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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 .
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Implantes de Mama , Mamoplastia , Mama/cirurgia , Censos , Estética , Feminino , Humanos , Masculino , Mamoplastia/métodos , Mamilos/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
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.
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Anticoncepcionais Orais Combinados/farmacologia , Folistatina/sangue , Hormônios Esteroides Gonadais/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Músculo Esquelético/efeitos dos fármacos , Miostatina/sangue , Adulto , Células Cultivadas , Feminino , Humanos , Músculo Esquelético/metabolismo , Miogenina/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismoRESUMO
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.
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Síndromes Compartimentais , Miostatina , Biomarcadores , Síndromes Compartimentais/diagnóstico , Síndromes Compartimentais/cirurgia , Humanos , Masculino , MioglobinaRESUMO
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.
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Queimaduras , Queimaduras/terapia , Grécia , HumanosRESUMO
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.
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Fraturas não Consolidadas/patologia , Inflamação/patologia , Osteoclastos/patologia , Animais , Atrofia , Proliferação de Células , Citocinas/sangue , Modelos Animais de Doenças , Feminino , Fraturas não Consolidadas/sangue , Inflamação/sangue , Mediadores da Inflamação/sangue , Mediadores da Inflamação/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Osteoblastos/patologia , Osteoprotegerina/metabolismo , Ligante RANK/metabolismoRESUMO
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.
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Queimaduras/metabolismo , Miostatina/fisiologia , Síndrome de Emaciação/etiologia , Adolescente , Adulto , Idoso , Queimaduras/complicações , Queimaduras/psicologia , Células Cultivadas , Doença Crônica , Folistatina/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/metabolismo , Mioblastos/metabolismo , Qualidade de Vida , Transdução de Sinais/fisiologia , Proteína Smad2/análise , Regulação para Cima , Adulto JovemRESUMO
Burn injuries represent a special type of injury that requires special expertise. Both in adequate wound treatment and in intensive medical care, there are various special features that must be considered and due to which treatment by experienced medical personnel is necessary. In the clinical, but also in the preclinical course, the most important points in the treatment of the burn injury should be known to be able to guarantee adequate treatment. In this context, in addition to the knowledge of the different degrees of burns, the estimation of the burned body surface area (VKOF) is essential. Intensive medical treatment as well as surgical therapy of deep burn wounds should then be performed in a burn center. The article provides an overview of the classifications of burn injuries, the management of wound care, the various therapeutic options, both conservative and surgical, and the special features of burn disease.
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Cuidados Críticos , Pessoal de Saúde , HumanosRESUMO
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.
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Retalhos de Tecido Biológico , Procedimentos de Cirurgia Plástica , Idoso de 80 Anos ou mais , Humanos , Idoso , Octogenários , Estudos Retrospectivos , Procedimentos de Cirurgia Plástica/efeitos adversos , Extremidade Inferior/cirurgia , Retalhos de Tecido Biológico/cirurgia , Salvamento de Membro/efeitos adversos , Doença Crônica , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Resultado do TratamentoRESUMO
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.
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Internet , Mídias Sociais , Adulto , Feminino , Humanos , Estados Unidos , Aprendizado de Máquina , PercepçãoRESUMO
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.
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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.
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Bone regeneration and fracture healing are impaired in diabetic patients due to defective functions of associated cells. Thus, the search for molecular causes and new treatment strategies are of particular clinical relevance. We investigated the gene expression profile of bones from type 2 diabetic (db- /db- ) mice and wild-type (wt) mice by comparative microarray analyses before and after placing tibial defects and examined the expression of several osteogenesis- and osteoclastogenesis-related markers by quantitative real-time polymerase chain reaction. In regenerating wt bones, pathways related to, for example, inhibition of matrix metalloproteases were activated, whereas in db- /db- bones activation of pathways related to, for example, osteoarthritis, transforming growth factor-beta (Tgfb), or hypoxia-inducible factor 1a were detected during regeneration. We defined the Tgfb pathway as a potential therapeutic target and locally applied a single dose (0.5 µg) of the Tgfb 1, 2, and 3 neutralizing antibody 1D11 on tibial defects in db- /db- mice (n = 7). Seven days postoperation, histological and immunohistochemical stainings were performed. Decreased bone regeneration, osteogenic differentiation, osteoclast invasion, and angiogenesis in db- /db- mice were significantly restored by local 1D11 application in comparison to the phosphate-buffered saline controls. Thus, local treatment of db- /db- bony defects with Tgfb neutralizing antibody 1D11 might be considered a good candidate for the successful acceleration of bone regeneration.
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Diabetes Mellitus , Osteogênese , Aceleração , Animais , Anticorpos Neutralizantes/farmacologia , Regeneração Óssea , Camundongos , Fator de Crescimento Transformador beta/metabolismoRESUMO
BACKGROUND: Body image research deals a lot with awareness of the body as an entity. Studies that consider individual anatomical aspects and place them in an intercultural context are rarely present. METHODS: For this purpose, general data, body perception and judgment of body images from 2163 (48% female and 52% male) participants from Germany, Nigeria, the USA and Japan were evaluated as part of a survey. RESULTS: There were clear differences in the personal body image of the participants' own buttocks, the buttocks as a beauty ideal and the way in which dissatisfaction was dealt with in different countries. In addition to sexual well-being (importance score: 0.405 a.u.), the country of origin (0.353), media consumption (0.042) and one's own weight (0.069) were also identified as influencing factors for satisfaction with one's own buttocks. A clear evolution could be derived regarding a WHR (waist-to-hip ratio) of well below 0.7, which was consistently favored by the participants but also propagated by influencers through images (p < 0.001). In this context, participants who indicated celebrities as role models for the buttocks showed a correspondingly high level of dissatisfaction with their own buttocks (R = -0.207, p < 0.001, ρ = -0.218). CONCLUSION: Overall, a highly significant correlation was shown between the consumption frequency of Instagram, TikTok and pornography with the negative perception of women's own buttocks.
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Imagem Corporal , Satisfação Pessoal , Feminino , Humanos , Masculino , Nádegas , Japão , Nigéria , AlemanhaRESUMO
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.
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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.
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Apoptose , Citoproteção , Miostatina/deficiência , Estresse Oxidativo , Aldeídos/metabolismo , Animais , Hipóxia Celular , Linhagem Celular , Movimento Celular , Proliferação de Células , Replicação do DNA , Peroxidação de Lipídeos , MAP Quinase Quinase 3/metabolismo , MAP Quinase Quinase 6/metabolismo , Camundongos , Miostatina/metabolismo , Estresse Nitrosativo , Oxigênio , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Tirosina/análogos & derivados , Tirosina/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
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.
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Receptores de Activinas Tipo II/genética , Traumatismos Cardíacos/genética , Miostatina/genética , Traumatismo por Reperfusão/genética , Animais , Modelos Animais de Doenças , Traumatismos Cardíacos/patologia , Traumatismos Cardíacos/cirurgia , Humanos , Fígado/metabolismo , Fígado/patologia , Camundongos , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/patologia , Miostatina/deficiência , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/cirurgia , Transdução de Sinais/genéticaRESUMO
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.
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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.
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Impaired bone homeostasis caused by osteomyelitis provokes serious variations in the bone remodeling process, thereby involving multiple inflammatory cytokines to activate bone healing. We have previously established a mouse model for post-traumatic osteomyelitis and studied bone regeneration after sufficient debridement. Moreover, we could further characterize the postinfectious inflammatory state of bony defects after debridement with elevated osteoclasts and decreased bone formation despite the absence of bacteria. In this study, we investigated the positive effects of Wnt-pathway modulation on bone regeneration in our previous established mouse model. This was achieved by local application of Wnt3a, a recombinant activator of the canonical Wnt-pathway. Application of Wnt3a could enhance new bone formation, which was verified by histological and µ-CT analysis. Moreover, histology and western blots revealed enhanced osteoblastogenesis and downregulated osteoclasts in a RANKL-dependent manner. Further analysis of Wnt-pathway showed downregulation after bone infections were reconstituted by application of Wnt3a. Interestingly, Wnt-inhibitory proteins Dickkopf 1 (DKK1), sclerostin, and secreted frizzled protein 1 (sFRP1) were upregulated simultaneously to Wnt-pathway activation, indicating a negative feedback for active form of Beta-catenin. In this study, we could demonstrate enhanced bone formation in defects caused by post-traumatic osteomyelitis after Wnt3a application. KEY MESSAGES: Osteomyelitis decreases bone regeneration Wnt3a restores bone healing after infection Canonical Wnt-pathway activation with negative feedback.
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Regeneração Óssea/efeitos dos fármacos , Osteomielite/metabolismo , Osteomielite/terapia , Proteínas Recombinantes/administração & dosagem , Proteína Wnt3A/administração & dosagem , Animais , Desbridamento , Gerenciamento Clínico , Modelos Animais de Doenças , Suscetibilidade a Doenças , Feminino , Imunofluorescência , Glicogênio Sintase Quinase 3 beta/metabolismo , Processamento de Imagem Assistida por Computador , Masculino , Camundongos , Osteoclastos/metabolismo , Osteogênese/genética , Osteomielite/diagnóstico , Osteomielite/etiologia , Via de Sinalização Wnt/efeitos dos fármacos , Microtomografia por Raio-X , beta Catenina/metabolismoRESUMO
Acute ischemia reperfusion injury in skeletal muscle remains an important issue in several fields of regenerative medicine. Thus, a valid model is essential to gain deeper insights into pathophysiological relations and evaluate possible treatment options. While the vascular anatomy of mice regularly prevents sufficient vessel occlusion by invasive methods, there is a multitude of existing models to induce ischemia reperfusion injury without surgical procedures. Since there is no consensus on which model to prefer, this study aims to develop and evaluate a novel, optimized low-pressure tourniquet model. C57BL/6 mice underwent an ischemic procedure by either tourniquet or invasive artery clamping. A sham group served as control. With exception of the sham group, mice underwent 2 hours of ischemia followed by 4 hours of reperfusion. Groups were compared using microcirculatory and spectroscopic measurements, distinctions in tissue edema, histological and immunohistochemical analyses. Both procedures led to a significant decrease in tissue blood flow (- 97% vs. - 86%) and oxygenation (- 87% vs. - 75%) with a superiority of the low-pressure tourniquet. Tissue edema in the tourniquet cohort was significantly increased (+ 59%), while the increase in the clamping cohort was non-significant (+ 7%). Haematoxylin Eosin staining showed significantly more impaired muscle fibers in the tourniquet group (+ 77 p.p. vs. + 11 p.p.) and increased neutrophil infiltration/ROI (+ 51 vs. + 8). Immunofluorescence demonstrated an equal increase of p38 in both groups (7-fold vs. 8-fold), while the increase in apoptotic markers (Caspase-3, 3-Nitrotyrosine, 4-Hydroxynonenal) was significantly higher in the tourniquet group. The low-pressure tourniquet has been proven to produce reproducible and thus reliable ischemia reperfusion injury. In addition, significantly less force was needed than previously stated. It is therefore an important instrument for studying the pathophysiology of ischemia reperfusion injury and for the development of prophylactic as well as therapeutic interventions.