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BACKGROUND The nose is at the center of the face and has essential functional and aesthetic properties. Over recent years, rhinoplasty has gained increasing popularity through the influence of "selfies" and social media. As a result, a growing demand for secondary correction has also emerged. Revision rhinoplasty is more complex than primary cases and often requires the use of extranasal grafting material. The authors sought to analyze the indications, techniques, and outcomes after primary and revision rhinoplasty. METHODS A total of 245 patients (153 primary cases and 92 revisions) undergoing surgery at the authors' specialized clinic for facial plastic surgery were included. All patients were treated by an experienced facial plastic surgeon according to the authors' established clinic standards. A retrospective data analysis was performed to evaluate the differences between the groups regarding the indications, intraoperative techniques, and postoperative outcomes. RESULTS Although more patients sought revision surgery for aesthetic reasons alone than isolated functional issues, almost two-thirds of the revision patients had functional and aesthetic problems in combination. Complex reconstructive techniques, extracorporeal septoplasties, and extranasal grafts were more commonly used in revision cases. The occurrence of another revision during the follow-up period was significantly higher after revision surgery compared to primary rhinoplasty cases (primary rhinoplasty, 10.5 percent; revision surgery, 23.9 percent; p = 0.006). CONCLUSIONS There are differences between primary and revision rhinoplasty that must be appreciated by the treating surgeon. The patient should be informed about the increased complexity of the secondary procedure, the possible need for extranasal grafts, and the increased risk of a further revision. CLINICAL QUESTION/LEVEL OF EVIDENCE Therapeutic, IV.

Background: Breast reconstruction has a positive impact on body image and quality of life for women after experiencing the physically and psychologically demanding process of mastectomy. Previous studies have presented body mass index (BMI) as a predictor for postoperative complications after breast reconstruction, however, study results vary. This retrospective study aimed to investigate the impact of patients’ BMI on postoperative complications following implant-based breast reconstruction. Methods: All implant-based breast reconstructions performed at the Department of Plastic, Reconstructive and Aesthetic Surgery at the Medical University of Vienna from January 2001 to March 2018 were evaluated. A total of 196 reconstructed breasts among 134 patients met eligibility criteria. Demographic data, surgical techniques, as well as major and minor complications within a one-year follow-up period were analyzed. Results: Patients’ BMI did not show a significant impact on complication rates. The overall incidence of postoperative complications was 30.5% (40/131) of which 17.6% required reoperation. Impaired wound healing (18.3%), seroma (6.1%), hematoma (4.6%), capsular contraction (4.6%) and infection (3.8%) were the most common complications. Conclusion: In our study cohort, BMI was not associated with a significantly higher risk of complications. However, postoperative complications significantly increased with a longer operative time and resulted in an extended length of hospital stay.

ObjectivesBurn injuries elicit a unique and dynamic stress response which can lead to burn injury progression. Though neutrophils represent crucial players in the burn-induced immunological events, the dynamic secretion pattern and systemic levels of neutrophil-derived factors have not been investigated in detail so far.MethodsSerum levels of neutrophil elastase (NE), myeloperoxidase (MPO), citrullinated histone H3 (CitH3), and complement factor C3a were quantified in burn victims over 4 weeks post injury. Furthermore, the potential association with mortality, degree of burn injury, and inhalation trauma was evaluated. In addition, leukocyte, platelet, neutrophil, and lymphocyte counts were assessed. Lastly, we analyzed the association of neutrophil-derived factors with clinical severity scoring systems.ResultsSerum levels of NE, MPO, CitH3, and C3a were remarkably elevated in burn victims compared to healthy controls. Leukocyte and neutrophil counts were significantly increased on admission day and day 1, while relative lymphocytes were decreased in the first 7 days post burn trauma. Though neutrophil-derived factors did not predict mortality, patients suffering from 3rd degree burn injuries displayed increased CitH3 and NE levels. Accordingly, CitH3 and NE were elevated in cases with higher abbreviated burn severity indices (ABSI).ConclusionsTaken together, our data suggest a role for neutrophil activation and NETosis in burn injuries and burn injury progression. Targeting exacerbated neutrophil activation might represent a new therapeutic option for severe cases of burn injury.

Treatment of ruptured ulnar collateral thumb metacarpophalangeal (MCP) joint ligaments (UCL) necessitate a profound anatomic knowledge for optimal surgical repair in order to preserve range of motion and ensure postoperative joint stability. Therefore, knowledge of the angle between the UCL and the longitudinal axis of the first metacarpal bone could be useful. In this study 46 ulnar collateral thumb MCP joint ligaments in 15 male and 15 female embalmed anatomic specimens were dissected and the angles between the longitudinal axis of the first metacarpal bone and the proper (PUCL) as well as the accessory ulnar collateral thumb MCP ligament (AUCL) were measured. In male specimens the angle for the PUCL measured on average 133.5° (±2.35°) and 122.75° (±3.8°) for the AUCL. A significantly different angle was measured for female specimens which showed on average 137.88° (±3.51°) for the PUCL and 128.65° (±4.14°) for the AUCL. Optimal surgical repair or reconstruction of torn ulnar collateral thumb MCP joint ligaments should aim for an angle of approximately 135° in PUCL and 126° in AUCL in relation to the longitudinal axis of the metacarpal bone. Differences in men and women should be considered if possible. IV (anatomic study).

According to the ABSI - Abbreviated Burn Severity Index - women exhibit an increased risk of succumbing to burn injuries. In contrast, following non-thermal trauma, increased mortality has been shown for the male gender. Therefore, the purpose of this study was to evaluate gender-specific differences among burn patients with special regard to burn mortality.We retrospectively studied 839 patients who were admitted to the Burn Intensive Care Unit (BICU) and underwent surgical treatment between June 1994 and December 2014. In-hospital mortality was the main clinical endpoint. Odds ratios (ORs) were calculated using univariate and multivariate logistic regression models for the association between sex and mortality.In total, we included 530 male and 309 female burn patients. All patients had at least partial-thickness burns and underwent one or more operative procedures. Women were significantly older than men (mean 60.0 years vs 46.2 years; p0.001). Despite having smaller injuries (24.6% vs 30.3% total body surface area (TBSA); p0.001), burn mortality among women significantly differed from that of men (27.8% vs 21.7%; OR 1.39, p=0.045, 95% CI 1.01-1.92). This association, however, did not persist after adjusting for age, %TBSA, inhalation injury and full-thickness burns (OR 1.07, p=0.77, 95% CI 0.68-1.70).Despite increasing research directed at women's health, the assoziation between gender and burn mortality has yielded conflicting results. This study does not support a gender-specific difference in burn mortality in our study population.

The importance of a straight and stable central framework is beyond dispute. Many authors allude to technical aspects how to achieve the above-mentioned requirements. Far less is said about the contact zones of the framework and how to achieve a long-lasting and solid fixation. In the authors' patient group, they found the need to work on the septum/the central framework in approximately 84% of the cases. In 61% of the patients, the authors had to operate on the fixation point. Of course, there is a great variety of anatomical findings. So the required techniques differ immensely. The surgeon must be prepared for all kinds of different situations. Especially the dorsal fixation and the anchoring on the maxilla without having a standard anterior nasal spine can be a great challenge. In their daily routine, suture techniques (e.g., the transcutaneous transosseous cerclage suture) have become the authors' working horse for these complex fixation situations.

Purpose As critical parameter after extravasation of cytotoxic vesicants, anthracyclines were determined in removed tissue from patients requiring surgical intervention due to tissue necrosis. We monitored their distribution within the affected lesion to establish a possible dose–toxicity relation. Methods From six patients scheduled for surgery, removed tissue flaps were systematically analysed by HPLC (epirubicin: 5 subjects; doxorubicin: 1 subject). Results After extravasation, tissue concentrations were highly variable with an individual anthracycline distribution pattern ranging from a few nanograms up to 17 µg per 100 mg tissue, which indicated a substantial difference in tissue sensitivity among patients. The resection borders coincided with the extension of the erythema and guided the surgical intervention after demarcation of the lesion, which occurred usually 2 or 3 weeks after extravasation. At that time, drug was hardly detected at the resection borders. Wound drains were negative for the extravasated drugs while showing a time profile of vascular growth factors and inflammatory cytokines, which was highly similar to routine surgery. In all six patients, surgical debridement with immediate wound closure led to healing within approximately 2 weeks, when therapy was resumed in all patients with reasonable time delay. Conclusion Surgical intervention after demarcation of the extravasation lesion allows for almost uninterrupted continuation of treatment independent of the amount of extravasated anthracycline. As even minor amounts of the vesicants may trigger tissue necrosis, preventive measures merit the highest priority.

Background Even today, severe septal deformities are a challenging problem for any rhinoplasty surgeon. Standard techniques are often not able to achieve satisfactory long-term results regarding function or aesthetic form. In such severe cases, a partial or total extracorporeal septal reconstruction may be used, as these techniques provide reliable and lasting results. Methods The aim of this work is to present the authors' experience with the technique of total extracorporeal septal reconstruction and its development to today's standard and to prove its effectiveness in the long-term follow-up. Results This article presents 40 years of clinical experience in this field and describes the technical changes that have evolved. Low complication rates, safe techniques, and favorable long-term outcomes of the total extracorporeal septal reconstruction show the benefits of this technique. Conclusion The indication for a total extracorporeal septal reconstruction has been limited by the development of less complex surgical procedures, but it still represents the best technique to achieve long-term functional and aesthetic results in patients with very complex septal deformities. Clinical question/level of evidence Therapeutic, V.

Reconstructive surgery transfers viable tissue to cover defects and to restore aesthetic and functional properties. Failure rates after free flap surgery range from 3 to 7%. Co‐morbidities such as diabetes mellitus or peripheral vascular disease increase the risk of flap failure up to 4.5‐fold. Experimental therapeutic concepts commonly use a monocausal approach by applying single growth factors. The secretome of γ‐irradiated, stressed peripheral blood mononuclear cells (PBMCsec) resembles the physiological environment necessary for tissue regeneration. Its application led to improved wound healing rates and a two‐fold increase in blood vessel counts in previous animal models. We hypothesized that PBMCsec has beneficial effects on the survival of compromised flap tissue by reducing the necrosis rate and increasing angiogenesis. Surgery was performed on 39 male Sprague–Dawley rats (control, N = 13; fibrin sealant, N = 14; PBMCsec, N = 12). PBMCsec was produced according to good manufacturing practices (GMP) guidelines and 2 ml were administered intraoperatively at a concentration of 2.5 × 107 cells/ml using fibrin sealant as carrier substance. Flap perfusion and necrosis (as percentage of the total flap area) were analyzed using Laser Doppler Imaging and digital image planimetry on postoperative days 3 and 7. Immunohistochemical stainings for von Willebrand factor (vWF) and Vascular Endothelial Growth Factor‐receptor‐3 (Flt‐4) were performed on postoperative day 7 to evaluate formation of blood vessels and lymphatic vessels. Seroma formation was quantified using a syringe and flap adhesion and tissue edema were evaluated clinically through a cranial incision by a blinded observer according to previously described criteria on postoperative day 7. We found a significantly reduced tissue necrosis rate (control: 27.8% ± 8.6; fibrin: 22.0% ± 6.2; 20.9% reduction, p = .053 vs. control; PBMCsec: 19.1% ± 7.2; 31.1% reduction, p = .012 vs. control; 12.9% reduction, 0.293 vs. fibrin) together with increased vWF+ vessel counts (control: 70.3 ± 16.3 vessels/4 fields at 200× magnification; fibrin: 67.8 ± 12.1; 3.6% reduction, p = .651, vs. control; PBMCsec: 85.9 ± 20.4; 22.2% increase, p = .045 vs. control; 26.7% increase, p = .010 vs. fibrin) on postoperative day 7 after treatment with PBMCsec. Seroma formation was decreased after treatment with fibrin sealant with or without the addition of PBMCsec. (control: 11.9 ± 9.7 ml; fibrin: 1.7 ± 5.3, 86.0% reduction, 0.004 vs. control; PBMCsec: 0.6 ± 2.0; 94.8% reduction, p = .001 vs. control; 62.8% reduction, p = .523 vs. fibrin). We describe the beneficial effects of a secretome derived from γ‐irradiated PBMCs on tissue survival, angiogenesis, and clinical parameters after flap surgery in a rodent epigastric flap model.

Background: Large burn injuries induce a systemic response in affected patients. Soluble ST2 (sST2) acts as a decoy receptor for interleukin-33 (IL-33) and has immunosuppressive effects. sST2 has been described previously as a prognostic serum marker. Our aim was to evaluate serum concentrations of sST2 and IL-33 after thermal injury and elucidate whether sST2 is associated with mortality in these patients. Methods: We included 32 burn patients (total body surface area [TBSA] >10%) admitted to our burn intensive care unit and compared them to eight healthy probands. Serum concentrations of sST2 and IL-33 were measured serially using an enzyme-linked immunosorbent assay (ELISA) technique. Results: The mean TBSA was 32.5%±19.6%. Six patients (18.8%) died during the hospital stay. Serum analyses showed significantly increased concentrations of sST2 and reduced concentrations of IL-33 in burn patients compared to healthy controls. In our study cohort, higher serum concentrations of sST2 were a strong independent predictor of mortality. Conclusions: Burn injuries cause an increment of sST2 serum concentrations with a concomitant reduction of IL-33. Higher concentrations of sST2 are associated with increased in-hospital mortality in burn patients.

Partial penectomy (glansectomy with/or without distal corporectomy) is an acceptable alternative for smaller distal pT3 penile carcinoma lesions in highly motivated and compliant patients. The authors describe a novel technique of neo-glans reconstruction using a tunica vaginalis (TV) testis allograft. However, due to an unclear resection margin on final histology, the patient underwent re-do surgery with a neo-glans revision using the well-established mesh split-thickness skin graft (STSG) technique. The penile length was preserved and the penile and bulbar part of the urethra was additionally mobilised in order to obtain a natural and aesthetic result for the meatus. Neo-glans reconstruction with TV coverage may be another promising alternative, which certainly requires further evaluation. We believe that the donor-site associated morbidity is minimal when compared to other harvesting sites. However, this is just an assumption, because direct comparison data on grafting techniques and neo-glans reconstruction are not available. Nevertheless, we think that for re-do procedures a standardised approach using a STSG technique should be the treatment method of choice.

BACKGROUND Split-thickness skin grafting is the gold standard to cover extensive acute and chronic wounds with a well-vascularized wound bed. Although some headway has been made in developing biological agents to speed up healing, there is still no treatment that sufficiently replaces skin grafts to date. The use of secretory factors of adipose tissue may be a feasible approach to developing topical wound applications for faster wound healing. METHODS In this study, the effect of conditioned media (CMs) of human adipose-derived stem cells (ASCs), adipocytes, or adipose tissue on human skin cells was evaluated for viability, proliferation, and migration in vitro. Differentiation potential of stem cells treated with CM was monitored by AdipoRed staining and qualitative real-time polymerase chain reaction. Angiogenic potential of human endothelial cells treated with CM was tested via sprouting assay. RESULTS The CM of adipose tissue significantly enhanced ASC proliferation (P < 0.01). Treatment with CM showed no inductive effect on ASC differentiation into adipocytes but, at the same time, significantly induced cell sprouting of endothelial cells (P < 0.001). We show for the first time that CM of adipose tissue is a potent inducer of proliferation of ASCs and angiogenesis, with comparable effects with those of stem cell-enriched CM. CONCLUSIONS We suggest the use of the secretome of adipose tissue to produce CM for topical application on wounds, rather than working with adipose tissue or including the difficult process of enriching the patients' stem cells in vitro.

BACKGROUND Hypothenar hammer syndrome is a rare vascular lesion of the distal ulnar artery in Guyon tunnel caused by acute or repetitive blunt trauma to the hypothenar eminence. Described treatment options vary greatly, from nonoperative management treatments to surgical interventions. The aim of this study was to evaluate the long-term outcomes of patients after surgical reconstruction of the ulnar artery. METHODS In this retrospective study, the results of 12 patients treated for hypothenar hammer syndrome were evaluated. Preoperative and postoperative examinations of the hand were recorded. Function impairment was assessed with the "Disabilites of the Arm, Shoulder and Hand" questionnaire. Comparisons were also made based on ulnar artery patency versus occlusion. All patients were evaluated for ulnar artery patency as determined by Allen's test and magnetic resonance angiography. RESULTS All patients were men with an average age of 42.8 years. In 3 patients, a direct end-to-end anastomosis of the ulnar artery was performed, and 9 patients received a reconstruction with a reverse interpositional vein graft. Nine vascular reconstructions remained patent after a mean follow-up period of 56.9 months. These patients had a complete or at least partial relief of their pain, dysesthesia, and cold intolerance compared with preoperatively. Patients with reoccluded ulnar arteries were statistically significant younger (P = 0.036) than patients with patent ulnar artery. They also had a higher pain level (P = 0.009) and a longer follow-up period (P = 0.036) than those with patent reconstruction. There was a trend for higher functional impairment in patients with reoccluded ulnar artery (P = 0.100). Smoking habits showed no influence on ulnar artery patency. CONCLUSIONS For patients with symptomatic hypothenar hammer syndrome and failed nonoperative treatment, surgical intervention is a good option. After more than 4.5 years after surgery 9 of 12 vascular reconstructions remained patent (75% patency rate), ensuring an immediate and long-term improvement of symptoms.

The demand for high-bandwidth, low-latency services is rapidly increasing. Content Distribution Networks (CDNs) have addressed this by providing content from within or close to the Internet Service Provider (ISP). Still, the most common bottleneck for high service quality is the 'last mile' between ISP and end user. Serving content from small caches on end-user devices promises to increase service quality of the respective content. Similarly, fog computing promises to provide low-latency services from arbitrary nodes within the network. Both require additional functionality provided by network functions virtualization (NFV), redirecting traffic to the appropriate destinations. Still, the cost and performance of possible solutions are not well analyzed. Hence, this paper analyzes the forwarding and computing performance of a number of single-board computers (SBCs) from which models for the performance and energy cost of different loads are derived. Furthermore, the development of energy efficiency gains over the last years is analyzed, confirming Koomey's law also for SBCs, leading to an increase of computational efficiency by a factor of 5.5 to 7.5 over the course of four years, which relates to a doubling time of 1.62 years.

BACKGROUND The latissimus dorsi muscle flap represents a valuable option in breast reconstruction but can result in postoperative twitching and retraction, discomfort, arm movement limitations, and breast deformation. These complications can be avoided by denervation of the thoracodorsal nerve; however, the optimal method of nerve management is unknown. This study presents the authors' experience with the outcomes of latissimus dorsi flaps for breast reconstruction in the light of thoracodorsal nerve management strategies. METHODS The authors retrospectively collected data from 74 patients who underwent partial or total breast reconstruction with a latissimus dorsi flap alone or with an implant between January of 1999 and October of 2011. Follow-up data were collected at 12 and 24 months postoperatively. RESULTS In 56 patients (75.7 percent), the latissimus dorsi muscle was denervated at the time of surgery, whereas the thoracodorsal nerve remained intact in 18 patients (24.3 percent). No partial or total flap loss was observed. At 12 and 24 months' follow-up, all patients with an intact thoracodorsal nerve showed twitching of the muscle, and 50 percent and 67.9 percent, respectively, of the denervated patients showed twitching (p < 0.001). No patient had twitching if more than 4 cm of nerve was excised at 12 or 24 months postoperatively, and the length of nerve resection was predictive of the presence of twitching. CONCLUSION Denervation of the latissimus dorsi is a safe and reliable procedure that should be performed at the time of breast reconstruction and should include more than 4 cm to achieve a nontwitching breast with a stable volume and shape.

Aims Supernatants of serum-free cultured mononuclear cells (MNC) contain a mix of immunomodulating factors (secretome), which have been shown to attenuate detrimental inflammatory responses following myocardial ischaemia. Inflammatory dilated cardiomyopathy (iDCM) is a common cause of heart failure in young patients. Experimental autoimmune myocarditis (EAM) is a CD4+ T cell-dependent model, which mirrors important pathogenic aspects of iDCM. The aim of this study was to determine the influence of MNC secretome on myocardial inflammation in the EAM model. Methods and results BALB/c mice were immunized twice with an alpha myosin heavy chain peptide together with Complete Freund adjuvant. Supernatants from mouse mononuclear cells were collected, dialysed, and injected i.p. at Day 0, Day 7, or Day 14, respectively. Myocarditis severity, T cell responses, and autoantibody formation were assessed at Day 21. The impact of MNC secretome on CD4+ T cell function and viability was evaluated using in vitro proliferation and cell viability assays. A single high-dose application of MNC secretome, injected at Day 14 after the first immunization, effectively attenuated myocardial inflammation. Mechanistically, MNC secretome induced caspase-8-dependent apoptosis in autoreactive CD4+ T cells. Conclusion MNC secretome abrogated myocardial inflammation in a CD4+ T cell-dependent animal model of autoimmune myocarditis. This anti-inflammatory effect of MNC secretome suggests a novel and simple potential treatment concept for inflammatory heart diseases.

Video constitutes the majority of traffic in ISP networks. The demand for more and higher quality videos is growing rapidly while network capacities are limited. Today, OTT video is mostly delivered over CDNs. For ISP-internal video such as IPTV channels, IP multicast provides an efficient delivery method. However, this does not scale for OTT videos due to their large number and their Zipf-distributed popularity. SDN-based multicast enables ISPs to deliver content based on efficient network-level multicast. However, so far this concept has not been applied for OTT Video-on-Demand (VoD) scenarios. To this end, this paper's contribution is threefold. First, a novel network-based multicast approach for OTT VoD delivery is presented, named VoDCast. Second, trace-based network simulations are designed and conducted. Third, the achievable bandwidth reduction and practicability of VoDCast is shown based on a two-week YouTube trace of a nation-wide mobile provider. VoDCast is able to decrease traffic volume and variance, while keeping network provider costs in terms of state overhead and state change low.

Background Thymomas and thymic carcinomas are rare malignant tumors. We report the experience with the resection and multimodal treatment at a single department in Central Europe in the years 2001 to 2010. Objective We sought to determine prognostic factors in this patient population. Methods A 10-year retrospective analysis of 84 resections on 72 patients for thymomas/thymic carcinomas or their recurrences was performed. Results Patients admitted to a single thoracic surgery center presented with Masaoka–Koga stage I (29.2%), II (43.1%), III (13.9%), and IV (13.9%). In approximately 88.9% of cases, a complete resection could be reached. Using overall survival as an outcome measure, the 5-year survival rate was 87%. Of all the cases presented, 9.7% cases showed tumor recurrence and 6.9% cases showed tumor progression. There was decreased survival rate with increasing Masaoka–Koga stage (p = 0.017) and incomplete resection (p Conclusion Completeness of resection and Masaoka–Koga stage were significant prognostic factors. Multidisciplinary treatments of patients with thymoma or thymic carcinoma result in good patient care, and global efforts with larger number of patients are needed to elucidate more about the biology, diagnosis, and treatment of these tumors.

Background Body contouring surgery after massive weight loss remains a fast growing field due to the rising number of postbariatric surgery patients, and it can improve patients' quality of life substantially. Patient expectations in these procedures are very high, but only little is known as to whether these procedures have a long lasting influence on body image, patient satisfaction, and quality of life. Setting University hospital, Austria. Methods We evaluated 40 consecutive female patients who underwent a lower body lift between 2009 and 2013. Patients took part in a prospective pre- and postoperative questionnaire survey inquiring about their psychological and physical wellbeing. The mean postoperative follow up interval was 61±14 months. We used 2 validated (Body Image Questionnaire and Body Appraisal Inventory) and one self-designed questionnaires (body lift follow-up questionnaire). The postoperative response rate in January 2016 was 72.5%. Results Lower body lift significantly reduced dismissive body ratings and increased long-term feelings of attractiveness and self-esteem, and significantly reduced discomfort associated with excess skin. Patients reported feeling happier, more attractive, and more self-confident. The procedure enhanced their physical wellbeing, even years after surgery. Conclusion Lower body lift satisfied patients' expectations and improved long-term quality of life. Therefore, it is an essential component in the treatment of patients who have experienced massive weight loss.

Burn wounds pose a serious threat to patients and often require surgical treatment. Skin grafting aims to achieve wound closure but requires a well-vascularized wound bed. The secretome of peripheral blood mononuclear cells (PBMCs) has been shown to improve wound healing and angiogenesis. We hypothesized that topical application of the PBMC secretome would improve the quality of regenerating skin, increase angiogenesis, and reduce scar formation after burn injury and skin grafting in a porcine model. Full-thickness burn injuries were created on the back of female pigs. Necrotic areas were excised and the wounds were covered with split-thickness mesh skin grafts. Wounds were treated repeatedly with either the secretome of cultured PBMCs (SecPBMC), apoptotic PBMCs (Apo-SecPBMC), or controls. The wounds treated with Apo-SecPBMC had an increased epidermal thickness, higher number of rete ridges, and more advanced epidermal differentiation than controls. The samples treated with Apo-SecPBMC had a two-fold increase in CD31+ cells, indicating more angiogenesis. These data suggest that the repeated application of Apo-SecPBMC significantly improves epidermal thickness, angiogenesis, and skin quality in a porcine model of burn injury and skin grafting.

IntroductionLung cancer represents a major healthcare problem. Accordingly, there is an urgent need to identify serum biomarkers for early diagnosis of lung pathology. We have recently described that patients with manifest COPD evidence elevated levels of heat shock proteins (HSPs). Based on these data, we speculated whether HSPs are also increased in patients with diagnosed lung cancer.MethodsSerum levels of HSP27, phospho-HSP27 (pHSP27) and HSP70 in patients with non-small cell lung cancer (NSCLC) diagnosed at an early (stages I–II, n=37) or advanced (stages IIIA–IV, n=72) stage were determined by using ELISA. Healthy smokers (n=24), healthy never-smoker volunteers (n=33) and COPD patients (n=34) according to GOLD classification served as control population.ResultsSerum levels of HSP27 were elevated in patients with NSCLC diagnosed at an early or advanced stage when compared with both healthy control groups (P

Background Evidence regarding hypercoagulability in the first week after burn trauma is growing. This hypercoagulable state may partly be caused by increased fibrinogen levels. Rotational thrombelastometry offers a test which measures functional fibrinogen (FIBTEM®). To test the hypothesis that in patients with severe burn injury fibrinogen function changes over time, we simultaneously measured FIBTEM® and fibrinogen concentration early after burn trauma. Methods After Ethics Committee approval consecutive patients with severe burn trauma admitted to the burn intensive care unit of the General Hospital of Vienna were included in the study. Blood examinations were done immediately and 12, 24 and 48 h after admission. At each time point fibrinogen level (Clauss) and 4 commercially available ROTEM® tests were performed. Results 20 consecutive patients were included in the study. Fibrinogen level and FIBTEM® MCF were within the reference range until 24 h after burn trauma but increased significantly 48 h after trauma. There was a significant correlation between FIBTEM® MCF and fibrinogen level (R = 0.714, p Conclusion The results of this prospective observational clinical study show that fibrinogen function changes early after burn trauma and can be visualized by ROTEM® with the fibrinogen-sensitive FIBTEM® test.

Drug monitoring of low molecular weight heparin is generally not recommended, but could be reasonable in critically ill patients, whose risk for bleeding or thrombosis shows a high interpatient variability. Anti-Xa assays are not available around the clock even in central hospitals, whereas rotational thrombelastometry (ROTEM) becomes increasingly used at the bedside. Prothrombinase-induced clotting time (PiCT) reagent allows determination of factor Xa-inhibition in plasma. The aim of our study was to evaluate enoxaparin determination in whole blood with the ROTEM using specific test modifications, including PiCT. After ethics committee's approval, citrated whole blood obtained from overall 16 healthy volunteers was incubated with enoxaparin at 16 different anti-Xa concentrations. Main endpoint was the clotting time (CT) in ROTEM representing initial activation of clot formation. CT was determined in the new PiCT-ROTEM test, in a low-tissue factor-activated modification (LowTF-ROTEM) as well as in the commercially available heparin-sensitive ROTEM assays (HEPTEM and INTEM). In the absence of enoxaparin, CT values were 168.6 +/- 6.1 s (PiCT-ROTEM), 247.3 +/- 18.6 s (LowTF-ROTEM), and -6.2 +/- 7.9 s (INTEM-HEPTEM). A linear dependency (P < 0.01) between anti-Xa concentration and CT was found for PiCT-ROTEM, LowTF-ROTEM, and for INTEM-HEPTEM with correlation coefficients of 0.93 for PiCT-ROTEM, 0.94 for LowTF-ROTEM, and 0.81 for INTEM-HEPTEM. This in-vitro experiment demonstrates a strong correlation between enoxaparin anti-Xa concentrations and specific ROTEM tests. These promising assays should be further evaluated for monitoring anticoagulation in high-risk patients in clinical studies.

Background: Inflammatory processes are involved in the pathogenesis of coronary artery disease and acute myocardial infarction (AMI). Yet there is little known about concentrations of pro-inflammatory mediators in the cardiac milieu of patients suffering from AMI. The aim of this study was to evaluate blood samples directly obtained from the culprit coronary artery during AMI. Materials and Methods: Serum samples were obtained from the culprit coronary artery of AMI patients (n=39) using a X-sizer thrombectomy system. Sera from patients with stable angina (SA, n=34) and unstable angina (UA, n=37) served as controls. Levels of sCD40, sCD40L, TNFα, and sTNF-RI were determined by enzyme-linked immunosorbent assays. Results: Levels of sCD40L and sCD40 were increased in the AMI group when compared to patients suffering from SA and UA. Levels of both inflammatory markers were highest in the culprit coronary artery. Increased concentrations of TNFα and sTNF-RI evidenced a further inflammatory response at the site of infarction. Conclusions: We conclude that mediators of inflammation are heightened in the coronary blood flow during myocardial infarction. Our observations extend the current knowledge of the inflammatory cascade during myocardial infarction.

The pro-inflammatory cytokine IL-18 and its activator Caspase-1 are involved in acute liver failure and acute-on-chronic-liver-failure. In acute liver failure and acute-on-chronic-liver-failure, the MARS system has been used to support liver function. Enhancement of IL-18, as seen in other extracorporeal-support systems like hemodialysis might thus have mitigated beneficial effects of the MARS system in acute hepatic failure.We measured serum concentrations of IL-18 and Caspase-1 in 10 patients with acute liver failure and 10 patients suffering from acute-on-chronic-liver-failure, who were all treated with MARS. Thirteen patients suffering from chronic hepatic failure and 15 healthy individuals served as controls. Data are given as mean with 95% CI.Baseline IL-18 serum concentrations were significantly increased in acute liver failure and acute-on-chronic-liver-failure patients as compared to chronic hepatic failure (P=0.0039 and P=0.0011, respectively) and controls (P=0.0028 and P=0.0014, respectively). Caspase-1 serum concentrations were as well significantly elevated in the acute liver failure and acute-on-chronic-liver-failure groups as compared to chronic hepatic failure patients (P=0.0039 and P=0.0232, respectively) and controls P0.0001 and P0.0007, respectively). IL-18 and Caspase-1 did not change significantly during MARS treatment in acute liver failure and acute-on-chronic-liver-failure patients.MARS had no effect on IL-18 and Caspase-1 serum concentrations in acute liver failure and acute-on-chronic-liver-failure, providing no evidence of harmful effects by the increase of these potentially hepatocidal cytokines.

Background Acute myocardial infarction (AMI) is followed by post AMI cardiac remodelling, often leading to congestive heart failure. Homing of c-kit+ endothelial progenitor cells (EPC) has been thought to be the optimal source for regenerating infarcted myocardium. Methods Immune function of viable peripheral blood mononuclear cells (PBMC) was evaluated after co-culture with irradiated apoptotic PBMC (IA-PBMC) in vitro. Viable PBMC, IA-PBMC and culture supernatants (SN) thereof were obtained after 24 h. Reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay were utilized to quantify interleukin-8 (IL-8), vascular endothelial growth factor, matrix metalloproteinase-9 (MMP9) in PBMC, SN and SN exposed fibroblasts. Cell suspensions of viable- and IA-PBMC were infused in an experimental rat AMI model. Immunohistological analysis was performed to detect inflammatory and pro-angiogenic cells within 72 h post-infarction. Functional data and determination of infarction size were quantified by echocardiography and Elastica van Gieson staining. Results The IA-PBMC attenuated immune reactivity and resulted in secretion of pro-angiogenic IL-8 and MMP9 in vitro. Fibroblasts exposed to viable and IA-PBMC derived SN caused RNA increment of IL-8 and MMP9. AMI rats that were infused with IA-PBMC cell suspension evidenced enhanced homing of endothelial progenitor cells within 72 h as compared to control (medium alone, viable-PBMC). Echocardiography showed a significant reduction in infarction size and improvement in post AMI remodelling as evidenced by an attenuated loss of ejection fraction. Conclusion These data indicate that infusion of IA-PBMC cell suspension in experimental AMI circumvented inflammation, caused preferential homing of regenerative EPC and replaced infarcted myocardium.

BACKGROUND We have previously shown that the alpha-Gal (Galalpha1.3-Galbeta1-4GlcNAc-R) epitope is a relevant xenoantigen present on bioprostheses utilized in cardiac surgery and elicits an alpha-Gal specific IgM immune response. We sought to investigate whether that immune response continues after valve implantation. MATERIALS AND METHODS We collected plasma samples from patients who underwent bioprosthesis implantation (n = 19) or mechanical valve replacement (n = 8), respectively, prior to, at 10 days and at 3 months after cardiac surgery. ELISA was utilized to quantify alpha-Gal specific IgG and IgG subclasses. 3 bioprosthetic tissue samples were obtained from patients who had to undergo re-operation within 1 week (n = 1) or at 12-15 months (n = 2) after the initial operation. We utilized confocal laser scanning microscopy (CLSM) to detect the presence of alpha-Gal epitopes (IB4) and cell nuclei (DAPI). RESULTS alpha-Gal specific IgG was significantly increased 3 months after implantation of bioprostheses compared to preoperative values (p < 0.001) and was significantly higher than alpha-Gal specific IgG levels of the control group (p < 0.05). IgG3 was the major subclass directed against alpha-Gal (p < 0.05, pre- vs. postoperative values). In CLSM analysis we demonstrated that bioprostheses explanted 1 week after implantation contained IB4/DAPI positive cells within the collagen matrix. In contrast, in patients who underwent reoperation after 12 months, porcine tissue showed a complete lack of IB4/DAPI. CONCLUSION Our results indicate that the implantation of bioprostheses elicits a specific humoral immune response against alpha-Gal bearing cells compared to controls within 3 months after cardiac surgery. The complete absence of IB4/DAPI positive structures 12 months after implantation indicates a specific degradation of alpha-Gal bearing cells through previous exposure to the human blood circuit.

SummaryPathogenetic mechanisms leading to chronic obstructive pulmonary disease (COPD) remain poorly understood. Because clonogenic T cells (CD4+CD28null) were shown to be increased in autoimmune diseases we hypothesized that CD4+CD28null T cells play a role in COPD. Here we describe that enhanced presence of CD4+CD28null cells is associated with impaired lung function. Sixty-four patients and controls were included. T cell phenotype was analysed using flow cytometry. Enzyme-linked immunosorbent assays were utilized to determine cytokines. Statistical evaluations were performed using non-parametric group comparisons and correlations. A logistic regression model was used to determine predictive values of CD4+CD28null in the diagnosis of COPD. Populations of CD4+ T cells lacking surface co-stimulatory CD28 were enlarged significantly in evaluated patients when compared with controls. Natural killer (NK)-like T cell receptors (CD94, 158) and intracellular perforin, granzyme B were increased in CD4+CD28null cells. Cytokine production after triggering of peripheral blood mononuclear cells (PBMCs) was elevated in patients at early disease stages. Receiver operating characteristic curve plotting revealed that presence of CD4+CD28null T cells has a diagnostic value. These CD4+CD28null T cells show increased expression of NK-like T cell receptors (CD94, 158) and intracellular perforin and granzyme B. Furthermore, triggering of PBMCs obtained from patients with mild COPD led to increased interferon-γ and tumour necrosis factor-α production in vitro compared with controls. Our finding of increased CD4+CD28null T cells in COPD indicates that chronic antigen exposure, e.g. through contents of smoke, leads to loss of CD28 and up-regulation of NK cell receptors expression on T cells in susceptible patients.

Summary Background Intravenous immunoglobulins (IVIg) and cytomegalovirus immunoglobulins (CMVIg) are currently finding increased acceptance in clinical states of high immune activity and in transplant recipients. A rare side-effect of their application is intravascular thrombosis, which is thought to be related to pre-existing hyperviscosity. In a previous study we have shown that rabbit antithymocyte globulin causes platelet aggregation in vitro via the Fc IgG receptor (CD32). Objectives To investigate if IVIg and CMVIg have the potential to cause CD32-dependent platelet aggregation. Methods The influence of CMVIg or IVIg on platelets pre-incubated with or without monoclonal antibody AT10 was studied in an aggregometer. Expression of platelet surface activation marker CD62P was determined by fluorescence-activated cell sorting analysis and presence of soluble CD40L (sCD40L) was evaluated by enzyme-linked immunosorbent assay. All in vitro experiments were performed using platelet concentrates from the blood bank, at therapeutic concentrations of immunoglobulins. Results Incubation of platelets with CMVIg and IVIg markedly induced platelet aggregation, and increased expression of CD62P and secretion of sCD40L. The capacity of CMVIg and IVIg to induce platelet aggregation was completely abrogated by adding the blocking antibody AT10 directed against the low-affinity Fc IgG receptor (CD32). Conclusions Our results suggest that CMVIg and IVIg solutions with activating Fc domains are able to bind CD32 on platelets and cause platelet aggregation in vitro. These results indicate a mechanism by which in vivo intravascular thrombosis may be explained and suggest caution with concomitant use of packed platelets and IVIg in autoimmune diseases in the clinical setting.

Background Systemic inflammation and apoptosis-specific immune activation play a major role in acute coronary syndromes (ACS) including acute myocardial infarction (AMI). The role of systemic and coronary obtained inflammatory plasma protein interleukin-1β precursor (IL-1βp), IL-1β-converting enzyme (ICE) and the apoptosis-specific caspase-cleaved cytokeratin-18 (ccCK-18) are not known in ACS. Materials and methods Plasma samples were obtained from stable angina (SA, n = 34), unstable angina (UA, n = 37) and patients with AMI (n = 39). Coronary blood was acquired by means of thrombectomy devices (X-sizer) in AMI patients. IL-1βp, ICE and ccCK-18 were determined by enzyme-linked immunosorbent assay (ELISA). Group comparisons were evaluated by parametric Tukey test. Multivariate logistic regression analysis was performed to determine predictive values of IL-1βp, ICE and ccCK-18 as compared to creatine kinase (CK) and troponin T (TnT) in order to relate these markers with the occurrence of myocardial damage. Results IL-1βp, ICE and ccCK-18 were identified to be significantly altered in the peripheral blood of patients suffering from AMI as compared to SA and UA. ROC curves were plotted and revealed that ccCK-18 is a novel sensitive marker for the detection of myocardial damage as compared to TnT or CK. (AUC ccCK-18 0·925, TnT AUC 0·62 and CK AUC 0·858.) Moreover, ICE and ccCK-18 were significantly increased at the site of coronary occlusion as compared to peripheral blood samples in AMI patients (both P

We have read with great interest the work by Cui et al. (2015) and the letter to the Editor by Cappello et al. (2015). Historical knowledge of data acquisition and interpretation is paramount in the field of applied medical research. Our group was the first to describe increased HSP27 serum concentrations in patients with incipient and manifest COPD, in patients with lung cancer (Hacker et al. 2009; Ankersmit et al. 2012; Zimmermann et al. 2012) and patients with end-stage kidney disease (Lebherz-Eichinger et al. 2008). All these information originated from our research dating back to 2006. In this work, our group (a) investigated serum HSP27/60/70/90 content in patients that underwent coronary artery bypass grafting (CABG) surgery (Szerafin et al. 2008) and (b) identified COPD as an autoimmune disease (Lambers et al. 2009). How was this serum HSP27 insight generated in our laboratory? (a) We have collected serum samples of mild and severe COPD and these were stored at our biobank; (b) A Croatian research group had investigated for the first time the role of HSP27/70 in peripheral blood mononuclear cells (PBMC) derived from COPD patients (Lada et al., 2008); (c) Serendipity was in play since the right R&D HSP27/70 ELISA kit, as “left over” from a prior CABG study and was present in our fridge. All these coincidences led to granted patents stating that HSP27 has the potential to be a serum biomarker for early and manifest COPD and lung cancer (EP2141499, EP2652504). By interpreting the report by Cui et al. (2015) and its comment by Cappello et al. (2015), we want to allude to a recent publication by our research group (Zimmermann et al. 2014). It has to be accepted by the community that an ELISA detection kit for protein XY is sometimes not detecting protein XY (Mueller et al. 2012). In order to investigate this question, we have selected lung cancer patients with known increased serum HSP27 and evaluated five commercially available assays for HSP27 measurement with respect to their capabilities to differentiate non-small cell lung cancer (NSCLC) patients from healthy controls. The following HSP27 ELISA kits were utilized: RD Enzo Life Sciences, 0.823; Invitrogen, 0.780; Abcam 0.642; and MyBioSource, 0.523. From these results, we concluded that it was pure coincidence that we have unintentionally picked the “right” ELISA kit for our investigations in our study period (2007–2015). Abcam or MyBioSource commercial ELISA system would have completely failed to show any difference in our laboratory investigations. We conclude that the results of our clinical method comparison study revealed that commercially available HSP27 assays are not equally useful in detecting increased serum HSP27. By looking at Cui et al. (2015), we observed that a Stressgen Bioreagent HSP27 ELISA was utilized. Since we have not included this commercially available ELISA system in our study, we have difficulty in interpreting the presented results. Since our R&D HSP27 ELISA has repetitively corroborated our primary data set in COPD/lung cancer (>400 patients), it might be possible that Stressgen is detecting another moiety of HSP27 as compared to the R&D HSP27 system. As far as we are concerned, we believe that scientific statements, discussions and publications dealing with serum HSP27 and COPD/lung cancer are important when comparative methodologies are utilized. In conclusion, from an epistemological standpoint, it is of great interest to accept that non-hypothesis-driven “luck factor” has helped to gain a better understanding in COPD genesis. The future will show whether the scientific community will be able to present a biomarker to the public that is able to identify patients with risk to develop COPD or lung cancer. We are deeply convinced that only commercial interest will bring this important knowledge into the realm of clinics.

Background Although implantation of a central venous device such as a Port-a-Cath was initially considered safe, extravasation rates up to 4.7% have been reported. Therefore, the objective of this study was to propose a structured procedure for the management of extravasation of a cytotoxic treatment. Methods A total of eight patients were evaluated after port extravasation of epirubicin ( n = 3), platinum compounds ( n = 3), paclitaxel ( n = 1), or trabectedin ( n = 1) into the subcutaneous space. Immediate explantation of the port was performed in combination with a "Subcutaneous Wash-Out Procedure" (SWOP). When removal of the port was delayed, debridement and flap coverage were performed as necessary. Epirubicin concentrations present in the samples obtained during surgical intervention were subsequently analysed using high-performance liquid chromatography (HPLC). Patients were followed for at least six months and were examined for sequelae such as pain, induration, redness, and limited movement. Results All three patients whose extravasation event was detected during chemotherapy administration benefited from SWOP with acceptable side effects (e.g., erythema). The analysis of epirubicin concentrations demonstrated the active removal of relevant amounts of the compound by wound rinsing. In contrast, late detection of extravasation led to major debridement and flap coverage in four out of five patients. A high body mass index (BMI) value was associated with all of the patients that experienced port extravasation. Conclusion Depending on when Port-a-Cath ® extravasations into subcutaneous tissue are detected, different treatments are appropriate. When extravasation is detected early, the SWOP was found to be beneficial.

Nipple reconstruction is of importance in achieving the best possible aesthetic outcome after breast reconstruction. Nipple sharing is a common technique; this study focused on the potential morbidity at the donor nipple. Between 2008 and 2012, 26 patients underwent nipple sharing at our institution. The donor nipple was examined before and after the procedure (mean follow-up of 21 months). Sensitivity, projection, diameter, and patient satisfaction were evaluated. The sensitivity in the donor nipple decreased, albeit insignificantly, from 1.2 g/mm2 (0.8-1.6) to 1.8 g/mm2 (0.8-4.8) (p=0.054, n=26). The projection due to graft removal decreased from 8.0 mm (6.8-10.0) to 4.5 mm (4.0-5.0) (p=0.001). Of the patients, 88% were "very satisfied" or "somewhat satisfied" with the sensitivity and 89% with the symmetry between the donor and reconstructed nipple. At least 60% of the patients were "very satisfied" with all aesthetic outcome parameters (projection, appearance, naturalness, color, and shape). All patients would agree to undergo this procedure again, if necessary. Nipple sharing was associated with minimal morbidity at the donor nipple. The postoperative projection was adequate. Regardless of whether simultaneous mastopexy was performed, the loss of sensitivity was minimal and presumably imperceptible to the patient. By using no sutures after graft removal and letting the donor nipple heal spontaneously, scarring was minimized and the natural appearance and good sensitivity of the donor nipple were preserved.

Adequate monitoring of the effect of the direct thrombin inhibitor argatroban may facilitate individualized dosing and perioperative management of anticoagulation. Ecarin Clotting Time is proposed for this purpose, but has the major disadvantage of limited availability. There is a point-of-care applicable ecarin-activated test modification for rotational thrombelastometry (ROTEM®) which is sensitive to direct thrombin inhibitors. The aim of the study was to evaluate the correlation between argatroban concentration and this ecarin modified thrombelastometry (EMT). In this in vitro experiment, blood drawn from healthy volunteers was spiked with argatroban at clinically relevant concentrations and analyzed with ROTEM® using EMT. The main endpoint was the clotting time (CT). EMT-CT was prolonged with increasing argatroban concentrations (from 83.3 ± 6.7 s without argatroban to 743.5 ± 138.2 s at 2 μg/ml argatroban). The correlation between argatroban concentration and EMT-CT was high (r = 0.94) and statistically significant (p

Summary Background Lower body lift procedures are in high demand following the increase of massive weight loss patients. As surgical complication rates in this patient group are generally high, patients need to be prepared for risk factors and complications in lower body lift surgery. The aim of this study was to identify the complications and possible risk factors of a lower body lift as concrete data for this procedure are limited. Methods A prospective study on 50 consecutive patients who underwent a lower body lift procedure was performed. Measures included co-morbidities and complications. Risk factors assessed included patient age, gender, highest lifetime body mass index (BMI) (BMI max), current BMI, excess weight loss (EWL), type of weight loss and nicotine consumption. Results There were 50 patients (44 females, six males) with a mean age of 41 ± 10.8 years and a mean EWL of 86.4 ± 15.6%. Mean BMI max was 49.5 ± 10.5 kg m −2 , current BMI was 27.8 ± 4.0 kg m −2 . A total of 35 (70%) patients developed at least one complication. Five patients (10%) suffered a major complication that necessitated surgical revision. Wound dehiscence occurred in 30 patients (60%), followed by seroma in 17 patients (34%). A surgical complication was directly related to BMI max ( p = 0.02) and age of the patient at the time of surgery ( p = 0.03). Conclusions The overall complication rate following a lower body lift was 70%, which is comparable with that known for high-risk patient groups. The most important risk factors are BMI max and age of the patient (Clinical trial registration number (ISRCTN): NCT01551862).

Introduction: Chronic obstructive pulmonary disease (COPD) is a worldwide burden and a major cause of death. The disease is accompanied by chronic inflammation and increased cellular turnover that is partly due to an overwhelming induction of apoptosis. In this study, we hypothesized that systemic markers of apoptosis are altered in patients with mild‐to‐severe COPD. Materials and Methods: A total number of 64 patients and controls were enrolled in the study. Lung function parameters of all groups (nonsmoker, healthy smoker, COPD GOLD I&II, COPD GOLD III&IV) were evaluated at the time of inclusion. Enzyme‐linked immunosorbent assays were used to quantify protein levels in serum samples. Results: Serum contents of apoptotic end‐products caspase‐cleaved cytokeratin‐18 and histone‐associated‐DNA‐fragments were increased in patients with COPD, whereas anti‐inflammatory soluble ST2 showed a peak in patients with COPD I&II (P=0.031) compared to healthy smokers. Levels of pro‐inflammatory caspase‐1/ ICE correlated significantly with the number of pack years (R=0.337; P=0.007). Discussion: Our results indicate a systemic release of apoptosis‐specific proteins as markers for increased cellular turnover accompanied by progression of COPD. Furthermore, soluble ST2 seems to have a critical role in the anti‐inflammatory regulatory mechanism at early stages of the disease. J. Clin. Lab. Anal. 23:372–379, 2009. © 2009 Wiley‐Liss, Inc.

Histological response of colorectal cancer liver metastases to chemotherapy may be graded based on the extent of tumor regression. The knowledge about the effect of bevacizumab, if given in addition to fluoropyrimidines and oxaliplatin, on tumor regression and its consequences on clinical outcome is limited. Resected liver metastases from patients of 2 prospective nonrandomized trials (fluoropyrimidines and oxaliplatin ± bevacizumab) were analyzed retrospectively. Histological response was analyzed according to an established tumor regression grading for colorectal cancer liver metastases. Tumor regression grades (TRGs) were correlated to progression-free and overall survival. Bevacizumab improved tumor regression to chemotherapy significantly. Improvement in histological response was translated into a significant prolongation of progression-free and overall survival. Classifying histological response based on tumor regression grades qualifies to predict the outcome of patients with colorectal cancer liver metastases. Tumor regression grading provides a standardized pathological response evaluation, against which radiologic response on chemotherapy including biologicals can be prospectively evaluated.

BACKGROUND Cardiopulmonary bypass is known to affect cytokine release leading to a generalized endogenous immune reaction similar to that described in sepsis, without having been explored in great detail. Therefore we evaluated the anti- and pro-inflammatory cytokine responses after heart surgery. METHODS 16 patients who underwent coronary artery bypass graft (CABG) surgery with extracorporeal circulation were included. ST2, IL-4 and IL-10 served as markers for TH2 cytokine response; IL-6, IL-8 and IFN-gamma as TH1 markers. Furthermore, total immunoglobulin subtype analysis (IgM, IgG, IgE) was performed. RESULTS Serum levels of soluble ST2 started to climb at 60 minutes (from 38 +/- 14 preoperatively to 1 480 +/- 890 pg/ml) and peaked 24 hours after surgery (13 360 +/- 2 840 pg/ml, P < 0.001). IL-10 reached a maximum at 60 minutes and returned to baseline levels 24 hours later. IL-6 and IL-8 levels peaked 60 minutes after surgery. IL-4 and IFN-gamma did not change. Only IgM showed a significant peak on day eight ( P < 0.001). CONCLUSION Our results demonstrate that CABG surgery induces a massive long-lasting secretion of ST2, a protein related to immune suppression.

Aim In patients suffering from colorectal cancer liver metastases, 5-fluorouracil-based chemotherapy plus oxaliplatin ensures superior response rates at the cost of hepatic injury. Knowledge about the consequences of bevacizumab on chemotherapy-induced hepatic injury and tumor response is limited. Methods Resected liver specimens from patients of two prospective, non-randomized trials (5-fluorouracil/oxaliplatin ± bevacizumab) were analyzed retrospectively. Hepatotoxicity to the non-tumor bearing liver was evaluated for sinusoidal obstruction syndrome, hepatic steatosis and fibrosis. Tumor response under chemotherapy was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST). Results Bevacizumab decreased the severity of the sinusoidal obstruction syndrome. Bevacizumab had no impact on hepatic steatosis and fibrosis. The addition of bevacizumab to chemotherapy had no effect on tumor response compared to combination chemotherapy alone. Conclusions This analysis shows that bevacizumab protects against the sinusoidal obstruction syndrome and thus provides the histological explanation of the safe use of bevacizumab prior to liver resection. Furthermore, we show that bevacizumab does not improve tumor response according to RECIST.

Pulmonary benign metastasizing leiomyomatosis (BML) is a rare smooth-muscle cell disorder of the lung. Most BML lesions stay constant in size for a long time. The prevailing treatment option is primary excision of the nodules or if unresectable, long-time hormone therapy. Herein, we present a case of BML in which a wait-and-see strategy after diagnosis was decided. Fourteen years later a routine chest roentgenogram revealed multiple bi-lobar BML lesions with a giant cyst filling the whole left lung cavity. We conclude that a wait-and-see procedure for BML is feasible, but primary resection of the BML tumor masses is preferable to avoid complications as described in our case.

Aim The aim of this study was to assess chemotherapy associated hepatotoxicity after 3 months' treatment and to correlate patterns of hepatotoxicity with perioperative morbidity. Methods Liver specimens of 50 patients with liver metastases from colorectal cancer receiving XELOX or FOLFOX4 for six cycles and 13 specimens of non-chemotherapy patients subjected to liver resection were analyzed. Different patterns of hepatotoxicity were evaluated according to widely accepted pathohistological scores. Furthermore, the histomorphological findings were correlated with perioperative morbidity. Results Steatosis grades did not differ among the chemotherapy treated groups and non-chemotherapy patients. Chemotherapy showed an independent effect on fibrosis stage. Age and chemotherapy were independently associated with sinusoidal dilatation. Centrilobular vein fibrosis correlated with administration of chemotherapy. Higher fibrosis stages were associated with increased transfusion requirements. Conclusion XELOX and FOLFOX4 do not correlate with the development of steatosis or steatohepatitis. We do not detect a difference in liver injury between the XELOX and FOLFOX4 group. Although 5-fluorouracil based chemotherapy may cause profound changes in liver parenchyma, it can be safely applied. However, age and oxaliplatin predispose for the development of sinusoidal dilatation; therefore caution must be taken in old patients treated with oxaliplatin.

The secretion of heat shock protein (HSP) 27, HSP60, HSP70, HSP90alpha, 20S proteasome, and their correlations to proinflammatory cytokine interleukin-6 is unknown in patients undergoing on-pump versus off-pump coronary artery bypass graft (CABG) operation.Forty patients were included in this explorative study (on- versus off-pump CABG, each n = 20). Serum samples were obtained before and 30 minutes, 60 minutes, and 24 hours after CABG operation. Enzyme-linked immunosorbent assay technique was utilized to determine soluble HSP27, 60, 70, and 90alpha, 20S proteasome, and levels of interleukin-6.Serum levels of HSP are increased in patients undergoing on-pump CABG operation as compared with off-pump CABG technique. These differences were highly significant for HSP27, 70, and 90alpha at 60 minutes after initiation of cardiopulmonary bypass (all, p0.001). Concentrations of soluble 20S proteasome were increased 24 hours after operation in on- and off-pump CABG patients (p0.001) and correlated significantly with the serum content of HSP 27, 70, and 90alpha at 60 minutes after initiation of cardiopulmonary bypass (p0.001). No correlation was found when comparing interleukin-6 levels with intravascular leakage of HSP and 20S proteasome after CABG operation.We conclude from our data that the innate immune system is activated owing to spillage of known immune modulatory and apoptosis-associated proteins after CABG operation.

Giant cell myocarditis (GCM) is a rare and frequently fatal disorder. Patients suffer of ventricular arrhythmias or congestive heart failure. Here we describe a patient with cardiogenic shock and histological verified GCM. The patient was saved by implantation of extracorporeal membrane oxygeneation (ECMO) device and concomitant application of Rabbit antithymocyte globuline (rATG, Thymoglobulin, Sangstat), cyclosporine, and steroids in the acute event. 12 months after the crisis the patient evidences NYHA class I heart function and only a moderate impairment of heart function (EF 55%). The novel utilisation of ECMO in GCM related cardiogenic shock and application of rATG have prooven life-saving in this patient. Studies utilizing rATG in the treatment of GCM are warrented.