Remote Ischemic Conditioning als Möglichkeit zur Verbesserung der kutanen Mikrozirkulation in Lappenplastiken?

In der Plastischen Chirurgie finden Lappenplastiken regelmäßig Anwendung zur Deckung von Defekten der Körperoberfläche. Aufgrund des im Rahmen der Operation stark beschnittenen vaskulären Versorgungsnetzes sind Lappenplastiken postoperativ anfällig für Perfusionsstörungen, die zu Gewebenekrosen führen können. Das Remote Ischemic Conditioning (RIC) stellt eine Möglichkeit zur akuten, nicht-invasiven Perfusionsverbesserung von Geweben dar. Erstmalig sollte im Rahmen dieses Promotionsprojektes der Effekt des RIC auf die postoperative Perfusion von Lappenplastiken untersucht werden. In einer prospektiven klinischen Studie, in die 30 Patienten eingeschlossen werden konnten, zeigte sich durch das RIC eine signifikante Verbesserung der Perfusion der Lappenplastiken im postoperativen Behandlungsverlauf. Neben den Blutflussverbesserungen zeigten sich eine ebenfalls signifikante Verbesserung der Gewebesauerstoffwerte. RIC könnte zu einer Verringerung des Auftretens von Gewebenekrosen führen

Tissue conditioning - strategies to improve perfusion and reduce ischemia - reperfusion injury

Ischemia as well as ischemia-reperfusion injury (IRI) can cause serious tissue damage and therefore is a feared complication in reconstructive surgery. This is the reason why researchers around the world invest their efforts to improve tissue viability after ischemic events. Tissue conditioning offers a broad scope of different techniques which can be applied pre-, peri- or postoperatively to adapt the affected tissue to the subsequent stress during and after ischemia to prevent or minimize IRI. The different ways of tissue conditioning in flap surgery include surgical delay, ischemic conditioning, remote ischemic conditioning as well as thermic preconditioning and other techniques, using growth factors, pharmaceutical agents, extracorporeal shock waves as well as stemm cells. Therefore, we want to shed some light on the effects of ischemia and ischemia-reperfusion injury and further illustrate the different strategies of tissue conditioning with special concern to flap surgery but also regarding wound healing in general

Improvement of Superficial and Deep Cutaneous Microcirculation Due to Axillary Plexus Anesthesia Impaired by Smoking

Background: Understanding microvascular physiology is key to any reconstructive procedure. Current concepts in anesthesia increasingly involve regional peripheral nerve blockade during microvascular reconstructive procedures. Whereas favorable effects on perfusion due to these techniques have been reported earlier, little evidence focusing on its effects in most peripheral vascular compartments is available. Methods: A total of 30 patients who were to receive axillary plexus blockade (APB) were included. Microcirculatory assessment of the dependent extremity was conducted utilizing combined laser-Doppler flowmetry and white light spectroscopy. Two probes (1–2 and 7–8 mm penetration depth) were used to assess changes in microcirculation. Results: APB resulted in significant changes to both superficial and deep cutaneous microcirculation. Changes in blood flow were most prominent in superficial layers with a maximum increase of +617% compared to baseline values. Significantly lower values of +292% were observed in deep measurements. Consecutively, a significant enhancement in tissue oxygen saturation was observed. Further analysis revealed a significant impairment of perfusion characteristics due to reported nicotine consumption (max Bf: +936% vs. +176%). Conclusion: Cutaneous microcirculation is strongly affected by APB, with significant differences regarding microvascular anatomy and vascular physiology. Smoking significantly diminishes the elicited improvements in perfusion. Our findings could influence reconstructive strategies as well as dependent perioperative anesthetic management

Inhibition of Pathological Increased Matrix Metalloproteinase (MMP) Activity for Improvement of Bone Regeneration in Diabetes

Patients with diabetes suffer from poor fracture healing. Molecular reasons are not fully understood and our previous gene expression microarray analyses of regenerating bones from mice with type 2 diabetes (db−/db−) revealed accelerated activation of pathways concerning matrix metalloproteases (MMPs). Thus, we picked out the pathological MMP acceleration as a target for profound gene expression analyses and additional therapeutic intervention in the present study. In the first part, gene expression of ECM degrading proteinases and inhibitors was investigated three and seven days postoperatively. Mmp3, Mmp9, Mmp13 and gene expression of MMP inhibitor Timp2 was significantly higher in regenerating bone fractures of db−/db− compared to wild type animals. Timp1 and metalloproteinase AdamTS4 showed no differences. In the second part, we locally applied a single dose (1 µL of 5 µM solution) of the broad-spectrum molecular MMP inhibitor Marimastat on tibial defects in db−/db−. We performed immunohistochemical and histological stainings seven days post operation. Impaired bone healing, collagen content, angiogenesis, and osteoclast invasion in db−/db− were restored significantly by application of Marimastat compared to PBS controls (n = 7/group). Hence, local intervention of bone defects by the molecular MMP inhibitor Marimastat might be an alternative therapeutic intervention for bone healing in diabetes

The Use of Intact Fish Skin as a Novel Treatment Method for Deep Dermal Burns Following Enzymatic Debridement: A Retrospective Case-Control Study

Background: The optimal therapy for deep burn wounds is based on the early debridement of necrotic tissue followed by wound coverage to avoid a systemic inflammatory response and optimize scar-free healing. The outcomes are affected by available resources and underlying patient factors, which represent challenges in burn care and suboptimal outcomes. In this study, we aimed to determine optimal burn-wound management using enzymatic debridement (NexoBrid™, MediWound Germany GmbH, Rüsselsheim, Germany) and intact fish skin (Kerecis® Omega3 Wound, Isafjordur, Iceland). Methods: In this retrospective case series, 12 patients with superficial or deep dermal burn wounds were treated with enzymatic debridement followed by fish skin, Suprathel® (PolyMedics Innovations GmbH, Denkendorf, Germany), or a split-thickness skin graft (STSG). Patients’ outcomes regarding healing and scar quality were collected objectively and subjectively for 12 months after the burn injury. Results: Wounds treated with fish skin demonstrated accelerated wound healing, a significantly higher water-storage capacity, and better pain relief. Furthermore, improved functional and cosmetic outcomes, such as elasticity, skin thickness, and pigmentation, were demonstrated. The pain and itch expressed as POSAS scores (Patient and Observer Scar Assessment Scale) for fish skin decreased compared to those for wounds managed with an STSG or Suprathel. Importantly, fish skin-treated wounds had significantly improved sebum production and skin elasticity than those treated with Suprathel but showed no significant superiority compared to STSG-treated wounds. Conclusions: Enzymatic debridement in combination with intact fish skin grafts resulted in the faster healing of burn wounds and better functional and aesthetic outcomes than split-thickness skin grafts and Suprathel treatment

Role of Autonomous Neuropathy in Diabetic Bone Regeneration

Diabetes mellitus has multiple negative effects on regenerative processes, especially on wound and fracture healing. Despite the well-known negative effects of diabetes on the autonomous nervous system, only little is known about the role in bone regeneration within this context. Subsequently, we investigated diabetic bone regeneration in db−/db− mice with a special emphasis on the sympathetic nervous system of the bone in a monocortical tibia defect model. Moreover, the effect of pharmacological sympathectomy via administration of 6-OHDA was evaluated in C57Bl6 wildtype mice. Diabetic animals as well as wildtype mice received a treatment of BRL37344, a β3-adrenergic agonist. Bones of animals were examined via µCT, aniline-blue and Masson–Goldner staining for new bone formation, TRAP staining for bone turnover and immunoflourescence staining against tyrosinhydroxylase and stromal cell-derived factor 1 (SDF-1). Sympathectomized wildtype mice showed a significantly decreased bone regeneration, just comparable to db−/db− mice. New bone formation of BRL37344 treated db−/db− and sympathectomized wildtype mice was markedly improved in histology and µCT. Immunoflourescence stainings revealed significantly increased SDF-1 due to BRL37344 treatment in diabetic animals and sympathectomized wildtypes. This study depicts the important role of the sympathetic nervous system for bone regenerative processes using the clinical example of diabetes mellitus type 2. In order to improve and gain further insights into diabetic fracture healing, β3-agonist BRL37344 proved to be a potent treatment option, restoring impaired diabetic bone regeneration

Superior enhancement of cutaneous microcirculation due to "cyclic" application of a negative pressure wound therapy device in humans

$\bf Objectives:$ Despite a common utilization of "Negative Pressure Wound Therapy" (NPWT) Devices in a wide range of specialties, some of the basic mechanisms of action of the techniques are still on debate. Conflicting results from prior studies demonstrate our lack of understanding how wound-bed perfusion or cutaneous microcirculation is affected by NPWT. $\bf Methods:$ We conducted a prospective randomized study which included 45 healthy subjects to further investigate the acute effects of NPWT on cutaneous microcirculation underneath the applied dressing. Three modes of application, namely, continuous, intermittent, cyclic, were tested. Amongst others, measurements of elicited surface pressure and a comprehensive microcirculatory analysis were carried out by utilizing an O2C-device. For the detection of (systemic) remote effects, perfusion changes of the contra-lateral thigh were evaluated. $\bf Results:$ All three tested modes of application led to a significant ($\it p$ < 0.05) improvement in local tissue perfusion with an increased blood flow of max +151% and tissue oxygen saturation of +28.2% compared to baseline values. Surface pressure under the dressing significantly increased up to 29.29 mmHg due to the activation of the NPWT device. Continuous, intermittent, and cyclic application of negative pressure were accurately sensed by participants, resulting in reported pain values that mirrored the different levels of applied suction. Although the cyclic application mode showed the most pronounced effects regarding microcirculatory changes, no statistical significance between groups was observed. $\bf Conclusion:$ We could demonstrate a significant improvement of cutaneous microcirculation under an applied NPWT dressing with favorable effects due to cyclic mode of application. An increased surface pressure leads to a better venous drainage of the tissue, which was shown to increase arterial inflow with a consecutive improvement of oxygen supply. Further research is warranted to evaluate our findings regarding wound bed perfusion in the clinical field with respect to formation of granulation tissue and wound healing

Posttraumatic Lymphedema after Open Fractures of the Lower Extremity—A Retrospective Cohort Analysis

Secondary lymphedema is a very common clinical issue with millions of patients suffering from pain, recurrent skin infections, and the constant need for a decongestive therapy. Well-established as a consequence of oncologic procedures, secondary lymphedema is also a well-known phenomenon after trauma. However, precise epidemiological data of lymphedema progress upon severe extremity injuries are still missing. In the present work, we analyzed a patient cohort of 94 individuals who suffered open fractures of the lower extremity and soft tissue injury, of 2nd and 3rd grade according to Tscherne classification, between 2013 and 2019. Typical symptoms of lymphedema have been obtained via interviews and patient medical records in a retrospective cohort analysis. Of all patients, 55% showed symptoms of secondary lymphedema and 14% reported recurrent skin infections, indicating severe lymphedema. Furthermore, comparing patients with and without lymphedema, additional parameters, such as obesity, total number of surgeries, infections, and compartment syndrome, related to lymphedema progress could be identified. According to these data, posttraumatic secondary lymphedema has a highly underestimated clinical prevalence. Further prospective studies are needed to validate this first observation and to identify high-risk groups in order to improve patient’s health care

Antibiotic prophylaxis for prevention of wound infections after soft tissue sarcoma resection

Background and Objectives The use of antibiotic prophylaxis for soft tissue sarcoma resection varies widely while little evidence on this topic exists. The aim of this study was to determine the impact of antibiotic prophylaxis on the occurrence of wound infections. Methods A single institutional retrospective cohort study was performed on patients who underwent truncal or extremity soft tissue sarcoma resection. The use of antibiotic prophylaxis was assessed and univariate and multivariate analysis of predictors of wound infections was performed. Results Nine hundred and fifty-eight patients could be included. Thirty-two percent of patients had no antibiotic prophylaxis, 44% of patients received single-shot prophylaxis, and 24% of patients received single-shot plus continued antibiotic treatment. Wound infections occurred in 140 patients (15%). Independent risk factors for wound infections upon multivariate analysis were obesity, high American Society of Anesthesiologists (ASA) status, high tumor size and grade, operation time over 120 minutes, and other complications. Antibiotic prophylaxis could not be identified as a protective factor in univariate or multivariate analysis. Conclusions A favorable effect of antibiotic prophylaxis on the occurrence of wound infections could not be observed. Although more studies on this subject are needed, our data do not support the general use of antibiotic prophylaxis for soft tissue sarcoma resection