Epidemiology, species distribution, and outcome of nosocomial Candida spp. bloodstream infection in Shanghai: an 11-year retrospective analysis in a tertiary care hospital.

BACKGROUND: The incidence of Candida bloodstream infections (BSIs), has increased over time. In this study, we aimed to describe the current epidemiology of Candida BSI in a large tertiary care hospital in Shanghai and to determine the risk factors of 28-day mortality and the impact of antifungal therapy on clinical outcomes. METHODS: All consecutive adult inpatients with Candida BSI at Ruijin Hospital between January 1, 2008, and December 31, 2018, were enrolled. Underlying diseases, clinical severity, species distribution, antifungal therapy, and their impact on the outcomes were analyzed. RESULTS: Among the 370 inpatients with 393 consecutive episodes of Candida BSI, the incidence of nosocomial Candida BSI was 0.39 episodes/1000 hospitalized patients. Of the 393 cases, 299 (76.1%) were treated with antifungal therapy (247 and 52 were treated with early appropriate and targeted antifungal therapy, respectively). The overall 28-day mortality rate was 28.5%, which was significantly lower in those who received early appropriate (25.5%) or targeted (23.1%) antifungal therapy than in those who did not (39.4%; P = 0.012 and P = 0.046, respectively). In multivariate Cox regression analysis, age, chronic renal failure, mechanical ventilation, and severe neutropenia were found to be independent risk factors of the 28-day mortality rate. Patients who received antifungal therapy had a lower mortality risk than did those who did not. CONCLUSIONS: The incidence of Candida BSI has increased steadily in the past 11 years at our tertiary care hospital in Shanghai. Antifungal therapy influenced short-term survival, but no significant difference in mortality was observed between patients who received early appropriate and targeted antifungal therapy.

High-dose vitamin C alleviates pancreatic injury via the NRF2/NQO1/HO-1 pathway in a rat model of severe acute pancreatitis.

BACKGROUND: Oxidative stress plays a pivotal role in the progress of severe acute pancreatitis (SAP). Vitamin C (VC) is the most important antioxidant in plasma. However, the effects of an intravenous administration of high-dose VC and the mechanisms by which it exerts its antioxidant function in an experimental model of SAP have not been determined. METHODS: Sodium taurocholate was used to induce rat pancreatic injury and AR42J cells injury. After the establishment of SAP model, SAP rat and injured AR42J cells were treated with VC. For the injured AR42J cells, small interfering RNA-mediated knockdown of NRF2 was conducted after VC treatment. The histopathological characteristics, the apoptosis of pancreatic acinar cells, oxidative stress markers and levels of enzymes, biochemical indicators, and inflammatory cytokines were examined in vivo and in vitro. Furthermore, the mortality of rats was assessed. RESULTS: In vivo and in vitro results demonstrated that VC treatment ameliorated apoptosis of pancreatic acinar cells, as evidenced by the increase in Bcl-2, Bcl-XL, and MCL-1 expressions and decrease in Bax and cleaved caspase-3 expression along with decreased TUNEL-positive cells. Also, we found that the elevation of MDA and decrease of SOD, GPx, GSH/GSSG, and T-AOC induced by SAP were reversed by VC treatment in vivo and in vitro, and VC treatment increased expressions of Nrf2, NQO1, and HO-1 in SAP model at protein and gene level, indicating that VC attenuated oxidative stress via the NRF2/NQO1/HO-1 pathway. Meanwhile, it was found that sodium taurocholate significantly induced the release of amylase, lipase, IL-1ß, and IL-6 in rat plasma and AR42J cells, which were declined by VC treatment. In vitro results also revealed that these alterations in sodium taurocholate-injured AR42J cells due to VC treatment was attenuated by NRF2 knockdown. In addition, VC at a dose of 500 mg/kg decreased the levels of lactic acid, Cre, NGAL, AST, and ALT in the plasma of SAP rats, suggesting the improvement of renal and pancreatic injury and liver function of SAP rats. Furthermore, the mortality of SAP rats was 50%, which declined to 30% after VC treatment. CONCLUSIONS: The present study suggests that high-dose of VC ameliorate pancreatic injury of SAP via the NRF2/NQO1/HO-1 pathway to inhibit oxidative stress.

Vitamin C treatment attenuates hemorrhagic shock related multi-organ injuries through the induction of heme oxygenase-1.

BACKGROUND: Vitamin C (VitC) has recently been shown to exert beneficial effects, including protecting organ function and inhibiting inflammation, in various critical care conditions, but the specific mechanism remains unclear. Induction of heme oxygenase (HO)-1, a heat shock protein, has been shown to prevent organ injuries in hemorrhagic shock (HS) but the relationship between VitC and HO-1 are still ill-defined so far. Here we conducted a systemic in vivo study to investigate if VitC promoted HO-1 expression in multiple organs, and then tested if the HO-1 induction property of VitC was related to its organ protection and anti-inflammatory effect. METHODS: Firstly, to determine the HO-1 induction property of VitC, the HO-1 level were measured in tissues including kidney, liver and lung of the normal and HS model of Sprague-Dawley (SD) rats after VitC treatment (100 mg/kg body weight). Secondly, to testify if VitC prevented HS related organ injuries via inducing HO-1, the HS model of rats were separately pre- and post-treated with VitC, and some of them also received Zinc protoporphyrin (Znpp), a specific HO-1 inhibitor. The HO-1 activity in tissues was tested; the organ injuries (as judged by histological changes in tissues and the biochemical indicators level in serum) and inflammatory response in tissues (as judged by the level of pro-inflammatory cytokines Tumor necrosis factor-α and Interleukin-6 ) were analyzed. RESULTS: The HO-1 mRNA and protein level in kidney, liver, and lung were highly induced by VitC treatement under normal and HS conditions. The HO-1 activity in tissues was enhanced by both VitC pre- and post-treatment, which was shown to improve the organ injuries and inhibit the inflammatory response in the HS model of rats. Of note, the beneficial effects of VitC were abolished after HO-1 activity was blocked by Znpp. CONCLUSIONS: VitC led to a profound induction of HO-1 in multiple organs including the kidney, liver and lung, and this property might be responsible for the organ protection and inflammation inhibitory effects of both pre- and post-treatment with VitC in HS.

Formalized therapeutic guideline for hyperlipidemic severe acute pancreatitis.

AIM: To investigate a formalized therapeutic guideline for hyperlipidemic severe acute pancreatitis (HL-SAP). METHODS: Thirty-two consecutive patients with severe acute pancreatitis were included in the clinical trial. All of them met the following five criteria for admission to the study, namely the Atlanta classification and stratification system for the clinical diagnosis of SAP, APACHEII score more than 8, time interval for therapeutic intervention less than 72 hours after onset of the disease, serum triglyceride (TG) level 6.8 mmol/l or over, and exclusion of other etiologies. They were divided into severe acute pancreatitis group (SAP, 22 patients) and fulminant severe acute pancreatitis group (FSAP, 10 patients). Besides the conventional therapeutic measures, Penta-association therapy was also applied in the two groups, which consisted of blood purification (adsorption of triglyceride and hemofiltration), antihyperlipidemic agents (fluvastatin or lipanthyl), low molecular weight heparin (fragmin), insulin, topical application of Pixiao (a traditional Chinese medicine) over the whole abdomen. Serum triglyceride, pro-inflammatory cytokines and anti-inflammatory cytokines were determined before blood purification (PF), at the end of blood purification (AFE) and on the 7th day after onset of the disease (AF7) respectively. Simultaneously, severity of the diseases was assessed by the APACHE II system. PROGNOSIS was evaluated by non-operation cure rate, absorption rate of pseudocyst, time interval pseudocyst absorption, hospital stay and survival rate. RESULTS: Serum triglyceride level (mmol/L), TNFalpha (U/ml) concentration and APACHE II score were significantly decreased (P<0.05) at AFE and AF7, as compared with PF. However, serum IL-10 concentration (pg/ml) was increased significantly (P<0.001) at AFE, and decreased significantly (P<0.05) at AF7 when compared with PF. OPERATIONS: The First surgical intervention time was 55.8+/-42.6 days in SAP group (5 patients) and 12.2+/-6.6 days in FSAP group (7 patients), there was a significant difference between the two groups (P=0.02). The number of operations in the two groups was 1.33+/-0.5 vs 3.5+/-1.2 (P=0.0037), respectively. PROGNOSIS: Non-operation cure rate, absorption rate of pseudocyst, hospital stay and survival rate in SAP group and FSAP group were 100% (22/22) vs 11.1% (1/9), 77.3% (17/22) vs 11.1% (1/9), 54.2+/-35.9 vs 99.1+/-49.5 days (P=0.008) and 100%(22/22) vs 66.7% (6/9) (P=0.0044). The time for absorption of pseudocyst was 135.1+/-137.5 days in SAP group. CONCLUSION: Penta-association therapy is an effective guideline in the treatment of hyperlipidemic severe acute pancreatitis at its early stage (within 72 hours).