Aim. Daptomycin plus fosfomycin combination therapy is a valuable strategy for treating staphylococcal osteoarticular infections. Considernig that each gram of fosfomycin contains 330 mg of sodium, electrolytic imbalance due to sodium overload could pose safety issues, especially in the cardiopatic patients and/or in the frail elderly. The aim of this study was to compare the efficacy of using reduced vs. standard daily dose fosfomycin in combination with daptomycin in a cohort of patients with osteoarticular infections. Method. This analysis included adult patients with osteoarticular infections admitted to the Infectious Diseases Unit of our University hospital in the period Nov 2022 – Feb 2024 and who were treated with daptomycin (8-10 mg/kg/daily) plus 24h-continuous infusion (CI) fosfomycin at the standard-dose of 16 g daily (standard-dose group) or at the reduced-dose of 8-12 g daily (reduced-dose group). All the patients underwent therapeutic drug monitoring (TDM) of fosfomycin for granting a pharmacodynamic target attainment of 24h-area under the concentration-time curve over minimum inhibitory concentration (AUC24h/MIC) >95 against Staphylococcus aureus with an MIC value up to 32 mg/L and of 70%t>MIC. Estimated glomerular filtration rate (eGFR) was assessed at each TDM session. Patient clinical outcome was assessed. Results. The standard- and the reduced-dose groups included 43 (29 males, 67.4%) and 21 (11 males, 52.4%) patients, respectively. No differences in median age (54 vs. 63 years, p=36), weight (80 vs. 76 kg, p=0.13) and type of diagnosis [prosthetic joint infections (16 vs. 29, p=0.38), osteomyelitis (2 vs. 9, p=0.72), septic arthritis (3 vs. 3, p=0.39) and spondilodiscitis (0 vs. 2, p=1.0)] were observed between the two groups. Median eGFR was similar in the standard vs. the reduced-dose group (109 vs. 98 mL/min/1.73m2, p=0.004). In the reduced-dose group, CI fosfomycin was administerd at 8 and 12 g/daily in 12 and 9 patients, respectively. There was no difference between the standard- and reduced-dose groups in attainment of the pharmacodynamic targets of AUC24h/MIC>95 (41/43 vs. 20/21, p=1.0), of 70%t>MIC (43/43 vs. 21/21 p=1.0) and of clinical cure (39/43 vs. 19/21, p=1.0). Conclusions. Combination therapy of 8-10 mg/kg/daily daptomycin plus 8-12 g/daily CI fosfomycin may be as effective as that of 8-10 mg/kg/daily daptomycin plus 16 g/daily CI fosfomycin. The fosfomycin reduced-dose strategy allows to decrease the daily sodium load by 25-50% compared to the standard dose, thus reducing the risk of cardiac adverse events. TDM may be a valuable strategy for individualizing fosfomycin dose in patients with osteoarticular infections

Aim. Swedish guidelines on antibiotic prophylaxis in arthroplasty surgery recommend cloxacillin in fixed doses that pay little attention to the patient's renal function and weight. Nevertheless, there are no studies on whether the resulting free prophylactic cloxacillin in vivo concentrations are optimal. We aimed to evaluate whether the current recommended prophylactic dosage of cloxacillin is adequate. Method. We performed a prospective two-centre study, measuring the free (active) cloxacillin concentrations in plasma throughout surgery, in patients subject to primary hip and knee prosthetic joint replacements, aiming at 100 patients per centre. To account for plasma-bone exposure differences, concentrations were considered adequate if twice the epidemiological cut-off value for cloxacillin concerning wild type Staphylococcus aureus whereas two-three times were labelled threshold values. The two enrolling hospitals are acute care hospitals in central Sweden, also performing 600 - 1200 primary hip and knee joint arthroplasties annually. All patients scheduled for elective primary hip or knee replacements from January 2022 to April 2024 were eligible for participation. Exclusion criteria were allergy towards penicillins, cognitive disorders leading to inability to sign informed consent, and an absence of interpreter in case of a patient not speaking Swedish or English. Results. We present results from the first 49 patients included. Four patients had free cloxacillin concentrations below cut-off (8.2%). These four cases had prolonged surgeries of 77-100 minutes. An additional 5/49 (10.2%) had threshold values. Conversely 5/49 (10.2%) cases had concentrations exceeding 15 times the needed. No cases with threshold or low cloxacillin concentrations were attributable to a lack of concerning timing and dosing of cloxacillin. All concentrations were above or equal to our cut-off at the start of surgery. Eighteen percent of patients were of normal of weight (BMI 18.5- 25). Of the rest 4% were morbidly obese (BMI >40), 41% obese (BMI 30-40) and 37% overweight (BMI 25-30). Twenty seven percent (43/159) had diabetes and 45% suffered cardiac disease. Conclusions. Some patients in our cohort had insufficient active cloxacillin levels at the end of prosthetic joint surgery. Previous studies indicate that insufficient prophylactic antibiotic concentrations might lead to an enhanced risk of prosthetic joint infections. Other patients were massively overdosed, leading to unnecessary ecological effects and potentially adverse reactions. As inadequate cloxacillin concentrations were not associated with a lack of compliance to current guidelines a change in practise might be needed. Our final results may help to determine how dosing should be adjusted

Aim. Periprosthetic joint infection (PJI) is a complication of total joint arthroplasty that typically requires revision surgery for treatment. Systemic antibiotics are usually held prior to surgery to improve yield of intraoperative cultures. However, recent studies suggest that preoperative aspirations have a high concordance with intraoperative cultures, which may allow surgeons to initiate antibiotic treatment earlier. The purpose of the study was to investigate the effect of Pre-surgical systemic antibiotic therapy on the bacterial burden within the periprosthetic space and systemic immune reaction. Method. PJI was induced with MSSA (Xen36) S. aureus in the right knee of 16-week old, female, C57BL6 mice using a previously validated murine model. Mice were randomized to three groups (n=8, each): control; Vanc, receiving systemic vancomycin (110mg/kg, SQ, twice daily); or VancRif receiving vancomycin same as in Vanc group, plus rifampin (12mg/kg dose, IV, once daily). Following 2 weeks of treatment, mice were euthanized and periprosthetic bone, soft tissue and the implant were harvested. Bacterial burden, colony forming units (CFUs), was quantified in soft tissue, tibial bone, and on the implant. Specifically, tissues were homogenized and serially plated for CFUs, while the implant was sonicated and then plated for CFUs. The host immune response was analysed through weighing inguinal and iliac lymph nodes and through measuring serum amyloid A (SAA). Non-parametric pairwise group comparisons of the three outcome measures were performed using a Mann-Whitney U test. Results. VancRif, the combined treatment significantly reduced bacterial burden in the periprosthetic soft tissue, bone, and implant compared to control (p<0.001) and Vanc alone (p<0.001). While not significant, Vanc alone did reduce bacterial load as compared to control. The ipsilateral weight of the iliac lymph nodes was significantly reduced in Vanc and VancRif mice compared to controls (p<0.001), was well as in VancRif versus Vanc alone (p<0.001). Interestingly, SAA levels did not significantly differ among all groups. During tissue harvesting, minimal purulence was observed in antibiotic treatment groups, unlike controls. Conclusions. Treating active PJI with vancomycin alone decreases periprosthetic bacterial loads and reduces the local immunological response. This effect is significantly enhanced with the combined rifampin use. These findings could suggest that when culture positive PJI is diagnosed, pre-surgical treatment with antibiotics may decrease immunosuppression and soft tissue infiltration, leading to a better chance of infection cure with subsequent surgical debridement. Histological investigations and repeat experiments involving subsequent surgical treatment are underway. Acknowledgements. Funding comes from internal institutional grants

Aim. Aim of this study was to establish the first clinical results after implantation of ultrathin silver-polysiloxane-coated. 1. plates in the treatment of infected non-union of the femoral shaft. Method. As part of the REFECT study, a prospective, non-interventional analysis was conducted encompassing all patients who received internal stabilization with a silver-coated. 1. plate from 01/2023 to 09/2024 as part of the treatment for infected non-union of the femur. Standardized clinical follow-ups including PROMs (WOMAC-Index, LEF-S, EQ-5D, VAS) and X-rays were performed 3, 6, 12 (and 24) months postoperatively. For comparison, a retrospective analysis of 76 patients with infected femoral non-union, who had received a stabilization with an uncoated plate in the past 10 years, was performed. Results. The mean follow-up of the 8 included patients (mean bone defect: 3.6 cm) was 9 months (as of 04/24). Multiresistant bacteria were found in the intraoperative samples of 5 patients. The concentration of silver ions in blood serum reached a maximum of 0.014 mg/l in the laboratory controls. All patients showed a positive healing process with no sign of re-infection and no adverse procedure-associated events. Full weight bearing was achieved after an average of 4 months (n=6) with improved WOMAC-, LEF-S-, EQ-5D and VAS-score at 1-year FU. In the reference group (uncoated, mean FU: 3.5 years), there was a re-infection rate of 25 %, mostly in the first 2 years. Difficult-to-treat bacteria were detected in 22%, multiresistant Staph. epidermidis in 28% of cases. Conclusions. -. The silver-coated. 1. implants showed good biocompatibility with no evidence of procedure-associated complications. -. The use of silver-coated. 1. implants could reduce the risk of re-infection. -. Further clinical data with longer follow-up are needed to assess the long-term value of the procedure

Introduction. As per national guidelines for Ankle fractures in the United Kingdom, fractures considered stable can be treated with analgesia, splinting and allowed to weight bear as tolerated. The guidelines also suggest further follow-up not mandatory. This study was aimed at evaluating the current clinical practice of managing stable ankle fractures at a university hospital against national guidelines. Method. The study was undertaken using retrospectively collected data, the inclusion criteria being all adults with stable ankle fracture pattern treated non-operatively between December 2022 and April 2023. Collected data included age of patient, date of injury, type of immobilization, number of clinical visits and any complications. Results. 41 cases were identified and analyzed. The mean age of the cohort was 49.8 years (Standard deviation 20.01). Twelve percent (n = 5) were reviewed in clinic, treated and discharged as stable Weber B type fracture pattern as per national guidelines after the first visit. About 52% (n = 21) were seen in clinic twice before discharge, first visit between 1-2 weeks and the last clinic visit between 5-7 weeks. About a third of patients (30%, n = 12) were seen in clinic on more than two occasions. At the first clinic visit 87% (n = 36) were given a boot and allowed to weight bear as tolerated. Two patients were diagnosed with deep vein thrombosis/pulmonary embolism during the treatment duration. Three patients had extended duration of follow up for ongoing symptoms. None discharged after first or second visit needed surgery for displaced or malunited fracture. Conclusion. Patients discharged from clinic after first or second visit did not need any further surgery. As per national guidelines, patients deemed stable weber B lateral malleolus fracture pattern after weight bearing radiograph can be treated safely with a weight bearing walking boot with no further follow up

Introduction. In tissue engineering, the establishment of sufficient vascularization is essential for tissue viability and functionality. Inadequate vascularization disrupts nutrients and oxygen supply. Nonetheless, regenerating intricate vascular networks represents a significant challenge. Consequently, research efforts devoted to preserving and regenerating functional vascular networks in engineered tissues are of paramount importance. The present work aims to validate a decellularisation process with preservation of the vascular network and extracellular matrix (ECM) components in fasciocutaneous flaps. Method. Five vascularized fasciocutaneous flaps from cadaveric donors were carefully harvested from the anterolateral thigh (ALT), preserving the main perforator of the fascia lata. The entire ALT flap underwent decellularization by perfusion using a clinically validated chemical protocol. Fluoroscopy and computed tomography (CT) were used to analyze the persistence of the vascular network within the flap, pre- and post-decellularization. Histological analysis, including hematoxylin and eosin staining, and quantitative DNA assessment evaluated decellularization efficacy. Further qualitative (immunohistochemistry, IHC) and quantitative analyses were conducted to assess the preservation of ECM components, such as collagen, glycosaminoglycans, and elastin. Result. On average, the ALT flap maintains 82% of the perfusion area (p = 0.094) post-treatment. Histological analysis confirmed decellularization efficacy and revealed structural rearrangement. Paired analysis revealed a significant decrease in DNA levels (<14.8 ng/mg of dry weight, p****< 0.0001) and well-maintained ECM. IHC indicated the persistence of elastine, collagen IV and laminin. Quantitative analysis confirmed elastin (p = 0.44) and collagen persistence (+74%, p*** = 0.001, albeit with a decrease in matrix glycosaminoglycans (-41%, p*** = 0.01). Conclusion. Decellularization effectively removed cells, while preserving the ECM overall and maintaining some vascular network integrity. Yet, further study is needed to validate these findings, involving microCT examination of the vascular network and its ability to support cell colonization and viability

Introduction. Weight is a modifiable risk factor for osteoarthritis (OA) progression. Despite the emphasis on weight loss, data quantifying the changes seen in joint biomechanics are limited. Bariatric surgery patients experience rapid weight loss. This provides a suitable population to study changes in joint forces and function as weight changes. Method. 10 female patients undergoing gastric bypass or sleeve gastrectomy completed 3D walking gait analysis at a self-selected pace, pre- and 6 months post-surgery. Lower limb and torso kinematic data for 10 walking trials were collected using a Vicon motion capture system and kinetics using a Kistler force plate. An inverse kinematic model in Visual 3D allowed for no translation of the hip joint centre. 6 degrees of freedom were allowed at other joints. Data were analysed using JASP with a paired samples t-test. Result. On average participants lost 28.8±7.60kg. No significant changes were observed in standing knee and hip joint angles. Walking velocity increased from 1.10±0.11 ms. -1. to 1.23±0.17 ms. -1. (t(9)=-3.060, p = 0.014) with no change in step time but a mean increase in stride length of 0.12m (SE: 0.026m; t(9)=-4.476, p = 0.002). A significant decrease of 21.5±4.2% in peak vertical ground reaction forces was observed (t(9)=12.863, p <0.001). Stride width significantly decreased by 0.04m (SE: 0.010m; t(9)=4.316, p = 0.002) along with a decrease in lateral impulse of 21.2Ns (SE: 6.977Ns; t(7), p = 0.019), but no significant difference in knee joint angles were observed. Double limb support time also significantly reduced by 0.02s (SE: 0.006s; t(9) = 3.639, p=0.005). Conclusion. The reduction in stance width and lateral impulse suggests a more sagittal compass-gait walk is being achieved. This would reduce valgus moments on the knee reducing loading in the medial compartment. The reduction in peak ground reaction force would reduce knee contact forces and again potentially slow OA progression

Introduction. Understanding knee joint biomechanics is crucial, but studying Anterior cruciate ligament (ACL) biomechanics in human adolescents is challenging due to limited availability cadaveric specimens. This study aims to validate the adolescent porcine stifle joint as a model for ACL studies by examining the ACL's behavior under axial and torsion loads and assessing its deformation rate, stiffness, and load-to-failure. Methods. Human knee load during high-intensity sports can reach 5-6 times body weight. Based on these benchmarks, the study applied a force equivalent to 5-times body weight of juvenile porcine samples (90 pounds), estimating a force of 520N. Experiments involved 30 fresh porcine stifle joints (Yorkshire breed, Avg 90 lbs, 2-4 months old) stored at -22°C, then thawed and prepared. Joints were divided into three groups: control (load-to-failure test), axially loaded, and 30-degree torsion loaded. Using a servo-hydraulic material testing machine, the tibia's longitudinal axis was aligned with the load sensor, and specimens underwent unidirectional tensile loading at 1 mm/sec until rupture. Data on load and displacement were captured at 100 Hz. Results. One-way ANOVA showed statistically significant differences in maximum failure force among loading conditions (p = 0.0039). Post hoc analysis indicated significant differences between the control and 500N (non-twisted) groups (p = 0.014) and between the control and 500N (twisted) groups (p = 0.003). However, no significant difference was found between 500N (non-twisted) and 500N (twisted) groups (p = 0.2645). Two samples broke from the distal femur growth plates, indicating potential growth plate vulnerability in adolescent porcines. Conclusions. The study validates the adolescent porcine stifle joint as a suitable model for ACL biomechanical research, demonstrating that torsional loads are as damaging to the ACL's integrity as equivalent axial loads. It also highlights the potential vulnerability of growth plates in younger populations, reflected in the porcine model

Introduction. Osteoarthritis (OA) is a chronic degenerative disease of the entire joint leading to joint stiffness and pain (PMID:33571663). Recent evidence suggests that the sympathetic nervous system (SNS) plays a role in the pathogenesis of OA (PMID:34864169). A typical cause for long-term hyperactivity of the SNS is chronic stress. To study the contribution of increased sympathetic activity, we analyzed the progression of OA in chronically stressed mice. Method. We induced OA in male C57BL/6J mice by destabilizing the medial meniscus (DMM)(PMID:17470400) and exposed half of these mice to chronic unpredictable mild stress (CUMS)(PMID:28808696). Control groups consisted of sham-operated mice with and without CUMS exposure. After 12 weeks, CUMS efficacy was determined by assessing changes in body weight gain and activity of mice, measuring splenic norepinephrine and serum corticosterone levels. OA progression was studied by histological analysis of cartilage degeneration and synovitis, and by μCT to evaluate changes in calcified cartilage and subchondral bone microarchitecture. A dynamic weight-bearing system was used to assess OA-related pain. Result. CUMS resulted in significantly decreased body weight gain and activity, as well as increased splenic norepinephrine and serum corticosterone concentrations compared to the respective controls. Surprisingly, already DMM alone resulted in elevated stress hormone levels. CUMS significantly exacerbated cartilage degeneration and synovial inflammation and increased OA pain in DMM mice. The underlying cellular and molecular mechanisms are currently being analyzed using FACS, single cell RNAseq, and spatial proteomics. Conclusion. Overall, chronic stress exacerbates OA severity and pain. Moreover, increased levels of stress hormones were observed in OA mice without CUMS induction, suggesting a complex bi-directional interaction between the SNS and OA. Targeting the autonomic nervous system, such as attenuating the SNS but also stimulating the activity of the parasympathetic nervous system, as a counterpart of the SNS, may therefore be promising for novel preventive or causal treatments of OA

Introduction. Many patients with obesity experience knee pain. Excess body weight is a modifiable risk factor for osteoarthritis (OA) and weight loss is encouraged in patients with OA. Bariatric surgery could improve or limit the progression of these conditions through significant weight loss. The Oxford Knee Score (OKS) is a validated tool in the assessment of knee replacement surgery for OA. We present a novel application of the OKS to assess knee pain & function after weight loss surgery. The primary aim of this study was to assess whether there was a significant difference in mean OKS before and 24 months after weight loss surgery. Method. Eighteen female participants were included in this study. They underwent sleeve gastrectomy or Roux-en-Y gastric bypass. Patient demographics, body mass index (BMI) and OKS were collected pre- and 24 months post operatively. Result. There was an increase in the mean OKS from 31.8 (SD 11.8) pre surgery to 36.6 (SD 12.3) at 24 months. This was statistically significant (95% CI 0.99-10.5, p=0.02). Mean BMI reduced from 46.6 kg/m. 2. (SD 5.8) to 33.0 kg/m. 2. (SD 3.5). Conclusion. A significant improvement in mean OKS was seen after weight loss surgery. These findings demonstrate an improvement in knee pain & function with weight loss. This study contributes to a larger project evaluating the kinetic and kinematic changes to walking gait from weight loss

Aims

The incidence of limb fractures in patients living with HIV (PLWH) is increasing. However, due to their immunodeficiency status, the operation and rehabilitation of these patients present unique challenges. Currently, it is urgent to establish a standardized perioperative rehabilitation plan based on the concept of enhanced recovery after surgery (ERAS). This study aimed to validate the effectiveness of ERAS in the perioperative period of PLWH with limb fractures.

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Lower limb fractures are common in low- and middle-income countries (LMICs) and represent a significant burden to the existing orthopaedic surgical infrastructure. In high income country (HIC) settings, internal fixation is the standard of care due to its superior outcomes. In LMICs, external fixation is often the surgical treatment of choice due to limited supplies, cost considerations, and its perceived lower complication rate. The aim of this systematic review protocol is identifying differences in rates of infection, nonunion, and malunion of extra-articular femoral and tibial shaft fractures in LMICs treated with either internal or external fixation.

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The mechanism by which synovial fluid (SF) kills bacteria has not yet been elucidated, and a better understanding is needed. We sought to analyze the antimicrobial properties of exogenous copper in human SF against Staphylococcus aureus.

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While residual fixed flexion deformity (FFD) in unicompartmental knee arthroplasty (UKA) has been associated with worse functional outcomes, limited evidence exists regarding FFD changes. The objective of this study was to quantify FFD changes in patients with medial unicompartmental knee arthritis undergoing UKA, and investigate any correlation with clinical outcomes.

Understanding spinopelvic mechanics is important for the success of total hip arthroplasty (THA). Despite significant advancements in appreciating spinopelvic balance, numerous challenges remain. It is crucial to recognize the individual variability and postoperative changes in spinopelvic parameters and their consequential impact on prosthetic component positioning to mitigate the risk of dislocation and enhance postoperative outcomes. This review describes the integration of advanced diagnostic approaches, enhanced technology, implant considerations, and surgical planning, all tailored to the unique anatomy and biomechanics of each patient. It underscores the importance of accurately predicting postoperative spinopelvic mechanics, selecting suitable imaging techniques, establishing a consistent nomenclature for spinopelvic stiffness, and considering implant-specific strategies. Furthermore, it highlights the potential of artificial intelligence to personalize care.

Cite this article: Bone Joint J 2024;106-B(11):1206–1215.

Aims

Venous thromboembolism (VTE) is a potential complication of foot and ankle surgery. There is a lack of agreement on contributing risk factors and chemical prophylaxis requirements. The primary outcome of this study was to analyze the 90-day incidence of symptomatic VTE and VTE-related mortality in patients undergoing foot and ankle surgery and Achilles tendon (TA) rupture. Secondary aims were to assess the variation in the provision of chemical prophylaxis and risk factors for VTE.

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The aim of this study was to review the provision of total elbow arthroplasties (TEAs) in England, including the incidence, the characteristics of the patients and the service providers, the types of implant, and the outcomes.

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The efficacy of saline irrigation for treatment of implant-associated infections is limited in the presence of porous metallic implants. This study evaluated the therapeutic efficacy of antibiotic doped bioceramic (vancomycin/tobramycin-doped polyvinyl alcohol composite (PVA-VAN/TOB-P)) after saline wash in a mouse infection model implanted with titanium cylinders.

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The purpose of this study was to develop a convolutional neural network (CNN) for fracture detection, classification, and identification of greater tuberosity displacement ≥ 1 cm, neck-shaft angle (NSA) ≤ 100°, shaft translation, and articular fracture involvement, on plain radiographs.