Gastrointestinal (GI) bacterial translocation in sepsis is well known, but the role of species probiotics is still controversial. We evaluated the therapeutic effects of L34 in a new sepsis model of oral administration of pathogenic bacteria with GI leakage induced by either an antibiotic cocktail (ATB) and/or dextran sulfate sodium (DSS). GI leakage with ATB, DSS, and DSS plus ATB (DSS+ATB) was demonstrated by fluorescein isothiocyanate (FITC)-dextran translocation to the circulation. The administration of pathogenic bacteria, either or serovar Typhimurium, enhanced translocation. Bacteremia was demonstrated within 24 h in 50 to 88% of mice with GI leakage plus the administration of pathogenic bacteria but not with GI leakage induction alone or bacterial gavage alone. bacteremia was found in only 16 to 29% and 0% of mice with and administrations, respectively. bacteremia was demonstrated in 25 to 33% and 10 to 16% of mice with and administrations, respectively. L34 attenuated GI leakage in these models, as shown by the reductions of FITC-dextran gut translocation, serum interleukin-6 (IL-6) levels, bacteremia, and sepsis mortality. The reduction in the amount of fecal bacteria with treatment was demonstrated. In addition, an anti-inflammatory effect of the conditioned medium from L34 was also demonstrated by the attenuation of cytokine production in colonic epithelial cells In conclusion, L34 attenuated the severity of symptoms in a murine sepsis model induced by GI leakage and the administration of pathogenic bacteria.

The outcomes of kidney transplantation (KT) from hepatitis B surface antigen-positive [HBsAg(þ)] donors to HBsAg(À) recipients remain inconclusive, possibly due to substantial differences in methodological and statistical models, number of patients, follow-up duration, hepatitis B virus (HBV) prophylactic regimens and hepatitis B surface antibody (anti-HBs) levels. The present retrospective, longitudinal study (clinicaltrial. gov NCT02044588) using propensity score matching technique was conducted to compare outcomes of KT between HBsAg(À) recipients with anti-HBs titer above 100 mIU/mL undergoing KT from HBsAg(þ) donors (n ¼ 43) and HBsAg(À) donors (n ¼ 86). During the median follow-up duration of 58.2 months (range 16.7-158.3 months), there were no significant differences in graft and patient survivals. No HBV-infective markers, including HBsAg, hepatitis B core antibody, hepatitis B extracellular antigen and HBV DNA quantitative test were detected in HBsAg(þ) donor group. Renal pathology outcomes revealed comparable incidences of kidney allograft rejection while there were no incidences of HBV-associated glomerulonephritis and viral antigen staining. Recipients undergoing KT from HBsAg(þ) donors with no HBV prophylaxis (n ¼ 20) provided comparable outcomes with those treated with lamivudine alone (n ¼ 21) or lamivudine in combination with HBV immunoglobulin (n ¼ 2). In conclusion, KT without HBV prophylaxis from HBsAg(þ) donors without hepatitis B viremia to HBsAg(À) recipients with anti-HBs titer above 100 mIU/mL provides excellent graft and patient survivals without evidence of HBV transmission.

BackgroundAn early sepsis-induced acute kidney injury (sepsis-AKI) biomarker is currently in needed. Urinary neutrophil gelatinase-associated lipocalin (uNGAL) is a candidate of sepsis-AKI biomarker but with different cut-point values. Urinary exosomal activating transcriptional factor 3 (uATF3) has been mentioned as an interesting biomarker.MethodsWe conducted experiments in mice and a prospective, multicenter study in patients as a proof of concept that urine exosome is an interesting biomarker. An early expression of ATF3 in kidney of CD-1 mice at 6 h after cecal ligation and puncture implied the possibility of uATF3 as an early sepsis-AKI biomarker. Increase serum creatinine (Scr) ≥0.3 mg/dL from the baseline was used as an AKI diagnosis and urine was analyzed for uATF3 and uNGAL. Patients with baseline Scr at admission ≥1.5 mg/dL were excluded.ResultsThe analysis showed higher Scr, uNGAL and uATF3 in patients with sepsis-AKI in comparison with patients with sepsis-non-AKI and healthy volunteers. A fair correlation, r2 = 0.47, between uATF3 and uNGAL was showed in sepsis-AKI group with Scr ≥2 mg/dL. To see if uATF3 could be an early sepsis-AKI biomarker, urine sample was collected daily during the first week of the admission. In sepsis-AKI and sepsis-non-AKI groups, uNGAL were 367 ± 43 ng/mL and 183 ± 23 ng/mL, respectively; and uATF3 were 19 ± 4 ng/mL and 1.4 ± 0.8 ng/mL, respectively. With the mean value of uNGAL and uATF3 in sepsis AKI as a cut-off level, AUROC of uNGAL and uATF3 were 64% (95% CI 0.54 to 0.74) and 84% (95% CI 0.77 to 0.91), respectively.ConclusionsUrine exosome is an interesting source of urine biomarker and uATF3 is an interesting sepsis-AKI biomarker.

We demonstrated that prior serum cytokine accumulation increased serum miR-122 in indirect liver injury induced by BUO/BiNx and less severe sepsis mouse models. Cytokine accumulation may be responsible for miR-122 expression in these models. The clinical importance of liver injury demonstrated by the discordance between serum miR-122 and ALT was an interesting issue.