug is administered as a rechallenge. Prompt identification of OIIS can be expected to reduce the risk of iatrogenic morbidity and mortality. © 2016 Elsevier Inc. Source


Ferraresso M.,University of Milan | Belingheri M.,Dialysis and Transplant Unit | Ginevri F.,Giannina Gaslini | Murer L.,University of Padua | And 7 more authors.
Pediatric Transplantation | Year: 2014

The three yr results of a multicenter trial in de novo pediatric KT treated with a proliferative signal inhibitor and low dose CNI are presented. Thirty-seven children (9.1 ± 5 yr old) received basiliximab, cyclosporine A (CyA C2:1400 ng/mL), (MMF C0:1.5-3 μg/mL), and prednisone. Three wk later everolimus was started (C0:5-10 ng/mL), CyA was reduced (C2:600 ng/mL after 90 days 300 ng/mL), and MMF discontinued. During the three-yr period patient and graft survivals were 96%. One patient died for causes unrelated to the immunosuppression. Cumulative acute rejection rate including protocol and indication biopsies was 21.9%. None of the patients had signs of chronic humoral rejection. Incidence of dnDSA was 5%, 11%, and 22% at one, two, and three yr post-transplant, respectively. Mean glomerular filtration rate measured at one yr and three yr post-transplant was 105.5 ± 31 and 110.7 ± 27 mL/min/1.73 m2, respectively. A growth velocity of 7.7 ± 6.7 cm/yr was achieved with positive catch-up growth. No malignancy or post-transplant lymphoproliferative diseases were diagnosed. In conclusion, the treatment based on basiliximab induction, everolimus, low-dose cyclosporine, and low-dose prednisone leads to good long-term efficacy in de novo pediatric KT recipients. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Source


Losito A.,Dialysis and Transplant Unit | Pittavini L.,Dialysis and Transplant Unit | Ferri C.,Clinical Pathology Laboratories | de Angelis L.,Clinical Pathology Laboratories
Journal of Nephrology | Year: 2011

Background: The aim of this study was to investigate the association of reduced kidney function, diabetes and arterial hypertension with mortality in cardiovascular disease patients admitted to hospital. Methods: This was a prospective cohort study. The setting was the reference hospital for the population area. Unselected consecutive patients (n=7,487) admitted to the hospital over 12 months were enrolled. In all subjects, the estimated glomerular filtration rate (eGFR) was determined, and the association of acute and 36-month mortality with kidney function impairment, diabetes and arterial hypertension was assessed. Results: Short-term mortality (314 deaths) was significantly associated with reduced eGFR only in patients with chronic ischemic heart disease. The study of 36-month survival in the whole cohort showed that mortality (918 deaths) was significantly associated with age, male sex and reduced eGFR. The study repeated for the individual CV conditions showed that reduced eGFR was associated with mortality only in chronic ischemic heart disease. No association with sex of patient, diabetes or arterial hypertension was found. Conclusions: Although the association between reduced kidney function and CV diseases was confirmed, the analysis of survival in the individual conditions shows that only in chronic ischemic disease is mortality associated with reduced eGFR. Any interaction with 2 major predisposing diseases - diabetes and arterial hypertension-has not been shown. © 2011 Società Italiana di Nefrologia. Source


Montinaro V.,Dialysis and Transplant Unit | Iaffaldano G.P.,Dialysis and Transplant Unit | Granata S.,University of Bari | Porcelli P.,Psychosomatic Unit | And 5 more authors.
Clinical Nephrology | Year: 2010

Background: Mental disorders are frequent in hemodialysis (HD) patients. Depression and anxiety along with physical co-morbidity affect quality of life (QOL). Uremia is associated with inflammation and release of cytokines by lymphomonocytes. Inflammatory cytokines are relevant in depression. The aim of this study was to assess the psychological alterations and QOL in HD patients, and to correlate them with pattern of cytokine production. Methods: Patients: 30 HD patients and 20 subjects with CKD Stage I-II K-DOQI. Psychometric tests were administered: 1) Hospital Anxiety and Depression Scale (HADS) composed of an anxiety subscale (HADS-A) and a depression subscale (HADS-D); 2) Kidney Disease Quality of Life (KDQOL) modified, including a cognitive function subscale (KDQOL-CF). Whole blood samples collected at beginning of HD session were diluted with RPMI/heparin and incubated for 24 h in presence of lipopolysaccharide (LPS). IL-1β, IL-6, TNF-α and IL-10 were assayed on supernatants and results were normalized per number of lymphomonocytes (ng/106 cells). Results: A depressive mood was more frequent in HD patients (50%) than controls (20%, p < 0.0001). No difference for anxiety (HD = 43%, controls = 45%) was observed. QOL score was significantly lower in HD than controls (p = 0.006) and correlated inversely with HADS total, HADS-A and HADS-D (p < 0.0001). Albumin, Kt/V and phosphate were comparable in patients with or without anxiety or depression. Cytokine production was significantly higher in HD patients than controls (IL-1βp= 0.05; IL-6 p = 0.010; TNF-α p < 0.0001; IL-10, p = 0.0019). HD patients with the HADS-A positive for anxiety showed higher IL-6 production (p = 0.026), while IL-1β levels were not associated with symptoms of depression. KDQOL-CF correlated inversely with levels of IL-6, TNF-α and IL-10. Conclusions: HD patients have symptoms of depression and anxiety that negatively affect QOL. These symptoms are independent of the efficiency of dialysis and nutritional status. On the contrary, IL-6 is linked to the presence of psychological discomfort in these patients. © 2010 Dustri-Verlag Dr. K. Feistle. Source


Coppo R.,University of Turin | Coppo R.,Dialysis and Transplant Unit | Fonsato V.,University of Turin | Balegno S.,University of Turin | And 13 more authors.
Kidney International | Year: 2010

The reaction of mesangial cells with aberrantly glycosylated IgA1 has been implicated in the etiology of IgA nephropathy (IgAN). Tumor necrosis factor, which is assumed to mediate the interaction between mesangial cells and podocytes, also induces the expression of platelet-activating factor (PAF). In this study, we determined whether PAF affects the expression of nephrin (an adhesion molecule critical to glomerular permselectivity) and cytoskeletal F-actin organization in podocytes. We treated human mesangial cells with atypically glycosylated IgA1 either prepared in vitro or derived from the sera of patients with IgAN. We then prepared conditioned media from these cells and added them to cultured human podocytes in the presence of PAF receptor antagonists. Podocytes transfected to overexpress acetylhydrolase, the main catabolic enzyme of PAF, served as controls. Downregulation of nephrin expression and F-actin reorganization occurred when podocytes were cultured with mesangial cell-conditioned medium. Preincubation of podocytes with a PAF receptor antagonist prevented the loss and redistribution of nephrin. In control podocytes overexpressing acetylhydrolase, nephrin loss was abrogated. Our results suggest that atypically glycosylated IgA-induced PAF from mesangial cells is a mediator of podocyte changes, which, when more directly tested elsewhere, were found to be associated with proteinuria. Hence, it is possible that these in vitro findings may be relevant to the proteinuria of IgAN. © 2010 International Society of Nephrology. Source

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