Implementation of a Machine Learning Approach Evaluating Risk Factors for Complications after Single-Stage Augmentation Mastopexy.

BACKGROUND: Single-stage mastopexy augmentation is a much-debated intervention due to its complexity and the associated relatively high complication rates. This study aimed to reevaluate the risk factors for these complications using a novel approach based on artificial intelligence and to demonstrate its possible limitations. PATIENTS AND METHODS: Complete datasets of patients who underwent single-staged augmentation mastopexy during 2014-2023 at one institution by a single surgeon were collected retrospectively. These were subsequently processed and analyzed by CART, RF and XGBoost algorithms. RESULTS: A total of 342 patients were included in the study, of which 43 (12.57%) reported surgery-associated complications, whereby capsular contracture (n = 19) was the most common. BMI represented the most important variable for the development of complications (FIS = 0.44 in CART). 2.9% of the patients expressed the desire for implant change in the course, with absence of any complications. A statistically significant correlation between smoking and the desire for implant change (p < 0.001) was revealed. CONCLUSION: The importance of implementing artificial intelligence into clinical research could be underpinned by this study, as risk variables can be reclassified based on factors previously considered less or even irrelevant. Thereby we encountered limitations using ML approaches. Further studies will be needed to investigate the association between smoking, BMI and the current implant size with the desire for implant change without any complications. Moreover, we could show that the procedure can be performed safely without high risk of developing major complications. LEVEL OF EVIDENCE IV: 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.

Pharmacological elevation of sphingosine-1-phosphate by S1P lyase inhibition accelerates bone regeneration after post-traumatic osteomyelitis.

Posttraumatic osteomyelitis and the ensuing bone defects are a debilitating complication after open fractures with little therapeutic options. We have recently identified potent osteoanabolic effects of sphingosine-1-phosphate (S1P) signalling and have now tested whether it may beneficially affect bone regeneration after infection. We employed pharmacological S1P lyase inhibition by 4-deoxypyrodoxin (DOP) to raise S1P levels in vivo in an unicortical long bone defect model of posttraumatic osteomyelitis in mice. In a translational approach, human bone specimens of clinical osteomyelitis patients were treated in organ culture in vitro with DOP. Bone regeneration was assessed by µCT, histomorphometry, immunohistology and gene expression analysis. The role of S1P receptors was addressed using S1PR3 deficient mice. Here, we present data that DOP treatment markedly enhanced osteogenesis in posttraumatic osteomyelitis. This was accompanied by greatly improved osteoblastogenesis and enhanced angiogenesis in the callus accompanied by osteoclast-mediated bone remodelling. We also identified the target of increased S1P to be the S1PR3 as S1PR3-/- mice showed no improvement of bone regeneration by DOP. In the human bone explants, bone mass significantly increased along with enhanced osteoblastogenesis and angiogenesis. Our data suggest that enhancement of S1P/S1PR3 signalling may be a promising therapeutic target for bone regeneration in posttraumatic osteomyelitis.

Autologous Reconstruction After Failed Implant-Based Breast Reconstruction: A Comparative Multifactorial Outcome Analysis.

INTRODUCTION: Failure of an implant-based breast reconstruction often requires a change to an autologous procedure (salvage autologous breast reconstruction [Salv-ABR]). The aim of this study was to compare surgical and patient-reported outcomes of Salv-ABR to immediate or delayed-immediate ABR (I/DI-ABR), which has hardly been addressed in the existing literature. METHODS: All patients undergoing Salv- or I/DI-ABR between January 2014 and December 2020 were asked to participate in this study. Complication rates, the aesthetic outcome (5-point Likert scale), and quality of life (EORTC QLQ-C30 and -BR23, Breast-Q, Center for Epidemiology Studies Depression Scale) were compared between both procedures. RESULTS: Seventy patients participated in the study (Salv-ABR: n = 23; mean ± SD age, 53.5 ± 9.1 years; follow-up, 28.6 ± 18.5 month; I/DI-ABR: n = 45, mean ± SD age: 50.2 ± 7.3 years; follow-up, 32.8 ± 18.5 month). Main indication for Salv-ABR was a major capsular contracture (n = 14 [60.1%]). Early unplanned reoperation rates were significantly increased in the Salv-ABR (56.5% vs 14.9%; P < 0.01). Patients with I/DI-ABR showed a significantly improved overall aesthetic outcome (2.7 ± 0.9 vs 3.3 ± 0.7; P < 0.01) and scored significantly higher in several subscales of EORTC QLQ-C30/BR23 (Global Health Status, Role Functioning, Body Image; P < 0.05) and the Breast-Q (Psychosocial Well-being, Satisfaction with Breast; P < 0.05) compared with patients with Salv-ABR. CONCLUSIONS: Salvage ABR is associated with a higher complication rate, compromised aesthetic outcome, and quality of life compared with I/DI-ABR. This should be considered and discussed with the patient when planning any kind of reconstructive breast surgery.

The Partner Perspective on Autologous and Implant-Based Breast Reconstruction.

INTRODUCTION: Partner involvement in the decision-making process concerning breast reconstruction (BR) after a breast cancer diagnosis may be very supportive for the patient. So far, no study evaluates partner satisfaction with the outcome after BR and the relationship to patient satisfaction. The aim of this study was to assess and compare partner satisfaction of BR with autologous tissue (ABR) and prosthetic implants (IBR), respectively, and compare it to patient-reported outcomes. PATIENTS AND METHODS: All patients undergoing ABR and IBR between January 2014 and December 2020 were asked to participate with their partners. Patient and partner satisfaction with breast reconstruction, overall outcome as well as patient's perceived and self-reported psychosocial well-being were evaluated using the Breast-Q and a modified partner questionnaire, respectively. RESULTS: Fifty-three couples participated (IBR: n=30, ABR: n = 23). Patient and partner satisfaction with breast (r = 0.552), outcome (r = 0.465) as well as patient's perceived and self-report psychosocial well-being (r = 0.495) were highly correlated with partners scoring significantly higher (p<0.001). In terms of partner satisfaction, both reconstructive procedures achieved satisfactory results. ABR scored higher in terms of softness of breast and how natural the breast feels to touch whereas IBR was rated superior evaluating the breast size. CONCLUSION: Both reconstructive procedures achieve satisfactory results in terms partner satisfaction whereas patient's psychosocial well-being was highly overestimated by their partners. Hence, partner inclusion in the regular psycho-oncological support might further sensitize them of the high psychological burden of a breast cancer diagnosis and therefore stabilize patients private support system. 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 .

Wnt3a and ASCs are capable of restoring mineralization in staph aureus-infected primary murine osteoblasts.

INTRODUCTION: Bone infections are one of the main reasons for impaired bone regeneration and non-union formation. In previous experimental animal studies we could already demonstrate that bone defects due to prior infections showed a markedly reduced healing capacity, which could effectively be enhanced via application of Wnt3a and Adipose-derived stromal cells (ASCs). For a more in-depth analysis, we investigated proliferation and mineralization of cultured osteoblasts infected with staph aureus and sought to investigate effects of Wnt3a and ASCs on infected osteoblasts. MATERIALS AND METHODS: Primary murine osteoblasts were isolated from calvariae and infected with staph aureus. Infected osteoblasts received treatment via application of recombinant Wnt3a, ASC conditioned medium and were furthermore cocultured with ASCs. Osteoblasts were evaluated by Alamar blue assay for metabolic activity, TUNEL-assay for apoptosis, ALP and Alizarin Red staining for mineralization. In addition, immunoflourescent staining (IF) and qRT-PCR analyses were performed. RESULTS: Infected osteoblasts showed a markedly reduced ability for mineralization and increased apoptosis, which could be restored to physiological levels by Wnt3a and ASC treatment. Interestingly, metabolic activity of osteoblasts seemed to be unaffected by staph aureus infection. Additional analyses of Wnt-pathway activity revealed effective enhancement of canonical Wnt-pathway activity in Wnt3a-treated osteoblasts. CONCLUSIONS: In summary, we gained further osteoblast-related insights into pathomechanisms of reduced bone healing capacity upon infections.

Prophylactic lymphaticovenous anastomoses for resection of soft tissue tumors of the thigh to prevent secondary lymphedema-a retrospective comparative cohort analysis.

BACKGROUND: Patients with soft tissue tumors of extremities are at risk to develop secondary lymphedema after tumor resection caused by disruption of lymphatic vessels and sclerosis. Subsequently, this study aimed to evaluate the beneficial effects of lymphaticovenous anastomoses (LVAs) after soft tissue tumor resection of the thigh in a prophylactic approach. METHODS: In a retrospective cohort study, we compared eight patients with a median age of 68.5 years (49-80) who received LVAs in combination with tumor resection for treatment of soft tissue tumors of the thigh region with a prior cohort of 20 patients with a median age of 63.0 years (23-84) who received soft tissue sarcoma resection of the thigh region. All patients of LVA cohort received 1-2 LVAs (mean 1.25 ± 0.49) at the dorsum of the foot and three patients at the SEKI-point (mean 0.375 ± 0.51). Mean maximum tumor diameter of LVA group was 19.5 ± 5.2 cm and 12.3 ± 6.6 cm of control group. All patients receiving LVA were assessed for development of lymphedema via bilateral measurements of circumference and assessment of lymphedema quality of life index (LyQLI). RESULTS: One of the eight patients who received LVAs showed moderate impairment in the LyQLI at a follow-up of 12 months while 45% of the control cohort complained about symptoms of secondary lymphedema at a median follow-up of 22 months (p-values LyQLI: p = .018 [physical domain]; p = .018 [psychosocial domain]; p = .020 [practical domain]). CONCLUSION: LVAs performed in combination with tumor resection of thigh soft tissue tumors reduce negative consequences of lymph stasis and prevent development of secondary lymphedema.

A Machine Learning Approach to Identify Previously Unconsidered Causes for Complications in Aesthetic Breast Augmentation.

INTRODUCTION: Primary breast augmentation is one of the most commonly requested aesthetic procedures. Considering the large number of procedures performed in connection with a high demand, it is crucial to prevent complications. For this reason, finding and avoiding possible sources of complications is decisive. METHODS: Between January 2010 and December 2021, 1625 female patients underwent an aesthetic breast augmentation performed by a single surgeon. The data collected were analyzed through a machine learning technique for binary recursive partitioning. This made it possible to detect unknown sources of a complication and determine a vertex for the various features. RESULTS: When analyzing the data, for most features a high importance score with low entropy was achieved, concluding a high significance. In addition, reproducibility was demonstrated through detailed testing and training accuracies in the algorithm. With this procedure, in addition to known risks such as a high BMI and round implant shape, a larger than A preoperative bra-cup size (OR: 2.7) and a taller body could also be identified as most significant influencing factors for complications. DISCUSSION: Preoperative breast size plays an exceptionally important role in the occurrence of complications and should be a factor held in a surgeon's considerations. In addition, this study shows ways to transfer artificial intelligence into plastic surgery to increase medical quality. LEVEL OF EVIDENCE IV: 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 .

The Search for the Ideal Female Breast: A Nationally Representative United-States-Census Study.

INTRODUCTION: Many studies have started to search for the perfect aesthetic breast in order to create a pars-pro-toto for reconstruction, but especially for aesthetic surgery. To date, no representative study with anatomically accurate models was performed. METHODS: In an online based United-States-census-representative survey with 1049 participants, questions regarding the preferred breast were asked utilizing lifelike morphed 3D-generated female models for the first time. Attributes such as breast pole ratio, areola size, breast direction and projection were asked. RESULTS: The results show that, contrary to what has been claimed in previous studies, an upper-pole-to-lower-pole ratio of 55:45 is preferred by both female and male participants. When it comes to breast size, on the other hand, there are clear gender-specific differences. While women opted for a cup size around B, the men preferred larger cup sizes. Moreover, the smallest depicted areola size of 30 mm was favored among all groups in the survey. DISCUSSION: Most publications used rather detrimental models for their surveys. We therefore opted for computer-generated 3D models and varied their naturalness. This enabled us to ensure a more aesthetic and accurate illustration and thus obtained more comparable and reliable results paired with the representation of the US-population. Taken together this study unveiled unexpected insights into the population favored breast attributes that might change operative planning in breast surgery. LEVEL OF EVIDENCE V: 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 http://www.springer.com/00266 .

Hierarchical Ceramic Coating Reduces Adherence of Cells, Blood, Bacteria, and Tissue on Titanium Microsurgical Instruments.

BACKGROUND: Progress in the field of microsurgery allows more detailed reconstructions of the smallest tissue structures. The applied instruments are left with biological residues after coming into contact with body fluids or tissue, leading to compromised surgical precision. Designing of residue-free innovative instruments would reduce the necessity of subsidiary practices and would improve the surgical precision. METHODS: We designed a ceramic coating (Lotus ceramic coating system 26-LCC-26) that exhibits self-cleaning surface properties on coated titanium specimens. A titanium surface was modified by blasting technology and electropolishing, followed by applying a high-performance ceramic and sol-gel finish layer. The physical surface characterization was performed by scanning electron microscopy and measuring the contact angle. The cell-repellent properties and cytotoxicity were investigated using live-dead staining, BrdU, and lactate dehydrogenase assay. Furthermore, bacterial and fluid-adhesion tests were performed. Finally, blood compatibility was analyzed according to DIN ISO 10993. RESULTS: The composite system LCC-26 increased the hydrophobic character of the titanium surface (the water contact angle of 74.9 degrees was compared with 62.7 degrees of the uncoated native titanium; p < 0.01) and led to the fluid and cell-repellent properties shown by the reduction in fibroblast adherence by ∼50.7% (p < 0.05), the reduction in Staphylococcus aureus pathogen colonization by 74.1% (p < 0.001), and the decrease in erythrocyte adherence by 62.9% (p < 0.01). Furthermore, the LCC-26 coated titanium microforceps dipped in human whole blood exhibited blood-repellent character (reduction in blood adherence by 46.1%; p < 0.05). Additionally, cyto- and hemocompatibility was guaranteed in direct and indirect tests. CONCLUSION: Titanium surface modification on surgical instruments exhibits cell, bacteria, and blood-repellent properties with a full guarantee of cyto- and hemocompatibility. Thus, innovatively coated instruments could contribute to increased precision during microsurgical interventions and optimized medical operation routines in the future.

Stevens-Johnson syndrome and toxic epidermal necrolysis: a systematic review and meta-analysis.

OBJECTIVE: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare and severe skin and mucosal reactions that are associated with high mortality. Despite the severity, an evidence-based treatment protocol for SJS/TEN is still lacking. METHOD: In this systematic review and meta-analysis, the PubMed database was searched using the following terms: [Stevens-Johnson syndrome] OR [toxic epidermal necrolysis] AND [therapy] OR [treatment] over a 20-year period (1999-2019) in the German and English language. All clinical studies reporting on the treatment of SJS/TEN were included, and epidemiological and diagnostic aspects of treatment were analysed. A meta-analysis was conducted on all comparative clinical studies that met the inclusion criteria. RESULTS: A total of 88 studies met the inclusion criteria, reporting outcomes in 2647 patients. Treatment was either supportive or used systemic corticosteroid, intravenous immunoglobulin, plasmapheresis, cyclosporine, thalidomide or cyclophosphamide therapy. The meta-analysis included 16 (18%) studies, reporting outcomes in 976 (37%) patients. Systemic glucocorticoids showed a survival benefit for SJS/TEN patients in all analyses compared with other forms of treatment. Cyclosporine treatment also showed promising results, despite being used in a small cohort of patients. No beneficial effects on mortality could be demonstrated for intravenous immunoglobulins. CONCLUSION: Glucocorticoids and cyclosporine may be tentatively recommended as the most promising immunomodulatory therapies for SJS/TEN, but these results should be investigated in future prospective controlled trials.

Controllable Factors to Reduce the Rate of Complications in Primary Breast Augmentation: A Review of the Literature.

BACKGROUND: Aesthetic augmentation mammoplasties are one of the most demanded procedures performed in the aesthetic surgical sector. Because of the high epidemiological impact, the evaluation of measures to reduce the risk of complications is highly needed. The goal of this review is to evaluate the current literature for successful actions to reduce the risk of complications in aesthetic breast augmentation. METHODS: We searched Medline-listed journals for "complications primary breast augmentation" and defined surgeon-dependent and patient-dependent factors within those. RESULTS: Most of the strategies to reduce the risk of any complication are based on meticulous hygienic precautions and adequate training of the surgeon. The current literature suggests complications such as capsular contracture, infection and BIA-ALCL are closely linked with bacterial contamination and therefore can be avoided with different hygienic measures. 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 .

Comparative proteomic analysis of osteogenic differentiated human adipose tissue and bone marrow-derived stromal cells.

Mesenchymal stromal cells are promising candidates for regenerative applications upon treatment of bone defects. Bone marrow-derived stromal cells (BMSCs) are limited by yield and donor morbidity but show superior osteogenic capacity compared to adipose-derived stromal cells (ASCs), which are highly abundant and easy to harvest. The underlying reasons for this difference on a proteomic level have not been studied yet. Human ASCs and BMSCs were characterized by FACS analysis and tri-lineage differentiation, followed by an intraindividual comparative proteomic analysis upon osteogenic differentiation. Results of the proteomic analysis were followed by functional pathway analysis. 29 patients were included with a total of 58 specimen analysed. In these, out of 5148 identified proteins 2095 could be quantified in >80% of samples of both cell types, 427 in >80% of ASCs only and 102 in >80% of BMSCs only. 281 proteins were differentially regulated with a fold change of >1.5 of which 204 were higher abundant in BMSCs and 77 in ASCs. Integrin cell surface interactions were the most overrepresented pathway with 5 integrins being among the proteins with highest fold change. Integrin 11a, a known key protein for osteogenesis, could be identified as strongly up-regulated in BMSC confirmed by Western blotting. The integrin expression profile is one of the key distinctive features of osteogenic differentiated BMSCs and ASCs. Thus, they represent a promising target for modifications of ASCs aiming to improve their osteogenic capacity and approximate them to that of BMSCs.

Antibiotic prophylaxis for prevention of wound infections after soft tissue sarcoma resection: A retrospective cohort study.

BACKGROUND AND OBJECTIVES: The use of antibiotic prophylaxis for soft tissue sarcoma resection varies widely while little evidence on this topic exists. The aim of this study was to determine the impact of antibiotic prophylaxis on the occurrence of wound infections. METHODS: A single institutional retrospective cohort study was performed on patients who underwent truncal or extremity soft tissue sarcoma resection. The use of antibiotic prophylaxis was assessed and univariate and multivariate analysis of predictors of wound infections was performed. RESULTS: Nine hundred and fifty-eight patients could be included. Thirty-two percent of patients had no antibiotic prophylaxis, 44% of patients received single-shot prophylaxis, and 24% of patients received single-shot plus continued antibiotic treatment. Wound infections occurred in 140 patients (15%). Independent risk factors for wound infections upon multivariate analysis were obesity, high American Society of Anesthesiologists (ASA) status, high tumor size and grade, operation time over 120 minutes, and other complications. Antibiotic prophylaxis could not be identified as a protective factor in univariate or multivariate analysis. CONCLUSIONS: A favorable effect of antibiotic prophylaxis on the occurrence of wound infections could not be observed. Although more studies on this subject are needed, our data do not support the general use of antibiotic prophylaxis for soft tissue sarcoma resection.

Molecular Mechanisms of Hair Growth and Regeneration: Current Understanding and Novel Paradigms.

Hair is a defining feature of mammals and has critical functions, including protection, production of sebum, apocrine sweat and pheromones, social and sexual interactions, thermoregulation, and provision of stem cells for skin homeostasis, regeneration, and repair. The hair follicle (HF) is considered a "mini-organ," consisting of intricate and well-organized structures which originate from HF stem and progenitor cells. Dermal papilla cells are the main components of the mesenchymal compartments in the hair bulb and are instrumental in generating signals to regulate the behavior of neighboring epithelial cells during the hair cycle. Mesenchymal-epithelial interactions within the dermal papilla niche drive HF embryonic development as well as the postnatal hair growth and regeneration cycle. This review summarizes the current understanding of HF development, repair, and regeneration, with special focus on cell signaling pathways governing these processes. In particular, we discuss emerging paradigms of molecular signaling governing the dermal papilla-epithelial cellular interactions during hair growth and maintenance and the recent progress made towards tissue engineering of human hair follicles.

Regulatory aspects of myogenic factors GDF-8 and Follistatin on the intake of combined oral contraceptives.

Combined oral contraceptives are one of the most prescribed drugs in the western world. While there is little evidence regarding effects of estrogen or gestagens on muscle metabolism, androgens are well-known for their anabolic characteristics. In this study, we seeked to investigate potential correlations of the myokines GDF-8, IGF-1 and Follistatin with female sexual hormones and likewise possible interactions with combined oral contraceptives (Dienogest and Ethyl Estradiol) intake. We obtained serum samples of young healthy women to measure hormone correlations. Furthermore, we simulated combined oral contraceptive blood circulating hormone concentrations to identify myogenic effects on HSkM in vitro. GDF-8, IGF-1 and Follistatin showed concentration correlations (p = .005) in overall patients' serum, while Follistatin as a promyogenic protein additionally showed a positive correlation with testosterone and estradiol (p < .05). Lower GDF-8 levels were also linked to a higher BMI (p = .009). Upon combined oral contraceptives (COC) intake, patients showed decreased GDF-8 (p = .006) but increased Follistatin (p = .0001) concentrations compared to patients without COC intake. In vitro, addition of Ethyl Estradiol and Dienogest to HSkM cells revealed a pro-myogenic, proliferative, chemosensitized pattern. Our data support a pro-myogenic effect of combined oral contraceptives.

Burns: modified metabolism and the nuances of nutrition therapy.

OBJECTIVE: To review the effects of burn injury on nutritional requirements and how this can best be supported in a healthcare setting. METHOD: A literature search for articles discussing nutrition and/or metabolism following burn injury was carried out. PubMed, Embase and Web of Science databases were searched using the key search terms 'nutrition' OR 'metabolism' AND 'burn injury' OR 'burns'. There was no limitation on the year of publication. RESULTS: A total of nine articles met the inclusion criteria, the contents of which are discussed in this manuscript. CONCLUSION: Thermal injury elicits the greatest metabolic response, among all traumatic events, in critically ill patients. In order to ensure burn patients can meet the demands of their increased metabolic rate and energy expenditure, adequate nutritional support is essential. Burn injury results in a unique pathophysiology, involving alterations in endocrine, inflammatory, metabolic and immune pathways and nutritional support needed during the inpatient stay varies depending on burn severity and idiosyncratic patient physiologic parameters.

[Elevation of Myostatin as a Potential Marker for Compartment Syndrome in Electrical Injuries]. / Myostatin als potenzieller Marker für das Kompartmentsyndrom bei elektrischen Verletzungen.

INTRODUCTION: Electrical accidents and particularly subsequent compartment syndromes are challenging injuries for clinical treatment. Creatinine kinase (CK) and myoglobin are known lab parameters to detect a compartment syndrome. METHODS: We followed up patients with electrical injuries between the years 2006 and 2016 at our burn unit. We aimed to analyse the role of myostatin as marker for compartment syndrome through serum measurements within 48 hours after injury. RESULTS: We collected data from 24 patients hospitalised with high-voltage electrical injury. All patients were male. We measured myostatin in 14 of these patients. While CK-MB (creatinine kinase muscle-brain type [MB]) showed no significant correlation to compartment syndrome, CK and myostatin gave highly significant increases. Interestingly, myostatin was significantly increased in electrical injuries but not burn injuries, while CK did not show a significant difference. CONCLUSION: Thus, besides CK, myostatin can serve as reliable early marker for compartment syndrome in electrical injuries.

Burn Care in the Greek and Roman Antiquity.

The last century brought about more rapid new developments in the treatment of burns, which significantly lowered the mortality of burn injuries. However, burns were already treated in antiquity, where the threshold from spirituality to scientific medicine originated. The existing literature on burn treatment is very limited and there are many cross-references, some of them incorrect. The aim of this work by an interdisciplinary team of historians and physicians is to offer a more precise reproduction of the burn treatment of Greek and Roman antiquity using original texts in context and with a modern scientific background. There are many sources from ancient doctors on the subject of burn treatment, as well as the treatment of burned-out wounds and frostbite, which have not yet been mentioned. The literature research also showed an understanding of scientific contexts in ancient medicine, such as antiseptics or rheology. Interestingly, there was a change in burn medicine from everyday Greek medicine to Roman military medicine with other burn patterns. The care of patients using analgetics and the therapy of burn shock arose from the literature. The ancient world is considered to be the foundation of medicine, but it is believed to have been based mainly on shamanism rather than science. However, already more than two millennia ago, burns were correctly assessed and treated according to today's scientific standards and scientific relationships were recognized.

Inflammatory processes and elevated osteoclast activity chaperon atrophic non-union establishment in a murine model.

BACKGROUND: Delayed bone healing, especially in long bones poses one of the biggest problems in orthopeadic and reconstructive surgery and causes tremendous costs every year. There is a need for exploring the causes in order to find an adequate therapy. Earlier investigations of human scaphoid non-union revealed an elevated osteoclast activity, accompanied by upregulated levels of TGF-beta and RANKL. Interestingly, scaphoid non-union seemed to be well vascularized. METHODS: In the current study, we used a murine femur-defect model to study atrophic non unions over a time-course of 10 weeks. Different time points were chosen, to gather insights into the dynamic processes of non-union establishment. RESULTS: Histological analyses as well as western blots and qRT-PCR indicated enhanced osteoclast activity throughout the observation period, paralleled by elevated levels of TGF-beta, TNF-alpha, MMP9, MMP13 and RANKL, especially during the early phases of non-union establishment. Interestingly, elevated levels of these mediators decreased markedly over a period of 10 weeks, as inflammatory reaction during non-union establishment seemed to wear out. To our surprise, osteoblastogenesis seemed to be unaffected during early stages of non-union establishment. CONCLUSION: Taken together, we gained first insights into the establishment process of atrophic non unions, in which inflammatory processes accompanied by highly elevated osteoclast activity seem to play a leading role.

Myostatin Upregulation in Patients in the Chronic Phase of Severe Burn Injury Leads to Muscle Cell Catabolism.

BACKGROUND: Burn injury leads to a hypercatabolic response and ultimately muscle wasting with drastic implications for recovery of bodily functions, patient's quality of life (QoL), and long-term survival. Several treatment options target the body's initial stress response, but pharmacological approaches to specifically address muscle protein metabolism have only been poorly investigated. OBJECTIVE: The aim of this study was to assess the role of myostatin and follistatin in burn injury and its possible implications in muscle wasting syndrome. METHODS: We harvested serum from male patients within 48 h and again 9-12 months after severe burn injury (>20% of total body surface area). By means of myoblast cultures, immunohistochemistry, immunoblotting, and scratch assay, the role of myostatin and its implications in post-burn muscle metabolism and myoblast proliferation and differentiation was analyzed. RESULTS: We were able to show increased proliferative and myogenic capacity, decreased myostatin, decreased SMAD 2/3, and elevated follistatin concentrations in human skeletal myoblast cultures with serum conditioned medium of patients in the acute phase of burn injury and conversely a reversed situation in patients in the chronic phase of burn injury. Thus, there is a biphasic response to burn trauma, initiated by an anabolic state and followed by long-term hypercatabolism. CONCLUSION: We conclude that the myostatin signaling pathway plays an important regulative role in burn-associated muscle wasting and that blockade of myostatin could prove to be a valuable treatment approach improving the rehabilitation process, QoL, and long-term survival after severe burn injury.