Deep Partial Thickness Burns Research Articles

31 A phase 3 open-label, controlled, randomized trial evaluating the efficacy and safety of a bioengineered allogeneic cellularized construct in patients with deep partial-thickness thermal burns

Abstract Introduction Autograft (AG) is the standard of care for treatment of severe burns. While AG provides effective wound closure (WC), the procedure creates a donor site wound prone to pain and scarring. In a phase 1b trial, no deep partial-thickness (DPT) wound treated with a bioengineered allogeneic cellularized construct (BACC) required AG by Day 28 and WC at the BACC site was achieved in 93% of patients by Month (M) 3. This phase 3 study (NCT03005106) evaluated the efficacy and safety of this BACC in patients with DPT burns. Methods Enrolled patients were aged ≥18 years with 3–49% TBSA thermal burns on the torso or extremities. In each patient, two DPT areas (≤2,000 cm2 total) deemed comparable following excision were randomized to treatment with either cryopreserved BACC or AG. Coprimary endpoints were 1) the difference in percent area of BACC treatment site and AG treatment site autografted at M3 and 2) the proportion of patients achieving durable WC of the BACC treatment site without AG at M3. Ranked secondary endpoints were: 1) the difference between BACC and AG donor sites in average donor site pain intensity through Day 14; 2) the difference between BACC and AG donor site cosmesis at M3; and 3) the difference between BACC and AG treatment site cosmesis at M12. Safety assessments were performed in all patients through M12. Results Seventy-one patients were enrolled. By M3, there was a 96% reduction in mean percent area of BACC treatment sites that required AG, compared with AG treatment sites (4.3% vs 102.1%, respectively; P<.0001). BACC treatment resulted in durable WC at M3 without AG in 92% (95% CI: 85.6, 98.8; 59/64) of patients for whom data was available. By M3, mean donor site Patient and Observer Scar Assessment Scale (POSAS) observer total score (±SD) was significantly lower (more like normal skin) for BACC donor sites compared with AG donor sites (6.3 ± 1.71 vs 16.3 ± 7.71; P<.0001). At M12, mean POSAS observer total score (±SD) was 15.6 (± 8.34) for BACC treatment sites compared with 16.3 (± 9.41) for AG treatment sites (P=.4268). The most common BACC-related adverse event (AE) was pruritus, which occurred in 11 (15%) patients. All BACC-related AEs were mild or moderate in severity. Conclusions This phase 3 study achieved both coprimary endpoints, including significant autograft sparing and durable WC in DPT burns. Both donor site pain and donor site cosmesis were favorable outcomes of significantly reduced use of AG in BACC-treated patients. M12 POSAS for BACC did not differ significantly from AG. This BACC may offer a new treatment for severe burns to reduce or eliminate the need for AG. Applicability of Research to Practice This BACC has shown clinical benefit in patients with DPT thermal burns, potentially mitigating donor site morbidity. External Funding Stratatech, a Mallinckrodt Company; Funding and technical support for the Phase 3 clinical study were provided by the Biomedical Advanced Research and Development Authority (BARDA), under the Assistant Secretary for Preparedness and Response, within the U.S. Department of Health and Human Services, under Project BioShield Contract No. HHSO100201500027C.

632 How A Recurring Problem Prompted the Combination of Technologies. Our Institutional Experience with The Simultaneous Application of Poly Lactic Acid Polymer Dressings After Application of Suspension Epidermal Autografts.

Abstract Introduction Our institution has utilized the suspension epidermal autograft solution since a first application with FDA compassionate use protocol. We have since used this commercially available technology for the management of deep partial thickness and full thickness burn wounds. There is a non-adherent dressing in the commercially available kits to cover the suspension in a semi-porous fashion. We often would have beautifully dressed extremities and trunks only to find that in positions of function the non-adherent layer would pop through the intact staples. We then investigated the source of this discrepancy and found the non-elastic property of the dressing the likely culprit. We then began the process to determine an alternative dressing that could work more efficiently. Methods In an effort to determine if the institutional standard of care could be benefitted by this patient-based observation, the charts of patients that underwent simultaneous application of the epidermal autograft suspension and the poly lactic acid polymer dressing were interrogated. The data was identified by the institutional tissue tracker. Once the patient was identified, the chart was then reviewed to determine the desired data points. We evaluated the charts of patients that were recorded as utilizing the suspension epidermal autograft charge as wells charges for the poly lactic acid polymer skin substitute. The charts were then evaluated to determine if there were any deviations from our expected outcomes using the suspension alone. Results Our preliminary results indicate that the patients were able to discharge sooner as the wound care associated with the polymer skin substitute is more streamlined. It did not reflect any areas of graft loss but did in 2 instances remained in place longer than our standard. The wound was healed beneath but the skin substitute remained adhered. Conclusions The simultaneous use of suspension epidermal autografts and poly lactic acid skin substitutes has become common place for our institution. A quick review as a QI project has resulted in the desire to delve further into comparative data points. A formal retrospective review of the charts will be undertaken for a case series of about 20 patients.

664 “Minimally Invasive” Skin Grafting with Enzymatic Debridement and Autologous Skin Cell Spray

Abstract Introduction Minimally invasive surgery is increasingly becoming standard of care across numerous subspecialties. However, burn surgery has lagged behind; as the mainstay of reconstruction still involves wound excision with a knife, a commensurately sized skin graft, and a painful donor site. In recent years, several new technologies have the potential to be used synergistically to perform “minimally invasive” skin grafts. Enzymatic debridement with bromelain and autologous skin cell spray (ASCS) have independently been shown to reduce the need for split-thickness skin graft (STSG) and decrease the donor site size when grafting is performed. Bromelain is more likely to preserve healthy dermis and ASCS allows an 80:1 expansion. Due to constraints regarding the temporal course of these products only being available via studies before one was FDA approved, these two therapies have not been utilized together in the US until recently. A paucity of literature regarding their use in combination currently exists. Methods This study is a single site review of patients treated the continued access study protocol for bromelain-based enzymatic debridement and with ASCS per the FDA-approved instructions for use. Enzymatic debridement was performed over a 4-hour period with appropriate analgesia. Deep partial-thickness burns with residual dermis were treated with ASCS after enzymatic debridement and superficial dermabrasion. Wounds were dressed with a small pore non-adherent film and layered gauze. Full-thickness burn injuries were treated with conventional STSG. Results Two patients were treated over a 2 week period. One was a 51 yr old male with 17% TBSA superficial and deep partial thickness flame burns, of which 11% were deemed deep enough to warrant treatment with enzymatic debridement. 15% TBSA was treated with ASCS including the arms, back, and posterior neck with a 24 sq cm donor site. Wound closure was noted post-operative day 7 with complete re-epithelialization. The second patient was a 21-year-old male with several comorbidities impairing wound healing (diabetes [HgbA1c of 9.9], scurvy, and zinc deficiency. He had deep-partial and full-thickness burns to bilateral feet. The dorsum of the right foot was reconstructed with ASCS only and a 6 sq cm donor site, and the left foot was treated with a 3:1 meshed STSG and ASCS overspray with 100% take. Conclusions Enzymatic debridement and ASCS can be utilized to treat deep partial-thickness burns with a “minimally invasive” reconstruction. The donor sites in both patients were much smaller than had they been treated with a conventional meshed STSG. Further study is needed to determine which subsets of patients and burn wound characteristics are optimal for this combination of technologies. More data regarding outcomes such as length of stay, costs, and scar formation compared to standard of care is also warranted.

666 Autologous Skin Cell Therapy After Dermal Matrix with STSG in a 5-year-old African-American Female - How Adjunct Therapies are Refining the Dogmatic Treatment Approach to Burns

Abstract Introduction Split-thickness skin grafting (STSG) is the standard of care for the treatment of full thickness skin injuries. Skin grafts are associated with long-term morbidity including graft loss, adjacent structural injury, anesthetic complications, scarring, and scar contractures. Large surface area burns are additionally challenging due to limited donor site availability. Autologous skin cell suspension (ASCS) is a new adjunct for STSG using device that provides a suspension of non-cultured, autologous skin cells applied overtop of STSG. Dermal matrix templates are placed on wounds after burn excision and induces dermal regeneration in preparation for STSG, allowing for a thinner graft to be harvested and applied. This technique has been shown to require both smaller areas of donor skin as well as thinner skin harvest which improves both healing time and aesthetic outcomes of donor sites, enhancing the time-tested and well accepted technique of STSG. Methods We present the case of a 5-year-old African American female who suffered 18% TBSA deep partial thickness burns and full thickness burns to her abdomen, trunk and left back after her shirt was accidentally lit on fire at home. She was transferred from a local hospital to our burn center for further evaluation. She was evaluated by both the burn surgery and pediatric teams and admitted for wound cares and surgical planning. Results On hospital day five she underwent burn excision and placement of acellular dermal regeneration template. She returned to the operating room on hospital day 22 after daily wound cares for autografting with autologous skin cell suspension application to anterior and posterior torso and left arm, as well as to back and thigh donor sites. Her takedown on hospital day 29 showed excellent graft take. She was ultimately discharged on hospital day 47. She continued to undergo wound care in the outpatient burn clinic and daily physical and occupational therapy. Conclusions This case illustrates the use of dermal matrix and ASCS on a large burn with excellent aesthetic outcomes and improved healing time. This case is unique in highlighting the versatility of this therapy in a darker skinned patient. There are significant challenges with long term morbidity from STSG and the use of both dermal regenerative matrix and ASCS may provide surgeons with new approaches to decreasing depth and size of donor sites, as well as improving the length of hospital stay and overall aesthetic outcomes of donor and graft sites, specifically in darker skinned patients.

634 Utilizing Simulation Based Training to Teach Wound Management Strategies When Caring for Burns Treated with Autologous Skin Cell Suspension

Abstract Introduction Simulation based training (SBT) is an experience meant to replace real-life events with guided simulated clinical scenarios. The goal is fully interactive training that closely replicates the real world. SBT is well known in military and aviation and has been well integrated into the education of new nurses and physicians however, it has not been fully integrated into the ongoing development of skills for clinicians practicing in hospitals that are learning new technologies. Following FDA approval of a regenerative medicine platform that prepares autologous skin cell suspension (ASCS), an opportunity was identified to augment conventional training with a SBT educational program giving clinicians the opportunity to practice wound care in a simulated learning environment. Methods A prototype was developed alongside experts from a university-based experiential learning center. It included an anatomical silicone mold of a thigh (model) with silicone cartridges of ASCS treatment areas (excised deep partial-thickness burn with dermis and excised full-thickness burn with wide meshed split thickness skin graft). The cartridges fit in a depressed area of the thigh and can be exchanged between case scenarios. The cartridge allows for moulage to be applied, enhancing the life-like appearance of the model. The initial prototype was tested during a pilot with burn center staff. A total of 4 case scenarios related to ASCS aftercare were evaluated. Following the pilot, the program was demonstrated to our internal clinical team to gain additional insight. The feedback was incorporated into a final design. Results There were 17 participants in the pilot training (6 hands-on/11 observers). All hands-on participants either agreed or strongly agreed that SBT was useful to their clinical practice. Comments included: “Very realistic”, “really liked the hands-on”, “confidence booster”, “these are the most common scenarios we see”. One participant commented that even though she had never participated in an ASCS dressing change, she has the confidence to do so now. Soliciting feedback from our internal team on the design and portability of the model was an important step to ensure barriers to use were removed. To date, 11 training systems including models, cartridges, case scenarios, debrief tools and dressing kits have been distributed with a total of 30 systems expected by the end of 2020. Conclusions During development of the SBT program, input from clinicians and educators helped gain insight to the program and ensured the scenarios were relative to real-world experiences. Early findings suggest SBT is a value add for clinicians caring for patients post ASCS application.

658 Early Interventions with Autologous Skin Cell Suspension Leads to Positive Outcomes

Abstract Introduction Following initial stabilization, the primary goal of burn care is rapid wound closure to restore the barrier function and mechanical integrity of the skin. Time to wound closure is an important consideration when establishing the treatment plan, with a goal of re-epithelialization by 21 days to reduce the risks of hypertrophic scars (HTS), however, new research suggests that HTS can occur when healing is achieved as early as day 8. Early treatment of deep partial-thickness burns with autologous skin cell suspension (ASCS) was implemented at our burn center to achieve early wound closure and decrease hospital length of stay (LOS). Methods An IRB-approved, retrospective chart review of patients admitted between January 2020 to July 2020 was completed to evaluate the effectiveness of ASCS when applied as an early treatment defined as within 3 days of injury. Burn patients were excluded with delayed presentation >7 days, patients who only received ASCS to donor sites, and patients who died from unrelated comorbidities. Patients were excised to viable tissue. Patients with intact dermis were treated with ASCS. Patients without intact dermis were treated with ASCS and widely meshed autograft. Non-absorbent, small pore dressings were applied to the wound then covered with bismuth-petrolatum dressing, dry gauze, and compression bandage. Patients appropriate for discharge were followed-up in clinic for the first dressing change. Results Twenty-three patients were treated with ASCS utilizing this early intervention approach with 16 patients meeting inclusion criteria. Patients ranged from 15 months to 73 years of age and included 6 females and 10 males. The median total body surface area (TBSA) was 7.3% (range 2-23). Patients were taken for ASCS application between post burn day 0-3 (average 1.5). Average hospital LOS was 2.4 days. Operative dressings were removed between day 7-12 and >90% re-epithelization was noted between day 7-18 (mean 11). The mean LOS/%TBSA was 0.3. No patients required re-operation for closure of their wounds or reconstructive interventions for scarring. Conclusions Early excision of deep partial-thickness burns with application of ASCS allowed for healing to be achieved in a timely fashion. Implementation of an early operative approach to burn care allowed for a decrease in LOS and a decreased overall number of dressing changes.

Comparison of early surgical intervention to delayed surgical intervention for treatment of thermal burns in adults: A systematic review and meta-analysis

BackgroundBurns are one of the most prevalent forms of wound in children and adults, although timing of surgical excision for deep partial or full thickness burns remains controversial. ObjectivesTo determine if early surgical intervention (excision and grafting within 7 days) improves outcomes when compared to delayed surgical intervention (excision and grafting after 7 days) in adults with thermal burns. MethodsWe searched the following electronic databases: Cochrane Wound Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and CINAHL. We hand searched the references of included studies and major review articles. We contacted authors of included trials for information about any ongoing trials or unpublished studies. Selection criteria: We included randomized controlled trials, both published and unpublished, comparing early versus delayed surgical intervention for treatment of thermal burns of all degrees and percent total body surface areas (%TBSA) in adult patients. Data collection and analysis: Two authors independently, and in duplicate, screened the titles abstracts and then full texts of all citations for possible inclusion. Data from eligible studies were extracted independently and in duplicate using Microsoft Excel. We pooled outcome data according to the guidelines of the Cochrane Collaboration using Review Manager 5.3 software and random effects model. We assessed Risk of Bias (RoB) in individual studies using the Cochrane Collaboration’s tool and overall certainty of evidence for each outcome using the GRADE framework. Main resultsA total of 9 RCTs were included in the systematic review; 6 in the quantitative meta-analysis. Early surgical intervention may result in a small albeit imprecise reduction in mortality (risk ratio (RR) 0.78, 95% confidence interval (CI) 0.53 to 1.14, I2 = 46%, very low certainty) and a reduction in length of hospital stay (days) (mean difference (MD) 12.66 days fewer; 95% CI 9.80 days fewer to 15.53 days fewer, I2 = 88%, low certainty), but increased need for red blood cell (RBC) units (MD 27.11; 95% CI 20.17 to 34.06 units, I2 = 99%, low certainty) compared to delayed surgical intervention. Additionally, early excision and grafting may result in better functional and cosmetic outcomes; both based on low certainty evidence. However, no difference in scar quality and proportion of burns requiring re-operation was found (both low certainty). ConclusionEarly excision and grafting may reduce mortality and improve other patient important outcomes in adults with thermal burns, however most outcomes are based on low or very low certainty evidence. Higher quality, methodologically rigorous studies examining health-related quality of life are warranted in order to best inform this clinical question.

Effects of Virtual Reality and Task-Oriented Training on Hand Function and Activity Performance in Pediatric Hand Burns: A Randomized Controlled Trial

ObjectiveTo assess the efficacy of a motion-sensing, hands-free gaming device and task-oriented training (TOT) programs on improving hand function, activity performance, and satisfaction in pediatric hand burns. DesignA randomized controlled trial. SettingOutpatient rehabilitation center. ParticipantsFifty children with deep partial-thickness or full-thickness hand burns. (N=50; mean age, 10.70±1.64y; range, 7-14y) InterventionsChildren were randomized into 1 of the following 3 groups: the motion-sensing, hands-free gaming device group that used interactive video games plus traditional rehabilitation (TR); the TOT group that used real materials plus TR; and the control group that only received TR, all groups received the interventions 3 days per week for 8 weeks. Main Outcome MeasuresWe assessed the children at the baseline and after 8 weeks of intervention. The primary outcome measures were the Jebsen-Taylor Hand Function Test, Duruoz Hand Index (DHI), and Canadian Occupational Performance Measure (COPM). The secondary outcome measures were range of motion (ROM) of the digits, grip strength, and pinch strengths (tip, palmer, and lateral pinch). ResultsThere was a significant increase in all measurements of the motion-sensing, hands-free gaming device and TOT groups compared with that of the control group postintervention (P<.05). There was no significant change in Jebsen-Taylor Hand Function Test, COPM performance, ROM, grip strength, and tip and lateral pinch strengths between the motion-sensing, hands-free gaming device group and TOT group (P>.05), whereas there was a significant increase in DHI, COPM satisfaction, and palmer pinch strength (P<.05) in the motion-sensing, hands-free gaming device group compared with the TOT group postintervention. ConclusionsThe motion-sensing, hands-free gaming device and TOT programs resulted in significant improvement in hand function, activity performance and satisfaction, ROM of the digits, grip strength, and pinch strengths in pediatric hand burns compared with the traditional hand rehabilitation.

Value of renal injury marker protein in early diagnosis of acute kidney injury in burn patients with delayed resuscitation

Objective: To explore the value of renal injury marker protein in early diagnosis of acute kidney injury (AKI) in burn patients with delayed resuscitation. Methods: The retrospective case-control research was conducted. Forty-three burn patients with delayed resuscitation (27 males and 16 females, with age of 18-75 (35±3) years)who were admitted to Zhengzhou First People's Hospital from May 2018 to May 2020 met the inclusion criteria. The patients were divided into AKI group with 23 patients and non-AKI group with 20 patients according to whether AKI occurred within 7 days after burns. The gender, age, deep partial-thickness burn area, full-thickness burn area, and acute physiology and chronic health evaluation Ⅱ of patients were compared between the two groups.The fluid supplement volume and serum creatinine at 12, 24, and 48 h after burn, serum albumin/fibrinogen ratio (AFR), urinary heat shock protein 70 (HSP70), tissue inhibitor of metalloproteinase-2 (TIMP-2)×insulin-like growth factor binding protein 7 (IGFBP-7), and neutrophil gelatinase associated lipocalin (NGAL)at 12, 24, 48, 72, 120, and 168 h after burn were detected.Data were statistically analyzed with Mann-Whitney U test, analysis of variance for repeated measurement, independent-samples t test, chi-square test and Bonferroni correction. The independent variable to predict the occurrence of AKI was screened by multi-factor logistic regression analysis. The receiver's operating characteristic curve was drawn for predicting the occurrence of AKI in burn delayed resuscitation patients, and the area under the curve (AUC), the best threshold, and the sensitivity and specificity under the best threshold were calculated. Results: The gender, age, deep partial-thickness burn area, full-thickness burn area, acute physiology and chronic health evaluation Ⅱ of patients in two groups were similar (χ(2)=1.98, t=1.98, 1.99, 1.99, 1.99, P>0.05). The fluid supplement volume of patients in AKI group at 24 and 48 h after burn was significantly less than that in non-AKI group (t=15.37, 6.51, P<0.01). The serum creatinine of patients in AKI group at 12, 24, and 48 h after burn was significantly higher than that in non-AKI group (Z=2.16, 5.62, 6.72, P<0.01). The serum AFR of patients in AKI group at 12, 24, 48, 72, 120, and 168 h after burn was significantly lower than that in non-AKI group (t=16.14, 35.35, 19.60, 20.47, 30.20, 20.17, P<0.01). The levels of urinary HSP70 of patients in AKI group at 12, 24, 48, 72, 120, and 168 h after burn were (6.89±0.87), (6.42±0.73), (5.81±0.72), (5.17±0.56), (4.63±0.51), (3.89±0.51) μg/L, which were significantly higher than (3.89±0.75), (3.57±0.63), (2.66±0.41), (1.83±0.35), (1.48±0.19), (1.28±0.19) μg/L in non-AKI group (t=12.00, 13.61, 17.39, 22.98, 26.34, 21.59, P<0.01). Urinary TIMP-2×IGFBP-7 and NGAL of patients in AKI group at 12, 24, 48, 72, 120, 168 h after burn were significantly higher than those in non-AKI group (t=26.94, 101.11, 35.50, 66.89, 17.34, 14.30, 14.00, 13.78, 12.32, 14.80, 21.36, 22.62, P<0.01). Urinary HSP70 and serum AFR at 12 h after burn, urinary TIMP-2×IGFBP-7 and NGAL at 24 h after burn were included into multi-factor logistic regression analysis (odds ratio=2.42, 3.47, 7.52, 5.61, 95% confidence interval=1.99-2.95, 1.86-3.92, 2.87-9.68, 2.14-14.69, P<0.01). For 43 patients with burn delayed resuscitation, the AUC of receiver's operating characteristic curve of serum AFR at 12 h after burn for predicting AKI was 0.739 (95% confidence interval=0.576-0.903), the optimal threshold was 9.90, the sensitivity was 82%, and the specificity was 90%. The AUC of urinary HSP70 at 12 h after burn was 0.990 (95% confidence interval=0.920-1.000), the optimal threshold was 1.40 μg/L, the sensitivity was 98%, and the specificity was 96%. The AUC of urinary TIMP-2×IGFBP-7 at 24 h after burn was 0.715 (95% confidence interval=0.512-0.890), the optimal threshold was 114.20 μg(2)/L(2), the sensitivity was 91%, and the specificity was 95%. The AUC of urinary NGAL at 24 h after burn was 0.972 (95% confidence interval=0.860-1.000), the optimal threshold was 78 μg/L, the sensitivity was 95%, and the specificity was 96%. Conclusions: Urinary HSP70 and NGAL have higher value in early diagnosis of AKI in burn patients with delayed resuscitation.

The use of haemoglobin spray (Granulox) in a complicated burns patient

A 72-year-old male patient presented with 1% total body surface area superficial partial thickness burns, with small areas of deep partial and full thickness burns. Granulox, a commercial porcine-derived haemoglobin-containing spray, was used as an adjunct in healing the wounds, and improved local healing of the wound, decreased the length of stay in hospital and provided a favourable outcome.

Improving burn depth assessment for pediatric scalds by AI based on semantic segmentation of polarized light photography images

This paper illustrates the efficacy of an artificial intelligence (AI) (a convolutional neural network, based on the U-Net), for the burn-depth assessment using semantic segmentation of polarized high-performance light camera images of burn wounds. The proposed method is evaluated for paediatric scald injuries to differentiate four burn wound depths: superficial partial-thickness (healing in 0–7 days), superficial to intermediate partial-thickness (healing in 8–13 days), intermediate to deep partial-thickness (healing in 14–20 days), deep partial-thickness (healing after 21 days) and full-thickness burns, based on observed healing time.In total 100 burn images were acquired. Seventeen images contained all 4 burn depths and were used to train the network. Leave-one-out cross-validation reports were generated and an accuracy and dice coefficient average of almost 97% was then obtained. After that, the remaining 83 burn-wound images were evaluated using the different network during the cross-validation, achieving an accuracy and dice coefficient, both on average 92%.This technique offers an interesting new automated alternative for clinical decision support to assess and localize burn-depths in 2D digital images. Further training and improvement of the underlying algorithm by e.g., more images, seems feasible and thus promising for the future.

Accelerated Wound Closure of Deep Partial Thickness Burns with Acellular Fish Skin Graft.

Thermal injuries are caused by exposure to a variety of sources, and split thickness skin grafts are the gold standard treatment for severe burns; however, they may be impossible when there is no donor skin available. Large total body surface area burns leave patients with limited donor site availability and create a need for treatments capable of achieving early and complete coverage that can also retain normal skin function. In this preclinical trial, two cellular and tissue based products (CTPs) are evaluated on twenty-four 5 × 5 deep partial thickness (DPT) burn wounds. Using appropriate pain control methods, DPT burn wounds were created on six anesthetized Yorkshire pigs. Wounds were excised one day post-burn and the bleeding wound beds were subsequently treated with omega-3-rich acellular fish skin graft (FSG) or fetal bovine dermis (FBD). FSG was reapplied after 7 days and wounds healed via secondary intentions. Digital images, non-invasive measurements, and punch biopsies were acquired during rechecks performed on days 7, 14, 21, 28, 45, and 60. Multiple qualitative measurements were also employed, including re-epithelialization, contraction rates, hydration, laser speckle, and trans-epidermal water loss (TEWL). Each treatment produced granulated tissue (GT) that would be receptive to skin grafts, if desired; however, the FSG induced GT 7 days earlier. FSG treatment resulted in faster re-epithelialization and reduced wound size at day 14 compared to FBD (50.2% vs. 23.5% and 93.1% vs. 106.7%, p < 0.005, respectively). No differences in TEWL measurements were observed. The FSG integrated into the wound bed quicker as evidenced by lower hydration values at day 21 (309.7 vs. 2500.4 µS, p < 0.05) and higher blood flow at day 14 (4.9 vs. 3.1 fold change increase over normal skin, p < 0.005). Here we show that FSG integrated faster without increased contraction, resulting in quicker wound closure without skin graft application which suggests FSG improved burn wound healing over FBD.

Case Report: Bilateral Ultrasound-guided Serratus Anterior Plane Blocks for a Chest Wall Burn.

IntroductionThe serratus anterior plane block (SAPB) has been shown to effectively treat pain following breast surgery, thoracotomies, and rib fractures. We present the first reported case of a bilateral ultrasound-guided SAPB in a multimodal analgesic regimen after an acute large, thoracic, deep partial-thickness burn.Case ReportA 72-year-old male presented in severe pain two days after sustaining a deep partial- thickness burn to his anterior chest wall after his shirt caught on fire while cooking. The area of injury was on bilateral chest walls, and the patient was consented for bilateral SAPBs at the level of the third thoracic ribs (T3). With ultrasound guidance, a mixture of ropivacaine and lidocaine with epinephrine was injected into the fascial plane overlying bilateral serratus muscles at T3. The patient reported complete resolution of pain for approximately 15 hours and required minimal additional intravenous analgesia.ConclusionThe ultrasound-guided SAPB may be an excellent addition to the multimodal analgesic regimen in superficial and partial-thickness burns of the anterior chest wall.

GDF-5 promotes epidermal stem cells proliferation via Foxg1-cyclin D1 signaling

ObjectiveEpidermal stem cells (EpSCs) can self-renew, which are responsible for the long-term maintenance of the skin, and it also plays a critical role in wound re-epithelization, but the mechanism underlying EpSCs proliferation is unclear. GDF-5, also known as BMP-14, is a member of the BMP family and can be used as a self-renewal supporter. Here, we studied the effects of GDF-5 on mouse EpSCs proliferation mechanism in wound healing.MethodsFirstly, the effects of GDF-5 on EpSCs proliferation was tested by using CCK8 reagent and PCNA expression was analyzed by Western blotting. Secondly, we screened genes that promote EpSCs proliferation in the FOX and cyclin family by qPCR, and then the protein expression level of the selected genes was further analyzed by Western blotting. Thirdly, siRNA plasmids and pAdEasy adenovirus were transfected or infected, respectively, into mouse EpSCs to detect the effect of target genes on GDF-5-induced cell proliferation. Furthermore, we injected GDF-5 to a deep partial thickness burn mouse model for finding out whether EpSCs proliferation can be detected by immunohistochemical. Finally, the relevant target genes were analyzed by qPCR, immunoblotting, and dual-luciferase reporter gene detection.ResultsWe discovered that 100 ng/ml recombinant mouse GDF-5 was the optimal concentration for promoting mouse EpSCs proliferation. Through preliminary screened by qPCR, we found that Foxg1 and cyclin D1 could be the downstream molecules of GDF-5, and the results were confirmed by Western blotting. And the effect of GDF-5 on mouse EpSCs proliferation was adjusted by Foxg1/cyclin D1 in vitro and in vivo. Besides, GDF-5-induced transcription of cyclin D1 was regulated by Foxg1-mediated cyclin D1 promoter activity.ConclusionThis paper showed that GDF-5 promotes mouse EpSCs proliferation via Foxg1-cyclin D1 signal pathway. It is suggested that GDF-5 may be a new approach to make EpSCs proliferation which can be used in wound healing.

Isolated penile injury in boys: Accident, negligence, or abuse?

Aim:The aim of the study was to highlight the etiology, spectrum of presentation, and management of isolated penile trauma in boys.Methods:A retrospective review of boys treated for isolated penile trauma between January 2015 and June 2019 at a tertiary-level hospital.Results:Nine children were admitted over 4½ years. Etiology: The mechanism of penile injury (PI) was penile hair tourniquet (n = 5), postcircumcision (n = 2), dog bite (n = 1), and scald injury (n = 1). Extent of injury includes complete urethral transection at corona (n = 4); loss of urethral plate in a case of hypospadias (n = 1); complete loss of glans (n = 1); penile transection at corona (n = 1); total penile amputation (n = 1); and deep partial-thickness burns of penile shaft and adjacent suprapubic skin (n = 1). Management: One patient absconded. The remaining patients were managed as follows: calibration of urethral meatus (n = 1); penile burn was managed with dressing and antibiotics; coring of glans with urethral end–end anastomoses (n = 4); Bettocchi's quadrangular lower abdominal flap phalloplasty (n = 1); and Bracka's staged urethroplasty (n = 1). Complications include wound infection following trauma (n = 4), postsurgical infection (n = 3), urethrocutaneous fistula (n = 2), and reapplication of penile hair tourniquet (n = 1).Conclusion:Isolated PI in boys is not uncommon. Most are preventable if the parents are apprized and watchful. The clinician should also be vigilant regarding child maltreatment. A staged approach tailored to the type of injury provides a satisfactory outcome.

Epidermal Growth Factor and Tocotrienol-Rich Fraction Cream Formulation Accelerates Burn Healing Process Based on Its Gene Expression Pattern in Deep Partial-Thickness Burn Wound Model.

Our previous study has demonstrated that epidermal growth factor (EGF) with tocotrienol-rich fraction (TRF) cream formulation accelerating postburn wound healing with deep partial-thickness burn in rats. Current study was conducted to determine the gene expression levels related to burn wound healing process. A total of 180 Sprague-Dawley rats were randomly divided into 6 groups: untreated control, treated with Silverdin cream, base cream, base cream with 0.00075% EGF, base cream with 3% TRF or base cream with 0.00075% EGF, and 3% TRF, respectively. Burn wounds were created and the above-mentioned creams were applied once daily. Six animals from each group were sacrificed on days 3, 7, 11, 14, and 21 postburn. RNA was extracted from wound tissues and quantitative real-time polymerase chain reaction was performed to analyze the 9 wound healing-related genes against time postburn. Results demonstrated that topically applied EGF + TRF formulation downregulated the expression levels of IL-6 (interluekin-6), TNF-α (tumor necrosis factor-α) and iNOS (inducible nitric oxide synthase) throughout the whole healing process. TGF-β1 (transforming growth factor-β) and VEGF-A (vascular endothelial growth factor-A) were reduced on day 14 postburn. On the contrary, increased expression of Collagen-1 in the early stage of wound healing was observed with no effects on epidemal growth factor receptor (EGFR). The results showed beneficial application of EGF + TRF cream in the treatment of burn wound since it accelerated wound healing by relieving oxidative stress, decreasing inflammation, and promoting proper tissue modelling in the burn wound.

Establishment and test results of an artificial intelligence burn depth recognition model based on convolutional neural network

Objective: To establish an artificial intelligence burn depth recognition model based on convolutional neural network, and to test its effectiveness. Methods: In this evaluation study on diagnostic test, 484 wound photos of 221 burn patients in Xiangya Hospital of Central South University (hereinafter referred to as the author's unit) from January 2010 to December 2019 taken within 48 hours after injury which met the inclusion criteria were collected and numbered randomly. The target wounds were delineated by image viewing software, and the burn depth was judged by 3 attending doctors with more than 5-year professional experience in Department of Burns and Plastic Surgery of the author's unit. After marking the superficial partial-thickness burn, deep partial-thickness burn, or full-thickness burn in different colors, the burn wounds were cut according to 224×224 pixels to obtain 5 637 complete wound images. The image data generator was used to expand images of each burn depth to 10 000 images, after which, images of each burn depth were divided into training set, verification set, and test set according to the ratio of 7.0∶1.5∶1.5. Under Keras 2.2.4 Python 2.8.0 version, the residual network ResNet-50 of convolutional neural network was used to establish the artificial intelligence burn depth recognition model. The training set was input for training, and the verification set was used to adjust and optimize the model. The judging accuracy rate of various burn depths by the established model was tested by the test set, and precision, recall, and F1_score were calculated. The test results were visualized to generate two-dimensional tSNE cloud chart through the dimensionality reduction tool tSNE, and the distribution of various burn depths was observed. According to the sensitivity and specificity of the model for the recognition of 3 kinds of burn depths, the corresponding receiver operator characteristics (ROC) curve was drawn, and the area under the ROC curve was calculated. Results: (1) After the testing of the test set, the precisions of the artificial intelligence burn depth recognition model for the recognition of superficial partial-thickness burn, deep partial-thickness burn, or full-thickness burn were 84% (1 095/1 301), 81% (1 215/1 499) and 82% (1 395/1 700) respectively, the recall were 73% (1 095/1 500), 81% (1 215/1 500) and 93% (1 395/1 500) respectively, and the F1_scores were 0.78, 0.81, and 0.87 respectively. (2) tSNE cloud chart showed that there was small overlapping among different burn depths in the test results for the test set of artificial intelligence burn depth recognition model, among which the overlapping between superficial partial-thickness burn and deep partial-thickness burn and that between deep partial-thickness burn and full-thickness burn were relatively more, while the overlapping between superficial partial-thickness burn and full-thickness burn was relatively less. (3) The area under the ROC curve for 3 kinds of burn depths recognized by the artificial intelligence burn depth recognition model was ≥0.94. Conclusions: The artificial intelligence burn depth recognition model established by ResNet-50 network can rather accurately identify the burn depth in the early wound photos of burn patients, especially superficial partial-thickness burn and full-thickness burn. It is expected to be used clinically to assist the diagnosis of burn depth and improve the diagnostic accuracy.

Pirfenidone regulates LPS mediated activation of neutrophils

Excessive inflammation or its absence may result in impaired wound healing. Neutrophils are among the first innate immune cells to arrive at the injury site. They participate in infection control and debris removal to initiate healing. If not timely resolved, neutrophils can cause excessive tissue inflammation and damage. Drugs with anti-inflammatory and anti-fibrotic effects are of promise for improving healing by balancing the primary defensive functions and excessive tissue damage actions. Of interest, pirfenidone (Pf), an FDA approved anti-fibrotic drug to treat idiopathic pulmonary fibrosis, has been shown to ameliorate inflammation in several animal models including mouse deep partial-thickness burn wounds. However, there is a lack of mechanistic insights into Pf drug action on inflammatory cells such as neutrophils. Here, we examined the treatment effects of Pf on LPS-stimulated neutrophils as a model of non-sterile inflammation. Firstly, Pf reduced chemotaxis and production of pro-inflammatory ROS, cytokines, and chemokines by LPS-activated neutrophils. Secondly, Pf increased anti-inflammatory IL-1RA and reduced neutrophil degranulation, phagocytosis, and NETosis. Thirdly, Pf affected downstream signaling kinases which might directly or indirectly influence neutrophil responses to LPS. In conclusion, the results suggest that Pf lessens the inflammatory phenotypes of LPS-activated neutrophils.

Determining clinically meaningful thresholds for innovative burn care products to reduce autograft: A US burn surgeon Delphi panel

Reducing the amount of donor skin needed for definitive wound closure can improve outcomes in patients with severe burns. This Delphi Consensus Panel (DCP) aimed to achieve expert consensus on the percentage reduction in donor skin for autograft that constitutes a clinically meaningful benefit. A two-round DCP of fifteen US burn surgeons was conducted via a web-based survey platform. Fourteen panelists (93.3%) completed both rounds. In Round 2, consensus, defined as ≥70% agreement, was achieved for five of the seven consensus statements. All panelists agreed that a clinically meaningful reduction in the amount of donor skin required would facilitate wound management and decrease donor site morbidity experienced by patients. Furthermore, based on three treatment scenarios, consensus was achieved for a clinically meaningful reduction in the amount of donor skin required for autograft for the adult population in deep partial-thickness and full-thickness burns. Findings from this DCP indicate that an innovative cellular and/or tissue product that would reduce the needed amount of donor skin, by the identified thresholds, has the potential to improve the outcomes for patients with severe burn injuries in a meaningful way.

The Guru-UKM Method: Synergistic Effect of Hydrogel, Hydrofibre and Dermal Conservation in Burn Wound Management

Initial wound care idioms were designed around a moist dressing in presumed better wound healing. As wound care advances, innovations of dressings were formed. In the Guru-UKM Method (GUM), we combined two well-established dressings producing a synergistic effect in burn wound management. Patients with deep partial thickness burns were selected for the GUM. From the time of admission, they receive 2 cycles of paraffin tulle dressings once every two days to allow demarcation, then are reassessed for suitability of the GUM technique. We discuss 7 different burn cases that presented to our Burn Unit from January 2014 – June 2015.All dressings should create a suitable moist environment for healing, yet should be a painless dressing to help the patient return to normal function as soon as possible. In burn wounds, a suitable dressing ideally also biochemically debrides fibrin and softens hardened eschar and slough, without necessitating the patient to undergo general anaesthesia and surgical debridement. The Guru-UKM Method is a combination dressing technique that facilitates optimal burn wound management.