Do High Doses of Multiple Antibiotics Loaded into Bone Cement Spacers Improve the Success Rate in Staphylococcal Periprosthetic Joint Infection When Rifampicin Cannot Be Employed?

Rifampicin is one of the mainstays in treating staphylococcal prosthetic joint infection (PJI). However, discontinuation due to intolerance, drug interactions, and adverse events is common. Two-stage revision surgery remains the gold standard, with the number of revision arthroplasties steadily increasing. This study aims to evaluate the effectiveness and safety of a novel two-stage revision protocol for staphylococcal prosthetic joint infection (PJI) utilizing bone cement spacers loaded with multiple high doses of antibiotics. Additionally, it seeks to analyze outcomes in patients ineligible for rifampicin treatment. A retrospective review of 43 cases of staphylococcal hip and knee prosthetic joint infections (PJIs) from 2012 to 2020 was conducted. In all instances, a commercial cement containing 1 g of gentamicin and 1 g of clindamycin, augmented with 4 g of vancomycin and 2 g of ceftazidime, was employed to cast a spacer manually after thorough surgical debridement. We report an eradication rate of 82%, with no significant differences observed (p = 0.673) between patients treated with (84%, n = 19) and without rifampicin (79%, n = 24). There were no disparities in positive culture rates (7%), spacer replacement (18%), or survival analysis (p = 0.514) after an average follow-up of 68 months (range 10-147) in the absence of systemic toxicity and surgical complications superimposable to those previously reported. In conclusion, two-stage revision with local high doses of ceftazidime, vancomycin, gentamicin, and clindamycin demonstrates high effectiveness in treating staphylococcal PJIs. Notably, systemic rifampicin does not influence the outcomes. This protocol, with multiple high doses of antibiotics loaded into the bone cement spacer, is presented as a viable and safe alternative for patients unsuitable for rifampicin treatment.

Extremity high-grade sarcomas in elderly patients, are they candidates for surgery? Experience in a sarcoma referral center.

The number of elderly patients diagnosed with cancer is increasing. However, knowledge regarding cancer in elderly patients is very scarce. The aim of this study is to analyze the differences in management and outcomes of high-grade extremity sarcomas between elderly and middle-aged patients. Two cohorts were made (> 70 and 30/50 years old) among patients treated in a multidisciplinary unit of a national reference center between 2011 and 2017 with a minimum of 2 years of follow-up. The management and outcomes between these two cohorts were compared. Seventy patients were included, 34 young patients and 36 elderly patients. The only difference between the treatment schemes was the chemotherapy used, 67.6% of the young patients received chemotherapy versus 16.7% of the elderly patients (p = 0.000015). There were no differences either in the overall survival or the progression-free survival between groups at 1 and 2-year follow-up. Deceases for other causes were nearly exclusive of elderly patients at a median of 45.57 months. Surgery is the treatment of choice for sarcomas in both elderly and young patients having similar results in terms of progression-free survival, overall survival, and surgery outcomes. The use of chemotherapy is the only difference in the treatment schemes between both groups. In the elderly patient with minimal or no comorbidity and good functional reserve, surgical curative treatment should be chosen. As for frail elderly patients, the therapeutic objectives must be focused mainly on quality of life and palliation of symptoms.

Is a greater degree of constraint really harmful? Clinical biomechanical comparative study between condylar constrained knee and rotating hinge prosthesis.

BACKGROUND: The real degree of constraint of rotating hinge knee and condylar constrained prostheses is a matter of discussion in revision knee arthroplasty. The objective of this study is to compare the tibial rotation between implants in the clinical settings. METHODS: An investigator blinded experimental study was designed including 20 patients: in 10 of them a rotating hinge knee prosthesis (Endomodel®, LINK) was implanted and in the remaining 10 a constrained condylar knee prosthesis (LCCK®, Zimmer) was used. A medial parapatellar approach was performed and implantation was performed according to conventional surgical technique. Tibial rotation was measured with two accelerometers in full extension and at 30°, 60° and 90° of flexion. Pre and postoperative Knee Injury and Osteoarthritis Outcome Score was recorded. FINDINGS: Both groups were homogenous in age (73.4 years in rotating hinge knee prosthesis vs 74 years in constrained condylar knee group), sex, laterality and preoperative Knee Injury and Osteoarthritis Outcome Score (p > 0.05). The postoperative Knee Injury and Osteoarthritis Outcome Score was significantly higher in the rotating hinge knee prosthesis group (80.98 vs 76.28). The degrees of tibial rotation measured by inertial sensors in the rotating hinge knee prosthesis group were also significantly higher than those measured in the constrained condylar knee group (5.66° vs 2.1°) with p = 0.001. INTERPRETATION: Rotating hinge knee prosthesis appears to represent a lower rotational constraint degree than constrained condylar knee systems in clinical practice and it may increase the clinical satisfaction. The clinical significance: Rotating hinge knee prosthesis appears to represent a lower constraint degree than constrained condylar knee systems in clinical practice.

Ultrasound-Guided A1 Pulley Release Versus Classic Open Surgery for Trigger Digit: A Randomized Clinical Trial.

OBJECTIVES: We compared an ultra-minimally invasive ultrasound-guided percutaneous A1 pulley release and a classic open surgery for trigger digit. METHODS: We designed a single-center randomized control trial. All cases had clinical signs of primary grade III trigger digit. Concealed allocation (1:1) was used for assigning patients to each group and data collectors were blinded. The Quick-Disabilities of the Arm, Shoulder, and Hand (Quick-DASH) questionnaire was our primary variable. Quick-DASH, two-point discrimination, grip strength, time until stopping analgesics, having full digital range of motion and restarting everyday activities were registered on the 1st, 3rd, and 6th weeks, 3rd and 6th months, and 1st year after the procedure. RESULTS: We randomized 84 patients to ultrasound-guided release and classic open surgery. Quick-DASH scores significantly favored the percutaneous technique until the 3rd month: 7.6 ± 1.2 versus 15.3 ± 2.4 (mean ± standard error of the mean). The percutaneous group obtained significantly better results in all the variables studied: time until stopping analgesics, achieving full range of motion and restarting everyday activities. Grip strength was significantly better in the percutaneous group for the 1st week only. Five cases of moderate local pain were observed in the open technique. There was one case of transient nerve numbness per group. CONCLUSIONS: The ultra-minimally invasive ultrasound-guided A1 pulley release was clinically superior to the classic open surgery in functional recovery with a lower complication rate.

The tale of microencapsulated rifampicin: is it useful for the treatment of periprosthetic joint infection?

PURPOSE: Microencapsulation techniques have allowed the addition of rifampicin to bone cement, but its in vivo efficacy has not been proven. The aim of our study is to determine the superiority of cement containing gentamicin and rifampicin microcapsules in the treatment of PJI versus cement exclusively containing gentamicin. METHODS: An S. aureus PJI was induced in 15 NZW rabbits. A week after inoculation, the first stage of replacement was carried out, and the animals were divided into two groups: group R received a spacer containing gentamicin and rifampicin microcapsules, and group C received a spacer containing gentamicin. Intra-articular release curve of rifampicin and infection and toxicity markers were monitored for four weeks post-operatively, when microbiological analysis was performed. RESULTS: The microbiological cultures showed a significantly lower growth of S. aureus in soft tissue (2.3·104 vs 0; p = 0.01) and bone (5.7·102 vs 0; p = 0.03) in the group with rifampicin microcapsules. No differences were found in systemic toxicity markers. Rifampicin release from the cement spacer showed higher concentrations than the staphylococcal MIC throughout the analysis. CONCLUSION: The in vivo analyses demonstrated the superiority of cement containing gentamicin and rifampicin microcapsules versus the isolated use of gentamicin in the treatment of PJI in the rabbit model without serious side effects due to the systemic absorption of rifampicin. Given the increasing incidence of staphylococci-related PJI, the development of new strategies for intra-articular administration of rifampicin for its treatment has a high clinical impact.

Conceptual evolution of 3D printing in orthopedic surgery and traumatology: from "do it yourself" to "point of care manufacturing".

BACKGROUND: 3D printing technology in hospitals facilitates production models such as point-of-care manufacturing. Orthopedic Surgery and Traumatology is the specialty that can most benefit from the advantages of these tools. The purpose of this study is to present the results of the integration of 3D printing technology in a Department of Orthopedic Surgery and Traumatology and to identify the productive model of the point-of-care manufacturing as a paradigm of personalized medicine. METHODS: Observational, descriptive, retrospective and monocentric study of a total of 623 additive manufacturing processes carried out in a Department of Orthopedic Surgery and Traumatology from November 2015 to March 2020. Variables such as product type, utility, time or materials for manufacture were analyzed. RESULTS: The areas of expertise that have performed more processes are Traumatology, Reconstructive and Orthopedic Oncology. Pre-operative planning is their primary use. Working and 3D printing hours, as well as the amount of 3D printing material used, vary according to the type of product or material delivered to perform the process. The most commonly used 3D printing material for manufacturing is polylactic acid, although biocompatible resin has been used to produce surgical guides. In addition, the hospital has worked on the co-design of customized implants with manufacturing companies. CONCLUSIONS: The integration of 3D printing in a Department of Orthopedic Surgery and Traumatology allows identifying the conceptual evolution from "Do-It-Yourself" to "POC manufacturing".

Point-of-care manufacturing: a single university hospital's initial experience.

BACKGROUND: The integration of 3D printing technology in hospitals is evolving toward production models such as point-of-care manufacturing. This study aims to present the results of the integration of 3D printing technology in a manufacturing university hospital. METHODS: Observational, descriptive, retrospective, and monocentric study of 907 instances of 3D printing from November 2015 to March 2020. Variables such as product type, utility, time, or manufacturing materials were analyzed. RESULTS: Orthopedic Surgery and Traumatology, Oral and Maxillofacial Surgery, and Gynecology and Obstetrics are the medical specialties that have manufactured the largest number of processes. Working and printing time, as well as the amount of printing material, is different for different types of products and input data. The most common printing material was polylactic acid, although biocompatible resin was introduced to produce surgical guides. In addition, the hospital has worked on the co-design of custom-made implants with manufacturing companies and has also participated in tissue bio-printing projects. CONCLUSIONS: The integration of 3D printing in a university hospital allows identifying the conceptual evolution to "point-of-care manufacturing."

Application of 3D printing and distributed manufacturing during the first-wave of COVID-19 pandemic. Our experience at a third-level university hospital.

BACKGROUND: 3D printing and distributed manufacturing represent a paradigm shift in the health system that is becoming critical during the COVID-19 pandemic. University hospitals are also taking on the role of manufacturers of custom-made solutions thanks to 3D printing technology. CASE PRESENTATION: We present a monocentric observational case study regarding the distributed manufacturing of three groups of products during the period of the COVID-19 pandemic from 14 March to 10 May 2020: personal protective equipment, ventilatory support, and diagnostic and consumable products. Networking during this period has enabled the delivery of a total of 17,276 units of products manufactured using 3D printing technology. The most manufactured product was the face shields and ear savers, while the one that achieved the greatest clinical impact was the mechanical ventilation adapters and swabs. The products were manufactured by individuals in 57.3% of the cases, and our hospital acted as the main delivery node in a hub with 10 other hospitals. The main advantage of this production model is the fast response to stock needs, being able to adapt almost in real time. CONCLUSIONS: The role of 3D printing in the hospital environment allows the reconciliation of in-house and distributed manufacturing with traditional production, providing custom-made adaptation of the specifications, as well as maximum efficiency in the working and availability of resources, which is of special importance at critical times for health systems such as the current COVID-19 pandemic.

A new biarticular cement spacer technique for infected total hip and knee arthroplasty with massive bone loss.

INTRODUCTION: The management of massive femoral bone defects following prosthetic infection remains a surgical challenge, particularly when the entire femur is affected. METHODS: We present the first results of a new biarticular cement spacer with antibiotic technique using a cephalomedullary nail for the treatment of infected hip arthroplasty involving complete femoral bone loss. RESULTS: 5 patients with a minimum follow-up of 1 year were included. In all cases 2-stage replacement due to hip periprosthetic infection was carried out, with the need for a biarticular complete femoral spacer in view of the magnitude of the bone defect. The infection was resolved in all patients, with no complications (spacer fracture or dislocation) associated to spacer use, and the patients were all able to maintain the sitting position with active knee movements between the 2 surgical stages. Improvement with respect to preoperative functional status was observed in all cases, as evidenced by the Harris Hip Score (HHS) (from 24.2 to 73; p < 0.001) and 12-Item Short-Form Health Survey (SF-12) (from 16.8 to 33.2; p = 0.001), with a lessened need for walking aids. DISCUSSION: The described technique offers a possible solution to a number of complications observed with the use of spacers in massive defects, affording greater patient comfort and autonomy while waiting to receive total femoral replacement.

Surgical treatment of hip fracture in centenarians: Complications and independent risk factors of death.

BACKGROUND: The increase in life expectancy has led to the appearance of a subgroup of hip fracture (HF) patients with special characteristics known as centenarians. The aim of the present study is to analyse the demographic characteristics, complications and mortality rate of this subgroup in order to identify the specific risk factors for mortality in these patients. METHODS: Retrospective analysis of 69 patients (58 women and 11 men) aged 100 years or older admitted to a tertiary hospital for HF between 1999 and 2018. RESULTS: The average age was 101.3 years (100-108, median 101). More than half (62.3%) of all patients presented with extracapsular fractures. The most common complications observed were delirium (52.3%) and urinary retention (27.7%). Haematoma (9.2%) was the most common surgical complication. Only 3 patients (7.3%) changed their place of residence after admission. In-hospital, 30-day and 1-year mortality rates were 13.8%, 21.5% and 54.2%, respectively. A high Charlson Comorbidity Index and baseline Functional Ambulation Classification (FAC) <3 were associated with a higher in-hospital mortality rate (OR = 1.95 95% CI [1.03-3.69] and OR = 5.7 95% CI [1.2-26.8]), respectively. The presence of more than 3 comorbidities and baseline FAC <3 were associated with a higher risk of 30-day mortality (OR = 6, 95% CI [1.4-24.7] and OR = 4, 95% CI [1.13-14.2]), respectively. Dementia has been associated with a higher risk of 30-day and 1-year mortality (OR = 4.6, 95% CI [1.2-16.7]) and OR = 5.11, 95% CI [1.6-21]) respectively. CONCLUSION: FAC score, number of comorbidities, dementia and the Charlson Comorbidity Index have been shown to be risk factors of mortality in centenarians with HF.

Experimental reproduction of periprosthetic joint infection: Developing a representative animal model.

BACKGROUND: Infection after arthroplasty (prosthetic joint infection; PJI) is a devastating complication that can lead to functional loss of the affected limb. The purpose of the present study is to develop an animal model of PJI using a three-dimensional printed species-specific implant, which is a step forward for future research to develop new therapeutic strategies. METHODS: Fifteen New Zealand White rabbits were employed to reproduce PJI by intra-articular inoculation of 105 cfu/ml of Staphylococcus aureus ATCC® 29213. Three-dimensional printing technology was used to design a species-specific four-millimeter-thick implant maintaining the anatomical irregularities of the tibial-articular surface. Response to bacterial inoculation was monitored by clinical (weight and temperature), hematological (leukocyte, lymphocyte and platelet counts) and biochemical (erythrocyte sedimentation rate) analyses at the time of inoculation and seven days thereafter, when microbiological samples for culture were also taken. RESULTS: All animals recovered from surgery and all displayed full weight-bearing four days postoperatively. Fourteen of the 15 tested animals (93.3%) presented positive microbiological cultures. A statistically significant increase was found in the number of platelets and leukocytes, as well as a significant decrease in the percentage of lymphocytes, with P = 0.0001 in all cases. CONCLUSIONS: An experimental model faithfully reproducing the periprosthetic infection environment and achieving a high rate of infection has been designed. The use of three-dimensional printed species-specific implants allows rapid postoperative recovery of animals and the development of a stable biofilm. These characteristics make it an interesting model to study its pathogenesis and possible therapeutic strategies.

Ultrasound-guided supra-acetabular pelvic external fixator (US-SA FIX).

BACKGROUND: Between the different options in pelvic external fixation, the supra-acetabular pin placement is considered the best option by many authors. The aim of this study is to describe the surgical technique of the ultrasound-guided supra-acetabular pelvic external fixator (US-SA FIX). SURGICAL TECHNIQUE: Description of the steps to perform the US-SA FIX technique. DISCUSSION: The supra-acetabular pin placement is considered the best option and it is the most wildly used because it combines three crucial qualities: safety, simplicity, and effectiveness. Notwithstanding, when a severely multiple injured patient arrives at the emergency room we need to perform an emergency external fixation, however trained x-ray technicians or pelvic surgeons are not always present, making it difficult to perform the surgery with the proper intra-operative imaging, increasing the surgical time with potentially serious repercussions, a case scenario where the ultrasound can be a very helpful tool. Ultrasound-guided supra-acetabular pelvic external fixator pin placement is feasible without compromising the reliability of its placement, and the application of this new technique in clinical practice in our centre brings encouraging results.

3D printing in experimental orthopaedic surgery: do it yourself.

INTRODUCTION: Periprosthetic infection is considered an increasing incidence pathology whose therapeutic strategies can be defined as unsatisfactory. Currently, animal models are employed to study its physiopathology and strategic therapies, but non-species-specific materials are implanted as foreign bodies. The use of these implants implies intrinsic instability, which hinders the development of a biofilm on their surfaces and complicates the post-operative recovery of the animal. The objective of the present study is the design of a species-specific implant for the New Zealand white (NZW) rabbit by means of 3D printing. MATERIALS AND METHODS: A CT scan of the knee of a NZW rabbit was performed, and the tibial surface was reconstructed in order to fabricate a species-specific tibial plateau using Horos® and Autodesk® Meshmixer™ software. This implant was inserted in fifteen NZW rabbits, and the assessment of its stability was based on the position of the limb at rest and the animal weight-bearing capacity. Biofilm formation on the surface was demonstrated by crystal violet staining. RESULTS: A 1.81 cm × 1 cm × 1.24 cm stainless steel implant was designed. It consisted of a 4-mm-thick tibial plate with a rough surface and an eccentric metaphyseal anchoring. All of the animals exhibited hyperflexion of the operated limb immediately post-operative, and 100% could apply full weight bearing from day 5 after surgery. CONCLUSIONS: The species-specific design of implants in experimental surgery encourages rapid recovery of the animal and the development of a biofilm on their surfaces, making them ideal for the study of the physiopathology and for establishing possible therapeutic targets for prosthetic infection.

Patient-Specific Instrument Can Improve Functional and Radiographic Results during Learning Curve for Oxford Unicompartmental Knee Arthroplasty.

The true value of use of patient-specific instrumentation (PSI) systems by inexperienced surgeons during their learning curve to improve the clinical and radiographic outcome of unicompartmental knee arthroplasty (UKA) has not been previously studied. Fifty patients with a mean age of 64.3 years undergoing surgery for Oxford UKA were prospectively divided into two groups. Twenty-five patients were operated on by a surgeon with no prior experience in UKA using a PSI system and the other 25 patients by an experienced surgeon using a conventional procedure. Patients were scored using joint range of motion (ROM), the Knee Society Score (KSS), the Knee Injury and Osteoarthritis Outcome Score (KOOS), and the 12-item Short-Form (SF-12) before and 3 months and 2 years after surgery. Impact of use of PSI was measured by comparing clinical and radiographic outcome, complications, and implant survival. No evidence of poorer clinical outcome was seen in any subscale of KSS, KOOS, and SF-12 for inexperienced surgeons using PSI (p = 0.45, p = 0.32, and p = 0.61, respectively). No difference was found between the two procedures in precision of radiographic alignment of components (p = 0.53). No complication occurred in any group. PSI may improve precision of component alignment during the learning curve of surgeons, thus achieving functional results similar to those of more experienced surgeons using a conventional procedure.

3D surgical printing for preoperative planning of trabecular augments in acetabular fracture sequel.

We describe the methodical and possibilities of 3D surgical printing in preoperative planning for a total hip arthroplasty in acetabular deformity after acetabular fractures, showing a case of a 43-year-old with posttraumatic arthritis after both column fracture of the left acetabulum that was treated non operatively, supporting the do it yourself mode.

Biarticular total femur spacer for massive femoral bone loss: the mobile solution for a big problem.

Bone cement spacers loaded with antibiotic are the gold standard in septic revision. However, the management of massive bone defects constitutes a surgical challenge, requiring the use of different nails, expensive long stems, or cement-coated tumor prostheses for preparing the spacer. In most cases, the knee joint must be sacrificed. We describe a novel technique for preparing a biarticular total femur spacer with the help of a trochanteric nail coated with antibiotic loaded cement, allowing mobility of the hip and knee joints and assisted partial loading until second step surgery. This technique is helpful to maintain the length of the leg, prevent soft tissue contracture, and help eradicate the infection preserving the patient comfort and autonomy while waiting to receive total femoral replacement.

A Multicentric, Open-Label, Randomized, Comparative Clinical Trial of Two Different Doses of Expanded hBM-MSCs Plus Biomaterial versus Iliac Crest Autograft, for Bone Healing in Nonunions after Long Bone Fractures: Study Protocol.

ORTHOUNION is a multicentre, open, comparative, three-arm, randomized clinical trial (EudraCT number 2015-000431-32) to compare the efficacy, at one and two years, of autologous human bone marrow-derived expanded mesenchymal stromal cell (hBM-MSC) treatments versus iliac crest autograft (ICA) to enhance bone healing in patients with diaphyseal and/or metaphysodiaphyseal fracture (femur, tibia, and humerus) status of atrophic or oligotrophic nonunion (more than 9 months after the acute fracture, including recalcitrant cases after failed treatments). The primary objective is to determine if the treatment with hBM-MSCs combined with biomaterial is superior to ICA in obtaining bone healing. If confirmed, a secondary objective is set to determine if the dose of 100 × 106 hBM-MSCs is noninferior to that of 200 × 106 hBM-MSCs. The participants (n = 108) will be randomly assigned to either the experimental low dose (n = 36), the experimental high dose (n = 36), or the comparator arm (n = 36) using a central randomization service. The trial will be conducted in 20 clinical centres in Spain, France, Germany, and Italy under the same clinical protocol. The confirmation of superiority for the proposed ATMP in nonunions may foster the future of bone regenerative medicine in this indication. On the contrary, absence of superiority may underline its limitations in clinical use.

Microencapsulation of rifampicin: A technique to preserve the mechanical properties of bone cement.

Two-stage exchange with antibiotic-loaded bone cement spacers remains the gold standard for chronic periprosthetic joint infection (PJI). Rifampicin is highly efficient on stationary-phase staphylococci in biofilm; however, its addition to PMMA to manufacture spacers prevents polymerization and reduces mechanical properties. Isolation of rifampicin during polymerization by microencapsulation could allow manufacturing rifampicin-loaded bone cement maintaining elution and mechanical properties. Microcapsules of rifampicin with alginate, polyhydroxybutyratehydroxyvalerate (PHBV), ethylcellulose and stearic acid (SA) were synthesized. Alginate and PHBV microcapsules were added to bone cement and elution, compression, bending, hardness, setting time and microbiological tests were performed. Repeated measures ANOVA and Bonferroni post-hoc test were performed, considering a p < 0.05 as statistical significance. Bone cement specimens containing alginate microcapsules eluted more rifampicin than PHBV microcapsules or non-encapsulated rifampicin over time (p < 0.012). Microencapsulation of rifampicin allowed PMMA to preserve mechanical properties in compression and bending tests. Cement with alginate microcapsules showed similar behavior in hardness tests to control cement over the study period (73 ± 1.68HD ). PMMA with alginate microcapsules exhibited the largest zones of inhibition in microbiological tests. Statistically significant differences in mean diameters of zones of inhibition between PMMA loaded with alginate-rifampicin (p = 0.0001) and alginate-PHBV microcapsules (p = 0.0001) were detected. Rifampicin microencapsulation with alginate is the best choice to introduce rifampicin in PMMA preserving mechanical properties, setting time, elution, and antimicrobial properties. The main applicability of this study is the opportunity for obtaining rifampicin-loaded PMMA by microencapsulation of rifampicin in alginate microparticles, achieving high doses of rifampicin in infected tissues, increasing the successful of PJI treatment. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:459-466, 2018.