The asynchronous dynamic changes and interrelationships between leukocyte composition and inflammatory markers and potential clinical significance in the early stage and sepsis stage in severe burns.

OBJECTIVE: The aim of this study is to investigate the dynamic changes and interrelationships between leukocyte components and inflammatory markers in the early stages and sepsis stage in severe burns, and explore their potential clinical significance. METHODS: This is a 5-year retrospective cohort study involving 107 patients with severe burns (the total body surface area of burn (TBSA) > 50%), in which, neutrophil count, lymphocyte count, monocyte count, the ratio of the product of monocyte and lymphocyte count to neutrophil count (MLPN), procalcitonin (PCT), C-reactive protein (CRP), capillary leakage index (CLI) and creatinine (Scr) were investigated. RESULTS: Within one week after injury, the leukocyte components and MLPN showed a V-shaped change, with a peak immediately after injury and a trough on the 4th or 5th day after injury, while CRP showed a continuous upward trend, and the leukocyte compositions of all patients were negatively correlated with CRP values. The counts of leukocytes components and CRP values in deceased patients were higher than those in surviving patients within 2 days after injury. In the resorption stage, although no significant difference in lymphocyte and monocyte counts between surviving and deceased patients was found, the monocyte and lymphocyte counts in deceased patients were lower than those in surviving patients on the 5th to 7th day after injury, while neutrophils counts and CRP values remained higher than those in surviving patients. And the dynamic changes of MLPN were consistent with those of leukocyte compositions and opposite to those of PCT values. Moreover, MLPN were negatively correlated with CRP, CLI, and Scr values in the early stage of severe burns. In sepsis stage, as the condition worsened, the values of CRP, PCT and neutrophil counts continuously increased with varying degree, while lymphocyte and monocyte counts, and MLPN showed continuously decrease, but rebounded to increase before death. And the occurrence of the trough of monocyte counts was earlier than that of lymphocyte counts, a negative correlation between neutrophil counts and PCT values was found. CONCLUSION: The results of this study revealed the dynamic interrelationships between leucocyte components and inflammatory indicators in the early stages and sepsis stage in severe burns, reflecting the different weightings of inflammatory responses and immune dysfunction in different disease stages and its correlation with outcomes, which providing useful clinical information for dynamic immunomodulatory therapy. Moreover, dynamic monitoring of MLPN value can provide timely information for clinical evaluation.

The Monocyte-to-Lymphocyte Ratio on the 6th Day Postburn Is Associated with Clinical Outcome of Severe Burns.

OBJECTIVE: As an immune/inflammatory indicator, the application of monocyte-lymphocyte ratio (MLR) in the treatment of severe burns is lacking. The aim of this study was to investigate the dynamic changes of the MLR value in the early stage of severe burns and its clinical value. METHODS: This is a 5-year retrospective cohort study involving 100 patients with severe burns (II-III degree and total body surface area (TBSA) >50%), in which the lymphocyte count, monocyte count, MLR value, C-reactive protein (CRP), creatinine (Scr), and capillary leakage index (CLI) were evaluated soon after injury, and 30-day mortality rates were investigated. RESULTS: The MLR values in non-survivors with severe burns were higher than those in survivors in the first two days after injury, while the values on the 3rd, 5th, 6th and 7th day after injury were lower than those in survivors. The differences between the 6th and 7th days after injury were statistically significant. According to the results of logistic and Cox regression analysis, the MLR values on the 6th day after injury were independent predictors of mortality, and the area under the ROC curve of the 6th day MLR for severe burn-delayed death prediction was 0.658 (95% confidence interval, 0.541-0.774), and the optimal cut-off value was 0.991. The 30-day mortality rates differed significantly between the MLR6 ≥0.991 group and the MLR6≤0.991 group (P<0.05). Within one week after injury, the MLR values were negatively correlated with Scr, CRP and CLI levels for severe burns. CONCLUSIONS: Our results revealed the dynamic characteristics of the MLR value in the early stage of severe burns, reflecting important changes in the immune/inflammatory related stress response soon after injury, low MLR level was associated with the worsening of disease condition.

Fluid balance in the resorption stage correlates with outcomes of severe burn patients.

OBJECTIVE: The resorption stage is an important period involving early anti-shock treatment for severe burn patients. We aimed to investigate the quantitative variability in fluid balance during the resorption stage in severe burn patients, and to study its effect on patient outcomes. METHODS: We conducted a single-centre retrospective study of 100 severe burn patients with involvement of > 50% total body surface area (TBSA). We extracted clinical data on demographics, clinical characteristics and outcomes; calculated the daily net fluid balance (difference between fluid intake and fluid output) and daily fluid intake/output within one week after injury; and analysed the association between fluid balance and functional outcomes and prognosis. The relative volume (ml/kg/TBSA) was used for the determination of daily fluid volume in this study. RESULTS: The daily net fluid balance (ml/kg/TBSA) of the deceased patients on the 4th, 5th, 6th, and 7th days after injury was higher than that of the surviving patients, but the opposite trend was found for the daily fluid output (ml/kg/TBSA). The partial correlation test showed that in the resorption stage of severe burn patients, fluid output was negatively correlated with the index levels of renal function and liver function, CRP level, blood lactic acid (LA) level, frequency of ventilator treatment, and capillary leakage index (CLI), but net fluid balance showed a completely opposite correlation. Moreover, fluid intake was negatively correlated with the index level of renal function and LA level, but positively correlated with the frequency of ventilator treatment. Furthermore, the logistic regression analysis showed that the net fluid balance and fluid output on Day 6 post-injury were independent risk factors for prognosis. CONCLUSION: This study suggested that greater fluid output in the resorption stage of severe burn patients was closely related to better outcomes, in addition, a gradually decreasing, lower positive net fluid balance may contribute to the improvement of functional outcomes, which will provide useful information for early fluid management and further prospective clinical study of severe burns.

Skin perfusion pressure for the prediction of wound healing in critical limb ischemia: a meta-analysis.

INTRODUCTION: The purpose of this meta-analysis was to determine the value and efficacy of skin perfusion pressure (SPP) for the prediction of wound healing in patients with critical limb ischemia. MATERIAL AND METHODS: Medline, Cochrane, EMBASE, and Google Scholar databases were searched from inception until December 31, 2014 using combinations of the following keywords: skin perfusion pressure, limb ischemia, wound healing, prediction. Randomized controlled trials, 2-arm prospective studies, and retrospective studies that measured SPP in patients with limb ischemia were included. The outcome was the sensitivity and specificity of SPP for the prediction of wound healing. RESULTS: Five studies were included in the meta-analysis. The mean patient age ranged from 62.2 to 71.5 years, and the majority were male. The pooled sensitivity of SPP for the prediction of wound healing was 79.9% using 30 mm Hg as the cut-off, 67.1% using 40 mm Hg, and 76.1% for all included studies (95% CI: 73.9-84.9%, 55.8-76.8%, and 70.7-80.8%, respectively). The pooled specificity was 78.2% using 30 mm Hg, 84.2% using 40 mm Hg, and 82.1% for all included studies (95% CI: 61.5-89.0%, 74.0-90.9%, 73.7-88.3%, respectively). CONCLUSIONS: Skin perfusion pressure can accurately predict wound healing in patients with critical limb ischemia.

Elevated serum uric acid after injury correlates with the early acute kidney in severe burns.

OBJECTIVE: Early acute kidney injury (AKI) is one of the most serious and common complications in the early stage of severe burns, but the pathological mechanisms still need to be elucidated. High uric acid (UA) has been found to be correlated with renal dysfunction in some experimental and clinical studies; however, the study of the dynamic correlation between AKI and UA in severe burns is still lacking. METHODS: The diagnosis and classification of AKI were performed according to RIFLE criteria, UA, serum creatinine (Scr), estimated glomerular filtration rate (eGFR), C-reactive protein (CRP) and lactic acid (LA) were dynamically monitored within 2 days after injury in 59 severely burned patients. RESULTS: Within 2 days after injury, AKI occurred in 23 of 59 patients (risk in 12 cases, injury in seven cases and failure in four cases), UA level in AKI patients was significantly higher than that in No-AKI patients, and referring to the cutoff level of UA (375.5 µmol/l) from ROC curve for predicting AKI, the abnormal increase of UA levels was earlier than acute deterioration of renal function in most of the AKI patients after injury. Among AKI patients, the Scr/eGFR levels were closely related to UA levels for 2 days after injury. Moreover, UA level in cases with severe grade of AKI was significantly higher than that in those with less severe grade of AKI. Furthermore, there was a positive correlation between UA and CRP for 2 days after injury in AKI patients, and a significant correlation between CRP and Scr/eGFR was found 1 day after injury. The positive correlation was also found between LA and UA after injury in AKI patients. CONCLUSION: The results suggest that elevated serum UA after injury due to hypoxia is closely correlated with early AKI after severe burns, and UA-related aberrant inflammation also appears to be one of the pathogenic factors, providing the useful information for potential therapy.

The characteristics and correlation between the ischemia-reperfusion and changes of redox status in the early stage of severe burns.

OBJECTIVE: Both the ischemia-reperfusion injury and the abnormal changes of redox status are the important pathologic changes in the burn shock stage for severe burns. The study of clinical dynamic, quantitative relevance about them was performed. METHODS: In this study, blood redox potential (ORP) values (ΔORP value was adopted, as the quantitative index to reflect the overall redox status), plasma uric acid levels (important antioxidant, as antioxidant index), and the burn shock state-related indicators (lactic acid and hematocrit) of 48 burn patients were dynamically, quantitatively monitored during the early stage after injury. RESULTS: The results revealed that the duration of abnormal fluctuation of redox status in the early stage of severe burns was longer than that of the traditional clinical shock stage (2-3 days). The changes of overreduction soon after injury were closely related to the hypovolemia-related hypoxia, and the following overoxidation status was consistent with the pathophysiological changes related to the reperfusion, and the degrees of variation were closely related to the severity of burn injury and prognosis. Moreover, early surgery (3 days after injury) had no significant influence on the changing trend of abnormal redox status in the early stage of severe burns. CONCLUSION: The ischemia-reperfusion injury caused by burn shock appears the main factor contributing to the abnormal biphasic changes of redox status in the early stage of severe burns. Our findings provide useful information for the redox regulation treatment for burn shock.

Biphasic changes (overreduction and overoxidation) of plasma redox status and clinical implications in early stage of severe burns.

PURPOSE: Although the changes of redox status in the early stage of severe burns are considered to be associated with the disease progression, whereas antioxidant therapy cannot improve the prognosis, the characteristics and mechanisms of dynamic change of redox status related with the disease progression deserve further study. METHODS: Blood redox potential (ORP) values (ΔORP value was adopted), plasma uric acid (UA) levels, and the inflammation-related indicators of 67 burn patients were dynamically monitored in the early stage. RESULTS: Compared with healthy persons, the results revealed the biphasic changes of redox status in the early stage after burns, and both of them were closely related to the prognosis of severe burns. Overreduction status and overoxidation status were related to the dynamic changes of plasma UA level and the inflammation-related indicators of severe burns. In addition, the change of ΔORP value was found to associate with the traditional prognostic markers. CONCLUSIONS: This study firstly revealed the excessive, biphasic changes of redox status and clinical implications in the early stage of severe burns, providing a new viewpoint for early pathological changes of severe burns and will be helpful for corresponding early treatment. ΔORP value also appears to be a potential early prognostic marker.

Effect of heparin on prevention of flap loss in microsurgical free flap transfer: a meta-analysis.

The effectiveness of heparin for thromboprophylaxis during microvascular free flap transfer is uncertain. The purpose of this meta-analysis was to determine the effect of heparin on the prevention of flap loss in microsurgical free flap transfer.A search of PubMed, Cochrane databases, and Google Scholar using combinations of the search terms heparin, free flap, flap loss, free tissue transfer was conducted on March 15, 2013. Inclusion criteria were: 1) Prospective randomized trials. 2) Retrospective, non-randomized studies. 3) Patients received free tissue transfer. Flap loss rate was used to evaluate treatment efficacy. Odds ratios (ORs) with 95% confidence intervals (CI) were calculated and compared between therapies. Four studies meet the criteria for analysis and were included. Two studiescompared aspirin and heparin, and the ORs of the 2 studies were 1.688 and 2.087. The combined OR of 2.003 (95% CI 0.976-4.109, p = 0.058) did not indicate any significant difference between heparin and aspirin therapies. Two studiescompared high and low doses of dalteparin/heparin therapies, and the ORs of the 2 studies were 4.691 and 11.00. The combined OR of 7.810 (95% CI 1.859-32.808, p = 0.005) revealed a significant difference indicating that high dose dalteparin or heparin therapy is associated with a greater flap loss rate than low dose therapy. Heparin and aspirin prophylaxis are associated with similar flap loss rates after free flap transfer, and high dose dalteparin or heparin therapy is associated with a greater flap loss rate than low dose therapy.

The reliability of clinical dynamic monitoring of redox status using a new redox potential (ORP) determination method.

PURPOSE: Quantitative monitoring of the redox status is the foundation for redox-related treatment. The purpose of this study was to evaluate the reliability of a new depolarization curve method for plasma redox potential (ORP) monitoring. METHODS: Using the new method, we performed redox determinations for the first time under different sample-handling conditions, including redox titration experiments using KMnO4 and vitamin C and dynamic redox monitoring in burn patients. The relative ORP value (ΔORP) method (improved traditional method) was used as the reference. RESULTS: The new method's better reliability, electrochemical specificity and practicability, and known group validity, which are closely associated with the redox-related pathological processes of severe burns, were confirmed. Furthermore, bidirectional change in the redox status in severe burn patients was also observed for the first time. CONCLUSIONS: This simple, stable new method could be a better practical tool for making the dynamic monitoring of the redox status feasible and for providing useful quantitative information for the judgment of redox-related pathological process, thus improving corresponding individualized treatments that rely on quantitative adjustments to the redox status.

K-ras and p53 gene mutations in noncancerous biliary lesions of patients with pancreaticobiliary maljunction.

BACKGROUND/PURPOSE: We investigated the molecular mechanisms of carcinogenesis in the biliary epithelium in patients with pancreaticobiliary maljunction. METHODS: Point mutations of the K- ras gene and the p53 gene, and the overexpression of p53 gene products were examined in the cancerous and noncancerous biliary epithelium of 37 patients with pancreaticobiliary maljunction, with or without biliary dilatation. RESULTS: In the gallbladder epithelium of 5 patients with pancreaticobiliary maljunction associated with biliary carcinoma, K- ras gene mutations were detected in 3 (60%), p53 gene mutations in 3 (60%), and the overexpression of p53 gene products in 4 (80%), while in the bile duct epithelium of these patients, these features were found in 2 of 3 (66.7%), in all of 3 (100%), and none of 3 (0%) specimens, respectively. In the gallbladder epithelium of patients with pancreaticobiliary maljunction without biliary carcinoma, K- ras gene mutations were detected in 8 of 24 (33.3%) specimens, p53 gene mutations were detected in 16 of 27 specimens (59.3%), and the overexpression of p53 protein was detected in 5 of 27 (18.5%) specimens, while in the bile duct epithelium of these patients, these features were found in 10 of 25 (40%) specimens, 14 of 25 (56%) specimens, and 6 of 24 (25%) specimens, respectively. CONCLUSIONS: These results suggest that noncancerous lesions of the biliary epithelium in patients with pancreaticobiliary maljunction have mutations of the K- ras gene and/or the p53 gene, which provides genetic evidence that biliary epithelium has high carcinogenic potential.