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INTRODUCTION: Despite advancements in transplant immunology and vascularized composite allotransplantation (VCA), the longevity of allografts remains hindered by the challenge of allograft rejection. The acute-phase response, an immune-inflammatory reaction to ischemia/reperfusion that occurs directly after allogeneic transplantation, serves as a catalyst for graft rejection. This immune response is orchestrated by acute-phase reactants through intricate crosstalk with the mononuclear phagocyte system. OBJECTIVE: C-reactive protein (CRP), a well-known marker of inflammation, possesses pro-inflammatory properties and exacerbates ischemia/reperfusion injury. Thus, we investigated how CRP impacts acute allograft rejection. METHODS: Prompted by clinical observations in facial VCAs, we employed a complex hindlimb transplantation model in rats to investigate the direct impact of CRP on transplant rejection. RESULTS: Our findings demonstrate that CRP expedites allograft rejection and diminishes allograft survival by selectively activating non-classical monocytes. Therapeutic stabilization of CRP abrogates this activating effect on monocytes, thereby attenuating acute allograft rejection. Intravital imagining of graft-infiltrating, recipient-derived monocytes during the early phase of acute rejection corroborated their differential regulation by CRP and their pivotal role in driving the initial stages of graft rejection. CONCLUSION: The differential activation of recipient-derived monocytes by CRP exacerbates the innate immune response and accelerates clinical allograft rejection. Thus, therapeutic targeting of CRP represents a novel and promising strategy for preventing acute allograft rejection and potentially mitigating chronic allograft rejection.
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BACKGROUND: Wide resection remains the cornerstone of localized soft-tissue sarcomas (STS) treatment. Neoadjuvant radiation therapy (NRT) may decrease the risk of local recurrences; however, its effectiveness for different histological STS subtypes has not been systematically investigated. The proposed prospective study evaluates the NRT response in STS using liquid biopsies and the correlation of multiparametric magnetic resonance imaging (mpMRI) with histopathology and immunohistochemistry. METHODS: Patients with localized high-grade STS, who qualify for NRT, are included in this study. LIQUID BIOPSIES: Quantification of circulating tumor DNA (ctDNA) in patient blood samples is performed by targeted next-generation sequencing. Soft-tissue sarcoma subtype-specific panel sequencing in combination with patient-specific exome sequencing allows the detection of individual structural variants and point mutations. Circulating free DNA is isolated from peritherapeutically collected patient plasma samples and ctDNA quantified therein. Identification of breakpoints is carried out using FACTERA. Bioinformatic analysis is performed using samtools, picard, fgbio, and the MIRACUM Pipeline. MPMRI: Combination of conventional MRI sequences with diffusion-weighted imaging, intravoxel-incoherent motion, and dynamic contrast enhancement. Multiparametric MRI is performed before, during, and after NRT. We aim to correlate mpMRI data with the resected specimen's macroscopical, histological, and immunohistochemical findings. RESULTS: Preliminary data support the notion that quantification of ctDNA in combination with tumor mass characterization through co-registration of mpMRI and histopathology can predict NRT response of STS. CLINICAL RELEVANCE: The methods presented in this prospective study are necessary to assess therapy response in heterogeneous tumors and lay the foundation of future patient- and tumor-specific therapy concepts. These methods can be applied to various tumor entities. Thus, the participation and support of a wider group of oncologic surgeons are needed to validate these findings on a larger patient cohort.
Subject(s)
Circulating Tumor DNA , Multiparametric Magnetic Resonance Imaging , Sarcoma , Soft Tissue Neoplasms , Humans , Circulating Tumor DNA/genetics , Prospective Studies , Neoadjuvant Therapy , Sarcoma/diagnostic imaging , Sarcoma/genetics , Sarcoma/radiotherapyABSTRACT
This case report describes the interdisciplinary treatment of a complex shrapnel injury to the right femur of an 18-year-old Ukrainian soldier. This open multifragmentary fractur of the femur with a large bone defect, soft tissue damage and osteomyelitis was complicated by several multidrug-resistant bacteria, including Acinetobacter baumanii, which could not be eradicated by antibiotic treatment. Sterility was only achieved by multiple radical debridement and by negative pressure wound therapy with instillation (NPWTi) using hypochlorous acid. The femur was then reconstructed with a chimeric double-barrel fibula free flap. This report highlights the importance of multimodal antimicrobial wound treatments in an era of increasing antibiotic resistance to enable a successful und functional reconstruction of complex and infected fractures.
Subject(s)
Fractures, Bone , Free Tissue Flaps , Negative-Pressure Wound Therapy , Humans , Adolescent , Debridement , Fractures, Bone/surgery , Lower Extremity , Anti-Bacterial Agents/therapeutic use , Treatment OutcomeABSTRACT
BACKGROUND: Breast implant-associated squamous cell carcinoma (BIA-SCC) is being discussed as a distinct malignant tumour entity originating from the implant capsule. The FDA and the ASPS published a safety communication on BIA-SCC in 2022, with a first case report of BIA-SCC having been published in the 1990s. This manuscript summarises the current scientific data on this rare tumour entity. MATERIAL AND METHODS: This systematic literature review from two independent databases includes all publications of cases with histopathologically confirmed BIA-SCC. Data extraction included study design, demographic data, implant information and details regarding diagnosis and treatment. RESULTS: Nineteen cases of BIA-SCC with a mean age of 57±10 years were reported in 16 publications. In most cases, the indication was aesthetic augmentation (n=13). Both silicone (n=11) and saline (n=7) implants with different surfaces (smooth n=3, textured n=3, polyurethane n=1) were used. Symptoms such as unilateral swelling (n=18), pain (n=14) and erythema (n=5) occurred on an average of 23±9 years after implantation. Imaging showed fluid collection (n=8) or a tumour mass (n=4) around the breast implant. The most common surgical treatment was explantation with capsulectomy. Metastasis was described in 6 cases. CONCLUSIONS: BIA-SCC is a malignant tumour entity associated with breast implant capsules. Based on current low-quality data (level of evidence class V), no definitive conclusion regarding correlation and causality of SCC in patients with breast implants can be drawn. There is an urgent need for national and international breast implant and breast cancer registries to obtain valid data on the incidence, pathogenesis and clinical presentation of rare tumour entities.
Subject(s)
Breast Implantation , Breast Implants , Breast Neoplasms , Carcinoma, Squamous Cell , Humans , Middle Aged , Aged , Female , Breast Implants/adverse effects , Breast Neoplasms/surgery , Breast Neoplasms/pathology , Breast Implantation/adverse effects , Device Removal/adverse effects , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/surgeryABSTRACT
BACKGROUND: Dermatofibrosarcoma protuberans is a rare, slow-growing soft-tissue malignancy originating in the dermis that is characterized by an infiltrating growth pattern with a marked tendency of local recurrence. Complete surgical resection with pathological margin clearance must be achieved to reduce the risk of tumor recurrence. Resulting defects often require extensive reconstructive procedures. Dermatofibrosarcoma protuberans of the scalp poses particular challenges owing to the proximity to the face and brain. This study aims to evaluate treatment options and proposes an algorithm for management of scalp dermatofibrosarcoma protuberans based on a multicentric case series and systematic review of the literature. METHODS: A retrospective multicentric chart analysis of 11 patients with scalp dermatofibrosarcoma protuberans who presented within the last 20 years was performed regarding demographic data, pathological tumor characteristics, and surgical management (resection and reconstruction). Additionally, a further 42 patients (44 cases) were identified through a systematic Preferred Reporting Systems for Systematic Reviews and Meta-Analysis-based review of the literature searching the Medline and Embase databases. RESULTS: In total, 30 cases were classified as primary and 20 cases as recurring scalp dermatofibrosarcoma protuberans (data from 5 cases were missing). The median tumor size was 24 cm2 (interquartile range 7.8-64), and the median defect size was 55.8 cm2 (interquartile range 48-112). Recurring scalp dermatofibrosarcoma protuberans was more often associated with invasion of deeper layers and required more extensive tumor resection to achieve negative margins. Within the subgroup that was managed with peripheral and deep en face margin assessment, no recurrence was observed. Most patients required local (41. 8%) or free flap (27.8%) reconstruction after dermatofibrosarcoma protuberans resection. CONCLUSION: Whenever possible, peripheral and deep en face margin assessment-based techniques should be preferred for resection of scalp dermatofibrosarcoma protuberans because they provide superior oncological safety while preserving uninvolved tissue. Patients with locally advanced and recurring scalp dermatofibrosarcoma protuberans often require multidisciplinary treatment including neurosurgery, radiotherapy, and microvascular reconstructive surgery and should be referred to a specialized center.
Subject(s)
Dermatofibrosarcoma , Skin Neoplasms , Humans , Dermatofibrosarcoma/surgery , Dermatofibrosarcoma/pathology , Neoplasm Recurrence, Local/surgery , Neoplasm Recurrence, Local/pathology , Retrospective Studies , Scalp/surgery , Scalp/pathology , Skin Neoplasms/pathologyABSTRACT
C-reactive protein (CRP) is an early-stage acute phase protein and highly upregulated in response to inflammatory reactions. We recently identified a novel mechanism that leads to a conformational change from the native, functionally relatively inert, pentameric CRP (pCRP) structure to a pentameric CRP intermediate (pCRP*) and ultimately to the monomeric CRP (mCRP) form, both exhibiting highly pro-inflammatory effects. This transition in the inflammatory profile of CRP is mediated by binding of pCRP to activated/damaged cell membranes via exposed phosphocholine lipid head groups. We designed a tool compound as a low molecular weight CRP inhibitor using the structure of phosphocholine as a template. X-ray crystallography revealed specific binding to the phosphocholine binding pockets of pCRP. We provide in vitro and in vivo proof-of-concept data demonstrating that the low molecular weight tool compound inhibits CRP-driven exacerbation of local inflammatory responses, while potentially preserving pathogen-defense functions of CRP. The inhibition of the conformational change generating pro-inflammatory CRP isoforms via phosphocholine-mimicking compounds represents a promising, potentially broadly applicable anti-inflammatory therapy.
Subject(s)
C-Reactive Protein , Phosphorylcholine , Humans , Phosphorylcholine/pharmacology , Inflammation/drug therapy , Inflammation/metabolism , Cell Membrane/metabolism , Anti-Inflammatory AgentsABSTRACT
A central element of modern sarcoma therapy is complete surgical tumor resection with an adequate safety margin, embedded in an interdisciplinary multimodal therapy concept. Along with ensuring patient survival, functional limb preservation is an important goal for sarcomas of the extremities. This review provides an overview of the relevant literature on indications and goals of reconstructive options, the scope and contribution of microsurgical reconstructive procedures, and the associated interdisciplinary decision making and workup. Furthermore, the impact of (neo)-adjuvant therapy on reconstructive decisions will be highlighted. These aspects will be illustrated by four comprehensive case studies that demonstrate both useful strategies and the need for individually tailored therapies. Nowadays, extremity-preserving therapy is possible in more than 90% of sarcomas. Technical and procedural innovations such as microsurgery and microsurgical reconstructive procedures have significantly contributed to this evolution of therapy.
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Soft tissue sarcomas (STS) are rare tumors of mesenchymal origin with high mortality. After curative resection, about one third of patients suffer from distant metastases. Tumor follow-up only covers a portion of recurrences and is associated with high cost and radiation burden. For metastasized STS, only limited inferences can be drawn from imaging data regarding therapy response. To date there are no established and evidence-based diagnostic biomarkers for STS due to their rarity and diversity. In a proof-of-concept study, circulating tumor DNA (ctDNA) was quantified in (n = 25) plasma samples obtained from (n = 3) patients with complex karyotype STS collected over three years. Genotyping of tumor tissue was performed by exome sequencing. Patient-individual mini-panels for targeted next-generation sequencing were designed encompassing up to 30 mutated regions of interest. Circulating free DNA (cfDNA) was purified from plasma and ctDNA quantified therein. ctDNA values were correlated with clinical parameters. ctDNA concentrations correlated with the tumor burden. In case of full remission, no ctDNA was detectable. Patients with a recurrence at a later stage showed low levels of ctDNA during clinical remission, indicating minimal residual disease. In active disease (primary tumor or metastatic disease), ctDNA was highly elevated. We observed direct response to treatment, with a ctDNA decline after tumor resections, radiotherapy, and chemotherapy. Quantification of ctDNA allows for the early detection of recurrence or metastases and can be used to monitor treatment response in STS. Therapeutic decisions can be made earlier, such as the continuation of a targeted adjuvant therapy or the implementation of extended imaging to detect recurrences. In metastatic disease, therapy can be adjusted promptly in case of no response. These advantages may lead to a survival benefit for patients in the future.
Subject(s)
Cell-Free Nucleic Acids , Circulating Tumor DNA , Sarcoma , Soft Tissue Neoplasms , Biomarkers, Tumor/genetics , Circulating Tumor DNA/genetics , Humans , Karyotype , Mutation , Sarcoma/diagnosis , Sarcoma/geneticsABSTRACT
Atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) are two distinct designations for a rare dermal sarcoma entity. These tumors arise predominantly in the sun-damaged skin of elderly patients. Although both AFX and PDS have a similar clinical presentation and nearly identical genetic features, they significantly differ in prognosis. Here we present a retrospective single-center chart review analyzing the outcomes of patients treated for dermal sarcoma. The radicality of the tumor-resection extent and soft-tissue reconstructive options were assessed. Patients between January 2010 and August 2021 were included. We recorded resection margins, tumor recurrence, overall survival, number of operations until complete tumor resection, and reconstructive procedures; any complications were recorded. Furthermore, we analyzed a subgroup of patients with satellite metastases. A total of 32 patients met the inclusion criteria (30 male, 2 female, median age of 77.5 years (interquartile range (IQR) 74-81)). Histopathology revealed AFX in 14 patients and PDS in 18 patients. Margin-free resection was achieved in 31 cases, and 27 patients were remission free over the reported period. The local recurrence rate was 5, and distant metastasis was detected in four cases. Of all the PDS cases, nine presented with satellite metastasis. No AFX had satellite metastases. Due to their rarity, managing these tumors requires an interdisciplinary setting in a specialized sarcoma center.
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This study investigated eye movement patterns using eye tracking technology when looking at preoperative and postoperative images of patients that underwent bilateral periorbital cosmetic surgery. The sequence of facial recognition before surgery was periorbital-nose-perioral, whereas following surgery it was nose-periorbital-perioral. This study revealed that the sequence of facial feature recognition is influenced by the aesthetic liking of the observer and that alteration to facial features influences the sequence of facial feature recognition. The eye movement pattern, however, seems to follow the internal representation of beauty where aesthetically pleasing facial features are observed later during first image exposure and are viewed shorter.
Subject(s)
Blepharoplasty , Facial Recognition , Blepharoplasty/adverse effects , Blepharoplasty/methods , Eye-Tracking Technology , Eyelids , Humans , Skin TransplantationABSTRACT
BACKGROUND: Synovial sarcoma (SS) is a malignant soft tissue tumor of mesenchymal origin that frequently occurs in young adults. Translocation of the SYT gene on chromosome 18 to the SSX genes on chromosome X leads to the formation of oncogenic fusion genes, which lead to initiation and proliferation of tumor cells. The detection and quantification of circulating tumor DNA (ctDNA) can serve as a non-invasive method for diagnostics of local or distant tumor recurrence, which could improve survival rates due to early detection. METHODS: We developed a subtype-specific targeted next-generation sequencing (NGS) approach specifically targeting SS t(X;18)(p11;q11), which fuses SS18 (SYT) in chromosome 18 to SSX1 or SSX2 in chromosome x, and recurrent point mutations. In addition, patient-specific panels were designed from tumor exome sequencing. Both approaches were used to quantify ctDNA in patients' plasma. RESULTS: The subtype-specific assay allowed detection of somatic mutations from 25/25 tumors with a mean of 1.68 targetable mutations. The minimal limit of detection was determined at a variant allele frequency of 0.05%. Analysis of 29 plasma samples from 15 tumor patients identified breakpoint ctDNA in 6 patients (sensitivity: 40%, specificity 100%). The addition of more mutations further increased assay sensitivity. Quantification of ctDNA in plasma samples (n = 11) from one patient collected over 3 years, with a patient-specific panel based on tumor exome sequencing, correlated with the clinical course, response to treatment and tumor volume. CONCLUSIONS: Targeted NGS allows for highly sensitive tumor profiling and non-invasive detection of ctDNA in SS patients, enabling non-invasive monitoring of tumor dynamics.
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Autologous fillet flaps are a common reconstructive option for large defects after forequarter amputation (FQA) due to advanced local malignancy or trauma. The inclusion of osseous structures into these has several advantages. This article therefore systematically reviews reconstructive options after FQA, using osteomusculocutaneous fillet flaps, with emphasis on personalized surgical technique and outcome. Additionally, we report on a case with an alternative surgical technique, which included targeted muscle reinnervation (TMR) of the flap. Our literature search was conducted in the PubMed and Cochrane databases. Studies that were identified were thoroughly scrutinized with regard to relevance, resulting in the inclusion of four studies (10 cases). FQA was predominantly a consequence of local malignancy. For vascular supply, the brachial artery was predominantly anastomosed to the subclavian artery and the brachial or cephalic vein to the subclavian or external jugular vein. Furthermore, we report on a case of a large osteosarcoma of the humerus. Extended FQA required the use of the forearm for defect coverage and shoulder contour reconstruction. Moreover, we performed TMR. Follow-up showed a satisfactory result and no phantom limb pain. In case of the need for free flap reconstruction after FQA, this review demonstrates the safety and advantage of osteomusculocutaneous fillet flaps. If the inclusion of the elbow joint into the flap is not possible, we recommend the use of the forearm, as described. Additionally, we advocate for the additional implementation of TMR, as it can be performed quickly and is likely to reduce phantom limb and neuroma pain.
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Phagocytosis and the formation of reactive oxygen species (ROS) in phagocytic leukocytes are an effective killing mechanism of the innate host defense. These cellular processes of innate immunity function in a complex interplay with humoral factors. C-reactive protein (CRP) in its activated, monomeric isoform (mCRP) has been shown to activate immune cells via the classical complement pathway. We investigated the complement-dependent effects of monomeric CRP (mCRP) on neutrophils and monocyte subtypes using complement-specific inhibitors by both flow cytometry and confocal fluorescence microscopy. We demonstrate that CRP-induced ROS generation is a conformation-specific and complement-dependent process in leukocyte subsets with classical monocytes as the primary source of ROS amongst human monocyte subsets. Elucidation of this complex interplay of CRP and complement in inflammation pathophysiology might help to improve anti-inflammatory therapeutic strategies.
Subject(s)
C-Reactive Protein/metabolism , Complement Activation/immunology , Complement System Proteins/immunology , Cytotoxicity, Immunologic , Immunity, Innate , Phagocytosis/immunology , Reactive Oxygen Species/metabolism , Host-Pathogen Interactions/immunology , Humans , Leukocytes/immunology , Leukocytes/metabolism , Monocytes/immunology , Monocytes/metabolism , Neutrophils/immunology , Neutrophils/metabolismABSTRACT
BACKGROUND: Since the emergence of the COVID-19 pandemic facecovers have become a common sight. The effect of facecovers on the gaze when looking at faces has not yet been assessed. OBJECTIVES: The aim of the present study was to investigate any potential differences in eye movement pattern in observers exposed to images showing a face without and with a facecover to identify if there is truly a change of gaze when identifying (masked) facial features. METHODS: The eye movement of 64 study participants (28 males and 36 females) with a mean [standard deviation] age of 31.84 [9.0] years was analyzed in this cross-sectional observational study. Eye movement analysis was conducted based on positional changes of eye features within an x- and y-coordinate system while two images (face without/with facecover) were displayed for 8 seconds. RESULTS: The results of this study revealed that the sequence of focusing on facial regions was not altered when wearing a facecover and followed the sequence: perioral, nose, periorbital. Wearing a facecover significantly increased the time spent focusing on the periorbital region and also increased the number of repeated eye fixations during the 8-second visual stimulus presentation. No statistically significant differences were observed between male and female participants in their eye movement pattern across all investigated variables (Pâ >â 0.433). CONCLUSIONS: The altered eye movement pattern caused by wearing facecoverings that this study has revealed suggests that, during the COVID-19 pandemic, aesthetic practitioners might consider developing marketing and treatment strategies that principally target the periorbital area.
Subject(s)
COVID-19 , Eye Movements , Child , Cross-Sectional Studies , Female , Humans , Male , Pandemics , SARS-CoV-2ABSTRACT
In addition to outcome assessments, cost effectiveness of surgical treatments becomes increasingly important. Both, insurance companies and hospital administrations aim for short and efficient procedures to reduce costs.Microsurgical procedures are often surpassing traditional treatment options in terms of function and aesthetics. However, they are more expensive as they require a high level of surgical expertise, more theatre capacity and longer inpatient treatment. Adequate reimbursement is mandatory, if we want to continuously perform these procedures with the best possible quality and outcome. To cover the case-related expenses of each specialty, multidisciplinary procedures require appropriate distribution of reimbursements to each department.The main diagnosis as well as all complications and relevant comorbidities should be documented to obtain the correct DRG. The additional financial benefit of a microsurgical procedure in a multidisciplinary case can be calculated by specifying the procedural increment in pay. Therefore, a fair distribution of revenues to each participating department should be performed. Different models exist, which lead to a benefit in compensation for all departments. Unfortunately, distribution of resources is still insufficiently managed in many hospitals, which hampers high quality multidisciplinary microsurgical procedures. Still, picking the best possible procedure for our patients, independently of financial incentives, is of utmost importance.
Subject(s)
Economic Factors , Microsurgery , Consensus , Cost-Benefit Analysis , Humans , Peripheral Nerves/surgeryABSTRACT
The first case of a SARS-Cov-2 virus infection was confirmed on January 27th in Munich. For both, plastic and hand surgeons it is crucial to act responsible, minimize the transmission of the virus and aid in reasonable and adequate allocation of resources for the treatment of affected patients during this pandemia. This article aims to provide an overview over the latest developments and insights that affect plastic and hand surgeons. At the same time plastic and hand surgeons are required to participate actively in the discussion of new regulatory measures that on one hand aim to ensure a proper medical care of COVID-19 patients and on the other hand need to guarantee coverage of all other patients. Furthermore exit - strategies after the pandemia need to be discussed by our societies. Naturally, this manuscript provides insight into the current situation, which might undergo changes due to the swift progression of the pandemia.
Subject(s)
Betacoronavirus , Coronavirus Infections , Hand/surgery , Pandemics , Pneumonia, Viral , Surgery, Plastic , COVID-19 , Coronavirus Infections/epidemiology , Humans , Pneumonia, Viral/epidemiology , SARS-CoV-2 , Surgery, Plastic/trendsABSTRACT
Objective: Chronic neural implants require energy and signal supply. The objective of this work was to evaluate a multichannel transcutaneous coupling approach in an ex vivo split-concept study, which minimizes the invasiveness of such an implant by externalizing the processing electronics. Methods: Herein, the experimental work focused on the transcutaneous energy and signal transmission. The performance was discussed with widely evaluated concepts of neural interfaces in the literature. Results: The performance of the transcutaneous coupling approach increased with higher channel count and higher electrode pitches. Electrical crosstalk among channels was present, but acceptable for the stimulation of peripheral nerves. Conclusions: Transcutaneous coupling with extracorporeal transmitting arrays and subcutaneous counterparts provide a promising alternative to the inductive concept particularly when a fully integration of the system in a prosthetic shaft is intended. The relocation of the electronics can potentially prevent pressure sores, improve accessibility for maintenance and increase lifetime of the implant.
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Background: Sarcomas are tumors of mesenchymal origin with high variation in anatomical localization. Sarcomas affecting the bone often require an interdisciplinary resection and reconstruction approach. However, it is critical that microsurgical reconstruction strategies do not negatively impact tumor safety and overall survival, as limb salvage is only the secondary goal of tumor surgery. Here, we analyzed the efficacy and safety of microsurgery in interdisciplinary treatment of sarcoma affecting the bone. Patients and Methods: We performed a retrospective chart review of all patients treated for soft-tissue and bone sarcoma at the senior author's institution with a focus on bone affection and microsurgical reconstruction between 2000 and 2019. This particular subgroup was further investigated for tumor resection status, 5-year survival rate, length of hospital stay, as well as overall complication and amputation rates. Results: Between 2000 and 2019, 803 patients were operated for sarcoma resection and reconstruction by the Department of Plastic and Hand Surgery. Of these, 212 patients presented with sarcoma of the extremity affecting the bone. Within this subgroup, 40 patients required microsurgical reconstruction for limb salvage, which was possible in 38 cases. R0 resection was achieved in 93.8%. The 5-year survival was 96.7%, and the overall complication rate was 25%, of which 40% were microsurgery associated complications. Conclusion: Safe and function-preserving treatment of soft-tissue and bone sarcoma is challenging. Primary reconstruction with microsurgical techniques of sarcoma-related defects enables limb-sparing and adequate oncosurgical cancer treatment without increasing the risk for local recurrence or prolonged hospital stay. The treatment of sarcoma patients should be reserved to high-volume centers with experienced plastic surgeon embedded in a comprehensive treatment concept.
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BACKGROUND: Microvesicles (MVs) are small cell-derived vesicles, which are mainly released by activated cells. They are part of a communication network delivering biomolecules, for example, inflammatory molecules, via the blood circulation to remote cells in the body. Platelet-derived MVs are known to induce vascular inflammation. Research on the mediators and mechanisms of their inflammatory effects has attracted major interest. We hypothesize that specific lipids are the mediators of vascular inflammation caused by platelet-derived MVs. METHODS AND RESULTS: Liquid chromatography electrospray ionization-tandem mass spectrometry was used for lipid profiling of platelet-derived MVs. Lysophosphatidylcholine (LPC) was found to be a major component of platelet-derived MVs. Investigating the direct effects of LPC, we found that it induces platelet activation, spreading, migration and aggregation as well as formation of inflammatory platelet-monocyte aggregates. We show for the first time that platelets express the LPC receptor G2AR, which mediates LPC-induced platelet activation. In a mouse model of atherosclerotic plaque instability/rupture, circulating LPC was detected as a surrogate marker of plaque instability. These findings were confirmed by matrix-assisted laser desorption ionization imaging, which showed that the LPC concentration of human plaques was highest in vulnerable plaque regions. CONCLUSION: LPC is a major component of platelet-derived MVs and via its interaction with G2AR on platelets contributes to platelet activation, spreading, migration and aggregation and ultimately to vascular inflammation. Circulating LPC reports on atherosclerotic plaque instability in mice and is significantly increased in unstable areas of atherosclerotic plaques in both mice and humans, linking LPC to plaque instability.