No abstract

Background Timing of initiation of kidney-replacement therapy (KRT) in critically ill patients remains controversial. The Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial compared two strategies of KRT initiation (accelerated versus standard) in critically ill patients with acute kidney injury and found neutral results for 90-day all-cause mortality. Probabilistic exploration of the trial endpoints may enable greater understanding of the trial findings. We aimed to perform a reanalysis using a Bayesian framework. Methods We performed a secondary analysis of all 2927 patients randomized in multi-national STARRT-AKI trial, performed at 168 centers in 15 countries. The primary endpoint, 90-day all-cause mortality, was evaluated using hierarchical Bayesian logistic regression. A spectrum of priors includes optimistic, neutral, and pessimistic priors, along with priors informed from earlier clinical trials. Secondary endpoints (KRT-free days and hospital-free days) were assessed using zero–one inflated beta regression. Results The posterior probability of benefit comparing an accelerated versus a standard KRT initiation strategy for the primary endpoint suggested no important difference, regardless of the prior used (absolute difference of 0.13% [95% credible interval [CrI] − 3.30%; 3.40%], − 0.39% [95% CrI − 3.46%; 3.00%], and 0.64% [95% CrI − 2.53%; 3.88%] for neutral, optimistic, and pessimistic priors, respectively). There was a very low probability that the effect size was equal or larger than a consensus-defined minimal clinically important difference. Patients allocated to the accelerated strategy had a lower number of KRT-free days (median absolute difference of − 3.55 days [95% CrI − 6.38; − 0.48]), with a probability that the accelerated strategy was associated with more KRT-free days of 0.008. Hospital-free days were similar between strategies, with the accelerated strategy having a median absolute difference of 0.48 more hospital-free days (95% CrI − 1.87; 2.72) compared with the standard strategy and the probability that the accelerated strategy had more hospital-free days was 0.66. Conclusions In a Bayesian reanalysis of the STARRT-AKI trial, we found very low probability that an accelerated strategy has clinically important benefits compared with the standard strategy. Patients receiving the accelerated strategy probably have fewer days alive and KRT-free. These findings do not support the adoption of an accelerated strategy of KRT initiation.

The present study evaluated the effects of maternal dietary energy intake and starch-to-fat ratio during late gestation on the performance and lipid metabolism of sows and their offspring. On day 84 of gestation, 80 Landrace × Yorkshire primiparous sows were assigned to 2 × 2 factorial arrangements according to body weight following a randomized complete block design. The factors were daily energy intake (8,375 kcal ME/d [CE] vs. 9,600 kcal ME/d [HE]) and dietary starch-to-fat ratio (10:1 [CR] vs. 15:1 [HR]). All sows were fed one of four diets from day 85 of gestation until farrowing. Data were analyzed using the GLM procedure in SPSS. High energy intake increased the body weight of sows on day 110 of gestation (P = 0.031) as well as the weight of piglets at birth (P = 0.018). Increased energy intake elevated the plasma triglyceride concentrations in sows (P = 0.027) and piglets (P = 0.044). Maternal high energy intake altered the liver metabolome of newborn piglets in terms of metabolites related to carbohydrate and linoleic acid metabolism. Moreover, maternal high energy intake increased hepatic total cholesterol (P = 0.023) and triglyceride (P = 0.026) concentration in newborn piglets. Furthermore, maternal high energy intake significantly increased the transcript abundance of fatty acid synthase (FAS; P = 0.001) and protein abundance of phosphorylated protein kinase B (P =0.001) in the liver of newborn piglets. A high starch-to-fat ratio reduced low-density lipoprotein cholesterol (LDL-C) concentration in the plasma of sows (P = 0.044) and newborn piglets (P = 0.048) as well as in the liver of newborn piglets (P = 0.015). Furthermore, maternal high starch-to-fat ratio increased the transcript abundances of FAS (P = 0.004) in newborn piglets. In conclusion, high daily energy intake of sows increased the birth weight of newborn piglets. Moreover, maternal high daily energy intake and high dietary starch-to-fat ratio improved the lipid metabolism of newborn piglets.

The enteric nervous system (ENS) is important for the intestinal barrier to defend and regulate inflammation in the intestine. The aim of this study was to investigate the effect of pyrroloquinoline quinone (PQQ) on regulating neuropeptide secretion by ENS neurons of rats challenged with lipopolysaccharide (LPS) to create enteritis. Thirty Sprague Dawley rats were divided into five groups, namely, basal (CTRL), basal plus LPS challenge (LPS), basal with 2.5 mg/kg b.w./day of PQQ plus challenge with LPS (PQQ 2.5), basal with 5.0 mg/kg b.w./day PQQ plus challenge with LPS (PQQ 5), and basal with 10.0 mg/kg b.w./day PQQ plus challenge with LPS (PQQ 10). After treatment with basal diet or PQQ for 14 days, rats were challenged with LPS except for the CTRL group. Rats were euthanized 6 h after the LPS challenge. Rats showed an increased average daily gain in PQQ treatment groups (P < 0.05). Compared with the LPS group, PQQ 5 and PQQ 10 rats showed increased villus height and villus height/crypt depth of jejunum (P < 0.05). In PQQ treatment groups, concentrations of IL-1β and TNF-α in serum and intestine of rats were decreased, and IL-10 concentration was increased in serum compared with the LPS group (P < 0.05). Compared with the LPS group, the concentration of neuropeptide Y (NPY), nerve growth factor (NGF), vasoactive intestinal peptide (VIP), substance P (SP), calcitonin gene-related peptide (CGRP), and brain-derived neurotropic factor (BDNF) in serum were decreased in PQQ treatment groups (P < 0.05). Compared with the LPS group, ileal mRNA levels of BDNF, NPY, and NGF were decreased in PQQ treatment groups (P < 0.05). Jejunal concentrations of SP, CGRP, VIP, BDNF, NPY, and NGF were decreased in PQQ treatment groups compared with the LPS group (P < 0.05). Compared with the LPS group, phosphor-protein kinase B (p-Akt)/Akt levels in jejunum and colon were decreased in PQQ treatment groups (P < 0.05). In conclusion, daily treatment with PQQ improved daily gain, jejunal morphology, immune responses. PQQ-regulated enteric neurochemical plasticity of ENS via the Akt signaling pathway of weaned rats suffering from enteritis.

This experiment aimed to evaluate the effects of dietary starch-to-fat ratio on reproductive performance and lipid metabolism of sows and newborn piglets. A total of 75 Landrace × Yorkshire multiparous sows at d 84 of gestation were selected and randomly divided into three groups based on body weight. From d 85 of gestation to farrowing, sows were fed one of three dietary starch-to-fat ratios (20:1, 10:1, and 5:1). Dietary high starch-to-fat ratio increased the birth weight of piglets (p < 0.05). The apparent total digestibility of dry matter, organic matter, and gross energy of sows was improved by an increasing starch-to-fat ratio during gestation (p < 0.05). Decreased dietary starch-to-fat ratio increased the concentration of plasma triglycerides, total cholesterol, and GSH-Px in sows (p < 0.05). During parturition, sows had increased plasma interleukin (IL) -1β, IL-6, and tumor necrosis factor α in the low ratio group (p < 0.05). The relative abundance of Streptococcaceae in the low ratio group was significantly higher (p < 0.05). The medium dietary starch-to-fat ratio significantly increased the concentrations of short chain fatty acids. In conclusion, this study suggested that for sows a diet with ahigh starch to fat ratio could ameliorate lipid metabolism disorder and maternal inflammation during late gestation.