To compare the efficacy of intra-articular and intravenous modes of administration of tranexamic acid in primary total knee arthroplasty in terms of blood loss and fall in haemoglobin level. Study Design: Randomized controlled trial. Duration of Study: Six months, from May 2019 to Nov 2019. Seventy-eight patients were included in the study. All patients undergoing unilateral primary total knee replacement were included in the study. Exclusion criteria were patients with hepatitis B and C, history of previous knee replacement, bilateral total knee replacement, allergy to TXA, Hb less than 11g/dl in males and less than 10g/dl in females, renal dysfunction, use of anticoagulants for 7 days prior to surgery and history of thromboembolic diseases. Patients were randomly divided into group A and B. Group A patients undergoing unilateral primary total knee replacement (TKR) were given intravenous tranexamic acid (TXA) while group B were infiltrated with intra-articular TXA. Volume of drain output, fall in haemoglobin (Hb) level and need for blood transfusion were measured immediately after surgery and at 12 and 24 hours post operatively in both groups. The study included 35 (44.87%) male and 43 (55.13%) female patients. Mean age of patients was 61 ± 6.59 years. The mean drain output calculated immediately after surgery in group A was 45.38 ± 20.75 ml compared with 47.95 ± 23.86 ml in group B (p=0.73). At 24 hours post operatively, mean drain output was 263.21 ± 38.50 ml in intravenous group versus 243.59 ± 70.73 ml in intra-articular group (p=0.46). Regarding fall in Hb level, both groups showed no significant difference (p>0.05). About 12.82% (n=5) patients in group A compared to 10.26% (n=4) patients required blood transfusion post operatively (p=0.72). Intra-articular and intravenous TXA are equally effective in patients undergoing primary total knee arthroplasty in reducing post-operative blood loss

Objectives. We have increased the dose of tranexamic acid (TXA) in our enhanced total joint recovery protocol at our institution from 15 mg/kg to 30 mg/kg (maximum 2.5 g) as a single, intravenous (IV) dose. We report the clinical effect of this dosage change. Methods. We retrospectively compared two cohorts of consecutive patients undergoing total hip arthroplasty (THA) or total knee arthroplasty (TKA) surgery in our unit between 2008 and 2013. One group received IV TXA 15 mg/kg, maximum 1.2 g, and the other 30 mg/kg, maximum 2.5 g as a single pre-operative dose. The primary outcome for this study was the requirement for blood transfusion within 30 days of surgery. Secondary measures included length of hospital stay, critical care requirements, re-admission rate, medical complications and mortality rates. Results. A total of 1914 THA and 2537 TKA procedures were evaluated. In THA, the higher dose of TXA was associated with a significant reduction in transfusion (p = 0.02, risk ratio (RR) 0.74, 95% confidence interval (CI) 0.58 to 0.96) and rate of re-admission (p < 0.001, RR 0.50, 95% CI 0.35 to 0.71). There were reductions in the requirement for critical care (p = 0.06, RR 0.55, 95% CI 0.31 to 1.00), and in the length of stay from 4.7 to 4.3 days (p = 0.02). In TKA, transfusion requirements (p = 0.049, RR 0.64, 95% CI 0.41 to 0.99), re-admission rate (p = 0.001, RR 0.56, 95% CI 0.39 to 0.80) and critical care requirements (p < 0.003, RR 0.34, 95% CI 0.16 to 0.72) were reduced with the higher dose. Mean length of stay reduced from 4.6 days to 3.6 days (p < 0.01). There was no difference in the incidence of deep vein thrombosis, pulmonary embolism, gastrointestinal bleed, myocardial infarction, stroke or death in THA and TKA between cohorts. Conclusion. We suggest that a single pre-operative dose of TXA, 30 mg/kg, maximum 2.5g, results in a lower transfusion requirement compared with a lower dose in patients undergoing elective primary hip and knee arthroplasty. However, these findings should be interpreted in the context of the retrospective non-randomised study design. Cite this article: R. J. M. Morrison, B. Tsang, W. Fishley, I. Harper, J. C. Joseph, M. R. Reed. Dose optimisation of intravenous tranexamic acid for elective hip and knee arthroplasty: The effectiveness of a single pre-operative dose. Bone Joint Res 2017;6:499–505. DOI: 10.1302/2046-3758.68.BJR-2017-0005.R1

We examined the effect on bone mineral density (BMD) of a single dose of 3 mg/kg of the bisphosphonate, pamidronate (Novartis) in distraction osteogenesis in immature rabbits.

Seventeen rabbits (9 control, 8 given pamidronate) were examined by dual-energy x-ray absorptiometry. There was a significant increase in the BMD in the pamidronate group compared with the control animals. The mean areal BMD (g/cm²) in the bone proximal and distal to the regenerate was increased by 40% and 39%, respectively, compared with the control group (p < 0.05). The BMD of the regenerate bone was increased by a mean of 43% (p < 0.05). There was an increase of 22% in the mean area of regenerate formed in the pamidronate group (p< 0.05).

Histological examination of bone in nine rabbits (5 control, 4 pamidronate) showed an increase in osteoblastic rimming and mineralisation of the regenerate, increased formation of bone around the pin sites and an increase in the cortical width of the bone adjacent to the regenerate in the rabbits given pamidronate.

Pamidronate had a markedly positive effect. It reduced the disuse osteoporosis normally associated with lengthening using an external fixator and increased the amount and density of the regenerate bone. Further study is required to examine the mechanical properties of the regenerate after the administration of pamidronate.

Infections represent a devastating complication in orthopedic and traumatological surgery, with high rates of morbidity and mortality. An early intervention is essential, and it includes a radical surgical approach supported by targeted intravenous antimicrobial therapy. The availability of parenteral antibiotics at the site of infection is usually poor, so it is crucial to maximize local antibiotic concentration using local carriers. Our work aims to describe the uses of one of these systems, Stimulan®, for the management and prevention of infections at our Institution. Analysing the reported uses of Stimulan®, we identified two major groups: bone substitute and carrier material for local antibiotic therapy. The first group includes its application as a filler of dead spaces within bone or soft tissues resulting from traumatic events or previous surgery. The second group comprehends the use of Stimulan® for the treatment of osteomyelitis, post-traumatic septic events, periprosthetic joint infections, arthroplasty revision surgery, prevention in open fractures, surgery of the diabetic foot, oncological surgery and for all those patients susceptible to a high risk of infection. We used Stimulan® in several complex clinical situations: in PJIs, in DAPRI procedure and both during the first and the second stage of a 2-stage revision surgery; furthermore, we started to exploit this antibiotic carrier also in prophylaxis of surgical site infections, as it happens in open fractures, and when a surgical site remediation is required, like in osteomyelitis following ORIF. Stimulan® is an extremely versatile and polyhedric material, available in the form of beads or paste, and can be mixed to a very broad range of antibiotics to better adapt to different bacteria and their antibiograms, and to surgeon's needs. These properties make it a very useful adjuvant for the management of complex cases of infection, and for their prevention, as well

In orthopedic surgery, implant infections are a serious issue and difficult to treat. The aim of this study was to use superparamagnetic nanoporous silica nanoparticles (MNPSNP) as candidates for directed drug delivery. Currently, short blood circulation half-life due to interactions with the host's immune system hinder nanoparticles in general from being clinically used. PEGylation is an approach to reduce these interactions and to enhance blood circulation time. The effect of PEGylation of the used . 68. Ga-labelled MNPSNP on the distribution and implant accumulation was examined by PET/CT imaging and gamma counting in an implant mouse model. Female Balb/c mice (n=24) received a magnetic implant subcutaneously on the left and a titanium implant on the right hind leg. On day one, 12 of these mice received an additional clodronate®-injection for macrophage depletion. On the second postoperative day, mice were anaesthetized and MNPSNP (native or PEGylated) injected intravenously, followed by a dynamic PET-scan over 60 minutes, a CT- and a static PET-scan at 120 min. As control, 12 mice received only . 68. Ga-MNPSNP (native or PEGylated). Gamma counting of inner organs, urine, blood and implant area was performed as further final analysis. Although PEGylation of the nanoparticles already resulted in lower liver uptakes, both variants of . 68. Ga-labeled MNPSNP accumulated in liver and spleen. Combination of PEGylation with clodronate®-injection led to a highly significant effect whereas clodronate®-injection alone could not reveal significant differences. In gamma counting, a significantly higher %I.D./g was found for the tissue surrounding the magnetic implants compared to the titanium control, although in a low range. PEGylation and/or clodronate®-injection revealed no significant differences regarding nanoparticle accumulation at the implantation site. PEGylation increases circulation time, but MNPSNP accumulation at the implant site was still insufficient for treatment of infections. Additional efforts have to further increase circulation time and local accumulation. Acknowledgements: This work is funded by the German Research Foundation (DFG, project number 280642759)

Introduction. Immunomodulation represents a novel strategy to improve bone healing in combination with low doses of bone morphogenetic growth factors like BMP-2. This study aims to investigate the effect and timing of monoclonal anti-IL-1ß antibody administration with 1μg BMP-2 on bone healing over 14 weeks in a rat femur segmental defect model. Method. 2 mm femoral defects were created in 22-27 weeks-old female Fischer F344 rats, internally fixed with a plate (animal license: GR/19/2022) using established protocols for analgesia and anesthesia. Animals (n=4/group) received either a collagen sponge, a collagen sponge+1μg BMP-2 (InductOs, Medtronic) or a collagen sponge+1μg BMP-2 with a monoclonal anti-IL-1ß antibody (BioXCell, 10 mg/ml), administered intravenously under anesthesia every third day until day 15, from day 0 or 3. In vivo micro-CT was performed after surgery and at 2, 3, 4, 6, 8, 10 and 14-weeks post-OP. Mechanical properties of the operated femurs were assessed by 4-point bending (Instron5866) and compared to contralateral femurs (one-way ANOVA, GraphPad Prism8). Histopathological analysis was performed semi-quantitatively on Giemsa-Eosin-stained sections (Olympus BX63) using a six-grade severity grading scale. Result. Operated femurs with BMP-2 reached an average stiffness of 91±37% of contralateral femurs, femurs in IL-1ß groups 105±11% (day 0) and 111±12% (day 3). Administration of anti-IL-1ß+1μg BMP-2 led to faster cortical bridging (3/4 femurs bridged by week 4 for day 0, 4/4 for day 3) than 1μg BMP-2 alone (0/4 by week 4). Micro-CT results confirmed histopathological evaluation, as collagen sponge alone led to non-union, complete bicortical bridging was observed for 3/4 femurs in the BMP-2 group and for 4/4 femurs in the IL-1β groups after 14 weeks. Conclusion. Anti-IL-1ß had a beneficial effect on late fracture healing with faster cortical bridging and new bone formation than 1μg BMP-2 alone. Acknowledgments. AO foundation. We thank Andrea Furter, Alisa Hangartner and Thomas Krüger for technical support

Introduction. The management of pathologic fractures (PF) following osteomyelitis (especially acute subtype) has not been widely investigated. This is challenging due to the infection-induced destructive process causing bone architecture defects. Therefore, this study aims to assess a stepwise treatment plan for the acute incidence of PF in long bone following pediatric acute Hematogenous osteomyelitis(AHO) (the most common mechanism in children). Method. This case series was conducted in a tertiary pediatric center. Patients with fracture incidence within the first 10 days after AHO diagnosis were included. Patients’ characteristics were retrospectively reviewed. Result. Nine patients (7 boys, involved bone: the femur(4), tibia(3), Radius(1), and Ulna(1)) were included, with a mean age of 52.56±66.18 months (7-216) and a follow-up time of 11.62±3.61 years (6.5-16 years). The etiology in all patients was hematological(Methicillin-resistant Staphylococcus aureus). Our stepwise treatment plan was as follows:. 1. Intravenous antibiotics until ESR<20, then oral to ESR<5. 2. Debridemnt surgery was performed if abscesses were detected. 3. Fracture type determined initial fixation: external fixation (4 patients, 2 unions) or casting (2 patients, both unions). 4. If the union was not obtained, internal fixation (with (2 patients) or without (2 patients) bone graft) was applied (all obtained union). 5. Circular external fixation was applied if the union was not obtained or leg length discrepancy occurred (1 case). A mean of 3.2 surgical procedures (1-6) was required to control the infection, and 1.4 surgical procedures (0-4) were required to obtain union. Except for one patient who died of septic shock, all other patients (88.8%) reached complete recovery (average length of hospital stay of 19.2 days (5-35).), and the union was obtained (the average union time of 17.25 months(4-36)) without long-term sequelae of osteomyelitis. Conclusion. The outcome of the stepwise plan in this study suggests that acute PF following AHO in pediatrics can be managed efficiently

Tourniquet is widely used in orthopedic surgery to reduce intraoperative bleeding and improve visualization. We evaluated the effect of tourniquet application on both peri- and postoperative cefuroxime concentrations in subcutaneous tissue, skeletal muscle, calcaneal cancellous bone, and plasma. The primary endpoint was the time for which the free drug concentration of cefuroxime was maintained above the clinical breakpoint minimal inhibitory concentration (T>MIC) forStaphylococcus aureus (4 µg/mL). Ten patients scheduled for hallux valgus or hallux rigidus surgery were included. Microdialysis catheters were placed for sampling of cefuroxime concentrations bilaterally in subcutaneous tissue, skeletal muscle, and calcaneal cancellous bone. A tourniquet was applied on the thigh of the leg scheduled for surgery. Cefuroxime (1.5 g) was administered intravenously as a bolus 15 minutes prior to tourniquet inflation, followed by a second dose 6 hours later. The mean tourniquet duration (range) was 65 (58; 77) minutes. Dialysates and venous blood samples were collected for 12 hours. For cefuroxime the T>MIC (4 μg/mL) ranged between 4.8–5.4 hours across compartments, with similar results for the tourniquet and non-tourniquet leg. Comparable T>MIC and penetration ratios were found for the first and second dosing intervals. We concluded that administration of cefuroxime (1.5 g) 15 minutes prior to tourniquet inflation is safe in order to achieve tissue concentrations above 4 µg/mL throughout surgery. A tourniquet application time of approximately 1 hour did not affect the cefuroxime tissue penetration in the following dosing interval

Tourniquet is widely used in extremity surgery. In order to prevent surgical site infection, correct timing of antimicrobial prophylaxis and tourniquet inflation is important. We aimed to evaluate the time for which the free drug concentration of cefuroxime is maintained above the minimal inhibitory concentration (T>MIC) in subcutaneous tissue and calcaneal cancellous bone during three clinically relevant tourniquet application scenarios. Twenty-four female pigs were included. Microdialysis catheters were placed for sampling of cefuroxime concentrations bilaterally in calcaneal cancellous bone and subcutaneous tissue, and a tourniquet cuff was applied on a randomly picked leg of each pig. Subsequently, the pigs were randomized into three groups to receive 1.5 g of cefuroxime by intravenous injection 15 min prior to tourniquet inflation (Group A), 45 min prior to tourniquet inflation (Group B), and at the tourniquet release (Group C). The tourniquet duration was 90 min in all groups. Dialysates and venous blood samples were collected eight-hours postcefuroxime administration. Cefuroxime concentrations were maintained above the clinical breakpoint MIC for Staphylococcus aureus (4 μg/mL) in calcaneal cancellous bone and subcutaneous tissue throughout the 90 min tourniquet duration in Group A and B. Cefuroxime administration at tourniquet release (Group C) resulted in concentrations above 4 μg/mL for a minimum of 3.5 hours in the tissues on the tourniquet side. There were no significant differences in the T>MIC (4 μg/mL) in subcutaneous tissue or calcaneal cancellous bone between the three groups. However, Group A tended toward shorter T>MIC in tourniquet calcaneal cancellous bone compared to Group C (p=0.08). We conclude that administration of cefuroxime (1.5 g) in the 15–45 min window prior to tourniquet inflation resulted in sufficient calcaneal cancellous bone and subcutaneous tissue concentrations throughout the 90 min tourniquet application. If the target is to maintain postoperative cefuroxime concentrations above relevant MIC values, our results suggest that a second dose of cefuroxime should be administered at tourniquet release

This edition of Cochrane Corner looks at some of the work published by the Cochrane Collaboration, covering pharmacological interventions for the prevention of bleeding in people undergoing definitive fixation or joint replacement for hip, pelvic, and long bone fractures; interventions for reducing red blood cell transfusion in adults undergoing hip fracture surgery: an overview of systematic reviews; and pharmacological treatments for low back pain in adults: an overview of Cochrane Reviews

The Cochrane Collaboration has produced five new reviews relevant to bone and joint surgery since the publication of the last Cochrane Corner These reviews are relevant to a wide range of musculoskeletal specialists, and include reviews in Morton’s neuroma, scoliosis, vertebral fractures, carpal tunnel syndrome, and lower limb arthroplasty.

Objectives. In order to ensure safety of the cell-based therapy for bone regeneration, we examined in vivo biodistribution of locally or systemically transplanted osteoblast-like cells generated from bone marrow (BM) derived mononuclear cells. Methods. BM cells obtained from a total of 13 Sprague-Dawley (SD) green fluorescent protein transgenic (GFP-Tg) rats were culture-expanded in an osteogenic differentiation medium for three weeks. Osteoblast-like cells were then locally transplanted with collagen scaffolds to the rat model of segmental bone defect. Donor cells were also intravenously infused to the normal Sprague-Dawley (SD) rats for systemic biodistribution. The flow cytometric and histological analyses were performed for cellular tracking after transplantation. Results. Locally transplanted donor cells remained within the vicinity of the transplantation site without migrating to other organs. Systemically administered large amounts of osteoblast-like cells were cleared from various organ tissues within three days of transplantation and did not show any adverse effects in the transplanted rats. Conclusions. We demonstrated a precise assessment of donor cell biodistribution that further augments prospective utility of regenerative cell therapy. Cite this article: Bone Joint Res 2014;3:76–81

The treatment of chronic osteomyelitis requires both appropriate surgical and antibiotic management. Prolonged intravenous antibiotic therapy followed by oral therapy is widely adopted. Despite this, the long-term recurrence rate is around 20% to 30%. The aim of this cohort study was to examine the effectiveness of surgical marginal resection in combination with local application of antibiotics (Collatamp G - gentamicin in a collagen fleece). Post-operatively this was followed by a short course of intravenous antibiotics, then oral antibiotics, to 6 weeks in total. A cohort of 50 patients from a 10-year period, 2000 to 2010, with chronic osteomyelitis was identified. Most were male (n= 35, 70%) and the average age is 40.9 years (SD 15.9). The mean follow-up duration was 3.2 years (SD 1.8). The average length of admission was 9.8 days (SD 11.4). 6 patients (12%) suffered recurrence of infection requiring further treatment. We used the Cierny and Mader classification to further stratify the patients. ‘A’ hosts had a shorter duration of admission (7.1 days) than ‘B’ hosts (12.3 days). There was no significant difference between recurrence rates of ‘A’ and ‘B’ hosts. Where available, we found pre-operative C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels had no correlation with disease recurrence. Disease-free probability for this cohort compared favourably with a cohort treated with prolonged systemic and oral antibiotics (Simpson and colleagues, JBJS Br 2001). We believe local administration of gentamicin in a collagen fleece is a useful component in the management of chronic osteomyelitis

Introduction. Recently, oxidative stress has been implicated in the development of osteonecrosis. Here we focused on vitamins with marked antioxidant potency to see whether their use might prevent the development of osteonecrosis associated with corticosteroid administration. Methods. Fifteen male Japanese white rabbits weighing about 3.5 kg were injected once into the right gluteal muscle with methylprednisolone (MPSL) 40 mg/kg (S Group). Ten other rabbits, in addition, received consecutive daily intravenous injections of vitamin E 50 mg/kg starting from the day of MPSL administration (E Group), and 10 other animals similarly received consecutive daily intravenous injections of vitamin C 30 mg/kg (C Group). All animals were euthanized 2 weeks after MPSL administration, and femurs were extracted, and stained with hematoxylin-eosin. Blood levels of glutathione (GSH) were also measured. Results. In S Group, the osteonecrosis development rate was 93%, in contrast to 60% in C Group, and none in E Group (P<0.05). Also, GSH levels in both S and C Groups abruptly decreased from the 1st day after MPSL administration, whereas, in E Group, the decline in GSH levels was significantly suppressed on days 1 and 3 after MPSL administration (P<0.05). Conclusion. Vitamin E significantly inhibited the decrease in blood GSH levels noted in the groups not receiving it. Since GSH reflects oxidative stress in vivo, vitamin E administration may be preventative in the setting of this kind of corticosteroid-induced osteonecrosis rabbit model

Summary. The two-step labeling protocol using Lysostaphin and bio-orthogonal click chemistry for staining bacteria is described. The click protocol is efficient in labeling staphylococci and is non-toxic. This protocol promises the efficient of infections that are difficult to assess by conventional imaging. Introduction. Infection diagnostics in clinics is time consuming, invasive and relays on microbiological cultures. New probes and labeling protocols enabling rapid and specific detection of infection in vivo shall improve the situation. We investigated the potential of a new click labeling protocol to detect staphylococci. Azido (N3) - modified Lysostaphin and DIBO (Di-benzocyclooctyne) - dye were used in the two-step bacteria-labeling protocol. N3 and DIBO were the counterparts of the bioorthogonal “click” reaction. In the first step, Lysostaphin-N3 bound to Staphylococcus aureus. In the second step, N3 clicked to DIBO thus achieving S. aureus selective labeling. Methods. S. aureus NCTC 10788 and E. coli NCTC 12241 (from National Collection of Type Cultures), primary sheep osteoblasts and C57BL/6 mice were used for this study. DIBO-Alexa488 (Invitrogen ®), DyeLight488 (Thermofisher ®), NHS-N3 (Lumiprobe ®), Lysostaphin (Sigma-Aldrich ®) were purchased. In vitro we used standard microbiological protocols to assess antimicrobial and labeling activity of the “click” probe (Lysostaphin-N3 plus DIBO-dye), one-step-labeled Lysostaphin-Dye and non-labeled Lysostaphin. Flow cytometry, Fluorescence microscopy, and Spectrophotometry were employed to measure binding of the probes to bacteria. The cytotoxicity of the probes on osteoblasts was performed using Presto Blue Cell Viability test (Invitrogen ®). In vivo we used Fluorescence Intravital Microscopy and mice with dorsal skin-fold chambers (approved by the local governmental animal care committee). Subsequently to anesthesia each mouse received S. aureus strain Cowan I intravenously. This was followed by intravenous injections of the test probes. Results. Lysostaphin-N3 partially lost its antimicrobial property if compare to Lysostaphin alone, but still bound to S. aureus efficiently and clicked DIBO-dye afterwards. There was no significant cytotoxicity of “click” reagents on sheep osteoblasts. In vitro the two-step labeling with Lysostaphin-Click was more efficient than the one-step labeling with Lysostaphin-Dye. In vivo the two-step and one-step labeling differed rather qualitatively. In the two-step protocol the “click” probe labeled bacteria adherent to the blood vessels and bacteria extravasated into the soft tissue around 30 minutes post-injection. In the one-step protocol bacteria were labeled quickly (within minutes) in the blood flow and on the blood vessels but not in the soft tissue. Discussion/Conclusion. Effective labeling bacteria with the click probe could be useful for a quantitative and selective assessment of infection, in particular for staphylococci infections, which are common in orthopedic implants but often difficult to detect. The one and two-step protocols successfully labeled bacteria in mice but the labeling was different. In the one-step protocol bacteria were labeled in the blood flow quickly; in the two-step protocol bacteria adherent to the blood vessels and extravasated into the soft tissue bacteria were labeled with a delay

Summary Statement. The stable inhibition of miR-214 in the aged osteoporotic rats induced by OVX could be achieved by periodic administration of AntagomiR-214 at a dosage of 4 mg/kg and at an interval of 7 days, which will provide a potential bone anabolic strategy for treatment of osteoprosis. Introduction. MiR-214 has a crucial role in suppressing bone formation and miR-214 inhibition in osteogenic cells may be a potential anabolic strategy for ameliorating osteoporosis (Wang X, et al. 2013). An aged ovariectomised rat has been regarded as a golden model to test bone anabolic agents for reversing established osteoporosis in aged postmenopausal women (Li X, et al. 2009). However, there is still lack of evidence to demonstrate bone anabolic potential of therapeutic inhibition of miR-214 within osteogenic cells in the golden model. So, it should be necessary to establish RNAi-based administration protocol toward stable inhibition of miR-214 at a low level in the golden model. A targeted delivery system specifically facilitating Antagomir-214 approaching osteogenic cells, i.e. (Asp-Ser-Ser). 6. -liposome (Zhang G, et al 2012), was employed in this study. Objectives. This study was to investigate optimal dosage and duration for therapeutic inhibition of miR-214 within osteogenic cells in the aged osteoporotic rats induced by ovariectomy. Materials and Methods. Six-month-old female Sprague-Dawley rats were ovariectomised (OVX) and left untreated for 12 months to establish aged osteoporosis. To determine the optimal dosage for therapeutic inhibition of miR-214, the OVX rats were injected intravenously with the AntagomiR-214 at a dosage of 0.5mg/kg, 1mg/kg, 2mg/kg, 4mg/kg, 6mg/kg and 8mg/kg (n=6 for each dosage group) delivered by (Asp-Ser-Ser). 6. -liposome, respectively. Thereafter, miR-214 expression level in osteogenic cells from bilateral femur was quantified at day 2 post injection by real-time PCR analysis in combination with laser captured dissection (LCM). To determine the optimal duration of miR-214, the OVX rats were intravenously injected with the AntagomiR-214 (AntagomiR-214 group) or non-sense AntagomiR-214 (NC group) delivered by (Asp-Ser-Ser). 6. -liposome at the optimal dosage or (Asp-Ser-Ser). 6. -liposome alone (Vehicle group). Then, the miR-214 level in osteogenic cells from bilateral femur was quantified at 1, 3, 5, 7, 9, 12, 14, 16, 21 day after the single dosing (n=6 for each time-point) by real-time PCR analysis in combination with LCM, respectively. To examine the long-term effect of the AntagomiR-214 after periodic pulsed dosing, the OVX rats were administrated with the AntagomiR-214 at the optimal dosage and duration for 5 repeated injections and then the miR-214 level in osteogenic cells from bilateral femur was quantified by real-time PCR analysis in combination with LCM. Results. The miR-214 level was efficiently decreased in a dose-dependent manner by the AntogomiR-214 and reached the level lower than 10% of the baseline at a dosage of 4 mg/kg at least in the aged osteoporotic rats. The effective duration for miR-214 at a level lower than 50% of the baseline lasted for 7 days in the osteoporotic rats after the single dosing. The miR-214 level was continuously lowered until 28 days and continuously maintained later at the level lower than 10% of the baseline by the 5 pulsed dosing of the AntagomiR-214 at an interval of 7 days and at a dosage of 4 mg/kg in the osteoporotic rats. Conclusions. The stable inhibition of miR-214 for bone anabolic strategy in the aged osteoporotic rats induced by OVX could be achieved by periodic administration of AntagomiR-214 at a dosage of 4 mg/kg and at an interval of 7 days

Several experimental models have been used to produce intravascular fat embolism. We have developed a simple technique to induce fat embolism using corn oil emulsified with distilled water to form fatty micelles. Fat embolism was produced by intravenous administration of these fatty micelles in anaesthetised rats, causing alveolar oedema, haemorrhage and increased lung weight. Histopathological examination revealed fatty droplets and fibrin thrombi in the lung, kidney and brain. The arteriolar lumen was filled with fatty deposits. Following fat embolism, hypoxia and hypercapnia occurred. The plasma phospholipase A. 2. , nitrate/nitrite, methylguidanidine and proinflammatory cytokines were significantly increased. Mass spectrometry showed that the main ingredient of corn oil was oleic acid. This simple technique may be applied as a new animal model for the investigation of the mechanisms involved in the fat embolism syndrome

Summary. Pyogenic spondylodiscitis is an uncommon but severe spinal infection. In majority of cases treatment is based on intravenous antibiotics and rigid brace immobilization. Posterior percutaneous spinal instrumentation is a safe alternative procedure in relieving pain, preventing deformity and neurological compromise. Introduction. Pyogenic spondylodiscitis (PS) is an uncommon but severe spinal infection. Patients affected by a non-complicated PS and treatment is based on intravenous antibiotics and rigid brace immobilization with a thoracolumbosacral orthosis (TLSO) suffices in most cases in relieving pain, preventing deformity and neurological compromise. Since January 2010 we started offering patients percutaneous posterior screw-rod instrumentation as alternative approach to TLSO immobilization. The aim of this study was to evaluate safety and effectiveness of posterior percutaneous spinal instrumentation for single level lower thoracic (T9-T12) or lumbar pyogenic spondylodiscitis. Materials and Methods. Retrospective cohort analysis on 27 patients diagnosed with PS who were offered to choose between 24/7 TLSO rigid bracing for 3 to 4 months and posterior percutaneous screw-rod instrumentation bridging the infection level followed by soft bracing for 4 weeks after surgery. All patients underwent antibiotic therapy. Fifteen patients chose conservative treatment, 12 patients chose surgical treatment. Patients were seen at 1, 3, 6, 9 months after diagnosis. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and complete blood count were measured at each follow-up visit. Segmental kyphosis was measured at diagnosis and at 9 months. VAS, SF-12, and EQ-5D questionnaires were recorded at each follow-up visit. Baseline groups’ demographic characteristics were assessed using independent sample t-tests for continuous variables and χ2 tests for frequency variables. Results. Complete healing was achieved in all patients, no difference was observed in healing time between the two groups (77.3±7.2 days vs 80.2±4.4). Instrumentation failure and screw loosening was not observed in any patient. In both group CRP and ESR decreased accordingly with response to antibiotic therapy. Surgically treated patients had significantly lower VAS scores at 1 month (3.05±0.57 in surgery group vs 5.20±1.21 in TLSO group) and 3 months (2.31±0.54 in surgery group vs 2.85±0.55 in TLSO group) post-diagnosis. Both groups had similar trends toward fast recovery in both mental (MCS) and physical components (PCS) of SF-12 questionnaire, surgically treated patients showed steeper and statistically significative improvement at 1 month (37.83±4.57 MCS in surgery group vs 24.52±3.03 MCS in TLSO group and 35.46±4.43 PCS in surgery group vs 27.07±4.45 PCS in TLSO group, p<0.001), 3 months (52.94±3.82 MCS in surgery group vs 39.45±4.92 MCS in TLSO group and 44.93±3.73 PCS in surgery group vs 35.33±6.44 PCS in TLSO group, p<0.001), and 6 months (54.93±3.56 MCS in surgery group vs 49.99±5.82 MCS in TLSO group) post-diagnosis, no statistically significant differences were detected at the other time points (9 months post-diagnosis). EQ-5D index was significantly higher in surgery patients at 1 month (0.764±0.043 in surgery group vs 0.458±0.197 in TLSO group) and 3 months (0.890±0.116 in surgery group vs 0.688±0.142 in TLSO group); no statistically significant changes were observed in segmental kyphosis between the two groups. Conclusion. Posterior percutaneous spinal instrumentation is a safe, feasible, and effective procedure in relieving pain, preventing deformity and neurological compromise. Surgical stabilization was associated with faster recovery, lower pain scores, and improved quality of life compared with TLSO conservative treatment at 1 and 3 months after diagnosis

Background. Adequate pain management is mandatory for patients' early rehabilitation and improvement of outcome after total knee arthroplasty (TKA). Conventional pain management, consisted of mainly opioids, has some adverse effects such as dizziness and nausea. Motor blockade occasionally resulted from epidural analgesics. A novel multimodal analgesic strategy with peripheral nerve block, peri-articular injection (PAI) and intravenous patient controlled analgesia (IVPCA) were utilized for our patients receiving TKA. In this study, we compared the clinical efficacy and adverse effects in the group of multimodal analgesia (MA) or epidural analgesia alone. Methods. One hundred and eighteen patients undergoing TKA with spinal anesthesia were enrolled. Patients of TKA received either our protocol of multimodal analgesia or patient controlled epidural analgesia (PCEA) alone. MA included ultrasound guided nerve block in femoral and obturator nerves before spinal anesthesia, and PAI mixed with NSAID, morphine, ropivacaine and epinephrine, as well as IVPCA after surgeries. The analgesic effect with numeric rating scale (NRS) and occurrence of adverse effects, including motor blockade, numbness, postoperative nausea/vomiting (PONV), and dizziness were recorded for all patients. Results. Thirty-one patients received MA, and eighty-seven patients received PCEA. No significant difference of NRS in MA and PCEA group within 24 hours after surgery either in rest (0.2 ± 1 compared with 0.22 ± 0.98; p = 0.930) or motion (0.40 ± 1.56 compared with 0.31± 1.23; p = 0.764). MA group sustained lesser motor blockade than PCEA (6.45% compared with 22.98%; p = 0.028) beyond 24 hours after surgery. The occurrence of numbness is lower in MA group (18.52%) compared with PCEA group(43.33%) (p=0.031). No statistic difference of PONV and dizziness is noted between two groups. However, there is a trend that lesser PONV and dizziness occurred in MA group than PCEA group. Conclusion. TKA patients receiving either MA or PCEA have adequate analgesic efficacy after surgeries. MA group has a lower incidence of motor blockade and PONV than PCEA. This multimodal analgesia proposed here has shown patients' safety and improved pain control after TKA, decreased narcotics use and their associated side effects. Besides, lesser motor blockade and adequate pain relief may encourage patient's early rehabilitation

INTRODUCTION. Adequate osseointegration of knee resurfacing implants for the treatment of focal cartilage defects is an important prerequisite for good clinical outcomes. Inadequate initial fixation and sustained micromotion may lead to osteolysis and ultimately implant failure. PET/CT with the bone seeking tracer 18F-sodium fluoride (18F-NaF) allows for localisation and quantification of abnormalities in bone metabolism. 18F-NaF PET/CT has been shown to correlate with loosening of implants in the hip and spine. Here, we asses osseointegration of the knee resurfacing implants using micro-computed tomography (µCT) and correlate µCT parameters to 18F-NaF uptake on PET/CT scans taken 3 and 12 weeks after surgery. We hypothesize that 18F-NaF uptake at 12 weeks and its relative decrease between 3 and 12 weeks correlates with osseointegration at 12 weeks postoperatively. Polymer implants with Young”s moduli approximately equal to- and below the Young's modulus of bone, with- and without surface modification were used in this study next to a control metal implant. METHODS. Five different osteochondral implants were implanted bilaterally in critically-sized osteochondral defects in 16 goats. At 3 and 12 weeks postoperatively, a 10-minute static PET/CT-scan (Philips, Gemini TF PET/CT) was made 60 minutes after intravenous injection of 18F-NaF. Image processing resulted in an overall bone metabolism parameter, i.e. standardized uptake value (SUV). A cylindrical region of interest was drawn around each implant to obtain the maximum SUV (SUVmax). Bone quality parameters were quantified in a cylinder surrounding the implant using µCT after sacrifice as a measure for osseointegration. The in vivo 18F-NaF PET/CT uptake parameters were correlated to the bone quality parameters. RESULTS. Implant osseointegration strongly varied for the different implants. Some implant groups exhibited very poor osseointegration with clear signs of osteolysis, while titanium implants exhibited good osseointegration. A strong correlation was observed between bone quality parameters as determined using µCT and SUVmax at 12 weeks. The SUVmax of the implants with poor osseointegration remained high, while implants with good osseointegration showed a relative decrease in SUVmax between 3 and 12 weeks. CONCLUSION. This study suggests that the SUVmax of PET/CT 12 weeks after surgery correlates well for the quality of osseointegration assessed on µCT 12 weeks after surgery. De relative decrease of SUVmax between the given time points had a strong correlation with the degree of osseointegration. In this study, large differences in the quality of osseointegration were observed. The role of surface modification, elasticity and micromotion still remain to be determined as well as if 18F-NaF is sensitive enough to discriminate between smaller differences and what the optimum time point would be to predict the ultimate osseointegration