Improvement of Predictive Scores in Burn Medicine through Different Machine Learning Approaches.

The mortality of severely burned patients can be predicted by multiple scores which have been created over the last decades. As the treatment of burn injuries and intensive care management have improved immensely over the last years, former prediction scores seem to be losing accuracy in predicting survival. Therefore, various modifications of existing scores have been established and innovative scores have been introduced. In this study, we used data from the German Burn Registry and analyzed them regarding patient mortality using different methods of machine learning. We used Classification and Regression Trees (CARTs), random forests, XGBoost, and logistic regression regarding predictive features for patient mortality. Analyzing the data of 1401 patients via machine learning, the factors of full-thickness burns, patient's age, and total burned surface area could be identified as the most important features regarding the prediction of patient mortality following burn trauma. Although the different methods identified similar aspects, application of machine learning shows that more data are necessary for a valid analysis. In the future, the usage of machine learning can contribute to the development of an innovative and precise predictive score in burn medicine and even to further interpretations of relevant data regarding different forms of outcome from the German Burn registry.

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 .

Free-flap reconstruction of the lower limb in octogenarians - A comparative analysis of indications, management, and outcomes.

INTRODUCTION: Impaired microcirculation, along with an increase in chronic medical conditions in the geriatric cohort, may favor the development of soft-tissue defects in the lower extremity and equally impair the options for plastic-reconstructive surgery. In particular, outcome analyses in the increasing patient cohort ≥ 80 years (octogenarians) are limited. METHODS: Setting 80 years as the cutoff, we conducted an age-related outcome analysis of all patients undergoing free-flap reconstruction of the lower extremity from 2014 to 2020, comprising the American Society of Anesthesiologists (ASA) score and Charlson Comorbidity Index (CCI) as the possible outcome predicting factors. RESULTS: During the study period, a total of 424 free flaps were performed in 385 patients (∅: 54.7 years ± 16.1; range: 9-89), including 19 octogenarians. Compared with the younger patient cohort, there was a significantly higher rate of early flap revision (p = 0.023) and flap loss (p = 0.028). Furthermore, the mean length of hospital (60.6 ± 37.6 vs. 51.1 ± 37.0) and intensive care unit/intermediate care stay (6.5 ± 15.0 vs. 3.5 ± 8.5) was extended (n.s.). The ASA score presented an independent predictor for major surgical [odds ratio (OR): 1.66; p = 0.041) and medical complications (OR: 3.97; p<0.001). Neither the CCI nor the ASA served as an independent predictor for total flap loss. CONCLUSION: Free-flap reconstruction of the lower extremity in octogenarians is associated with a higher risk of flap revision and flap loss. Considering the prolonged immobilization associated with increased morbidity following limb amputation, it presents still a reasonable option to achieve limb salvage in carefully chosen patients. An adequate tool to predict the success of free-flap survival is still unavailable.

Digital Media Play a Key Role in Influencing Female Breast Perception.

The female breast is a symbol of femininity and plays a key role in the female body image. However, factors influencing the preferences for different breast shapes and sizes are still not elucidated. In particular, the role of the emerging social media in breast perception has not been analyzed yet. A representative cohort of 1,049 adults completed a web-based questionnaire containing hyperrealistic 3D models of the female breast in the United States. A machine-learning algorithm (Classification and Regression Tree [CART]) was implemented to identify the most influential factors. The study was able to identify the frequency of pornographic and social media consumption as the most influencing factor for altered breast preferences. Although digital media exposure did not alter satisfaction with the own breast among female participants, the tendency to undergo or history of conducted aesthetic surgery correlated with higher access frequency to digital media. Taken together, the overpowering impact of social media and pornographic consumption on the own body image was shown in preference alterations for different anatomical aspects of the breast in the whole population and distorted self-perception about the breast in female participants.

[Analysis of Efficency, Cost Structure and Revenues of ALT Free Flaps in Extremity Reconstruction]. / Analyse der Effizienz, Kostenstruktur und Erlössituation von freien ALT-Lappenplastiken zur Extremitätenrekonstruktion.

Microvascular reconstructions can be lengthy procedures lasting the entire day. As a result of unforeseeable events, the standardization of these procedures can be challenging. Moreover, the length of these procedures varies strongly, which impedes adequate scheduling and, therefore, optimal capacity utilization. Within the years 2018-2020, the duration of ALT free flap extremity reconstructions was correlated with the experience of the microsurgeon (category 1:<50 free flaps life-time experience, category 2: 50-200, category 3:>200) and comorbidities. The resulting costs were compared with the matrix of the German DRG Institute InEK. The surgical experience of the microsurgeon had a significant impact on the duration of surgery in extremity reconstruction. In due consideration of potential complications, category 2 microsurgeons were 45 minutes faster and category 3 microsurgeons were 167 minutes faster than category 1 microsurgeons. Comorbidities, by contrast, did not have a significant impact on procedure duration. Cost analysis revealed deficits for these procedures in relation to the InEK matrix. However, an additional analysis showed that the duration of surgery was within the German average while costs for personnel/OR minute were slightly below the average. According to this calculation, costs for microsurgical training were approximately 1000€/case. The reimbursement for flaps in extremity reconstruction is not entirely mapped in the German DRG system. Given the longer procedure times, microsurgical training is associated with higher costs. Defining the duration of microsurgery based on the level of expertise should result in improved adherence to schedule and more efficient utilization of the valuable operating room time.

Autologous vs. implant-based breast reconstruction after skin- and nipple-sparing mastectomy-A deeper insight considering surgical and patient-reported outcomes.

Introduction: Autologous (ABR) and implant-based breast reconstruction (IBR) represent the most common procedures after skin- and nipple-sparing mastectomy. This cross-sectional study is a comprehensive analysis of ABR and IBR considering surgical and patient-reported outcomes. Patients and methods: Eligible patients underwent breast reconstruction (ABR and IBR) after skin- and nipple-sparing mastectomy between January 2014 and December 2020. Outcome parameters included quality of life (European Organisation for Research and Treatment of Cancer - EORTC - QLQ30, BR23, Breast-Q, CES-D), complication rates, aesthetic result, and breast sensitivity. Results: 108 patients participated in the study (IBR: n = 72, age 48.9 ± 9.9 years; ABR: n = 36, age: 46.6 ± 7.3 years). Mean follow-up was 27.1 ± 9.3 (IBR) and 34.9 ± 20.5 (ABR), respectively. IBR patients suffered significantly more often from major complications (30.6% vs. 8.3%; p = 0.01), while ABR patients underwent secondary procedures significantly more often to improve the aesthetic result (55.6% vs. 29.2%, p = 0.004). Unilateral reconstructions revealed superior aesthetic results in ABR (n.s.), while in bilateral reconstruction IBR tended to score higher (n.s.). Scar evaluation resulted in a better result of IBR in both categories (p < 0.01). Breast sensitivity was severely impaired in both groups. The Breast-Q revealed a significantly higher "patient satisfaction with breast" after ABR (p = 0.033), while the other QoL-tests and subscales showed no significant differences between the two procedures. Conclusion: ABR is associated with a higher patient satisfaction despite the high probability of secondary procedures to improve the aesthetic outcome, whereas IBR-patients suffer more often from major complications. Furthermore, the laterality of reconstruction should be included in the individual decision-making process.

[Fatal necrotizing fasciitis with clostridium perfringens infection following resection of soft tissue sarcoma of the thigh]. / Letaler Verlauf einer fulminanten nekrotisierenden Fasziitis und Clostridium-perfringens-Infektion nach Resektion eines Weichteil-Sarkoms.

We present the case of a 57-year-old male patient with a fatal outcome after resection of a soft tissue sarcoma of the lateral thigh. A polymicrobial surgical site infection with Staphylococcus lugdunensis and Clostridium perfringens caused fulminant necrotising fasciitis with an additional gas gangrene. The patient suffered a severe sepsis with consecutive haemolysis and multiorgan failure. The authors recapitulate the deadly progress of a rarely reported complication after oncological resection. The therapeutic approach and surgical interventions are discussed based on the current literature.

Risk Factors for Occurrence and Relapse of Soft Tissue Sarcoma.

The diagnosis and prognostic outcome of STS pose a therapeutic challenge in an interdisciplinary setting. The treatment protocols are still discussed controversially. This systematic meta-analysis aimed to determine prognostic factors leading to the development and recurrence of STS. Eligible studies that investigated potential risk factors such as smoking, genetic dispositions, toxins, chronic inflammation as well as prognostic relapse factors including radiation, chemotherapy and margins of resection were identified. Data from 24 studies published between 1993 and 2019 that comprised 6452 patients were pooled. A statistically significant effect developing STS was found in overall studies stating a causality between risk factors and the development of STS (p < 0.01). Although subgroup analysis did not meet statistical significances, it revealed a greater magnitude with smoking (p = 0.23), genetic predisposition (p = 0.13) chronic inflammation, (p = 0.20), and toxins (p = 0.14). Secondly, pooled analyses demonstrated a higher risk of relapse for margin of resection (p = 0.78), chemotherapy (p = 0.20) and radiation (p = 0.16); after 3 years of follow-up. Therefore, we were able to identify risk and relapse prognostic factors for STS, helping to diagnose and treat this low incidental cancer properly.

Role of Autonomous Neuropathy in Diabetic Bone Regeneration.

Diabetes mellitus has multiple negative effects on regenerative processes, especially on wound and fracture healing. Despite the well-known negative effects of diabetes on the autonomous nervous system, only little is known about the role in bone regeneration within this context. Subsequently, we investigated diabetic bone regeneration in db-/db- mice with a special emphasis on the sympathetic nervous system of the bone in a monocortical tibia defect model. Moreover, the effect of pharmacological sympathectomy via administration of 6-OHDA was evaluated in C57Bl6 wildtype mice. Diabetic animals as well as wildtype mice received a treatment of BRL37344, a ß3-adrenergic agonist. Bones of animals were examined via µCT, aniline-blue and Masson-Goldner staining for new bone formation, TRAP staining for bone turnover and immunoflourescence staining against tyrosinhydroxylase and stromal cell-derived factor 1 (SDF-1). Sympathectomized wildtype mice showed a significantly decreased bone regeneration, just comparable to db-/db- mice. New bone formation of BRL37344 treated db-/db- and sympathectomized wildtype mice was markedly improved in histology and µCT. Immunoflourescence stainings revealed significantly increased SDF-1 due to BRL37344 treatment in diabetic animals and sympathectomized wildtypes. This study depicts the important role of the sympathetic nervous system for bone regenerative processes using the clinical example of diabetes mellitus type 2. In order to improve and gain further insights into diabetic fracture healing, ß3-agonist BRL37344 proved to be a potent treatment option, restoring impaired diabetic bone regeneration.

Inhibition of Pathological Increased Matrix Metalloproteinase (MMP) Activity for Improvement of Bone Regeneration in Diabetes.

Patients with diabetes suffer from poor fracture healing. Molecular reasons are not fully understood and our previous gene expression microarray analyses of regenerating bones from mice with type 2 diabetes (db-/db-) revealed accelerated activation of pathways concerning matrix metalloproteases (MMPs). Thus, we picked out the pathological MMP acceleration as a target for profound gene expression analyses and additional therapeutic intervention in the present study. In the first part, gene expression of ECM degrading proteinases and inhibitors was investigated three and seven days postoperatively. Mmp3, Mmp9, Mmp13 and gene expression of MMP inhibitor Timp2 was significantly higher in regenerating bone fractures of db-/db- compared to wild type animals. Timp1 and metalloproteinase AdamTS4 showed no differences. In the second part, we locally applied a single dose (1 µL of 5 µM solution) of the broad-spectrum molecular MMP inhibitor Marimastat on tibial defects in db-/db-. We performed immunohistochemical and histological stainings seven days post operation. Impaired bone healing, collagen content, angiogenesis, and osteoclast invasion in db-/db- were restored significantly by application of Marimastat compared to PBS controls (n = 7/group). Hence, local intervention of bone defects by the molecular MMP inhibitor Marimastat might be an alternative therapeutic intervention for bone healing in diabetes.

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 .

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.

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.

Posttraumatic Lymphedema after Open Fractures of the Lower Extremity-A Retrospective Cohort Analysis.

Secondary lymphedema is a very common clinical issue with millions of patients suffering from pain, recurrent skin infections, and the constant need for a decongestive therapy. Well-established as a consequence of oncologic procedures, secondary lymphedema is also a well-known phenomenon after trauma. However, precise epidemiological data of lymphedema progress upon severe extremity injuries are still missing. In the present work, we analyzed a patient cohort of 94 individuals who suffered open fractures of the lower extremity and soft tissue injury, of 2nd and 3rd grade according to Tscherne classification, between 2013 and 2019. Typical symptoms of lymphedema have been obtained via interviews and patient medical records in a retrospective cohort analysis. Of all patients, 55% showed symptoms of secondary lymphedema and 14% reported recurrent skin infections, indicating severe lymphedema. Furthermore, comparing patients with and without lymphedema, additional parameters, such as obesity, total number of surgeries, infections, and compartment syndrome, related to lymphedema progress could be identified. According to these data, posttraumatic secondary lymphedema has a highly underestimated clinical prevalence. Further prospective studies are needed to validate this first observation and to identify high-risk groups in order to improve patient's health care.

A Highly Reliable Convolutional Neural Network Based Soft Tissue Sarcoma Metastasis Detection from Chest X-ray Images: A Retrospective Cohort Study.

INTRODUCTION: soft tissue sarcomas are a subset of malignant tumors that are relatively rare and make up 1% of all malignant tumors in adulthood. Due to the rarity of these tumors, there are significant differences in quality in the diagnosis and treatment of these tumors. One paramount aspect is the diagnosis of hematogenous metastases in the lungs. Guidelines recommend routine lung imaging by means of X-rays. With the ever advancing AI-based diagnostic support, there has so far been no implementation for sarcomas. The aim of the study was to utilize AI to obtain analyzes regarding metastasis on lung X-rays in the most possible sensitive and specific manner in sarcoma patients. METHODS: a Python script was created and trained using a set of lung X-rays with sarcoma metastases from a high-volume German-speaking sarcoma center. 26 patients with lung metastasis were included. For all patients chest X-ray with corresponding lung CT scans, and histological biopsies were available. The number of trainable images were expanded to 600. In order to evaluate the biological sensitivity and specificity, the script was tested on lung X-rays with a lung CT as control. RESULTS: in this study we present a new type of convolutional neural network-based system with a precision of 71.2%, specificity of 90.5%, sensitivity of 94%, recall of 94% and accuracy of 91.2%. A good detection of even small findings was determined. DISCUSSION: the created script establishes the option to check lung X-rays for metastases at a safe level, especially given this rare tumor entity.

Myostatin Deficiency Protects C2C12 Cells from Oxidative Stress by Inhibiting Intrinsic Activation of Apoptosis.

Ischemia reperfusion (IR) injury remains an important topic in clinical medicine. While a multitude of prophylactic and therapeutic strategies have been proposed, recent studies have illuminated protective effects of myostatin inhibition. This study aims to elaborate on the intracellular pathways involved in myostatin signaling and to explore key proteins that convey protective effects in IR injury. We used CRISPR/Cas9 gene editing to introduce a myostatin (Mstn) deletion into a C2C12 cell line. In subsequent experiments, we evaluated overall cell death, activation of apoptotic pathways, ROS generation, lipid peroxidation, intracellular signaling via mitogen-activated protein kinases (MAPKs), cell migration, and cell proliferation under hypoxic conditions followed by reoxygenation to simulate an IR situation in vitro (hypoxia reoxygenation). It was found that mitogen-activated protein kinase kinase 3/6, also known as MAPK/ERK Kinase 3/6 (MEK3/6), and subsequent p38 MAPK activation were blunted in C2C12-Mstn-/- cells in response to hypoxia reoxygenation (HR). Similarly, c-Jun N-terminal kinase (JNK) activation was negated. We also found the intrinsic activation of apoptosis to be more important in comparison with the extrinsic activation. Additionally, intercepting myostatin signaling mitigated apoptosis activation. Ultimately, this research validated protective effects of myostatin inhibition in HR and identified potential mediators worth further investigation. Intercepting myostatin signaling did not inhibit ROS generation overall but mitigated cellular injury. In particular, intrinsic activation of apoptosis origination from mitochondria was alleviated. This was presumably mediated by decreased activation of p38 caused by the diminished kinase activity increase of MEK3/6. Overall, this work provides important insights into HR signaling in C2C12-Mstn-/- cells and could serve as basis for further research.

[Necrotizing Fasciitis]. / Die nekrotisierende Fasziitis.

Necrotizing fasciitis (NF) is a soft tissue infection spreading along the fasciae to the surrounding subcutaneous fat, overlying skin and finally musculature, that may rapidly lead to septic shock and death. In order to avoid a massive systemic spread of the infective process, an immediate and extensive radical debridement of necrotic tissues is mandatory complemented by a broad spectrum intravenous antibiotic therapy. Nevertheless, mortality is persistently high at 20-40 %. Because of the lack of specific clinical features in the initial stage of the disease, it is often underestimated or confused with cellulitis or abscess. Hence, early diagnosis is missed or delayed in 85 %-100 % of cases with the passage of valuable time.The aim of this review is to give an overview of the clinical and laboratory elements to be considered for diagnosis as well as the essential therapeutic patterns.

Deficiency of myostatin protects skeletal muscle cells from ischemia reperfusion injury.

Ischemia reperfusion (IR) injury plays a pivotal role in many diseases and leads to collateral damage during surgical interventions. While most studies focus on alleviating its severity in the context of brain, liver, kidney, and cardiac tissue, research as regards to skeletal muscle has not been conducted to the same extent. In the past, myostatin (MSTN), primarily known for supressing muscle growth, has been implicated in inflammatory circuits, and research provided promising results for cardiac IR injury mitigation by inhibiting MSTN cell surface receptor ACVR2B. This generated the question if interrupting MSTN signaling could temper IR injury in skeletal muscle. Examining human specimens from free myocutaneous flap transfer demonstrated increased MSTN signaling and tissue damage in terms of apoptotic activity, cell death, tissue edema, and lipid peroxidation. In subsequent in vivo MstnLn/Ln IR injury models, we identified potential mechanisms linking MSTN deficiency to protective effects, among others, inhibition of p38 MAPK signaling and SERCA2a modulation. Furthermore, transcriptional profiling revealed a putative involvement of NK cells. Collectively, this work establishes a protective role of MSTN deficiency in skeletal muscle IR injury.