Efficacy and Cost-Benefit Analysis of Magnetic Resonance Imaging in the Follow-Up of Soft Tissue Sarcomas of the Extremities and Trunk.

There is no consensus regarding follow-up after soft tissue sarcoma (STS) treatment. This study examines the efficacy and the cost-benefit of MRI imaging for discovering recurrence. A retrospective analysis was performed, collecting data on patient demography, tumor characteristics, treatment, and follow-up. Imaging was correlated to the clinical course, and sensitivity, specificity, and predictive values were calculated. The number needed to screen and costs of finding recurrence are reported. Amongst 216 sarcomas, 73 (35%) exhibited local recurrence during a follow-up of 5.3 ± 3.5 years. 173 entities had complete MRI follow-up with 58 (34%) local recurrences. Thirty-three (57%) were discovered by MRI, 8 (14%) by clinical presentation, and 17 (29%) simultaneously. There was a sensitivity of 100.00%, a specificity of 89%, a positive predictive value of 32%, and a negative predictive value of 100% for detecting local recurrence with MRI. Our data confirm the modalities and intervals proposed by the German guidelines for sarcoma care. The recommended MRI intervals should not be extended. MRI is more cost-effective than clinical examination; still, both modalities should be performed together to discover the maximum number of recurrences.

Keratinocyte Monolayers on Hyaluronic Acid Membranes as "Upside-Down" Grafts Reconstitute Full-Thickness Wounds.

BACKGROUND Skin replacement by means of cultured epithelial keratinocytes is a well-accepted method. However, several clinical drawbacks of sheet autografts (CEA - cultured epithelial autografts) have stimulated various efforts to optimize cell culture and cell delivery. Recent developments include use of cell monolayers instead of a fully differentiated epithelium, as well as use of various biomaterials to grow and transport the cultured cells. To optimize the transfer of human keratinocytes directly to the recipient wound bed, we used an "upside-down" technique, delivering cultured cells directly to the wound with the carrier material on top. MATERIAL AND METHODS Subconfluent second-passage human keratinocyte monolayers on esterified hyaluronic acid membranes (KHAMC - Keratinocyte-Hyaluronic-Acid-Membrane-Composites) were transplanted either as upside-down grafts or as upside-up grafts onto standardized full-thickness wounds in athymic nude mice versus controls with the cell-free membrane alone. RESULTS In the upside-down group, 14 days after grafting, a multi-layered, differentiating epidermis was found, whereas the wounds in the upside-up group and in the control group were not completely closed up to day 21. Persistence of human keratinocytes was shown in the upside-down group only, from day 7 until day 35 after grafting. CONCLUSIONS This study confirms that upside-down grafting of subconfluent monolayers of serum-free cultured human keratinocytes on esterified hyaluronic acid membranes is a suitable means to transfer actively proliferative keratinocytes, and reduces wound contraction. Compared to standard grafting protocols of cultured epithelium, such as CEA sheet grafts, it is easier to apply, does not need enzymatic detachment of cells from the culture dish, and limits the number of production steps required.

Genotyping of circulating cell-free DNA enables noninvasive tumor detection in myxoid liposarcomas.

Soft tissue sarcomas (STS) are rare tumors of mesenchymal origin. About 50% of patients with STS experience relapse and more than 30% will die within 10 years after diagnosis. In this study we investigated circulating free DNA (cfDNA) and tumor-specific genetic alterations therein (circulating tumor DNA, ctDNA) as diagnostic biomarkers. Plasma concentrations and fragmentation of cfDNA was analyzed with quantitative PCR. Patients with STS (n = 64) had significantly higher plasma concentrations and increased fragmentation of cfDNA when compared to patients in complete remission (n = 19) and healthy controls (n = 41) (p < 0.01 and p < 0.001). Due to overlapping values between patients with STS and controls, the sensitivity and specificity of these assays is limited. Sensitive assays to detect genomic alterations in cfDNA of synovial sarcomas (t(X;18)), myxoid liposarcomas (t(12;16) and TERT C228T promoter mutation) and well-differentiated/de-differentiated liposarcomas (MDM2 amplifications) were established. ctDNA was quantified in nine liposarcoma patients during the course of their treatment. Levels of breakpoint t(12;16) and TERT C228T ctDNA correlated with the clinical course and tumor burden in patients with myxoid liposarcomas (n = 4). ctDNA could detect minimal residual disease and tumor recurrence. In contrast, detection of MDM2 amplifications was not sensitive enough to detect tumors in patients with well-differentiated/de-differentiated liposarcomas (n = 5). Genotyping of cfDNA for tumor specific genetic alterations is a feasible and promising approach for monitoring tumor activity in patients with myxoid liposarcomas. Detection of ctDNA during follow-up examinations despite negative standard imaging studies might warrant more sensitive imaging (e.g. PET-CT) or closer follow-up intervals to timely localize and treat recurrences.

[Breast reconstruction with the free TRAM or DIEP flap ­ What is the current standard? Consensus Statement of the German Speaking Working Group for Microsurgery of the Peripheral Nerves and Vessels]. / Brustrekonstruktion mit freien TRAM oder DIEP Lappen ­ Was ist zeitgemäßer Standard?

The most common donor-site for autologous breast reconstruction is the abdomen. Over the past several decades technical advances have resulted in the development of flaps that have been associated with a progressive decrease in abdominal wall morbidity. However, controversy exists related to the differences between muscle-sparing (MS)-TRAM and deep inferior epigastric perforator (DIEP) flaps. Hence, the question which approach should be considered standard of care remains unanswered. To address this question the current literature and published evidence was critically reviewed and discussed by an expert panel at the 39th Annual Meeting of the German-speaking Society for Micro surgery of the Peripheral Nerves and Vessels (DAM). Based on this discussion a consensus statement was developed that incorporates contemporary data regarding postoperative complication rate, donor site morbidity, as well as expert opinion regarding technical details in autologous breast reconstruction with free TRAM and DIEP flaps.

A Conformational Change in C-Reactive Protein Enhances Leukocyte Recruitment and Reactive Oxygen Species Generation in Ischemia/Reperfusion Injury.

Introduction: C-reactive protein circulates as a pentameric protein (pCRP). pCRP is a well-established diagnostic marker as plasma levels rise in response to tissue injury and inflammation. We recently described pro-inflammatory properties of CRP, which are mediated by conformational changes from pCRP to bioactive isoforms expressing pro-inflammatory neo-epitopes [pCRP* and monomeric C-reactive protein (mCRP)]. Here, we investigate the role of CRP isoforms in renal ischemia/reperfusion injury (IRI). Methods: Rat kidneys in animals with and without intraperitoneally injected pCRP were subjected to IRI by the time of pCRP exposure and were subsequently analyzed for monocyte infiltration, caspase-3 expression, and tubular damage. Blood urea nitrogen (BUN) was analyzed pre-ischemia and post-reperfusion. CRP effects on leukocyte recruitment were investigated via intravital imaging of rat-striated muscle IRI. Localized conformational CRP changes were analyzed by immunohistochemistry using conformation specific antibodies. 1,6-bis(phosphocholine)-hexane (1,6-bisPC), which stabilizes CRP in its native pentameric form was used to validate CRP effects. Leukocyte activation was assessed by quantification of reactive oxygen species (ROS) induction by CRP isoforms ex vivo and in vitro through electron spin resonance spectroscopy. Signaling pathways were analyzed by disrupting lipid rafts with nystatin and subsequent ROS detection. In order to confirm the translational relevance of our findings, biopsies of microsurgical human free tissue transfers before and after IRI were examined by immunofluorescence for CRP deposition and co-localization of CD68+ leukocytes. Results: The application of pCRP aggravates tissue damage in renal IRI. 1,6-bisPC reverses these effects via inhibition of the conformational change that leads to exposure of pro-inflammatory epitopes in CRP (pCRP* and mCRP). Structurally altered CRP induces leukocyte-endothelial interaction and induces ROS formation in leukocytes, the latter can be abrogated by blocking lipid raft-dependent signaling pathways with Nystatin. Stabilizing pCRP in its native pentameric state abrogates these pro-inflammatory effects. Importantly, these findings are confirmed in human IRI challenged muscle tissue. Conclusion: These results suggest that CRP is a potent modulator of IRI. Stabilizing the native pCRP conformation represents a promising anti-inflammatory therapeutic strategy by attenuation of leukocyte recruitment and ROS formation, the primary pathomechanisms of IRI.

Comparison of symmetry after smile reconstruction for flaccid facial paralysis with combined fascia lata grafts and functional gracilis transfer for static suspension or gracilis transfer alone.

PURPOSE: Facial paralysis has a profound impact on functionality and esthetics of the oral region. In patients with strong skin laxity and soft tissue ptosis, functional smile reconstruction is challenging due to the accentuated asymmetry at rest. Thus, the purpose of the study was to analyze facial symmetry in this patient clientele following a combination of dynamic reanimation with fascial strips for static suspension compared to functional gracilis transfer alone. METHODS: In 2014, we altered the single-stage approach for microsurgical smile reconstruction in patients with significant soft tissue ptosis by adding fascia lata grafts for static support. We evaluated 6 patients (mean age 57.8 ± 5.2, group A) who underwent the combined procedure, and compared their results to 6 patients with flaccid facial paralysis who were treated before 2014 and received a functional gracilis transfer alone (mean age 52.5 ± 7.5, group B). To test the efficacy of the technique, we retrospectively analyzed the correction of the oral asymmetry as well as nasal and philtral deviation by computer-assisted photograph analysis 6 months postoperatively. RESULTS: The comparative analysis revealed a significant postoperative improvement of the oral asymmetry (A: 90.0 ± 5.0% relative correction at rest vs. B: 62.6 ± 17.2%, P < .05), nasal (A: 0.4 ± 0.2 vs. B: 0.7 ± 0.4 mm, P < .05), and philtral deviation (A: 0.5 ± 0.6 vs. B: 2.8 ± 1.8 mm, P < .05) in group A. CONCLUSIONS: The combined procedure for dynamic facial reanimation allows for immediate correction of the oral asymmetry and improves overall outcome in patients with advanced soft tissue ptosis and oral asymmetry at rest.

Evaluation of the Implantable Doppler Probe for Free Flap Monitoring in Lower Limb Reconstruction.

BACKGROUND: Timely reexploration and reanastomoses can salvage failing free flaps. The use of the implantable Doppler probe provides direct evidence of vascular impairment of the microvascular anastomoses and allows for postoperative NPWT. The aim of this retrospective study was to compare the Doppler probe to conventional monitoring techniques for free flap monitoring in lower limb reconstruction and to identify risk factors for perfusion disturbance and reexploration. METHODS: All patients receiving free muscle flap reconstruction for lower limb soft tissue defects at our department from 2000 to 2013 were included, and all adverse events, timely detection of perfusion problems, and outcome of revision surgery were assessed by chart analysis. RESULTS: For lower limb reconstruction, 110 free muscle transfers were performed of which 41 muscle flaps were conventionally monitored and 69 flaps were monitored using the implantable Doppler probe. In 18 cases, the free muscle flaps needed revision because of perfusion disturbances. The salvage rate was 80% with monitoring by the implantable Doppler probe compared with 62.5% using conventional monitoring methods resulting in success rates of 95.7 and 92.7%, respectively. CONCLUSION: The use of the implantable Cook-Swartz Doppler probe represents a safe monitoring method for lower limb reconstruction, which allows for the additional use of NPWT. Higher salvage and revision success rates can be attributed to an earlier detection of perfusion impairment. However, a larger patient cohort is necessary to verify superiority over conventional postoperative monitoring.

Pedicled and free flaps for intrathoracic fistula management.

OBJECTIVES: Intrathoracic fistulae are among the potential sequelae of radiation therapy, empyema and abscess clearance and surgical tumour resections. Interdisciplinary plastic-reconstructive flap surgery is a helpful tool for the successful treatment of intrathoracic fistulae. METHODS: From February 2006 to April 2016, 13 patients (3 females and 10 males) underwent flap surgery for bronchial (n = 5), tracheal (n = 2), oesophageal (n = 2), post-pneumonectomy bronchopleural fistula (n = 2), tracheo-oesophageal (n = 1), gastrobronchial (n = 1) and oesophagobronchial (n = 1) fistulae. Patient characteristics, identified pathogenic micro-organisms, treatment and decision criteria, long-term outcome and postoperative complications were evaluated by analysing patient charts and surgical reports. RESULTS: The mean age of the 13 patients who underwent reconstructive surgery was 55.5 years (range: 42-66 years). The median follow-up time was 31.4 months (range: 2-96 months). American Society of Anaesthesiologists classification was II for 1 patient, III for 8 patients and IV for 4 patients. In total, 18 flaps were performed (7 latissimus dorsi pedicled flaps, 7 pectoralis major pedicled flaps, 2 rectus abdominis myocutaneous flaps, 1 free temporo-parietal fascia flap and 1 intercostal muscle flap). A second flap was indicated in 5 cases (38.5%) due to fistula recurrence; of these, 1 patient developed a bronchial fistula after successful reconstruction of a gastrobronchial fistula. Eight of the 13 patients (61.5%) were evaluated postoperatively at regular intervals for at least 1 year and showed no signs of fistula recurrence. CONCLUSIONS: Our study showed that plastic-reconstructive flap surgery, although associated with significant morbidity and mortality, can be a life-saving tool for intrathoracic fistula reconstruction. CLINICAL TRIAL REGISTRATION: DRKS00010447.

Analysis of the ideal muscle weight of gracilis muscle transplants for facial reanimation surgery with regard to the donor nerve and outcome.

BACKGROUND: Free functional muscle transfers represent the 'criterion standard' for smile reconstruction in facial paralysis. The gracilis muscle is a common donor muscle; however, no data exist regarding the volume of the muscle tissue that is necessary for symmetric commissure excursion. METHODS: All patients with facial paralysis receiving a free functional muscle transfer for facial reanimation surgery between January 2009 and November 2015 were retrospectively analysed. Only patients with unilateral facial paralysis and documented weight of the muscle portion were included. The extent of oral commissure amplitude was determined from standardised photographs. RESULTS: In total, 42 free functional gracilis transfers were performed during the study period, of which 22 met the inclusion criteria. Eight muscles were innervated by a cross-facial nerve graft (CFNG) and 14 by the masseteric nerve. Segments between 19 and 50 g of weight (mean: CFNG, 33.9 g and masseteric nerve, 31.7 g; p = 0.59) were transferred. Coaptation to the masseteric nerve led to increased commissure excursion compared to coaptation to the CFNG. We observed a significant increase in commissure excursion with increasing muscle weight in the masseteric nerve group. In this group, four patients underwent secondary flap debulking in flaps weighing ≥27 g. In the CFNG group, only one patient, who had an initial flap weight of 50 g, underwent secondary flap reduction. Thinning reduced the oral commissure movement but improved the symmetry of commissure excursion and the aesthetic result. CONCLUSION: The ideal muscle weight depends on the donor nerve and should be smaller for masseteric nerve than for CFNG coaptation in adults.

Microsurgical reconstruction of oncological scalp defects in the elderly.

The incidence of scalp tumors requiring radical excision increases with age. Free flap surgery is the standard reconstructive option for large defects; however, there is an ongoing uncertainty about its safety in the elderly. We conducted a review of data and report on 19 patients aged ≥75 years and 13 < 75 years. Data regarding patient demographics, types of tumors, surgery, size of defect, flaps used, and prevalence of complications were analyzed. The patients in the elderly group had more accompanying medical conditions and a higher ASA score. Squamous cell carcinoma was the predominant tumor in the elderly and sarcoma in the younger patients. The defect size was similar in both groups. The latissimus dorsi (LD) and the anterolateral thigh (ALT) flaps were flaps of first choice, with temporal vessels most commonly used for anastomosis. Surgery lasted longer in the younger patients. There was no difference in the duration of hospital stay. No significant correlation was found between age and the flap-related or medical complications. Revision surgery was more often required in the younger patients. We conclude that free flap surgery is safe and reliable in the elderly population. The LD and the ALT are the most commonly used flaps. Advanced age should not be considered a risk factor for free flap surgery in these patients.

Soft Tissue Sarcomas of the Arm - Oncosurgical and Reconstructive Principles within a Multimodal, Interdisciplinary Setting.

Soft tissue sarcomas of the upper extremity represent a severe threat for the patient and a difficult task for the treatment team. Due to the complex anatomy of the arm, most sarcomas involve valuable functional structures. Nonetheless, a large portion of the patients can be treated in a limb-sparing manner, and surgery is the mainstay of local tumor control. This review gives an overview of the disease entities and their epidemiology, on necessary patient work-up, staging, and imaging modalities, as well as the importance of interdisciplinary decision-making. The surgical therapies and principles of tumor excision are outlined, as well as reconstructive options. Furthermore, adjuvant treatments are discussed with a special focus on the various application techniques for radiation therapy. In spite of established treatment algorithms, each case is an individual challenge and individually tailored therapy is required. This aspect is illustrated by presenting three comprehensive cases demonstrating useful strategies. A summary of the relevant literature is given.

Long-Term Comparison of Rib and Ear Cartilage Grafts in Autologous and Allogenic Fascia Lata: An Experimental Study in a White Rabbit Model.

BACKGROUND: Diced cartilage in fascia has become the graft material of choice for dorsal grafts in rhinoplasty. Allogenic fascia lata has not yet been investigated as an isolated fascial graft or as a combined graft with ear and rib cartilage, especially in comparison with autologous fascia and over a long implantation period. METHODS: Ten different grafts were built from either autologous or allogenic fascia lata alone or as diced cartilage in fascia grafts with diced costal or ear cartilage and implanted into the dorsal skin of 15 rabbits. After 3 or 9 months, the grafts were explanted and analyzed histologically. Chondrocytes and cartilage matrix characteristics, including calcification, ossification, formation of bone marrow, fibrosis ingrowth and fibrotic transformation, the presence of immune reactions, vascular ingrowth, regenerative capacity, and capsule formation, were examined in a semiquantitative manner. RESULTS: All grafts were vital and without inflammatory response. The cartilage showed regular nuclei, a normal matrix, and regenerative capacity. A higher grade of calcification and ossification was observed in the fascia/cartilage grafts than in isolated cartilage grafts, and was more pronounced for costal cartilage. Both types of fascia were shown to be equally stable and without degradation. There were no significant differences in the diced cartilage in fascia grafts built with autologous compared to allogenic fascia. CONCLUSIONS: This study shows the equivalency of diced cartilage in fascia grafts and isolated fascial grafts using allogenic fascia lata compared to autologous fascia. The type of cartilage used accounts for different long-term characteristics of diced cartilage in fascia grafts.

Is revisional surgery mandatory when an unexpected sarcoma diagnosis is made following primary surgery?

BACKGROUND: Soft tissue sarcomas (STS) are often diagnosed unexpectedly after surgery, and many excisions are incomplete. As histopathological assessments are challenging, patients later referred to comprehensive cancer centers (CCC) often come with an unclear status. This can make treatment planning problematic. We investigated the reliability of primary histopathological assessments, whether revisional surgery improved resection status, and the prognostic value of residual tumor at re-excision. METHODS: We analyzed the demographic and clinical characteristics of all patients referred to our CCC between 2003 and 2013. We compared patients treated exclusively at our CCC with those who had primary surgery elsewhere, and focused on resection margins, re-excision type, residual tumor, resection status after re-excision, and oncological outcome. RESULTS: Over half (n = 110) of all patients (n = 204) were referred from elsewhere. Seventy-one had undergone an excision without suspicion of malignancy. Resection status in referred patients was significantly inferior to the CCC group (p < 0.0001), although the latter had significantly more serious tumors and advanced disease stages (p < 0.05). The residual tumor rate was 53.13%, with a significantly higher probability in an upper extremity (p = 0.001). Initial histopathological classification was misleading in 46.9% of cases. Re-excision improved resection status in 69% of cases. Residual tumor presumably leads to higher rates of local recurrence (p = 0.057) and significantly shorter times to recurrence (p < 0.05). CONCLUSIONS: Re-excision should always follow unplanned STS excisions. Resection margins and histopathological assessments from referring institutions are often unreliable and unsuitable for treatment planning. Residual tumor is a risk factor for earlier and more likely local recurrence.

Identification of a blood-borne miRNA signature of synovial sarcoma.

BACKGROUND: Synovial sarcoma account for approximately 10 % of all soft-tissue tumors and occur most frequently in young adults. A specific translocation in this sarcoma induces fusion of the SYT gene on chromosome 18 to the SSX genes on chromosome X, leading to proliferation of the tumor cells. The need for non-invasive biomarkers indicating recurrence and activity of this disease has sparked research into short non-coding RNA known as microRNA (miRNA). METHODS: Blood samples of patients with active synovial sarcoma and of synovial sarcoma patients in complete remission as well as of healthy donors and patients with active leiomyosarcoma, MPNST, Ewing sarcoma and liposarcoma were collected. Whole blood RNA was extracted and samples of patients with active synovial sarcoma and of healthy donors were analyzed using an Affymetrix GeneChip miRNA Array v. 4.0. qRT-PCR was carried out to confirm a panel of miRNAs which where differentially expressed in the miRNA array. This miRNA-panel was further evaluated in patients with synovial sarcoma in complete remission and patients with active leiomyosarcoma, MPNST, Ewing sarcoma and liposarcoma as well as in an independent cohort of synovial sarcoma patients. RESULTS: Unsupervised hierarchical clustering of the miRNA arrays separated patients with active synovial sarcoma from healthy controls. A panel of seven miRNAs (miR-99a-5p, miR-146b-5p, miR-148b-3p, miR-195-5p, miR-223-3p, miR-500b-3p and miR-505-3p) was further validated by qRT-PCR to be significantly upregulated in synovial sarcoma patients. Moreover, most of the analyzed miRNAs were shown to be significantly upregulated in synovial sarcoma patients compared to leiomyosarcoma, MPNST, Ewing sarcoma and liposarcoma patients. Validation of the miRNA panel in an independent cohort of synovial sarcoma patients confirmed higher expression levels compared to healthy controls and patients in complete remission. CONCLUSION: Our results have identified a specific whole blood miRNA signature that may serve as an independent biomarker for the diagnosis of local recurrence or distant metastasis of synovial sarcoma. It even distinguishes synovial sarcoma from other sarcoma subtypes, thus potentially serving as a specific biomarker for synovial sarcoma.

Single-stage dynamic reanimation of the smile in irreversible facial paralysis by free functional muscle transfer.

Unilateral facial paralysis is a common disease that is associated with significant functional, aesthetic and psychological issues. Though idiopathic facial paralysis (Bell's palsy) is the most common diagnosis, patients can also present with a history of physical trauma, infectious disease, tumor, or iatrogenic facial paralysis. Early repair within one year of injury can be achieved by direct nerve repair, cross-face nerve grafting or regional nerve transfer. It is due to muscle atrophy that in long lasting facial paralysis complex reconstructive methods have to be applied. Instead of one single procedure, different surgical approaches have to be considered to alleviate the various components of the paralysis. The reconstruction of a spontaneous dynamic smile with a symmetric resting tone is a crucial factor to overcome the functional deficits and the social handicap that are associated with facial paralysis. Although numerous surgical techniques have been described, a two-stage approach with an initial cross-facial nerve grafting followed by a free functional muscle transfer is most frequently applied. In selected patients however, a single-stage reconstruction using the motor nerve to the masseter as donor nerve is superior to a two-stage repair. The gracilis muscle is most commonly used for reconstruction, as it presents with a constant anatomy, a simple dissection and minimal donor site morbidity. Here we demonstrate the pre-operative work-up, the post-operative management, and precisely describe the surgical procedure of single-stage microsurgical reconstruction of the smile by free functional gracilis muscle transfer in a step by step protocol. We further illustrate common pitfalls and provide useful tips which should enable the reader to truly comprehend the procedure. We further discuss indications and limitations of the technique and demonstrate representative results.

Salvage procedures after failed facial reanimation surgery using the masseteric nerve as the motor nerve for free functional gracilis muscle transfer.

IMPORTANCE: Free muscle transfer innervated by a cross-facial nerve graft represents the criterion standard for smile reconstruction in facial paralysis. If primary reconstruction fails, a second muscle transfer is usually needed. Herein, we investigated the possibility of avoiding a second free muscle transfer by in situ coaptation of the gracilis muscle to the masseteric nerve. OBSERVATIONS: We report a series of 3 failed free muscle transfers for facial reanimation among 21 free flap transfers performed for facial reanimation between March 2008 and August 2013. To salvage the muscle, we performed coaptation of the neural pedicle from the cross-facial nerve graft to the masseteric nerve. This method allows for leaving the fixation sutures of the muscle at the oral commissure in place. All patients showed muscle contraction after 3 months and a smile with open mouth after 6 months. No significant difference in the range of commissure excursion was observed between the healthy and operated sides. CONCLUSIONS AND RELEVANCE: Recoaptation of the neural pedicle from the cross-facial nerve graft to the masseteric nerve, leaving the muscle transplant in place, is a suitable salvage procedure after unsuccessful reconstruction with a cross-facial nerve graft, avoiding a second free muscle transfer. LEVEL OF EVIDENCE: 4.

Dissociation of pentameric to monomeric C-reactive protein localizes and aggravates inflammation: in vivo proof of a powerful proinflammatory mechanism and a new anti-inflammatory strategy.

BACKGROUND: The relevance of the dissociation of circulating pentameric C-reactive protein (pCRP) to its monomeric subunits (mCRP) is poorly understood. We investigated the role of conformational C-reactive protein changes in vivo. METHODS AND RESULTS: We identified mCRP in inflamed human striated muscle, human atherosclerotic plaque, and infarcted myocardium (rat and human) and its colocalization with inflammatory cells, which suggests a general causal role of mCRP in inflammation. This was confirmed in rat intravital microscopy of lipopolysaccharide-induced cremasteric muscle inflammation. Intravenous pCRP administration significantly enhanced leukocyte rolling, adhesion, and transmigration via localized dissociation to mCRP in inflamed but not noninflamed cremaster muscle. This was confirmed in a rat model of myocardial infarction. Mechanistically, this process was dependent on exposure of lysophosphatidylcholine on activated cell membranes, which is generated after phospholipase A2 activation. These membrane changes could be visualized intravitally on endothelial cells, as could the colocalized mCRP generation. Blocking of phospholipase A2 abrogated C-reactive protein dissociation and thereby blunted the proinflammatory effects of C-reactive protein. Identifying the dissociation process as a therapeutic target, we stabilized pCRP using 1,6-bis(phosphocholine)-hexane, which prevented dissociation in vitro and in vivo and consequently inhibited the generation and proinflammatory activity of mCRP; notably, it also inhibited mCRP deposition and inflammation in rat myocardial infarction. CONCLUSIONS: These results provide in vivo evidence for a novel mechanism that localizes and aggravates inflammation via phospholipase A2-dependent dissociation of circulating pCRP to mCRP. mCRP is proposed as a pathogenic factor in atherosclerosis and myocardial infarction. Most importantly, the inhibition of pCRP dissociation represents a promising, novel anti-inflammatory therapeutic strategy.

A conformational change of C-reactive protein in burn wounds unmasks its proinflammatory properties.

Tissue damage in burn injury leads to a rapid increase of leukocytes and acute phase reactants. Plasma levels of C-reactive protein (CRP) rise within hours after the insult. No deficiency of this protein has been reported in humans, suggesting it plays a pivotal role in innate immunity. CRP in circulation is composed of five identical subunits [pentameric CRP (pCRP)]. Recently, deposits of structurally modified CRP (mCRP) have been found in inflammatory diseases. Little is known about this structural change and how it affects CRP functions. We analyzed CRP deposits in burn wounds and serum by immunohistochemistry, western blot and dot blot analysis. CRP was deposited in necrotic and inflamed tissue, but not in adjacent healthy tissue. Tissue deposited CRP was detected by mCRP-specific antibodies and structurally different from serum pCRP. mCRP but not pCRP induced reactive oxygen species production by monocytes and facilitated uptake of necrotic Jurkat cells by macrophages. In addition, it accelerated migration of keratinocytes in a scratch wound assay. The structural changes that occur in pCRP upon localization to damaged and inflamed tissue in burn wounds result in a functionally altered protein with distinct functions. mCRP exhibits opsonic, proinflammatory and promigratory properties which modulate wound healing.

Aesthetic surgery performed by plastic surgery residents: an analysis of safety and patient satisfaction.

BACKGROUND: Aesthetic surgery is an integral component of plastic surgery. Despite its importance, adequate training in aesthetic surgery is met with challenges. Although the educational benefit of resident clinics has been demonstrated, such clinics are rarely found outside the United States. The objective of the present study was to assess safety and patient satisfaction associated with aesthetic surgery procedures performed by plastic surgery residents at a German academic medical center. METHODS: The study had 2 components, namely, a retrospective chart review and an administration of a patient satisfaction survey. Only patients who underwent a surgical intervention by a plastic surgery resident between 2003 and 2011 were included in the study. Parameters of interest included age, sex, procedure performed, number of procedures, revenue (in &OV0556;), length of follow-up, revision rate, and postoperative complication rate. Patient satisfaction was assessed by the client satisfaction questionnaire-8. RESULTS: A total of 273 aesthetic procedures were performed in 206 patients with an increase in recent years. The median follow-up period was 49.5 months. The most frequently performed procedures were liposuction (n = 59), breast augmentation (n = 53), and upper eyelid blepharoplasty (n = 31). One hundred ninety-two (90.3%) patients had an uneventful postoperative course. The client satisfaction questionnaire-8 questionnaire was completed by 110 patients (response rate, 50.2%). The median value of 28 indicates a high degree of patient satisfaction. An association between occurrence of major complications and patient satisfaction was seen. CONCLUSIONS: Aesthetic surgery performed by plastic surgery residents under supervision by attending physicians is safe and provides for high levels of patient satisfaction postoperatively. Offering these services may be able to bridge the gap between providing high-quality aesthetic surgery training while yet recruiting an increasing number of patients who may appreciate the lower fees associated with these services.