Arterial Embolism After Facial Fat Grafting: A Systematic Literature Review.

BACKGROUND: While autologous fat grafting of the face is considered a generally safe procedure, severe complications such as arterial embolism (AE) have been reported. OBJECTIVE: To summarize data on injection-related visual compromise, stroke, and death caused by arterial embolism after facial fat transplantation. MATERIALS AND METHODS: Plastic surgery societies were contacted for reports on AE after autologous facial fat injection. In addition, a systematic literature review was performed. Data extracted included study design, injection site/technique, symptoms, management, outcome, and etiology. RESULTS: 61 patients with a mean age of 33.56 ± 11.45 years were reported. Injections targeted the glabella or multiple facial regions (both n = 16/61, 26.2%) most commonly, followed by injections in the temples (n = 10/61, 16.4%) and the forehead (n = 9/61, 14.8%). The mean volume injected was 21.5 ± 21.5 ml. Visual symptoms were described most frequently (n = 24/58, 41.4%) followed by neurological symptoms (n = 20/58, 34.5%), or both (n = 13/58, 22.4%). Ophthalmic artery (OA, n = 26/60, 43.3%), anterior or middle cerebral artery (CA, n = 11/60, 18.3%) or both (n = 14/60, 23.3%) were most frequently occluded. Outcome analysis revealed permanent vision loss in all patients with OA occlusion (n = 26/26, 100%), neurological impairment in most patients with CA occlusion (n = 8/10, 80%), and vision loss in most patients suffering from both OA and CA occlusion (n = 7/11, 63.6%). Six patients died following embolisms. CONCLUSIONS: AE causes severe complications such as blindness, stroke, and death. Due to a lack of high-quality data, no evidence-based treatment algorithms exist. To increase patient safety, a database collecting cases and complications should be established. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Infections in Burn Patients: A Retrospective View over Seven Years.

Backgroundand objectives: Burn patients represent a challenging cohort because the injuries entail a vulnerability to colonisation by microorganisms. The ensuing infections can lead to serious complications and, in many cases, to the death of the burn patient. Surgical intervention and wound dressings, as well as antibiotic treatment, are crucial for optimising the treatment of the patient. Materialand Methods: In this retrospective analysis, we analysed the treatment course, antibiotic therapy, and general complications of 252 burn patients with second- or third-degree burns over a time span of 7 years. Results: Patients who developed infections tended to have, on average, a higher total body surface area (TBSA), higher abbreviated burn severity index (ABSI) scores, and longer hospital stays. Patients who were admitted to the burn unit after 2006 had significantly shorter stays in the burn unit. TBSA and ABSI scores were lower in the patient cohort admitted after 2006. Patients exhibiting a TBSA greater than 30% had significantly longer hospital stays and antibiotic treatment periods. TBSA and ABSI scores were significantly higher in patients who died. The results of binary logistic regression indicate that a higher ABSI score increases the odds ratio of developing an infection. Bacteria number had no significant effect on the odds of patient death but positively influenced the odds ratio of developing an infection. TBSA was negatively associated with the risk of developing an infection and was an insignificant predictor of mortality. Conclusions: To gauge the optimal treatment for a burn patient, it is crucial for practitioners to correctly select, dose, and time antibiotics for the patient. Monitoring bacterial colonisation is vital to nip rising infection in the bud and ensure the correct antibiotic selection. This will help prevent the development of multi-resistant bacteria.

Proliferation of endothelial cells (HUVEC) on specific-modified collagen sponges loaded with different growth factors.

In general, matrices for tissue engineering must maintain structural integrity during the process of tissue formation and promote vascularization of developing tissue. Therefore, collagen sponges, manufactured by an approach that offers the potential of unidirectional pore size, were seeded with human umbilical vein endothelial cells (HUVEC) to demonstrate a positive effect on cell proliferation. In addition, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) have been used to promote proliferation of HUVEC on optimized collagen sponges. Growth and viability of the cells were evaluated. Potential unidirectional pore structure demonstrated an improvement of both, endothelial cell growth and viability. Supplementation of growth factors showed an additional increase of endothelial cell growth on collagen sponges, which confirmed the high potential of combining this biomaterial with growth factors. The results suggest that a collagen sponge with a potential specific pore size could be a suitable scaffold for endothelial cells and might be a promising implantable biomaterial with enhanced angiogenic capabilities for future clinical applications.

The Role of Macrophage Migration Inhibitory Factor in Adipose-Derived Stem Cells Under Hypoxia.

Background: Adipose-derived stem cells (ASCs) are multipotent mesenchymal stem cells characterized by their strong regenerative potential and low oxygen consumption. Macrophage migration inhibitory factor (MIF) is a multifunctional chemokine-like cytokine that is involved in tissue hypoxia. MIF is not only a major immunomodulator but also is highly expressed in adipose tissue such as subcutaneous adipose tissue of chronic non-healing wounds. In the present study, we investigated the effect of hypoxia on MIF in ASCs isolated from healthy versus inflamed adipose tissue. Methods: Human ASCs were harvested from 17 patients (11 healthy adipose tissue samples, six specimens from chronic non-healing wounds). ASCs were treated in a hypoxia chamber at <1% oxygen. ASC viability, MIF secretion as well as expression levels of MIF, its receptor CD74, hypoxia-inducible transcription factor-1α (HIF-1α) and activation of the AKT and ERK signaling pathways were analyzed. The effect of recombinant MIF on the viability of ASCs was determined. Finally, the effect of MIF on the viability and production capacity of ASCs to produce the inflammatory cytokines tumor necrosis factor (TNF), interleukin (IL)-6, and IL-1ß was determined upon treatment with recombinant MIF and/or a blocking MIF antibody. Results: Hypoxic treatment inhibited proliferation of ASCs derived from healthy or chronic non-healing wounds. ASCs from healthy adipose tissue samples were characterized by a low degree of MIF secretion during hypoxic challenge. In contrast, in ASCs from adipose tissue samples of chronic non-healing wounds, secretion and expression of MIF and CD74 expression were significantly elevated under hypoxia. This was accompanied by enhanced ERK signaling, while AKT signaling was not altered. Recombinant MIF did stimulate HIF-1α expression under hypoxia as well as AKT and ERK phosphorylation, while no effect on ASC viability was observed. Recombinant MIF significantly reduced the secretion of IL-1ß under hypoxia and normoxia, and neutralizing MIF-antibodies diminished TNF-α and IL-1ß release in hypoxic ASCs. Conclusions: Collectively, MIF did not affect the viability of ASCs from neither healthy donor site nor chronic wounds. Our results, however, suggest that MIF has an impact on the wound environment by modulating inflammatory factors such as IL-1ß.

Macrophage Migration Inhibitory Factor-An Innovative Indicator for Free Flap Ischemia after Microsurgical Reconstruction.

(1) Background: Nowadays, the use of microsurgical free flaps is a standard operative procedure in reconstructive surgery. Still, thrombosis of the microanastomosis is one of the most fatal postoperative complications. Clinical evaluation, different technical devices and laboratory markers are used to monitor critical flap perfusion. Macrophage migration inhibitory factor (MIF), a structurally unique cytokine with chemokine-like characteristics, could play a role in predicting vascular problems and the failure of flap perfusion. (2) Methods: In this prospective observational study, 26 subjects that underwent microsurgical reconstruction were observed. Besides clinical data, the number of blood leukocytes, CRP and MIF were monitored. (3) Results: Blood levels of MIF, C-reactive protein (CRP) and leukocytes increased directly after surgery. Subjects that needed surgical revision due to thrombosis of the microanastomosis showed significantly higher blood levels of MIF than subjects without revision. (4) Conclusion: We conclude that MIF is a potential and innovative indicator for thrombosis of the microanastomosis after free flap surgery. Since it is easy to obtain diagnostically, MIF could be an additional tool to monitor flap perfusion besides clinical and technical assessments.

The Effect of Hyperbaric Oxygen Therapy on Human Adipose-Derived Stem Cells.

BACKGROUND: Adipose-derived stem cells are considered as candidate cells for regenerative plastic surgery. Measures to influence cellular properties and thereby direct their regenerative potential remain elusive. Hyperbaric oxygen therapy-the exposure to 100% oxygen at an increased atmospheric pressure-has been propagated as a noninvasive treatment for a multitude of indications and presents a potential option to condition cells for tissue-engineering purposes. The present study evaluates the effect of hyperbaric oxygen therapy on human adipose-derived stem cells. METHODS: Human adipose-derived stem cells from healthy donors were treated with hyperbaric oxygen therapy at 2 and 3 atm. Viability before and after each hyperbaric oxygen therapy, proliferation, expression of surface markers and protein contents of transforming growth factor (TGF)-ß, tumor necrosis factor-α, hepatocyte growth factor, and epithelial growth factor in the supernatants of treated adipose-derived stem cells were measured. Lastly, adipogenic, osteogenic, and chondrogenic differentiation with and without use of differentiation-inducing media (i.e., autodifferentiation) was examined. RESULTS: Hyperbaric oxygen therapy with 3 atm increased viability, proliferation, and CD34 expression and reduced the CD31/CD34/CD45 adipose-derived stem cell subset and endothelial progenitor cell population. TGF-ß levels were significantly decreased after two hyperbaric oxygen therapy sessions in the 2-atm group and decreased after three hyperbaric oxygen therapy sessions in the 3-atm group. Hepatocyte growth factor secretion remained unaltered in all groups. Although the osteogenic and chondrogenic differentiation were not influenced, adipogenic differentiation and autodifferentiation were significantly enhanced, with osteogenic autodifferentiation significantly alleviated by hyperbaric oxygen therapy with 3 atm. CONCLUSION: Hyperbaric oxygen therapy with 3 atm increases viability and proliferation of adipose-derived stem cells, alters marker expression and subpopulations, decreases TGF-ß secretion, and skews adipose-derived stem cells toward adipogenic differentiation. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

Occult Pathologic Findings in Reduction Mammaplasty in 5781 Patients-An International Multicenter Study.

Breast cancer is among the most commonly diagnosed cancers in the world, affecting one in eight women in their lifetimes. The disease places a substantial burden on healthcare systems in developed countries and often requires surgical correction. In spite of this, much of the breast cancer pathophysiology remains unknown, allowing for the cancer to develop to later stages prior to detection. Many women undergo reduction mammaplasties (RM) to adjust breast size, with over 500,000 operations being performed annually. Tissue samples from such procedures have drawn interest recently, with studies attempting to garner a better understanding of breast cancer's development. A number of samples have revealed nascent cancer developments that were previously undetected and unexpected. Investigating these so-called "occult" findings of cancer in otherwise healthy patients may provide further insight regarding risk factors and countermeasures. Here, we detail occult findings of cancer in reduction mammaplasty samples provided from a cohort of over 5000 patients from 16 different institutions in Europe. Although the majority of our resected breast tissue specimens were benign, our findings indicate that there is a continued need for histopathological examination. As a result, our study suggests that preoperative imaging should be routinely performed in patients scheduled for RM, especially those with risk factors of breast cancer, to identify and enable a primary oncologic approach.

The short scar three-block L-wing technique.

INTRODUCTION: Numerous techniques have been proposed for the plastic surgical treatment of hypertrophic breasts. Challenges of the procedure include the preservation of vascular supply and sensitivity of the nipple areola complex (NAC), breast feeding, and an esthetically pleasing result. OBJECTIVES: In the present preliminary report, we introduce a new technique called the three-block L-wing reduction mammaplasty that addresses the aforementioned difficulties. MATERIALS AND METHODS: The three-block L-wing reduction mammaplasty with a thick hemispheric superiorly based NAC pedicle and a medial as well as lateral pillar was performed in a total of 60 patients. RESULTS: Our technique increases both, vascular safety and the sensory supply to the NAC, as it conceptually decreases the need for dissection of breast tissue and skin. The incidence of fat necrosis and wound healing disorders may be reduced with this technique. Because the ducts of the breast-gland underneath the NAC are not dissected, this technique also promises a higher probability of regular breast-feeding. Finally, our technique permits a cosmetically pleasing round-shaped mound of the breast. CONCLUSION: The three-block modification simplifies the procedure of the superior pedicle L-wing mammaplasty markedly. It may increase the esthetic as well as the functional outcome and decrease postoperative complications.

Impact of growth factor content on proliferation of mesenchymal stromal cells derived from adipose tissue.

Autologous adipose tissue (AT) transfer has gained widespread acceptance and is used for a broad variety of regenerative clinical indications. It is assumed that the successful outcome of AT transfer essentially depends on the amount of autocrine-generated growth factors (GF). It is supposed that several GF enhance and improve the anatomic and functional integration of the transplanted AT grafts at the site of implantation. In the present study we have investigated for the first time the correlation between the concentration of GF of freshly isolated AT and the proliferation and migration capacity of mesenchymal stroma cells (MSCs) derived from the respective AT sample. We here show that the proliferation and migration capacity of MSCs strongly depends on the GF content of the AT the cells were isolated from but in an inversely proportional manner. The lower the GF content of an AT sample was, the higher was the proliferation and migration capacity of the respective MSC population contained in the AT and vice versa. Furthermore, we found that supplementation with recombinant GFs only in the case of AT samples with low but not with higher growth factor contents led to a significant enhancement of proliferation and migration of the AT-resident MSCs. As we further show, this inefficiency of GFs to enhance MSC proliferation and migration in AT samples with high GF contents indicates a GF-mediated negative feedback mechanism leading to an impaired GF signaling in MSC obtained from those AT samples. Our results might explain why the successful use of AT grafting is frequently limited by low and unpredictable survival rates, and we suggest to use the knowledge of GF content of harvested AT as a predictive clinical parameter for risk assessment of the therapeutic outcome of autologous AT transfer.

The effect of the macrophage migration inhibitory factor (MIF) on excisional wound healing in vivo.

Background: The macrophage migration inhibitory factor (MIF) has been determined as a cytokine exerting a multitude of effects in inflammation and angiogenesis. Earlier studies have indicated that MIF may also be involved in wound healing and flap surgery. Methods: We investigated the effect of MIF in an excisional wound model in wildtype, Mif-/- and recombinant MIF treated mice. Wound closure rates as well as the macrophage marker Mac-3, the pro-inflammatory cytokine tumor necrosis factor α (TNFα) and the pro-angiogenic factor von Willebrand factor (vWF) were measured. Finally, we used a flap model in Mif-/- and WT mice with an established perfusion gradient to identify MIF's contribution in flap perfusion. Results: In the excision wound model, we found reduced wound healing after MIF injection, whereas Mif deletion improved wound healing. Furthermore, a reduced expression of Mac-3, TNFα and vWF in Mif-/- mice was seen when compared to WT mice. In the flap model, Mif-/- knockout mice showed mitigated flap perfusion with lower hemoglobin content and oxygen saturation as measured by O2C measurements when compared to WT mice. Conclusions: Our data suggest an inhibiting effect of MIF in wound healing with increased inflammation and perfusion. In flaps, by contrast, MIF may contribute to flap vascularization.

Differential regulation of macrophage activation by the MIF cytokine superfamily members MIF and MIF-2 in adipose tissue during endotoxemia.

Sepsis is a leading cause of death worldwide and recent studies have shown white adipose tissue (WAT) to be an important regulator in septic conditions. In the present study, the role of the inflammatory cytokine macrophage migration inhibitory factor (MIF) and its structural homolog D-dopachrome tautomerase (D-DT/MIF-2) were investigated in WAT in a murine endotoxemia model. Both MIF and MIF-2 levels were increased in the peritoneal fluid of LPS-challenged wild-type mice, yet, in visceral WAT, the proteins were differentially regulated, with elevated MIF but downregulated MIF-2 expression in adipocytes. Mif gene deletion polarized adipose tissue macrophages (ATM) toward an anti-inflammatory phenotype while Mif-2 gene knockout drove ATMs toward a pro-inflammatory phenotype and Mif-deficiency was found to increase fibroblast viability. Additionally, we observed the same differential regulation of these two MIF family proteins in human adipose tissue in septic vs healthy patients. Taken together, these data suggest an inverse relationship between adipocyte MIF and MIF-2 expression during systemic inflammation, with the downregulation of MIF-2 in fat tissue potentially increasing pro-inflammatory macrophage polarization to further drive adipose inflammation.

Microfat and Lipoconcentrate for the Treatment of Facial Scars.

Fat grafting is as a unique regenerative filler with soluble factors and progenitor cells that may remodel scar tissue in an easy yet effective way. A combination of microfat grafting, lipococoncentrate injection, scar subcision, and platelet-rich plasma supplementation may be used to treat the majority of facial scars. The lipoconcentrate technique condenses the lipoaspirate to a progenitor cell-rich fluid of low volume by a combination of centrifugation and emulsification steps. In this article, the authors' methods for scar treatment by fat grafting are discussed. Choice of technique for facial scars, precise indications, and contraindications are introduced.

Concentration of Chondrogenic Soluble Factors in Freshly Harvested Lipoaspirate.

BACKGROUND: Cartilage tissue has a limited capacity for healing with the consequence that patients are often treated symptomatically until they become candidates for osteotomy or total joint replacement. Alternative biological therapies, for example, application of platelet-rich plasma and implantation of chondrocytes and mesenchymal stem cells, have emerged as a new treatment modality to repair articular cartilage. In addition, autologous fat transfer is performed for treatment of cartilage defects, example given, in osteoarthrosis, but several questions regarding basic biochemical properties of the transplant remain unanswered. Bone morphogenetic protein 4 (BMP4), matrix metalloproteinase (MMP)-8, cartilage oligomeric matrix protein (COMP), and chitinase-3-like protein 1 (CHI3L1) have been shown to be involved in chondrogenic regeneration and represent potential therapeutic agents for cartilage repair. However, no study regarding naturally occurring levels of these soluble factors in transplanted adipose tissue has yet been performed. METHODS: To investigate the influence of age, body mass index, donor site, and sex on the concentration of BMP4, MMP-8, COMP, and CHI3L1 in freshly aspirated adipose tissue, their content was measured by means of enzyme-linked immunosorbent assay readings. RESULTS: There were significant quantities of BMP4, MMP-8, COMP, and CHI3L1 (23.6, 249.9, 298.0, and 540.6 pg/mg, respectively) in the lipoaspirate harvested for transplantation. There was no correlation between the content of soluble factors and the patients' age or body mass index. Furthermore, the sex did not affect the amount of the investigated factors. However, there were significantly lower contents of BMP4, COMP, and CHI3L1 found in lipoaspirates harvested from the abdomen compared with nonabdominal donor sites. CONCLUSIONS: Naturally occurring differences in the concentrations of the investigated soluble factors will favor certain donor sites for autologous fat transfer in the field of cartilage repair. Thus, increasing knowledge will enable researchers and clinicians to make autologous fat transfer procedures more reliable and efficient for treatment of articular cartilage defects.

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.

Cell-enrichment with olfactory ensheathing cells has limited local extra beneficial effects on nerve regeneration supported by the nerve guide Perimaix.

The reconstruction of peripheral nerve injuries is clinically challenging, and today, the autologous nerve transplantation is still considered as the only gold standard remedy for nerve lesions where a direct nerve coaptation is not possible. Nevertheless, the functional merits of many biomaterials have been tested as potential substitutes for the autologous nerve transplant. One of the strategies that have been pursued is the combination of bioengineered nerve guides with cellular enrichment. In this present study, we combined the previously evaluated collagen-based and microstructured nerve guide Perimaix with olfactory ensheathing cell enrichment. Rat sciatic nerve defects of 20 mm were either bridged by a cell-seeded or nonseeded nerve guide or an autologous nerve transplant. Animals were monitored for 12 weeks for structural and functional parameters. Seeded cells survived on Perimaix, and following implantation aligned along the microstructured Perimaix framework. Axonal densities within the cell-seeded nerve guides were higher than in the nonseeded nerve guides and were comparable to the autograft. Additionally, cell-seeding had local beneficial effects on myelination within the nerve guide, as myelin sheath thickness was enhanced when compared with the empty scaffold. Nevertheless, for bridging the nerve gap of 20 mm, both the cell-seeded as well as nonseeded scaffolds were equally efficient regarding the functional outcome, which did not differ between the autograft, seeded or nonseeded groups. Our data demonstrate that olfactory ensheathing cell enrichment has local effects on nerve regeneration in combination with the Perimaix nerve guide. Surprisingly, for traversing the lesion gap, additional cell-seeding is not crucial.

Enhancement of Progenitor Cells by Two-Step Centrifugation of Emulsified Lipoaspirates.

BACKGROUND: Adipose-derived stem cells, endothelial progenitor cells, and soluble factors jointly contribute to the regenerative effect of fat grafts. Nanofat grafting emulsifies the lipoaspirate and increases the progenitor cell yield. In the present study, the authors evaluated their extended nanofat grafting method that includes two additional centrifugation steps and results in a lipoaspirate of low volume that they termed "lipoconcentrate." Furthermore, the authors investigated the oily fractions after centrifugation for their regenerative potential. METHODS: Lipoaspirates of 20 healthy patients were processed by emulsification and/or centrifugation. Six groups were created: native (not emulsified) fat, 1× centrifuged native fat, 2× centrifuged native fat, nanofat (emulsified), 1× centrifuged nanofat, and lipoconcentrate (i.e., 2× centrifuged nanofat). The oily phases after the centrifugation steps were collected. Progenitor cells and basic fibroblast growth factor, insulin-like growth factor 1, matrix metalloproteinase-9, platelet-derived growth factor-BB, and vascular endothelial growth factor-A levels were measured by flow cytometry and immunoassays. RESULTS: Lipoconcentrate contained significantly higher numbers of adipose-derived stem cells and endothelial progenitor cells per gram compared with all other fractions. No difference of all five soluble factors between groups was found. The oily phases after centrifugation showed no or very few adipose-derived stem cells and endothelial progenitor cells, and no or very low levels of soluble factors. CONCLUSIONS: Centrifugation of emulsified lipoaspirates increases the progenitor cell count in the lipoaspirate. The oily phase after centrifugation of lipoaspirates may be disposable because of the minuscule content of progenitor cells and soluble factors.

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.

Macrophage Migration Inhibitory Factor - A Favorable Marker in Inflammatory Diseases?

BACKGROUND: Macrophage migration inhibitory factor (MIF) was firstly described in the 1960s as a pleiotropic cytokine affecting a variety of immune cells. Different physiological functions mainly involving inflammatory reactions such as chemokine-like function and regulating systemic stress responses have been reported. OBJECTIVE: In several clinical studies the use of MIF as a biomarker has been investigated promising support for diseases with an inflammatory aspect such as sepsis, systemic infections and autoimmune diseases. This article in detail reviews clinical data and evaluates the function as biomarker focusing on inflammatory and autoimmune diseases. CONCLUSION: Recent studies suggest MIF to be a marker for different inflammatory diseases and might serve as therapeutic target in the future.

The effect of mechanical stress on the proliferation, adipogenic differentiation and gene expression of human adipose-derived stem cells.

To allow for a better implementation of external volume expansion to clinical applications for soft tissue regeneration, it is necessary to comprehensively understand the underlying mechanisms. As human adipose-derived stem cells (hASCs) play a crucial role in soft tissue enlargement, we investigated the impact of cyclic stretch on gene expression, proliferation rate and adipogenic differentiation of these cells. After cyclic stretching, RNA was extracted and subjected to DNA microarray analysis and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Also, the expression of FABP4 mRNA was analysed by RT-qPCR to test whether mechanical stretch affected adipogenic differentiation of hASCs. The proliferation rate was assessed using the alamarBlue assay and Ki-67 staining. A cell cycle analysis was performed with flow cytometry and Western blot. We found that cyclic stretch significantly induced the expression of CYP1B1 mRNA. Furthermore, the adipogenic differentiation of hASCs was impaired, as was the proliferation. This was partly due to a decrease in extracellular signal-regulated kinase (ERK) 1/2 and histone H3 phosphorylation, suggesting a growth arrest in the G2 /M phase of the cell cycle. Enrichment analyses demonstrated that stretch-regulated genes were over-represented in pathways and biological processes involved in extracellular matrix organization, vascular remodelling and responses to cell stress. Taken together, mechanical stress impaired both proliferation and adipogenic differentiation, but led to a tissue-remodelling phenotype of hASCs. These data suggest that extracellular matrix remodelling and neoangiogenesis may play a more important role in external volume expansion than proliferation and adipogenesis of hASCs. Copyright © 2017 John Wiley & Sons, Ltd.