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Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_34 | Pages 261 - 261
1 Dec 2013
Parekh J Jones H Chan N Noble P
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Introduction:. Angular mismatch of the modular junction between the head and the trunion has been recognized as a contributing factor to fretting and corrosion of hip prostheses. Excessive angular-mismatch can lead to relative motion at the taper interface, and tribo-corrosion of the head-neck junction secondary to disruption of the passive oxide layer. Although manufacturing standards have been adopted to define acceptable tolerances for taper angles of mating components, recent investigations of failed components have suggested that stricter tolerances or changes in taper design may be necessary to avoid clinical failures secondary to excessive taper wear and corrosion. In this study we examine the effect of angular-mismatch on relative motion between the taper and bore subjected to normal gait load using finite element methods. Methods:. Computer simulations were executed using a verified finite element model (FEM), the results from which were determined to be consistent with literature. A stable, converging hexahedral mesh was defined for the trunnion (33648 elements) and a tetrahedral mesh for the femoral head (51182 elements). A friction-based sliding contact was defined at the taper-bore interface. A gait load of 1638N (2.34 × BW, BW = 700N) was applied at an angle of 30° to the trunnion axis (Figure 1) on an assembled FEM. A linear static solution was set up using Siemens NX-Nastran solver. Angular-mismatch was simulated by incrementing the conical half-angle of the bore to examine these cases: 0°, 0.005°, 0.010°, 0.015°, 0.030°, 0.050°, 0.075°, 0.100°, 0.200°and 0.300°. Results:. Relative interface micro-motion at the proximal-medial point of the taper demonstrated a lack of dependence upon angular-mismatch for tolerances up to 0.075° and a monotonic increase in micro-motion for higher tolerances (0.075–0.3 °; Figure 2). A similar trend was observed with respect to the average values of contact pressure, max von Mises stress and shear stress acting at the proximal-medial aspect of the taper (Figure 3). Non-linear correlation tests indicate a significant correlation (p < 0.0001) of mismatch angle with peak von Mises stress (r = 0.965) and relative micro-motion (r = 0.964). Discussion:. The FEA results corroborate the notion that high angular-mismatch tolerances have a deleterious effect of fretting at the trunnion-head interface. Although, stability of the implant did not appear to be compromised at relatively lower tolerances, the propensity for it is higher at higher mismatches. The simulation was, however, executed as a single-step static analysis ignoring the effect of cyclical loading often observed during gait. This abstract serves as a proof of concept to justify the further development of this FEA to study the effect of angular-mismatch tolerances on micro-motion at the trunnion-head interface. However, current results strongly indicate that tolerance for angular-mismatch can be more liberal without increasing the micro-motion and stresses at the trunnion-head interface. Significance: The effect of angular-mismatch suggests a threshold tolerance different from the industry accepted tolerance of 0.0167°. Mismatches smaller than 0.075° demonstrated only modest variation in the interface micro-motion. Additionally, the results corroborate recent clinical evidence that even with perfectly fit implants, the potential for interface micro-motion can lead to fretting-induced corrosion


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_14 | Pages 27 - 27
1 Dec 2019
Triffault-Fillit C Eugenie M Karine C Becker A Evelyne B Michel T Goutelle S Fessy M Dupieux C Laurent F Lustig S Chidiac C Ferry T Valour F
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Aim. The use of piperacillin/tazobactam with vancomycin as empirical antimicrobial therapy (EAT) for prosthetic joint infection (PJI) has been associated with an increased risk of acute kidney injury (AKI), leading to propose cefepim as an alternative since 2017 in our reference center. The present study compared microbiological efficacy and tolerance of these two EAT strategies. Method. All patients with PJI empirically treated by vancomycin-cefepim (n=90) were prospectively enrolled in an observational study, and compared with vancomycin-piperacillin/tazobactam-treated historical controls (n=117), regarding: i) the proportion efficacious empirical regimen (i.e., at least one of the two molecules active against the identified organism(s) based on in vitro susceptibility testing); and ii) the incidence of empirical therapy-related adverse events (AE), classified according to the Common terminology criteria for AE (CTCAE). Results. Among the 146 (67.3%) documented infections, the EAT was considered as efficacious in 99 (99.0%) and 66 (98.5%) in the piperacillin-tazobactam and cefepim-treated patients, respectively (p=0.109). The rate of adverse events, and in particular AKI, was significantly higher in the vancomycin-piperacillin/tazobactam (n=38 [32.5%] and 32 [27.6%]) compared to the vancomycin-cefepim (n=13 [14.4%] and 5 [5.7%]) group (p=0.003 and <0.001, respectively). Of note, sex, age, and the proportion of patients receiving other nephrotoxics were similar among piperacillin/tazobactam- and cefepim-treated patients. However, in comparison with patients receiving cefepim, a higher modified Charlson's comorbitidy index (4 [IQR, 3–5] versus 2 [IQR, 2–4], p<0.001) has to be acknowledged, mainly related to a higher prevalence of baseline chronic renal injury (n=62, 53.4% versus n=34, 38.6%; p=0.035). Conclusions. The empirical use of vancomycin-cefepim in PJI was as efficient as vancomycin-piperacillin/tazobactam, and was associated with a significantly lower incidence of AKI


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_2 | Pages 18 - 18
10 Feb 2023
Foster A Boot W Stenger V D'Este M Jaiprakash A Crawford R Schuetz M Eglin D Zeiter S Richards R Moriarty T
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Local antimicrobial therapy is an integral aspect of treating orthopaedic device related infection (ODRI), which is conventionally administered via polymethylmethacrylate (PMMA) bone cement. PMMA, however, is limited by a suboptimal antibiotic release profile and a lack of biodegradability. In this study, we compare the efficacy of PMMA versus an antibioticloaded hydrogel in a single- stage revision for chronic methicillin-resistant Staphylococcus aureus (MRSA) ODRI in. sheep. Antibiofilm activity of the antibiotic combination (gentamicin and vancomycin) was determined in vitro. Swiss alpine sheep underwent a single-stage revision of a tibial intramedullary nail with MRSA infection. Local gentamicin and vancomycin therapy was delivered via hydrogel or PMMA (n = 5 per group), in conjunction with systemic antibiotic therapy. In vivo observations included: local antibiotic tissue concentration, renal and liver function tests, and quantitative microbiology on tissues and hardware post-mortem. There was a nonsignificant reduction in biofilm with an increasing antibiotic concentration in vitro (p = 0.12), confirming the antibiotic tolerance of the MRSA biofilm. In the in vivo study, four out of five sheep from each treatment group were culture negative. Antibiotic delivery via hydrogel resulted in 10–100 times greater local concentrations for the first 2–3 days compared with PMMA and were comparable thereafter. Systemic concentrations of gentamicin were minimal or undetectable in both groups, while renal and liver function tests were within normal limits. This study shows that a single-stage revision with hydrogel or PMMA is equally effective, although the hydrogel offers certain practical benefits over PMMA, which make it an attractive proposition for clinical use


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_2 | Pages 13 - 13
1 Feb 2020
Tanaka S Tei K Minoda M Matsuda S Takayama K Matsumoto T Kuroda R
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Introduction. Acquiring adaptive soft-tissue balance is one of the most important factors in total knee arthroplasty (TKA). However, there have been few reports regarding to alteration of tolerability of varus/valgus stress between before and after TKA. In particular, there is no enough data about mid-flexion stability. Based on these backgrounds, it is hypothesized that alteration of varus/valgus tolerance may influence post-operative results in TKA. The purpose of this study is an investigation of in vivo kinematic analyses of tolerability of varus/valgus stress before and after TKA, comparing to clinical results. Materials and Methods. A hundred knees of 88 consecutive patients who had knees of osteoarthritis with varus deformity were investigated in this study. All TKAs (Triathlon, Stryker) were performed using computer assisted navigation system. The kinematic parameters of the soft-tissue balance, and amount of coronal relative movement between femur and tibia were obtained by interpreting kinematics, which display graphs throughout the range of motion (ROM) in the navigation system. Femoro-tibial alignments were recorded under the stress of varus and valgus before the procedure and after implantation of all components. In each ROM (0, 30, 60, 90, 120 degrees), the data of coronal relative movement between femur and tibia (tolerability) were analyzed before and after implantation. Furthermore, correlations between tolerability of varus/valgus and clinical improvement revealed by ROM and Knee society score (KSS) were analyzed by logistic regression analysis. Results. Evaluation of soft tissue balance with navigation system revealed that the tolerance of coronal relative movement between femur and tibia (varus/valgus) after implantation was significantly decreased compared with before implantation even in mid-flexion range. There were no significant correlations between tolerability of coronal relative movement and improvement of extension range and KSS. However, mid-flexion tolerability showed negative correlation with flexion range. Discussion. One of the most important principles for ligament balancing in TKA for varus knees is involved that the medial extension gap should be within 1–3mm to avoid flexion contracture and a feeling of instability, the medial flexion gap should be equal or 1–2mm larger to the medial extension gap, and lateral extension laxity up to 5 degrees is acceptable. However, there have been few reports measuring laxity from 30 to 60 degrees. In this study, the tolerance of coronal relative movement was significantly limited even in mid-flexion. However, mid-flexion tightness was not significantly correlated with clinical results except for flexion range. This result might be suggested that high tolerability of coronal relative movement in mid-flexion range may lead to widening of flexion range of motion of the knee after TKA. For any figures or tables, please contact authors directly


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_5 | Pages 14 - 14
1 Apr 2018
Bitter T Khan I Marriott T Lovelady E Verdonschot N Janssen D
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Introduction. Fretting corrosion of the modular taper junction in total hip arthroplasty has been studied in several finite element (FE) studies. Manufacturing tolerances can result in a mismatch between the femoral head and stem, which can influence the taper mechanics leading to possibly more wear. Using FE models the effect of these manufacturing tolerances on the amount of volumetric wear can be studied. The removal of material in the FE model was validated against experiments simulating the clinical fretting wear process, subsequently the mismatch and assembly force were varied to study the effect on the volumetric wear. Methods. An FE model was developed in which the geometry can be updated to account for material removal due to wear. In this model the geometry was updated based on Archard's Law, using contact pressures, micromotions and a wear factor, which was determined based on accelerated fretting experiments. The linear wear was calculated using H=k*p*S. Where H is the linear wear depth in mm, k is a wear factor (mm. 3. /Nmm), p is the contact pressure (MPa) and S is the sliding distance (mm). 10 million cycles were simulated using 50 virtual steps. Using this scaling and the measured volumetric wear from the experiments a wear factor of 2.7*10. −5. was applied. Based on general manufacturing tolerances the resulting mismatch in taper angles were determined to be ± 1.26°. Using this mismatch a tip fit (figure 1a) and base fit (Figure 1b) model were created. In combination with a perfect fit, meaning no mismatch, and two different assembly forces of 4 kN and 15 kN, 6 different situations were studied. Results. No mismatch proved to result in the least amount of wear after 10 million simulated cycles (Figure 2). Assembling with 15 kN instead of 4 kN reduced the total volumetric wear and the volumetric wear rate. A base fit mismatch resulted in less volumetric wear than a tip fit mismatch. The 15 kN assembled mismatch cases showed a large initial amount of material removal after which the wear rate was lower than the 4 kN assembled cases. Discussion and conclusion. The results show that a perfect fit between the head and stem results in the least amount of wear. Furthermore a larger assembly force of 15 kN resulted in less wear than a 4 kN assembly force. The tip fit mismatch showed up to 144% more wear than the perfect fit where the base fit only had an increase in volumetric wear of 12%. The relative large tolerances in this study may overestimate actual mismatch, but give good insight into the effect that manufacturing tolerances can have on the taper mechanics and volumetric wear. Since manufacturing a perfect fit is impossible it is important to use a sufficiently high assembly force, when clinically possible, in order to reduce the amount of wear and wear rate significantly. For any figures or tables, please contact the authors directly


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_6 | Pages 22 - 22
1 Jul 2020
Tsang J Gwynne P Gallagher M Simpson H
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Staphylococcus aureus is responsible for 60–70% infections of surgical implants and prostheses in Orthopaedic surgery, with cumulative treatment costs for all prosthetic joint infections estimated to be ∼ $1 billion per annum (UK and North America). Its ability to develop resistance or tolerance to a diverse range of antimicrobial compounds, threatens to halt routine elective implant surgery. One strategy to overcome this problem is to look beyond traditional antimicrobial drug therapies and investigate other treatment modalities. Biophysical modalities, such as ultrasound, are poorly explored, but preliminary work has shown potential benefit, especially when combined with existing antibiotics. Low intensity pulsed ultrasound is already licensed for clinical use in fracture management and thus could be translated quickly into a clinical treatment. Using a methicillin-sensitive S. aureus reference strain and the dissolvable bead assay, biofilms were challenged with gentamicin +/− low-intensity ultrasound (1.5MHz, 30mW/cm2, pulse duration 200µs/1KHz) for 180 minutes and 20 minutes, respectively. The primary outcome measures were colony-forming units/mL (CFU/mL) and the minimum biofilm eradication concentration (MBEC) of gentamicin. The mean number of S. aureus within control biofilms was 1.04 × 109 CFU/mL. Assessment of cellular metabolism was conducted using a liquid-chromatography-mass spectrometry, as well as a triphenyltetrazolium chloride assay coupled with spectrophotometry. There was no clinically or statistically significant (p=0.531) reduction in viable S. aureus following ultrasound therapy alone. The MBEC of gentamicin for this S. aureus strain was 256 mg/L. The MBEC of gentamicin with the addition of ultrasound was reduced to 64mg/L. Metabolic activity of biofilm-associated S. aureus was increased by 25% following ultrasound therapy (p < 0 .0001), with identification of key biosynthetic pathways activated by non-lethal dispersal. Low intensity pulsed ultrasound was associated with a four-fold reduction in the effective biofilm eradication concentration of gentamicin, bringing the MBEC of gentamicin to within clinically achievable concentrations. The mechanism of action was due to partial disruption of the extracellular matrix which led to an increase of nutrient availability and oxygen tension within the biofilm. This metabolic stimulus was responsible for the reversal of gentamicin tolerance in the biofilm-associated S. aureus


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_2 | Pages 11 - 11
1 Feb 2020
Ruhr M Polster V Morlock M
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INTRODUCTION. Precise determination of material loss is essential for failure analysis of retrieved hip cups. To determine wear, the measured geometry of the retrieval hast to be compared to its pristine geometry, which usually is not available. There are different approaches to generate reference geometries to approximate the pristine geometry that is commonly assumed as sphere. However, the geometry of press fit cup retrievals might not be spherical due to deformation caused by excessive press-fitting. The effect of three different reference geometries on the determined wear patterns and material loss of pristine and worn uncemented metal-on-metal hip cups was determined. METHODS. The surfaces of two cups (ASR, DePuy, Leeds; one pristine, one a worn retrieval) were digitized using a coordinate measurement machine (CRYSTA-Apex S574, Mitutoyo; 3 µm accuracy). Both cups were measured undeformed and while being deformed between a clamp. Three different methods for generating reference geometries were investigated (PolyWorks|Inspector 2018, InnovMetric). Method 1: A sphere with the nominal internal cup dimensions was generated. Method 2: A sphere was fitted to the measured data points after removing those from worn areas (deviation > 3 µm is defined as wear) to eliminate the influence of manufacturing tolerances on the nominal diameter. Method 3: Measurements, which displayed visual deformation in the computed wear pattern based on the best fit sphere, were fitted with an ellipsoid. The direction of the deformation axes and the amount of deformation were used to scale the best fit ellipsoid. Linear wear was calculated from the distance of the respective reference geometry to the measured point cloud. Finally, material loss is defined as the difference in volume of the reference geometry and the measured geometry. RESULTS. The method used for generating the reference geometry affected the determined wear greatly. Using the nominal manufacturing radius (larger than the best fit radius) for the worn cup falsely indicates deposit. This leads to approx. 39 % less wear volume compared to the best fit sphere analysis. Using an ellipsoid as reference geometry for both deformed cups improves the determination of the wear pattern and indicates areas of material loss better than a reference sphere. Additionally, the mistake in material loss determination is decreased, especially for the worn cup almost exactly to the wear volume analyzed with the best fit sphere before deformation. DISCUSSION. For correct determination of material loss best fit geometries instead of nominal sizes have to be used to compensate the differences due to manufacturing tolerances. Furthermore, deformation always has to be eliminated to generate correct wear patterns and volumes. Using an ellipsoid as reference geometry improves the outcome. For generating an even more accurate reference geometry, the exact behavior of the cup during deformation must be understood. Limitations to this method are cups that do not provide pristine areas in order to generate an appropriate best fit geometry. For any figures or tables, please contact authors directly


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_15 | Pages 5 - 5
1 Dec 2021
Alagboso F Mannala G Steinmann S Docheva D Rupp M Brochhausen C Alt V
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Aim. Bone regeneration following the treatment of Staphylococcal bone infection or osteomyelitis is challenging due to the ability of Staphylococcus aureus to invade and persist within bone cells, which could possibly lead to antimicrobial tolerance and incessant bone destruction. Here, we investigated the influence of Staphylococcal bone infection on osteoblasts metabolism and function, with the underlying goal of determining whether Staphylococcus aureus-infected osteoblasts retain their ability to produce extracellular mineralized organic matrix after antibiotic treatment. Method. Using our in vitro infection model, human osteoblasts-like Saos-2 cells were infected with high-grade Staphylococcus aureus EDCC 5055 strain, and then treated with 8 µg/ml rifampicin and osteogenic stimulators up to 21-days. Results. Immunofluorescence and transmission electron microscopic (TEM) imaging demonstrated the presence of intracellular bacteria within the infected osteoblasts as early as 2 hours post-infection. TEM micrographs revealed intact intracellular bacteria with dividing septa indicative of active replication. The infected osteoblasts showed significant amounts of intracellular bacteria colonies and alteration in metabolic activity compared to the uninfected osteoblasts (p≤0.001). Treatment of S. aureus-infected osteoblasts with a single dose of 8 µg/ml rifampicin sufficiently restored the metabolic activity comparative to the uninfected groups. Alizarin red staining and quantification of the rifampicin-treated infected osteoblasts revealed significantly lower amount of mineralized extracellular matrix after 7-days osteogenesis (p<0.05). Interestingly, prolonged osteogenic stimulation and rifampicin-treatment up to 21 days improved the extracellular matrix mineralization level comparable to the rifampicin-treated uninfected group. However, the untreated (native) osteoblasts showed significantly more quantity of mineral deposits (p≤0.001). Ultrastructural analysis of the rifampicin-treated infected osteoblasts at 21-days osteogenesis revealed active osteoblasts and newly differentiated osteocytes, with densely distributed calcium crystal deposits within the extracellular organic matrix. Moreover, residual colony of dead bacteria bodies and empty vacuoles of the fully degraded bacteria embedded within the mineralized extracellular matrix. Gene expression level of prominent bone formation markers, namely RUNX2, COL1A1, ALPL, BMP-2, SPARC, BGLAP, OPG/RANKL showed no significant difference between the infected and uninfected osteoblast at 21-days of osteogenesis. Conclusions. Staphylococcus aureus bone infection can drastically impair osteoblasts metabolism and function. However, treatment with potent intracellular penetrating antibiotics, namely rifampicin restored the metabolic and bone formation activity of surviving osteoblasts. Delay in early osteogenesis caused by the bacterial infection was significantly improved over time after successful intracellular bacteria eradication


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_34 | Pages 335 - 335
1 Dec 2013
Haeussler K Flohr M Preuss R Streicher R
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Introduction. Dislocation is one of the major factors for revision surgery. Current literature states that the usage of larger bearing couples (> 36 mm) have the potential of reducing the risk of dislocation. Smaller ceramic-on-ceramic bearing couples (< 36 mm) have demonstrated very low wear rates. But does the wear behaviour change with increasing diameter? Therefore, the aim of this study was to compare wear rates of larger ceramic-on-ceramic bearing couples for total hip arthroplasty. Materials and Methods. Wear tests according to ISO 14242 with 36, 40 and 44 mm zirconia platelet toughened alumina (ZPTA) bearings were performed in a servo-hydraulic hip simulator. In total, the specimens were loaded up to 5 million cycles. Wear was measured gravimetrically every million cycles. For each diameter three different combinations regarding clearance and roundness were chosen. One combination represented in tolerance parts (70 μm clearance, < 5 μm roundness). The other two combinations represented parts at the lower end and at twice the upper end of the tolerance band regarding clearance and out of specification parts regarding the roundness. Results. In general, ball heads showed higher wear than liners. 44 mm bearings showed highest and 36 mm bearings showed lowest run-in wear rates (Table 1). Except for the 36 mm bearing negligible influence on wear rates caused by the different clearance and roundness was found. The highest linear wear rate was found for the 36 mm bearing having a clearance of 20 μm and a roundness of 15 μm. The smallest linear wear rate was also found for the 36 mm bearing. Here, in tolerance parts were tested. Discussion and Conclusion. Generally, the current study shows extremely low wear rates for ZPTA/ZPTA even for larger diameter bearings. Except for the 36 mm bearing different machining tolerances in the investigated range seem to have only minor effects on the wear rates of larger diameter bearings under ISO 14242 test conditions. The wear rates determined in the current study might be lower in reality due to metal transfer from the tapers and the cups to the ball heads and liners occurring while assembling and disassembling procedures throughout testing. Larger diameter bearings increase range of motion, stability and reduce the risk of impingement. Thus, larger diameter ZPTA bearings have the potential to minimize the dislocation risk while at the same time having maintained the extremely low wear rates of small diameter ceramic articulations


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_3 | Pages 1 - 1
1 Mar 2021
Taha M Werier J Abdelbary H
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Periprosthetic joint infection (PJI) remains one of the most devastating complications that can occur following total joint arthroplasty. Failure rate of standard treatment for PJI is estimated to be around 40% at two years post revision surgery. A major clinical challenge contributing to treatment failure and antibiotics tolerance is the biofilm formation on implant surfaces. Lytic bacteriophages (phages) can target biofilm associated bacteria at localized sites of infection by penetrating and disrupting biofilm matrices; furthermore, phage replication within the biofilm leads to high local concentrations resulting in a powerful therapeutic effect. The aim of this study is to test if phage cocktail has better antimicrobial effect than vancomycin or a single agent phage against biofilm forming MRSA clinical strain Staphylococcus aureus (S. aureus). S. aureus BP043 was utilized in this study. This strain is a PJI clinical isolate, methicillin resistant (MRSA) and biofilm-former. Three lytic phages, namely, 44AHJD, Team1 and P68, known to infect S. aureus, were tested for their efficiency against S. aureus BP043. The ability of the phages to eliminate S. aureus BP043 planktonic or biofilm cultures was tested either as singular phages or as a cocktail of the three phages. Planktonic cells were adjusted to ∼ 1×109 CFU/mL in tryptic soy broth (TSB) and each phage was added alone or as a cocktail at ∼ 1×109 PFU/mL with moi of 1 (a multiplicity of infection). Bacterial growth was assessed by measuring optical densities at 24hr and was compared to the control of S. aureus BP043 with no phage. BP043 biofilms was grown for 24hr on plasma sprayed titanium (Ti-6Al-4V) alloy disc surfaces. Mature biofilms were then treated with one of the three phages or a cocktail of the 3 phages for 24hr at ∼ 1×109 PFU/mL in TSB. Then, biofilms were dislodged, and bacterial survival was assessed by plating on tryptic soy agar plates. Survival in treated biofilms was compared to control biofilm that was exposed only to TSB. Planktonic cells growth in the presence of phage 44AHJD was reduced significantly (p <0.0001) after 24hr compared to the control. The other two phages did not show a similar pattern when used alone. The reduction in growth was more pronounced when the three phages were combined together (p <0.0001, compared to the control, p=0.011 3, 44AHJD alone versus 3 phages). Exposing BP043 biofilm to the phage cocktail resulted in more than three logs (CFU/mL) reduction in bacterial load residing in the biofilm while no effect was detected when either vancomycin or each phage was used solely. We have demonstrated that the usage of lytic phage cocktail contributes to better clearance of planktonic cultures of the S. aureus MRSA isolate. More importantly, viable bacteria in the biofilms that were grown on plasma sprayed titanium discs were reduced by more than 37% when a phage cocktail was used compared to using a single phage or vancomycin. This work is aimed at gathering preclinical evidence for using phage as a new therapeutic avenue to treat PJI


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_9 | Pages 86 - 86
1 May 2016
Parekh J Chan N Noble P
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Introduction. Angular mismatch between the head and trunnion is recognized as a contributing factor to mechanically-assisted corrosion of modular hip prostheses. Although manufacturing standards have been adopted to define acceptable tolerances for taper angles of mating components, the relationship between the head and trunnion taper angles (positive or negative) differs between manufacturers. In this study, we investigated the effect of positive and negative angular mismatch on the interface mechanics of a standard design of taper junction using finite element analysis (FEA). Methods. Computer simulations were executed using an FE model which had been previously verified through direct comparison with experimental studies. The neck and trunnion of a Ti6Al4V femoral component (taper size: 12/14mm) were modelled using a stable hexahedral mesh (33,648 elements), while the femoral head (CoCrMo, size: 32mm) was modelled using a tetrahedral mesh (51,182 elements). Assembly of the head on the trunnion was simulated through the application of a load of 4000N along the trunnion axis. This was followed by the application of a gait load of 1638N (2.34×700N BW) at an angle of 30o to the trunnion axis. A friction-based sliding interface (mu=0.12) was simulated at the trunnion-head junction. A linear static solution was set up using Siemens NX Nastran. In addition to a perfect match, 7 positive and negative mismatch angles were simulated ranging from −0.100 to 0.100 degrees. Head taper interface motion, contact pressure and internal stresses (von Mises) were calculated for each mating condition. Results. During gait loading, the maximum tangential displacement at the head-trunnion interface was 34µm, virtually identical for positive and negative mismatches in taper angle. There was minimal change in interface motion (5 µm) with variations in taper mismatch. The maximum contact pressure between the trunnion and the head increased dramatically with the magnitude of the mismatch from 144Mpa for a per4fect fit to 924MPa and 555MPa for taper clearances of 0.1 degrees for −0.1degrees, respectively. Smaller changes were seen in the maximum internal stresses developed within the trunion, which rose by a factor of approximately X2.5 over the same range of taper mismatch (perfect fit: 85MPa vs 220Mpa for 0.1deg. and 228MPa for −0.1 deg.). One difference between cases examined was the magnitude of the dilation of the bore within the femoral head during gait loading which increased from 2.19µm to 4.23µm with a change in mismatch from +0.015o to −0.015o. Discussion. The results support the conclusion that, provided that manufacturing tolerances are maintained to within ±0.015o, both a positive and negative angular mismatch results in similar levels of contact stress and interface micromotion in modular junctions. As expected, peak stresses were located at the proximal edge of the contact zone with a negative taper mismatch and at the distal edge with a positive mismatch. This may have important implications in vivo, due to differences in the chemical environment (pH and oxygen tension) at each of these locations


Aim. Cutibacterium acnes (CA) is one of the crucial actors in spine instrumentation or shoulder prosthesis. Its population is subdivided into 6 major phylotypes: IA1, IA2, IB, IC, II and III. Recent methods for discriminating subpopulations within CA phylotypes highlight the predominance of SLST types H1 to 6 or K1 to 20 in bone and joint infection (BJI). The impact of their ability to produce a biofilm during the development of the infection (with resistance / tolerance to antibiotics used for treatment) remains little studied. Method. The purpose of this study was to determine whether the ability to establish a biofilm varied according to the different subtypes of clinical strains of CA previously characterized and involved in BJI (hip, knee and shoulder prosthesis). The BioFilm ring test (BioFilm Control®) method with index determination, called BFI (BioFilm Index) inversely proportional to the level of biofilm production was used (BFI = 0.00 indicates a high production of biofilm versus BFI = 20.00 indicates zero production). The BFI was determined after 3 h (T3) and 6 h (T6) incubation. The strains used came from patients, 5 belonging to the IA1 phylotype (SLST A1 and D1 types) and 4 to different phylotypes (IA2, IB, II and III). Results. The results show that the kinetics of establishment of an early CA biofilm turns out to be phylotype dependent. The most productive strains are those belonging to phylotype II (BFI T3 = 5.73, BFI T6 = 0.00) and to type SLST D1 belonging to phylotype IA1 (BFI T3 = 4.07, BFI T6 = 0.00). The other strains did not demonstrate saturated BFI, even after 6 h of incubation. Conclusions. The exact role of CA, as well as its ability to produce a biofilm in the pathophysiology of BJI, remains poorly understood and the prolonged use of antibiotics to treat these infections is necessary, especially if devices have not been removed, with potential risk of increasing antibiotic resistance and therapeutic failures. CA's different phylotypes demonstrate different biofilm production capabilities, which could have an impact on the antibiotic efficacy suggesting the interest of effective anti-biofilm molecules on metabolically less active strains


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_14 | Pages 24 - 24
1 Dec 2019
Butini ME Abbandonato G Rienzo CD Trampuz A Luca MD
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Aim. Most orthopedic infections are due to the microbial colonization of abiotic surfaces, which evolves into biofilm formation. Within biofilms, persisters constitute a microbial subpopulation of cells characterized by a lower metabolic-activity, being phenotipically tolerant to high concentrations of antibiotics. Due to their extreme tolerance, persisters may cause relapses upon treatment discontinuation, leading to infection recalcitrance hindering the bony tissue regeneration. Using isothermal microcalorimetry (IMC), we aimed to evaluate in vitro the presence of persisters in a methicillin-resistant Staphylococcus aureus (MRSA) biofilm after treatment with high concentrations of vancomycin (VAN) and their ability to revert to a normal-growing phenotype during incubation in fresh medium without antibiotic. Moreover, the ability of daptomycin to eradicate the infection by killing persisters was also investigated. Method. A 24h-old MRSA ATCC 43300 biofilm was exposed to 1024 µg/ml VAN for 24h. Metabolism-related heat of biofilm-embedded cells, either during or after VAN-treatment, was monitored in real-time by IMC for 24 or 48h, respectively. To evaluate the presence of VAN-derived “persisters” after antibiotic treatment, beads were sonicated and detached free-floating bacteria were further challenged with 100xMIC VAN (100 µg/ml) in PBS+1% Cation Adjusted Mueller Hinton Broth (CAMHB).. Suspensions were plated for colony counting. The resumption of persister cells' normal growth was analysed by IMC on dislodged trated cells for 15h in CAMHB. Activity of 16 µg/ml daptomycin was assessed against persister cells by colony counting. Results. When incubated with 1024 µg/ml VAN, MRSA biofilm produced undetectable heat, suggesting a strong reduction of cell viability and/or cellular metabolism. However, the same samples re-inoculated in fresh medium produced a detectable and delayed metabolism-related heat signal, similarly to that generated by persister cells. The following exposure to 100xMIC VAN resulted in neither complete killing nor bacterial growth, strongly supporting the hypothesis of a persistent phenotype. IMC analysis indicated that VAN-treated biofilm cells resumed normal growth with a ∼3h-delay, as compared to the untreated growth control. Daptomycin treatment yielded a complete eradication of persister cells selected after VAN treatment. Conclusions. Hostile environmental conditions (e.g. high antibiotic bactericidal concentrations) select for persister cells in MRSA biofilm after 24h-treatment in vitro. A staggered treatment vancomycin/daptomycin allows complete biofilm eradication. These results support the use in clinical practice of a therapeutic regimen based on the combined use of antibiotics to kill persisters and eradicate MRSA biofilms. IMC represents a suitable technique to detect persisters and characterize in real-time their reversion to a metabolically-active phenotype


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_1 | Pages 133 - 133
1 Jan 2016
Haeussler K Kruse C Flohr M Preuss R Streicher R Morlock M
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Introduction. For a safe design of ceramic components in total hip arthroplasty it is important to know the stress state within each part of the system under in vivo loading scenarios. Besides several design parameters, e.g. diametrical clearance between ball head and liner or angular mismatch in the taper region of metal shell and liner, also physiological factors, like patients' weight or bone quality, influence the stresses within the components. Therefore, the aim of the current study was to experimentally determine the stresses in a ceramic liner varying two of the factors: clearance and inclination angle of the liner. Materials and Methods. Two ceramic liners were instrumented at the outer contour with five strain gauge (SG) rosettes (measuring grid length: 1.5 mm) on each liner (Fig.1). Metal shells were seated in an asymmetric press-fit Sawbones® model using a 0.5 mm under-reaming, and liners were afterwards axially assembled with a 2 kN load. SG5 was placed at the flat area of the liner, the other four were placed circumferentially in 90 degrees offset on the rear side of the liner. SG2 and SG4 were mounted opposite to each other in press-fit direction (contact of metal shell to the Sawbones® block) whereas SG1 and SG3 were placed in the non-supported direction (no contact of metal shell to the Sawbones® block). Four different inclination angles (0°, 30°, 45°, 60°) were tested under in vivo relevant loads of 4.5 and 11 kN. Two ceramic ball heads were used to examine a mid tolerance clearance and a clearance at the lower tolerance limit. Strain data was converted to stresses and compared using a paired two-sided Wilcoxon Rank Sum Test at an α-level of 0.05. Results. Generally, similar stress distributions under the two in vivo relevant loads were found (Fig.1, Fig.2). Highest stresses were found for the 0° inclination and decreased with increasing inclination angle. Due to the asymmetric press-fit distinctively higher stresses for SG2 and SG4 were found. For these stresses no significant difference was found throughout the whole testing. Larger clearance in combination with different inclination angles have had a significant effect on the stresses where SG1 and SG5 were affected the most. At 0° inclination SG5 showed significantly higher stresses for the larger clearance. With increasing inclination angle this effect switched towards SG1. Stresses of SG3 stayed constant with increasing inclination angle. Discussion. The results show that the ceramic liner examined here is well adapted to in vivo loading conditions showing decreasing stresses with increasing inclination angle. Nevertheless, 0° inclination was identified to be the most critical load case. As expected, the stresses resulting from different clearances are attributed to the contact area where higher stresses were found for a smaller contact area. Due to the dimension of strain gauges the strain measurements are limited to a defined region and thus no complete strain map of the whole component could be determined. Therefore, the current data will be used to calibrate finite element models to perform parametrical studies


Introduction. Limb-length discrepancy (LLD) is a common postoperative complication after total hip arthroplasty (THA). This study focuses on the correlation between patients’ perception of LLD after THA and the anatomical and functional leg length, pelvic and knee alignments and foot height. Previous publications have explored this topic in patients without significant spinal pathology or previous spine or lower extremity surgery. The objective of this work is to verify if the results are the same in case of stiff or fused spine. Methods. 170 patients with stiff spine (less than 10° L1-S1 lordosis variation between standing and sitting) were evaluated minimum 1 year after unilateral primary THA implantation using EOS® images in standing position (46/170 had previous lumbar fusion). We excluded cases with previous lower limbs surgery or frontal and sagittal spinal imbalance. 3D measures were performed to evaluate femoral and tibial length, femoral offset, pelvic obliquity, hip-knee-ankle angle (HKA), knee flexion/hyperextension angle, tibial and femoral rotation. Axial pelvic rotation was measured as the angle between the line through the centers of the hips and the EOS x-ray beam source. The distance between middle of the tibial plafond and the ground was used to investigate the height of the foot. For data with normal distribution, paired Student's t-test and independent sample t-test were used for analysis. Univariate logistic regression was used to determine the correlation between the perception of limb length discrepancy and different variables. Multiple logistic regression was used to investigate the correlation between the patient perception of LLD and variables found significant in the univariate analysis. Significance level was set at 0.05. Results. Anatomical femoral length correlated with patients’ perception of LLD but other variables were significant (the height of the foot, sagittal and frontal knee alignment, pelvic obliquity and pelvic rotation more than 10°). Interestingly some factors induced an unexpected perception of LLD despite a non-significant femoral length discrepancy less than 1cm (pelvic rotation and obliquity, height of the foot). Conclusions. LLD is a multifactorial problem. This study showed that the anatomical femoral length as the factor that can be modified with THA technique or choice of prosthesis is not the only important factor. A comprehensive clinical and radiological evaluation is necessary preoperatively to investigate spinal stiffness, pelvic obliquity and rotation, sagittal and coronal knee alignment and foot deformity in these patients. Our study has limitations as we do not have preoperative EOS measurements for all patients. We cannot assess changes in leg length as a result of THA. We also did not investigate the degree of any foot deformities as flat foot deformity may potentially affect the patients perception of the leg length. Instead, we measured the distance between the medial malleolus and ground that can reflect the foot arch height. More cases must be included to evaluate the potential influence of pelvis anatomy and functional orientation (pelvic incidence, sacral slope and pelvic tilt) but this study points out that spinal stiffness significantly decreases the LLD tolerance previously reported in patients without degenerative stiffness or fusion


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_14 | Pages 31 - 31
1 Dec 2019
Gabriela I Costache AL Lacassin-Beller F Loutfi B Hoskovec C Mathieu P Acra M Rogero MJ Mondon D
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Aim. bone and joint infection (BJI) in aging population, continues to be associated with significant morbi-mortality. In western Europeans countries, the Gram positive BJI are preponderant. Vancomycin was the “gold standard” and the full treatment requires prolonged antibiotic therapy. Dalbavancin is a semi-synthetic lipoglycopeptideanalog of teicoplanin class of antibiotics with bactericidal activity and a long half-life. The use of dalbavancin in BJI could be an option. Methods. during November 2017 and April 2019, Dalbavancin was used in monotherapy as salvage option in BJI: 1500 mg, 1. st. (D1) and 8. th. day (D8), repeated if needed. The clinical and biological follow up was for 6 months if osteomyelitis or BJI without prosthesis and 1 year if prosthesis (PJI). Results. the demographics of 16 patients are: 75.0% men (n=12), mean age 77.8 years [64–90], 37.5% (n=6) diabetes, 68.8% (n=11) renal failure, 37.5% (n=6) atrial fibrillation, 18.8% (n=3) cardiac bioprosthesis, 31.2% (n=5) lower limb arteriopathy, and one patient with active neoplasia. The BJI characteristic's: 50% (n=8) secondary to health care;5 vertebral osteomyelitis; 12 lower limb BJI : 8 joint infection of witch 6 PJI (4 knee, 2 hip) and 4 foot osteomyelitis; 2 shoulder PJI; 3 patients had 2 or more localisations of BJI. In 68.8% (11/16) BJI, bacteraemia occurred with 68.8% (n=11) of possible or certain infective endocarditis (Duke criteria) and 37.5% (n=6) of deep abscess. The DAIR was of 83.4% (5/6). Monobacterian biopsy in 75.0% (n=12). Out of 32 micro-organisms, 25 were Dalbavancin susceptible:56.0% (14/25) Staphylococcus aureus (10 methicillin susceptible), 3 Streptococcus, 5 Enterococcus faecalis, 2 Corynebacterium, 1 coagulase negative staphylococcus. Mean of 1. st. antibiotherapy: 18.3 days [0–49], with 2 patients who had dalbavancine as only antibiotic. Number of dalbavancine doses: 75% (n=12) patients had 2 injection (D1, D8), 18.8% (n=3), 4 injections D1, D8, D28 and D35 and 1 patient had one dose. Principal reason of changing by dalbavancine: 50% (8/16) poor tolerance of antibiotics, 12.5% (2/16) poor compliance of patient, 18.8% (3/16) poor efficacy of 1. st. antibiotherapy, 18.8 %(3/16) only for the patient's comfort. Clinically success: 75% (12/16) with 5 patients in follow up today. Three patients died and one is cured with teicoplanin and rifampicin. Three patients presented side effects: one diarrhea, one headache and one transient asthenia. No renal damage was found and no allergy. Conclusion. This report highlights the potential role of dalbavancin in treating unstable and weak patients who require long-term antimicrobial therapy with fewer antibiotic choices


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_1 | Pages 147 - 147
1 Jan 2013
Gudipati S Fogerty S Chami G Scott B
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Aim. To assess the results of Castles procedure performed at our hospital compared with those available in literature. Introduction. Fifteen patients (19 hips) with severe disability and hip subluxation/dislocation underwent proximal femoral resection arthroplasty (Castles procedure) over a 10 year period under the care of 2 paediatric orthopaedic surgeons. We conducted a retrospective study of case series whether the surgery (Castles procedure) improved the pain levels, sitting tolerance, ability to use commode/nappy change, ease of dressing and the carers overall satisfaction with the procedure. Patients and methods. We reviewed the surgeons' and theatre log books for patients' details. We then contacted the patients' parents/guardian by telephone, and using a set questionnaire, we obtained valuable information on how successful the surgery had been in their opinion. Results. Out of 15 patients, 14 had severe cerebral palsy and one had severe brain damage secondary to trauma. The average age at surgery was 4.23 years (range 6–118 months). 14 patients obtained significant pain relief but one patient remained the same. 13 patients were found to have both sitting tolerance and sleeping improved. One patient suffered a pressure sore which has healed with conservative management. 2 patients had additional trimming procedure for heterotopic ossification excision. Apart from this there were no cases of skin breakdown. All patients found the bathing and dressing change was easier post operatively. 2 carers required extra help as the limbs were floppy but not a major issue compared to the overall benefits from the Castles procedure. Overall 13 carers were very satisfied with the procedure, two were satisfied and none were unsatisfied. Conclusion. Our telephone survey shows the Castles procedure was a successful salvage procedure for painful dislocated hips in non-ambulatory patients with severe disability


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_III | Pages 80 - 80
1 Feb 2012
Wharton R Kuiper J Kelly C
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Objective. To compare the ability of a new composite bio-absorbable screw and two conventional metal screws to maintain fixation of scaphoid waist-fractures under dynamic loading conditions. Methods. Fifteen porcine radial carpi, with morphology comparable to human scaphoids, were osteotomised at the waist. Specimens were randomised in three groups: Group I were fixed with a headed metal screw, group II with a headless tapered metal screw and group III with a bio-absorbable composite screw. Each specimen was oriented at 45° and cyclically loaded using four blocks of 1000 cycles, with peak loads of 40, 60 (normal load), 80 and 100 N (severe load) respectively. Permanent displacement and translation (step-off) at the fracture site was measured after each loading block from a standardised high-magnification photograph using image analysis software (Roman v1.70, Institute of Orthopaedics, Oswestry). Statistical analysis was by ANOVA and tolerance limits. Results. No gross failure or fracture gap displacement occurred. Average translations (step-off) at the fracture site after 4000 cycles up to 100N were 0.05mm±0.02SD (headed metal), 0.14mm±0.14SD (headless metal) and 0.29mm±0.11SD (composite) and differed significantly (p<0.01). Using tolerance limits, the data allowed us to predict that, with 95% certainty, the maximum average translation (step-off) following severe loading in 95% of any sample fixed with a headed metal screw will be below 0.17mm, headless metal screw below 0.74mm, and composite screw below 0.76mm. Conclusion. We observed only small average translations (step-off) for all three screws. Moreover, translations of more than 1mm that would predispose to non-union were highly unlikely for any of the screws, even after severe cyclic loading. We therefore conclude that a new bio-absorbable composite screw can serve as an alternative to conventional screws when fixing scaphoid fractures


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_34 | Pages 204 - 204
1 Dec 2013
Wentorf F Bandi M Sauerberg I Mane A
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Introduction:. Following total knee arthroplasty, patients often complain of an unnatural feeling in their knee joint, which in turn limits their activities [Noble et al, CORR 2006]. To develop an implant design that recreates the motion of the natural knee, both the functional kinematics as well as the laxity of the joint need to be understood. In vitro testing that accurately quantifies the functional kinematics and laxity of the knee joint can facilitate development of implant designs that are more likely to result in a natural feeling, reconstructed knee. The objective of this study is to demonstrate that robotic in vitro testing can produce clinically relevant functional kinematics and joint laxities. Methods:. All testing was performed using a KUKA (KUKA Robotics, Augsburg, Germany) 6 degree of freedom robotic arm and a six degree of freedom load cell (ATI Industrial Automation, Apex, North Carolina, USA), attached to the arm (Figure 1). FUNCTIONAL KINEMATICS: Eight cadaveric specimens implanted with contemporary cruciate retaining implants were used for this evaluation. The functional activity, lunge, was simulated using kinematic control for flexion/extension and force-torque control for the other degrees of freedom. The inputs for the force-torque control were obtained from e-tibia data from live patients during the lunge activity [Varadarajan et al, J Biomech 2008]. At a given flexion angle, the robot moved in force-torque control to obtain the desired values within given tolerances (± 2.5N & ± 0.1 Nm). When these tolerances were met the position of femur with respect to the tibia was recorded and the knee flexed to the next level. The lunge simulation began at full extension and ended at 120 degrees of knee flexion, through 1 degree increments. The kinematic data from the contemporary CR implants were compared to in vivo kinematics of patients that were implanted with the same knee replacements performing a lunge activity [Varadarajan et al, Med Eng Phys 2009]. JOINT LAXITY: Eight native, unimplanted knees were used for this evaluation. Joint laxity of the knee joint was evaluated at 0, 30, 60, 90, and 120 degrees of knee flexion by applying various loads to the tibia and quantifying the resulting motion of the tibia. The resulting laxities were compared to various knee laxity studies in the literature. Results:. The in vitro functional kinematics correlated well with the in vivo results. Femoral external rotation and tibial varus angulation were found not be statistically different between the in vitro and in vivo results (Figure 2). The laxities measurements correlated well with reported values in the literature. Discussion:. In vitro robotic evaluations allow for a better understanding of the motion at the knee joint by simulating clinically relevant functional kinematics as well as quantifying joint laxities in the same testing system. Both of these metrics are needed to understand how the knee moves and should be used to evaluate the performance of new knee designs (Figure 3)


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_8 | Pages 22 - 22
1 May 2019
Romeo A
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Patient perceptions regarding the functional outcomes and return to sports after shoulder replacement are often pessimistic, with many patients presenting for shoulder replacement surgery after months or years of avoiding the procedure so they could continue to live the current life they have, despite the increasing pain and dysfunction. Less common, but becoming more frequent, patients present with expectations that they will be able to return to all activities including heavy resistance training, cross-fit, rock climbing, and other strenuous overhead sports. In the past, little information has been available regarding the activities of shoulder arthroplasty patients after surgery. Typically, the boundaries have been set by the surgeon, with many patients cautioned or even prohibited from overhead sports, weight training, or heavy work responsibilities. A typical set of guidelines may include no repetitive overhead sports, except for recreational swimming, and no lifting over 20 pounds. Golf, jogging, hiking and other activities are allowed. The origin of these restricted guidelines and expectations is unknown, but many believe that since the results of shoulder replacements are less favorable in younger patients, it may be due to the overuse or abuse of the shoulder joint that is more typical at a younger age. Others have suggested that common sense prevails and that an artificial joint made of metal and plastic has a finite number of total movements and tolerance to resistance activities, and therefore keeping these activities at a minimum would extend the longevity of the artificial joint. None of these concepts are backed up by evidence-based literature, essentially reflecting the personal bias of the surgeons who care for patients with these problems. Despite all of the sophisticated research, scoring scales, outcome measures, and value-based metrics, the only outcome that really matters is whether the patient can return back to their normal way of life, at home, at work, during sport, or any activity that is important to them. Recent studies of patients who have had joint replacement surgery have revealed that our patients who participated in sports and work activities before surgery have a strong predilection to returning to those activities after successful shoulder replacement. The most common sports that shoulder arthroplasty patients enjoy including golf, swimming, tennis, but may also include many other choices including fitness activities, rowing, skiing, basketball, and softball. As expected, the return to these sports is less for reverse shoulder arthroplasty patients vs. anatomic shoulder arthroplasty patients. In a systematic review, more than 90% of anatomic shoulder replacement patients returned to sport, while 75% of reverse shoulder arthroplasty patients returned to some sporting activity. This may reflect the constraints of the reverse prosthesis, or, quite possibly reflect the typically older age and more sedentary lifestyle of patients who are indicated for reverse shoulder arthroplasty. In addition, if the patient had a preoperative expectation of return to recreational and sports activities as part of their normal way of life, their final results demonstrated better overall outcomes. Shoulder arthroplasty surgeons should be concerned about the outcomes desired by our patients, and the results that provide true value to their lives. We are now more aware of the activities that they are going to return to, whether we recommend restrictions or not