Mannose-binding lectin (MBL) and the lectin complement pathway play a role in cutaneous ischemia and reperfusion injury.

OBJECTIVES: Cutaneous ischemia/reperfusion (CI/R) injury has shown to play a significant role in chronic wounds such as decubitus ulcers, diabetic foot ulcers, atherosclerotic lesions, and venous stasis wounds. CI/R also plays a role in free tissue transfer in reconstructive microsurgery and has been linked to clinical burn-depth progression after thermal injury. While the role of the complement system has been elucidated in multiple organ systems, evidence is lacking with respect to its role in the skin. Therefore, we evaluated the role of the complement system in CI/R injury. METHODS: Using a single pedicle skin flap mouse model of acute CI/R, we performed CI/R in wild-type (WT) mice and complement knock out (KO) mice, deficient in either C1q (C1q KO; classical pathway inhibition), mannose-binding lectin (MBL null; lectin pathway inhibition) or factor B (H2Bf KO; alternative pathway inhibition). Following 10 h ischemia and 7 days reperfusion, mice were sacrificed, flaps harvested and flap viability assessed via Image J software. The flap necrotic area was expressed as % total flap area. In another group, mice were sacrificed following CI/R with 10 h ischemia and 48 h reperfusion. Two cranial skin flap samples were taken for gene expression analysis of IL1b, IL6, TNFα, ICAM1, VCAM1, IL10, IL13 using real-time polymerase chain reaction (RT-PCR). RESULTS: Following CI/R, MBL null mice had a statistically significant smaller %necrotic flap area compared to WT mice (10.6 vs. 43.1%; p<0.05) suggesting protection from CI/R. A significantly reduced mean %necrotic flap area was not seen in either C1q KO or H2Bf KO mice relative to WT (22.9 and 31.3 vs. 43.1%; p=0.08 and p=0.244, respectively). There were no statistically significant differences between groups for markers of inflammation (TNFα, ICAM1, VCAM1, IL1b, IL6). In contrast, mRNA levels of IL10, a regulator of inflammation, were significantly increased in the MBL null group (p=0.047). CONCLUSIONS: We demonstrated for the first time a significant role of MBL and the lectin complement pathway in ischemia/reperfusion injury of the skin and a potential role for IL10 in attenuating CI/R injury, as IL10 levels were significantly increased in the tissue from the CI/R-protected MBL null group.

Autologous fat transplantation: volumetric tools for estimation of volume survival. A systematic review.

UNLABELLED: Autologous fat transplantation has gained great recognition in aesthetic and reconstructive surgery. Two main aspects are of predominant importance for progress control after autologous fat transplantation to the breast: quantitative information about the rate of fat survival in terms of effective volume persistence and qualitative information about the breast tissue to exclude potential complications of autologous fat transplantation. There are several tools available for use in evaluating the rate of volume survival. They are extensively compared in this review. The anthropometric method, thermoplastic casts, and Archimedes' principle of water displacement are not up to date anymore because of major drawbacks, first and foremost being reduced reproducibility and exactness. They have been replaced by more exact and reproducible tools such as MRI volumetry or 3D body surface scans. For qualitative and quantitative progress control, MRI volumetry offers all the necessary information: evaluation of fat survival and diagnostically valuable imaging to exclude possible complications of autologous fat transplantation. For frequent follow-up, e.g., monthly volume analysis, repeated MRI exams would not be good for the patient and are not cost effective. In these cases, 3D surface imaging is a good tool and especially helpful in a private practice setting where fast data acquisition is needed. This tool also offers the possibility of simulating the results of autologous fat transplantation. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Evaluation of prophylactic anticoagulation, deep venous thrombosis, and heparin-induced thrombocytopenia in 21 burn centers in Germany, Austria, and Switzerland.

Heparin-induced thrombocytopenia (HIT) is a life-threatening complication in intensive care settings. The timely diagnosis and management of HIT are challenging, and the incidences of HIT and deep venous thrombosis (DVT) may be related to prophylactic anticoagulation standards in burn units. We therefore evaluated, using a questionnaire, prophylactic anticoagulation, HIT management, and incidences of DVT and HIT in burn centers located in the German-speaking part of Europe. In the 21 responding burn centers, 1611 patients were treated and the overall incidences for clinically overt DVT and HIT in 2008 were 1.1% and 1.4%, respectively. Burn centers using low molecular weight heparin (LMWH) subcutaneous for all patients had a low rate of DVT (0.9%) and significantly lower rates of HIT (0.2%) relative to all other centers (P < 0.05). The highest rates of HIT (2.7%) and DVT (3.8%) were found in burn centers administering unfractionated heparin intravenous. While current HIT guidelines do not specify the administration of unfractionated heparin or LMWH for burn patients, these data warrant controlled prospective studies to confirm the advantage of LMWH administration in burn patients.

Angiographic findings in patients with postoperative soft tissue defects following total knee arthroplasty.

PURPOSE: A postoperative defect of the surrounding soft tissue is one main risk factor for implant exposure and infection following total knee arthroplasty (TKR). The main factors that promote infection, tissue ischemia, and hypoxia are strongly associated with arterial insufficiency and the prevalence of impaired peripheral perfusion. We hypothesized that vascular malperfusion is the predisposing reason for soft tissue complications following TKR necessitating plastic reconstructive surgery. METHODS: A retrospective chart review was made among patients (n = 12) with soft tissue defects due to wound infection following a total knee arthroplasty referred to plastic reconstructive surgery. All patients presented with an exposed implant, and angiographic imaging was performed prior to reconstructive procedures. RESULTS: Eight out of twelve patients (67%) had a pathological vascular status. In three of these patients, interventional procedures were performed to ameliorate perfusion. In ten patients (83%), the defect was covered with a plastic reconstructive regional or free tissue transfer. Four patients received a free latissimus dorsi flap and six patients a pedicled a gastrocnemius muscle flap. In one patient, a secondary wound closure was needed after knee arthrodesis and an amputation was performed in another patient due to a multiresistant staphylococcus aureus infection and massive tissue destruction at the time of admission. CONCLUSIONS: We suggest to rule out peripheral occlusive disease among patients undergoing TKR at best prior to orthopedic surgery using pulses and, if in doubt ankle-brachial index and doppler sonography Consequently, if vascular occlusions are then confirmed by angiography, dilatation and stenting or revascularization should be performed, to ameliorate perfusion.

Solid organ procurement from donors with carbon monoxide poisoning and/or burn--a systematic review.

INTRODUCTION: Traditionally, carbon monoxide poisoning and/or burn are considered contraindications to organ procurement. Previously reported cases have shown mixed results and many have been redundantly reported in the literature. METHODS: We performed a systematic review of all reported cases of organ transplantation procured from donors with carbon monoxide poisoning and/or burn to investigate whether these patients are suitable donors for solid organ transplantations. RESULTS: Organ survival rates of reported organs were high (86%). All organs procured from donors with carbon monoxide poisoning and burn survived during follow-up. Mean donors' peak carbon monoxide levels were comparable for organs surviving or failing during follow-up (31 ± 2.7 vs. 29 ± 26.8; p=0.95). Eighty-seven per cent of organs procured from donors supported with inotropes or vasopressors prior to organ procurement and 91% of organs procured from donors who were cardiopulmonary resuscitated prior to organ procurement survived during follow-up. CONCLUSIONS: Burn, carbon monoxide poisoning, high peak carbon monoxide-levels, use of inotropes or vasopressors or cardiopulmonary resuscitation prior to procurement are not contraindications for organ procurement and transplantation. New guidelines for burn units defining the special requirements for organ procurement from donors with carbon monoxide poisoning and/or burn are needed to raise the awareness for potential organ donors and to ultimately increase the donor pool and save patients' lives.

Evaluation of infrastructure, equipment and training of 28 burn units/burn centers in Germany, Austria and Switzerland.

Treatment of burn patients requires special training and skills, and an adequate infrastructure. In the United States, burn center referral criteria and requirements of burn centers are defined by the American Burn Association (ABA) in the Guidelines for the Operation of Burn Centers, and in Germany, by the German Society for Burn Treatment (DGV). The European Burn centers in Austria and the German-speaking part of Switzerland share the standards in the setting of the German-speaking Association for Burn Therapy (DAV) with some modifications. The aim of this study was to evaluate the current infrastructure of burn centers in the three German-speaking countries with respect to the existing guidelines. Therefore, guidelines for burn center referral criteria and burn center requirements were compared between the USA (ABA) and Germany (DGV). In addition, a questionnaire was sent to all burn centers in Germany, Austria and the German-speaking part of Switzerland, in order to collect current information regarding the architectural and medical infrastructure, available equipment and care-providing personnel. The comparison of guidelines for the USA and Germany revealed similar burn center referral criteria for both countries. With respect to burn center requirements, both the USA and Germany have similar requirements, albeit with different focus points. In Germany, the main focus lies on the infrastructural requirements for burn centers, while in the US, the main focus lies on the requirements for medical and nursing personnel. Critical review of the responses from the burn centers of German-speaking countries revealed that the biggest infrastructural differences among centers were observed in burn units providing pediatric care, as compared to adult burn centers. In summary, the DGV guidelines for German-speaking countries reflect an overall adoption of the ABA guidelines, and the burn centers included in this study met those requirements. As a result of the positive experience and effective treatment of burn patients in German-speaking countries, we recommend an adoption of the ABA guidelines to those countries and societies that are in need of appropriate standards of burn care.

Role of the complement components C5 and C3a in a mouse model of myocardial ischemia and reperfusion injury.

OBJECTIVE: Ischemic heart disease is the leading cause of death worldwide. The complement system plays a major role in inflammation and tissue injury following myocardial ischemia and reperfusion (MI/R) injury. Systemic C5 inhibition in clinical studies has resulted in mixed results and the role of earlier complement components (e.g., C3a), upstream from C5 cleavage, has not been elucidated for MI/R injury. Therefore, we evaluated the role of C5 or C3a in a mouse model of MI/R injury. METHODS: We performed experimental MI/R with 30 min of ischemia and 4 hr of reperfusion in 8-12 wk old C57BL/6 (WT) mice. Systemic C5 or C3a inhibition was performed with an anti-C5 monoclonal antibody (BB5.1) 30 min prior to reperfusion or with a C3a receptor antagonist (C3aRA). Since the C3aRA induces neutropenia that resolves within 120 min, we administered C3aRA at two different time points in two separate groups: 30 min prior to reperfusion within the neutropenic time frame and 120 min prior to reperfusion, when the neutropenia had resolved, but C3aRA remained active. Following MI/R, cardiac function was assessed via echocardiography, serum troponin I concentrations were measured as an index of myocardial cell death and myocardial inflammation was determined via myocardial polymorphonuclear leukocyte (PMN) infiltration. RESULTS: In wild type mice, MI/R significantly decrease myocardial ejection fraction and increased serum troponin I levels and myocardial PMN infiltration compared to sham-operated animals. Systemic C5 inhibition, 30 min prior to reperfusion, significantly protected mice from MI/R injury, confirming an important role for C5 in murine MI/R injury.Treatment with the C3aRA, 30 min prior to reperfusion (i.e., within the neutropenic time frame), protected mice significantly from MI/R related injury. In contrast, administration of the C3aRA 120 min prior to reperfusion, when the neutropenia had resolved, but C3aRA remained active, did not prevent MI/R injury. CONCLUSIONS: These results confirm an important role for C5 cleavage in murine MI/R injury. At the same time, they suggest a minimal role for C3a, since neutropenia rather than C3a receptor antagonism appears to be responsible for C3aRA related amelioration in MI/R injury. While C5 inhibition in the clinical setting of MI/R does not appear to be therapeutic, our results raise the possibility that inhibition of either C5a or C5b-9 may be more advantageous than inhibition of C3a or complete inhibition of C5 in humans.

Myocardial ischemia and reperfusion injury is dependent on both IgM and mannose-binding lectin.

Complement activation has been shown to play an important role in the inflammation and tissue injury following myocardial ischemia and reperfusion (MI/R). Several recent studies from our laboratory demonstrated the importance of mannose-binding lectin (MBL) as the initiation pathway for complement activation and the resulting pathological effects following MI/R. However, other studies from the past suggest an important role of the classical pathway and perhaps natural antibodies. In the present study, we used newly generated genetically modified mice that lack secreted IgM (sIgM), MBL-A, and MBL-C (sIgM/MBL null) in a plasma reconstitution mouse model of MI/R. Following 30 min of ischemia and 4 h of reperfusion, left ventricular ejection fractions were significantly higher in sIgM/MBL null mice reconstituted with MBL null or sIgM/MBL null plasma compared with reconstitution with wild-type (WT) plasma or WT mice reconstituted with WT plasma following MI/R. Serum troponin I concentration, myocardial polymorphonuclear leukocyte infiltration, and C3 deposition were dependent on the combined presence of sIgM and MBL. These results demonstrate that MI/R-induced complement activation, inflammation, and subsequent tissue injury require both IgM and MBL. Thus MBL-dependent activation of the lectin pathway may not be completely antibody independent in I/R models.

Stress fracture of the hamate body and fourth metacarpal base following military style push-ups: an unusual trauma mechanism.

We report the case of a 19-year-old male soldier, who sustained stress fractures of the hamate body and fourth metacarpal base due to his daily knuckle push-up routine in the military. We introduce repetitive microtrauma due to daily knuckle push-ups as an unusual, but potential trauma mechanism for metacarpal and carpal stress fractures.

Mannose-binding lectin is a regulator of inflammation that accompanies myocardial ischemia and reperfusion injury.

The mannose-binding lectin (MBL), a circulating pattern recognition molecule, recognizes a wide range of infectious agents with resultant initiation of the complement cascade in an Ab-independent manner. MBL recognizes infectious non-self and altered self in the guise of apoptotic and necrotic cells. In this study, we demonstrate that mice lacking MBL, and hence are devoid of MBL-dependent lectin pathway activation but have fully active alternative and classical complement pathways, are protected from cardiac reperfusion injury with resultant preservation of cardiac function. Significantly, mice that lack a major component of the classical complement pathway initiation complex (C1q) but have an intact MBL complement pathway, are not protected from injury. These results suggest that the MBL-dependent pathway of complement activation is a key regulator of myocardial reperfusion ischemic injury. MBL is an example of a pattern recognition molecule that plays a dual role in modifying inflammatory responses to sterile and infectious injury.