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Advanced strategies in reconstructive microsurgery and especially free tissue transfer with advanced microvascular techniques have been routinely applied and continously refined for more than three decades in day-to-day clinical work. Bearing in mind the success rates of more than 95%, the value of these techniques in patient care and comfort (one-step reconstruction of even the most complex tissue defects) cannot be underestimated. However, anticoagulative protocols and practices are far from general acceptance and – most importantly – lack the benchmark of evidence basis while the reconstructive and microsurgical methods are mostly standardized. Therefore, the aim of our work was to review the actual literature and synoptically lay out the mechanisms of action of the plethora of anticoagulative substances. The pharmacologic prevention and the surgical intervention of thrombembolic events represent an established and essential part of microsurgery. The high success rates of microvascular free tissue transfer as of today are due to treatment of patients in reconstructive centers where proper patient selection, excellent microsurgical technique, tissue transfer to adequate recipient vessels, and early anastomotic revision in case of thrombosis is provided. Whether the choice of antithrombotic agents is a factor of success remains still unclear. Undoubtedly however the lack of microsurgical experience and bad technique can never be compensated by any regimen of antithrombotic therapy. All the more, the development of consistent standards and algorithms in reconstructive microsurgery is absolutely essential to optimize clinical outcomes and increase multicentric and international comparability of postoperative results and complications.

Abstract Background Adenoviral vectors have provided effective methods for in vivo gene delivery in therapeutic applications. However, these vectors can induce immune responses that may severely affect the ability of vector re-application. There is limited information about the mechanisms and signal transduction pathways involved in adenoviral recognition. For optimization of cutaneous gene therapy it is necessary to investigate molecular mechanisms of virus recognition in epidermal cells. The aim of this study was to investigate the signal transduction of the innate immunity after adenoviral DNA internalization in keratinocytes. Methods In vitro, keratinocytes were transfected with DNA, in the presence and absence of inhibitors for signalling molecules. In vivo, immunocompetent and athymic mice (n = 3 per group) were twice transduced with an Ad-vector. Results The results show an acute induction of type-I-interferon after in vitro transfection. Inhibition of PI3K, p38 MAPK, JNK and NFkappaB resulted in a decreased expression of type-I-interferon. In contrast to immunocompetent mice, athymic mice demonstrated a constant transgene expression and reduced inflammatory response in vivo. Conclusion The results suggest an induction of the innate immunity triggered by cytoplasm localised DNA which is mediated by PI3K-, p38 MAPK-, JNK-, NFkappaB-, JAK/STAT- and ERK1/2-dependent pathways. A stable transgene expression and a reduced inflammatory response in immunodeficient mice have been observed. These results provide potential for an effective adenoviral gene delivery into immunosupressed skin.

Abstract Background Complications arising from accidental intraarterial drug injections have been described in the past. However, given the multitude of injected substances and complex pathophysiology, guidelines regarding diagnosis and management of patients with intraarterial injections remain vague. As such it remains unclear, when to expect limb ischemia and whether and for how long to monitor patients after intraarterial injections. Case report We present the case of a "near miss event" in an i.v. drug abuser presenting to the emergency department 3 hours after injection of water dissolved zolpidem (Ambien™) tablets into the right ulnar artery. Chief complaint was forearm pain. Clinical examination at the time revealed no concern for limb ischemia and patient was discharged. The patient returned unplanned 18 hours after injection with an ischemic right hand. Angiography revealed no flow in the distal ulnar artery and minimal flow in the palmar arch. Emergent intraarterial thrombolysis with Urokinase was performed and restored hand perfusion. Clinical follow-up 3 months after injury showed full recovery with regular recapillarisation and normal Allen test. Conclusion This case report highlights the need to rigorously monitor patients with suspected intraarterial injections for potential delayed onset of limb ischemia. This is to our knowledge the first described case report of a successful revascularization after prolonged ischemia with delayed onset after zolpidem injection. We recommend close monitoring of these patients for at least 24 hours in addition to starting prophylactic anticoagulation.

Background: Adenoviral vectors have provided effective methods for in vivo gene delivery in therapeutic applications. However, these vectors can induce immune responses that may severely affect the ability of vector reapplication. There is limited information about the mechanisms and signal transduction pathways involved in adenoviral recognition. For optimization of cutaneous gene therapy it is necessary to investigate molecular mechanisms of virus recognition in epidermal cells. The aim of this study was to investigate the signal transduction of the innate immunity after adenoviral DNA internalization in keratinocytes. Methods: In vitro, keratinocytes were transfected with DNA, in the presence and absence of inhibitors for signalling molecules. In vivo, immunocompetent and athymic mice (n = 3 per group) were twice transduced with an Ad-vector. Results: The results show an acute induction of type-I-interferon after in vitro transfection. Inhibition of PI3K, p38 MAPK, JNK and NFkappaB resulted in a decreased expression of type-I-interferon. In contrast to immunocompetent mice, athymic mice demonstrated a constant transgene expression and reduced inflammatory response in vivo. Conclusion: The results suggest an induction of the innate immunity triggered by cytoplasm localised DNA which is mediated by PI3K-, p38 MAPK-, JNK-, NFkappaB-, JAK/STAT- and ERK1/2-dependent pathways. A stable transgene expression and a reduced inflammatory response in immunodeficient mice have been observed. These results provide potential for an effective adenoviral gene delivery into immunosupressed skin. [ABSTRACT FROM AUTHOR]

Zusammenfassung  Das septische Krankheitsbild zeichnet sich durch eine enorme Dynamik aus. Dies macht sofortiges Einschreiten notwendig, um das Fortbestehen der pathologischen Systemdysregulation zu unterbinden und ein Fortschreiten der Erkrankung hin zum septischen Schock und Multiorganversagen zu verhindern. Neben umgehenden Bemühungen die Sauerstoffgewebeversorgung durch kreislaufunterstützende Maßnahmen zu normalisieren, gilt es, den Infektherd zu identifizieren und zu eliminieren. Sofern möglich, muss eine chirurgische Herdsanierung durchgeführt werden (Inzision und Drainage). Es ist gegebenenfalls sinnvoll, mittels Spülkathetern den Infektionsherd regelmäßig mit antiseptischen Lösungen zu spülen. Bei ausgedehnten Befunden zählt die Durchführung sog. „Second-look-Operationen“ zum chirurgischen Standardvorgehen. Die Behandlung des septischen Patienten bedarf eines integrativen Ansatzes, sowohl interdisziplinär die ärztlichen Fachgebiete betreffend als auch im Hinblick auf die Zusammenarbeit zwischen ärztlichem Dienst und Pflegedienst. Entsprechend berücksichtigt dieser Beitrag gleichermaßen ärztliche wie pflegerische Aspekte. [ABSTRACT FROM AUTHOR]

Defective cardiac function during sepsis has been referred to as "cardiomyopathy of sepsis." It is known that sepsis leads to intensive activation of the complement system. In the current study, cardiac function and cardiomyocyte contractility have been evaluated in rats after cecal ligation and puncture (CLP). Significant reductions in left ventricular pressures occurred in vivo and in cardiomyocyte contractility in vitro. These defects were prevented in CLP rats given blocking antibody to C5a. Both mRNA and protein for the C5a receptor (C5aR) were constitutively expressed on cardiomyocytes; both increased as a function of time after CLP. In vitro addition of recombinant rat C5a induced dramatic contractile dysfunction in both sham and CLP cardiomyocytes, but to a consistently greater degree in cells from CLP animals. These data suggest that CLP induces C5aR on cardiomyocytes and that in vivo generation of C5a causes C5a-C5aR interaction, causing dysfunction of cardiomyocytes, resulting in compromise of cardiac performance. [ABSTRACT FROM AUTHOR]

distal nerve. At 8 months the number of axons/mm2 was significantly lower in the isograft compared to the midconduit experimental group (p = 0.006). The number of axons/mm2 in the distal nerve and the nerve fiber density in the midconduit and distal nerve were not significantly different between the two groups. The study confirmed our initial hypothesis that PLLA conduits are a viable scaffold for clinical long-term nerve gap replacement. We are critically aware however that longer evaluation of polymer degradation is warrented. Further studies on these individual nerve components are continuing, with the ultimate goal being the fabrication of a bioactive conduit that meets or exceeds the functional results of isografts. [ABSTRACT FROM AUTHOR]