Reconstruction of Upper and Lower Limb Defects with Medial Sural Artery Perforator Flaps: Is Aesthetics Worth the Effort? A Retrospective Analysis.

Background One of the most essential goals in managing complex limb defects is obtaining adequate soft tissue coverage with excellent functional and aesthetic outcomes. Free perforator skin flaps represent an optimal option for such defects. Therefore, our intention was to reconstruct these kinds of defects with thin fasciocutaneous flaps without the need for debulking. Herein, we define the legitimate use of the medial sural artery perforator (MSAP) flaps for small-moderate size defect coverage of the hand and foot. Patients and Methods Seven patients received MSAP flaps for reconstruction of different hand and foot defects, of which the majority were males (4/7). Age, sex, flap size, location, number of perforators, recipient vessel, type of anastomosis, technique of donor site closure, and postoperative morbidity were recorded. Patients' age ranged from 48 to 84 years. Results Single-stage debridement followed by reconstruction was performed. Flap sizes ranged from 6 to 18 cm in length and 4 to 10 cm in width. The pedicles of 6 flaps were anastomosed to the tibial artery system (three posterior tibial artery, three dorsalis pedis artery) and one to the ulnar artery. Conclusion MSAP flap can be a versatile option for single-stage reconstruction of small-moderate size defects of the extremities, where thin, soft tissue envelope is required. This flap has lower donor site morbidity, more tedious elevation process, and has a good reconstructive and aesthetic result without the need for debulking in the future.

Burn Injury: Mechanisms of Keratinocyte Cell Death.

Cutaneous burn injury is associated with epidermal loss in the zone of coagulation zone and delayed tissue loss in the zone of stasis. Thus, thermal stress can trigger both necrosis and regulated cell death (RCD) or apoptosis. Experimental in vitro and in vivo work has clearly demonstrated apoptotic events of thermally injured keratinocytes that are accompanied by morphological and biochemical markers of regulated cell death. However, in vivo data for the different pathways of regulated cell death are sparse. In vitro experiments with heat-stressed human keratinocytes have demonstrated death receptor involvement (extrinsic apoptosis), calcium influx, and disruption of mitochondrial membrane potential (intrinsic apoptosis) in regulated cell death. In addition, caspase-independent pathways have been suggested in regulated cell death. Keratinocyte heat stress leads to reduced proliferation, possibly as a result of reduced keratinocyte adhesion (anoikis) or oncogene involvement. Understanding the underlying mechanisms of RCD and the skin's responses to thermal stress may lead to improved strategies for treating cutaneous burn trauma.

Does Increased Patient Load Improve Mortality in Burns?: Identifying Benchmark Parameters Defining Quality of Burn Care.

INTRODUCTION: In burn care, as in other medical fields, there is a tendency to increase the required number of patients for center certifications. Does the increase in patient load automatically improve the quality of burn care? What are the benchmark parameters that have been shown to improve burn care? METHODS: To answer these questions, Medline, Cochrane Library, and Livivo were searched from inception through January 2018 for all studies evaluating the influence of treatment parameters on outcomes in different burn care settings. RESULTS: Fifteen studies were included in this systematic review. In adults, not a single study showed a decreased mortality due to a higher patient load. However, in children, 2 studies demonstrated a further decrease of the already low mortality due to an increase in patient load. In contrast to patient load, benchmark parameters that had a significant influence on the outcome of burn care for adults and children were: single bed isolation, residency programs, American Burn Association certifications of burn centers, speed of wound closure, and standard operating procedures for burn care. CONCLUSIONS: This systematic review demonstrates that a clear correlation between patient load and mortality reduction in adult burn treatment is not supported by the existing literature, requiring future studies. In contrast, all efforts aiming to improve the quality of burn care, such as isolation of burn patients, speed of wound closure, American Burn Association verification and especially standard operating procedures for burn care improve survival and quality of burn care.

Porcine-derived biomaterials in tissue engineering and reconstructive surgery: Considerations and alternatives in Muslim patients.

During the last three decades, tissue engineering and reconstructive surgery have become standard therapeutic options in the world of medicine. Several biomaterials, either alone or in combination with cultured cellular products, have been introduced to compensate for the scarcity of autologous donor tissue or to improve healing in a variety of surgical specialties, for example, abdominal/visceral surgery, plastic surgery, and cardiovascular surgery. Many of these biomaterials are of porcine origin. It is well known that Islam has prohibited the consumption of porcine or any of its products. With Muslims accounting for 23% (1.6 billion) of the global population, a thorough review of the implications of porcine-derived tissue-engineered products in surgery seems necessary. In life-threatening conditions as well as severe diseases, the use of porcine-derived products is permissible if similar non-porcine-derived materials are not available. In this case, the use of porcine-derived products represents a necessity and is allowed. Therefore, this distinction between sole need and necessity has great importance not only for the medical community but also for researchers in biotechnology and industry who may consider alternatives to porcine-derived materials.

Healing Time Correlates With the Quality of Scaring: Results From a Prospective Randomized Control Donor Site Trial.

BACKGROUND: Scar formation remains a potential problem after surgery or trauma. Factors influencing scar tissue have been recognized, most notably healing time and wound depth. OBJECTIVE: To examine the association between healing time and the quality of scar tissue formation. MATERIALS AND METHODS: Scarring was assessed at 3 and 12 months after treatment in an RCT of 219 patients and consecutive 438 split-thickness skin graft donor sites. The primary end point of the study was healing time and the quality of scar tissue, which was scored by a validated scar scale evaluating scar height, surface, and color. RESULTS: The mean time of wound healing was 15.8 days, with a mean scar score of 6.89 at 3 months and 4.66 at 12 months. There was a significant (p < .000001) and linear correlation between healing time and scar quality. Of particular note, at 12 months, all subparameters of the score demonstrated worsening with prolonged time to heal. CONCLUSION: The authors could objectively demonstrate that epithelialization time is an important factor influencing scar quality. In contrast to previous assumptions, this correlation follows linearly. It is reasonable then to assume that treatment strategies expediting healing will also improve scar outcome.

Interleukin-6 Serum Levels Correlate With Severity of Burn Injury but Not With Gender.

Gender-specific differences in the outcome of patients with burn injury have been recognized in the past with female patients being at a higher risk of mortality. We hypothesized that early post-burn interleukin-6 (IL-6) cytokine levels may contribute to the different gender-specific outcome. We retrospectively examined 94 burned patients who were treated in the Burn Intensive Care Unit at the University Hospital Aachen. Age, gender, presence of inhalation injury, depth, TBSA, and clinical outcome were documented. Serum samples for IL-6 analysis were collected within 24 hours posttrauma. The relationship between IL-6 levels, gender, survival, and abbreviated burn severity index score was investigated. Male patients (64.9%; n = 61) presented a higher median TBSA (26%) than female patients (20%). The mortality rate of male patients (27.9%; n = 17) and female patients (21.2%; n = 7) was similar. Deceased patients had significant higher TBSA (P = 0.0005) and IL-6 levels (P = 0.0007) than burn survivors. A moderate correlation between IL-6 levels and abbreviated burn severity index score was observed (r = 0.554; P < 0.0001). While TBSA showed a significant influence on IL-6 levels (P = 0.0003), gender did not (P = 0.7395) and inhalation injury indicated a minor influence (P = 0.0780). Only TBSA and age presented a significant influence on mortality (P = 0.0028 and P = 0.0031, respectively). All patients with burn trauma were characterized by elevated IL-6 levels with higher TBSA values resulting in more pronounced levels. Deceased patients had higher initial IL-6 serum levels reflecting higher TBSA and severity. In contrast to other defined trauma mechanisms, gender had no significant influence on postburn IL-6 serum levels and mortality in our patient population.

Adipokine concentrations in lipoaspirates may have a role in wound healing.

OBJECTIVES: In addition to its use as a volume filler, fat grafting may have a potential role in wound healing based on the concentration of growth factors in the lipoaspirate. In this study, we compare the quantitative and qualitative concentration of the various growth factors and adipokines using the Shippert or the Coleman techniques to prepare the lipoaspirate. METHODS: We measured leptin, adiponectin and the growth factors, i.e., acidic fibroblast growth factor (aFGF), basic FGF (bFGF), keratinocyte growth factor (KGF), bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) by ELISA in solid and liquid fractions obtained with both techniques in human fat obtained with Coleman technique and Shippert technique. RESULTS: All of these peptides, except BMP-2, were detected in relevant quantities in the solid fraction. The Coleman but not the Shippert technique resulted in statistically higher adiponectin concentrations in the solid tissue fraction. The other four growth factors occurred in significantly higher concentrations in the solid fractions compared to the liquid fractions, independent of the processing technique. CONCLUSION: In summary, we demonstrated that KGF, aFGF, bFGF and VEGF, as well as leptin and adiponectin, are contained in fat suspensions obtained by liposuction and in the supernatant. Only the concentration of adiponectin was in the range reported to contribute to wound healing.

Autologous Fat Transfer for Thumb Carpometacarpal Joint Osteoarthritis: A Prospective Study.

BACKGROUND: Most operations for carpometacarpal joint osteoarthritis of the thumb irreversibly alter or destroy the anatomy. There is a high demand for minimally invasive alternatives. The authors report the results of autologous fat transfer for treatment of thumb carpometacarpal joint osteoarthritis. METHODS: In a prospective study, 50 patients with thumb carpometacarpal joint osteoarthritis were observed for 1 year after autologous fat transfer. Manual liposuction and centrifugation were performed. Pain rating according to visual analogue pain scale; objective force of pinch grip and fist closure; and Disabilities of the Arm, Shoulder, and Hand questionnaire scores before and after treatment were analyzed. RESULTS: The average pain in stage 2 patients preoperatively was 7.7 ± 1.3; it was 1.8 ± 1.9 after 6 months and 2.4 ± 3.1 after 12 months. Patients with stage 2 osteoarthritis demonstrated a superior benefit from this treatment compared with patients with either stage 3 or stage 4 thumb carpometacarpal joint osteoarthritis. There were similar improvements for the parameters strength and Disabilities of the Arm, Shoulder, and Hand questionnaire score. No serious adverse events were observed. CONCLUSIONS: Autologous fat transplantation is an appealing alternative, especially in early-stage basal joint osteoarthritis of the thumb. The low invasiveness of the procedure and early recovery of patients compared with classical procedures such as trapeziectomy, and the superior long-term results compared with classical injection therapy, make this approach feasible as a first-line therapy in early-stage basal joint osteoarthritis of the thumb. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Accelerated re-epithelialization of partial-thickness skin wounds by a topical betulin gel: Results of a randomized phase III clinical trials program.

The clinical significance of timely re-epithelialization is obvious in burn care, since delayed wound closure is enhancing the risk of wound site infection and extensive scarring. Topical treatments that accelerate wound healing are urgently needed to reduce these sequelae. Evidence from preliminary studies suggests that betulin can accelerate the healing of different types of wounds, including second degree burns and split-thickness skin graft wounds. The goal of this combined study program consisting of two randomized phase III clinical trials in parallel is to evaluate whether a topical betulin gel (TBG) is accelerating re-epithelialization of split-thickness skin graft (STSG) donor site wounds compared to standard of care. Two parallel blindly evaluated, randomised, controlled, multicentre phase III clinical trials were performed in adults undergoing STSG surgery (EudraCT nos. 2012-003390-26 and 2012-000777-23). Donor site wounds were split into two equal halves and randomized 1:1 to standard of care (a non-adhesive moist wound dressing) or standard of care plus TBG consisting of 10% birch bark extract and 90% sunflower oil (Episalvan, Birken AG, Niefern-Oeschelbronn, Germany). The primary efficacy assessment was the intra-individual difference in time to wound closure assessed from digital photographs by three blinded experts. A total of 219 patients were included and treated in the two trials. Wounds closed faster with TBG than without it (15.3 vs. 16.5 days; mean intra-individual difference=-1.1 days [95% CI, -1.5 to -0.7]; p<0.0001). This agreed with unblinded direct clinical assessment (difference=-2.1 days [95% CI, -2.7 to -1.5]; p<0.0001). Adverse events possibly related to treatment were mild or moderate and mostly at the application site. TBG accelerates re-epithelialization of partial thickness wounds compared to the current standard of care, providing a well-tolerated contribution to burn care in practice.

The effect of lipoaspirates vs. dissected abdominal fat on breast cancer cells in vitro.

BACKGROUND: Cancer cells are typically surrounded by stromal cells and embedded in extracellular matrix (ECM). The stromal compartment interacts with cancer cells to promote growth and metastasis. For decades, autologous fasciocutaneous flaps have been safely applied for breast reconstruction after mastectomy. In contrast, the safety of fat grafting (lipofilling) procedure has been under debate regarding the risk of cancer recurrence. METHODS: Harvested fat tissue (lipoaspirates) and dissected abdominal fat (DAF) were co-cultured with MCF-7 breast cancer cells. The vitality of MCF-7 cells was measured using AlamarBlue® consecutively for 5 days. ECM degradation was determined by detection of matrix metalloproteinase-1 (MMP-1) expression in MCF-7 cells. Integrin α2 was measured by Western blot to assess the degree of adhesion and motility of MFC-7 cells. RESULTS: The MCF-7 proliferation increased substantially when co-cultured with fat tissue. However, there was no significant difference between the proliferation stimulating effects of lipoaspirates and DAF. Similarly, MMP-1 protein expression was equally elevated in MCF-7 cells by both lipoaspirates and DAF. Importantly, MCF-7 cells showed an increased level of integrin α2 once co-cultured with either lipoaspirates or DAF. CONCLUSION: Fat tissue increases the proliferation of MCF-7 cells in vitro. Our data suggest that lipoaspirates as well as DAF might possess a considerable potency to promote tumorigenic growth of breast cancer cells. Thus, clinical trials are needed to address the safety of lipofilling by breast reconstruction surgery after mastectomy.

Current Concepts in Tissue Engineering: Skin and Wound.

BACKGROUND: Pure regenerative healing with little to no donor morbidity remains an elusive goal for both surgeon and patient. The ability to engineer and promote the development of like tissue holds so much promise, and efforts in this direction are slowly but steadily advancing. METHODS: Products selected and reviewed reflect historical precedence and importance and focus on current clinically available products in use. Emerging technologies we anticipate will further expand our therapeutic options are introduced. The topic of tissue engineering is incredibly broad in scope, and as such the authors have focused their review on that of constructs specifically designed for skin and wound healing. A review of pertinent and current clinically related literature is included. RESULTS: Products such as biosynthetics, biologics, cellular promoting factors, and commercially available matrices can be routinely found in most modern health care centers. Although to date no complete regenerative or direct identical soft-tissue replacement exists, currently available commercial components have proven beneficial in augmenting and improving some types of wound healing scenarios. Cost, directed specificity, biocompatibility, and bioburden tolerance are just some of the impending challenges to adoption. CONCLUSIONS: Quality of life and in fact the ability to sustain life is dependent on our most complex and remarkable organ, skin. Although pure regenerative healing and engineered soft-tissue constructs elude us, surgeons and health care providers are slowly gaining comfort and experience with concepts and strategies to improve the healing of wounds.

Evaporative Water Loss in Superficial to Full Thickness Burns.

INTRODUCTION: Increased evaporative water loss (EWL) in burn patients leads to dehydration and hypothermia. Early clinical studies performed with outdated hygrometers suggested a 17 to 75 times increased EWL in burns with contradicting results for the different burn depths.Our study proposals were: (1) obtain reliable data of the EWL of all burn depths, (2) compare these results with findings from earlier studies, (3) evaluate the usefulness of the EWL in differentiating between superficial and deep partial thickness burns, (4) determine the effect of Biobrane on the EWL of superficial partial thickness burns in vivo, and (5) evaluate the effect of the sterile incision foil Opraflex on the EWL in split skin graft donor sites. METHODS: We measured the EWL of all burn depths in 28 patients under stable and recorded conditions regarding room temperature and humidity with a modern digital evaporimeter (Tewameter TM 300). For the first time in vivo, we also determined the effect of Biobrane on the EWL of burns and evaluated the EWL in split skin graft donor sites covered with Opraflex. RESULTS: The EWL in all burn depths was significantly increased (P < 0.001) compared with unburned skin. There was no significant difference (P > 0.05) in the EWL of superficial compared with deep partial thickness burns, whereas full thickness burns had a significantly lower EWL (P < 0.05) compared with superficial and deep partial thickness burns. Biobrane significantly reduced the EWL (P < 0.05) of superficial partial thickness burns. The EWL of Opraflex covered skin graft donor sites was significantly reduced compared with uncovered donor sites (P < 0.05). CONCLUSIONS: Our data suggest that the actual EWL in burns is approximately 3 times higher in full thickness burns and approximately 4 times higher in superficial and deep partial thickness burns compared with normal skin and therefore much lower than suggested previously.Because there was no significant difference in the EWL of superficial compared with deep partial thickness burns, the EWL cannot be used to differentiate between these burn depths.Biosynthetic wound dressings can significantly reduce the EWL of superficial partial thickness burns and sterile incision foil protects split skin graft donor sites from an increased EWL.

The Effect of Lipoaspirates on Human Keratinocytes.

BACKGROUND: One increasingly important trend in plastic, reconstructive, and aesthetic surgery is the use of fat grafts to improve cutaneous wound healing. In clinical practice, lipoaspirates (adipose tissue harvested by liposuction) are re-injected in a procedure called lipofilling. Previous studies, however, mainly evaluated the regenerative effect of isolated adipocytes, adipose-derived stem cells, and excised en bloc adipose tissue on keratinocytes, whereas no study to date has examined the effect of lipoaspirates. OBJECTIVES: The authors aimed to investigate differences in the regenerative property of en bloc adipose tissue and lipoaspirates on keratinocytes. METHODS: Human keratinocytes, lipoaspirates, and en bloc adipose tissue from 36 healthy donors were isolated. In vitro proliferation, differentiation, migration, stratification, and wound healing of keratinocyte monolayers were measured. Furthermore, secreted levels of VEGF, bFGF, IGF-1, MMP-9, and MIF were detected by ELISA. RESULTS: Migration, proliferation, and wound healing of keratinocytes were increased by lipoaspirates. Interestingly, the effect of lipoaspirates on keratinocyte proliferation was significantly higher than by en bloc adipose tissue after 5 days. The differentiation of keratinocytes was equally attenuated by lipoaspirates and en bloc adipose tissue. Stratification of keratinocyte layers was enhanced by lipoaspirates and en bloc fat when compared to controls. Lipoaspirates secrete higher levels of bFGF, whereas higher levels of VEGF and IGF-1 are released by en bloc adipose tissue. CONCLUSION: We show that lipoaspirates and en bloc adipose tissue have a regenerative effect on keratinocytes. One reason for the higher effect of lipoaspirates on keratinocyte proliferation may be the secretion of different cytokines.

Macrophage Migration Inhibitory Factor in Acute Adipose Tissue Inflammation.

Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine and has been implicated in inflammatory diseases. However, little is known about the regulation of MIF in adipose tissue and its impact on wound healing. The aim of this study was to investigate MIF expression in inflamed adipose and determine its role in inflammatory cell recruitment and wound healing. Adipose tissue was harvested from subcutaneous adipose tissue layers of 24 healthy subjects and from adipose tissue adjacent to acutely inflamed wounds of 21 patients undergoing wound debridement. MIF protein and mRNA expression were measured by ELISA and RT-PCR. Cell-specific MIF expression was visualized by immunohistochemistry. The functional role of MIF in cell recruitment was investigated by a chemotaxis assay and by flow cytometry of labeled macrophages that were injected into Mif-/-and wildtype mice. Wound healing was evaluated by an in vitro scratch assay on human fibroblast monolayers. MIF protein levels of native adipose tissue and supernatants from acutely inflamed wounds were significantly elevated when compared to healthy controls. MIF mRNA expression was increased in acutely inflamed adipose tissue indicating the activation of MIF gene transcription in response to adipose tissue inflammation. MIF is expressed in mature adipocytes and in infiltrated macrophages. Peripheral blood mononuclear cell migration was significantly increased towards supernatants derived from inflamed adipose tissue. This effect was partially abrogated by MIF-neutralizing antibodies. Moreover, when compared to wildtype mice, Mif-/-mice showed reduced infiltration of labeled macrophages into LPS-stimulated epididymal fat pads in vivo. Finally, MIF antibodies partially neutralized the detrimental effect of MIF on fibroblast wound healing. Our results indicate that increased MIF expression and rapid activation of the MIF gene in fat tissue adjacent to acute wound healing disorders may play a role in cell recruitment to the site of inflammation and wound healing.

Cell-Enriched Lipoaspirate Arthroplasty: A Novel Approach to First Carpometacarpal Joint Arthritis.

We report a novel, minimal invasive technique for the treatment of symptomatic arthritis of the carpometacarpal (CMC) joint of the thumb, here termed Cell-Enriched Liposaspirate Arthroplasty (CELA). For CELA, autologous fat tissue was harvested using standard liposuction technique followed by an extra-corporal cellular enrichment step. Finally, 1 ml of cell-enriched lipoaspirate was injected into the CMC-joint. Following CELA, the treated patient became pain free within five weeks with a follow-up of 12 months. We conclude that CELA performed on selected cases of arthritis of finger joints such as the basal joint of the thumb has the potential to greatly reduce or delay the necessity for more invasive procedures which tend to improve symptoms of pain at the cost of grip strength and range-of-motion.

Intraoperative use of enriched collagen and elastin matrices with freshly isolated adipose-derived stem/stromal cells: a potential clinical approach for soft tissue reconstruction.

BACKGROUND: Adipose tissue contains a large number of multipotent cells, which are essential for stem cell-based therapies. The combination of this therapy with suitable commercial clinically used matrices, such as collagen and elastin matrices (i.e. dermal matrices), is a promising approach for soft tissue reconstruction. We previously demonstrated that the liposuction method affects the adherence behaviour of freshly isolated adipose-derived stem/stromal cells (ASCs) on collagen and elastin matrices. However, it remains unclear whether freshly isolated and uncultured ASCs could be directly transferred to matrices during a single transplantation operation without additional cell culture steps. METHODS: After each fat harvesting procedure, ASCs were isolated and directly seeded onto collagen and elastin matrices. Different time intervals (i.e. 1, 3 and 24 h) were investigated to determine the time interval needed for cellular attachment to the collagen and elastin matrices. Resazurin-based vitality assays were performed after seeding the cells onto the collagen and elastin matrices. In addition, the adhesion and migration of ASCs on the collagen and elastin matrices were visualised using histology and two-photon microscopy. RESULTS: A time-dependent increase in the number of viable ASCs attached to the collagen and elastin matrices was observed. This finding was supported by mitochondrial activity and histology results. Importantly, the ASCs attached and adhered to the collagen and elastin matrices after only 1 h of ex vivo enrichment. This finding was also supported by two-photon microscopy, which revealed the presence and attachment of viable cells on the upper layer of the construct. CONCLUSION: Freshly isolated uncultured ASCs can be safely seeded onto collagen and elastin matrices for ex vivo cellular enrichment of these constructs after liposuction. Although we observed a significant number of seeded cells on the matrices after a 3-h enrichment time, we also observed an adequate number of isolated cells after a 1-h enrichment time. However, this approach must be optimised for clinical use. Thus, in vivo studies and clinical trials are needed to investigate the feasibility of this approach.

Surgical amputation of the digit: an investigation into the technical variations among hand surgeons.

OBJECTIVE: Digital injuries are common and frequently complicate occupational hazards and trauma. The management of these injuries often necessitates digital amputation, and a variety of different amputation techniques are advocated and employed by hand surgeons. In this survey study, we investigate the variation in technical detail among a group of hand surgeons when performing digital amputations, specifically the preferred management of the residual articular cartilage, transected nerves, and phalangeal contouring. METHODS: We reviewed the literature on techniques in digital amputation and created a 7-question survey that targeted controversial issues within this specific topic. We then sent this survey electronically to the members of the American Society for Surgery of the Hand and reviewed the responses of the respondents (n = 592, 20%). RESULTS: There was a mixed response regarding whether or not to remove the articular cartilage when disarticulating, nearly a 50% split between the respondents. Most would perform a "pull and resect" technique for transected nerves. Phalangeal contouring was generally agreed upon, though the technique in doing so varied from performing condylectomies, to bony contouring only, to some combination of both. CONCLUSIONS: We detected a substantial variation in technique among our group of hand surgeons regarding the treatment of articular cartilage and the method of phalangeal contouring. There was more consensus regarding the treatment of transected nerve. It is interesting that to date, the aforementioned issues in digital amputation have not been critically evaluated by definitive and well-controlled studies.