Toll-like receptor 10 rs10004195 variation may be protective against Bacillus Calmette-Guérin osteitis after newborn vaccination.

AIM: Toll-like receptor 1 (TLR1), TLR2, TLR6 and TLR10 form the TLR2 subfamily. In our previous controlled studies in 132 subjects with osteitis after newborn Bacillus Calmette-Guérin (BCG) vaccination, TLR1, TLR2 and TLR6 variations were associated with the risk of BCG osteitis. Now, we evaluated the role of ten single nucleotide polymorphisms (SNP) of the TLR10 gene in this cohort. METHODS: Five synonymous TLR10 SNPs (rs10004195, rs10856837, rs10856838, rs1109695 and rs11466652), and five missense TLR10 SNPs (rs11096955, rs11096957, rs11466649, rs11466653 and rs11466658) were determined by polymerase chain reaction (PCR)-based sequencing in 132 former BCG osteitis patients. RESULTS: TLR10 rs10004195 polymorphism was associated with the risk of BCG osteitis, compared to Finnish population controls. The variant genotype (AT/AA) was present in 13.6% of cases versus 26.2% of controls (p = 0.024). Correspondingly, the minor allele frequency (MAF) was lower (0.075) in cases than in controls (0.152; p = 0.009). There were no significant differences in the genotypes of the other nine studied TLR10 SNPs or in the corresponding MAFs between cases and controls. CONCLUSION: Among ten studied TLR10 gene polymorphisms, the variation only in the TLR10 rs10004195 was associated with the BCG osteitis risk after newborn BCG vaccination.

Vasoinhibin reduces joint inflammation, bone loss, and the angiogenesis and vasopermeability of the pannus in murine antigen-induced arthritis.

Increased permeability and growth (angiogenesis) of blood vessels play a key role in joint swelling and pannus formation in inflammatory arthritis, a family of diseases influenced by reproductive hormones. The hormone prolactin (PRL) protects against joint inflammation, pannus formation, and bone destruction in adjuvant-induced arthritis and these effects may involve its proteolytic conversion to vasoinhibin, a PRL fragment that inhibits angiogenesis and vasopermeability. Here, we show that the intra-articular injection of an adeno-associated virus type-2 (AAV2) vector encoding vasoinhibin reduced joint inflammation, the hyperplasia, vascular density, and vasopermeability of the pannus, and the loss of bone in mice subjected to antigen-induced arthritis. In agreement, the AAV2 vasoinhibin vector reduced the expression of proinflammatory cytokines (interleukin-1ß, interleukin-6), an endothelial cell marker (platelet endothelial cell-adhesion molecule 1), and proangiogenic molecules [vascular endothelial growth factor (VEGF), VEGF receptor 2, and hypoxia-inducible factor 1α] in the arthritic joint. Also, vasoinhibin reduced the synovial vasopermeability induced by the intra-articular injection of VEGF in healthy mice. Finally, vasoinhibin signals by blocking the phosphorylation/activation of endothelial nitric oxide synthase (eNOS) at Ser1179 and the AAV2 vasoinhibin vector inhibited the enhanced phosphorylation of eNOS Ser1179 in the arthritic joint. We conclude that vasoinhibin reduces joint inflammation and bone loss in arthritis by inhibiting pannus angiogenesis and vasopermeability via the blockage of VEGF-induced eNOS activation. These findings suggest the potential therapeutic benefit of AAV2-mediated vasoinhibin gene delivery in arthritis.

The polymethoxy flavonoid sudachitin suppresses inflammatory bone destruction by directly inhibiting osteoclastogenesis due to reduced ROS production and MAPK activation in osteoclast precursors.

Inflammatory bone diseases, including rheumatoid arthritis, periodontitis and peri-implantitis, are associated not only with the production of inflammatory cytokines but also with local oxidative status, which is defined by intracellular reactive oxygen species (ROS). Osteoclast differentiation has been reported to be related to increased intracellular ROS levels in osteoclast lineage cells. Sudachitin, which is a polymethoxyflavone derived from Citrus sudachi, possesses antioxidant properties and regulates various functions in mammalian cells. However, the effects of sudachitin on inflammatory bone destruction and osteoclastogenesis remain unknown. In calvaria inflamed by a local lipopolysaccharide (LPS) injection, inflammation-induced bone destruction and the accompanying elevated expression of osteoclastogenesis-related genes were reduced by the co-administration of sudachitin and LPS. Moreover, sudachitin inhibited osteoclast formation in cultures of isolated osteoblasts and osteoclast precursors. However, sudachitin rather increased the expression of receptor activator of NF-κB ligand (RANKL), which is an important molecule triggering osteoclast differentiation, and the mRNA ratio of RANKL/osteoprotegerin that is a decoy receptor for RANKL, in the isolated osteoblasts, suggesting the presence of additional target cells. When osteoclast formation was induced from osteoclast precursors derived from bone marrow cells in the presence of soluble RANKL and macrophage colony-stimulating factor, sudachitin inhibited osteoclastogenesis without influencing cell viability. Consistently, the expression of osteoclast differentiation-related molecules including c-fos, NFATc1, cathepsin K and osteoclast fusion proteins such as DC-STAMP and Atp6v0d2 was reduced by sudachitin. In addition, sudachitin decreased activation of MAPKs such as Erk and JNK and the ROS production evoked by RANKL in osteoclast lineage cells. Our findings suggest that sudachitin is a useful agent for the treatment of anti-inflammatory bone destruction.

Do Postoperative Antibiotics Decrease the Frequency of Inflammatory Complications Following Third Molar Removal?

PURPOSE: The purpose of this study was to answer the following clinical question: among patients who have their third molars (M3s) removed, do those who receive only postoperative antibiotics compared with those who receive no perioperative antibiotics have a lower frequency of postoperative inflammatory complications? MATERIALS AND METHODS: The authors designed and implemented a prospective cohort study and enrolled a sample of patients who had at least 1 M3 removed in an ambulatory private practice setting from June 2011 through May 2012 by oral and maxillofacial surgeons participating in a practice-based research collaborative. The predictor variable was postoperative antibiotic use categorized as postoperative antibiotics alone or no antibiotics. The primary outcome variable was the presence or absence of an inflammatory complication (ie, alveolar osteitis or surgical site infection) after M3 removal. Descriptive, bivariate, and multiple logistic regression statistics (adjusted for clustering within surgical practices) were computed to measure the association between postoperative antibiotic use alone and inflammatory complications after M3 removal, with statistical significance set at a P value less than or equal to .05. RESULTS: The study sample was composed of 1,877 patients having 5,631 M3s removed, of which 61% received postoperative antibiotics only. The overall inflammatory complication frequencies in the groups receiving postoperative antibiotic only and no antibiotic were 4.3 and 7.5%, respectively (P = .003). After adjusting for differences between the 2 study groups and clustering of patients within surgical practices, postoperative antibiotic use was associated with a 40% decreased risk of developing postoperative inflammatory complications (P = .04) with marginal statistical significance. CONCLUSIONS: The results of this study suggest that postoperative antibiotic therapy is associated with a statistically meaningful decreased risk of inflammatory complications after M3 removal compared with no antibiotic therapy.

Potential Role of L-Arginine and Vitamin E Against Bone Loss Induced by Nano-Zinc Oxide in Rats.

The purpose of this study was to illustrate the effects of zinc oxide nanoparticles (ZnO-NPs) administration on bone turnover and bone resorbing agents in rats and how L-arginine (L-arg) or vitamin E (vit E) co-administrations might affect them. Fasting rats were randomly divided into four groups (n = 10): G1-normal healthy animals; G2-ZnO-NPs-exposed rats (600 mg/kg-1/day-1); G3-ZnO-NPs-exposed rats co-administrated L-arg (200 mg/kg-1/day-1); G4-ZnO-NPs-exposed rats co-administrated vit E (200 mg/kg-1/day-1). The ingredients were orally administered daily. The body weight and food consumption of rats were recorded during the administration period and the experiment continued for three consecutive weeks. The results demonstrated that ZnO-NPs administration induced bone loss in rats as manifested by reduced activity of bone alkaline phosphatase (B-ALP) and increased level of C-terminal peptide type I collagen (CTx). The increase of inflammatory markers, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) by ZnO-NPs suggests that deleterious effects of ZnO-NPs on bone turnover were, in part, due to inflammation. Confirming to this suggestion, both L-arg and vit E reduced TNF-α and IL-6 levels and consequently decreased bone resorption as indicated by reduced serum CTx level. This study proved that ZnO-NPs can induce bone turnover, which may be reduced by L-arg or vit.E co-administration, partly by anti-inflammatory mechanism.

Lysostaphin-coated titan-implants preventing localized osteitis by Staphylococcus aureus in a mouse model.

The increasing incidence of implant-associated infections induced by Staphylococcus aureus (SA) in combination with growing resistance to conventional antibiotics requires novel therapeutic strategies. In the current study we present the first application of the biofilm-penetrating antimicrobial peptide lysostaphin in the context of bone infections. In a standardized implant-associated bone infection model in mice beta-irradiated lysostaphin-coated titanium plates were compared with uncoated plates. Coating of the implant was established with a poly(D,L)-lactide matrix (PDLLA) comprising lysostaphin formulated in a stabilizing and protecting solution (SPS). All mice were osteotomized and infected with a defined count of SA. Fractures were fixed with lysostaphin-coated locking plates. Plates uncoated or PDLLA-coated served as controls. All mice underwent debridement and lavage on Days 7, 14, 28 to determine the bacterial load and local immune reaction. Fracture healing was quantified by conventional radiography. On Day 7 bacterial growth in the lavages of mice with lysostaphin-coated plates showed a significantly lower count to the control groups. Moreover, in the lysostaphin-coated plate groups complete fracture healing were observed on Day 28. The fracture consolidation was accompanied by a diminished local immune reaction. However, control groups developed an osteitis with lysis or destruction of the bone and an evident local immune response. The presented approach of terminally sterilized lysostaphin-coated implants appears to be a promising therapeutic approach for low grade infection or as prophylactic strategy in high risk fracture care e.g. after severe open fractures.

Management of upper limb bone defects using free vascularized osteoseptocutaneous fibular bone graft.

Sixteen patients (11 men and 5 women), who formed the basis of the study, underwent surgery in the Hand and Reconstruction Microsurgical Unit, Orthopedic Department, Sohag Faculty of Medicine, from January 2001 to January 2009.The right side was involved in 7 cases and the left side in 9 cases. Average age was 35.2 years. The causes of bone defects were infected nonunion of both bone forearms in 5 cases, infected nonunion of the middle part of radius in 4 cases, posttraumatic bone loss of distal radius in 4 cases, and tumor of shaft humerus in 3 cases (aneurysmal bone cyst in 1 and osteosarcoma in 2 patients).The principle of treatment was debridement and excision of either infected unhealthy bone or tumor tissues with wide safety margin.The average bone defect was 8 cm (range, 6-14 cm). The defect was bridged by osteoseptocutaneous vascularized fibular bone graft. The donor bone was the right fibula in 7 cases and the left fibula in 10 cases. Two grafts were used in 1 patient because of soft tissue injuries, which included the peroneal vessels during osteotomy. The vascularized fibula was fixed by small dynamic compression plate. The operative time ranged between 7 and 11 hours. Blood transfusion was indicated in all the cases and its average transfusion was 1000 mL. The average follow-up was 84 months. Bone union was ultimately obtained in 15 patients except 1 who had failure of the graft. Arthrodesis of the distal ulna with the wrist joint was done during the follow-up. Arthrodesis of the wrist joint was also performed for 1 patient who had loss of carpal bones, distal radius, and wrist and finger extensors. The average time for union was 3.5 months. The hand function was normal in all cases. Stress fracture and fibular donor-site morbidity did not occur in this series. Neither shoulders nor elbows were affected postoperatively. There was no recurrence for either infection or tumor.

Epidemiology and prevention of surgical site infections after cardiac surgery.

Deep sternal wound infection is the major infectious complication in patients undergoing cardiac surgery, associated with a high morbidity and mortality rate, and a longer hospital stay. The most common causative pathogen involved is Staphylococcus spp. The management of post sternotomy mediastinitis associates surgical revision and antimicrobial therapy with bactericidal activity in blood, soft tissues, and the sternum. The pre-, per-, and postoperative prevention strategies associate controlling the patient's risk factors (diabetes, obesity, respiratory insufficiency), preparing the patient's skin (body hair, preoperative showering, operating site antiseptic treatment), antimicrobial prophylaxis, environmental control of the operating room and medical devices, indications and adequacy of surgical techniques. Recently published scientific data prove the significant impact of decolonization in patients carrying nasal Staphylococcus aureus, on surgical site infection rate, after cardiac surgery.

The effects of a systemic single dose of zoledronic acid on post-implantation bone remodelling and inflammation in an ovariectomised rat model.

Bisphosphonates reverse the negative effects of ovariectomy on bone, but they have also been associated with adverse processes in human jawbone. The molecular events determining bone regeneration and implant integration in osteoporotic conditions, with and without bisphosphonate treatment, are unclear. In this study, ovariectomised rats, to which a single dose of saline (NaCl) or zoledronic acid (Zol) was administered, received titanium alloy implants in their tibiae and mandibles. An enzyme-linked immunosorbent assay, gene expression analysis and histomorphometry were performed. The results show that ovariectomy, per se, upregulated the expression of genes denoting bone formation in the tibia, bone remodelling in the mandible and apoptosis in the tibia and mandible. Zoledronic acid administration resulted in lower levels of a remodelling marker in serum and downregulated gene expression for inflammation, bone formation, angiogenesis and apoptosis, mainly in the mandible, after 28 d of healing. Histomorphometry revealed improved bone-to-implant contact in the tibia, while the opposite was observed in the mandible. The present data show that a systemic single dose of zoledronic acid, in ovariectomised animals, results in site-specific differences in the regulation of genes involved in bone healing and regeneration in association with implant installation. These events occur in parallel with site-specific differences in the rate of osseointegration, indicating diverse tissue responses in the tibia and mandible after zoledronic acid treatment. The zoledronic acid effect on gene expression, during the late phase of healing in the mandible, suggests negative effects by the anti-resorptive agent on osseointegration at that particular site.

Heme oxygenase-1 mediates protective effects on inflammatory, catabolic and senescence responses induced by interleukin-1ß in osteoarthritic osteoblasts.

Osteoarthritis (OA) is a chronic degenerative joint disease showing altered bone metabolism. Osteoblasts contribute to the regulation of cartilage metabolism and bone remodeling. We have shown previously that induction of heme oxygenase-1 (HO-1) protects OA cartilage against inflammatory and degradative responses. In this study, we investigated the effects of HO-1 induction on OA osteoblast metabolism. HO-1 was induced with cobalt protoporphyrin IX (CoPP) and by transduction with LV-HO-1. In osteoblasts stimulated with interleukin (IL)-1ß, CoPP enhanced mineralization, the expression of a number of markers of osteoblast differentiation such as Runx2, bone morphogenetic protein-2, osteocalcin, and collagen 1A1 and 1A2, as well as the ratio osteoprotegerin/receptor activator of nuclear factor-κB ligand. HO-1 induction significantly reduced the expression of matrix metalloproteinase (MMP)-1, MMP-2 and MMP-3, and the production of pro-inflammatory cytokines such as tumor necrosis factor-α and IL-6 whereas IL-10 levels increased. HO-1 also exerted inhibitory effects on prostaglandin (PG)E(2) production which could be dependent on cyclooxygenase-2 and microsomal PGE synthase-1 down-regulation. The activity of senescence-associated ß-galactosidase and the expression of the senescence marker caveolin-1 were significantly decreased after HO-1 induction. The inhibition of nuclear factor-κB activation induced by IL-1ß in OA osteoblasts may contribute to some HO-1 effects. Our results have shown that HO-1 decreases the production of relevant inflammatory and catabolic mediators that participate in OA pathophysiology thus eliciting protective effects in OA osteoblasts.

Dual-purpose bone grafts improve healing and reduce infection.

OBJECTIVE: To determine if a dual-purpose bone graft can regenerate bone and reduce infection in highly contaminated bone critical size defects in rats. METHODS: Biodegradable polyurethane (PUR) scaffolds were loaded with recombinant human bone morphogenetic protein-2 (BMP-2) and vancomycin (Vanc). The release kinetics of the BMP-2 were tuned to take advantage of its mechanism of action (ie, an initial burst to recruit cells and sustained release to induce differentiation of the migrating cells). The Vanc release kinetics were designed to protect the graft from contamination until it is vascularized by having a burst for a week and remaining well over the minimum inhibitory concentration for Staphylococcus aureus for 2 months. The bone regeneration and infection reduction capability of these dual-purpose grafts (PUR+Vanc+BMP-2) were compared with collagen sponges loaded with BMP-2 (collagen+BMP-2) and PUR+BMP-2 in infected critical size rat femoral segmental defects. RESULTS: The dual-delivery approach resulted in substantially more new bone formation and a modest improvement in infection than PUR+BMP-2 and collagen+BMP-2 treatments. CONCLUSIONS: The PUR bone graft is injectable, provides a more sustained release of BMP-2 than the collagen sponge, and can release antibiotics for more than 8 weeks. Thus, the dual-delivery approach may improve patient outcomes of open fractures by protecting the osteoinductive graft from colonization until vascularization occurs. In addition, the more optimal release kinetics of BMP-2 may reduce nonunions and the amount of growth factor required.

Nanocomposite therapy as a more efficacious and less inflammatory alternative to bone morphogenetic protein-2 in a rodent arthrodesis model.

The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in spine fusion has led to concerns regarding a potential accompanying inflammatory response. This study evaluates a combination therapy (TrioMatrix®; Pioneer Surgical, Inc., Marquette, MI) comprised of a demineralized bone matrix (DBM), hydroxyapatite, and a nanofiber-based collagen scaffold in a rodent spine fusion model. Thirty-six athymic rats that underwent a posterolateral intertransverse spinal fusion were randomly assigned to 1 of 5 treatment groups: absorbable collagen sponge alone (ACS, negative control), 10 µg rhBMP-2 on ACS (positive control), TrioMatrix®, Grafton® (Osteotech, Inc., Eatontown, NJ), and DBX® (Synthes, Inc., West Chester, PA). Both TrioMatrix® and rhBMP-2-treated animals demonstrated 100% fusion rates as graded by manual palpation scores 8 weeks after implantation. This rate was significantly greater than those of the ACS, Grafton®, and DBX® groups. Notably, the use of TrioMatrix® as evaluated by microCT quantification led to a greater fusion mass volume when compared to all other groups, including the rhBMP-2 group. T2-weighted axial MRI images of the fusion bed demonstrated a significant host response associated with a large fluid collection with the use of rhBMP-2; this response was significantly reduced with the use of TrioMatrix®. Our results therefore demonstrate that a nanocomposite therapy represents a promising, cost-effective bone graft substitute that could be useful in spine fusions where BMP-2 is contraindicated.

Evaluation of a multidisciplinary consultation of diabetic foot.

OBJECTIVES: To evaluate the effectiveness of a multidisciplinary consultation of diabetic foot in terms of ulcer healing rate and podiatric complications prevention. METHODS: A longitudinal observational study was conducted on 78 patients consulting multidisciplinary clinic of diabetic foot between the 1st January 2005 and the 31th December 2006. There were two evaluations: the first one in June 2008, the second one in January 2010, at a medium follow-up of 48 months. RESULTS: 30.8% of diabetic patients were addressed in primary prevention, 53.8% for treatment of foot ulcer, and 15.4% in secondary prevention. The global healing rate was 76.19% after a medium follow-up of 29 months, and the recurrence rate at a medium follow-up of 48 months was 9.52%. Healing was achieved in 63.6% of patients with off-loading shoes versus 81.8% of whom with fiberglass cast boot. CONCLUSION: Care and follow-up of diabetic patients with foot at risk in multidisciplinary consultation seem to be effective not only in curative treatment, but also in primary and secondary prevention. The economic benefits need to be evaluated.

A novel tongue implant for tongue advancement for obstructive sleep apnea: feasibility, safety and histology in a canine model.

Obstructive sleep apnea (OSA) is a sleep related breathing disorder caused by partial or complete collapse of the upper airway during sleep. The disease is linked with important cardiovascular and cerebrovascular morbidity and mortality. Tongue base collapse is a major cause of upper airway occlusion in OSA and present surgical procedures to prevent this are invasive and inefficient. A novel implantable system to stabilize the tongue was evaluated in a canine model for feasibility, safety and histology. Successful implantation of the Advance System was performed in 21 canines and follow-up evaluations were performed at 30, 60, 90, 120 and 150 days. No technical or clinical adverse events were seen during the procedure. Minor clinical adverse events at some of the follow-up evaluations were treated successfully. Histologic evaluation of the implant was performed at different time points during follow-up and showed good biocompatibility, stability and osteointegration. The outcome of this study resulted in an implant for adjustable tongue advancement in humans with OSA.

BMP-2/PLGA delayed-release microspheres composite graft, selection of bone particulate diameters, and prevention of aseptic inflammation for bone tissue engineering.

Autogenous bone grafts are widely used in the repair of bone defects. Growth factors such as bone morphogenetic protein 2 (BMP-2) can induce bone regeneration and enhance bone growth. The combination of an autogenous bone graft and BMP-2 may provide a better osteogenic effect than either treatment alone, but BMP-2 is easily inactivated in body fluid. The objective of this study was to develop a technique that can better preserve the in vivo activity of BMP-2 incorporated in bone grafts. In this study, we first prepared BMP-2/poly(lactic-co-glycolic acid) (PLGA) delayed-release microspheres, and then combined collagen, the delayed-release microspheres, and rat autologous bone particulates to form four groups of composite grafts with different combinations: collagen in group A; collagen combined with bone particulates in group B; collagen combined with BMP-2/PLGA delayed-release microspheres in group C; and collagen combined with both bone particulates and BMP-2/PLGA delayed-release microspheres in group D. The four groups of composite grafts were implanted into the gluteus maximus pockets in rats. The ectopic osteogenesis and ALP level in group D (experimental group) were compared with those in groups A, B, and C (control groups) to study whether it had higher osteogenic capability. Results showed that the composite graft design increased the utility of BMP-2 and reduced the required dose of BMP-2 and volume of autologous bone. The selection of bone particulate diameter had an impact on the osteogenetic potential of bone grafts. Collagen prevented the occurrence of aseptic inflammation and improved the osteoinductivity of BMP-2. These results showed that this composite graft design is effective and feasible for use in bone repair.

The effect of Lipoxin A4 on the interaction between macrophage and osteoblast: possible role in the treatment of aseptic loosening.

BACKGROUND: Aseptic loosening (AL) is the main problem of total joints replacement (TJR) by the implantation of permanently prosthetic components. In vitro and in vivo studies have clearly demonstrated that wear debris and its byproducts could trigger inflammation in the peri-implant tissue. Lipoxins (LXs) are endogenous eicosanoids synthesized locally from arachidonate acid (AA) at sites of inflammation and mediate pro-resolving activity. A number of studies have demonstrated the effect of LXA4 to counteract inflammation in different cell and animal models, but till now, no relative report about the role of LXs in progress or prevention of AL. METHODS: Murine RAW264.7 macrophage cell line and MC3T3-E1 osteoblasts (OB) cell line were purchased. Co-cultured model of these two cell lines was established. To explore the effect of exogenous Lipoxin A4 (LXA4) on polymethylmethacrylate (PMMA) induced inflammation, pro-inflammatory cytokines including TNF-alpha, IL-1beta, PGE2 and GM-CSF were measured by ELISA kits and bone resorption was quantified by measuring calcium release from 5-day-old mice calvaria in vitro. To determine further the endogenous effect of LXA4, cells were co-cultured and with or without 15-lipoxygease (15-LO) blocking by 15-LO siRNA. Both real-time PCR and western blotting were applied to confirm the inhibitory efficiency of 15-LO by siRNA. RESULTS: 0.1 mg/ml, 0.5 mg/ml and 1.0 mg/ml PMMA showed a time-dependent manner to trigger production of all the pro-inflammatory cytokines studied. Exogenous 0-100 nM LXA4 presented an inhibitory effect on both generation of above cytokines and PMMA stimulated calvarial bone resorption with a dose-dependent manner. LXA4 in supernatant from neither rest macrophages nor macrophages cultured alone exposing to PMMA was detectable. In co-cultured cells challenged by PMMA, LXA4 was increased significantly, while, this enhance could be partly inhibited by 15-LO siRNA. When LXA4 generation was blocked with 15-LO siRNA, the PMMA induced pro-inflammatory cytokines were elevated and bone resorption was accelerated. CONCLUSION: In the present study, we demonstrated that LXA4 had a favorable inhibitory effect on PMMA-induced inflammation in a macrophage and OB co-culture system.

Can structural damage be prevented in ankylosing spondylitis?

PURPOSE OF REVIEW: Current treatment of ankylosing spondylitis such as non-steroidal anti-inflammatory drugs and tumor necrosis factor (TNF)-blockers have shown a good efficacy on sign and symptoms. However, it is less clear whether and how structural damage, determined mainly by new bone formation, can be prevented. Recent progress of the research addressing this question is presented here. RECENT FINDINGS: Although treatment with non-steroidal anti-inflammatory drugs over a 2-year period seem to retard growth of syndesmophytes this is not the case in patients treated with TNF-blockers over the same time. First data have been raised on whether new bone formation is coupled to (previous) inflammation or whether these two processes are uncoupled, which are not yet finally conclusive. A better understanding of the interaction between inflammation and new bone formation on the molecular level indicate that inflammatory molecules such as TNFalpha inhibit osteoblasts and that a TNF-blockade induces new bone formation. Thus, TNF-blockers can only be expected to prevent new bone formation if this is coupled to inflammation and if inflammation is treated early enough. Studies on bone biomarkers in ankylosing spondylitis patients support the view that suppression of inflammation induces new bone formation. SUMMARY: Future research has to clarify whether structural damage can best be prevented by early and effective treatment of inflammation or whether new bone formation has to be targeted additionally.

[What is the management for foot ulcers in diabetic patients?]. / Que faire devant un ulcère du pied chez un patient diabétique?

The "diabetic foot" covers the spectrum of neurological, arterial and infectious foot problems that occur as a consequence of diabetes. The wounds, often due to minor injuries, may lead to amputations if not quickly treated. The treatment consists of efficiently alleviating mechanical pressure from the wound (i.e. prevention of repeated trauma by walking on the ulcer) on the one hand, and using adequate local care on the other. In addition, the patient's vascular status needs to be assessed and corrected. If present, infections must be quickly and aggressively treated. The infection may be either superficial or deep and the presence of bone contact at clinical examination is suggestive of osteitis. Optimal care is provided in diabetic foot centers by multidisciplinary teams. These teams include a diabetologist, dermatologist, vascular surgeon, infectiologist, radiologist, podologist, shoemaker and specialized nurses. The main aim is to reduce the number of amputations. The best treatment, however, aims at prevention of foot wounds. It requires knowledge of the physiopathological mechanisms of diabetic foot, the screening for feet at risk, and the education of the patient, family and health care providers.

Patients' perception of recovery after third molar surgery following postoperative treatment with moxifloxacin versus amoxicillin and clavulanic acid: a randomized, double-blind, controlled study.

PURPOSE: To analyze the impact of the postoperative administration of moxifloxacin (MXF) on oral function and quality of life after third molar (TM) surgery. MATERIALS AND METHODS: A single-center, prospective, randomized, double-blind, controlled clinical trial was designed. The study population consisted of 100 patients who underwent impacted TM extractions. Patients were distributed into 2 groups of 50 individuals each. Postoperatively, one group was administered MXF (400 mg/24 hours for 5 days); the positive control group received amoxicillin and clavulanic acid (AMX-CLV) (500/125 mg/8 hours for 5 days). Follow-up was performed for 7 postoperative days, during which the patient recorded information on pain, the use of rescue analgesia, undesirable effects of the medication, difficulty in speaking, difficulty in chewing, diet consistency, difficulty performing oral hygiene, asthenia, time in bed, going out of the house, and returning to work. RESULTS: The administration of MFX was significantly associated with headache, and AMX-CLV was significantly associated with diarrhea. Greater difficulty in chewing and performing oral hygiene was observed in the AMX-CLV group compared with the MXF group. The percentage of patients who tolerated a diet of normal consistency was significantly higher in the MXF group compared with the AMX-CLV group. During the first 4 days of follow-up, the percentage of patients who returned to work was significantly higher in the MXF group than in the AMX-CLV group. CONCLUSIONS: Moxifloxacin shortens the period of postoperative recovery in terms of oral function and return to work. Therefore, MXF could be a useful option in TM surgery when antibiotics are indicated, particularly if patients are allergic to beta-lactams, their oral flora is resistant to macrolides, or they are intolerant of either of these antibiotics.