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.

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.

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.

MicroRNA-27a alleviates LPS-induced acute lung injury in mice via inhibiting inflammation and apoptosis through modulating TLR4/MyD88/NF-κB pathway.

Acute lung injury (ALI) is a critical clinical condition with a high mortality rate, characterized with excessive uncontrolled inflammation and apoptosis. Recently, microRNAs (miRNAs) have been found to play crucial roles in the amelioration of various inflammation-induced diseases, including ALI. However, it remains unknown the biological function and regulatory mechanisms of miRNAs in the regulation of inflammation and apoptosis in ALI. The aim of this study is to identify and evaluate the potential role of miRNAs in ALI and reveal the underlying molecular mechanisms of their effects. Here, we analyzed microRNA expression profiles in lung tissues from LPS-challenged mice using miRNA microarray. Because microRNA-27a (miR-27a) was one of the miRNAs being most significantly downregulated, which has an important role in regulation of inflammation, we investigated its function. Overexpression of miR-27a by agomir-27a improved lung injury, as evidenced by the reduced histopathological changes, lung wet/dry (W/D) ratio, lung microvascular permeability and apoptosis in the lung tissues, as well as ameliorative survival of ALI mice. This was accompanied by the alleviating of inflammation, such as the reduced total BALF cell and neutrophil counts, decreased levels of tumor necrosis factor alpha (TNF-α), interleukin-1 (IL-6) interleukin-1ß (IL-1ß) and myeloperoxidase (MPO) activity in BAL fluid. Toll-like receptor 4 (TLR4), an important regulator of the nuclear factor kappa-B (NF-κB) signaling pathway, was identified as a novel target of miR-27a in RAW264.7 cells. Furthermore, our results showed that LPS stimulation increased the expression of MyD88 and NF-κB p65 (p-p65), but inhibited the expression of inhibitor of nuclear factor-κB-α (IκB-α), suggesting the activation of NF-κB signaling pathway. Further investigations revealed that agomir-miR-27a reversed the promoting effect of LPS on NF-κB signaling pathway. The results here suggested that miR-27a alleviates LPS-induced ALI in mice via reducing inflammation and apoptosis through blocking TLR4/MyD88/NF-κB activation.

A quality improvement program with nutrition therapy: restriction of lipid emulsions in cardiac surgical patients.

BACKGROUND: To evaluate the effect of restriction of soybean-based intravenous fat emulsions (IVFEs) in clinical outcomes in cardiac surgical patients. METHODS: This was a before-and-after interventional study comparing the clinical outcomes regarding the intervention of IVFEs restriction. Before August 2015, parenteral nutrition (PN) using a soy-based lipid emulsion was routinely implemented if patients failed to meet >60% of energy requirements in 48 h post cardiac surgery (Period A). Beginning in August 2015, a lipid restriction strategy was implemented in our cardiac surgery intensive care unit (CSICU) unless enteral route could not be established within 7 days (Period B). The ICU and hospital mortality, nosocomial infections during ICU stay, length of ICU and hospital stay, ICU and hospital cost, mechanical ventilation time and postoperative complications were compared between two periods. RESULTS: A total of 761 patients (370 patients in Period A and 391 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. After the implementation of IVFEs restriction, the overall ICU mortality and hospital mortality were similar between two groups. Nosocomial infection rate was significantly reduced (3.84% vs. 7.84%, P=0.021). The mean length of ICU stay (3.15 vs. 3.74 days, P<0.001) and hospital stay (12.14 vs. 13.24 days, P<0.001) were significantly lower. The mean in-hospital cost (133,368 vs. 139,383 Yuan, P=0.037) was found to be reduced after implementation of IVFEs restriction. The duration of mechanical ventilation was shorter in the latter period (35.23±10.43 vs. 47.63±12.54 hours, P=0.011). IVFEs restriction was also associated with reduced cholestasis (2.81% vs. 6.76%, P=0.013). CONCLUSIONS: The implementation of soybean-based IVFEs restriction in cardiac surgical patients was associated with reduced postoperative nosocomial infection rate. It also led to reductions in the length of ICU/hospital stay, hospital costs and mechanical ventilation time and a lower incidence of cholestasis. Further studies are required to validate the conclusions.

The efficacy of parenteral fish oil in critical illness patients with sepsis: a prospective, non-randomized, observational study.

BACKGROUND AND OBJECTIVES: To investigate the clinical outcomes in septic patients receiving parenteral fish oil. METHODS AND STUDY DESIGN: A prospective, non-randomized, observational clinical study was carried out in 112 patients with sepsis from March, 2013 to May, 2015 in the surgical intensive care unit (SICU) of a tertiaryreferral hospital. The patients were put into one of two groups; either the control or the study group. Patients received the standard treatment of sepsis based on guidelines in the control group. In the study group, patients received parenteral nutrition (PN) containing fish oil. The Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, the length of ICU and hospital stay, duration of mechanical ventilation, mortality, and readmission into the ICU were recorded. Tumor necrosis factor (TNF)-α and procalcitonin (PCT) levels were also evaluated. RESULTS: The study group showed a significant reduction for all-cause mortality (20.0% vs 10.0% in study and control groups, p=0.034) and APACHE II score on day 5 (p=0.015), day 7 (p=0.036) and day out of SICU (p=0.045) compared with the control group. The study group tended to show a shortened length of stay in the ICU compared to the control group. However, TNF-α and PCT level, 28 d mortality, the length of hospital stay and the duration of mechanical ventilation did not show statistical differences between the two groups. There were no drug-related adverse effects shown during the study. CONCLUSIONS: PN with fish oil is probably safe and may improve clinical outcome in critical ill patients with sepsis.

Internal jugular vein variability predicts fluid responsiveness in cardiac surgical patients with mechanical ventilation.

BACKGROUND: To evaluate the efficacy of using internal jugular vein variability (IJVV) as an index of fluid responsiveness in mechanically ventilated patients after cardiac surgery. METHODS: Seventy patients were assessed after cardiac surgery. Hemodynamic data coupled with ultrasound evaluation of IJVV and inferior vena cava variability (IVCV) were collected and calculated at baseline, after a passive leg raising (PLR) test and after a 500-ml fluid challenge. Patients were divided into volume responders (increase in stroke volume ≥ 15%) and non-responders (increase in stroke volume < 15%). We compared the differences in measured variables between responders and non-responders and tested the ability of the indices to predict fluid responsiveness. RESULTS: Thirty-five (50%) patients were fluid responders. Responders presented higher IJVV, IVCV and stroke volume variation (SVV) compared with non-responders at baseline (P < 0.05). The relationship between IJVV and SVV was moderately correlated (r = 0.51, P < 0.01). The areas under the receiver operating characteristic (ROC) curves for predicting fluid responsiveness were 0.88 (CI 0.78-0.94) for IJVV compared with 0.83 (CI 0.72-0.91), 0.97 (CI 0.89-0.99), 0.91 (CI 0.82-0.97) for IVCV, SVV, and the increase in stroke volume in response to a PLR test, respectively. CONCLUSIONS: Ultrasound-derived IJVV is an accurate, easily acquired noninvasive parameter of fluid responsiveness in mechanically ventilated postoperative cardiac surgery patients, with a performance similar to that of IVCV.

Comparison of Percutaneous Dilatational Tracheostomy Guided by Ultrasound and Bronchoscopy in Critically Ill Obese Patients.

OBJECTIVES: This study aimed to compare the efficacy and safety of percutaneous dilatational tracheostomy (PDT) with ultrasound (US) or bronchoscopic guidance for critically ill patients, notably obese patients. METHODS: This work was a retrospective study. The study included mechanically ventilated patients who underwent PDT from August 2013 to July 2015 in the Department of Critical Care Medicine of Zhongshan Hospital. The patients were classified according to the different guidance methods during tracheotomy and their body mass index in the following 4 groups: normal bronchoscopy group, normal US group, obese bronchoscopy group, and obese US group. The parameters, including operation time, number of punctures, intraoperative and postoperative complications, duration of the intensive care unit stay, hospitalization time, and mortality, were recorded and compared between groups. RESULTS: Compared with the obese bronchoscopy group, the obese US group had a significantly shorter PDT operation time (mean ± SD, 12.8 ± 4.8 versus 16.2 ± 4.4 minutes; P = .026), fewer punctures (P = .011), and a lesser amount of intraoperative hemorrhage (12.1 ± 4.6 versus 16.8 ± 4.3 mL; P = .009). There were no significant differences in these parameters between the normal US and normal bronchoscopy groups. CONCLUSIONS: Ultrasound-guided PDT significantly reduced the number of punctures and the operation time compared with bronchoscopy-guided PDT, and it decreased intraoperative hemorrhage in critically ill obese patients. Percutaneous dilatational tracheostomy with US guidance was a faster, safer, and more accurate method of airway management.

Effect of Early Full-Calorie Nutrition Support Following Esophagectomy: A Randomized Controlled Trial.

BACKGROUND: Early use of enteral nutrition (EN) is indicated following surgical resection of esophageal cancer. However, early EN support does not always meet the optimal calorie or protein requirements, and the benefits of supplementary parenteral nutrition (PN) remain unclear. We aimed to evaluate the efficacy and safety of early supplementary PN following esophagectomy. MATERIALS AND METHODS: We enrolled 80 consecutive patients who underwent esophagectomy. Resting energy expenditure and body composition measurements were performed in all patients preoperatively and postoperatively. EN was administered after surgery, followed by randomization to either EN+PN or EN alone. The amount of PN administered was calculated to meet the full calorie requirement, as measured by indirect calorimetry, and 1.5 g protein/kg fat-free mass (FFM) per day was added as determined by body composition measurement. The clinical characteristics were compared between the 2 groups. RESULTS: Patients in the EN+PN group but not in the EN group preserved body weight (0.18 ± 3.38 kg vs -2.15 ± 3.19 kg, P < .05) and FFM (1.46 ± 2.97 kg vs -2.08 ± 4.16 kg) relative to preoperative measurements. Length of hospital stay, postoperative morbidity rates, and standard blood biochemistry profiles were similar. However, scores for physical functioning (71.5 ± 24.3 vs 60.4 ± 27.4, P < .05) and energy/fatigue (62.9 ± 19.5 vs 54.2 ± 23.5, P < .05) were higher in the EN+PN group 90 days following surgery. CONCLUSION: Early use of supplemental PN to meet full calorie requirements of patients who underwent esophagectomy led to better quality of life 3 months after surgery. Moreover, increased calorie and protein supplies were associated with preservation of body weight and FFM.

Alteration of histone H3 lysine 9 dimethylation in peripheral white blood cells of septic patients with trauma and cancer.

The present study aimed to investigate the clinical significance of histone methylation in sepsis. A total of 43 blood samples from trauma and esophageal cancer patients with or without sepsis were collected. Immunofluorescence staining of isolated peripheral white blood cells (WBCs) was conducted. Co­stained 293T cells served as a reference, to allow the levels of histone methylation in different types of WBCs from patients to be determined. Immunostaining analyses revealed different levels of histone 3 lysine 9 dimethylation (H3K9me2) in neutrophils (Neu), lymphocytes (Lym), and monocytes (Mon) from trauma patients. Compared with trauma patients, the levels of H3K9me2 were elevated in the three types of WBCs from cancer patients. When combined with sepsis, trauma patients demonstrated increased H3K9me2 levels in Neu (P=0.0005) and Mon (P=0.0002), whereas cancer patients had a significant decrease of H3K9me2 levels in the three types of WBCs (Neu, P=0.0003; Lym, P=0.007; Mon, P=0.007). The H3K9me2 alterations in patients with trauma and cancer were different with the occurrence of sepsis. A larger cohort study is warranted to explore the diagnostic significance and prognostic implications of altered histone methylation in septic patients.

Molecular Hydrogen Therapy Ameliorates Organ Damage Induced by Sepsis.

Since it was proposed in 2007, molecular hydrogen therapy has been widely concerned and researched. Many animal experiments were carried out in a variety of disease fields, such as cerebral infarction, ischemia reperfusion injury, Parkinson syndrome, type 2 diabetes mellitus, metabolic syndrome, chronic kidney disease, radiation injury, chronic hepatitis, rheumatoid arthritis, stress ulcer, acute sports injuries, mitochondrial and inflammatory disease, and acute erythema skin disease and other pathological processes or diseases. Molecular hydrogen therapy is pointed out as there is protective effect for sepsis patients, too. The impact of molecular hydrogen therapy against sepsis is shown from the aspects of basic vital signs, organ functions (brain, lung, liver, kidney, small intestine, etc.), survival rate, and so forth. Molecular hydrogen therapy is able to significantly reduce the release of inflammatory factors and oxidative stress injury. Thereby it can reduce damage of various organ functions from sepsis and improve survival rate. Molecular hydrogen therapy is a prospective method against sepsis.

A comparison of preemptive versus standard renal replacement therapy for acute kidney injury after cardiac surgery.

BACKGROUND: The optimal timing of renal replacement therapy (RRT) initiation in patients undergoing cardiac surgery remains controversial. This study aimed to determine whether preemptive RRT or standard RRT was associated with hospital mortality in cardiac surgical patients with acute kidney injury (AKI). METHODS: Data were retrospectively collected from patients who underwent cardiac surgery and experienced postoperative AKI requiring RRT at Zhongshan Hospital of Fudan University from September 1, 2006 to December 31, 2013. The patients were divided into two groups according to the RRT strategy applied. RESULTS: A total of 213 patients were enrolled in this study; 59 patients were categorized into the preemptive RRT group and 154 into the standard RRT group. The preemptive RRT group exhibited significantly lower mortality (33.90% versus 51.95%, P = 0.018) and time to recovery of renal function than the standard RRT group (15.34 ± 14.46 versus 22.88 ± 14.08 d, P = 0.022). Moreover, the preemptive RRT group showed significantly lower serum creatinine levels and higher proportions of recovery of renal function and weaning from RRT at death or discharge than the standard RRT group. There was no significant difference in the duration of mechanical ventilation, RRT, intensive care unit stay, or hospital stay between the two groups. CONCLUSIONS: In patients after cardiac surgery, preemptive RRT was associated with lower hospital mortality and faster and more frequent recovery of renal function than standard RRT. However, preemptive RRT did not affect other patient-centered outcomes including mechanical ventilation time, RRT time, or length of intensive care unit or hospital stay.

Cis-existence of H3K27me3 and H3K36me2 in mouse embryonic stem cells revealed by specific ions of isobaric modification chromatogram.

INTRODUCTION: Histone H3 lysine 27 trimethylation (H3K27me3) and H3 lysine 36 trimethylation (H3K36me3) are important epigenetic modifications correlated with transcription repression and activation, respectively. These two opposing modifications rarely co-exist in the same H3 polypeptide. However, a small but significant amount of H3 tails are modified with 5 methyl groups on K27 and K36 in mouse embryonic stem cells (mESCs) and it is unclear how the trimethylation is distributed on K27 or K36. METHODS: A label-free, bottom-up mass spectrum method, named specific ions of isobaric modification chromatogram (SIMC), was established to quantify the relative abundance of K27me2-K36me3 and K27me3-K36me2 in the same histone H3 tail. RESULTS: By using this method, we demonstrated that the H3K27me3-K36me2 comprises about 85 % of the penta-methylated H3 tails at K27 and K36 in mESCs. Upon mESC differentiation, the abundance of H3K27me3-K36me2 significantly decreased, while the level of H3K27me2-K36me3 remains unchanged. CONCLUSION: Our study not only revealed the cis-existence of H3K27me3-K36me2 in mESCs, but also suggested that this combinatorial histone modification may assume a specific regulatory function during differentiation.