Effect of goal-directed fluid therapy on renal function in critically ill patients: a systematic review and meta-analysis.

OBJECTIVE: To evaluate whether goal-directed fluid therapy (GDFT) reduces the risk of renal injury in critical illness. METHODS: MEDLINE via PubMed, EMBASE, CENTRAL and CBM was searched from inception to 13 March 2022, for studies comparing the effect of GDFT with usual care on renal function in critically ill patients. GDFT was defined as a protocolized intervention based on hemodynamic and/or oxygen delivery parameters. A fixed or random effects model was applied to calculate the pooled odds ratio (OR) based on heterogeneity through the included studies. RESULTS: A total of 28 studies with 9,019 patients were included. The pooled data showed that compared with usual care, GDFT reduced the incidence of acute kidney injury (AKI) in critical illness (OR 0.62, 95% confidence interval (CI) 0.47 to 0.80, p< 0.001). Sensitivity analysis with only low risk of bias studies showed the same result. Subgroup analyses found that GDFT was associated with a lower AKI incidence in both postoperative and medical patients. The reduction was significant in GDFT aimed at dynamic indicators. However, no significant difference was found between groups in RRT support (OR 0.88, 95% CI 0.74 to 1.05, p= 0.17). GDFT tended to increase fluid administration within the first 6 h, decrease fluid administration after 24 h, and was associated with more vasopressor requirements. CONCLUSIONS: This meta-analysis suggests that GDFT aimed at dynamic indicators may be an effective way to prevent AKI in critical illness. This may indicate a benefit from early adequate fluid resuscitation and the combined effect of vasopressors.

Renal echography for predicting acute kidney injury in critically ill patients: a prospective observational study.

Objective: To investigate the diagnostic performances of renal resistive index (RRI) and semiquantitative power Doppler ultrasound (PDU) scores in predicting acute kidney injury (AKI) stage 3 in critically ill patients.Methods: This prospective observational study included 148 patients (80 with reduced cardiac index [CI], 68 with maintained CI). RRI and semiquantitative PDU scores were measured within 6 h after intensive care unit admission. AKI was defined according to Kidney Disease Improving Global Outcomes criteria.Results: A negative correlation between RRI and PDU score (r = -0.517, p < 0.001) and a positive correlation between PDU score and CI (r = 0.193, p = 0.019) were found, whereas RRI was not correlated with CI (r = 0.131, p = 0.121). The predictive value of RRI for AKI stage 3 was similar between CI-reduced (area under the curve [AUC] 0.761, 95% confidence interval 0.650-0.851, p < 0.001) and CI-maintained (AUC 0.786, 95% confidence interval 0.665-0.878, p < 0.001) patients. Conversely, PDU score could effectively predict AKI stage 3 in CI-reduced patients (AUC 0.872, 95% confidence interval 0.778-0.936, p < 0.001) but not in CI-maintained patients (AUC 0.669, 95% confidence interval 0.544-0.778, p = 0.071). The predictive value of PDU score for AKI stage 3 was statistically different between CI-reduced and CI-maintained patients (p = 0.021).Conclusions: PDU scores could effectively predict AKI stage 3 in CI-reduced patients but not in CI-maintained patients. RRI is a poor predictor of AKI stage 3 in patients with reduced or maintained CI.

Peroxisome proliferator-activated receptor gamma participates in the acquisition of brain ischemic tolerance induced by ischemic preconditioning via glial glutamate transporter 1 in vivo and in vitro.

Glial glutamate transporter 1 (GLT-1) plays a vital role in the induction of brain ischemic tolerance (BIT) by ischemic preconditioning (IPC). However, the mechanism still needs to be further explained. The aim of this study was to investigate whether peroxisome proliferator-activated receptor gamma (PPARγ) participates in regulating GLT-1 during the acquisition of BIT induced by IPC. Initially, cerebral IPC induced BIT and enhanced PPARγ and GLT-1 expression in the CA1 hippocampus in rats. The ratio of nuclear/cytoplasmic PPARγ was also increased. At the same time, the up-regulation of PPARγ expression in astrocytes in the CA1 hippocampus was revealed by double immunofluorescence for PPARγ and glial fibrillary acidic protein. Then, the mechanism by which PPARγ regulates GLT-1 was studied in rat cortical astrocyte-neuron cocultures. We found that IPC [45 min of oxygen glucose deprivation (OGD)] protected neuronal survival after lethal OGD (4 h of OGD), which usually leads to neuronal death. The activation of PPARγ occurred earlier than the up-regulation of GLT-1 in astrocytes after IPC, as determined by western blot and immunofluorescence. Moreover, the preadministration of the PPARγ antagonist T0070907 or PPARγ siRNA significantly attenuated GLT-1 up-regulation and the neuroprotective effects induced by IPC in vitro. Finally, the effect of the PPARγ antagonist on GLT-1 expression and BIT was verified in vivo. We observed that the preadministration of T0070907 by intracerebroventricular injection dose-dependently attenuated the up-regulation of GLT-1 and BIT induced by cerebral IPC in rats. In conclusion, PPARγ participates in regulating GLT-1 during the acquisition of BIT induced by IPC. Cover Image for this issue: doi: 10.1111/jnc.14532. Open Science: This manuscript was awarded with the Open Materials Badge For more information see: https://cos.io/our-services/open-science-badges/.

Does training improve diagnostic accuracy and inter-rater agreement in applying the Berlin radiographic definition of acute respiratory distress syndrome? A multicenter prospective study.

BACKGROUND: Poor inter-rater reliability in chest radiograph interpretation has been reported in the context of acute respiratory distress syndrome (ARDS), although not for the Berlin definition of ARDS. We sought to examine the effect of training material on the accuracy and consistency of intensivists' chest radiograph interpretations for ARDS diagnosis. METHODS: We conducted a rater agreement study in which 286 intensivists (residents 41.3%, junior attending physicians 35.3%, and senior attending physician 23.4%) independently reviewed the same 12 chest radiographs developed by the ARDS Definition Task Force ("the panel") before and after training. Radiographic diagnoses by the panel were classified into the consistent (n = 4), equivocal (n = 4), and inconsistent (n = 4) categories and were used as a reference. The 1.5-hour training course attended by all 286 intensivists included introduction of the diagnostic rationale, and a subsequent in-depth discussion to reach consensus for all 12 radiographs. RESULTS: Overall diagnostic accuracy, which was defined as the percentage of chest radiographs that were interpreted correctly, improved but remained poor after training (42.0 ± 14.8% before training vs. 55.3 ± 23.4% after training, p < 0.001). Diagnostic sensitivity and specificity improved after training for all diagnostic categories (p < 0.001), with the exception of specificity for the equivocal category (p = 0.883). Diagnostic accuracy was higher for the consistent category than for the inconsistent and equivocal categories (p < 0.001). Comparisons of pre-training and post-training results revealed that inter-rater agreement was poor and did not improve after training, as assessed by overall agreement (0.450 ± 0.406 vs. 0.461 ± 0.575, p = 0.792), Fleiss's kappa (0.133 ± 0.575 vs. 0.178 ± 0.710, p = 0.405), and intraclass correlation coefficient (ICC; 0.219 vs. 0.276, p = 0.470). CONCLUSIONS: The radiographic diagnostic accuracy and inter-rater agreement were poor when the Berlin radiographic definition was used, and were not significantly improved by the training set of chest radiographs developed by the ARDS Definition Task Force. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (registration number NCT01704066 ) on 6 October 2012.

A mouthpart transcriptome for Spodoptera frugiperda adults: identification of candidate chemoreceptors and investigation of expression patterns.

Moth mouthparts, consisting of labial palps and proboscis, not only are the feeding device but also are chemosensory organs for the detection of chemical signals from surrounding environment. Up to now, the chemosensory systems in the mouthpart of moths are largely unknown. Here, we performed systematic analyses of the mouthpart transcriptome of adult Spodoptera frugiperda (Lepidoptera: Noctuidae), a notorious pest that spreads worldwide. A total of 48 chemoreceptors, including 29 odorant receptors (ORs), 9 gustatory receptors (GRs), and 10 ionotropic receptors (IRs), were annotated. Further phylogenetic analyses with these genes and homologs from other insect species determined that specific genes, including ORco, carbon dioxide receptors, pheromone receptor, IR co-receptors, and sugar receptors, were transcribed in the mouthpart of S. frugiperda adults. Subsequently, expression profiling in different chemosensory tissues demonstrated that the annotated ORs and IRs were mainly expressed in S. frugiperda antennae, but one IR was also highly expressed in the mouthparts. In comparison, SfruGRs were mainly expressed in the mouthparts, but 3 GRs were also highly expressed in the antennae or the legs. Further comparison of the mouthpart-biased chemoreceptors using RT-qPCR revealed that the expression of these genes varied significantly between labial palps and proboscises. This study provides the first large-scale description of chemoreceptors in the mouthpart of adult S. frugiperda and provides a foundation for further functional studies of chemoreceptors in the mouthpart of S. frugiperda as well as of other moth species.

Status and Risk Factors in Patients Requiring Unplanned Intensive Care Unit Readmission Within 48 Hours: A Retrospective Propensity-Matched Study in China.

Aim: This study investigated the current status and related risk factors of 48-hour unplanned return to the intensive care unit (ICU) to reduce the return rate and improve the quality of critical care management. Methods: Data were collected from 2365 patients discharged from the comprehensive ICU. Multivariate and 1:1 propensity score matching analyses were performed. Results: Forty patients (1.69%) had unplanned readmission to the ICU within 48 hours after transfer. The primary reason for return was respiratory failure (16 patients, 40%). Furthermore, respiratory failure (odds ratio [OR] = 5.994, p = 0.02) and the number of organ failures (OR = 5.679, p = 0.006) were independent risk factors for unplanned ICU readmission. Receiver operating characteristic curves were drawn for the predictive value of the number of organ injuries during a patient's unplanned transfer to the ICU (area under the curve [AUC] = 0.744, sensitivity = 60%, specificity = 77.5%). Conclusion: The reason for patient transfer and the number of organ injuries during the process were independent risk factors for patients who were critically ill. The number of organs damaged had a predictive value on whether the patient would return to the ICU within 48 hours.

Vancomycin dosing in an obese patient with acute renal failure: A case report and review of literature.

BACKGROUND: Vancomycin is the most commonly used drug for methicillin-resistant Staphylococcus aureus. The empirical clinical doses of vancomycin based on non-obese patients may not be optimal for obese ones. CASE SUMMARY: This study reports a case of vancomycin dosing adjustment in an obese patient (body mass index 78.4 kg/m2) with necrotizing fasciitis of the scrotum and left lower extremity accompanied with acute renal failure. Dosing adjustment was performed based on literature review and factors that influence pharmacokinetic parameters are analyzed. The results of the blood drug concentration monitoring confirmed the successful application of our dosing adjustment strategy in this obese patient. Total body weight is an important consideration for vancomycin administration in obese patients, which affects the volume of distribution and clearance of vancomycin. The alterations of pharmacokinetic parameters dictate that vancomycin should be dose-adjusted when applied to obese patients. At the same time, the pathophysiological status of patients, such as renal function, which also affects the dose adjustment of the patient, should be considered. CONCLUSION: Monitoring vancomycin blood levels in obese patients is critical to help adjust the dosing regimen to ensure that vancomycin concentrations are within the effective therapeutic range and to reduce the incidence of renal injury.

Efficacy and safety of methylene blue in patients with vasodilatory shock: A systematic review and meta-analysis.

Background: The role of methylene blue (MB) in patients with vasodilatory shock is unclear. The purpose of this systematic review and meta-analysis was to evaluate the efficacy and safety of MB in patients with vasodilatory shock. Methods: We searched MEDLINE at PubMed, Embase, Web of Science, Cochrane, CNKI, CBM and Wanfang Medical databases for all observational and intervention studies comparing the effect of MB vs. control in vasodilatory shock patients. This study was performed in accordance with the PRISMA statement. There were no language restrictions for inclusion. Results: A total of 15 studies with 832 patients were included. Pooled data demonstrated that administration of MB along with vasopressors significantly reduced mortality [odds ratio (OR) 0.54, 95% confidence interval (CI) 0.34 to 0.85, P = 0.008; I 2 = 7%]. This benefit in mortality rate was also seen in a subgroup analysis including randomized controlled trials and quasi-randomized controlled trials. In addition, the vasopressor requirement was reduced in the MB group [mean difference (MD) -0.77, 95%CI -1.26 to -0.28, P = 0.002; I 2 = 80%]. Regarding hemodynamics, MB increased the mean arterial pressure, heart rate and peripheral vascular resistance. In respect to organ function, MB was associated with a lower incidence of renal failure, while in regards to oxygen metabolism, it was linked to reduced lactate levels. MB had no effect on the other outcomes and no serious side effects. Conclusions: Concomitant administration of MB and vasopressors improved hemodynamics, decreased vasopressor requirements, reduced lactate levels, and improved survival in patients with vasodilatory shock. However, further studies are required to confirm these findings. Systematic review registration: Identifier: CRD42021281847.

Exploration of Clove Bud (Syzygium aromaticum) Essential Oil as a Novel Attractant against Bactrocera dorsalis (Hendel) and Its Safety Evaluation.

The oriental fruit fly Bactrocera dorsalis (Hendel) is a destructive polyphagous species that targets many economically important fruits and vegetables. The primary control of B. dorsalis relies mainly on the use of synthetic chemicals, and excessive use of these chemicals has adverse effects on both the environment and human health. Environmentally friendly management of pests involving plant essential oils is useful for controlling the populations of pests responsible for decreasing the yields and quality of crops. In the present study, we demonstrate that clove bud essential oil (CBEO) is strongly attractive to sexually mature males. Mature males responded to the CBEO differently throughout the day; the strongest response was elicited during the day and decreased at dusk. Virgin and mated mature males did not respond differently to CBEO. No obvious response behaviour to the CBEO was observed in two species of beneficial natural predator ladybirds. In addition, a cytotoxicity assessment demonstrated that CBEO is nontoxic to normal human and mouse cells. Based on our laboratory experiments, CBEO may serve as a promising, sustainable, and environmentally friendly attractant for B. dorsalis males; however, field experiments are needed to confirm this hypothesis.

Afterload-related cardiac performance predicts prognosis in critical ill patients with sepsis: A prospective observational pilot study.

ABSTRACT: To investigate the usefulness of afterload-related cardiac performance (ACP) for assessing cardiac impairment and predicting prognosis in septic patients.Adult patients with sepsis in the intensive care unit were included. Cardiac output, cardiac index, cardiac power index, and ACP were calculated at the time of admission (D0) and 48-72 h after admission (D3). They were correlated with Acute Physiology and Chronic Health Evaluation II and sequential organ failure assessment scores, then the prognostic values were analyzed.A total of 41 patients with sepsis were selected. ACP showed a stronger negative correlation with Acute Physiology and Chronic Health Evaluation II and sequential organ failure assessment scores than cardiac output, cardiac index, and cardiac power index. ACP predicted 28-day mortality with an area under the curve of 0.775 and 0.976 on D0 and D3, respectively. In addition, most non-survivors had emergent cardiac impairment (ACP ≤ 80%) on D0, and cardiac function was deteriorated on D3. Survival analysis showed that the patients with a decreased ACP from D0 to D3 had the highest mortality. The decrease of ACP on D3 was an independent risk factor for mortality (hazard ratio, 11.89; P = .0028).ACP can be used to assess the severity of cardiac impairment in sepsis. Continued decline of ACP during the first 3 days strongly suggests a poor prognosis.

Risk Factors for Postoperative Mortality in Patients with Acute Stanford Type A Aortic Dissection.

OBJECTIVE: The present study explored the risk factors of postoperative mortality in patients with acute Stanford type A aortic dissection (AD). METHODS: The study included 149 patients with acute Stanford type A AD who were treated at the Fourth Hospital of Hebei Medical University, China, from October 2016 to October 2018. The patients were divided into a death (n = 42) and survival group (n = 107) according to individual prognosis. Univariate analysis of all possible related risk factors was conducted; multivariate logistic regression analysis of the potential risk factors that showed statistical differences in the univariate analysis was also performed. RESULTS: The results of the univariate analysis showed that a body mass index (BMI) ≥25 kg/m2, surgery duration, duration of cardiopulmonary bypass, duration of cardiopulmonary bypass assistance, total transfusion of red blood cells, postoperative APACHE II score, sequential organ failure assessment (SOFA) score, low cardiac output, acute kidney injury (AKI), hypoxemia, diffuse intravascular coagulation (DIC), hepatic failure and other related complications, as well as postoperative stay duration in the intensive care unit (ICU), were closely correlated with a poor prognosis among patients. Multivariate logistic regression analysis showed that a BMI ≥25 kg/m2, SOFA score >8, duration of cardiopulmonary bypass assistance >70 minutes, postoperative low cardiac output, and postoperative DIC were independent risk factors for postoperative death in patients with acute Stanford type A AD. CONCLUSION: A BMI ≥25 kg/m2, SOFA score >8, duration of cardiopulmonary bypass assistance >70 min, postoperative DIC, and postoperative low cardiac output were the independent risk factors for postoperative death in acute Stanford type A AD. Intraoperative blood transfusion, postoperative hepatic failure, and AKI, among others, correlated with an increased risk of death but were not independent risk factors for death.

Protective effects and mechanisms of high-dose vitamin C on sepsis-associated cognitive impairment in rats.

Sepsis survivors present long-term cognitive deficits. The present study was to investigate the effect of early administration of high-dose vitamin C on cognitive function in septic rats and explore its possible cerebral protective mechanism. Rat sepsis models were established by cecal ligation and puncture (CLP). Ten days after surgery, the Morris water maze test was performed to evaluate the behavior and cognitive function. Histopathologic changes in the hippocampus were evaluated by nissl staining. The inflammatory cytokines, activities of antioxidant enzymes (superoxide dismutase or SOD) and oxidative products (malondialdehyde or MDA) in the serum and hippocampus were tested 24 h after surgery. The activity of matrix metalloproteinase-9 (MMP-9) and expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1(HO-1) in the hippocampus were measured 24 h after surgery. Compared with the sham group in the Morris water maze test, the escape latency of sepsis rats was significantly (P = 0.001) prolonged in the navigation test, whereas the frequency to cross the platform and the time spent in the target quadrant were significantly (P = 0.003) reduced. High-dose vitamin C significantly decreased the escape latency (P = 0.01), but increased the time spent in the target quadrant (P = 0.04) and the frequency to cross the platform (P = 0.19). In the CLP+ saline group, the pyramidal neurons were reduced and distributed sparsely and disorderly, the levels of inflammatory cytokines of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 in the serum and hippocampus were significantly increased (P = 0.000), the blood brain barrier (BBB) permeability in the hippocampus was significantly (P = 0.000) increased, the activities of SOD in the serum and hippocampus were significantly (P = 0.000 and P = 0.03, respectively) diminished while the levels of MDA in the serum and hippocampus were significantly (P = 0.007) increased. High-dose vitamin C mitigated hippocampus histopathologic changes, reduced systemic inflammation and neuroinflammation, attenuated BBB disruption, inhibited oxidative stress in brain tissue, and up-regulated the expression of nuclear and total Nrf2 and HO-1. High-dose vitamin C significantly (P < 0.05) decreased the levels of tumor necrosis factor- (TNF)-α, interleukin-6 (IL-6), MDA in the serum and hippocampus, and the activity of MMP-9 in the hippocampus, but significantly (P < 0.05) increased the levels of SOD, the anti-inflammatory cytokine (IL-10) in the serum and hippocampus, and nuclear and total Nrf2, and HO-1 in the hippocampus. In conclusion, high-dose vitamin C can improve cognition impairment in septic rats, and the possible protective mechanism may be related to inhibition of inflammatory factors, alleviation of oxidative stress, and activation of the Nrf2/HO-1 pathway.

Hydrogen Sulfide Attenuated Sepsis-Induced Myocardial Dysfunction Through TLR4 Pathway and Endoplasmic Reticulum Stress.

Aims: We examined the change in endogenous hydrogen sulfide (H2S) production and its role in sepsis-induced myocardial dysfunction (SIMD). Results: Significant elevations in plasma cardiac troponin I (cTnI), creatine kinase (CK), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) were noted in SIMD patients, whereas left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), and plasma H2S were significantly decreased relative to those in the controls. Plasma H2S was linearly related to LVEF and LVFS. Subsequently, an SIMD model was developed in mice by injecting lipopolysaccharide (LPS), and NaHS, an H2S donor, was used to elucidate the pathophysiological role of H2S. The mice showed decreased ventricular function and increased levels of TNF-α, IL-1ß, cTnI, and CK after LPS injections. Toll-like receptor (TLR) 4 protein and endoplasmic reticulum stress (ERS) proteins were over expressed in the SIMD mice. All of the parameters above showed more noticeable variations in cystathionine γ-lyase knockout mice relative to those in wild type mice. The administration of NaHS could improve ventricular function and attenuate inflammation and ERS in the heart. Conclusion: Overall, these findings indicated that endogenous H2S deficiency contributed to SIMD and exogenous H2S ameliorated sepsis-induced myocardial dysfunction by suppressing inflammation and ERS via inhibition of the TLR4 pathway.

[The effect of caspase-3 inhibitor on the concentrations of serum inflammatory cytokines in sepsis related acute kidney injury induced by peritoneal cavity infection in mice].

OBJECTIVE: To observe the effects of caspase-3 inhibitor Ac-DEVD-CHO on the concentrations of serum inflammatory cytokines in sepsis related acute kidney injury induced by peritoneal cavity infection in mice. METHODS: One hundred and two male C57BL/6 mice were subjected to cecal ligation and puncture (CLP, a model of polymicrobial sepsis) or sham operation. The animals were assigned into three equal groups (n=34) according to random number table: sham group, model group, and caspase-3 inhibitor (CI) group. Thirty minutes before CLP, Ac-DEVD-CHO (4 µg/g) was injected subcutaneously in CI group. The levels of blood urea nitrogen (BUN) and creatinine (Cr) were determined, and the concentrations of tumor necrosis factor-α (TNF-α), interleukins (IL-6 and IL-10) were measured by enzyme linked immunosorbent assay (ELISA), the renal cell apoptosis rate was determined by flow cytometry and the expression of caspase-3 mRNA was determined by real time reverse transcription-polymerase chain reaction (RT-PCR) at 6, 12 and 24 hours after operation. The 4-day and 7-day survival rates of three groups of mice were observed. RESULTS: Compared with sham group, the concentrations of serum BUN, TNF-α, IL-6, IL-10 and the renal cell apoptosis rates, the caspase-3 mRNA expression were increased significantly at all time points after CLP, the concentrations of serum Cr were increased significantly at 6 hours, with the 4-day and 7-day survival rates were decreased significantly. Compared with model group, in CI group, the concentrations of serum BUN were decreased significantly at all time points after operation and those of Cr were decreased significantly at 6 hours, then restored to those of the sham group at 12 hours and 24 hours; the concentrations of serum TNF-α, IL-6 were decreased and those of IL-10 elevated significantly at all time points [TNF-α (µg/L) 6 hours: 436.2±64.2 vs. 653.6±8.9, 12 hours: 233.4±85.4 vs. 579.7±137.1, 24 hours: 151.0±90.3 vs. 551.0±119.8; IL-6 (µg/L) 6 hours: 1 033.2±345.8 vs. 1 595.3±159.4, 12 hours : 366.3±68.3 vs. 1 330.7±249.8, 24 hours: 241.2±208.4 vs. 815.3±572.7; IL-10 (µg/L) 6 hours : 33.6±10.4 vs. 26.6±4.5, 12 hours: 37.2±5.0 vs. 24.5±4.3, 24 hours: 38.3±5.5 vs. 18.2±1.6, all P<0.05]; the renal cell apoptosis rate and the expression of caspase-3 mRNA were decreased significantly at all time points [apoptosis rates 6 hours: (13.9±3.2)% vs. (18.3±1.4)%, 12 hours: (10.5±3.6)% vs. (15.9±3.5)%, 24 hours: (8.4±1.8)% vs. (12.5±2.1)%; caspase-3 mRNA 6 hours: 1.95±0.16 vs. 3.84±0.35, 12 hours: 1.89±0.19 vs. 3.97±0.73, 24 hours : 2.01±0.20 vs. 4.97±0.24, all P<0.05]. The 4-day survival rate of CI group was improved (80% vs. 20%), but that of 7-day did not change (20% vs. 20%). CONCLUSION: The modulation of caspase-3 inhibitor on the concentrations of serum inflammatory cytokines in sepsis related acute kidney injury induced by peritoneal cavity infection may be associated with a decrease in renal cell apoptosis by Ac-DEVD-CHO.

[Changes in adrenal cortex function and protective effect of dexamethasone in septic rats during early phases].

OBJECTIVE: To affirm the presence of relative adrenal insufficiency (RAI) in the early phases of sepsis and its probable mechanisms, and to study the optimal time for glucocorticoid replacement therapy. METHODS: A total of 260 healthy male Wistar rats were randomized into five groups (each group n=52), including normal control group, sham operation group, cecal ligation and puncture (CLP) group, dexamethasone prevention group (with 10 mg/kg dexamethasone injection into the abdominal cavity before CLP) and dexamethasone treatment group (with 10 mg/kg dexamethasone injection into the abdominal cavity 7 hours after CLP). Each group was subdivided into five subgroups according to five time points: 2, 4, 6, 8 and 12 hours. Adrenocorticotrophic hormone (ACTH) test was conducted at 8 hours and 12 hours, and before and after 30 minutes of ACTH administration, the cortisol content in serum was determined with radioimmunoassay (RIA) and the expressions of Toll-like receptor 4 (TLR4), tumor necrosis factor-alpha (TNF-alpha) mRNA in adrenal glands were detected with semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). Ultrastructure of adrenal cortex was observed with transmission electron microscope. The survival rats was recorded in all groups. RESULTS: (1) The levels of cortisol in CLP group, dexamethasone prevention group and dexamethasone treatment group were respectively higher than those of normal control and sham operation groups (all P<0.05). But there was no marked change in the levels of cortisol between pre-and post-ACTH in rats with sepsis in the early phases. (2)The expressions of TLR4, TNF-alpha mRNA in adrenal both were significantly increased in CLP group, and they were higher than those in sham operation group (P<0.05 or P<0.01). The expressions of TLR4, TNF-alpha mRNA in dexamethasone prevention group and treatment group were significantly lower than those in CLP group, and those in the dexamethasone prevention group were lower than those in sham operation group. (3)In the groups of CLP, dexamethasone prevention and treatment, ultrastructure changes were observed in the adrenal, especially in CLP group. (4)The survival rate of the dexamethasone prevention and treatment groups at 12 hours were higher than that of CLP group (76.92%, 40.00% vs. 33.33%, P<0.01 and P<0.05). The survival rate of dexamethasone prevention group was higher than that of dexamethasone treatment group (P<0.05). CONCLUSION: (1)RAI occurs during the early stage of sepsis. (2)The expressions of TLR4, TNF-alpha mRNA in adrenal and changes in corticoadrenal ultrastructure participates in the pathogenesis of RAI in the early stage of sepsis in rat. (3) Dexamethasone therapy could effectively increase the survival rate and improve outcome through down-regulating the expression changes in TLR4, TNF-alpha mRNA and alleviating changes in ultrastructure of adrenal glands. Early administration of dexamethasone may give good result in the treatment of sepsis.

[Effect of diallyl trisulfide on tumor necrosis factor-alpha expression and nuclear factor-KappaB activity in mice with acute lung injury induced by lipopolysaccharide].

OBJECTIVE: To investigate the effect of diallyl trisulfide (DATS) on tumor necrosis factor-alpha (TNF-alpha) expression and nuclear factor-KappaB (NF-KappaB) activity in mice with acute lung injury (ALI) induced by lipopolysaccharide (LPS). METHODS: ALI murine model was reproduced by injection of LPS intraperitoneally. Mice were randomly divided into normal saline control group, ALI group, DATS prevention group, DATS treatment group, and DATS control group. The TNF-alpha levels in the serum and in the supernatant of lung homogenates were measured with enzyme linked immunoadsorbent assay (ELISA). The expression of TNF-alpha mRNA in the lung tissues was detected by reverse transcription polymerase chain reaction (RT-PCR). NF-KappaB activity in the lung tissues was detected by electrophoresis mobility shift assay (EMSA). RESULTS: The levels of TNF-alpha induced by LPS in the serum and the supernatant of lung homogenates were increased markedly at 2 hours in ALI group (both P<0.01), and decreased at 6 hours, but they were still higher than those of the control groups (all P<0.01). They were reduced in DATS prevention group at 2 and 6 hours compared with those of ALI group (P<0.05 or P<0.01), but no change was noted in DATS treatment group (all P>0.05). The expression of TNF-alpha mRNA in the lung tissues of ALI group increased markedly at 2 hours compared with those of control groups (both P<0.01), and it could be down-regulated by pretreatment with DATS (P<0.05). No change in DATS was found in treatment group. NF-KappaB activity in the lung tissue increased in ALI group compared with that of control groups (both P<0.05), and it was markedly reduced in DATS prevention group (P<0.05), but no change was found in DATS treatment group. CONCLUSION: Pretreatment of DATS for ALI in mice could inhibit NF-KappaB activity, TNF-alpha mRNA expression in lung tissues, and decrease the release of TNF-alpha in the serum and the lung homogenates, and they might be the underlying mechanisms of prevention of the occurrence of ALI by DATS.

Value of Kidney Disease Improving Global Outcomes Urine Output Criteria in Critically Ill Patients: A Secondary Analysis of a Multicenter Prospective Cohort Study.

BACKGROUND: Urine output (UO) is an essential criterion of the Kidney Disease Improving Global Outcomes (KDIGO) definition and classification system for acute kidney injury (AKI), of which the diagnostic value has not been extensively studied. We aimed to determine whether AKI based on KDIGO UO criteria (KDIGOUO) could improve the diagnostic and prognostic accuracy, compared with KDIGO serum creatinine criteria (KDIGOSCr). METHODS: We conducted a secondary analysis of the database of a previous study conducted by China Critical Care Clinical Trial Group (CCCCTG), which was a 2-month prospective cohort study (July 1, 2009 to August 31, 2009) involving 3063 patients in 22 tertiary Intensive Care Units in Mainland of China. AKI was diagnosed and classified separately based on KDIGOUOand KDIGOSCr. Hospital mortality of patients with more severe AKI classification based on KDIGOUOwas compared with other patients by univariate and multivariate regression analyses. RESULTS: The prevalence of AKI increased from 52.4% based on KDIGOSCrto 55.4% based on KDIGOSCrcombined with KDIGOUO. KDIGOUOalso resulted in an upgrade of AKI classification in 7.3% of patients, representing those with more severe AKI classification based on KDIGOUO. Compared with non-AKI patients or those with maximum AKI classification by KDIGOSCr, those with maximum AKI classification by KDIGOUOhad a significantly higher hospital mortality of 58.4% (odds ratio [OR]: 7.580, 95% confidence interval [CI]: 4.141-13.873, P< 0.001). In a multivariate logistic regression analysis, AKI based on KDIGOUO (OR: 2.891, 95% CI: 1.964-4.254, P< 0.001), but not based on KDIGOSCr (OR: 1.322, 95% CI: 0.902-1.939, P = 0.152), was an independent risk factor for hospital mortality. CONCLUSION: UO was a criterion with additional value beyond creatinine criterion for AKI diagnosis and classification, which can help identify a group of patients with high risk of death.