Free anterolateral thigh flaps for upper extremity soft tissue reconstruction.

INTRODUCTION: Limb-threatening wounds of the upper extremity pose a challenge to the micro vascular surgeon. The aim of this study is to analyze the outcome of free anterolateral thigh flaps for upper extremity soft tissue reconstruction. METHODS: A retrospective review of patients undergoing this procedure from 2005 to 2012 was performed. Case note analysis was performed to determine demographic and perioperative factors, and complications and outcomes. RESULTS: Thirty-two patients with a mean age of 53 years (9-84 yrs) underwent upper extremity reconstruction with an anterolateral thigh (ALT) flap. There were 24 (75%) males and 8 (25%) females. The etiology of the soft tissue defects was: infection (44.6%); post-tumor ablation (40%); and trauma (15.6%). The defect site was most commonly in the forearm (53.1%), followed by the elbow (12.5 %), arm (12.5%) and hand (21.9%). The mean timing of free flap transfer was 6.8 days after admission to our institution (minimum 1 days, maximum 9 days). Mean operative time of surgery was 4 h 39 min (minimum 3 h 2 min, maximum 6 h 20 min). The mean hospitalization was 24.8 days (minimum 5, maximum 85). The ALT success rate was at 92.3%. Partial flap necrosis was documented in five cases (15.6%). Complete flap loss occurred in two post-traumatic cases who both lost their limbs. DISCUSSION: This flap, in the hands of experienced surgeons, provides reliable coverage of upper extremity defects.

A synthetic sandalwood odorant induces wound-healing processes in human keratinocytes via the olfactory receptor OR2AT4.

As the outermost barrier of the body, the skin is exposed to multiple environmental factors, including temperature, humidity, mechanical stress, and chemical stimuli such as odorants that are often used in cosmetic articles. Keratinocytes, the major cell type of the epidermal layer, express a variety of different sensory receptors that enable them to react to various environmental stimuli and process information in the skin. Here we report the identification of a novel type of chemoreceptors in human keratinocytes, the olfactory receptors (ORs). We cloned and functionally expressed the cutaneous OR, OR2AT4, and identified Sandalore, a synthetic sandalwood odorant, as an agonist of this receptor. Sandalore induces strong Ca(2+) signals in cultured human keratinocytes, which are mediated by OR2AT4, as demonstrated by receptor knockdown experiments using RNA interference. The activation of OR2AT4 induces a cAMP-dependent pathway and phosphorylation of extracellular signal-regulated kinases (Erk1/2) and p38 mitogen-activated protein kinases (p38 MAPK). Moreover, the long-term stimulation of keratinocytes with Sandalore positively affected cell proliferation and migration, and regeneration of keratinocyte monolayers in an in vitro wound scratch assay. These findings combined with our studies on human skin organ cultures strongly indicate that the OR 2AT4 is involved in human keratinocyte re-epithelialization during wound-healing processes.

Amniotic membrane as part of a skin substitute for full-thickness wounds: an experimental evaluation in a porcine model.

BACKGROUND: We evaluated the use of human amniotic membrane (HAM) as a graft material for the treatment of iatrogenic full-thickness (FT) skin wounds in a porcine model with a view to reducing donor site morbidity in free flap transfer. METHODS: Forty experimental FT-wounds were covered with an autologous split-thickness skin graft (STSG) alone or in combination with a mono- or multilayer HAM or Integra(®). Untreated wounds served as controls. Clinical evaluation and biopsy-sampling for histological and immunohistochemical staining with von-Willebrand-factor (vWF) antibody, laminin antibody, Ki-67 antibody, and smooth muscle actin (αSMA) antibody were performed on days 5, 7, 10, 20, 40, and 60 after surgical intervention. RESULTS: Considerable disparities in the estimated criteria were observed between the various treatment groups of the FT-wounds. The use of HAM was found to have an accelerating impact on re-epithelialization. The multilayered amnion membrane showed better results than the Integra(®) and monolayer technique in terms of contraction rate, inflammation, and scarring and seemed useful as a dermal substitute in FT-wounds giving comparable results to STSG coverage alone. CONCLUSIONS: This study demonstrates the successful application of HAM as part of a skin substitute in FT-wounds in minipigs. The results offer promise as a simple and effective technique for the application of multilayer HAM in iatrogenic human skin defects and the acceleration of wound healing.

Reduction of donor site morbidity of free radial forearm flaps: what level of evidence is available?

BACKGROUND: The radial forearm free flap (RFFF) is the most commonly used free flap in head and neck reconstructive surgery. However, despite excellent results with respect to the site of reconstruction, donor site morbidity cannot be neglected. This review summarizes the current state of knowledge and analyzes the level of evidence with regard to perioperative management of the reduction of RFFF donor site morbidity. METHODS: The medical Internet source PubMed was screened for relevant articles. All relevant articles were tabulated according to the levels of scientific evidence, and the available methods for reduction of donor site morbidity are discussed. RESULTS: Classification into levels of evidence reveals 3 publications (1.5%) with level I (randomized controlled trials), 29 (14.0%) with level II (experimental studies with no randomization, cohort studies, or outcome research), 3 (1.5%) with level III (systematic review of case-control studies or individual case-control studies), 121 (58.7%) with level IV (nonexperimental studies, such as cross-sectional trials, case series, case reports), and 15 (7.3%) with level V (narrative review or expert opinion without explicit critical appraisal). Thirty-five (17.0%) articles could not be classified, because they focused on a topic other than donor site morbidity of the RFFF. CONCLUSIONS: Although great interest has been expressed with regard to reducing the donor site morbidity of the workhorse flap in microvascular reconstruction procedures, most publications fail to provide the hard facts and solid evidence characteristic of high-quality research.

Boric acid gel enrichment of glycosylated proteins in human wound fluids.

The enrichment of glycosylated proteins by glycocapturing materials plays a pivotal role for the investigation of polysaccharide containing proteins in disease pathogenesis. Hence, we investigated a boric acid gel as a binding material for glycoprotein enrichment. The bovine proteins alpha-1-acid-glycoprotein (A1AG) and alpha-2-HS-glycoprotein (fetuin A) were spiked in human chronic wound fluids and were subsequently enriched by a boric acid gel affinity chromatography (BAGAC). The enrichment efficiency was evaluated by western blot analysis and mass spectrometry. Additionally, glycoproteins of human wound fluids from diabetes mellitus patients with chronic foot ulcers were analyzed after BAGAC enrichments. In total 104 glycoproteins were identified, with reported glycosylation sites. 60 proteins were detected in at least 2 out of 3 biological replicates and were used for quantitative analysis between the bound and unbound fractions. Almost 80% of these glycoproteins were more prominent in the bound fraction. Only 2 glycoproteins revealed higher spectral counts in the flow through fraction compared to the bound fraction. These findings demonstrate the capability of the BAGAC material to enrich glycosylated proteins from complex human wound fluids.

Immunodepletion of high-abundant proteins from acute and chronic wound fluids to elucidate low-abundant regulators in wound healing.

BACKGROUND: The process of wound healing consists of several well distinguishable and finely tuned phases. For most of these phases specific proteins have been characterized, although the underlying mechanisms of regulation are not yet fully understood. It is an open question as to whether deficits in wound healing can be traced back to chronic illnesses such as diabetes mellitus. Previous research efforts in this field focus largely on a restricted set of marker proteins due to the limitations detection by antibodies imposes. For mechanistic purposes the elucidation of differences in acute and chronic wounds can be addressed by a less restricted proteome study. Mass spectrometric (MS) methods, e.g. multi dimensional protein identification technology (MudPIT), are well suitable for this complex theme of interest. The human wound fluid proteome is extremely complex, as is human plasma. Therefore, high-abundant proteins often mask the mass spectrometric detection of lower-abundant ones, which makes a depletion step of such predominant proteins inevitable. FINDINGS: In this study a commercially available immunodepletion kit was evaluated for the detection of low-abundant proteins from wound fluids. The dynamic range of the entire workflow was significantly increased to 5-6 orders of magnitude, which makes low-abundant regulatory proteins involved in wound healing accessible for MS detection. CONCLUSION: The depletion of abundant proteins is absolutely necessary in order to analyze highly complex protein mixtures such as wound fluids using mass spectrometry. For this the used immunodepletion kit is a first but important step in order to represent the entire dynamic range of highly complex protein mixtures in the future.

Limb salvage in malignant tumors.

Limb-sparing resection and reconstruction has become the treatment of choice in extremity malignancies, as amputation does not provide better long-term survival rates or functional advantages. R0 resection, the removal of the tumor in sano, remains the prerequisite and most important oncologic parameter to avoid local recurrence. Successful treatment requires the combination of surgical eradication and the patient's specific functional and aesthetic rehabilitation. Our clinical rationale resulting from more than 2000 cases will be demonstrated. The problematic aspects of different tumor entities and the locoregional clearance of lymphatic pathways will be discussed. Differential diagnosis and multimodality treatment in high-volume tumor centers is likely to achieve superior oncologic statistics. Long-term survivors after microsurgical reconstructions and possible secondary malignancies will be addressed.

HPV & head and neck cancer: a descriptive update.

The incidence of head and neck squamous cell carcinoma (HNSCC) has been gradually increasing over the last three decades. Recent data have now attributed a viral aetiology to a subset of head and neck cancers. Several studies indicate that oral human papillomavirus (HPV) infection is likely to be sexually acquired. The dominance of HPV 16 in HPV+ HNSCC is even greater than that seen in cervical carcinoma of total worldwide cases. Strong evidence suggests that HPV+ status is an important prognostic factor associated with a favourable outcome in head and neck cancers. Approximately 30 to 40% of HNSCC patients with present with early stage I/II disease. These patients are treated with curative intent using single modality treatments either radiation or surgery alone. A non-operative approach is favored for patients in which surgery followed by either radiation alone or radiochemotherapy may lead to severe functional impairment. Cetuximab, a humanized mouse anti-EGFR IgG1 monoclonal antibody, improved locoregional control and overall survival in combination with radiotherapy in locally advanced tumours but at the cost of some increased cardiac morbidity and mortality. Finally, the improved prognosis and treatment responses to chemotherapy and radiotherapy by HPV+ tumours may suggest that HPV status detection is required to better plan and individualize patient treatment regimes.

A follow-up study of adults with suicidal burns: psychosocial adjustment and quality of life.

The severity of the burn injuries, accompanying injuries, and the often concomitant psychiatric disease complicate the treatment of patients with suicidal burns. Data from 45 patients who were treated for suicidal burn injuries from 1994 to 2005 were acquired from the patients' charts and interviews with standardized questionnaires (n = 11) concerning their psychological status pretrauma and posttrauma, as well as their quality of life with special reference to psychosocial adjustments. None of the patients survived more than 69% TBSA burns; no one with 41% or less died. Most of the patients had prediagnosed psychiatric disorders. The educational and social background of the patients and religious beliefs played a minor role for choosing this method of suicide. Aggression levels were above the average population, whereas self-direction was underdeveloped. Forty percent, albeit unsuccessfully, committed subsequent suicide attempts. Most patients felt only moderate social impairment by the burn wound residuals, the majority had intensified and improved their social contacts, and most felt no relevant decrease of quality of life compared with their personal situation before the suicide attempt. Patients who survive the suicide attempt can become integrated in social life again. More data are needed to reliably identify patients at risk in advance.