Guosheng Wu

Blood transfusions in severe burn patients: Epidemiology and predictive factors

BACKGROUND Blood is a vital resource commonly used in burn patients; however, description of blood transfusions in severe burns is limited. The purpose of this study was to describe the epidemiology of blood transfusions and determine factors associated with increased transfusion quantity. METHODS This is a retrospective study of total 133 patients with >40% total body surface area (TBSA) burns admitted to the burn center of Changhai hospital from January 2008 to December 2013. The study characterized blood transfusions in severe burn patients. Univariate and Multivariate regression analyses were used to evaluate the association of clinical variables with blood transfusions. RESULTS The overall transfusion rate was 97.7% (130 of 133). The median amount of total blood (RBC and plasma), RBC and plasma transfusions was 54 units (Interquartile range (IQR), 20-84), 19 units (IQR, 4-37.8) and 28.5 units (IQR, 14.8-51.8), respectively. The number of RBC transfusion in and outside operation room was 7 (0, 14) and 11 (2, 20) units, and the number of plasma was 6 (0.5, 12) and 21 (11.5, 39.3) units. A median of one unit of blood was transfused per TBSA and an average of 4 units per operation was given in the series. The consumption of plasma is higher than that of RBC. On multivariate regression analysis, age, full-thickness TBSA and number of operations were significant independent predictors associated with the number of RBC transfusion, and coagulopathy and ICU length showed a trend toward RBC consumption. Predictors for increased plasma transfusion were female, high full-thickness TBSA burn and more operations. CONCLUSIONS Severe burn patients received an ample volume of blood transfusions. Fully understanding of predictors of blood transfusions will allow physicians to better optimize burn patients during hospitalization in an effort to use blood appropriately.

Relationship between elevated soluble CD74 and severity of experimental and clinical ALI/ARDS.

CD74 is expressed on the cell surface of pulmonary macrophages and contributes to macrophage migration inhibitory factor (MIF)-induced inflammatory response in acute lung injury (ALI). A circulating form of CD74 (soluble CD74, sCD74) was recently discovered in autoimmune liver disease. Using two murine ALI models and cells culture, we examined the presence of sCD74 in circulation and alveolar space and preliminarily assessed the biological function of sCD74. The concentrations of sCD74 were increased in serum and bronchoalveolar lavage fluids (BALF) of murine ALI models. The elevated levels of sCD74 in BALF positively correlated with lung permeability and inflammation. In addition, sCD74 is secreted by macrophages in response to MIF stimulation and itself can stimulate the production of inflammatory cytokines. Our clinical study confirmed some findings of basic research. Moreover, we also found Day 3 serum sCD74 levels were associated with worse clinical outcomes. In conclusion, higher serum sCD74 levels may reflect more severe lung injury and may be used to help physicians determine prognosis of acute respiratory distress syndrome (ARDS).

Epidemiology and outcome analysis of hand burns: A 5-year retrospective review of 378 cases in a burn center in Eastern China

Hands are frequent sites of burn but few related studies were reported in China. The aim of this study was to examine the impacts of gender, age, seasons, place, etiology, total body surface area (TBSA), depth, infection and comorbidities on prognosis following injury in a cohort of hand burn inpatients. This is a retrospective study of total 378 inpatients admitted to the burn center of Changhai hospital from January 2009 to December 2013. The present research showed the male inpatients were predominant and most of the inpatients aged from 20 to 49. Flame (37.04%) and electricity (25.40%) were the major causes of hand burns. Hand burns happened more commonly in work place (60.85%). The study preliminarily pointed out that male, flame and depth were the most significant factors impacting surgery. The main factors relevant to amputation were identified including the electrical burns and other etiology of burns. In addition, depth of hand burns was proved to have a higher impact on length of hospital stay (LOS) than other factors. The results of this study not only provide the necessary information of hand burns in Eastern China but also give the suggestions for the prevention of hand burns.

Risk Factors for Acute Kidney Injury in Patients With Burn Injury: A Meta-analysis and Systematic Review

Acute kidney injury (AKI) is a fatal complication of burn injury. Few systematic reviews to date have focused on the risk factors predisposing to AKI in patients with burn injury. The aim of this article is to identify the risk factors for the occurrence of AKI in burn patients, thus providing theoretical evidence for prevention and treatment. We performed a systematic review and meta-analysis of studies determining the prevalence, risk factors, and outcomes of AKI in patients with burn injury. An electronic search (up to April 2016) was performed using Pubmed, Embase, Web of Knowledge, and the Cochrane Library databases. Finally, a total of 18 articles (nine prospective cohort, seven retrospective cohort, two case–control) meeting the eligibility criteria were included. The pooled incidence of AKI was 39.6% (95% confidence interval = 34.7–44.4%). Significant risk factors for the occurrence of AKI included age (odds ratio [OR] = 3.78 [1.28–6.27]), TBSA (OR = 15.66 [11.01–20.31]), full-thickness TBSA (OR = 15.66 [11.01–20.31]), flame burn (OR = 1.56 [1.09–2.25]), inhalation injury (OR = 2.97 [1.80–4.89]), abbreviated burn severity index on admission (OR = 2.42 [1.87–2.98]), sequential organ failure assessment score on admission (OR = 2.69 [1.39–3.98]), baseline blood urea nitrogen (OR = 2.11 [0.72–3.51]), serum creatinine (OR = 2.69 [1.39–3.98]), and sepsis (OR = 4.42 [1.75–11.18]). In addition, burn patients with AKI are more likely to have long stay in intensive care unit and high mortality. AKI is a common complication and occurs at a remarkable rate in burn patients. We identified 10 variables as independent risk factors for the development of AKI in burn patients. Our findings may help clinicians to develop effective preventive and therapeutic strategies and provide appropriate, timely initial treatment.

The effects of porcine pulmonary surfactant on smoke inhalation injury.

BACKGROUND Our previous study, consistent with others, demonstrated that administering an exogenous surfactant was a potential therapy for acute lung injury and acute respiratory distress syndrome. However, the underlying mechanisms remain largely unknown. In the present study, we investigated the effect of instilled porcine pulmonary surfactant (PPS) on rat inhalation injury model induced by smoke and the possible mechanism. MATERIALS AND METHODS Fifteen Sprague-Dawley rats were equally randomized to three groups as follows (n = 5 in each group): sham control group (C group), inhalation injury group (II group), and inhalation injury + PPS treatment group (PPS group). Lung tissues were assayed for wet/dry ratio, histologic, terminal dUTP nick-end labeling staining, and Western blotting examinations. The myeloperoxidase activity was tested in lung tissues as well. Bronchoalveolar lavage fluid was collected to determine the total protein concentrations, inflammatory cytokines, surfactant protein A (SP-A), and SP-D. RESULTS Our present work exhibited that PPS had therapeutic effects on smoke inhalation injury reflected by significant increase of PaO2 values, improved edema status, decreased vascular permeability, amelioration of lung histopathology, and reduction of inflammatory response. In addition, PPS treatment could increase endogenous SP-A levels both in lung tissue and bronchoalveolar lavage fluid. Further correlation analysis showed that SP-A was negatively correlated with both myeloperoxidase activity and interleukin 8 levels. CONCLUSIONS These results indicate that PPS can attenuate smoke-induced inhalation injury at least partly through stimulating production of endogenous SP-A and inhibiting the release of proinflammatory cytokines such as interleukin 8. The increasing production of endogenous SP-A may be due to the antioxidant effect of PPS, which contains no SP-A.

Hydrostatin-SN1, a Sea Snake-Derived Bioactive Peptide, Reduces Inflammation in a Mouse Model of Acute Lung Injury

Snake venom has been used for centuries as a traditional Chinese medicine. Hydrostatin-SN1 (H-SN1), a bioactive peptide extracted from the Hydrophis cyanocinctus venom gland T7 phage display library, was reported to have the ability to reduce inflammation in a dextran sulfate sodium-induced murine colitis model. In this study, we sought to investigate the inhibitory potential of H-SN1 on inflammation in a murine model of lipopolysaccharide (LPS)-induced acute lung injury (ALI), and elucidate the anti-inflammatory mechanism in LPS-stimulated RAW 264.7 cells. In vivo, C57BL/6 male mice were intratracheally instilled with LPS or physiological saline with concurrent intraperitoneal injection of H-SN1 or saline alone. Lung histopathologic changes, lung wet-to-dry weight ratio, and myeloperoxidase activity in lung tissues were assessed. Total cell number, the protein concentration, and cytokine levels were determined in the bronchial alveolar lavage fluid. In vitro, RAW 264.7 cells were treated with various concentrations of H-SN1 for 2 h followed by incubation with or without 1 μg/ml LPS for 0.5 or 24 h. The mRNA expression of inflammatory cytokines was determined via RT-PCR and protein levels in the supernatants were measured via ELISA. Extracellular-signal related kinase 1/2 (ERK1/2) and nuclear factor-κB (NF-κB) pathways were analyzed via western blot. H-SN1 improved pulmonary edema status, decreased vascular permeability, suppressed pro-inflammatory cytokine production, and lessened lung morphological injury. H-SN1 also dose-dependently inhibited the mRNA expression and release of TNF-α, IL-6, and IL-1β in LPS-stimulated RAW 264.7 cells. Moreover, H-SN1 inhibited the LPS-induced phosphorylation of ERK1/2 and the nuclear translocation of NF-κB. Our results suggest that H-SN1 could attenuate LPS-induced ALI in mice, which is associated with the anti-inflammatory effect of H-SN1. The mechanism might involve inhibiting the production of inflammatory cytokines by, at least in part, interfering with the ERK1/2 and NF-κB signaling pathways.

Targeted release of stromal cell-derived factor-1α by reactive oxygen species-sensitive nanoparticles results in bone marrow stromal cell chemotaxis and homing, and repair of vascular injury caused by electrical burns

Rapid repair of vascular injury is an important prognostic factor for electrical burns. This repair is achieved mainly via stromal cell-derived factor (SDF)-1α promoting the mobilization, chemotaxis, homing, and targeted differentiation of bone marrow mesenchymal stem cells (BMSCs) into endothelial cells. Forming a concentration gradient from the site of local damage in the circulation is essential to the role of SDF-1α. In a previous study, we developed reactive oxygen species (ROS)-sensitive PPADT nanoparticles containing SDF-1α that could degrade in response to high concentration of ROS in tissue lesions, achieving the goal of targeted SDF-1α release. In the current study, a rat vascular injury model of electrical burns was used to evaluate the effects of targeted release of SDF-1α using PPADT nanoparticles on the chemotaxis of BMSCs and the repair of vascular injury. Continuous exposure to 220 V for 6 s could damage rat vascular endothelial cells, strip off the inner layer, significantly elevate the local level of ROS, and decrease the level of SDF-1α. After injection of Cy5-labeled SDF-1α-PPADT nanoparticles, the distribution of Cy5 fluorescence suggested that SDF-1α was distributed primarily at the injury site, and the local SDF-1α levels increased significantly. Seven days after injury with nanoparticles injection, aggregation of exogenous green fluorescent protein-labeled BMSCs at the injury site was observed. Ten days after injury, the endothelial cell arrangement was better organized and continuous, with relatively intact vascular morphology and more blood vessels. These results showed that SDF-1α-PPADT nanoparticles targeted the SDF-1α release at the site of injury, directing BMSC chemotaxis and homing, thereby promoting vascular repair in response to electrical burns.

Impregnated central venous catheters in children: a systematic review of randomized controlled trials

Dear Editor, Central venous catheters (CVCs) are widely used in clinical practice, but also bring some adverse events [1]. Several systematic reviews and randomized controlled trials (RCTs) have described the substantial benefits of impregnated CVCs for reducing catheter-related bloodstream infection (CRBSI) and thrombosis in adults. However, the number of RCTs conducted in children are limited. Furthermore, impregnated CVCs have not been recommended for children and there still remains controversy about the effectiveness of impregnated CVCs to reduce infection [2, 3]. Thus, we conducted a metaanalysis of RCTs to assessed the effect of anti-infective/ heparin-impregnated CVCs on CRBSI and thrombosis in children. RCTs related to CVCs in the pediatric population aged <18 years were retrieved from PubMed, Embase, Web of Science and the Cochrane Library up to 12 December 2016 [see Electronic Supplemental Material (ESM) E1 and Fig. S1]. Two reviewers independently screened the papers and extracted data according to the criteria, and the methodological quality of the trials was assessed (ESM E2) [4]. Statistical analyses were performed using Review Manager 5.1 and Stata 12.0 (ECM E2). Six RCTs with a total of 2318 children were included in this review (ESM E3 and Table 1). The results of the quality assessment of the RCTs included are presented in Fig. S2. The main analysis showed that impregnated CVCs have a trend in reducing the rate of CRBSI (RR 0.38, 95% CI 0.13–1.09, p = 0.07) (Fig. 1a). A significant decrease in CRBSI in the impregnated CVCs group was seen in a subgroup analysis in which anti-infective impregnated CVCs were compared with standard CVCs (RR 0.36, 95% CI 0.17– 0.77, p = 0.008) and another subgroup analysis comprising only heparin-bonded CVCs (RR 0.36, 95% CI 0.18–0.72, p = 0.004) (Fig. 1b). However, no significant difference was detected in the subgroup analysis by age (Fig. S3a). Funnel plots and Egger’s test showed no significant evidence of publication bias (Fig. S4). Impregnated CVCs were not associated with significantly fewer thrombosis compared with standard CVCs (RR 0.91, 95% CI 0.77–1.09, p = 0.30) (Fig. 1c). Furthermore, no significant difference was detected in subgroup analyses (Fig. 1d; Fig. S3b) and sensitivity analysis (Fig. 1e). In this review, one limitation was that there was significant heterogeneity among included RCTs. We attempted to eliminate this by subgroup and sensitivity analyses and found that subgroup analysis allowing reduced heterogeneity showed a significant decrease in the occurrence of CRBSI. Although the heterogeneity decreased significantly in the sensitivity analyses, no significant difference was detected regarding thrombosis. An important limitation was that the criteria for diagnosis of CRBSI and thrombosis were different between the included trials, and some studies even failed to give the definitions of CRBSI or thrombosis. In summary, our systematic review showed that both anti-infective and heparin-impregnated CVCs are efficacious in reducing the occurrence of CRBSI in children, but not in preventing thrombosis. Since studies of CVCs in children were limited and there is only one study that assessed the cost-effectiveness of impregnated CVCs in children from England [5], more trials recruiting children from other regions should be conducted in the future. *Correspondence: xiazhaofan_smmu@163.com Department of Burn Surgery, Changhai Hospital, The Second Military Medical University, Shanghai, People’s Republic of China

Response to Letter to the Editor: “Blood transfusions in severe burn patients: Epidemiology and predictive factors; Methodological issues”

WewouldliketothankDr.RezaPakzadetal.fortheirprofessional review and constructivecomments on ourpaper entitled“Blood transfusions in severe burn patients: Epidemiology and predictivefactors.”Theyclaimedthatthemethodologicalissuesofthis paper should be taken into account to avoid misinterpretations. We fully agree with the reviewers on this point and have performed additional analysis to address their concerns. First, Dr. Reza Pakzad et al. considered that inclusion of only those variables with p<0.05 in the multivariate model would lead to testimation bias. We agree that Dr. Reza Pakzad et al.’s comment is reasonable. Because of the limited samples size and large number of variables in the current analysis, we performed univariate regression analyses to exclude some variables that had no statistically significant effect or low clinical effect. Thus, only the remaining variables were included in the multivariate model. Using this method, the number of variables included in the multivariate model was reduced, which prevents the false appearance of a large R value. This method was also used in another study [1]. Second, Dr. Reza Pakzad et al. opined that the multivariate prediction model should be validated internally and externally using bootstrapping and split validation, respectively. These two statistical methods are indeed good ways to test the stability of the prediction model in the case of sufficient sample size. Because of the limitation of the sample size, we could not perform the bootstrapping and split validation. As far as clinical research is concerned, clinical interpretation is as important as statistical analysis. In this study, the results of statistical analysis match well with the clinical interpretation, which validates our prediction model. Similar ideas could be seen in other studies [2,3]. In addition, we also hope that statisticians such as Dr. Reza Pakzad can develop standard statistical programs or quality control procedures to standardize the statistical analysis for clinicians. Finally, the sample size of the study was queried by Dr. Reza Pakzad et al. We fully agree with this as adequate sample size is the primary guarantee for quality research and reliable conclusions. Our study is a retrospective study that included all the patients who met the criterions from January 2008 to December 2013. We did our best to include all the cases possible. The current sample size (133 cases) has been the biggest when compared with those of previous studies [4,5].