[Challenge of limb care after violence and war with a special focus on imaging procedures]. / Herausforderung der Extremitätenversorgung nach Gewalt und Krieg mit besonderer Betrachtung bildgebender Verfahren.

BACKGROUND: Injury patterns in the area of the extremities following violence and war harbor many special features and require special attention. Destructive and complex defect injuries are often present, which necessitate elaborate and special reconstruction approaches, predominantly as part of a staged and multistaged procedure. RESEARCH QUESTION: In this context, special attention must be paid to the diagnostic options as an essential aspect, as a clear diagnosis means that targeted treatment steps can be planned and implemented. MATERIAL AND METHOD: The authors' experience in this field from military operations in Afghanistan, Iraq, the Republic of Mali, Kosovo and Georgia, as well as the core content of the Terror and Disaster Surgical Care (TDSC®) course on this topic, have been contextualized and incorporated. In addition, aspects of interdisciplinary cooperation with radiological and, in particular, nuclear medicine disciplines are taken into account in the daily routine. RESULTS AND DISCUSSION: Extremity injuries in the context of violence and war are accompanied by complex bone and surrounding soft tissue defects due to the high energy impact. The principles of reconstruction familiar from everyday life can only be transferred one-to-one to a limited extent. The treatment pathways are often very long and complex and the questions of infection and tissue vitality must be answered again and again in stages. Interdisciplinary collaboration with the disciplines specialized in imaging procedures, particularly in the field of nuclear medicine, is one of the key building blocks for a successful treatment pathway.

Immediate Dose-Response Effect of High-Energy Versus Low-Energy Extracorporeal Shock Wave Therapy on Cutaneous Microcirculation.

Elucidation of the precise mechanisms and therapeutic options of extracorporeal shock wave therapy (ESWT) is only at the beginning. Although immediate real-time effects of ESWT on cutaneous hemodynamics have recently been described, the dose response to different ESWT energies in cutaneous microcirculation has never been examined. Thirty-nine Sprague-Dawley rats were randomly assigned to three groups that received either focused high-energy shock waves (group A: total of 1000 impulses, 10 J) to the lower leg of the hind limb, focused low-energy shock waves (group B: total of 300 impulses, 1 J) or placebo shock wave treatment (group C: 0 impulses, 0 J) using a multimodality shock wave delivery system (Duolith SD-1 T-Top, Storz Medical, Tägerwilen, Switzerland). Immediate microcirculatory effects were assessed with the O2C (oxygen to see) system (LEA Medizintechnik, Giessen, Germany) before and for 20 min after application of ESWT. Cutaneous tissue oxygen saturation increased significantly higher after high-energy ESWT than after low-energy and placebo ESWT (A: 29.4% vs. B: 17.3% vs. C: 3.3%; p = 0.003). Capillary blood velocity was significantly higher after high-energy ESWT and lower after low-energy ESWT versus placebo ESWT (group A: 17.8% vs. group B: -22.1% vs. group C: -5.0%, p = 0.045). Post-capillary venous filling pressure was significantly enhanced in the high-energy ESWT group in contrast to the low-energy ESWT and placebo groups (group A: 25% vs. group B: 2% vs. group C: -4%, p = 0.001). Both high-energy and low-energy ESWT affect cutaneous hemodynamics in a standard rat model. High-energy ESWT significantly increases parameters of cutaneous microcirculation immediately after application, resulting in higher tissue oxygen saturation, venous filling pressure and blood velocity, which suggests higher tissue perfusion with enhanced oxygen saturation, in contrast to low-energy as well as placebo ESWT. Low-energy ESWT also increased tissue oxygen saturation, albeit to a lower extent, and decreases both blood velocity and venous filling pressure. Low-energy ESWT reduced tissue perfusion, but improved oxygen saturation immediately after the application.

Repetitive shock wave therapy improves muscular microcirculation.

BACKGROUND: Extracorporeal shock wave therapy (ESWT) is mainly applied in tendon as well as bone problems based on stem-cell activation and healing acceleration. The effect of ESWT on muscle tissue is much less understood to date. However, from a clinical perspective, muscle injuries are of distinct interest especially in elite athletes such as soccer players. MATERIAL AND METHODS: A total of 26 rats were randomized into two groups. Group A received a single application of high-energetic focused ESWT (0.3 mJ/mm(2), 4 Hz, 1000 impulses, 10 J), whereas group B underwent the same procedure every 10 min for three sessions (3 × 0.3 mJ/mm(2), 4 Hz, 3 × 1000 impulses, totaling 30 J). Blood flow at a depth of 8 mm was measured continuously and noninvasively by a combined Laser-Doppler-Imaging and photospectrometric technique (Oxygen-to-see, O2C, LEA Medizintechnik, Germany). RESULTS: One minute after the application of high-energy ESWT blood flow in group A increased by 16.5% (P = 0.007). Thereafter, it decreased from minute 2 after application and remained significantly unchanged to baseline value until the end of the measuring period at 50 min (P = 0.550). Group B showed a similar significant increase in blood flow of 16.4% (P = 0.049) and a decrease afterward, too. After the second focused ESWT blood flow was boosted to 26.6% (P = 0.004), remaining significantly elevated until the third application was initiated. Muscular blood flow was increased to 29.8% after the third focused ESWT (P < 0.001), remaining significantly increased for another 10 min. CONCLUSIONS: Focused ESWT enhances blood flow in the muscle of rats. Moreover, repetitive ESWT extended this beneficial effect.

Remote effects of extracorporeal shock wave therapy on cutaneous microcirculation.

BACKGROUND: Extracorporeal shock wave treatment (ESWT) has proven its clinical benefits in different fields of medicine. Tissue regeneration and healing is improved after shock wave treatment. Even in the case of burn wounds angiogenesis and re-epithelialization is accelerated, but ESWT in extensive burn wounds is impracticable. HYPOTHESIS: High energy ESWT influences cutaneous microcirculation at body regions remote from application site. METHODS: Eighteen Sprague Dawley rats were randomly assigned to two groups and received either high energy ESWT (Group A: total 1000 impulses, 10 J) or placebo shock wave treatment (Group B: 0 impulses, 0 J), applied to the dorsal lower leg of the hind limb. Ten minutes later microcirculatory effects were assessed at the contralateral lower leg of the hind limb (remote body region) by combined Laser-Doppler-Imaging and Photospectrometry. RESULTS: In Group A cutaneous capillary blood velocity was significantly increased by 152.8% vs. placebo ESWT at the remote body location (p = 0.01). Postcapillary venous filling pressure remained statistically unchanged (p > 0.05), while cutaneous tissue oxygen saturation increased by 12.7% in Group A (p = 0.220). CONCLUSION: High energy ESWT affects cutaneous hemodynamics in body regions remote from application site in a standard rat model. The results of this preliminary study indicate that ESWT might be beneficial even in disseminated and extensive burn wounds by remote shock wave effects and should therefore be subject to further scientific evaluation.

Fractionated Repetitive Extracorporeal Shock Wave Therapy: A New Standard in Shock Wave Therapy?

BACKGROUND: ESWT has proven clinical benefit in dermatology and plastic surgery. It promotes wound healing and improves tissue regeneration, connective tissue disorders, and inflammatory skin diseases. However, a single treatment session or long intervals between sessions may reduce the therapeutic effect. The present study investigated the effects of fractionated repetitive treatment in skin microcirculation. METHODS: 32 rats were randomly assigned to two groups and received either fractionated repetitive high-energy ESWT every ten minutes or placebo shock wave treatment, applied to the dorsal lower leg. Microcirculatory effects were continuously assessed by combined laser Doppler imaging and photospectrometry. RESULTS: In experimental group, cutaneous tissue oxygen saturation was increased 1 minute after the first application and until the end of the measuring period at 80 minutes after the second treatment (P < 0.05). The third ESWT application boosted the effect to its highest extent. Cutaneous capillary blood flow showed a significant increase after the second application which was sustained for 20 minutes after the third application (P < 0.05). Placebo group showed no statistically significant differences. CONCLUSIONS: Fractionated repetitive extracorporeal shock wave therapy (frESWT) boosts and prolongs the effects on cutaneous hemodynamics. The results indicate that frESWT may provide greater benefits in the treatment of distinct soft tissue disorders compared with single-session ESWT.

Comprehensive analysis of glomerular mRNA expression of pro- and antithrombotic genes in atypical haemolytic-uremic syndrome (aHUS).

Atypical haemolytic-uremic syndrome (aHUS) is, in most cases, due to hereditary or acquired defects in complement regulation and a life-threatening disease. Despite the rapidly grown knowledge about the primary defects in aHUS, the pathogenesis that links complement dysregulation with microthrombus formation in aHUS is still unknown. Thus, we examined the glomerular microvascular expression of pro- and antithrombotic genes. Glomeruli were microdissected from 12 archival paraffin-embedded biopsies with aHUS and from seven control biopsies. Glomerular mRNA expression was quantified by single real-time PCR reactions after preamplification. In addition immunostains were performed for plasminogen activator inhibitor 1 (PAI-1) and for tissue plasminogen activator (tPA). Results were compared between cases and controls and with clinical data. Glomeruli in aHUS had increased mRNA expression of antifibrinolytic, prothrombotic PAI-1, antithrombotic thrombomodulin (THBD) and CD73 and decreased expression of profibrinolytic, antithrombotic tPA compared to controls. Impaired fibrinolysis due to increased microvascular expression of the antifibrinolytic PAI-1 in combination with the decreased expression of the profibrinolytic tPA seems to be a final common pathway in renal thrombotic microangiopathy that is also effective in aHUS. The concomitant induction of antithrombotic transcripts likely indicates counterregulatory efforts, demonstrating that the capillary bed is not a passive victim of complement attack. Future research should investigate if and how complement activation could induce the reported shift in the expression of PAI-1 and tPA.

Arteriolar vascular smooth muscle cell differentiation in benign nephrosclerosis.

BACKGROUND: Benign nephrosclerosis (bN) is the most prevalent form of hypertensive damage in kidney biopsies. It is defined by early hyalinosis and later fibrosis of renal arterioles. Despite its high prevalence, very little is known about the contribution of arteriolar vascular smooth muscle cells (VSMCs) to bN. We examined classical and novel candidate markers of the normal contractile and the pro-fibrotic secretory phenotype of VSMCs in arterioles in bN. METHODS: Sixty-three renal tissue specimens with bN and eight control specimens were examined by immunohistochemistry for the contractile markers caldesmon, alpha-smooth muscle actin (alpha-SMA), JunB, smoothelin and the secretory marker S100A4 and by double stains for caldesmon or smoothelin with S100A4. RESULTS: Smoothelin immunostaining showed an inverse correlation with hyalinosis and fibrosis scores, while S100A4 correlated with fibrosis scores only. Neither caldesmon, alpha-SMA nor JunB correlated with hyalinosis or fibrosis scores. Cells in the arteriolar wall were exclusively positive either for caldesmon/smoothelin or S100A4. CONCLUSIONS: This is the first systematic analysis of VSMC differentiation in bN. The results suggest that smoothelin is the most sensitive marker for the contractile phenotype and that S100A4 could be a novel marker for the secretory phenotype in vivo. The other markers did not seem to differentiate these phenotypes in bN. Thus, VSMC phenotype markers should be defined in the context of the vessel segment and disease under examination. S100A4 could not only be a marker of pro-fibrotic secretory VSMCs in bN but also an important mediator of arteriolar fibrosis.

ADAMTS13--marker of contractile phenotype of arterial smooth muscle cells lost in benign nephrosclerosis.

BACKGROUND: Hypertensive nephrosclerosis alone and in combination with other renal diseases is a leading cause of terminal renal insufficiency. Histologic lesions manifest as benign nephrosclerosis (bN) with arteriolar hyalinosis and later fibrosis. Procoagulant micromilieus have been implicated in fibrosis. Hyalinosis is considered to consist of plasma insudation possibly containing procoagulant factors like von Willebrand factor (VWF). Therefore, it is hypothesized that VWF cleaving protease ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type-1 motif, 13) is normally expressed by arteriolar vascular smooth muscle cells (VSMCs) and diminished in bN and that this reduction contributes to fibrosis in bN. METHODS: ADAMTS13 expression was examined by immunohistochemistry and quantitative real-time polymerase chain reaction in VSMCs of various human organs. Fifty-four specimens with and seven without bN were immunostained for ADAMTS13, VWF, CD61 and VSMC differentiation markers in arteriolar walls. RESULTS: Expression of ADAMTS13 is confirmed in VSMCs. In bN, ADAMTS13 immunostaining of arterial VSMCs correlated inversely with fibrotic but not hyalinotic lesions. Smooth muscle myosin heavy chain showed an inverse correlation with hyalinotic, as opposed to fibrotic lesions of bN. Smoothelin showed an inverse correlation with both hyalinotic and fibrotic lesions of bN. VWF was absent in normal controls and hyalinotic lesions, but present exclusively in fibrotic lesions in 7/54 (13%) bN cases. CD61 was absent in all arteriolar walls. CONCLUSIONS: The present results establish ADAMTS13 as a novel marker of contractile VSMCs that is retained in early hyalinotic bN but partially lost later in fibrotic bN. Loss of ADAMTS13 and accumulation of VWF in fibrotic but not hyalinotic arteriolar walls could further propagate fibrosis in bN.