Development and external validation of a nomogram for the early prediction of acute kidney injury in septic patients: a multicenter retrospective clinical study.

Background and purpose: Acute kidney injury (AKI) is a common serious complication in sepsis patients with a high mortality rate. This study aimed to develop and validate a predictive model for sepsis associated acute kidney injury (SA-AKI). Methods: In our study, we retrospectively constructed a development cohort comprising 733 septic patients admitted to eight Grade-A tertiary hospitals in Shanghai from January 2021 to October 2022. Additionally, we established an external validation cohort consisting of 336 septic patients admitted to our hospital from January 2017 to December 2019. Risk predictors were selected by LASSO regression, and a corresponding nomogram was constructed. We evaluated the model's discrimination, precision and clinical benefit through receiver operating characteristic (ROC) curves, calibration plots, decision curve analysis (DCA) and clinical impact curves (CIC) in both internal and external validation. Results: AKI incidence was 53.2% in the development cohort and 48.2% in the external validation cohort. The model included five independent indicators: chronic kidney disease stages 1 to 3, blood urea nitrogen, procalcitonin, D-dimer and creatine kinase isoenzyme. The AUC of the model in the development and validation cohorts was 0.914 (95% CI, 0.894-0.934) and 0.923 (95% CI, 0.895-0.952), respectively. The calibration plot, DCA, and CIC demonstrated the model's favorable clinical applicability. Conclusion: We developed and validated a robust nomogram model, which might identify patients at risk of SA-AKI and promising for clinical applications.

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.

Identification of Potential Biomarkers and Immune Features of Sepsis Using Bioinformatics Analysis.

Sepsis remains a major global concern and is associated with high mortality and morbidity despite improvements in its management. Markers currently in use have shortcomings such as a lack of specificity and failures in the early detection of sepsis. In this study, we aimed to identify key genes involved in the molecular mechanisms of sepsis and search for potential new biomarkers and treatment targets for sepsis using bioinformatics analyses. Three datasets (GSE95233, GSE57065, and GSE28750) associated with sepsis were downloaded from the public functional genomics data repository Gene Expression Omnibus. Differentially expressed genes (DEGs) were identified using R packages (Affy and limma). Functional enrichment of the DEGs was analyzed with the DAVID database. Protein-protein interaction networks were derived using the STRING database and visualized using Cytoscape software. Potential biomarker genes were analyzed using receiver operating characteristic (ROC) curves in the R package (pROC). The three datasets included 156 whole blood RNA samples from 89 sepsis patients and 67 healthy controls. Between the two groups, 568 DEGs were identified, among which 315 were upregulated and 253 were downregulated in the septic group. These genes were enriched for pathways mainly involved in the innate immune response, T-cell biology, antigen presentation, and natural killer cell function. ROC analyses identified nine genes-LRG1, ELANE, TP53, LCK, TBX21, ZAP70, CD247, ITK, and FYN-as potential new biomarkers for sepsis. Real-time PCR confirmed that the expression of seven of these genes was in accordance with the microarray results. This study revealed imbalanced immune responses at the transcriptomic level during early sepsis and identified nine genes as potential biomarkers for sepsis.

Intravenous Vitamin C attenuates hemorrhagic shock-related renal injury through the induction of SIRT1 in rats.

To investigate the effect of intravenous Vitamin C (VC) on hemorrhagic shock (HS)-associated rat renal injury and the involved mechanism. Thirty SD rats were randomly assigned to the sham surgery (sham), hemorrhagic shock (HS), HS+100 mg/kg VC (H + VL), HS+500 mg/kg VC (H + VH) and HS+100 mg/kg VC + EX527 (H + VL + E) groups. Tissue and blood samples were collected 6 h after surgery. Kidney pathological changes were scored. Creatinine (CRE), blood urea nitrogen (BUN), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) levels in serum and Vitamin C levels and superoxide dismutase (SOD) activity and the ability to suppress hydroxyl radical (RAFHR) in plasma were measured. The expression of Sirtuin1 (SIRT1), Acetyl-NF-κB (Ace-NF-κB), heme oxygenase-1 (HO-1), TNF-α, and IL-1ß in tissues was analyzed by ELISA or western-blot. In the HS group, the kidney pathological score and CRE, BUN, TNF-α, and IL-1ß levels in serum were significantly higher than in the Sham group (P < 0.05), while SOD and RAFHR were significantly decreased in the plasma (P < 0.05). SOD activity and SIRT1 expression were remarkably lower in the kidney in the HS group than in the Sham group (P < 0.05), while MDA, TNF-α, and IL-1ß concentrations and Acetyl-NF-κB andHO-1 expression in the kidney showed a noteworthy increase compared to the Sham group (P < 0.05). Compared to the HS group, VC treatment led to a remarkable reduction in the kidney pathological score and CRE,BUN,TNF-α, and IL-1ß levels (P < 0.05), and a significant increase in Vitamin C, SOD, and RAFHR levels in the plasma (P < 0.05). Additionally, MDA, TNF-α, IL-1ß and Acetyl-NF-κB expression levels were decreased in the kidney (P < 0.05), while SOD, SIRT1 and HO-1 levels were notably enhanced. There were no differences between the H + VL and H + VH groups aside from plasma Vitamin C levels. The effect of Vitamin C was decreased after the addition of EX527, which inhibits SIRT1. Intravenous Vitamin C might attenuate HS-related renal injury via the SIRT1 pathway, and it appears that there were no differences in the effects between the high and low doses.

Biliary tract external drainage protects against multiple organs injuries of severe acute pancreatitis rats via heme oxygenase-1 upregulation.

OBJECTIVE: To investigate the effect of biliary tract external drainage (BTED) on severe acute pancreatitis (SAP) in rats and the relationship with heme oxygenase-1 (HO-1) pathway. METHODS: Thirty SD rats weighing 250-300 g were randomly assigned into five groups (n = 6): sham surgery (SS) group, SAP group, SAP + BTED group, SAP + zinc protoporphyrin IX (ZnPP) group, SAP + BTED + ZnPP group. The SAP model was induced via retrograde injection of 4% sodium taurocholate (1 mL/kg) into biliopancreatic duct through duodenal wall. BTED was performed by inserting a cannula into the bile duct of SAP rats. Tissue and blood samples were collected 24 h after surgery. Pathological changes in organs were scored. The level of amylase, alanine transaminase (ALT), aspartate aminotransferase (AST), diamine oxidase (DAO), lipopolysaccharide (LPS), myeloperoxidase (MPO) and ability to inhibit hydroxyl radical(·OH) in serum were measured. The expression of hemeoxygenase-1 (HO-1), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in tissues were analyzed by RT- PCR and western-blot. RESULTS: Organs damage in SAP rats was significantly alleviated by BTED (p < 0.05). Compared to the SAP group, the serum level of amylase, ALT, AST, DAO, MPO, and LPS were significantly lower in the SAP + BTED group, and the ability to inhibit ·OH was significantly higher (p < 0.05). The BETD treatment led to a significant reduction of TNF-α, IL-6 level and a significant increase of HO-1 level in tissues than in SAP rats (p < 0.05). ZnPP significantly inhibited all above mentioned changes. CONCLUSIONS: BTED protected multiple organs against SAP related injuries via HO-1 upregulation.

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.

The pharmacokinetics of vancomycin in patients with severe acute pancreatitis.

OBJECTIVE: The aim of this study was to evaluate the pharmacokinetics of vancomycin in patients with severe acute pancreatitis (SAP). METHODS: Sixty-seven patients with SAP were included. The FPIA method was used to measure vancomycin serum trough concentrations, and the pharmacokinetic parameters were calculated using the Bayesian estimator. Comparisons of mean values were analyzed using SPSS 11.0. RESULTS: The average daily dose of vancomycin was 15.0 ± 3.7 mg/kg (q 12 h). Sixty-seven trough concentrations were collected. Compared with the recommended standard vancomycin trough concentration (15 mg/L), SAP patients had significantly lower vancomycin trough concentrations (6.1 ± 3.0 mg/L; p < 0.0001) while the volume of distribution (Vd) and clearance (CL) of vancomycin were significantly increased. Multiple regression analysis revealed that vancomycin trough concentration was strongly correlated not only with age and albumin but also with the duration from SAP onset to vancomycin therapy (p < 0.0001). Stepwise regression analysis revealed that the duration was the most important variable for vancomycin trough concentration (r (2) = 0.456). The relationships between vancomycin trough concentrations and the duration were further evaluated after the 67 patients were stratified into two groups according to the duration from SAP onset to vancomycin therapeutic drug monitoring (TDM) within or over 4 weeks. Early group had much lower trough concentrations compared to late group, and the CL was also significantly increased in the early group. Of these 67 patients, 24 patients made vancomycin dosage adjustment (increased to 18.5 ± 3.9 mg/kg, q 12 h) and the average trough concentrations increased to 12.6 ± 3.8 mg/L. CONCLUSIONS: The serum trough concentration of vancomycin was significantly reduced in SAP patients. Higher dosage regimens are needed to ensure the clinical effect.

Pre-Treatment Serum C-Reactive Protein Level Is An Independent Risk Factor for Development of Nephrotoxicity in Patients Receiving High-Dose Vancomycin.

High-dose vancomycin treatment increases the likelihood of vancomycin-related nephrotoxicity. C-reactive protein (CRP) is a sensitive marker of systemic inflammation. In this study, we evaluated the pre-treatment serum CRP level as a risk factor of the development of nephrotoxicity in patients receiving high total daily doses (>2.5 g) of vancomycin. Data extracted from medical records for 174 patients who received total daily doses of >2.5 g of intravenous vancomycin for a minimum of 48 h and had their serum CRP level and erythrocyte sedimentation rate tested within 24 h before vancomycin treatment were subject to final analyses. Univariate analyses showed that patients who developed nephrotoxicity during vancomycin treatment had significantly higher median vancomycin serum concentration, duration of vancomycin treatment, and the serum CRP level within 24 h before vancomycin treatment than the non-nephrotoxicity group. Multivariate logistic regression analysis showed that after adjustment for potential confounders, median vancomycin serum concentration, duration of treatment, serum CRP level within 24 h before vancomycin treatment, and nephrotoxic medication were found significantly associated with the development of nephrotoxicity. This was confirmed by multivariate hazard ratio analysis after adjustment for potential confounders. In conclusion, this study provides the first evidence supporting the fact that the serum CRP level within 24 h before vancomycin treatment is an independent risk factor for the development of nephrotoxicity in patients receiving total daily doses of >2.5 g of vancomycin. Therefore, the serum CRP level within 24 h before vancomycin treatment could be a potential biomarker or prognostic factor for the development of vancomycin nephrotoxicity.

The revised Atlanta criteria 2012 altered the classification, severity assessment and management of acute pancreatitis.

BACKGROUND: The Atlanta criteria for acute pancreatitis (AP) has been revised recently. This study was to evaluate its practical value in classification of AP, the severity assessment and management. METHODS: The clinical features, severity classification, outcome and risk factors for mortality of 3212 AP patients who had been admitted in Ruijin Hospital from 2004 to 2011 were analyzed based on the revised Atlanta criteria (RAC) and the original Atlanta criteria (OAC). RESULTS: Compared to the OAC group, the incidence of severe acute pancreatitis (SAP) was decreased by approximately one half (13.9% vs 28.2%) in the RAC group. The RAC presented a lower sensitivity but higher specificity, and its predictive value for severity and poor outcome was higher than those of the OAC. The proportion of SAP diagnosis and ICU admission in the early phase in the RAC group was significantly lower than that in the OAC group (P<0.05). Based on the RAC, the risk factors for death among SAP patients were older age, high CT severity index (CTSI), renal failure, cardiovascular failure, acute necrotic collection and walled-off necrosis. Compared to the OAC, the acute physiology and chronic health evaluation II (APACHE II) score, Ranson score, idiopathic etiology, respiratory failure and laparotomy debridement were not risk factors of death in contrast to walled-off necrosis. Interestingly, hypertriglyceridemia-related SAP had good outcomes in both groups. CONCLUSIONS: The RAC showed a higher predictive value for severity and poorer outcome than the OAC. However, the RAC resulted in fewer ICU admissions in the early phase due to its lower sensitivity for diagnosis of SAP. Among SAP cases, older age, high CTSI, renal and cardiovascular failure, complications of acute necrotic collection and walled-off necrosis were independent risk factors for mortality.

Biliary tract external drainage alleviates kidney injury in shock.

BACKGROUND: Kidney injury is common in hemorrhagic shock (HS). Kidney injury leads to a systemic increase in serum chemokines and cytokines and causes injuries to other vital organs. Our previous studies showed that vitamin C led to organ protection and inflammation inhibitory effects in rat models of HS via induction heme oxygenase-1 (HO-1). We also found that biliary tract external drainage (BTED) increased the expression levels of HO-1 in rat livers. We investigated roles of BTED in kidney injury and its relationship with the HO-1 pathway in HS in this research. METHODS: Rat models of HS were induced by drawing blood from the femoral artery. BTED was performed by inserting a catheter into the bile duct. Thirty-six Sprague-Dawley rats were randomized to sham group; HS group; zinc protoporphyrin IX (Znpp) group; BTED group; BTED + Znpp group, and BTED + bile infusion group. The expression levels of HO-1 in the kidney were analyzed by Western blotting. The expression levels of occludin messenger RNA in the kidney were analyzed by real-time reverse transcription-polymerase chain reaction. The expression levels of occludin in the kidney were analyzed by immunohistochemistry. Histology of renal was performed by hematoxylin and eosin staining. RESULTS: Occludin messenger RNA and protein levels in the kidney increased markedly after BTED under HS conditions. Renal histopathologic scores decreased significantly after BTED under HS conditions. Znpp significantly inhibited all mentioned effects. CONCLUSIONS: BTED alleviates kidney injury in rats of HS via the HO-1 pathway.

Epidemiology, species distribution and outcome of nosocomial Candida spp. bloodstream infection in Shanghai.

BACKGROUND: Yeasts, mostly Candida, are important causes of bloodstream infections (BSI), responsible for significant mortality and morbidity among hospitalized patients. The epidemiology and species distribution vary from different regions. The goals of this study were to report the current epidemiology of Candida BSI in a Shanghai Teaching Hospital and estimate the impact of appropriate antifungal therapy on the outcome. METHODS: From January 2008 to December 2012, all consecutive patients who developed Candida BSI at Ruijin University Hospital were enrolled. Underlying diseases, clinical severity, species distribution, antifungal therapy and its impact on the outcome were analyzed. RESULTS: A total of 121 episodes of Candida BSI were identified, with an incidence of 0.32 episodes/1,000 admissions (0.21 in 2008 and 0.42 in 2012) The proportion of candidemia caused by non-albicans species (62.8%), including C. parapsilosis (19.8%), C. tropicalis (14.9%), C. glabrata (7.4%), C. guilliermondii (5.8%), C. sake (5.0%) was higher than that of candidemia caused by C. albicans (37.2%). The overall crude 28-day mortality was 28.1% and significantly reduced with appropriate empiric antifungal therapy administered within 5 days (P = 0.006). Advanced age (OR 1.04; P = 0.014), neutropenia < 500/mm3 (OR 17.44; P < 0.001) were independent risk factors for 28-day mortality, while appropriate empiric antifungal therapy (OR 0.369; P = 0.035) was protective against 28-day mortality. CONCLUSION: The epidemiology of candidemia in Shanghai differed from that observed in Western countries. Appropriate empiric antifungal therapy influenced the short-term survival.

Relationship between CYP7A1 -204A>C polymorphism with gallbladder stone disease and serum lipid levels: a meta-analysis.

BACKGROUND: The CYP7A1 gene polymorphism has been reported to be associated with gallbladder stone disease (GSD) and serum lipid levels, but the results were inconsistent. This meta-analysis aimed to evaluate the influence of the -204A>C polymorphism in the promoter of CYP7A1 gene on the GSD and serum lipid levels. METHODS: According to inclusion/exclusion criteria, eligible studies on CYP7A1 gene -204A>C polymorphism of serum lipid levels and the risk of GSD were retrieved. Depending on the between-study heterogeneity, the fixed- or random-effects model was applied, and the data were analyzed using the RevMan software (V5.2). RESULTS: Five studies totaling 830 GSD patients and 882 healthy controls were used to evaluate the relation of CYP7A1 -204A>C polymorphism with GSD. Overall comparison of alleles A with C in all study population yielded 5% but non-significant increased risk of GSD (OR=1.05, 95% CI: 0.91 - 1.22, P=0.48). Subgroup analysis by ethnic differences did not show any association between CYP7A1 -204A>C polymorphism and GSD either. Four studies totaling 802 cases and 691 controls were used to assess the relation of CYP7A1 -204A>C polymorphism with serum lipid levels. All the subjects were from the Asian population. The pooled effects indicated that AC genotype had higher levels of TG than AA (MD=-0.42, 95% CI: -0.76 - -0.08, P=0.01). CC genotype in cases had higher levels of TC (MD=0.65, 95% CI: 0.25 - 1.05, P=0.001) and LDL-C (MD=0.40, 95% CI: 0.06 - 0.73, P=0.02) than AA, AA (MD = -0.35, 95% CI: -0.60 - -0.10, P=0.007) and AC (MD=-0.35, 95% CI: -0.61 - -0.08, P=0.01) genotypes in controls had higher levels of TC than CC, and AA genotype in controls had higher levels of HDL-C than CC (MD = -0.15, 95% CI: -0.21 - -0.09, P<0.00001). CONCLUSIONS: The CYP7A1 -204A>C polymorphism is significantly associated with serum lipid levels in Asian population, but not gallbladder stone disease.

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.

Clinical features and outcomes of patients with severe acute pancreatitis complicated with gangrenous cholecystitis.

BACKGROUND: The effects of gangrenous cholecystitis (GC) and consequent surgical interventions on the clinical outcomes and prognosis of patients with severe acute pancreatitis are not clear. The present study was to characterize the clinical outcomes of patients with severe acute pancreatitis complicated with GC. METHODS: We retrospectively analyzed 253 consecutive patients hospitalized for acute pancreatitis in intensive care unit. Among them, 68 were diagnosed as having severe acute pancreatitis; 10 out of the 68 patients had GC. We compared these 10 patients with GC and 58 patients without GC. The indices analyzed included sepsis/septic shock, pancreatic encephalopathy, acute respiratory distress syndrome, acute renal failure, multiple organ dysfunction syndrome, and death. RESULTS: Specific CT images of GC in patients with severe acute pancreatitis included enlarged and high-tensioned gallbladder, wall thickening, lumenal emphysema, discontinuous and/or irregular enhancement of mucosa, and pericholecystic effusion. The rates of severe sepsis/septic shock (70.0% vs 24.1%, P<0.01), pancreatic encephalopathy (50.0% vs 17.2%, P<0.05), acute respiratory distress syndrome (90.0% vs 41.4%, P<0.01), multiple organ dysfunction syndrome (70.0% vs 24.1%, P<0.01), acute renal failure (40.0% vs 27.6%, P<0.05), and death (40.0% vs 13.8%, P<0.05) were significantly higher in patients with GC than in those without GC. CONCLUSION: CT scans can help to identify early GC in patients with severe acute pancreatitis; early diagnosis and intervention for patients with GC can reduce morbidity and mortality.

Intrathecal or Intraventricular Tigecycline Therapy for Central Nervous System Infection Associated with Carbapenem-Resistant Klebsiella pneumoniae.

Purpose: Infection with carbapenem-resistant Klebsiella pneumoniae (CRKP) is a great challenge. Central nervous system (CNS) infection caused by CRKP is rarely reported, and effective treatment is limited. Thus, this study aimed to assess intrathecal (IT) or intraventricular (IVT) injection of tigecycline for clearing infection with CRKP in CNS. Patients and Methods: Two patients who had intracranial infection with CRKP after craniotomy were treated in our institution and analyzed retrospectively, summarizing their therapeutic schedules. Results: They all had a fever with the positive results of cerebrospinal fluid (CSF) test, and CSF culture showed positive for CPKP, which was sensitive only to tigecycline. In addition, the MIC of polymyxin B was not tested due to the limited laboratory conditions. After IT or IVT injection of tigecycline treatment, the temperature of the patients became normal in 3 days, with normal levels of white blood cells, protein, glucose and chlorine concentrations in the CSF. Crucially, twice CSF cultures also became negative with no clinical symptoms of intracranial infection after IT or IVT injection of tigecycline treatment. Moreover, there were no adverse drug reactions observed. Conclusion: IT or IVT injection of tigecycline may be a bright choice to control intracranial infection with CRKP.

Mucin 1 Inhibits Ferroptosis and Sensitizes Vitamin E to Alleviate Sepsis-Induced Acute Lung Injury through GSK3ß/Keap1-Nrf2-GPX4 Pathway.

Background: Ferroptosis is a nonapoptotic form of programmed cell death, which may be related to the occurrence and development of sepsis-induced acute respiratory distress syndrome (ARDS)/acute lung injury (ALI). Mucin 1 (MUC1) is a kind of macromolecule transmembrane glycoprotein. Previous studies have shown that MUC1 could relieve ALI in sepsis and predict whether sepsis patients would develop into ARDS. However, the role of MUC1 in the ferroptosis of sepsis-induced ALI/ARDS remains unclear. Materials and Methods: Sera samples from 50 patients with sepsis/septic shock were used to detect iron metabolism-related markers. Western blot and qRT-PCR were conducted to detect the expression levels of ferroptosis-related genes. Enzyme-linked immunosorbent assay (ELISA) was performed to evaluate inflammatory factors. Transmission electron microscopy (TEM) was used to assess morphological changes of cells. Results: The results showed that the iron metabolism-related indicators in sepsis-induced ARDS patients changed significantly, suggesting the iron metabolism disorder. The expression levels of ferroptosis-related genes in lung tissues of sepsis had marked changes, and the lipid peroxidation levels increased, while Ferrostatin-1 (Fer-1) could reverse the above results, which confirmed the occurrence of ferroptosis. In terms of mechanism studies, inhibition of MUC1 dimerization could increase the expression level of Keap1, reduce the phosphorylation level of GSK3ß, inhibit the entry of Nrf2 into the nucleus, further inhibit the expression level of GPX4, enhance the lipid peroxidation level of lung tissues, trigger ferroptosis, and aggravate lung injury. Besides, inhibiting MUC1 reversed the alleviating effect of vitamin E on ALI caused by sepsis, increased the aggregation of inflammatory cells in lung tissues, and aggravated alveolar injury and edema. Conclusions: Our study was the first to explore the changes of iron metabolism indicators in ALI/ARDS of sepsis, clarify the important role of ferroptosis in ALI/ARDS induced by sepsis, and reveal the effects and specific mechanisms of MUC1 in regulating ferroptosis, as well as the sensitization on vitamin E.

Establishment of a novel risk score for in-hospital mortality in adult sepsis patients.

Background: Existing scoring systems have limitations in predicting the in-hospital mortality of adult sepsis patients. We aimed to develop and validate a novel risk score for predicting the in-hospital mortality of adult sepsis patients. Methods: The clinical data of 1,335 adult sepsis inpatients were retrospectively analyzed. Enrolled patients were randomly divided into a modeling group and a validation group at a 3:2 ratio. The modeling group (n=801) was used to develop the risk score by univariate and multivariate logistic regression analyses. The score's performance was validated in the validation group (n=534). We classified patients into four risk levels according to the novel risk score. Results: Age, central vein catheterization, mechanical ventilation, vasopressin, Charlson comorbidity index (CCI), respiratory rate (RR), heart rate (HR), Glasgow coma scale (GCS) score, platelet (PLT), hematocrit (HCT), aspartate aminotransferase (AST), and activated partial thrombin time (APTT) were independent risk factors for in-hospital death in adult sepsis patients. Continuous variables were converted into classified variables to develop the risk score, with a total score of 39 points. Adult sepsis patients with low, lower medium, higher medium, and high risk levels had in-hospital mortality rates of 9.8%, 24.7%, 55.8%, and 83.5%, respectively. Conclusions: Compared with the Acute Physiology and Chronic Health Evaluation II scoring system (APACHE II) and the Modified Early Warning Score (MEWS), the novel risk score showed good predictive performance for in-hospital mortality in adult sepsis patients.

Free fatty acids-induced neutrophil extracellular traps lead to dendritic cells activation and T cell differentiation in acute lung injury.

This study aimed to investigate whether free fatty acids (FFAs) could induce the release of neutrophil extracellular traps (NETs), as well as the mechanism of FFAs-induced NETs in acute lung injury (ALI). FFAs were used to induce NETs production. The reactive oxygen species (ROS) production was detected after FFA and NADPH oxidase inhibitor treatments. The association between FFAs-induced NETs and the activation of p38, ERK, and JNK pathways was investigated. The effect of FFAs-induced NETs on the dendritic cells (DCs) activation and T cell differentiation was investigated. FFAs could induce neutrophils to produce NETs. FFAs significantly promoted ROS production and increased the expression of ERK, p38 and JNK, and treatment of the inhibitors of NAPDH oxidase (DPI), p38 (SB202190), ERK1/2 (U0126) and JNK (SP600125) inhibited FAAs-induced NETs production. FFAs induced NETs could promote DCs activation and consequently led to the differentiation of primary CD4+ T cells into Th1 and Th17 cells and the release of IL-1ß, IL-12 and TNF-α. FFAs are capable of inducing NETs via NOX, ERK, p38 and JNK pathways. FFA-induced NETs further lead to DCs activation and T cell differentiation, which can well explain the mechanism of ALI caused by FFAs.

Early Prediction for Persistent Inflammation-Immunosuppression Catabolism Syndrome in Surgical Sepsis Patients.

OBJECTIVE: To find the predictors for persistent inflammation-immunosuppression catabolism syndrome in ICU surgical septic patients. DESIGN: Single center observation study. PARTICIPANTS: Inclusion: 1) patients ≥18, 2) admitted to the ICU after major surgery or transferred to the ICU within 48 hours after the diagnosis of sepsis following the definition of sepsis-3.0. Exclusion: 1) pregnant or lactating patients, 2) patients with severe immune deficiency, 3) patients that expired within 14 days after the diagnosis of sepsis. RESULTS: A total of 169 participants were included. After propensity score matching, PICS patients were found to have higher intensive care unit (ICU) mortality (32.4% vs 12.4%, p=0.046), 90-day mortality (32.4% vs 9.1%, p=0.006), and ICU-acquired infection rate (44.1% vs 12.7%, p<0.001), and longer ICU stays (29 vs 11 days, p<0.001) comparing to non-PICS patients. In multivariate logistic regression, it demonstrated that the SOFA score, Charlson co-morbidity index (CCI), albumin level on the ICU day 1, and lymphocyte count on the ICU day 3 were statistically significant. Sensitivity analysis was conducted with the receiver operating characteristic curve for a combination of the four parameters and the area under the curve was 0.838 (95% confidence interval 0.774-0.901). CONCLUSION: The chronic disease condition and decreased immunity in the early course of sepsis were crucial for PICS. The combination of CCI, SOFA score, albumin level on ICU Day 1 and lymphocyte count on ICU Day 3 can be early predictor for PICS.