A novel real-time model for predicting acute kidney injury in critically ill patients within 12 hours.

BACKGROUND: A major challenge in prevention and early treatment of acute kidney injury (AKI) is the lack of high-performance predictors in critically ill patients. Therefore, we innovatively constructed U-AKIpredTM for predicting AKI in critically ill patients within 12 h of panel measurement. METHODS: The prospective cohort study included 680 patients in the training set and 249 patients in the validation set. After performing inclusion and exclusion criteria, 417 patients were enrolled in the training set and 164 patients were enrolled in the validation set finally. AKI was diagnosed by Kidney Disease Improving Global Outcomes (KDIGO) criteria. RESULTS: Twelve urinary kidney injury biomarkers (mALB, IgG, TRF, α1MG, NAG, NGAL, KIM-1, L-FABP, TIMP2, IGFBP7, CAF22 and IL-18) exhibited good predictive performance for AKI within 12 h in critically ill patients. U-AKIpredTM, combined with three crucial biomarkers (α1MG, L-FABP and IGFBP7) by multivariate logistic regression analysis, exhibited better predictive performance for AKI in critically ill patients within 12 h than the other twelve kidney injury biomarkers. The area under the curve (AUC) of the U-AKIpredTM, as a predictor of AKI within 12 h, was 0.802 (95% CI: 0.771-0.833, P < 0.001) in the training set and 0.844 (95% CI: 0.792-0.896, P < 0.001) in validation cohort. A nomogram based on the results of the training and validation sets of U-AKIpredTM was developed which showed optimal predictive performance for AKI. The fitting effect and prediction accuracy of U-AKIpredTM was evaluated by multiple statistical indicators. To provide a more flexible predictive tool, the dynamic nomogram (https://www.xsmartanalysis.com/model/U-AKIpredTM) was constructed using a web-calculator. Decision curve analysis (DCA) and a clinical impact curve were used to reveal that U-AKIpredTM with the three crucial biomarkers had a higher net benefit than these twelve kidney injury biomarkers respectively. The net reclassification index (NRI) and integrated discrimination index (IDI) were used to improve the significant risk reclassification of AKI compared with the 12 kidney injury biomarkers. The predictive efficiency of U-AKIpredTM was better than the NephroCheck® when testing for AKI and severe AKI. CONCLUSION: U-AKIpredTM is an excellent predictive model of AKI in critically ill patients within 12 h and would assist clinicians in identifying those at high risk of AKI.

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.

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.

The optimization of PLGA knitted mesh reinforced-collagen/chitosan scaffold for the healing of full-thickness skin defects.

Collagen-based scaffolds reveals promising to repair severe skin defects. The mechanical strength of collagen-based scaffold (CCS) limited its clinical application. Embedding poly(lactic-co-glycolic) acid (PLGA) knitted mesh into CCS improves the mechanical strength of the scaffold. This study was conducted to optimize the configuration of PLGA knitted mesh-collagen-chitosan scaffold (PCCS), and explore possible mechanisms. PLGA knitted mesh was embedded in CCS through freeze-drying method. With the PLGA knitted mesh located at the bottom, middle, or both bottom and top layers of the CCS, three kinds of PCCS were developed. A full-thickness skin wound model was established in Sprague Dawley rats to evaluate the therapeutic effects of different PCCS against CCS. The properties and healing effect of the scaffolds were investigated. Several growth factors and chemotactic factors, that is, VEGF, PDGF, CD31, α-SMA, TGF-ß1, and TGF-ß3 were analyzed and evaluated. Re-epithelialization and angiogenesis were observed in all animal groups with the treatment of three kinds of PCCS scaffolds and the CCS scaffold (control). The protein and gene expression of VEGF, PDGF, CD31, α-SMA, TGF-ß1, and TGF-ß3 showed different dynamics at different time points. Based on the healing effects and the expression of growth factors and chemotactic factors, scaffold with the PLGA knitted mesh located at the bottom layer of the CCS demonstrated the best healing effect and accelerated re-epithelialization and angiogenesis among all the scaffolds evaluated. PCCS with the PLGA mesh located in the bottom layer of the scaffold accelerated wound healing by creating a more supportive environment for re-epithelialization and angiogenesis.

Evaluation of Bacterial Cellulose Dressing versus Vaseline Gauze in Partial Thickness Burn Wounds and Skin Graft Donor Sites: A Two-Center Randomized Controlled Clinical Study.

Objective: Bacterial cellulose (BC) dressing, which can maintain a moist environment and prevent the invasion of pathogens, has become a competitive dressing material for burn wound treatment. This study was conducted to evaluate the treatment efficacy of a novel China-made BC dressing for the treatment of second-degree burn wounds and skin graft donor sites. Methods: 212 patients with second-degree burn wounds or skin graft donor sites were enrolled from two research centers. They were randomly assigned to the BC dressing group (study group) or the Vaseline gauze (VG) dressing group (control group). Wound conditions were assessed before and after treatment. Dressings were changed according to the condition of the wound bed. Healing rate and healing time were recorded as primary endpoints to evaluate the efficacy of BC dressing against VG dressing. Erythema, swelling, exudation, bleeding, subeschar purulence, and pain were assessed as secondary endpoints. Results: 207 participants completed the trial and their wounds all healed within 28 days. The average healing times for superficial and deep secondary burn wounds and skin graft donor sites in the BC group were 8.12, 15.77, and 10.55 days, respectively. In the VG group, the average healing times for superficial and deep secondary burn wounds and skin graft donor sites were 9.30, 15.27, and 11.19 days, respectively. The healing time of superficial burn wounds in the BC group was statistically shorter than that in the VG group. There was no difference in the frequency of dressing changing between two groups. The BC dressing showed equal efficacy with the VG dressing at all secondary endpoints. Conclusion: The novel BC dressing could be used for the management of second-degree burn wounds and skin graft donor sites. With a shorter healing time in superficial secondary burn wound than that of the VG dressing, the BC dressing showed noninferiority in the treatment of superficial and deep secondary burn wounds and skin graft donor sites versus the VG dressing. This study is registered with the Chinese Clinical Trial Registry (registry number: ChiCTR1800014377 (http://www.chictr.org.cn)).

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.

Skin perfusion pressure as a predictor of ischemic wound healing potential.

Skin perfusion pressure (SPP) is the blood pressure that is the requisite for the restoration of microcirculatory or capillary flow following controlled occlusion and subsequent flow return. The purpose of the current review was to evaluate the value of SPP for the prediction of wound healing in patients with limb ischemia. Articles published up to January 31, 2017 were searched in the PubMed database and Chinese database CNKI, using the keywords of 'skin perfusion pressure', 'limb ischemia' and 'wound healing'. Articles were obtained and reviewed to analyze the predictive value of SPP with regard to the healing potential of ischemia wounds on limbs. Three different types of techniques are currently used for the measurement of SPP, namely radioisotope clearance, photoplethysmography and laser Doppler, with laser Doppler as the most widely applied technique, due to its noninvasiveness and ease of operability. SPP may effectively assess wound healing potential in ischemic limbs with high sensitivity and specificity; however, its optimum cut-off point remains uncertain. Compared with other noninvasive microcirculatory assessment tools including ankle-brachial index, toe blood pressure and transcutaneous oxygen pressure, SPP has its advantages including that it is not affected by vascular calcification, anatomical structure or patient condition. In conclusion, SPP may be used as an index to accurately predict wound healing in patients with limb ischemia. However, it is difficult to determine the optimum cut-off of SPP due to the limitations of current data. Further study is necessary to confirm the optimum cut-off value of SPP in predicting wound healing potential.

Association of plasminogen activator inhibitor-1 and vitamin D receptor expression with the risk of keloid disease in a Chinese population.

Keloid disease (KD) is a benign fibroproliferative scarring condition of unknown etiopathogenesis. Plasminogen activator inhibitor-1 (PAI-1) and vitamin D receptor (VDR) have been shown to play important roles in the progression of tissue fibrosis; therefore, both these genes are potential susceptibility genes for KD. We aimed to determine whether the gene expression levels of PAI-1 and VDR are altered in Chinese KD patients. We measured the expression of PAI and VDR in human peripheral blood lymphocytes in 236 patients with keloid and 219 age- and sex-matched healthy controls by quantitative real-time polymerase chain reaction. We found that PAI-1 expression in peripheral blood lymphocytes was significantly higher in patients with KD than in control individuals (p < 0.0001), while VDR expression was significantly lower in KD patients than in control individuals (p < 0.0001). High levels of PAI-1 and low levels of VDR expression were significantly associated with an increased risk for KD. PAI-1 and VDR might play important roles in keloid development. Gene expression levels of PAI-1 and VDR may, therefore, be used as potential markers for the prediction of keloid development after scarring.

A randomized controlled trial to compare the effects of liquid versus powdered recombinant human growth hormone in treating patients with severe burns.

Recombinant human growth hormone (rhGH) promotes protein utilization and synthesis, and is widely used as a therapy to treat severe burns. The present randomized controlled trial evaluated the effects of different forms of rhGH on patients with severe burns. A total of 29 adult severe burns patients were enrolled between February 2009 and November 2011, and randomly assigned to either treatment group (T, liquid rhGH) or control group (C, powder rhGH). From days 5 to 7 following the infliction of burns, both patient groups received rhGH at 0.067 mg/kg/d, once for 10 days. Median serum pre-albumin levels increased in both groups following treatment, the elevation from baseline was significantly higher in the T group on day 10 compared to the C group (88 mg/l vs. 65 mg/l, P=0.046). C-reactive protein, fasting plasma glucose and body weight decreased in both groups. Body weight was significantly lower in the T compared to the C group at baseline, Day 5 and Day 10 (P=0.046, P=0.018 and P=0.006, respectively), however the decrease from baseline levels were not significantly different. Wound healing time was similar between groups (P=0.270). In conclusion the early use of liquid rather than powder rhGH may be more beneficial for treating adult patients with severe burns.

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.