Novel Mini-Invasive Surgical Technique for Treating Fifth Metacarpal Neck Fractures: A Case Report.

BACKGROUND Fracture of the fifth metacarpal of the hand is due to trauma to the clenched fist. The non-displaced fracture can be treated by splinting and immobilization, but fracture dislocation requires individualized management to ensure the return of function. The Jahss maneuver for reduction of volar displaced metacarpal neck fractures involves flexion of the metacarpophalangeal and proximal interphalangeal joint at 90°, with the proximal phalanx used to reduce the metacarpal head. This report is of a 25-year-old male Italian pianist with a displaced fifth metacarpal neck fracture successfully treated by reduction using the Jahss maneuver and K-wire attachment of subchondral bone to the metacarpal. CASE REPORT A pianist presented with a trauma to his right hand due to punching a wall. Radiograph images demonstrated an angulated, displaced right fifth neck fracture. A specific approach was decided, considering the complexity of the musical movements and the patient's performance needs. After fracture's reduction by the Jahss maneuver, 2 retrograde cross-pinning K-wires were inserted at the subchondral bone of the metacarpal head. Healing under splinting was uneventful, and the K-wires were removed after 45 days. At 4 months after surgery, the patient had complete recovery of both range of motion and strength. CONCLUSIONS Our technique avoided piercing the metacarpophalangeal joint capsule, preventing extensor tendon damage, dislocation, instability, and pain and retraction of the extensor cuff. This novel mini-invasive technique successfully achieved early metacarpophalangeal joint motion, joint stability, and complete recovery of movements in all planes.

Traumatic peripheral nerve injuries: a classification proposal.

BACKGROUND: Peripheral nerve injuries (PNIs) include several conditions in which one or more peripheral nerves are damaged. Trauma is one of the most common causes of PNIs and young people are particularly affected. They have a significant impact on patients' quality of life and on the healthcare system, while timing and type of surgical treatment are of the utmost importance to guarantee the most favorable functional recovery. To date, several different classifications of PNIs have been proposed, most of them focusing on just one or few aspects of these complex conditions, such as type of injury, anatomic situation, or prognostic factors. Current classifications do not enable us to have a complete view of this pathology, which includes diagnosis, treatment choice, and possible outcomes. This fragmentation sometimes leads to an ambiguous definition of PNIs and the impossibility of exchanging crucial information between different physicians and healthcare structures, which can create confusion in the choice of therapeutic strategies and timing of surgery. MATERIALS: The authors retrospectively analyzed a group of 24 patients treated in their center and applied a new classification for PNI injuries. They chose (a) five injury-related factors, namely nerve involved, lesion site, nerve type (whether motor, sensory or mixed), surrounding tissues (whether soft tissues were involved or not), and lesion type-whether partial/in continuity or complete. An alphanumeric code was applied to each of these classes, and (b) four prognostic codes, related to age, timing, techniques, and comorbidities. RESULTS: An alphanumeric code was produced, similar to that used in the AO classification of fractures. CONCLUSIONS: The authors propose this novel classification for PNIs, with the main advantage to allow physicians to easily understand the characteristics of nerve lesions, severity, possibility of spontaneous recovery, onset of early complications, need for surgical treatment, and the best surgical approach. LEVEL OF EVIDENCE: according to the Oxford 2011 level of evidence, level 2.

Volar Plate Interposition Arthroplasty of the Proximal Interphalangeal Joint: A Novel, Modified Malerich's Technique.

The choice of prosthetic or autologous reconstruction for proximal interphalangeal (PIP) joint arthroplasty in degenerative osteoarthritis represents a challenge for hand surgeons, especially in consideration of complications and patient's quality of life. We report the case of a 49-year-old woman who developed diffuse arthritis of the finger joints, especially at the PIP joint of the third right finger. Radiographs showed destruction of the PIP joint, large osteophytes, marked narrowing of joint space, severe sclerosis, and deformation of bone contour. Through a volar approach, we removed the osteophytes, reshaped the joint, and performed an arthroplasty with volar plate interposition. The patient had an improved range of motion at 3 months postoperatively. This case study gives a detailed description and discussion, together with literature revision, of volar plate interposition arthroplasty to treat PIP osteoarthritis, as an alternative to other methods.

Xeroderma Pigmentosum: A Genetic Condition Skin Cancer Correlated-A Systematic Review.

Background: Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder of UV radiation-induced damage repair that is characterized by photosensitivity and a propensity for developing, among many others, skin cancers at an early age. This systematic review focused on the correlation between the clinical, pathological, and genetic aspects of XP and skin cancer. Methods: A systematic review was conducted through a literature search of online databases PubMed, Cochrane Library, SciELO, and Google Scholar. Search terms were "Xeroderma pigmentosum", "XP", "XPC", "Nucleotide excision repair", "NER", "POLH", "Dry pigmented skin", and "UV sensitive syndrome" meshed with the terms "Skin cancer", "Melanoma", and "NMSC". Results: After 504 abstracts screening, 13 full-text articles were assessed for eligibility, and 3 of them were excluded. Ten articles were selected for qualitative assessment. Conclusions: Patients with XP usually suffer shorter lives due to skin cancer and neurodegenerative disease. Deletion/alteration of a distinct gene allele can produce different types of cancer. The XPC and XP-E variants are more likely to have skin cancer than patients in other complement groups, and the most common cause of death for these patients is skin cancer (metastatic melanoma or invasive SCC). Still, aggressive preventative measures to minimize UV radiation exposure can retard the course of the disease and improve the quality of life.

Development of Histologically Verified Thyroid Diseases in Women Operated for Breast Cancer: A Review of the Literature and a Case Series.

BACKGROUND: The possible relationships between breast and thyroid diseases have been reported in the literature. The purpose of our study was to evaluate the occurrence of histologically verified thyroid pathologies in women who were diagnosed with breast cancer and, after mastectomy/quadrantectomy complemented by oncological treatment, were thyroidectomized based on their periodic thyroid evaluation. PATIENTS AND METHODS: Our series consist of 31 women with a mean age of 62.9 ± 10.9 years (range, 45-81) treated for breast cancer (18 right-sided, 11 left-sided, and 2 bilateral), of whom 29 were thyroidectomized, since two women who developed Graves' disease refused thyroidectomy. These 31 women belong to a cohort of 889 women who referred to the Breast Surgery Unit of our university hospital during the period January 2010 through December 2020. RESULTS: The mean time interval between breast cancer and thyroid pathologies was 48.1 ± 23.4 months (range, 12-95). The final diagnosis at histopathology was infiltrating ductal breast carcinoma in 26 women (with 2/26 patients having bilateral carcinoma) and infiltrating lobular breast carcinoma in the other 5 women. Ten of the twenty-nine thyroidectomized women (34.5%) had a thyroid malignancy on histology: five papillary carcinomas, three papillary micro-carcinomas and two follicular carcinomas. Two of the five women with papillary carcinoma also had histological evidence of chronic lymphocytic thyroiditis/Hashimoto's thyroiditis, which was also detected in another five women with benign thyroid diseases. CONCLUSIONS: We suggest that breast cancer survivors should be made aware of the possible increased risk of thyroid pathologies (including thyroid malignancy) so that they can undergo screening and follow-up.

Lumbrical Muscles Neural Branching Patterns: A Cadaveric Study With Potential Clinical Implications.

BACKGROUND: Lumbrical muscles originate in the palm from the 4 tendons of the flexor digitorum profundus and course distally along the radial side of the corresponding metacarpophalangeal joints, in front of the deep transverse metacarpal ligament. The first and second lumbrical muscles are typically innervated by the median nerve, and third and fourth by the ulnar nerve. A plethora of lumbrical muscle variants has been described, ranging from muscles' absence to reduction in their number or presence of accessory slips. The current cadaveric study highlights typical and variable neural supply of lumbrical muscles. MATERIALS: Eight (3 right and 5 left) fresh frozen cadaveric hands of 3 males and 5 females of unknown age were dissected. From the palmar wrist crease, the median and ulnar nerve followed distally to their terminal branches. The ulnar nerve deep branch was dissected and lumbrical muscle innervation patterns were noted. RESULTS: The frequency of typical innervations of lumbrical muscles is confirmed. The second lumbrical nerve had a double composition from both the median and ulnar nerves, in 12.5% of the hands. The thickest branch (1.38 mm) originated from the ulnar nerve and supplied the third lumbrical muscle, and the thinnest one (0.67 mm) from the ulnar nerve and supplied the fourth lumbrical muscle. In 54.5%, lumbrical nerve bifurcation was identified. CONCLUSION: The complex innervation pattern and the peculiar anatomy of branching to different thirds of the muscle bellies are pointed out. These findings are important in dealing with complex and deep injuries in the palmar region, including transmetacarpal amputations.

Polydeoxyribonucleotide: A Promising Biological Platform to Accelerate Impaired Skin Wound Healing.

The normal wound healing process is characterized by a complex, highly integrated cascade of events, requiring the interactions of many cell types, including inflammatory cells, fibroblasts, keratinocytes and endothelial cells, as well as the involvement of growth factors and enzymes. However, several diseases such as diabetes, thermal injury and ischemia could lead to an impaired wound healing process characterized by wound hypoxia, high levels of oxygen radicals, reduced angiogenesis, decreased collagen synthesis and organization. Polydeoxyribonucleotide (PDRN) has been used to improve wound healing through local and systemic administration thanks to its ability to promote cell migration and growth, angiogenesis, and to reduce inflammation on impaired wound healing models in vitro, in vivo and clinical studies. In light of all these observations, the aim of this review is to provide a full overview of PDRN applications on skin regeneration. We reviewed papers published in the last 25 years on PubMed, inserting "polydeoxyribonucleotide and wound healing" as the main search term. All data obtained proved the ability of PDRN in promoting physiological tissue repair through adenosine A2A receptor activation and salvage pathway suggesting that PDRN has proven encouraging results in terms of healing time, wound regeneration and absence of side effects.

Surgical Reconstruction of Severe Tophaceous Gout in the Hand: A Customized Approach.

Tophaceous gout can represent a major problem for hand surgeons when it turns into aggressive nodules, spreading and destroying soft tissue and bone. The combination of ablative and reconstructive surgery may also be complex when the patient refuses amputations and multiple segments are involved. We present a difficult case, where a customized approach, chosen according to the different features of the osteoarticular and tendon involvement of fingers, adopted different solutions for the four affected rays. A patient suffering from severe gout arthritis with osteoarticular destruction in both hands refused amputations and was treated with several reconstructive procedures. After excision of the tophaceous deposits, a long bone autograft, two segmental cement spacers together with distal arthrodeses, and an osteoarticular allograft were used. Functional pinches were maintained in both hands, even at a 13-year follow up, with the allograft preserved and working. On the other hand, significant osteolysis and bone resorption in all the segments that had undergone stabilization was documented, producing extrusion of both cement and distal interphalangeal joint fusion screws. Pre- and postoperation range of motion, visual analogue scale, disabilities of the arm, shoulder, and hand score, and pinch strength tests showed reduced pain and improved function. A review of literature is presented in particular regarding different reconstructive approaches. Combining different techniques in the same hand can lead to successful osteoarticular reconstruction after tophi resection, above all to avoid amputation. However, long-term follow up shows that functional osteoarticular reconstructions seem to be more stable, whereas osteolysis may damage bone grafts used for arthrodesis and produce screw extrusion.

Nodular fasciitis of the anterior chest wall mimicking myxofibrosarcoma: A case report and literature review.

Nodular fasciitis is a benign tumor of soft tissues originating from the proliferation of fibroblasts and myofibroblasts, generally developing between the subcutaneous tissue and the underlying muscular layer. Nodular fasciitis predominantly localizes in the upper extremities, trunk, head and neck. Biomolecular and immunohistochemical analyses result essential to demonstrate the benign origin of the process, also confirmed by very low recurrence rate after complete excision, which represents the gold standard for treatment. We report the case of a 36 years-old man who developed a nodular protuberance clinically evident in the upper-left side of the thorax. We further, highlight the main characteristics of this rare neoplasm trough a thorough review of the literature.

Anterolateral Thigh Flap in a Chicken Model: A Novel Perforator Training Model.

BACKGROUND: Preclinical training in perforator flap harvesting is typically conducted on living animal models; however, repeated training is not possible with these models because of ethical and/or economical constraints. We describe an anterolateral thigh flap (ALT flap) training model using chicken thigh that seems to be an appropriate training model prior, for example, to raise a perforator flap in a living rat or swine model. METHODS: A total of 10 chicken legs were used in this study. Six chicken legs were anatomically dissected to confirm the presence of the perforator and to identify the main vascular tree. In four chicken legs, a skin flap was planned based on the perforator and intramuscular dissection was performed under magnification. RESULTS: The perforator was identified in all dissections and was consistently found 3 cm above the line extending from the patella to the head of the femur in its third proximal. Proximally, the mean diameter of the artery and vein was 0.56 (σ = 0.04) and 0.84 (σ = 0.06) mm, respectively. The mean dissection time to raise the flap was 88 (σ = 7) min. CONCLUSION: This is the first description of a nonliving biological simulation model for training in perforator flap dissection that mimics an ALT flap. As an ex vivo chicken model, it is a cost effective and readily accessible model suitable for repeated practice.

Acute Traumatic Swan Neck Deformity: A Case Report of the Oblique Retinacular Ligament Lesion.

Swan neck deformity (SND) can be the manifestation of an acute trauma. We present a case report of a young basketball player with an acute traumatic SND determined by the single ulnar oblique retinacular ligament rupture. The patient caught a ball directly upon the tip of his right's hand middle finger into extension. He immediately presented a SND with impossibility to actively flex the proximal interphalangeal joint (PIPJ), while preserving active flexion and extension of the distal interphalangeal joint (DIPJ). Hyperextension of PIPJ was reducible with passive mobilization, thus allowing full passive range of motion. The SND was seen to be caused by the lesion of the ulnar oblique retinacular ligament (ORL) on its distal insertion, with consequent dorsomedial migration of the ulnar lateral band. The early surgical distal reinsertion of the ORL allowed the restoration of the original kinematics of the finger flexion-extension.

Epoetin Alpha and Epoetin Zeta: A Comparative Study on Stimulation of Angiogenesis and Wound Repair in an Experimental Model of Burn Injury.

Deep second-degree burns are characterized by delayed formation of granulation tissue and impaired angiogenesis. Erythropoietin (EPO) is able to stimulate angiogenesis and mitosis, activating vascularization and cell cycle. The aim of our study was to investigate whether two biosimilar recombinant human erythropoietins, EPO-α and EPO-Z, may promote these processes in an experimental model of burn injury. A total of 84 mice were used and a scald burn was produced on the back after shaving, in 80°C water for 10 seconds. Mice were then randomized to receive EPO-α (400 units/kg/day/sc) or EPO-Z (400 units/kg/day/sc) or their vehicle (100 µL/day/sc 0.9% NaCl solution). After 12 days, both EPO-α and EPO-Z increased VEGF protein expression. EPO-α caused an increased cyclin D1/CDK6 and cyclin E/CDK2 expression compared with vehicle and EPO-Z (p<0.001). Our study showed that EPO-α and EPO-Z accelerated wound closure and angiogenesis; however EPO-α resulted more effectively in achieving complete skin regeneration. Our data suggest that EPO-α and EPO-Z are not biosimilars for the wound healing effects. The higher efficacy of EPO-α might be likely due to its different conformational structure leading to a more efficient cell proliferation and skin remodelling.

Reverse flow first dorsal metacarpal artery flap for covering the defect of distal thumb.

Reconstruction of distal thumb injuries still remains a challenge for hand surgeons. Surgical treatment includes the use of local, regional, and free flaps. The purpose of this report is to present the results of the use of a sensitive reverse flow first dorsal metacarpal artery (FDMA) flap. The skin flap was designed on the radial side of the proximal phalanx of the index finger based on the ulnar and radial branch of the FDMA and a sensory branch of the superficial radial nerve. This neurovascular flap was used in five patients to cover distal soft-tissue thumb defects. All flaps achieved primary healing except for one patient in whom superficial partial necrosis of the flap occurred, and the defect healed by second intention. All patients maintained the thumb original length and were able to return to their previous daily activities. The reverse flow FDMA flap is a reliable option to cover immediate and delayed defects of distal thumb, offering acceptable functional and cosmetic outcomes in respect to sensibility, durability, and skin-match.

Polydeoxyribonucleotide restores blood flow in an experimental model of ischemic skin flaps.

BACKGROUND: Ischemia is a major factor contributing to failure of skin flap surgery, which is routinely used for coverage of wounds to prevent infection and to restore form and function. An emerging concept is that adenosine A(2A) receptors can improve tissue oxygenation by stimulating angiogenesis, likely through vascular endothelial growth factor (VEGF). This study assessed the ability of polydeoxyribonucleotide (PDRN) to restore blood flow and improve wound healing, acting through the A(2A) receptor, in a rat model of ischemic skin flaps. METHODS: The H-shaped double-flap model was used in male Sprague-Dawley rats. After surgical procedures, the animals were randomized to receive intraperitoneal PDRN (8 mg/kg) or vehicle (NaCl 0.9%). Rats were euthanized 3, 5, and 10 days after skin injury, after the evaluation of skin perfusion by laser Doppler. The wounds underwent histologic analysis and were measured for VEGF messenger RNA and protein expression, hypoxia inducible factor-1-α (HIF-1α), and inducible nitric oxide synthase (iNOS) protein expression, and nitrite content. RESULTS: Blood flow markedly increased in blood flow in ischemic flaps treated with PDRN, with a complete recovery starting from day 5 (ischemic flap + vehicle, 1.80 ± 0.25; ischemic flap + PDRN, 2.46 ± 0.25; P < .001). Administration of PDRN enhanced the expression of VEGF (ischemic flap + vehicle, 5.3 ± 0.6; ischemic flap + PDRN, 6.2 ± 0.5; P < .01) at day 5, and iNOS (ischemic flap + vehicle, 3.9 ± 0.6; ischemic flap + PDRN, 5.3 ± 1; P < .01), but reduced HIF-1α expression (ischemic flap + vehicle, 7 ± 1.1; ischemic flap + PDRN, 4.8 ± 0.5; P < .05) at day 3. Histologically, the PDRN-treated group showed complete re-epithelialization and well-formed granulation tissue rich in fibroblasts. CONCLUSIONS: These results suggest that PDRN restores blood flow and tissue architecture, probably by modulating HIF-1α and VEGF expression, and may be an effective therapeutic approach in improving healing of ischemic skin flaps.

Systemic administration of high-molecular weight hyaluronan stimulates wound healing in genetically diabetic mice.

Hyaluronic acid (HA), an essential component of the extracellular matrix, is an efficient space filler that maintains hydration, serves as a substrate for assembly of proteoglycans and is involved in wound healing. Although numerous pieces of evidence demonstrate beneficial effects in promoting wound healing in diabetes, a systemic approach has never been tested. We used an incisional wound healing model in genetically diabetic mice to test the effects of systemic injection of HA. Diabetic (n=56) and normoglycemic (n=56) mice were subjected to incision and randomized (8 groups of 7 animals each) to receive HA at different doses, 7.5, 15 and 30mg/kg/i.p., or vehicle (0.9% NaCl solution) for 12days. At the end of the experiment animals were sacrificed and skin wounds were excised for histological, biochemical and molecular analysis. Histology revealed that the most effective dose to improve wound repair and angiogenesis in diabetic mice was 30mg/kg. Furthermore HA injection (30mg/kg) improved the altered healing pattern in diabetic animals, increased skin remodeling proteins TGF-ß and transglutaminase-II and restored the altered expression of cyclin B1/Cdc2 complex. Evaluation of skin from diabetic animals injected with HA revealed also an increase in HA content, suggesting that systemic injection may be able to restore the reduced intracellular HA pool of diabetic mice. Finally HA markedly improved skin mechanical properties. These promising results, if confirmed in a clinical setting, may improve the care and management of diabetic patients.

Activation of adenosine A2A receptors restores the altered cell-cycle machinery during impaired wound healing in genetically diabetic mice.

BACKGROUND: Cyclins drive cell-cycle progression by associating with their kinase partners, cyclin-dependent kinases (CDK). We investigated cyclin D1/CDK6, cyclin E/CDK2 complexes, and the cell-cycle negative regulators p15 and p27 in an incisional skin wound model. METHODS: Wounds were produced on the back of female diabetic mice and their normoglycemic littermates. Animals were treated with polydeoxyribonucleotide (PDRN, 8 mg/kg/i.p.), an agonist of adenosine A2(A) receptors, or its vehicle daily. Granulation tissue proliferation by Ki67 immunostaining, cyclin D/CDK6 and cyclin E/CDK2 complexes, and p21 and p16 proteins (Western blot analysis), and the histologic changes were assessed at different days (3, 6, and 12 days after injury). RESULTS: Numerous Ki67 positive cells were observed at day 3 and day 6 in the granulation tissue of normoglycemic mice. Ki67 positive cells were fewer in diabetic than in normoglycemic mice. PDRN increased Ki67 positive cells in diabetic mice. Normoglycemic mice showed the greatest upregulation of cyclin D1, CDK6, cyclin E, and CDK2 at day 6. Diabetic mice had a markedly lower expression of cyclin D1, CDK6, cyclin E, and CDK2 at day 6. They also showed a greater expression of p15 and p27 at day 6. PDRN administration in diabetic mice increased cyclin D1/CDK6 and cyclin E/CDK2 expression and reduced p15 and p27 inhibitors at day 6 after injury; moreover, it improved the impaired wound healing at day 12. CONCLUSION: Our results suggest that adenosine A2(A) receptor activation by PDRN might represent a therapeutic strategy to overcome the diabetes-impaired cell-cycle machinery.

A free vein graft cap influences neuroma formation after nerve transection.

INTRODUCTION: : Neuroma formation is a major problem in nerve surgery and consensus about its prevention has not been reached. It has been suggested that vein covering can reduce neuroma formation in transected nerves. In this article, the Authors propose an easy and novel method of covering by nerve stump capping with a free vein graft. METHODS: : Neuroma-like lesions were created on the rat thigh sectioning the femoral nerve above its division in 16 animals. The proximal nerve stump was invaginated into the lumen of a 1.5 cm long femoral free vein graft on the right side, and the vein was closed on itself by microsurgical sutures to form a cap for the nerve stump. On the left side acting as the control neuroma, the nerve was cut and left uncovered. Histological and immunohistochemical assessment was used to quantify the degree of neuroma formation. RESULTS: : Significant differences were found in both neuroma size and axon-glia organization between the treated and control sides indicating that free vein graft capping reduced neuroma formation in comparison to uncovered nerve stumps. CONCLUSIONS: : Our results confirm that vein-covering of a transected nerve stump can be effective in reducing neuroma formation. Moreover, unlike previous works that buried the nerve into an adjacent vein left in place, our experiments showed that also the use of a free vein graft cap can hinder neuroma formation. Although translation of rat experiments to the clinics should be dealt with caution, our data suggest a careful clinical use of the technique. (c) 2009 Wiley-Liss, Inc. Microsurgery, 2009.

Polydeoxyribonucleotide improves angiogenesis and wound healing in experimental thermal injury.

OBJECTIVE: Polydeoxyribonucleotide contains a mixture of nucleotides and interacts with adenosine receptors, stimulating vascular endothelial growth factor expression and wound healing. The purpose of this study was to investigate the effect of polydeoxyribonucleotide on experimental burn wounds. DESIGN: Randomized experiment. SETTING: Research laboratory at a university hospital. SUBJECTS: Thermal injury in mice. INTERVENTIONS: Mice were immersed in 80 degrees C water for 10 secs to achieve a deep-dermal second-degree burn. Animals were randomized to receive either polydeoxyribonucleotide (8 mg/kg/day intraperitoneally for 14 days) or its vehicle alone (0.9% NaCl solution at 100 microL/day intraperitoneally). On days 7 and 14 the animals were killed. Blood was collected for tumor necrosis factor-alpha measurement; burn areas were used for histologic and immunohistochemical examination, for the evaluation of vascular endothelial growth factor and nitric oxide synthases by Western blot, and for the determination of wound nitric oxide products. MEASUREMENTS AND MAIN RESULTS: Polydeoxyribonucleotide increased burn wound re-epithelialization and reduced the time to final wound closure. Polydeoxyribonucleotide improved healing of burn wound through increased epithelial proliferation and maturation of the extracellular matrix as confirmed by fibronectin and laminin immunostaining. Polydeoxyribonucleotide also improved neoangiogenesis as suggested by the marked increase in microvessel density and by the robust expression of platelet-endothelial cell adhesion molecule-1. Furthermore, polydeoxyribonucleotide blunted serum tumor necrosis factor-alpha and enhanced inducible nitric oxide synthase and vascular endothelial growth factor expression and the wound content of nitric oxide products. CONCLUSIONS: Our study suggests that polydeoxyribonucleotide may be an effective therapeutic approach to improve clinical outcomes after thermal injury.