Randomized controlled trial of sustained release tacrolimus vs twice daily tacrolimus in adult living donor liver transplantation.

BACKGROUND: To compare the safety and efficacy of once-daily tacrolimus (ODT) versus twice-daily tacrolimus (BDT) in adult live donor liver transplantation (LDLT). METHODS: In this open-labelled randomized trial, 174 adult patients undergoing LDLT were randomized into ODT or BDT, combined with basiliximab induction and mycophenolate mofetil (steroid-free regimen). Tacrolimus was started at a total dose of 1 mg and the trough level was aimed at 3-7 ng/ml. The primary endpoint was eGFR at 1,3- and 6 months post-transplant, using CKD- EPI equation. Secondary endpoints included biopsy-proven acute rejection (BPAR), metabolic complications, post-operative bilio-vascular complications and patient survival. RESULTS: There was no statistically significant difference in eGFR between the two groups at 6 months (ODT -96 ± 19, BDT -91 ± 21, p value-0.164). BPAR was comparable (18/84 in ODT, 19/88 in BDT, p value-0.981). For a similar dosage of tacrolimus, the median trough tacrolimus levels attained were significantly lower for ODT than BDT during the first-month post-transplant (p value-0.001). Metabolic complications due to immunosuppression, post-operative bilio-vascular complications and patient survival was similar between the two groups at 6 months. CONCLUSION: Once-daily tacrolimus has similar renal safety and efficacy as twice-daily tacrolimus when used in combination with basiliximab induction and mycophenolate in adult LDLT.

Randomized trial of steroid free immunosuppression with basiliximab induction in adult live donor liver transplantation (LDLT).

BACKGROUND: Corticosteroids are an integral part of immunosuppression following solid organ transplantation, despite their metabolic complications. We conducted a randomized trial to evaluate the efficacy of steroid-free immunosuppression following live donor liver transplantation (LDLT). METHODS: We randomized 104 patients stratified based on pre-transplant diabetic status to either a steroid-free arm (SF-arm) (Basiliximab + Tacrolimus and Azathioprine,n = 52) or Steroid arm (S-Arm) (Steroid + Tacrolimus + Azathioprine,n = 52). The primary endpoint was the occurrence of metabolic complications (new-onset diabetes after transplant (NODAT), new-onset systemic hypertension after transplant (NOSHT), post-transplant dyslipidemia) within 6 months after transplant. Secondary endpoints included biopsy-proven acute rejection (BPAR) within six months, patient and graft survival at 6 months. RESULTS: The incidence NODAT was significantly higher in S-arm at 3 months (64.5%vs. 28.1%,p-0.004) and 6 months (51.6% vs. 15.6%,p-0.006). Likewise, the incidence of NOSHT (27.8% vs. 4.8%,p-0.01) and hypertriglyceridemia (26.7% vs. 8%,p-0.03) at six months was significantly higher in S-arm. However, there were no differences in BPAR (19.2% vs. 21.2%, p-0.81), time to first rejection (58 vs. 53 days, p-0.78), patient and graft survival (610 vs. 554 days,p- 0.22). CONCLUSION: Following LDLT, basiliximab induction with tacrolimus and azathioprine maintenance resulted in significantly lower metabolic complications compared to the triple-drug regimen of steroid, tacrolimus, and azathioprine.

Enhancement of the pathogenicity of Staphylococcus aureus strain Newman by a small noncoding RNA SprX1.

The pathogenesis of Staphylococcus aureus from local infection to systemic dissemination involves a range of virulence factors including structural and secreted products. Among various control mechanisms, small noncoding RNAs are involved in the regulation of multiple pathogenicity factors in S. aureus. The sRNA SprX which is encoded in the pathogenicity island of methicillin-susceptible S. aureus strain Newman and was shown to influence antibiotic resistance previously, upregulated the expression of virulence genes, especially the cell wall-associated clumping factor B (ClfB) and delta hemolysin (Hld). Bioinformatic analysis revealed several multiple mRNAs associated with pathogenicity as targets for SprX1, one of the three copies of sprX. Both overexpression and chromosomal disruption of sprX1 supported the scheme of upregulation of clfB and hld expression. Altered expression of SprX1 altered the levels of Hld and ClfB mRNAs, hemolysis, clumping of cells, biofilm formation by plate adhesion studies and confocal microscopic analysis as well as infection pathology of modified strains in mice models. ClfB and Hld mRNAs interacted directly with SprX1 in in vitro assays. Increased level of the regulatory RNA, namely RNAIII, that comprises Hld mRNA and also regulates the biofilm formation, indicates that SprX1 may also function through RNAIII for regulating virulence factors. An immunodominant protein, antigen A, was downregulated by SprX1 in two-dimensional electrophoresis. Taken together, these results signify the role of sRNA SprX in the pathogenicity of S. aureus Newman.

A randomized, double-blinded, placebo-controlled trial analyzing the effect of synbiotics on infectious complications following living donor liver transplant-PREPRO trial.

BACKGROUND: Following liver transplantation (LT), bacterial infections occur in over 70% of recipients leading to significant morbidity and mortality. While synbiotics have been reported to decrease infectious complications in various surgical procedures, the evidence of their benefits following LT remains limited. METHODS: In this 18-month double-blinded, investigator-initiated, placebo-controlled trial, 100 recipients of live donor liver transplant (LDLT) were randomized to receive either the synbiotic drug Prowel® (Prepro arm) or a placebo, starting 2 days pretransplant and continued for 2 weeks. The primary endpoint was culture-proven bacterial infection in blood, urine or drain fluid within 30 days. Secondary endpoints were hospital stay, noninfectious complications, antibiotic usage and 30-day mortality. RESULTS: Overall infectious complications were significantly lower in the Prepro arm in comparison to the Placebo arm (44% vs 22%, P = .019, OR 0.359; CI: 0.150-0.858). Blood stream infections were significantly less in the study arm (21.7% vs 53.3%, P = .020, OR 0.243; CI: 0.072-0.826), whereas urinary tract and intra-abdominal infections were similar. Length of hospital stay, noninfectious complications, deviation from protocol antibiotics and 30-day mortality were comparable. CONCLUSION: Synbiotics administered for 2 weeks following LDLT significantly reduced overall and blood stream infectious complications in the early postoperative period. However, there was no difference in hospital stay, noninfectious complications, antibiotic usage and mortality. Clinical Trial Registry of India registration number - CTRI/2017/09/009869.