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Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_17 | Pages 23 - 23
24 Nov 2023
Xie C Ren Y Weeks J Lekkala S Rainbolt J Xue T Shu Y Lee K de Mesy Bentley KL Yeh S Schwarz E
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Title. Longitudinal Intravital Imaging to Quantify the “Race for the Surface” Between Host Immune Cell and Bacteria for Orthopaedic Implants with S. aureus Colonization in a Murine Model. Aim. To assess S. aureus vs. host cell colonization of contaminated implants vis intravital multiphoton laser scanning microscopy (IV-MLSM) in a murine model. Method. All animal experiments were approved by IACUC. A flat stainless steel or titanium L-shaped pin was contaminated with 10. 5. CFU of a red fluorescent protein (RFP) expressing strain of USA300LAC, and surgically implanted through the femur of global GFP-transgenic mice. IV-MLSM was performed at 2, 4, and 6 hours post-op. Parallel cross-sectional CFU studies were performed to quantify the bacteria load on the implant at 2,4,6,12,18 and 24 hours. Results. 1) We developed a high-fidelity reproducible IV-MLSM system to quantify S. aureus and host cell colonization of a bone implant in the mouse femur. Proper placement of all implants were confirmed with in vivo X-rays, and ex vivo photos. We empirically derive the ROI during each imaging session by aggregating the imaged volume which ranges from (636.4um × 636.4um × 151um) = 0.625 +/- 0.014 mm. 3. of bone marrow in a global GFP-transgenic mouse. 2) IV-MLSM imaging acquisition of the “race for the surface”.In vitro MPLSM images of implants partially coated with USA300LAC (RFP-MRSA) were verified by SEM image. Results from IV-MLSM of RFP-MRSA and GFP. +. host cell colonization of the contaminated implants illustrated the mutually exclusive surface coating at 3hrs, which to our knowledge is the first demonstration of “the race for the surface” between bacteria and host cells via intravital microscopy. 3) Quantifying the “race for the surface” with CFU verification of S. aureus on the implant. 3D volumetric rendering of the GFP. +. voxels and RFP+ voxels within the ROI were generated in Imaris. The voxel numbers suggeste that the fight for the surface concludes ∼3hrs post-infection, and then transitions to an aggressive MRSA proliferation phase. The results of WT control demonstrate a significant increase in CFU by 12hrs post-op for both stainless steel (P<0.01) and titanium (P<0.01). Conclusions. We developed IV-MLSM to quantify the “Race for the Surface” between host cells and contaminating S. aureus in a murine femur implant model. This race is remarkably fast, as the implant surface is completely covered with 3hrs, peak bacterial growth on the implant occurs between 2 and 12 hours and is complete by 12hrs


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 50 - 50
22 Nov 2024
Hvistendahl MA Bue M Hanberg P Tøstesen S Vittrup S Stilling M Høy K
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Aim. Antibiotic prophylaxis is central in preventing postoperative spine infections, yet knowledge of clinical spine tissue antibiotic concentrations remains limited. Pooled postoperative spine infection rates are constant (approximately 3%), resulting in severe patient morbidity, mortality, and prolonged hospitalization. Current antibiotic dosing regimens often involve fixed doses based on empirical knowledge, surrogate measures (plasma samples), non-clinical evidence (experimental models), and inferior methodology (tissue specimens). Therefore, personalized antibiotic dosing may be the future of antibiotic prophylaxis to prevent postoperative infections, especially implant infections. The aim was to continuously evaluate intra- and postoperative cefuroxime target spine tissue concentrations in long-lasting spine surgery after personalized dosing by repeated weight-dosed intravenous administrations. Method. Twenty patients (15 female, 5 male) scheduled for long-lasting spine deformity surgery with hypotensive anaesthesia were included; median age (range): 17.5 years (12-74), mean BMI (range): 22.2 (16.2-37.7), and mean surgery time (range): 4h 49min (3h 57min-6h 9min). Weight-dosed cefuroxime (20 mg/kg) was administered intravenously to all patients on average 25 min before incision and repeated after 4 hours. Microdialysis catheters were placed for sampling of cefuroxime concentrations in vertebral bone (only intraoperative sampling), paravertebral muscle, and subcutaneous tissue as soon as possible after surgery start. Upon wound closure, two additional catheters were placed in the profound and superficial part of the wound. Microdialysis and plasma samples were obtained continuously intra- and postoperative for up to 12 hours. The primary endpoint was (based on cefuroxime time-dependent efficacy) the time with cefuroxime concentrations above the clinical breakpoint minimal inhibitory concentration for Staphylococcus aureus of 4 µg/mL in percentage (%fT>MIC4) of. (a). patients’ individual surgery time,. (b). first dosing interval (0-4 hours),. (c). second dosing interval (4-12 hours). Results. Mean cefuroxime %fT>MIC4 (range) of:. (a). patients’ individual surgery time was 100% (100-100%) in all investigated tissues. (b). the first dosing interval was 93% (93-93%) in vertebral bone, paravertebral muscle, subcutaneous tissue, and 99% (99-100%) in plasma. (c). the second dosing interval was 87% (52-100%) in paravertebral muscle, 89% (52-100%) in subcutaneous tissue, 91% (71-100%) in the profound wound, 94% (72-100%) in the superficial wound, and 71% (42-100%) in plasma. Conclusions. Personalized cefuroxime dosing by repeated weight-dosed (20 mg/kg) intravenous administrations provided homogenous and therapeutic spine tissue exposure across all investigated tissues and plasma in long-lasting spine surgery with hypotensive anaesthesia (up to 11 hours). Thus, personalized cefuroxime dosing may decrease the risk of postoperative spine infection, especially in cases with implant insertion


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_15 | Pages 41 - 41
1 Dec 2021
Kipp JO Hanberg P Slater J Nielsen LM Jakobsen SS Stilling M Bue M
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Background. Systemically administered vancomycin may provide insufficient target-site concentrations. Intraosseous vancomycin administration has the potential to overcome this concern by providing high target-site concentrations. Aim. To evaluate the local bone and tissue concentrations following tibial intraosseous vancomycin administration in a porcine model. Method. Eight female pigs were assigned to receive 500 mg diluted vancomycin (50 mg/mL) through an intraosseous cannula into the proximal tibial cancellous bone. Microdialysis was applied for sampling of vancomycin concentrations in tibial cancellous bone adjacent to the intraosseous cannula, in cortical bone, in the intramedullary canal of the diaphysis, in the synovial fluid of the knee joint, and in the subcutaneous tissue. Plasma samples were obtained. Samples were collected for 12 hours. Results. High vancomycin concentrations were found in the tibial cancellous bone with a mean peak drug concentration of 1,236 (range 28–5,295) µg/mL, which remained high throughout the sampling period with a mean end concentration of 278 (range 2.7–1,362.7) µg/mL after 690 min. The mean (standard derivation (SD)) peak drug concentration in plasma was 19 (2) µg/mL, which was obtained immediately after administration. For the intramedullary canal, in the synovial fluid of the knee joint, and subcutaneous tissue, comparable mean peak drug concentration and mean time to peak drug concentration were found in the range of 7.5–8.2 µg/mL and 45–70 min, respectively. Conclusions. Tibial intraosseous administration of vancomycin provided high mean concentrations in tibial cancellous bone throughout a 12-hour period, but with an immediate and high systemic absorption. The concentrations in cancellous bone had an unpredictable and wide range of peak concentration. Low mean concentrations were found in all the remaining compartments. Our findings suggest that intraosseous vancomycin administration in proximal tibial cancellous bone only is relevant as treatment in cases requiring high local concentrations nearby the intraosseous cannula


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_7 | Pages 71 - 71
1 Jul 2020
Vissa D Lin C Ganapathy S Bryant D Adhikari D MacDonald S Lanting B Vasarhelyi E Howard J
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Dexmedetomidine, an alpha 2 agonist, has been approved for providing sedation in the intensive care unit. Along with sedative properties, it has analgesic activity through its highly selective action on alpha 2 receptors. Recent studies have examined the use of dexmedetomidine as an adjuvant to prolong the duration of peripheral nerve blocks. Studies showing effectiveness of dexmedetomidine for adductor canal block in knee surgery are small. Also, its effectiveness has not been compared to Epinephrine which is a strong alpha and beta receptor agonist. In a previous study, we showed that motor sparing knee blocks significantly increased the duration of analgesia compared with periarticular knee infiltration using local anesthetic mixture containing Epinephrine following total knee arthroplasty (TKA). In this study, we compared two local anesthetic mixtures: one containing Dexmedetomidine and the other Epinephrine for prolongation of motor sparing knee block in primary TKA patients. After local ethics board approval and gaining Notice of Compliance (NOC) from Health Canada for use of Dexmedetomidine perineurally, 70 patients between the ages 18 – 95 of ASA class I to III undergoing unilateral primary total knee arthroplasty were enrolled. Motor sparing knee block − 1) Adductor canal continuous catheter 2) Single shot Lateral Femoral Cutaneous Nerve block 3) Single shot posterior knee infiltration was performed in all patients using 60 ml mixture of 0.5% Ropivacaine, 10 mg Morphine, 30 mg Ketorolac. Patients randomized into the Dexmedetomidine group (D) received, in addition to the mixture, 1mcg/kg Dexmedetomidine and the Epinephrine (E) group received 200mcg in the mixture. The primary outcome was time to first rescue analgesia as a surrogate for duration of analgesia and secondary outcomes were NRS pain scores up to 24 hours and opioid consumption. The time to first rescue analgesia was not significantly different between Epinephrine and dexmedetomidine groups, Mean and SD 18.45 ± 12.98 hours vs 16.63 ± 11.80 hours with a mean difference of 1.82 hours (95% CI −4.54 to 8.18 hours) and p value of 0.57. Pain scores at 4, 6, 12, 18 and 24 hours were comparable between groups. Mean NRS pain scores Epinephrine vs Dexmedetomidine groups were 1.03 vs 0.80 at 4 hours, 1.48 vs 3.03 at 6 hours, 3.97 vs 4.93 at 12 hours, 5.31 vs 6.18 and 6.59 v 6.12 at 24 hours. Opioid consumption was also not statistically significant between both groups at 6, 12 18, 24 hours (p values 0.18, 0.88, 0.09, 0.64 respectively). Dexmedetomidine does not prolong the duration of knee motor sparing blocks when compared to Epinephrine for total knee arthroplasty. Pain scores and opioid consumption was also comparable in both groups. Further studies using higher dose of dexmedetomidine are warranted


Orthopaedic Proceedings
Vol. 97-B, Issue SUPP_16 | Pages 4 - 4
1 Dec 2015
Jorge J Grenho A Requicha F Alves S Arcângelo J Santos H Gonçalves S Rodrigues L
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Corynebacterium Jeikeium is a pathogen rarely involved in orthopaedic infections. Till date only 14 cases of osteomyelitis are described in the literature, envolving the tibia, foot and prosthethic (hip and joint) infection. To our knowledge, Corynebacterium Jeikeium as not been reported as an infectious agent of the spine. Our goal is to describe a case of scoliosis surgical site infection by a Corynebacterium Jeikeium specimen. This is a retrospective and descriptive case report based on data from clinical records, patient observation and analysis of complementary exams. We present a 24 year old female with a history of premature birth, West syndrome, spastic cerebral palsy and spina bifida. She was sent to our consult for evaluation of dorsolombar scoliosis. In October of 2014, she was submitted to surgery – posterior spine arthrodesis and instrumentation (D10 to L5) with bilateral pedicle screws and two chromium-cobalt bars. The early post-operative period was without complications. She was discharge at the seventh day of internment and was seen, fifteen days postoperative, at the consultation office, where the dressings were changed, with no signs of surgical site infection. One month post-operative, she recurs to the office because of an apparent seroma at the surgical site wound. There was no reference to fever or other signs of local/systemic infection. A swabbing of the wound was done and the patient was medicated with Ciprofloxacine, 500mg 12/12 hours – the culture came back negative. Seven days later she was seen again, maintaining the seroma with purge of a serous-aspect fluid. Antibiotic therapy was maintained and another swabbing was collected – culture came back negative. Because of suspected surgical site infection, she was re-operated at December of 2014. Surgical wound debridement was performed; three tissue samples and one exudate were sent to the microbiological department. In all samples but one was identified a Corynebacterium Jeikeium. No sensitivity test was performed. Intravenous Vancomicine, 1 gram 12/12 hours was started and maintained during 8 days. Eleven days post-operative she was discharged with oral Vibramicin, 100 milligrams 12/12 hours for two weeks. She is currently being followed at the doctor's office, with no sign of reinfection of the surgical site. This is the first reported case describing an infection of the spine by a Corynebactereium Jeikeium. Isolation of the causative agent of infection and literature-based directed antibiotherapy are important for a successful outcome


Rapid discharge pathways (RDP) have been implemented throughout most areas of orthopaedics. The primary goal of these pathways is to standardize the post-surgical hospital course for patients in order to decrease hospital length-of-stay (LOS). Surgical treatment of adolescent idiopathic scoliosis (AIS) remains one of the most invasive pediatric orthopaedic procedure and is routinely associated with a prolonged hospital stay. The implementation of RDPs following surgery for AIS has shown to be successful; however, all of these studies have been conducted within the United States and it has been shown previously that there exists major differences in hospital LOS and in post-operative complications between Canada and the United States. Therefore, the objective of this study was to determine if the implementation of a RDP at a single children's tertiary-referral centre in Canada could decrease hospital LOS without increasing post-operative complications. A retrospective chart review was completed for all patients who underwent posterior spinal instrumentation and fusion (PSIF) between March 1st, 2010 and February 28th, 2019, with date of implementation being March 1st, 2015. Patient pre-operative, operative, and post-operative information was collected from the charts along with the primary outcome variables: LOS, wound complication, 30-day return to the OR, 30-day emergency department admission, and 30-day hospital readmission. An interrupted time series analysis with a robust linear regression model was utilized to assess for any differences in outcomes following implementation of the RDP. Ninety days before and after the implementation of the RDP was not included in this analysis due to variances in practice that were occurring at this time. A total of 244 participants were identified, with 113 patients in the conventional pathway and 131 patients in the RDP cohort. No significant differences in pre-operative or operative characteristics existed between the groups, except for the RDP group having approximately a 50 larger pre-operative curve and the conventional pathway having on average 200mL greater intra-operative blood loss (p<0.05). Hospital LOS was found to be significantly shorter in the RDP group, with the median LOS being 5.2 [95% IQR 4.3–6.1] days in the conventional group and 3.4 [95% IQR 3.3–3.5] days in the RDP group (p<0.05). Patients in the RDP group were also found to stand 0.9 days earlier, walk 1.1 days earlier, their Foley catheter was discontinued 0.5 days earlier and their personal controlled analgesia was discontinued 12 hours sooner (p<0.05). There were no differences in post-operative complications between the two groups (p>0.05). This study demonstrates that implementing a RDP following PSIF for AIS can successfully decrease hospital LOS without increasing post-operative complications in a single payer universal healthcare system. The associated decrease in LOS could correlate with decreasing costs for both the healthcare system and for the patient's family


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_5 | Pages 86 - 86
1 Apr 2018
Xu J Zeng L Knight M Shelton J
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Introduction. Wear debris and metal ions originating from metal on metal hip replacements have been widely shown to recruit and activate macrophages. These cells secrete chemokines and pro-inflammatory cytokines that lead to an adverse local tissue reaction (ALTR), frequently requiring early revision. The mechanism for this response is still poorly understood. It is well documented that cobalt gives rise to apoptosis, necrosis and reactive oxygen species generation. Additionally, cobalt stimulates T cell migration, although the effect on macrophage motility remains unknown. This study tests the hypothesis that cobalt ions and nanoparticles affect macrophage migration stimulating an ALTR. Methods. This study used Co. 2+. ions (200µM) and cobalt nanoparticles (CoNPs, 100µM, 2–60nm diameter). PMA differentiation of the U937 cell line was used as macrophage-like cells. The effect of cobalt on macrophage migration was investigated by live cell imaging. After 12 hours of each treatment, timelapse images of 20 cells were collected over a 6 hour period with images captured every 5 min. Migration of individual cells was tracked in 2D using ImageJ software. The transwell migration assay was also applied to study the effect of cobalt on macrophage directional migration. U937 cells in serum free medium were added to the upper chamber of a 8µm pore size Transwell insert in the presence of cobalt, whilst the lower chamber was filled with medium plus 10% FBS. After 6 hours treatment, cells remaining on the membrane were fixed, stained with crystal violet and counted. Cellular F-actin and podosomes were visualized by labeling with TRITCconjugated phalloidin and anti-vinculin antibody after 12 hours of cobalt exposure (Co. 2+. and CoNPs). Results. Cells incubated with cobalt ions and nanoparticles showed a substantial reduction in cell migration compared with control cells. The total migration path length of cells treated with Co. 2+. (362.4±96.6µm) and CoNPs (217.3±128.1µm) were significantly shorter than those for untreated cells (801.1±198.3µm). The ability of macrophages to migrate through the transwell membrane was significantly impaired by pre-treatment with cobalt, with 16±4 and 18± migrated cells/field for Co. 2+. and CoNPs respectively with the control at 42±7 migrated cells/field. In addition, cobalt influenced macrophage morphology and actin cytoskeletal organization with a dramatic increase in the presence of intracellular podosome-type adhesions structure. Discussion. Co. 2+. ions and nanoparticles dramatically inhibited the migration of U937 macrophages in contrast to the enhanced migration reported for T cells. We propose that macrophages recruited into the area of CoCr implants would lose their responsiveness to migration signals and be retained in situ due to cobalt-induced cytoskeleton rearrangement. This enhanced macrophage accumulation and cobalt-induced formation of podosomes may therefore represent a mechanism through which cobalt wear debris and metal ions from joint prostheses exacerbate the ALTR leading to revision surgery


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_7 | Pages 4 - 4
1 Jul 2020
Gautreau S Forsythe ME Gould O Mann T Haley R Canales D
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Early mobilization within the first 12 hours (day zero) of total joint arthroplasty (TJA) has been shown to reduce length of stay (LoS) without risking clinical outcomes, patient safety or satisfaction. The purpose of this study was to investigate associations between the degree of mobilization on day zero (i.e., standing at the bedside versus walking in the hallway) and LoS in TJA patients. In addition, we investigated predictors of LoS and day zero mobilization. A retrospective cohort study was undertaken of the health records of patients in a community hospital setting who had an elective unilateral primary TJA between June 2015 and May 2017 and had mobilized on day zero. The total sample was 283 patients (184 TKA and 99 THA) across four mobilization categories: Sat on beside (n = 76), Stood by bed/marched in place (n = 83), Walked in the room (n = 79), and Walked in hall (n = 45). Analysis of variance found no significant group differences in age, ASA score, Charlson Comorbidity Index score, anesthesia, surgeon, procedure type, pain medication, and patient reported symptoms recorded by physiotherapists. Significantly more women were in the Sat group and significantly more men were in the Hall group (p < .001). Patient reported symptoms of nausea and drowsiness were significantly greater for the Sat group (p < .001). LoS was also significantly different across the groups. Post hoc Tukey comparisons found the Walked Hall group had significantly shorter LoS (M = 2.7 days) than the Sat group (M = 3.9, p < .001), Stood group (M = 3.4, p = .011), and the Walked Room group (M = 3.5, p = .004). A hierarchical regression was performed to determine predictors of LoS. Block 1 consisted of demographic, medical status, and patient reported symptoms as variables. Mobilization was entered in Block 2. The first model was significant (p < .001) and explained 24% of variance in LoS. The final model was also significant (p < .001), accounting for a total of 26% of the variance in LoS. Thus, block 2 (i.e., mobilization) accounted for a small but significant 2% incremental variance (p = .008) beyond the block 1 variables in the prediction of LoS. With mobilization added, only male gender (p = .002), lower BMI (p = .026), and lower ASA scores (p = .006) remained significant predictors of shorter LoS, and the predictive ability of several of the block 1 variables were reduced to non-significant levels. A simultaneous regression model was then used to predict degree of mobilization. The model accounted for 24% of the variance in mobilization (p < .001). Variables significantly associated with a greater degree of mobilization included: younger age, male gender, lower BMI, and fewer symptoms, namely nausea, numbness, lightheadedness, and drowsiness. This study found length of stay was shorter when patients mobilized farther on the day of surgery. Some factors predictive of mobilization may be modifiable. Focusing on symptom management could increase opportunities for farther mobilization on the day of surgery, and thus decrease length of stay


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXIX | Pages 47 - 47
1 Sep 2012
Hull P Jenkinson R Essue J Johnson S Kreder H
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Background. Traditional recommendations suggest that open fractures require urgent surgical debridement to reduce infection. However, this has recently been challenged by a number of investigations. However, in many cases, these studies were not able to control for important confounding factors. The purpose of our study was to evaluate the relationship between delay to definitive surgical debridement while controlling for important confounders. Method. 364 patients with 459 open fractures treated at a level one trauma centre over four years were reviewed. Time to definitive surgical debridement was modelled as a predictor of infection while controlling for fracture grade, anatomic site of fracture, and presence of significant contamination. Time to debridement was modelled as both a continuous variable and a categorical variable with cut off points at 6 and 12 hours of delay. Results. 46 deep infections occurred in 459 fractures(10%). There were no infections among grade one open fractures(0/55). Delay to debridement using cut-points of 6 hours and 12 hours was not associated with an increased infection rate. However, with delay to debridement analyzed as a continuous variable each additional hour of delay was associated with an increase in the odds of infection(OR=1.033 95%CI 1.01–1.057). Multivariable analysis also showed that infection was associated with tibial fractures(OR=2.44 95%CI 1.26–4.73), higher Anderson & Gustillo grade (OR=1.99 95%CI 1.004–3.954), and gross contamination (OR=3.12 95%CI 1.36–7.36). Among more severe open fractures the impact of delay to debridement translates into a larger absolute increase in probability of infection. Conclusion. We recommend that higher grade open fractures be treated with definitive debridement as soon as possible given that the risk of infection increases in a linear fashion with time delay. For severe open fractures, especially tibial, we recommend emergent debridement as soon as the patient has been resuscitated and is stable enough to undergo surgery


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_IV | Pages 115 - 115
1 Mar 2012
Sahu A Singh M Bharadwaj R Harshavardana N Hartley R
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Introduction. The aim of this study was to compare the results and length of stay of patients of early (within 12 hours) versus conventional (after 48 hours) ankle fixation our hospital. Methods of study. It was a retrospective study over 18 month period (July 2004 - Dec 2005) including 200 Patients (aged 16 or more). We looked into age, place of living, Weber classification, mechanism of injury, comorbidities especially diabetes, addictions mainly smoking, etc. Overlying skin condition, the amount of swelling at presentation, associated ankle dislocation or talar shift, acute medical comorbidities, injury types-open or closed were classified accordingly. Results. Out of 200 patients, only twenty-two had surgery done within 12 hours (mean length of stay, 3.3 days), and sixty-seven of these had surgery within 48 hours (mean length of stay, 4.9 days), while 111 had surgery after 48 hours (mean length of stay, 9.4 days). Finally we calculated the extra cost (784 bed days - £235,000) incurred to the trust in terms of extra bed occupancy and treating the complications as a result of wait. Main reasons for delay in theatre and discharge were swelling and blisters, delay in transit from Bournemouth A&E, delayed presentation, unavailability of theatre time or cancellation, further imaging required or senior opinion awaited. Conclusion. This study shows that initial delay may cause swelling and blistering to develop which mandates a further delay. Our message about ankle fractures is not to miss the boat and operate before the swelling appears. We want to emphasise on the ‘Window of Opportunity’ ie initial 12 hours to fix the ankle fractures to decrease overall morbidity and cost


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_17 | Pages 65 - 65
1 Dec 2018
Tkhilaishvili T Di Luca M Trampuz A
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Aim. Staphylococcus aureus and Pseudomonas aeruginosa are ubiquitous pathogens often found together in polymicrobial, biofilm-associated infections. The mixed-species biofilm are significantly more resistant to antimicrobial treatment and are associated with failures. Bacteriophages present a promising alternative to treat biofilm-related infections due to their rapid bactericidal activity on multi-drug resistant bacteria. In this study, we assess the simultaneous or sequential application of phages and ciprofloxacin on the mixed-species biofilm in vitro. Method. Ciprofloxacin was tested alone and in combination with Pyo-bacteriophage cocktail against P.aeurginosa ATCC 27853 and MRSA ATCC 43300 mixed-species biofilm. In order to evaluate the effect of combined treatment on biofilm-embedded cells, mature biofilms were grown on porous glass beads with MRSA (10. 6. CFU/ml) and P.aeruginosa (10. 3. CFU/ml) and incubated for 24h at 37° C in LB broth. The beads were then washed and placed in fresh LB in the presence of sub-eradicating titers/concentrations of phages and ciprofloxacin (corresponding to 1/4, 1/8, 1/16, 1/32, 1/64, 1/128 × MBEC. biofilm. ), respectively, simultaneous or in order (pretreated with phages for 3-6-12-24 hours) at 37°C. In all cases, heat flow produced by the viable cells still embedded in the biofilm was measured for 48 hours by isothermal microcalorimetry. Results. Simultaneous or sequential treatment with pyo-bacteriophage (10. 5. and 10. 6. PFU/ml) and ciprofloxacin, producing a synergistic effect resulting in the complete eradication of the biofilm was evaluated. When sub-eradicating concentrations of ciprofloxacin together with sub-eradicating titers of phages simultaneously used to treat mixed-species biofilm, a delay and/or reduction of heat flow produced by bacteria was observed. The same effect was seen when mix-biofilm was pre-treated with phages for 3 hours and 24 hours, respectively. However, antibiotic introduction after 6 and 12 hours resulted in a high synergistic eradicating effect with pyo-bacteriophage. The concentration of ciprofloxacin decreased dramatically from >512 μg/ml to < 16 μg/ml. Conclusions. While MBEC of ciprofloxacin against mixed-species biofilm of Pseudomonas aeruginosa and Staphylococcus aureus was above drug concentrations reachable in clinical practice, the co-administration with bacteriophage strongly reduced the antibiotic doses needed to eradicate biofilm. There is a specific time delay in antibiotic introduction to reach the eradication of mix-species biofilm. These results have implications for optimal combined treatment approaches


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXIII | Pages 186 - 186
1 May 2012
Miller D Van Der Westhuizen J Oldham D
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To examine all open fractures presenting to Bundaberg Base Hospital—from January 2007 to January 2009—by monitoring the clinical course of the patients, with attention to the time intervals between injury, presentation and orthopaedic treatment. The complications of treatment and the implications for future practice were also examined. A search was performed of all open fractures and compound fractures during the period of January 2007 until January 2009. The eligible patients were selected and their charts reviewed. The time of the injury, the time they presented to the emergency department (ED) and the time to orthopaedic treatment were noted. The site of the fracture, the Gustillo classification and the number of days of admission were recorded. Complications of the fractures were investigated. The impact of time delays and fracture severity on subsequent infections were correlated. A total of 127 admissions were recorded, 38 were excluded and 89 open fractures were included in the study: 54 upper limb, 34 lower limb and 1 pelvic fracture. Thirty-six patients had Gustillo I, 34 II, 9 IIIa, and 11 IIIb classifications. Patient arrival times were as follows: less than one hour (19%), 1–3 hours (44%), 3–6 hours (26%), 6–12 hours (8%) and greater than 12 hours (2%). From presentation, 28% of patients received treatment in 1–3 hours, 3–6 hours (27%), 6–12 hours (22%) and greater than 12 hours (22%). 40.4% of patients received treatment within 6 hours of injury and 59.5% greater than 6 hours. 33% of patients stayed in hospital 24 hours, 1–3 days (44%), 3–7 days (15%) and for greater than one week (1%). There were a total of 17 complications (19%), of which 11 (12%) were associated with infections. Of these, six were superficial wound infections and five were deep infections. Of these deep infections, two were associated with non-unions and one with a mal-union. Four complications were associated with non-infectious non-unions, one non-infectious mal-union. One had a missing bone fragment. Complications were found to be more prevalent when there was delayed treatment of the fractures. The results demonstrate that the majority of open fractures treated are upper limb and Gustillo I in classification. The complication rate for open fractures during the two year period was 19%. These findings provide a base for continued monitoring of open fracture management at Bundaberg Base Hospital


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_5 | Pages 55 - 55
1 Mar 2017
Nho J Suh Y Park J Lee Y Ha Y Koo K
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Introduction. Venous thromboembolism (VTE), including pulmonary embolism (PE) resulting from deep vein thrombosis (DVT), remains a well-known serious complication after femoral fractures. The low molecular heparin is widely used to prevent VTE. This study compared the effectiveness of VTE prevention between dalteparin and enoxaparin. Materials and Methods. From 2013 to 2014, we retrospectively recruited 712 patients who had femoral fractures with operative treatment. All patients receiving VTE chemoprophylaxis with perioperative period using dalateparin in Group 1(N=395) and enoxaparin in Group 2(N=317). The prophylactic dosing was determined using individual product labeling and identified as enoxaparin 40 mg every 12 hours and dalteparin 2500 international unit (IU) once daily, based on clinical practice guidelines. The prophylaxis was started at admission, and maintained during average 8.43.5 days after operation. The outcome including the incidence of clinically significant deep vein thrombosis, pulmonary embolism, perioperative bleeding and cost of drugs were evaluated between two groups. Results. The two study groups did not differ significantly in fracture type, age, gender, ASA score. The overall incidence of VTE is similar between two groups. However, the incidence of fatal PE is significantly lower in patients with dalteparin (Group 1: 4/395(1.00%), Group 2: 10/317(3.15%), p<0.001). And the overall cost of each group is significantly different between two groups (Group 1: average KRW 89,426, Group 2: average KRW 32,188, p<0.001). Conclusion. Both dalteparin and enoxaparin could be safely used without notable complications in VTE prophylaxis. However, dalteparin had more advantages for prevention of fatal PE, compared to enoxaparin in patients with femoral fractures with significant cost effectiveness


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_20 | Pages 93 - 93
1 Nov 2016
Weeks C Somerville L Phillips J Ganapathy S Howard J
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The use of spinal anesthesia with adjuvant intra-thecal opioids has been commonly used in total knee arthroplasty without documented clinical benefit. It has been associated with a potential increase in side effects, including nausea, vomiting, pruritus, urinary retention and oxygen usage. This double-blinded RCT investigated whether the addition of epimorph to spinal anesthesia in patients undergoing total knee arthroplasty resulted in superior pain control and decreased narcotic consumption without also causing an increase in postoperative complication rates. We performed a prospective double-blind trial in patients undergoing primary total knee arthroplasty (TKA). Patients were randomised to receive either spinal anesthesia alone or spinal anesthesia with epimorph (150 ug). All patients received infiltration of a local anesthetic cocktail intraoperatively. Both the study patients and staff measuring outcomes were blinded to the experimental treatment received during data collection. Postoperatively, visual analogue scale (VAS) for pain was recorded at 6, 12, 18, 24, 36 and 48hrs and a final value at 1 week. Narcotic use, Foley insertion, oxygen requirements, nausea, vomiting and pruritus were recorded during the course of hospitalisation. Forty-one patients were randomised into each of the spinal with epimorph and spinal alone treatment arms. The groups showed no significant differences in BMI, age, and gender distribution. In the first 12 hours postoperatively there was no difference in VAS for pain between the two groups, however there were significantly lower pain scores in the spinal alone patients at 18 hours (p=0.002), 24 hours (p=0.04) and 48 hours (p = 0.03) compared to the spinal with epimorph group. Narcotic usage was greater in the spinal group during the first 6 hours postoperatively, but beyond this time point narcotic usage was similar between the two groups. Additionally, there was a statistically significant increase in rate of complications with spinal epimorph including nausea (p=0.037) and pruritus (p=0.024). The incidence of urinary retention was greater in the spinal epimorph group, however this did not reach statistical significance. This study demonstrates no clinical benefit with the addition of intra-thecal opioids to spinal anesthetic in primary TKA. In addition to a failing to reduce VAS pain scores and overall narcotic consumption, increased complication rates were seen. For these reasons, this study does not support the use of epimorph in addition to spinal anesthesia for pain control in TKA


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_8 | Pages 144 - 144
1 May 2016
Park K Lee G Kim D Rim Y
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Purpose. There are still some controversies over the routine use of negative suction drainage after primary total hip arthroplasty (THA). In this study we are to know the benefits of new suction drainage management strategy after primary THA. Materials and methods. From 2010 to 2012, two hundred patients who had unilateral primary THA were randomly allocated into two groups. One group had negative suction drainage immediately after THA (Group 1). In the other group, the suction drainage was inserted but negative pressure was applied more than 12 hours after surgery, in the morning postoperative day one (Group 2). All surgeries were performed by one single hip surgeon using the same technique and postoperative rehabilitation protocol was all same. We checked the amount of blood loss, changes in hemoglobin (Hb), volume of blood transfusion, superficial or deep wound infection and hematoma. Clinical results were evaluated using HHS score. Results. The changes in hemoglobin (Hb) from postoperative 48hrs from immediate THA was not different between two groups (group 1: 0.91±1.10, group 2: 0.77±0.95, p=0.334). However, the changes in Hb postoperative day one from immediate was significantly lower in group 2 (group 1: 4.24±1.09, group 2: 3.61±0.96, p<0.001). The changes in Hb from posteroperative day one and seven were significantly lower in group 2 comparing preoperative Hb (group 1: 1.11±1.52, group 2:0.67±1.57, p=0.043). The amount of total blood drainage was different between two groups (group 1: 437.75±193.51, group 2: 377.25±185.19, p<0.001). The unit number of blood transfusion was also significantly lower in group 2 (group 1: 1.40±1.24, group 2: 0.74±1.03, p <0.001). There was no significant difference about the complication rate between two groups. There was no difference in HHS between two groups. Conclusions. The simple change of negative suction drainage management strategy can reduce the amount of blood loss after primary THA and the volume of blood transfusion


Orthopaedic Proceedings
Vol. 97-B, Issue SUPP_16 | Pages 94 - 94
1 Dec 2015
Maya JO Cruz JA Dubois JG Garduño AG
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Diagnosis, treatment and outcome in systemic infection caused by Coccidioides Immitis in a non endemic region. First case in Spain. 71 year old patient. Symptoms: stomach aches, tiredness and weight loss of 14kg. Imaging Investigations: Abdominal pelvic US and Gastroscopy were performed as cancer was suspected. This study showed a bilateral suprarrenal mass. Fearing a pulmonary mass a Thoracic Scan was requested. Results proved mediastinal and axillary nodes. Also found was interstitial illness which lead to a working diagnosis of Granulomatous Lymphangitis. BIOPSIES: An axillary lymph node, suprarrenal gland and pulmonary tissues. ANATOMOPATHOLOGY: Necrotising Granulomatous Lymphadenitis. DIFFERENTIAL DIAGNOSIS: TBC, Sarcoidosis and Autoinmune illnesses. SAMPLE CULTURES were repeatedly negative for funghi, bacteria and Mycobacterium. DIAGNOSIS The patient was subsequently he was commenced on Substitute Hormonal Therapy with improvement of symptoms. MANAGEMENT: Due to a gonarthrosis he required Total Knee Arthroplastia. During surgery a prominent SINOVITIS was noticed, with anatomopathology results of Chronic Necrotising Granulomatous Sinovitis with lymphoid folicules. FOLLOW UP: 7 years after the patient attends A&E with signs of infection on the replaced knee. A bacterial infection is suspected and the patient is admitted into hospital for the replacement extraction, cement substitution with Gentamicin and iv antibiotherapy with LEVOFLOXACIN. His symptoms improved up to a month when he returned to A&E with similar presentation THE PATIENT IS ADMITTED ONCE MORE FOR SURGERY:. Sample Cultures from the prosthesis showed positive growth for Coccidiodes Immitis. Article Reviews provided us with brand new information. A new approach was taken and anamnesis was geared towards finding out a possible contact with the funghi in the endemic region. It appeared that the patient had worked as a Shepherd for four years (1957–1961) in Bakersfield. A Southern Californian region north to LA and under San Francisco. After all, he was admitted for 25 days in a local hospital for pneumonia. DIAGNOSIS WAS REACHED thanks to these findings. The old spacer wasswapped for a Cement Spacer with Amphotericin B 250 mg. Oral treatment with FLUCONAZOL 400 mg/day was associated and after a few days changed to ITRACONAZOL 200 mg/12 hours orally. The patient improved local and systemically. After a few months he evolved as planned and now has a good general and local condition with normal biochemistry results. A final ARTHRODESIS was performed. It's quite likely that he may require long life therapy with Antifungals to avoid reactivations. We highlight the originality of the case, as the first diagnosis of articular Coccidioides diagnosed in Spain, and its successful outcome with prosthetic replacement rebound and chronic antifungal therapy


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_9 | Pages 100 - 100
1 May 2016
Onishi H Tsukamoto M Okabe S Mori T Uchida S Murata Y Moridera K Hirano F Ikei D Kamegawa S Akinori S
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Introduction. The purpose of this study was to introduce our perioperative prophylaxis method for infection and clarify surgical site infection rate in our patients performed total hip arthroplasty (THA). Method. Two hundred and eighty four THA (including revision 18 cases) performed by single surgeon between Oct. 2007 and Jan. 2013 were evaluated. The mean age of patients was 65.7 years old. The male to female ratio was 46 to 238. BMI was 23.6. Ninety patients (32%) were compromised host suffering from diabetes mellitus, rheumatoid arthritis, autoimmune disease, history of malignant tumor, hemodialysis or skin disease at surgical site respectively. At preoperative period, we checked decayed tooth, alveolar pyorrhea, hemorrhoids, and leg skin condition. In addition, we examined culture of nasal cavity. At the day of surgery, patient took a shower just before entering surgical room. All of THA was performed in clean room NASA class 100. Surgeons and assistant nurse put on nonwoven fabric gown, space suit and double rubber gloves. We wiped surgical site leg by gauze impregnated by 0.5% chlorhexidine alchohol to eliminate skin bacteria twice just before surgeons scrubbing hands. Surgical site was covered by povidone iodine containing drape. Surgeons or nurse changed gloves when glove was broken at each time. We cleaned surgical field by pulse washer whenever necessary. We did not use drain except for 5 revision THAs. Regarding to prophylactic antibiotics usage, we administered cefcapene pivoxil orally the day before surgery. Drip infusion antibiotics (PIPC: until Oct. 2008, CEZ: after Oct. 2008) was administered at the period of 30 min. before surgery and 4 hours after surgery in case of prolonged surgical time (4 hours >). Skin closure was performed by staple and covered by gauze until May 2010. After that, we used surgical tape and transparent water proof sheet. After finishing surgery, antibiotic was administered 8 hours interval at surgery day and 12 hours interval for additional two days. In case multi-drug resistant bacteria (MRSA, MRSE) was positive in nasal culture, we applied mupirocin ointment to nasal cavity for 3 days before surgery and administered vancomycin (from Aug. 2011) or linezolid (from 2012) for prophylactic antibiotics in perioperative period. Results. Multi-drug resistant bacteria was detected from nasal cavity in 23 patients (8%). The mean operation time was 194 min (due to education for young surgeon). Intraoperative bleeding was 598g. Length of skin incision was 13.6 cm. Intraoperative wash volume was 4500 ml. The infection rate were 0 % in early period and 0.7 % (two case) in late period respectively. One infected case was 75 years old female. Deep infection was occurred 3 years after surgery. She was administered steroid and immunosuppressive drug due to metal allergy after total knee arthroplasty. The other case was 64 years old female. Superficial infection happened 3 months after THA. The patient was suffered from collagen disease and diabetes. Conclusion. Our prophylaxis method for surgical site infection of THA achieved 0 % in early infection and 0.7% late chronic infection respectively


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_15 | Pages 155 - 155
1 Mar 2013
Ziaee H Daniel J Pradhan C McMinn D
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Introduction. Modern metal-on-metal bearing resurfacings have been in use for nearly two decades. Local and systemic metal ion exposure continues to cause concern. We could not find a prospective metal ion study in such patients with a 10-year follow-up. This is the first ten year prospective study of metal ion levels in blood and their release in urine following hybrid fixed metal-on-metal surface arthroplasty. Methods. Twenty six patients were included in an ongoing longitudinal metal ion study of patients with unilateral metal-on-metal hip resurfacings. Three of them were excluded due to subsequent contralateral resurfacing and one has relocated abroad. Cobalt and chromium levels were assessed in 12 hour urine collections before and periodically after operation (5 days to 10 years) using high resolution plasma mass spectrometry. Mean age at operation was 53 years and mean BMI 27.9. Results. Hip function questionnaires at the 10-year review showed that the patients have well-functioning pain-free resurfacings (mean Oxford hip score 14.3). Metal ion results show median cobalt and chromium release at 10 years were 8.3 μg/24 hr and 4.35 μg/24 hr respectively. A statistically significant early peak 6 months to 1 year after operation is followed by a steady decrease over the following seven years although the reductions are not statistically significant. Discussion and Conclusion. Elevated systemic metal ion exposure continues to cause concern in patients treated with metal-metal arthroplasties. Our results show that metal release in these bearings shows a reducing trend after an initial peak. The unknown significance of persistent metal ion elevation underlines the need for continued long-term monitoring


Introduction. Around the knee high-energy fractures/dislocation may present with vascular injuries. Ischaemia time i.e. the time interval from injury to reperfusion surgery is the only variable that the surgeon can influence. It has been traditionally taught that 6-8 hours is revascularisation acceptable. There are only limited case series that have documented the time-dependent lower limb salvage rate (LSR) or the lower limb amputation rate (LAR). We have conducted a meta-analysis to look at LSR and LAR to inform clinical standard setting and for medicolegal purposes. Methods. Two authors conducted an independent literature search using PubMed, Ovid, and Embase. In addition the past 5 years issues of Journal of Trauma, Injury and Journal of Vascular surgery were manually scrutinised. Papers included those in the English language that discussed limb injuries around the knee, and time to limb salvage or amputation surgery. The Oxman and Guyatt index was used to score each paper. Results. 21 retrospective case series articles were identified from 8 different journals. A total of 1575 patients were compiled, 92 patients were lost or died. 263 lower limbs underwent amputation and 1220 limbs were salvaged. 984 lower limbs were salvaged within the 8 hours. The LAR increased with time from 3% with reperfusion surgery in less than 4 hours to 13% at 6 hours and 32% at 8 hours. A lower LAR of 20% for patients presenting after 12 hours was seen


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXIX | Pages 190 - 190
1 Sep 2012
Dargan D Callachand F Connolly C
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Introduction. Intracapsular fractures of the femoral neck in young adults are a surgical emergency. Recent literature reviews have questioned whether the timing of surgery reduces the incidence of avascular necrosis, non-union and revision. A study was performed to determine how many patients met a 12-hour target for operative fixation with this injury. Possible sources of delay to theatre were reviewed. Methods. A Fractures Outcomes Research Database was used to identify patients aged 18–64 who were admitted to the Royal Victoria Hospital in Belfast between 1. st. Jan 2008 and 31. st. Dec 2009. Intracapsular fractures of the femoral neck which were treated with a 2-hole dynamic hip screw were included. Time of injury, time of presentation in A&E, time of admission to fracture ward, operation time, demographic data, and the mechanism of injury were extracted from the database. Results. 81 patients were identified who met the inclusion criteria. Median age was 56 years (range 26–64y). 64 injuries were low energy. 16 patients were alcoholics, 34 smoked cigarettes. 31 of 81 operations were performed within 12 hours of the injury. Of the delayed 50 patients, 25 sustained their injury between 1700–2359. 51 of 81 operations were performed on daytime lists (0900–1659), 23 in the evening (1700–2359) and 7 overnight (0000–0859). Median time from injury to presentation at A&E was 1 hour 39 minutes. Time from A&E presentation to ward admission was 4 hours. Time from ward admission to surgery was 8 hours 13 minutes. Conclusions. The time from ward admission to arrival in theatre accounted for the greatest delay, and is modifiable. Injuries which occur in the evening are often operated on the next day. The majority of the patients had low energy injuries, and a minority smoke cigarettes and abuse alcohol. The long-term implications of this delay will require further work