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.

Efficacy and Safety of Ciprofol Sedation in ICU Patients Undergoing Mechanical Ventilation: A Multicenter, Single-Blind, Randomized, Noninferiority Trial.

OBJECTIVES: To determine the effectiveness and safety of ciprofol for sedating patients in ICUs who required mechanical ventilation (MV). DESIGN: A multicenter, single-blind, randomized, noninferiority trial. SETTING: Twenty-one centers across China from December 2020 to June 2021. PATIENTS: A total of 135 ICU patients 18 to 80 years old with endotracheal intubation and undergoing MV, who were expected to require sedation for 6-24 hours. INTERVENTIONS: One hundred thirty-five ICU patients were randomly allocated into ciprofol ( n = 90) and propofol ( n = 45) groups in a 2:1 ratio. Ciprofol or propofol were IV infused at loading doses of 0.1 mg/kg or 0.5 mg/kg, respectively, over 4 minutes ± 30 seconds depending on the physical condition of each patient. Ciprofol or propofol were then immediately administered at an initial maintenance dose of 0.3 mg/kg/hr or 1.5 mg/kg/hr, to achieve the target sedation range of Richmond Agitation-Sedation Scale (+1 to -2). Besides, continuous IV remifentanil analgesia was administered (loading dose: 0.5-1 µg/kg, maintenance dose: 0.02-0.15 µg/kg/min). MEASUREMENTS AND MAIN RESULTS: Of the 135 patients enrolled, 129 completed the study. The primary endpoint-sedation success rates of ciprofol and propofol groups were 97.7% versus 97.8% in the full analysis set (FAS) and were both 100% in per-protocol set (PPS). The noninferiority margin was set as 8% and confirmed with a lower limit of two-sided 95% CI for the inter-group difference of -5.98% and -4.32% in the FAS and PPS groups. Patients who received ciprofol had a longer recovery time ( p = 0.003), but there were no differences in the remaining secondary endpoints (all p > 0.05). The occurrence rates of treatment-emergent adverse events (TEAEs) or drug-related TEAEs were not significantly different between the groups (all p > 0.05). CONCLUSIONS: Ciprofol was well tolerated, with a noninferior sedation profile to propofol in Chinese ICU patients undergoing MV for a period of 6-24 hours.

New mechanism for mesenchymal stem cell microvesicle to restore lung permeability: intracellular S1P signaling pathway independent of S1P receptor-1.

BACKGROUND: Microvesicles (MVs) derived from human bone marrow mesenchymal stem cell (MSC) were demonstrated to restore lung protein permeability and attenuate acute lung injury. In our previous study, we found that MSC MV increased sphingosine-1-phosphate (S1P) kinase1 mRNA levels in injured human lung microvascular endothelial cells (HLMVEC) significantly. However, the role of S1P signaling in MSC MV to restore lung protein permeability is unknown. METHODS: In this study, we hypothesized that MSC MV might restore lung permeability in part through increasing intracellular S1P signaling pathway in injured HLMVEC independent of S1P receptors. We used the transwell co-culture system to study the effect of MSC MV on protein permeability of Lipopolysaccharide (LPS) damaged HLMVEC. RESULTS: Our results showed that LPS significantly increased the permeability of HLMVEC to FITC-dextran (70 kDa) within 24 h. MSC MV restores this permeability and, to a large extent, prevents the cytoskeleton protein F-actin from recombining into "actin stress fibers," and restores the positions of tight junctions and adhesion junctions in the damaged HLMVEC. This therapeutic effect of MSC MV was related to the increase in the S1P level in injured HLMVEC and was not eliminated when adding the antagonist of S1P receptor, suggesting that MSC MV to restore lung permeability was independent of S1P receptors on HLMVEC. Laser confocal further observed that Ca2+ mobilization and Rac1 activation in LPS injured HLMVEC were increased in parallel with the increase in intracellular S1P level after MSC MV treatment. CONCLUSIONS: In short, MSC MV partially restored protein permeability across HLMVEC through the intracellular S1P signaling pathway independent of S1P receptor-1.

Metagenomic Next-Generation Sequencing Versus Traditional Laboratory Methods for the Diagnosis and Treatment of Infection in Liver Transplantation.

Background: Metagenomic next-generation sequencing (mNGS) has emerged as an effective method for the noninvasive and precise detection of infectious pathogens. However, data are lacking on whether mNGS analyses could be used for the diagnosis and treatment of infection during the perioperative period in patients undergoing liver transplantation (LT). Methods: From February 2018 to October 2018, we conducted an exploratory study using mNGS and traditional laboratory methods (TMs), including culture, serologic assays, and nucleic acid testing, for pathogen detection in 42 pairs of cadaveric liver donors and their corresponding recipients. Method performance in determining the presence of perioperative infection and guiding subsequent clinical decisions was compared between mNGS and TMs. Results: The percentage of liver donors with mNGS-positive pathogen results (64.3%, 27/42) was significantly higher than that using TMs (28.6%, 12/42; P<0.05). The percentage of co-infection detected by mNGS in liver donors was 23.8% (10/42) significantly higher than 0.0% (0/42) by TMs (P<0.01). Forty-three pathogens were detected using mNGS, while only 12 pathogens were identified using TMs. The results of the mNGS analyses were consistent with results of the TM analyses in 91.7% (11/12) of donor samples at the species level, while mNGS could be used to detect pathogens in 66.7% (20/30) of donors deemed pathogen-negative using TMs. Identical pathogens were detected in 6 cases of donors and recipients by mNGS, among which 4 cases were finally confirmed as donor-derived infections (DDIs). For TMs, identical pathogens were detected in only 2 cases. Furthermore, 8 recipients developed early symptoms of infection (<7 days) after LT; we adjusted the type of antibiotics and/or discontinued immunosuppressants according to the mNGS results. Of the 8 patients with infections, 7 recipients recovered, and 1 patient died of severe sepsis. Conclusions: Our preliminary results show that mNGS analyses can provide rapid and precise pathogen detection compared with TMs in a variety of clinical samples from patients undergoing LT. Combined with symptoms of clinical infection, mNGS showed superior advantages over TMs for the early identification and assistance in clinical decision-making for DDIs. mNGS results were critical for the management of perioperative infection in patients undergoing LT.

Feasibility and discriminatory value of tissue motion annular displacement in sepsis-induced cardiomyopathy: a single-center retrospective observational study.

BACKGROUND: There is no formal diagnostic criterion for sepsis-induced cardiomyopathy (SICM), but left ventricular ejection fraction (LVEF) < 50% was the most commonly used standard. Tissue motion annular displacement (TMAD) is a novel speckle tracking indicator to quickly assess LV longitudinal systolic function. This study aimed to evaluate the feasibility and discriminatory value of TMAD for predicting SICM, as well as prognostic value of TMAD for mortality. METHODS: We conducted a single-center retrospective observational study in patients with sepsis or septic shock who underwent echocardiography examination within the first 24 h after admission. Basic clinical information and conventional echocardiographic data, including mitral annular plane systolic excursion (MAPSE), were collected. Based on speckle tracking echocardiography (STE), global longitudinal strain (GLS) and TMAD were, respectively, performed offline. The parameters acquisition rate, inter- and intra-observer reliability, time consumed for measurement were assessed for the feasibility analysis. Areas under the receiver operating characteristic curves (AUROC) values were calculated to assess the discriminatory value of TMAD/GLS/MAPSE for predicting SICM, defined as LVEF < 50%. Kaplan-Meier survival curve analysis was performed according to the cutoff values in predicting SICM. Cox proportional hazards model was performed to determine the risk factors for 28d and in-hospital mortality. RESULTS: A total of 143 patients were enrolled in this study. Compared with LVEF, GLS or MAPSE, TMAD exhibited the highest parameter acquisition rate, intra- and inter-observer reliability. The mean time for offline analyses with TMAD was significantly shorter than that with LVEF or GLS (p < 0.05). According to the AUROC analysis, TMADMid presented an excellent discriminatory value for predicting SICM (AUROC > 0.9). Patients with lower TMADMid (< 9.75 mm) had significantly higher 28d and in-hospital mortality (both p < 0.05). The multivariate Cox proportional hazards model revealed that BMI and SOFA were the independent risk factors for 28d and in-hospital mortality in sepsis cases, but TMAD was not. CONCLUSION: STE-based TMAD is a novel and feasible technology with promising discriminatory value for predicting SICM with LVEF < 50%.

Preliminary Study on the Combination Effect of Clindamycin and Low Dose Trimethoprim-Sulfamethoxazole on Severe Pneumocystis Pneumonia After Renal Transplantation.

Objective: Evaluate the effect of the combination of clindamycin with low-dose trimethoprim-sulfamethoxazole (TMP/SMX) regimen on sever Pneumocystis pneumonia (PCP) after renal transplantation. Method: 20 severe PCP patients after renal transplantation were included in this historical-control, retrospective study. A 10 patients were treated with the standard dose of TMP/SMX (T group), the other 10 patients were treated with the combination of clindamycin and low dose TMP/SMX (CT group). Results: Although there was no significant difference in the hospital survival between the two groups, the CT protocol improved the PaO2/FiO2 ratio more significantly and rapidly after the 6th ICU day (1.51 vs. 0.38, P = 0.014). CT protocol also ameliorated the pulmonary infiltration and the lactate dehydrogenase level more effectively. Moreover, the CT protocol reduced the incidence of pneumomediastinum (0 vs. 50%, P = 0.008), the length of hospital staying (26.5 vs. 39.0 days, P = 0.011) and ICU staying (12.5 vs. 22.5 days, P = 0.008). Furthermore, more thrombocytopenia (9/10 vs. 3/10, P = 0.020) was emerged in the T group than in the CT group. The total adverse reaction rate was much lower in the CT group than in the T group (8/80 vs. 27/80, P < 0.001). Consequently, the dosage of TMP/SMX was reduced in 8 patients, while only 2 patients in the CT group received TMP/SMX decrement (P = 0.023). Conclusion: The current study proposed that clindamycin combined with low-dose TMP/SMX was more effective and safer the than single use of TMP/SMX for severe PCP patients after renal transplantation (NCT04328688).

Safety and efficacy of ciprofol vs. propofol for sedation in intensive care unit patients with mechanical ventilation: a multi-center, open label, randomized, phase 2 trial.

BACKGROUND: Ciprofol (HSK3486; Haisco Pharmaceutical Group Co., Ltd., Chengdu, China), developed as a novel 2,6-disubstituted phenol derivative showed similar tolerability and efficacy characteristics as propofol when applicated as continuous intravenous infusion for 12 h maintenance sedation in a previous phase 1 trial. The phase 2 trial was designed to investigate the safety, efficacy, and pharmacokinetic characteristics of ciprofol for sedation of patients undergoing mechanical ventilation. METHODS: In this multicenter, open label, randomized, propofol positive-controlled, phase 2 trial, 39 Chinese intensive care unit patients receiving mechanical ventilation were enrolled and randomly assigned to a ciprofol or propofol group in a 2:1 ratio. The ciprofol infusion was started with a loading infusion of 0.1-0.2 mg/kg for 0.5-5.0 min, followed by an initial maintenance infusion rate of 0.30 mg·kg -1 ·h -1 , which could be adjusted to an infusion rate of 0.06 to 0.80 mg·kg -1 ·h -1 , whereas for propofol the loading infusion dose was 0.5-1.0 mg/kg for 0.5-5.0 min, followed by an initial maintenance infusion rate of 1.50 mg·kg -1 ·h -1 , which could be adjusted to 0.30-4.00 mg·kg -1 ·h -1 to achieve -2 to +1 Richmond Agitation-Sedation Scale sedation within 6-24 h of drug administration. RESULTS: Of the 39 enrolled patients, 36 completed the trial. The median (min, max) of the average time to sedation compliance values for ciprofol and propofol were 60.0 (52.6, 60.0) min and 60.0 (55.2, 60.0) min, with median difference of 0.00 (95% confidence interval: 0.00, 0.00). In total, 29 (74.4%) patients comprising 18 (69.2%) in the ciprofol and 11 (84.6%) in the propofol group experienced 86 treatment emergent adverse events (TEAEs), the majority being of severity grade 1 or 2. Drug- and sedation-related TEAEs were hypotension (7.7% vs. 23.1%, P  = 0.310) and sinus bradycardia (3.8% vs. 7.7%, P  = 1.000) in the ciprofol and propofol groups, respectively. The plasma concentration-time curves for ciprofol and propofol were similar. CONCLUSIONS: ciprofol is comparable to propofol with good tolerance and efficacy for sedation of Chinese intensive care unit patients undergoing mechanical ventilation in the present study setting. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04147416.

Comparative study of high flow nasal catheter device and noninvasive positive pressure ventilation for sequential treatment in sepsis patients after weaning from mechanical ventilation in intensive care unit.

BACKGROUND: The hypoxemia condition after mechanical ventilation (MV) weaning is not rare among sepsis patients, so we compared the efficacy in two different intervention groups: high-flow nasal cannula device group and non-invasive positive pressure ventilation (NPPV) group. METHODS: This is a retrospective cohort study. Participants were patients with sepsis receiving high-flow nasal catheter (HFNC) device or NPPV within 24 hours after weaning from MV. The primary outcome was tracheal re-intubation within 72 hours after extubation. Secondary outcomes included: oxygenation index, complication rate, patient comfort evaluation, HFNC/NPPV treatment time, ICU length of stay (LOS), ICU mortality, and in-hospital 28-day mortality. RESULTS: A total of 283 patients were included in the study with 167 in the HFNC group and 116 in the NPPV group. The re-intubation rates after extubation in both groups were respectively 4.2% and 5.2% without significant difference. Patients in the HFNC group experienced lower incidence of delirium, reflux aspiration, facial pressure ulcer and other complications, and higher score of patients comfort than that in the NPPV group. There was no significant difference in ICU LOS, ICU mortality and in-hospital 28-day mortality between the two groups. CONCLUSIONS: HFNC and NPPV have similar efficacy in the sequential treatment of sepsis patients after weaning from MV. Compared with NPPV, those extubated to HFNC had lower rate of complications such as reflux aspiration and facial pressure ulcers. The patients extubation to HFNC is more comfortable (and associated with less delirium) than to NPPV.

PCR coupled to electrospray ionization mass spectrometry for microbiological diagnosis and surveillance of ventilator-associated pneumonia.

Etiological diagnosis is essential for anti-infective therapy in patients with ventilator-associated pneumonia (VAP). The present study aimed to evaluate the capacity of sequential PCR coupled to electrospray ionization mass spectrometry (PCR/ESI-MS) tests as a rapid diagnostic technique for patients with VAP. A total of 12 patients diagnosed with VAP were enrolled at the intensive care unit in Zhongshan Hospital, Fudan University. Mini-bronchoalveolar lavage fluid specimens were prospectively collected on VAP 0, 5 and 10 days following the beginning of mechanical ventilation. Routine clinical culture and PCR/ESI-MS were compared for identification of microorganisms in the specimens. A total of 51 bacterial species were detected by either of the two methods. The positive rates of routine clinical culture and PCR/ESI-MS were 38.2 and 88.2%, respectively. Out of the 16 specimens positive in routine cultures, 15 were also positive on PCR/ESI-MS, except for one, from which a mix of three distinct bacterial isolates were reported by culture. Among the 50 bacterial species identified by PCR/ESI-MS, 15 (35.7%) of the common VAP pathogens were confirmed by paired culture. Furthermore, of the 16 bacterial isolates that were finally confirmed to be responsible for VAP, 14 were identified by a sequential PCR/ESI-MS test concurrently when the culture results were obtained. PCR/ESI-MS identified pathogens that may cause VAP in 8 subjects prior to the occurrence of associated clinical manifestations. To conclude, PCR/ESI-MS was a potential rapid technique for diagnosis of VAP within 6 h. Regular respiratory specimen monitoring using PCR/ESI-MS provides information for selecting appropriate and adequate antibiotic therapies in ventilated patients.

Hemodynamic monitoring in patients with venoarterial extracorporeal membrane oxygenation.

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is an effective mechanical circulatory support modality that rapidly restores systemic perfusion for circulatory failure in patients. Given the huge increase in VA-ECMO use, its optimal management depends on continuous and discrete hemodynamic monitoring. This article provides an overview of VA-ECMO pathophysiology, and the current state of the art in hemodynamic monitoring in patients with VA-ECMO.

Inhibition of Sphingosine Kinase 1 Attenuates Sepsis-induced Microvascular Leakage via Inhibiting Macrophage NLRP3 Inflammasome Activation in Mice.

BACKGROUND: Sepsis is the overwhelming inflammatory response to infection, in which nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome plays a crucial role. Shingosine-1-phosphate is reported to evoke NLRP3 inflammasome activation. Sphingosine kinase 1 (SphK1) is the major kinase that catalyzes bioactive lipid shingosine-1-phosphate formation and its role in sepsis remains uncertain. The authors hypothesize that SphK1 elicits NLRP3 inflammasome activation and exacerbates sepsis. METHODS: Peripheral blood mononuclear cells were isolated from septic patients and healthy volunteers to measure messenger RNA (mRNA) expression. In mice, sepsis was induced by cecal ligation and puncture. Bone marrow-derived macrophages were prepared from C57BL/6J wild-type, Casp1, Nlrp3 and SphK1 mice. PF-543 was used as the specific inhibitor of SphK1. Mortality, peripheral perfusion, lung Evan's blue dye index, lung wet/dry ratio, lung injury score, lung myeloperoxidase activity, NLRP3 activation, and function of endothelial adherens junction were measured. RESULTS: SphK1 mRNA expression was higher in cells from septic patients versus healthy volunteers (septic patients vs. healthy volunteers: 50.9 ± 57.0 fold change vs. 1.2 ± 0.1 fold change, P < 0.0001) and was positively correlated with IL-1ß mRNA expression in these cells (r = 0.537, P = 0.012) and negatively correlated with PaO2/FIO2 ratios (r = 0.516, P = 0.017). In mice that had undergone cecal ligation and puncture, the 5-day mortality was 30% in PF-543-treated group and 80% in control group (n = 10 per group, P = 0.028). Compared with controls, PF-543-treated mice demonstrated improved peripheral perfusion and alleviated extravascular Evan's blue dye effusion (control vs. PF-543: 25.5 ± 3.2 ng/g vs. 18.2 ± 1.4 ng/g, P < 0.001), lower lung wet/dry ratio (control vs. PF-543: 8.0 ± 0.2 vs. 7.1 ± 0.4, P < 0.0001), descending lung injury score, and weaker lung myeloperoxidase activity. Inhibition of SphK1 suppressed caspase-1 maturation and interleukin-1ß release through repressing NLRP3 inflammasome activation, and subsequently stabilized vascular endothelial cadherin through suppressing interleukin-1ß-evoked Src-mediated phosphorylation of vascular endothelial cadherin. CONCLUSIONS: SphK1 plays a crucial role in NLRP3 inflammasome activation and contributes to lung injury and mortality in mice polymicrobial sepsis.

Neuroprotective Effect of the Inhibitor Salubrinal after Cardiac Arrest in a Rodent Model.

Cardiac arrest (CA) yields poor neurological outcomes. Salubrinal (Sal), an endoplasmic reticulum (ER) stress inhibitor, has been shown to have neuroprotective effects in both in vivo and in vitro brain injury models. This study investigated the neuroprotective mechanisms of Sal in postresuscitation brain damage in a rodent model of CA. In the present study, rats were subjected to 6 min of CA and then successfully resuscitated. Either Sal (1 mg/kg) or vehicle (DMSO) was injected blindly 30 min before the induction of CA. Neurological status was assessed 24 h after CA, and the cortex was collected for analysis. As a result, we observed that, compared with the vehicle-treated animals, the rats pretreated with Sal exhibited markedly improved neurological performance and cortical mitochondrial morphology 24 h after CA. Moreover, Sal pretreatment was associated with the following: (1) upregulation of superoxide dismutase activity and a reduction in maleic dialdehyde content; (2) preserved mitochondrial membrane potential; (3) amelioration of the abnormal distribution of cytochrome C; and (4) an increased Bcl-2/Bax ratio, decreased cleaved caspase 3 upregulation, and enhanced HIF-1α expression. Our findings suggested that Sal treatment improved neurological dysfunction 24 h after CPR (cardiopulmonary resuscitation), possibly through mitochondrial preservation and stabilizing the structure of HIF-1α.

The Prevalence, Risk Factors, and Outcomes of Sepsis in Critically Ill Patients in China: A Multicenter Prospective Cohort Study.

Background: Sepsis is a main cause of morbidity and mortality in critically ill patients. The epidemiology of sepsis in high-income countries is well-known, but information on sepsis in middle- or low-income countries is still deficient, especially in China. The purpose of this study was to explore the prevalence, characteristics, risk factors, treatment, and outcomes of sepsis in critically ill patients in tertiary hospitals in China. Methods: A multicenter prospective observational cohort study was performed with consecutively collected data from adults who stayed in any intensive care unit (ICU) for at least 24 h; data were collected from 1 January 2014 to 31 August 2015, and patients were followed until death or discharge from the hospital. Results: A total of 4,910 patients were enrolled in the study. Of these, 2,086 (42.5%) presented with sepsis or septic shock on admission to the ICU or within the first 48 h after admission to the ICU. ICU mortality was higher in patients with sepsis (13.1%) and septic shock (39.0%) and varied according to geographical region. Acinetobacter, Pseudomonas, and Staphylococcus infections were associated with increased ICU mortality. In addition, age, Acute Physiology, and Chronic Health Evaluation II (APACHE II) scores, pre-existing cardiovascular diseases, malignant tumors, renal replacement therapy (RRT), and septic shock were independent risk factors for mortality in patients with sepsis. The prompt administration of antibiotics (OR 0.65, 95% CI 0.46-0.92) and 30 mL/kg of initial fluid resuscitation during the first 3 h (OR 0.43, 95% CI 0.30-0.63) improved the outcome in patients with septic shock. Conclusions: Sepsis was common and was associated with a high mortality rate in critically ill patients in tertiary hospitals in China. The prompt administration of antibiotics and 30 mL/kg fluid resuscitation decreased the risk of mortality.

Changes in Stroke Volume Variation Induced by Passive Leg Raising to Predict Fluid Responsiveness in Cardiac Surgical Patients With Protective Ventilation.

OBJECTIVES: Stroke volume variation (SVV) has been used to predict fluid responsiveness. The authors hypothesized the changes in SVV induced by passive leg raising (PLR) might be an indicator of fluid responsiveness in patients with protective ventilation after cardiac surgery. DESIGN: A prospective single-center observational study. SETTING: A single cardiac surgery intensive care unit at a tertiary hospital. PARTICIPANTS: A total of 123 patients undergoing cardiac surgery with hemodynamic instability. Tidal volume was set between 6 and 8 mL/kg of ideal body weight. INTERVENTIONS: PLR maneuver, fluid challenge. MEASUREMENTS AND MAIN RESULTS: SVV was continuously recorded using pulse contour analysis before and immediately after a PLR test and after fluid challenge (500 mL of colloid given over 30 min). Sixty-three (51.22%) patients responded to fluid challenge, in which PLR and fluid challenge significantly increased the SV and decreased the SVV. The decrease in SVV induced by PLR was correlated with the SV changes induced by fluid challenge. A 4% decrease in the SVV induced by PLR-discriminated responders to fluid challenge with an area under the curve of 0.90. The gray zone identified a range of SVV changes induced by PLR (between -3.94% and -2.91%) for which fluid responsiveness could not be predicted reliably. The gray zone included 15.45% of the patients. The SVV at baseline predicted fluid responsiveness with an area under the curve of 0.72. CONCLUSIONS: Changes in the SVV induced by PLR predicted fluid responsiveness in cardiac surgical patients with protective ventilation.

Hydrogen gas protects against delayed encephalopathy after acute carbon monoxide poisoning in a rat model.

Objective: The protective effects of 2%-4% hydrogen gas in delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) have been previously reported. This study aimed to assess the neuroprotective effects of high concentration hydrogen (HCH) on DEACMP.Methods: A total of 36 male Sprague-Dawley rats were divided into 3 groups. In the DEACMP group, rats were exposed to CO to induce CO poisoning; in the HCH group, the animals were exposed to 67% H2 and 33% O2 at 3,000 mL/min for 90 min immediately after CO poisoning. Neurological function was evaluated at 1 and 9 days after poisoning. Then, the contents of malondialdehyde, 3-nitrotyrosine and 8-hydroxy-2-deoxyguanosine, as well as superoxide dismutase activity in the serum, cortex and hippocampus were detected by ELISA. Additionally, the mRNA and protein expression levels of Nrf2 and downstream genes were detected by RT-PCR and Western blotting, respectively.Results: Our results showed that CO poisoning significantly impaired neurological function which was improved over time, and HCH markedly attenuated neurological impairment following CO poisoning. In addition, CO poisoning resulted in increased levels of malondialdehyde, 3-nitrotyrosine and 8-hydroxy-2-deoxyguanosine and markedly reduced superoxide dismutase activity at 1 and 9 days, which were significantly inhibited by HCH at 9 days. Finally, CO poisoning increased the mRNA and protein levels of Nrf2 and downstream genes, and HCH further induced the anti-oxidative capability.Conclusion: These findings indicate the neuroprotective effects of HCH on DEACMP, which are related to the activation of Nrf2 signaling pathway.

Inflammatory biomarkers to predict adverse outcomes in postoperative patients with acute type A aortic dissection.

Objectives. The present study aimed to evaluate prognostic value of inflammatory markers for in-hospital mortality and renal complication in patients undergoing surgery for acute type A aortic dissection (ATAAD). Design. Serum concentration of C-reactive protein, leukocyte counts, procalcitonin (PCT), tumor necrosis factor (TNF)-α, interleukin-2 receptor (IL-2R), IL-6 and IL-8 were measured on the day of admission to the hospital (T0) and on 1st (T1), 2nd (T2), and 7th (T3) day after surgery. Results. 328 patients were included. There were significant differences between survivor group and non-survivor group in PCT, IL-2R, and IL-6 (p = .001, p = .015, and p = .005). There were significant differences between patients with different AKI stage in PCT and IL-2R (p = .001, p < .001). The area under receiver operating characteristics (ROC) curve on 30-day death was 0.686 for PCT, 0.718 for IL-2R, 0.694 for IL-6 and 0.627 for IL-8. The area under ROC curve on stage III AKI was 0.852 for PCT, 0.749 for IL-2R, 0.626 for IL-8, and 0.636 for TNF-α. IL-2 > 1438 U/ml and IL-6 > 45.5 pg/ml were independently associated with 30-day mortality (p = .014 and p < .001). The area under ROC curve was 0.849 on score 2 (using 1 point for PCT > 4.58 ng/ml, 1 point for IL-2R > 1438 U/ml, 1 point for APACHE II score >15.5, and 1 point for IL-6 > 45.5 pg/ml). Conclusions. PCT and cytokines may be considered as predictors for adverse renal outcomes and mortality in patients with ATAAD patients after surgery. They are earlier than traditional biomarkers and combination of these biomarkers will improve the accuracy.

Preemptive renal replacement therapy in post-cardiotomy cardiogenic shock patients: a historically controlled cohort study.

BACKGROUND: The aim of the study was to evaluate whether the preemptive renal replacement therapy (RRT) might improve outcomes in post-cardiotomy cardiogenic shock (PCCS) patients. METHODS: In Period A (September 2014-April 2016), patients with PCCS received RRT, depending on conventional indications or bedside attendings. In Period B (May 2016-November 2017), the preemptive RRT strategy was implemented in all PCCS patients in our intensive care unit. The goal-directed RRT was applied for the RRT patients. The hospital mortality and renal recovery were compared between the two periods. RESULTS: A total of 155 patients (76 patients in Period A and 79 patients in Period B) were ultimately enrolled in this study. There were no significant differences in demographic characteristics and intraoperative and postoperative parameters between the two groups. The duration between surgery and RRT initiation was significantly shorter in Period B than in Period A [23 (17, 66) vs. 47 (20, 127) h, P<0.01]. The hospital mortality in Period B was significantly lower than that in Period A (38.0% vs. 59.2%, P<0.01). There were fewer patients with no renal recovery in Period B (4.1% vs. 19.4%, P=0.026). Patients in Period B displayed a significantly shorter time to completely renal recovery (12±15 vs. 25±15 d, P<0.05). CONCLUSIONS: Among PCCS patients, preemptive RRT compared with conventional initiation of RRT reduced mortality in hospital and also led to faster and more frequent recovery of renal function. Our preliminary study supposed that preemptive initiation of RRT might be an effective approach to PCCS with acute kidney injury (AKI).

Ulinastatin ameliorates LPS­induced pulmonary inflammation and injury by blocking the MAPK/NF­κB signaling pathways in rats.

Ulinastatin, a urinary trypsin inhibitor (UTI) is commonly used to treat patients with acute inflammatory disease. However, the underlying mechanisms of its anti­inflammatory effect in acute lung injury (ALI) are not fully understood. The present study aimed to investigate the protective effect of UTI and explore its potential mechanisms by using a rat model of lipopolysaccharide (LPS)­induced ALI. Rats were treated with 5 mg/kg LPS by intratracheal instillation. The histological changes in LPS­induced ALI was evaluated using hematoxylin and eosin staining and the myeloperoxidase (MPO) activity was determined using ELISA. The wet/dry ratio (W/D ratio) of the lungs was used to assess the severity of pulmonary edema and Evans blue dye was used to evaluate the severity of lung vascular leakage. The results demonstrated that LPS administration induced histological changes and significantly increased the lung W/D ratio, MPO activity and Evans blue dye extravasation compared with the control group. However, treatment with UTI attenuated LPS­induced ALI in rats by modifying histological changes and reducing the lung W/D ratio, MPO activity and Evans blue dye extravasation. In addition, LPS induced the secretion of numerous pro­inflammatory cytokines in bronchoalveolar lavage fluid (BALF), including tumor necrosis factor­α, interleukin (IL)­6, IL­1ß and interferon­Î³; however, these cytokines were strongly reduced following treatment with UTI. In addition, UTI was able to reduce cellular counts in BALF, including neutrophils and leukocytes. Western blotting demonstrated that UTI significantly blocked the LPS­stimulated MAPK and NF­κB signaling pathways. The results of the present study indicated that UTI could exert an anti­inflammatory effect on LPS­induced ALI by inhibiting the MAPK and NF­κB signaling pathways, which suggested that UTI may be considered as an effective drug in the treatment of ALI.

M2 macrophages promote pulmonary endothelial cells regeneration in sepsis-induced acute lung injury.

BACKGROUND: Macrophages can polarize to M2 phenotype to decrease inflammation and encourage tissue repair. Nonetheless, its role in sepsis-induced acute lung injury and its effect on endothelial cells (ECs) regeneration remains unknown. The aim of the current study was to explore the impact of M2 macrophages on pulmonary ECs proliferation in sepsis-induced acute lung injury. METHODS: We co-cultured mouse lung microvascular endothelial cells (MLMVECs) with M2 macrophages following LPS challenge. M2 macrophages were intratracheally transplanted into mice subjected to cecal ligation and puncture (CLP). We further performed cytokine array for the supernatant from M2 macrophages and serum from mice subjected with CLP. RESULTS: We found both co-culture with M2 macrophages and treating with supernatant from M2 macrophages increased ECs viability following LPS challenge. Intratracheal transplantation of M2 macrophages markedly promoted pulmonary ECs proliferation, manifesting as attenuation of lung microvascular permeability and lung tissue edema, as well as improvement of survival rate. We further found that CXCL12, IL-1ra, TIMP-1, IL-4, and CXCL1 were increased in the supernatant of M2 macrophages in vitro. G-CSF and Complement Component 5a (C5/C5a) were increased in the serum of the M2-transplanted mice. CONCLUSIONS: The present study suggested M2 macrophages could promote ECs proliferation in sepsis-induced ALI through secretion of anti-inflammatory cytokines and growth factors.

Reliability of three-dimensional color flow Doppler and two-dimensional pulse wave Doppler transthoracic echocardiography for estimating cardiac output after cardiac surgery.

BACKGROUND: Three-dimensional color flow Doppler (3DCF) is a new convenient technique for cardiac output (CO) measurement. However, to date, no one has evaluated the accuracy of 3DCF echocardiography for CO measurement after cardiac surgery. Therefore, this single-center, prospective study was designed to evaluate the reliability of three-dimensional color flow and two-dimensional pulse wave Doppler (2D-PWD) transthoracic echocardiography for estimating cardiac output after cardiac surgery. METHODS: Post-cardiac surgical patients with a good acoustic window and a low dose or no dose of vasoactive drugs (norepinephrine < 0.05 µg/kg/min) were enrolled for CO estimation. Three different methods (third generation FloTrac/Vigileo™ [FT/V] system as the reference method, 3DCF, and 2D-PWD) were used to estimate CO before and after interventions (baseline, after volume expansion, and after a dobutamine test). RESULTS: A total of 20 patients were enrolled in this study, and 59 pairs of CO measurements were collected (one pair was not included because of increasing drainage after the dobutamine test). Pearson's coefficients were 0.260 between the CO-FT/V and CO-PWD measurements and 0.729 between the CO-FT/V and CO-3DCF measurements. Bland-Altman analysis showed the bias between the absolute values of CO-FT/V and CO-PWD measurements was - 0.6 L/min with limits of agreement between - 3.3 L/min and 2.2 L/min, with a percentage error (PE) of 61.3%. The bias between CO-FT/V and CO-3DCF was - 0.14 L/min with limits of agreement between - 1.42 L /min and 1.14 L/min, with a PE of 29.9%. Four-quadrant plot analysis showed the concordance rate between ΔCO-PWD and ΔCO-3FT/V was 93.3%. CONCLUSIONS: In a comparison with the FT/V system, 3DCF transthoracic echocardiography could accurately estimate CO in post-cardiac surgical patients, and the two methods could be considered interchangeable. Although 2D-PWD echocardiography was not as accurate as the 3D technique, its ability to track directional changes was reliable.