Indication-based protocols with different solutions for mechanical stromal-cell transfer

Background Regenerative medicine is the fastest developing branch of plastic surgery in recent times. Adipose tissue is one of the largest and most important sources in the body for stromal cells. Although mechanical isolation methods are both very popular and have many advantages, they still have no accepted protocols. Objective We developed new protocols called indication-based protocols (IPs) for standardization and new techniques called mechanical stromal-cell transfer (MEST) by using ultra-sharp blades and dilution of adipose tissue with different solutions (saline, Ringer and 5% Dextrose) Methods & material: In order to obtain the desired physical structure (liquid, gel, solid) and the desired volume, four different types of IPs have been defined. Adipose tissue was prediluted with different solutions using 10 or 20 cc injectors in IPs 1 and 2, while condensed adipose tissue was used directly in IPs 3 and 4. Results In MEST, stromal cells were obtained from 100 mL of condensed fat using different IPs with 92% mean viability and cell counts of 26.80–91.90 × 106. Stromal cells can be obtained in the desired form and number of cells by using four different IPs. Conclusion Isolation of stromal cells by cutting fat with sharp blades will prevent the death of fat tissue and stromal cells and will allow high viability and cell count with our new technique. Predilution with different solutions: Diluting the condensed adipose tissue with the desired solutions (saline, Ringer or 5% Dextrose) before the adinizing process will provide even more stromal cells. Lay Summary Obtaining regenerative stromal cells from adipose tissue can be done by two methods: Enzymatic and mechanical. Mechanical methods have many advantages. Although mechanical stromal cell extraction from adipose tissue is very popular and many techniques have been described, there are still no accepted protocols, definition for the end product, and no consensus on the status of the stromal cells. In this study, stromal cells were obtained mechanically by using ultra-sharp blade systems, without exposing adipose tissue to blunt trauma. Thus, a higher number of cells and higher viability could be obtained. An “Indication based” protocol has been defined for the first time in order to obtain the desired number and status (solid, semi-solid, liquid) end product. Diluting the condensed adipose tissue with the desired solutions (saline, Ringer or 5% Dextrose) before the adinizing process will provide even more stromal cells. This will provide an opportunity for clinicians to obtain and apply a stromal cell solution for different indications in different anatomical regions.

Evaluating serum level of thymidylate synthase in post burn keloid patients before and after intralesional injection of 5-fluorouracil

Background Keloids are fibrous lesions formed at the site of trauma due to types I and III collagen irregular production. The presence of thymidylate synthase (TS) is a must for DNA synthesis and repairs causing cell death. 5-fluorouracil (5-FU) is a fluorinated pyrimidine analogue acting as an anti-metabolic agent that inhibits thymidylate synthase and interferes with ribo-nucleic acid (RNA) synthesis. Objectives we aimed to evaluate the level of thymidylate synthase in post burn keloid patients before and after intralesional injection of 5-fluorouracil. Methods The study included 20 keloid patients and 20 healthy subjects as a control. Serum TS was estimated using commercially available enzyme-linked immunosorbent assay (ELISA) kits before and after treatment with 5-fluorouracil. Results There was a statistically significant difference in TS levels before and after 5-FU treatment (p < 0.05). Also, results have shown that 5-FU injection has good satisfactory results in treatment of keloid causing reduction in scar volume and symptoms improvement (90% of the patients improved). On the other hand, there was no statistically significant difference in TS levels and the outcomes of the treatment. Conclusion Our findings suggest that intralesional 5-FU injection in keloid has very satisfactory results. However, thymidylate synthase enzyme has a minimal role in evaluating the treatment of keloid, so further studies are required to elaborate the relation between this enzyme and keloid scars.

CO2 laser resurfacing for burn and traumatic scars of the hand and upper extremity

Background Scar formation is a normal part of the proliferative phase in wound healing where collagen is remodelled to better approximate normal skin. When collagen is not effectively redistributed, excessive scarring may occur. Recently, CO2 laser has emerged as an adjunct in improving scar quality via remodelling and redistribution of dermal collagen fibres. Due to the paucity of literature related to its use in the hands and upper extremities, we created a study to examine its effects on hypertrophic scars focused on the hands and upper extremities. Methods Patients treated with CO2 laser for hypertrophic scars of the hand and upper extremity were included. The Vancouver Scar Scale (VSS) and Patient and Observer Scar Assessment Scale (POSAS) were used to assess the progression of scar quality. Unpaired t-tests were performed to determine statistical difference between pre- and post-treatment scores on each scale. Pearson correlation coefficients were used to understand the relationship between number of treatments and scar quality. Results Of the 90 patients enrolled, 54 patients completed serial scar assessment forms. All patient and observer-reported POSAS domains showed improvement ( P < 0.05) apart from Itching. All VSS domains showed improvement ( P < 0.05). There was moderate correlation between overall patient-reported opinion of scar quality and Discoloration, Stiffness and Thickness, and strong correlation between overall patient opinion and Irregularity (r = 0.715). All observer-reported domains were strongly correlated (r = 7.56–8.74) with overall observer opinion of scar quality. Conclusion The results of this study may further substantiate CO2 laser as a treatment modality for excessive scarring in a variety of surgical subspecialties. Lay Summary Complex trauma and burns that impact the skin sometimes result in abnormal healing of the skin called, “hypertrophic scarring”. In our study we assessed how using focused CO2 laser therapy impacts patients and health care provider assessment of wound progression. Our results were based upon patient reported and healthcare provider observations based upon two standardized forms the Vancouver Scar Scale (VSS) and the Patient and Observer Scar Assessment Scale (POSAS). What we found is that after CO2 Laser Therapy, our 64 patients with 77 treated scars received on average almost 3 treatments and these treatments helped them with physical function and improved aesthetic appearance of their scars. The health care providers also found that the treatments improved functional and aesthetic end points. Overall, our study helps substantiate the body of evidence that using CO2 laser therapy improves aesthetics and function of hypertrophic scars in the upper extremity.

Evolution of a concept with enzymatic debridement and autologous in situ cell and platelet-rich fibrin therapy (BroKerF)

Background Deep partial-thickness burns are traditionally treated by tangential excision and split thickness skin graft (STSG) coverage. STSGs create donor site morbidity and increase the wound surface in burn patients. Herein, we present a novel concept consisting of enzymatic debridement of deep partial-thickness burns followed by co-delivery of autologous keratinocyte suspension and plated-rich fibrin (PRF) or fibrin glue. Material and methods In a retrospective case study, patients with deep partial-thickness burns treated with enzymatic debridement and autologous cell therapy combined with PRF or fibrin glue (BroKerF) between 2017 and 2018 were analysed. BroKerF was applied to up to 15% total body surface area (TBSA); larger injuries were combined with surgical excision and skin grafting. Exclusion criteria were age <18 or >70 years, I°, IIa°-only, III° burns and loss of follow-up. Results A total of 20 patients with burn injuries of 16.8% ± 10.3% TBSA and mean Abbreviated Burn Severity Score 5.45 ± 1.8 were identified. Of the patients, 65% (n = 13) were treated with PRF, while 35% (n = 7) were treated with fibrin glue. The mean area treated with BroKerF was 7.5% ± 0.05% TBSA, mean time to full epithelialization was 21.06 ± 9.2 days and mean hospitalization time was 24.7 ± 14.4 days. Of the patients, 35% (n = 7) needed additional STSG, 43% (n = 3) of whom had biopsy-proven wound infections. Conclusion BroKerF is an innovative treatment strategy, which, in our opinion, will show its efficacy when higher standardization is achieved. The combination of selective debridement and autologous skin cells in a fibrin matrix combines regenerative measures for burn treatment. Lay Summary Patients suffering from large burn wounds often require the use of large skin grafts to bring burned areas to heal. Before the application of skin grafts, the burned skin must be removed either by surgery or using enzymatic agents. In this article, we describe a method where small areas of skin are taken and skin cells are extracted and sprayed on wound areas that were treated with an enzymatic agent. The cells are held in place by a substance extracted from patients’ blood (PRF) that is sprayed on the wound together with the skin cells. We believe this technique can be helpful to reduce the need of skin grafts in burned patients and improve the healing process.

Electrochemical treatment of ex vivo human abdominal skin and potential use in scar management: A pilot study

Introduction: Scar treatments aim to address pathologic collagen deposition; however, they can be expensive or difficult to control. Electrochemical therapy (ECT) offers a simple alternative treatment. The purpose of this study is to examine the acid-base and histological changes in ex vivo human abdominal skin following ECT. Methods: Forty-two ex vivo human panniculus tissue sections collected from six individuals were tumesced with normal saline. ECT was performed by inserting two platinum needle electrodes connected to a DC power supply into each specimen. Voltage was varied (3–6 V) and applied for 5 minutes. Each specimen was sectioned across both electrode insertion sites and immediately stained with pH sensitive dye. The width of dye color change for each dosimetry pair was calculated. Hematoxylin and eosin staining was used to evaluate samples. Results and Discussion: ECT caused a spatially localised and dose-dependent increased area of acidic and basic pH around the anode and cathode, respectively. A significantly greater mean width of pH change was generated at the cathode compared to the anode in all treatment groups. Histological evaluation displayed broad condensation and hyalinisation of dermal collagen. Conclusion: ECT triggered dermal pH alterations and changed the underlying structural framework of the specimen. This technology may serve as a low-cost, minimally invasive local soft-tissue remodeling technique with potential application in scar management. Level of Evidence: 5 Lay Summary Electrochemical therapy is a novel treatment that causes spatially selective dermal injury in areas of interest. This study measures the effects of electrochemical therapy when applied to abdominal skin. Electrochemical therapy appears to have beneficial effects by causing a highly localised reduction in collagen content or local softening of tissue, which is consistent with other studies on scar therapies, including chemexfoliation, radiofrequency technologies, and lasers. However, electrochemical therapy can be performed at a fraction of the costs of these aforementioned modalities.

Use of tape for the management of hypertrophic scar development: A comprehensive review

Introduction: Tapes have been used to aid fresh wound closure. For hypertrophic scars, the use of tapes as a therapy to reduce the mechanical forces that stimulate excessive and long-term scarring is yet to be evaluated. The aim of this comprehensive review was to explore the current clinical application of tapes, as a minimally invasive option, as purposed specifically for the management of hypertrophic scarring, regardless of scar causation. Method: Databases were searched using MeSH terms including one identifier for hypertrophic scar and one for the intervention of taping. Studies included the following: patients who received tape for a minimum of 12 weeks as a method of wound closure specifically for the purpose of scar prevention; those who received tape as a method of scar management after scar formation; reported outcomes addressing subjective and/or objective scar appearance; and were available in English. Results: With respect to non-stretch tapes, their use for the prevention of linear surgical scarring is evident in reducing scar characteristics of height, colour and itch. Statistically significant results were found in median scar width, reduction in procedure times and overall scar rating. Tapes were predominately applied by participants themselves, and incidence of irritation was infrequently reported. After 12 months, significance with respect to scar pain, itch, thickness and overall scar elevation was reported in one study investigating paper tape. Two papers reported the use of high stretch tapes; however, subjective results limited formal analysis. Although the use of taping for abnormal hypertrophic scar management is in its infancy, emerging research indicates tapes with an element of stretch may have a positive impact. Conclusions: Non-stretch tapes, for the prevention of linear surgical scarring, are effective in reducing scar characteristics of height, colour and itch. Paper tapes have shown effectiveness when applied during wound remodelling or even on mature scarring, with reported subjective changes in scar colour, thickness and pliability. Preliminary evidence of the benefits of high-stretch, elasticised tapes for scar management in the remodelling phase of wound healing have also been reported. Lay Summary Patients are often concerned about unsightly scars that form on their bodies after trauma, especially burn injuries. These scars can be thick, red and raised on the skin, and can impact on the patient’s quality of life. For some scars, the process of skin thickening continues for up to two years after an injury. Unfortunately, scar formation is a part of the body’s healing process, whereby there is a constant pull or tension under and along the skin’s surface. The use of simple tapes, such as microporetm, to help with wound closure are sometimes used as a therapy to reduce the tension on the skin’s surface when a wound is healing to minimise scar formation. However, the effectiveness of taping has not been proven. This paper looks at the available evidence to support the use of taping to reduce scar features of height, thickness and colour. Initial evidence of mixed levels, suggests some benefits of tapes for scar management and show preliminary efficacy for reduction of scar height, thickness and colour. More research is required to determine the direct impact, comparison to other treatments available and patient viewpoint for this therapy.

Predictors of the recurrence of surgically removed previous caesarean skin scars at caesarean section: A retrospective cohort study

Background: Caesarean skin scars (CSS; hypertrophic scars and keloids) are very stressful for women and treatment strategies vary. However, there is a lack of knowledge about the outcome of surgical excision of CSS during caesarean section (CS). The study aims to determine the rate of recurrence and risk factors of recurrence for surgically removed CSS. Method: This is a retrospective cohort study that used STROBE guidelines. Pfannenstiel incisions of 145 patients were evaluated. Patients were divided into two groups: recurred (group 1, n = 19) and non-recurred group (group 2, n = 126). The groups were compared. Results: The rate of recurrence of CSS was 13% in the total cohort (19/145), one of the main outcomes of the study. While emergency CS was performed for 12 patients in group 1 (63%), CS was carried out in 25 patients in group 2 (20%); this difference was significant ( P = 0.001). Before surgery, white blood cell and neutrophil counts were significantly higher in group 1 ( P = 0.014 and P = 0.023, respectively). There were 11 dark-skinned women (26%; Fitzpatrick type 4) in group 1 and 31 (74%) in group 2. This difference was statistically significant ( P = 0.031). As the other main outcome, emergency CS could be accepted as a risk factor for recurrence in the multivariate regression analysis ( P = 0.060; odds ratio = 5.07; 95% confidence interval = 0.93–17.51). Conclusion: The rate of recurrence of surgically removed previous CSS at CS is promising without adjunct therapy. Emergency CS was found to be a risk factor for recurrence. Lay Summary Background Caesarean skin scars (CSS; hypertrophic scars and keloids) are very stressful and are generally itchy and painful for women. Treatment strategies vary. However, there is a lack of knowledge about the outcome of only surgical excision of CSS scars during caesarean section (CS). The issue being explored There are few data in the literature for CSS in the lower abdomen. These scars can be removed during the second or third CS, but the results are not known exactly. How was the work conducted? In our clinic, 145 patients with CSS were given a CS and their scars were removed at the same time. While most of these scars were reported as hypertrophic by pathological examination, some were reported as keloid. At the earliest, one year after surgery, the rate of recurrence was found to be 13%. What we learned from the study Asymptomatic patients who are planning another pregnancy and do not want to receive any other radiotherapy or steroid injection therapy can wait to remove their CSS at the next CS, especially elective CS with or without adjunct therapy. Emergency CS was found to be a risk factor for the recurrence of these scars.

Keloidal pathophysiology: Current notions

Introduction: Keloids are pathological scars that are notorious for their chronic and relentless invasion into adjacent healthy skin, with commonly seen post-therapeutic recurrence after monotherapies. Methods: An English literature review on keloid pathophysiology was performed by searching the PubMed, Embase and Web of Science databases, to find out the up-to-date relevant articles. The level of evidence was evaluated based on the included studies with the highest level of evidence first. Results: Keloid morphology, signs, symptoms and the histopathological changes that occur in the local cells and extracellular matrix components are described. The theories on the pathophysiology of keloidogenesis that have been proposed to date are also covered; these include endocrinological, nutritional, vascular, and autoimmunological factors. In addition, we describe the local mechanical forces (and the mechanosignalling pathways by which these forces shape keloid cell activities) that promote keloid formation and determine the direction of invasion of keloids and the body sites that are prone to them. Conclusion: A better understanding of this pathological entity, particularly its mechanobiology, will aid the development of new diagnostic and therapeutic strategies for use in the clinic to prevent, reduce or even reverse the growth of this pathological scar. Lay Summary Keloids are skin scars that are famous for their chronic invasion into healthy skin, with commonly seen recurrence after surgeries. Cells such as lymphocytes, macrophages, mast cells and endothelial cells are involved in keloid growth. Particularly, endocrinological, nutritional, vascular, autoimmunological and mechanical factors actively take part in keloid progression.

Intralesional cryotherapy with triamcinolone and onabotulinumtoxinA injections for umbilical keloid: A case report

Introduction Keloid scars are therapeutically challenging and although many treatment options exist, there are no specific guidelines, and few reports have discussed keloids in the umbilical region. Methods Here, we present a successful treatment of a 31-year-old female with a history of a recurrent keloid in the umbilical region. The keloid was treated using intralesional cryotherapy followed by intralesional onabotulinumtoxinA and triamcinolone acetonide injections. Discussion The patient expressed high satisfaction, minimal side effects, and no recurrence. Conclusion Overall, due to the low rate of side effects, high patient satisfaction, and absence of recurrence, this treatment modality should be considered as an option for umbilical keloids. Lay Summary Background to subject: Keloids are a type of scar that are difficult to treat. There are many treatment options available, but there is no single best treatment for keloids that form around the belly button region. Question being asked: Is intralesional cryotherapy with intralesional onabotulinumtoxinA and triamcinolone acetonide injections effective at treating keloids in the belly button region? How the work was conducted: We treated a 31-year-old female with a keloid around the belly button region that returned after prior treatment. The keloid was treated using combination therapy of freezing the keloid from the inside out, which is called intralesional cryotherapy. This was followed by two types of injections, called onabotulinumtoxinA and triamcinolone acetonide, directly into the keloid. What we learned: Overall, due to the low rate of side effects, high patient satisfaction and the keloid not returning, this treatment plan should be considered as an option for keloids in the belly button region. What we did not learn: This treatment may or may not be effective and safe for all patients of all skin types and demographics as this treatment was performed for only one patient.

Does the estimation of burn extent at admission differ from the assessment at discharge?

Introduction: Estimation of total body surface area (TBSA) burnt and burn depth are among the most central parts of acute burn assessment/treatment as they determine the level and type of care needed. Traditional methods for determining burn extent on admission often lead to inaccurate estimations, especially in paediatric or overweight patients. Aim: To compare %TBSA at admission with validated %TBSA at discharge in different patient populations to investigate if significant over- or underestimation occurs. Method: This retrospective observational study is based on a patient registry of all the patients (n = 863) treated at the Uppsala University Hospital’s Burn Centre between 2010 and 2018. The patients were divided into subgroups based on age, gender, body mass index (BMI) and validated burn extent. The %TBSA estimated at admission was compared to the validated %TBSA in all groups separately. Results: As has been published before, we also found that the %TBSA in paediatric patients was more often overestimated as were the smaller injuries, whereas larger injuries were often underestimated. BMI did not clearly affect the estimations and there was no clear difference between the genders in estimated %TBSA. Conclusion: Inaccurate estimations of %TBSA are common, particularly for paediatric patients and small or large injuries. We recommend a careful accurate approach when calculating %TBSA in the paediatric population to avoid over- and under-resuscitation. Increased education and training are recommended to improve accurate estimation in the future. Lay Summary The correct estimation of both extent and depth of burn is very important. This assessment guides the lever of care needed, the necessary amount of fluid resuscitation, the predicted outcome and more. It has been proven notably difficult to correct assess, especially the extent of a burn. Despite different tools as the “Rule of Nine” (body area divided into multiples of 9% body surfaces), the “Rule of Palm” (Patient’s palm, fingers included, approximates 1% of body surfaces), the Lund & Browder chart (detailed, age-specific body areas) and different more technical solutions. Often inaccurate estimations are done which thus affect the treatment. This depth and extent estimation is usually performed when the patient is admitted. However, it is known that burns change appearance during the first few days of care. In our Burn Center we have also performed this estimation when the patient is discharged. At this point it is known the true extent and depth of the initial burn. In this retrospective observational study, we compared the burn extent estimated on admission with the one on discharge to investigate whether the initial assessment is accurate. This study highlights the issue of frequent inaccurate burn extent estimations, especially in subgroups as overweight patient or pediatric patients.