Jeffrey F. Granger

Biomechanical effects of total knee arthroplasty component malrotation: a computational simulation.

Modern total knee arthroplasty (TKA) is an effective procedure to treat pain and disability due to osteoarthritis, but some patients experience quadriceps weakness after surgery and have difficulty performing important activities of daily living. The success of TKA depends on many factors, but malalignment of the prosthetic components is a major cause of postoperative complications. Significant variability is associated with femoral and tibial component rotational alignment, but how this variability translates into functional outcome remains unknown. We used a forward‐dynamic computer model of a simulated squatting motion to perform a parametric study of the effects of variations in component rotational alignment in TKA. A cruciate‐retaining and posterior‐stabilized version of the same TKA implant were compared. We found that femoral rotation had a greater effect on quadriceps forces, collateral ligament forces, and varus/valgus kinematics, while tibial rotation had a greater effect on anteroposterior translations. Our findings support the tendency for orthopedic surgeons to bias the femoral component into external rotation and avoid malrotation of the tibial component.

Elution of antibiotics from poly(methyl methacrylate) bone cement after extended implantation does not necessarily clear the infection despite susceptibility of the clinical isolates.

Chronic orthopedic infections are commonly caused by bacterial biofilms, which are recalcitrant to antibiotic treatment. In many cases, the revision procedure for periprosthetic joint infection or trauma cases includes the implantation of antibiotic-loaded bone cement to kill infecting bacteria via the elution of a strong local dose of antibiotic(s) at the site. While many studies have addressed the elution kinetics of both non-absorbable and absorbable bone cements both in vitro and in vivo, the potency of ALBC against pathogenic bacteria after extended implantation time is not clear. In this communication, we use two case studies, a Viridans streptococci infected total knee arthroplasty (TKA) and a MRSA-polymicrobial osteomyelitis of a distal tibial traumatic amputation (TA) to demonstrate that an antibiotic-loaded poly(methyl methacrylate) (ALPMMA) coated intermedullary rod implanted for 117 days (TKA) and three ALPMMA suture-strung beads implanted for 210 days (TA) retained killing ability against Pseudomonas aeruginosa and Staphylococcus aureus in vitro, despite different clinical efficacies. The TKA infection resolved and the patient progressed to an uneventful second stage. However, the TA infection only resolved after multiple rounds of debridement, IV vancomycin and removal of the PMMA beads and placement of vancomycin and tobramycin loaded calcium sulfate beads.

Effects of loading concentration, blood and synovial fluid on antibiotic release and anti-biofilm activity of bone cement beads

Abstract Antibiotic loaded cement beads are commonly used for the treatment of biofilm related orthopaedic periprosthetic infections; however the effects of antibiotic loading and exposure of beads to body fluids on release kinetics are unclear. The purpose of this study was to determine the effects of (i) antibiotic loading density (ii) loading amount (iii) material type and (iv) exposure to body fluids (blood or synovial fluid) on release kinetics and efficacy of antibiotics against planktonic and lawn biofilm bacteria. Short‐term release into an agar gel was evaluated using a fluorescent tracer (fluorescein) incorporated in the carrier materials calcium sulfate (CaSO4) and poly methyl methacrylate (PMMA). Different fluorescein concentrations in CaSO4 beads were evaluated. Mechanical properties of fluorescein‐incorporated beads were analyzed. Efficacy of the antibiotics vancomycin (VAN) or tobramycin (TOB) alone and in combination was evaluated against lawn biofilms of bioluminescent strains of Staphylococcus aureus and Pseudomonas aeruginosa. Zones of inhibition of cultures (ZOI) were measured visually and using an in‐vivo imaging system (IVIS). The influence of body fluids on release was assessed using CaSO4 beads that contained fluorescein or antibiotics and were pre‐coated with human blood or synovial fluid. The spread from the beads followed a square root of time relationship in all cases. The loading concentration had no influence on short‐term fluorescein release and pre‐coating of beads with body fluids did not affect short‐term release or antibacterial activity. Compared to PMMA, CaSO4 had a more rapid short term rate of elution and activity against planktonic and lawn biofilms. This study highlights the importance of considering antibiotic loading and packing density when investigating the clinical application of bone cements for infection management. Graphical Abstract Figure. No Caption available.

Biofilms in orthopedic infections: a review of laboratory methods

Bacterial infection after hardware implantation in orthopedic surgery is a devastating issue as it often necessitates increased hospital costs and stays, multiple revision surgeries, and prolonged use of antibiotics. Because of the nature of hardware implantation into the body, these infections are commonly in the form of attached biofilms. The current literature on a range of methodologies to study clinically explanted infected orthopedic hardware, with potential biofilm, in the laboratory setting is limited. General methods include traditional and advanced culturing techniques, microscopy imaging techniques, and techniques that manipulate genetic material. The future of diagnostic techniques for infected implants, innovative hardware design, and treatment solutions for patients all depend on the successful evaluation and characterization of clinical samples in the laboratory setting. This review provides an overview of current methods to study biofilms associated with orthopedic infections and insight into future directions in the field.

Calcium phosphate cement to prevent collapse in avascular necrosis of the femoral head

Subchondral and articular collapse following nontraumatic osteonecrosis of the femoral head is an important cause of osteoarthritis in patients between ages 20 and 40. Because hip arthroplasty in the younger population is prone to early wear and failure, it is paramount to prevent collapse once osteonecrosis is detected. Natural remodeling of the osteonecrotic areas by adjacent normal bone is predominated by osteoclastic resorption, which weakens the cancellous bone and allows microfractures to occur before full healing can take place. Current treatment modalities include core decompression and various adjuncts such as bone graft, mesenchymal stem cells and tantalum implants to provide structural integrity and to speed bony creeping substitution. Calcium phosphate cement has been reported in the treatment of fractures, especially depressed tibial plateau fractures. It is slow to resorb and is gradually replaced by bone, allowing prolonged support of periarticular fractures during healing. We hypothesize that calcium phosphate cement in conjunction with standard decompression of osteonecrotic femoral head lesions can prevent collapse.

Relationships between varus-valgus laxity of the severely osteoarthritic knee and gait, instability, clinical performance and function.

Increased varus–valgus laxity has been reported in individuals with knee osteoarthritis (OA) compared to controls. However, the majority of previous investigations may not report truly passive joint laxity, as their tests have been performed on conscious participants who could be guarding against motion with muscle contraction during laxity evaluation. The purpose of this study was to investigate how a measure of passive knee laxity, recorded when the participant is under anesthesia, is related to varus–valgus excursion during gait, clinical measures of performance, perceived instability, and self‐reported function in participants with severe knee OA. We assessed passive varus–valgus knee laxity in 29 participants (30 knees) with severe OA, as they underwent total knee arthroplasty (TKA). Participants also completed gait analysis, clinical assessment of performance (6‐min walk (6 MW), stair climbing test (SCT), isometric knee strength), and self‐reported measures of function (perceived instability, Knee injury, and Osteoarthritis Outcome Score (KOOS) a median of 18 days before the TKA procedure. We observed that greater passive varus–valgus laxity was associated with greater varus–valgus excursion during gait (R2 = 0.34, p = 0.002). Significant associations were also observed between greater laxity and greater isometric knee extension strength (p = 0.014), farther 6 MW distance (p = 0.033) and shorter SCT time (p = 0.046). No relationship was observed between passive varus–valgus laxity and isometric knee flexion strength, perceived instability, or any KOOS subscale. The conflicting associations between laxity, frontal excursion during gait, and functional performance suggest a complex relationship between laxity and knee cartilage health, clinical performance, and self‐reported function that merits further study.

Lower-extremity soft tissue infections with intra-abdominal sources.

This article describes a series of 3 patients who presented with lower-extremity soft tissue infections. Each patient was treated with prompt debridement by an orthopedic surgeon (J.F.G.) and required at least 1 additional procedure by another surgeon.These infections vary from superficial cellulitis to rapidly advancing necrotizing fasciitis. At times, the source of these infections is clear. Other times, no obvious source of infection exists, in which case the abdomen must be considered as a possible source of infection. A high level of suspicion, complete history and physical examination, and appropriate ancillary studies are required to make an accurate and prompt diagnosis. Options for the treatment of the intra-abdominal source of infection depend on the etiology of the infection and anatomic location of the process. Psoas abscesses can often be decompressed by an interventional radiologist using computed tomography guidance. In the case of bowel involvement, such as suspected carcinoma or diverticulitis, a general surgeon is necessary. When the appropriate diagnosis is made, soft tissue infections of the thigh often respond to appropriate surgical debridement and antibiotic therapy. It is important to remember the whole patient when evaluating soft tissue infections, especially in the thigh. A low threshold for imaging of the abdomen and pelvis is important, especially when the physical examination or medical history reveals the abdomen as a possible source of infection.

Estimating patient-specific soft-tissue properties in a TKA knee.

Surgical technique is one factor that has been identified as critical to success of total knee arthroplasty. Researchers have shown that computer simulations can aid in determining how decisions in the operating room generally affect post‐operative outcomes. However, to use simulations to make clinically relevant predictions about knee forces and motions for a specific total knee patient, patient‐specific models are needed. This study introduces a methodology for estimating knee soft‐tissue properties of an individual total knee patient. A custom surgical navigation system and stability device were used to measure the force–displacement relationship of the knee. Soft‐tissue properties were estimated using a parameter optimization that matched simulated tibiofemoral kinematics with experimental tibiofemoral kinematics. Simulations using optimized ligament properties had an average root mean square error of 3.5° across all tests while simulations using generic ligament properties taken from literature had an average root mean square error of 8.4°. Specimens showed large variability among ligament properties regardless of similarities in prosthetic component alignment and measured knee laxity. These results demonstrate the importance of soft‐tissue properties in determining knee stability, and suggest that to make clinically relevant predictions of post‐operative knee motions and forces using computer simulations, patient‐specific soft‐tissue properties are needed.

16S rRNA analysis provides evidence of biofilms on all components of three infected periprosthetic knees including permanent braided suture.

Bacterial biofilms are the main etiological agent of periprosthetic joint infections (PJI); however, it is unclear if biofilms colonize one or multiple components. Because biofilms can colonize a variety of surfaces, we hypothesized that biofilms would be present on all components. 16S ribosomal RNA (rRNA) gene sequencing analysis was used to identify bacteria recovered from individual components and non-absorbable suture material recovered from three PJI total knee revision cases. Bray-Curtis non-metric multidimensional scaling analysis revealed no significant differences in similarity when factoring component, material type, or suture versus non-suture material, but did reveal significant differences in organism profile between patients (P < 0.001) and negative controls (P < 0.001). Confocal microscopy and a novel agar encasement culturing method also confirmed biofilm growth on a subset of components. While 16S sequencing suggested that the microbiology was more complex than revealed by culture contaminating, bacterial DNA generates a risk of false positives. This report highlights that biofilm bacteria may colonize all infected prosthetic components including braided suture material, and provides further evidence that clinical culture can fail to sufficiently identify the full pathogen profile in PJI cases.

Targeting intracellular Staphylococcus aureus to lower recurrence of orthopaedic infection

Staphylococcus aureus is often found in orthopaedic infections and may be protected from commonly prescribed antibiotics by forming biofilms or growing intracellularly within osteoblasts. To investigate the effect of non‐antibiotic compounds in conjunction with antibiotics to clear intracellular and biofilm forming S. aureus causing osteomyelitis. SAOS‐2 osteoblast‐like cell lines were infected with S. aureus BB1279. Antibiotics (vancomycin, VAN; and dicloxacillin, DICLOX), bacterial efflux pump inhibitors (piperine, PIP; carbonyl cyanide m‐chlorophenyl hydrazone, CCCP), and bone morphogenetic protein (BMP‐2) were evaluated individually and in combination to kill intracellular bacteria. We present direct evidence that after gentamicin killed extracellular planktonic bacteria and antibiotics had been stopped, seeding from the infected osteoblasts grew as biofilms. VAN was ineffective in treating the intracellular bacteria even at 10× MIC; however in presence of PIP or CCCP the intracellular S. aureus was significantly reduced. Bacterial efflux pump inhibitors (PIP and CCCP) were effective in enhancing permeability of antibiotics within the osteoblasts and facilitated killing of intracellular S. aureus. Confocal laser scanning microscopy (CLSM) showed increased uptake of propidium iodide within osteoblasts in presence of PIP and CCCP. BMP‐2 had no effect on growth of S. aureus either alone or in combination with antibiotics. Combined application of antibiotics and natural agents could help in the treatment of osteoblast infected intracellular bacteria and biofilms associated with osteomyelitis.