Current Issue : April - June Volume : 2016 Issue Number : 2 Articles : 7 Articles
Background: Silibinin has been shown to have anti-HCV activity and immune-modulating properties by regulating\ndendritic cell (DC) function. DCs are antigen-presenting cells that, together with regulatory T cells (Treg), play a\npivotal role in controlling alloimmune, as well as anti-HCV immune responses.\nMethods: Twelve liver transplant patients with HCV recurrence received iv infusion of Silibinin (iv-SIL) for 14\nconsecutive days. Using flow cytometry, before and at the end of treatment, we determined the frequencies of\ncirculating myeloid (m) and plasmacytoid (p) DC and Treg and the expression of costimulatory/coregulatory molecules\nby the DC subsets and Treg. Statistical analysis was performed using the paired Student�s t test and Pearson\ncorrelation test.\nResults: After iv-SIL treatment, we observed an elevated plasmacytoid dendritic cell (pDC)/myeloid dendritic\ncell (mDC) ratio, while pDC displayed lower HLA-DR and higher immunoglobulin-like transcript 4 (ILT4), CD39,\nand HLA-G expression compared to the pretreatment baseline. In addition, after iv-SIL, mDC showed increased\ninducible costimulator ligand (ICOSL) expression. No changes were detected in Treg frequency or programed\ndeath (PD)-1 expression by these cells. Moreover, several correlations between DC/Treg markers and clinical\nparameters were detected.\nConclusions: This descriptive study, in liver transplant patients with HCV recurrence, reveals the impact of iv-SIL on\nDC and Treg. The changes observed in circulating pDC and mDC that have previously been associated with\ntolerogenic conditions shed new light on how iv-SIL may regulate anti-viral and alloimmunity. We have also\nobserved multiple clinical correlations that could improve the clinical management of liver transplant patients\nand that deserve further analysis....
Background. This is a single center oncological resume overlooking four decades of experience with liver transplantation (LT)\nfor hepatocellular carcinoma (HCC). Methods. All 319 LT for HCC that were performed between 1975 and 2011 were included.\nPredictors for HCC recurrence (HCCR) and survival were identified by Cox regression, Kaplan-Meier analysis, Log Rank, and\n...
Objective. The lung allocation score (LAS) resulted in a lung transplantation (LT) selection process guided by clinical acuity. We\nsought to evaluate the relationship between LAS and outcomes. Methods. We analyzed Scientific Registry of Transplant Recipient\n(SRTR) data pertaining to recipients between 2005 and 2012.We stratified them into quartiles based on LAS and compared survival\nand predictors of mortality. Results. We identified 10,304 consecutive patients, comprising 2,576 in each LAS quartile (quartile 1\n(26.3ââ?¬â??35.5), quartile 2 (35.6ââ?¬â??39.3), quartile 3 (39.4ââ?¬â??48.6), and quartile 4 (48.7ââ?¬â??95.7)). Survival after 30 days (96.9% versus 96.8%\nversus 96.0% versus 94.8%), 90 days (94.6% versus 93.7% versus 93.3% versus 90.9%), 1 year (87.2% versus 85.0% versus 84.8% versus\n80.9%), and 5 years (55.4% versus 54.5% versus 52.5% versus 48.8%) was higher in the lower groups. There was a significantly higher\n5-year mortality in the highest LAS group (HR 1.13,...
Background. Posttransplant recurrence of primary focal segmental glomerulosclerosis (rFSGS) in the form of massive proteinuria\nis not uncommon and has detrimental consequences on renal allograft survival. A putative circulating permeability factor has been\nimplicated in the pathogenesis leading to widespread use of plasma exchange (PLEX).We reviewed published studies to assess the\nrole of PLEX on treatment of rFSGS in adults. Methods. Eligible manuscripts compared PLEX or variants with conventional care\nfor inducing proteinuria remission (PR) in rFSGS and were identified through MEDLINE and reference lists. Data were abstracted\nin parallel by two reviewers. Results.We detected 6 nonrandomized studies with 117 cases enrolled. In a random effects model, the\npooled risk ratio for the composite endpoint of partial or complete PR was 0,38 in favour of PLEX (95% CI: 0,23ââ?¬â??0,61).No statistical\nheterogeneity was observed among included studies (...
Living donor liver donation (LDLD) is an alternative to cadaveric liver donation.We aimed at identifying risk factors and developing\na score for prediction of postoperative complications (POCs) after LDLD in donors. This is a retrospective cohort study in 688\ndonors between June 1995 and February 2014 at Hospital SÃ?´Ã?±rio-LibanÃ?â? es and A.C. Camargo Cancer Center, in SÃ?Å?ao Paulo, Brazil.\nPrimary outcome was POC graded ââ?°Â¥III according to the Clavien-Dindo classification. Left lateral segment (LLS), left lobe (LL),\nand right lobe resections (RL) were conducted in 492 (71.4%), 109 (15.8%), and 87 (12.6%) donors, respectively. In total, 43 (6.2%)\ndeveloped POCs, which were more common after RL than LLS and LL (14/87 (16.1%) versus 23/492 (4.5%) and 6/109 (5.5%), resp.,\n...
Background: Tacrolimus is available as twice-daily Prograf�® (Tac-BID) and the once-daily formulation, Advagraf�®\n(Tac-OD). Although therapeutically equivalent, some transplant recipients require dose adjustments to achieve\nsimilar tacrolimus trough concentrations [Tac C0] after conversion between formulations. Tacrolimus is primarily\nmetabolized by cytochrome P450 3A5 (CYP3A5). We sought to determine whether genetic polymorphisms in the\nCYP3A5 enzyme; CYP3A5 *1/*1 and CYP3A5 *1/*3 (expressers) compared to CYP3A5 *3/*3 (non-expressers) could\naccount for discrepancies in dose requirements following conversion from Tac-BID to Tac-OD.\nMethods: A cohort of 60 renal transplant recipients (RTR) from our larger conversion study of 496 patients underwent\nadditional testing for CY3A5 genetic polymorphisms. Analysis included demographics, tac dosing and [Tac C0] pre- and\npost-conversion and dosing changes relative to CYP3A5 genotypes. CYP3A5 genetic polymorphisms were identified\nthrough analysis of genomic DNA.\nResults: Conversion from tac bid to tac OD in this cohort required a mean (SD) dose increase from 3.1 (1.0) mg/day to\n3.8 (1.3) mg/day (p = 0.007), to achieve similar [Tac C0]. The *1/*3 expresser group required a greater percentage dose\nadjustment (56.7 %) in converting from Tac-BID to Tac-OD as compared to the *3/*3 non-expresser group (26.6 %). Similar\nfindings were observed with the both expresser groups combined (*1/*1 &*1/*3). The expressers were significantly more\nhighly represented in the East Asian cohort.\nConclusions: The CYP3A5 expresser polymorphism necessitates an increase in dosing upon conversion from Tac-BID\nto Tac-OD, with the expresser genotypes contributing significantly to this finding. Given the variability in frequency of\nCYP3A5 genotypes in various ethnic groups, future studies should account for both isoenzyme polymorphism and\nethnicity in optimizing dosing requirements....
Cytomegalovirus (CMV) infection after lung transplantation is associated with increased risk for pneumonitis and bronchiolitis\nobliterans as well as allograft rejection and opportunistic infections. Ganciclovir is the mainstay of prophylaxis and treatment but\nCMV infections can be unresponsive. Apart from direct antiviral drugs, CMV immunoglobulin (CMVIG) preparations may be\nconsidered but are only licensed for prophylaxis. A CMV-seronegative 42-year-old man with cystic fibrosis received a lung from\na CMV-seropositive donor. Intravenous ganciclovir prophylaxis was delayed until day 12 due to acute postoperative renal failure\nand was accompanied by five doses of CMVIG (10 g). By day 16, CMV-DNA was detectable and rising; CMV-specific T-cells were\nundetectable. Switch from ganciclovir to foscarnet prompted a transient decrease in CMV viral load, but after increasing again to\nreach 3600 copies/mL foscarnet was changed to intravenous cidofovir and CMVIG was restarted. CMV load continued to fluctuate\nand declined slowly, whereas CMV-specific T-cells were detected five months later and increased thereafter. At last follow-up, the\npatient was in very good clinical condition with no evidence of bronchiolitis obliterans. No side effects of this treatment were\nobserved. In this hard-to-treat case, the combination of cidofovir with off-label use of CMVIG contributed to a successful outcome....
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