Georgios I. Drosos

Neutrophil Extracellular Trap Formation Is Associated with IL-1β and Autophagy-Related Signaling in Gout

Background Gout is a prevalent inflammatory arthritis affecting 1–2% of adults characterized by activation of innate immune cells by monosodium urate (MSU) crystals resulting in the secretion of interleukin-1β (IL-1β). Since neutrophils play a major role in gout we sought to determine whether their activation may involve the formation of proinflammatory neutrophil extracellular traps (NETs) in relation to autophagy and IL-1β. Methodology/Principal Findings Synovial fluid neutrophils from six patients with gout crisis and peripheral blood neutrophils from six patients with acute gout and six control subjects were isolated. MSU crystals, as well as synovial fluid or serum obtained from patients with acute gout, were used for the treatment of control neutrophils. NET formation was assessed using immunofluorescence microscopy. MSU crystals or synovial fluid or serum from patients induced NET formation in control neutrophils. Importantly, NET production was observed in neutrophils isolated from synovial fluid or peripheral blood from patients with acute gout. NETs contained the alarmin high mobility group box 1 (HMGB1) supporting their pro-inflammatory potential. Inhibition of phosphatidylinositol 3-kinase signaling or phagolysosomal fusion prevented NET formation, implicating autophagy in this process. NET formation was driven at least in part by IL-1β as demonstrated by experiments involving IL-1β and its inhibitor anakinra. Conclusions/Significance These findings document for the first time that activation of neutrophils in gout is associated with the formation of proinflammatory NETs and links this process to both autophagy and IL-1β. Modulation of the autophagic machinery may represent an additional therapeutic study in crystalline arthritides.

Safety and efficacy of commercially available demineralised bone matrix preparations: a critical review of clinical studies.

Demineralised bone matrix (DBM), a form of allograft, possesses the properties of osteoinductivity and osteoconductivity. A large body of data obtained from extensive preclinical studies have clearly supported the utility of DBM in human clinical settings. However, it is now recognized that various DBM configurations may differ considerably with regard to their bone inductive activity. Several factors could account for such variability, including the biologic properties of the graft, the host environment, and the methods of allograft preparation. The differing efficacy of DBM products may also depend on differences in particle size and shape, donor selection criteria, protocols for collection and storage, as well as DBM carrier materials. Several comparative studies have confirmed the differences in the osteoinductive potential of various DBM preparations. The purpose of the present review is to provide a critical overview of the current applications of DBM in a clinical setting.

The association of adipokine levels in plasma and synovial fluid with the severity of knee osteoarthritis

OBJECTIVE We sought to determine the association between plasma and SF levels of leptin and adiponectin in patients with knee OA. METHODS Plasma and SF levels of adipokines and soluble leptin receptor (sOB-R) were determined by ELISA in 96 patients with knee OA at different stages, according to Ahlbacks classification. RESULTS Levels of adiponectin, leptin, sOB-R and free leptin in plasma and SF did not differ significantly across categories of OA severity. However, the ratio of SF to plasma leptin was significantly lower in the advanced OA stage compared with early stages of the disease (P = 0.02). After adjustment for sex and BMI, plasma leptin positively correlated with categories of OA severity (r = 0.23, P = 0.02), whereas SF/plasma leptin negatively correlated with OA stage (r = -0.27, P = 0.01). Cluster analysis showed that all men were included in one cluster and distributed in different stages of OA, whereas women formed three clusters with similar BMI, but those who were older and had the highest plasma leptin levels suffered from advanced OA. CONCLUSION Plasma leptin positively correlated with the severity of knee OA. The ratio of SF to plasma leptin might be a marker related to the severity of knee OA. Further studies should investigate whether similar associations exist in other joints affected by OA.

Functional bracing of humeral shaft fractures. A review of clinical studies.

Functional bracing has been widely accepted as the gold standard for treating humeral shaft fractures conservatively. We conducted a literature review to verify the efficacy of this treatment method. Sixteen case series and two comparative studies fulfilled the criteria set. Analysis of these clinical studies showed that humeral shaft fractures when treated with functional bracing heal in an average of 10.7 weeks. Union rate is high (94.5%). Statistical analysis showed that proximal third fractures and AO type A fractures have a higher non-union rate although this is not statistical significant. Residual deformity and joint stiffness are considered the main drawbacks of conservative treatment. Angulation--usually varus--rarely exceeded 10 degrees, while full shoulder and elbow motion was achieved in 80% and 85% of the patients, respectively. Nevertheless, in the few studies that subjective parameters such as functional scores, pain and quality of life were assessed results were not so promising.

Wound closure of leg fasciotomy: Comparison of vacuum-assisted closure versus shoelace technique. A randomised study

BACKGROUND Fasciotomies, though essential for the prevention and management of compartment syndromes, may increase morbidity and prolong hospitalisation. Two widely applied methods of delayed primary closure are compared in leg fasciotomy wounds. PATIENTS AND METHODS Two groups, each of 25 patients with leg fasciotomies due to fractures and soft tissue injuries, who were randomly assigned to be treated either by vacuum assisted closure (VAC®, n=42 wounds, group V) or by the shoelace technique (n=40 wounds, group S), were evaluated in this study. Wound length, time to definite closure, complications, need for additional interventions and daily treatment costs were data collected and statistically assessed. RESULTS Wound closure time was significantly higher in group V compared to group S (p=0.001; 95% CI of the difference, 1.8-6.3 days). Five group V patients required split thickness skin grafts. In six group S patients, the vessel loops had to be replaced. The mean daily cost of negative pressure therapy alone was 135 euro (range 117-144 euro), whilst the mean daily cost of treatment for the shoelace technique was 14 euro ranging from 8 to 18 euro (p=<0.001). CONCLUSIONS Both VAC® and the shoelace technique are safe, reliable and effective methods for closure of leg fasciotomy wounds. VAC® requires longer time to definite wound closure and is far more expensive than the shoelace technique, especially when additional skin grafting is required.

Systematic effects of surgical treatment of hip fractures: Gliding screw-plating vs intramedullary nailing

AIM Numerous studies have been published regarding the comparison between intramedullary nail and the dynamic hip screw and plate for the fixation of intertrochanteric fractures in elderly patients. In this paper we present a comparative study of these two methods regarding their systemic effects on this group of patients. MATERIALS-METHODS This is a randomized trial of 120 consecutive patients with an intertrochanteric fracture treated with either extramedullary fixation (dynamic hip screw and plate; DHS, Synthes-Stratec, Oberdorf, Switzerland) or intramedullary nail (Gamma nail, Stryker Howmedica, Freiburg, Germany and Endovis BA, Citieffe, Bologna, Italy). The parameters that we assessed pre-operatively, in addition to their demographics, included their mental state (MMSE), their nutritional and immune state and their pulmonary function. Intra-operatively we calculated the amount of radiation exposure, the amount of blood loss and the length of operative time for each procedure. Postoperatively we repeated the calculation of the mental and pulmonary state and the blood loss, during days 1, 3, and 10 and related them to the ease of the patients mobilization. RESULTS Decreased bleeding and post-operative pain, reduced post-operative morbidity and faster recovery of function were better but not significant in the group of intramedullary fixation (all p>0.05). However, in the same group there were slightly more patients in whom the MMSE was falling, together with their pulmonary function, suggesting that this method probably predisposes to higher chances of pulmonary dysfunction and the possibility of pulmonary embolism. CONCLUSION We found no significant differences between the two methods of stabilization of these fractures regarding their systemic effects perioperatively. The classic dynamic hip screw can preserve its position as a safe and effective solution for these already vulnerable patients having sustained a trochanteric fracture against the novel intramedullary techniques.

Use of demineralized bone matrix in the extremities

Autologous bone graft is considered as the gold standard for all indications for bone grafting procedures but the limited availability and complications in donor site resulted in seeking other options like allografts and bone graft substitutes. Demineralized bone matrix (DBM) is an allograft product with no quantity limitation. It is an osteoconductive material with osteoinductive capabilities, which vary among different products, depending on donor characteristics and differences in processing of the bone. The purpose of the present review is to provide a critical review of the existing literature concerning the use of DBM products in various procedures in the extremities. Clinical studies describing the use of DBM alone or in combination with other grafting material are available for only a few commercial products. The Level of Evidence of these studies and the resulting Grades of Recommendation are very low. In conclusion, further clinical studies of higher quality are required in order to improve the Recommendation Grades for or against the use of DBM products in bone grafting procedures.

Intravenous vs Topical Tranexamic Acid in Total Knee Arthroplasty Without Tourniquet Application: A Randomized Controlled Study.

BACKGROUND Use of tranexamic acid (TXA) is effective and safe in reducing the blood loss in total knee arthroplasty (TKR) performed using a tourniquet, but, data in TKR performed without tourniquet are limited, and there is no study comparing the topical (T) with intravenous (IV) TXA administration. Our aim was to compare the topical (T) with intravenous (IV) TXA administration in TKR performed without tourniquet. MATERIAL AND METHODS A total of 120 patients undergoing unilateral TKR for knee osteoarthritis were included in a prospective randomized study. Operations were performed under spinal anesthesia, no tourniquet was used, and the postoperative regime was the same for all patients. Patients were divided into 3 groups; in group C (control), 40 patients received no TXA, in group IV, 40 patients received 1 g of TXA intravenously, and in group L, 1 g of TXA was applied locally to 40 patients. The primary outcome measures included the calculated blood loss, the transfusion rate, and quantity of allogeneic blood units, whereas secondary outcome measures were complications. RESULTS There was no statistically significant difference in patients demographics and perioperative results. Calculated blood loss, allogeneic blood transfusion rate, and quantity in group C were significantly higher compared with those of TXA groups (P < .001). There was no significant difference in complications rate between the 3 groups. CONCLUSIONS According to the results of this study, IV or T administration of 1-g TXA significantly reduced the blood loss and the need for allogeneic blood transfusion in patients undergoing TKR without a tourniquet (with no significant difference between the 2 routes of administration).

Mechanical characterization of bone graft substitute ceramic cements

The aim of this laboratory work was to study the compressive and flexural characteristics of various commercially available bone graft substitute (BGS) ceramic cements, in their initial as-mixed condition, and compare them to polymethylmethacrylate (PMMA). The tested biomaterials were two different calcium phosphate cements, two different calcium sulphate cements, one nanocrystalline hydroxyapatite and one PMMA cement. All biomaterials were prepared according to manufacturers instructions and the methodology described in ISO 5833 (2002) for acrylic bone cement was followed, as the one closest approaching in vivo requirements. All BGS cements had a brittle behaviour and when subjected to mechanical stress they all failed under sudden crack propagations in their bulk. Both in compression and bending, all BGS cements failed under loads lower than those of PMMA. In compression, the calcium sulphate extra strength cement showed a strength value of approximately 60% of PMMA, the other cements following at a distance. In bending, all BGS cements showed strengths below 22% of PMMA. However, due to limited number and fragility of specimens, calculated bending strengths can only be considered as indicative figures with limited comparative value. The results of this in vitro study showed a varying mechanical performance between tested BGS ceramic cements, whilst all of them exhibited lower compression and bending strength than the selected PMMA. These findings, of course, cannot be directly extrapolated to surgical or clinical implications, since the adopted in vitro context does not necessarily reflect the actual in vivo conditions met by such biomaterials.

Peroneal nerve damage by oblique proximal locking screw in tibial fracture nailing: a new emerging complication?

Interlocking intramedullary nailing currently is the preferred treatment for most tibial fractures requiring operative treatment. Good results with a relative low complication rate have been reported in large clinical series, as well as in comparative series. The reported incidence of neurological complications after tibial nailing varies, involving mainly the peroneal nerve. The mechanism of peroneal nerve damage in tibial fracture nailing is usually indirect, caused by leg traction or compartment syndrome. Direct peroneal nerve damage related to the proximal locking screw seems to be very rare since we were able to identify only one report in the English literature. We report a case of partial peroneal nerve damage caused by a long oblique proximal locking screw. Removal of the proximal locking screw leaded to a gradual improvement of the nerve function and a complete resolution at one year. This seems to be a new emerging iatrogenic complication related to nails designed with oblique proximal locking screws. We feel that the placement of the oblique proximal screw from medial to lateral side needs an extra care. Even fluoroscopy, does not give enough safety due to the spatial geometry of the proximal tibia and the known problems of viewing oblique interlocking screws with a two-dimensional image-intensifier.