Immunomodulatory Peptide IDR-1018 Decreases Implant Infection and Preserves Osseointegration

Background

Innate defense regulator peptide-1018 (IDR-1018) is a 12-amino acid, synthetic, immunomodulatory host defense peptide that can reduce soft tissue infections and is less likely to induce bacterial resistance than conventional antibiotics. However, IDRs have not been tested on orthopaedic infections and the immunomodulatory effects of IDR-1018 have only been characterized in response to lipopolysacharide, which is exclusively produced by Gram-negative bacteria.

Questions/purposes

We sought (1) to more fully characterize the immunomodulatory effects of IDR-1018, especially in response to Staphylococcus aureus; and (2) to determine whether IDR-1018 decreases S aureus infection of orthopaedic implants in mice and thereby protects the implants from failure to osseointegrate.

Methods

In vitro effects of IDR-1018 on S aureus were assessed by determining minimum inhibitory concentrations in bacterial broth without and with supplementation of physiologic ion levels. In vitro effects of IDR-1018 on macrophages were determined by measuring production of monocyte chemoattractant protein-1 (MCP-1) and proinflammatory cytokines by enzyme-linked immunosorbent assay. In vivo effects of IDR-1018 were determined in a murine model of S aureus implant infection by quantitating bacterial burden, macrophage recruitment, MCP-1, proinflammatory cytokines, and osseointegration in nine mice per group on Day 1 postimplantation and 20 mice per group on Day 15 postimplantation.

Results

IDR-1018 demonstrated antimicrobial activity by directly killing S aureus even in the presence of physiologic ion levels, increasing recruitment of macrophages to the site of infections by 40% (p = 0.036) and accelerating S aureus clearance in vivo (p = 0.008) with a 2.6-fold decrease in bacterial bioburden on Day 7 postimplantation. In vitro immunomodulatory activity of IDR-1018 included inducing production of MCP-1 in the absence of other inflammatory stimuli and to potently blunt excess production of proinflammatory cytokines and MCP-1 induced by lipopolysaccharide. Higher concentrations of IDR-1018 were required to blunt production of proinflammatory cytokines and MCP-1 in the presence S aureus. The largest in vivo immunomodulatory effect of IDR-1018 was to reduce tumor necrosis factor-α levels induced by S aureus by 60% (p = 0.006). Most importantly, IDR-1018 reduced S aureus-induced failures of osseointegration by threefold (p = 0.022) and increased osseointegration as measured by ultimate force (5.4-fold, p = 0.033) and average stiffness (4.3-fold, p = 0.049).

Conclusions

IDR-1018 is potentially useful to reduce orthopaedic infections by directly killing bacteria and by recruiting macrophages to the infection site.

Clinical Relevance

These findings make IDR-1018 an attractive candidate to explore in larger animal models to ascertain whether its effects in our in vitro and mouse experiments can be replicated in more clinically relevant settings.     

In vitro study of elution kinetics and bio-activity of meropenem-loaded acrylic bone cement

Background

Use of antibiotic-loaded acrylic bone cement to treat orthopaedic infections continues to remain popular, but resistance to routinely used antibiotics has led to the search for alternative, more effective antibiotics. We studied, in vitro, the elution kinetics and bio-activity of different concentrations of meropenem-loaded acrylic bone cement.

Methods

Meropenem-loaded bone cement cylinders of different concentrations were serially immersed in normal saline. Elution kinetics was studied by measuring the drug concentration in the eluate, collected at pre-determined intervals, by high-performance liquid chromatography. Bio-activity of the eluate of two different antibiotic concentrations was tested for a period of 3 weeks against each of the following organisms: Staphylococcus aureus ATCC 2593 (MSSA), Enterococcus faecalis ATCC 29212, Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922, S. aureus ATCC 43300 (MRSA) and Klebsiella pneumoniae ATCC 700603 (ESBL).

Results

Meropenem elutes from acrylic bone cement for a period of 3–27 days depending on the concentration of antibiotic. Higher doses of antibiotic concentration resulted in greater elution of the antibiotic. The eluate was found to be biologically active against S. aureus ATCC 2593 (MSSA), P. aeruginosa ATCC 27853, E. coli ATCC 25922 and K. pneumoniae ATCC 700603 (ESBL) for a period of 3 weeks.

Conclusions

The elution of meropenem is in keeping with typical antibiotic-loaded acrylic bone cement elution characteristics. The use of high-dose meropenem-loaded acrylic bone cement seems to be an attractive option for treatment of resistant Gram-negative orthopaedic infections but needs to be tested in vivo.     

Does Vitamin E-blended UHMWPE Prevent Biofilm Formation?

Background

Biofilm-related periprosthetic infections are catastrophic to patients and clinicians. Data suggest the addition of vitamin E to UHMWPE may have the ability to reduce biofilm formation on the surface of UHMWPE; however, previous studies were performed using stagnant broth solutions that may not have simulated a physiologic environment. In addition, the observed differences in levels of bacterial attachment, though statistically significant, may not be clinically significant.

Questions/purposes

We blended vitamin E with UHMWPE material and tested it for the ability to resist biofilm formation using a clinical isolate of methicillin-resistant Staphylococcus aureus (MRSA). Three additional materials were tested for comparison: highly crosslinked UHMWPE, compression-molded UHMWPE, and polyetheretherketone. We also determined whether the surface roughness of these materials facilitated biofilm formation.

Methods

Using a flow cell system, samples of each material type were placed into separate chambers. A 10% solution of brain-heart infusion broth containing 10⁵ colony-forming units (CFUs)/mL was flowed through the flow cell over 48 hours. The number of bacteria that adhered to the surface was quantified and biofilm formation was observed qualitatively using scanning electron microscopy. Optical profilometry was used to determine the surface roughness of each material type.

Results

Vitamin E-blended UHMWPE did not reduce biofilm formation of a clinically relevant strain of MRSA compared to materials that did not have vitamin E. More specifically, vitamin E-blended materials had similar amounts of biofilm formation (~ 8 log₁₀ CFUs/cm²) compared to materials not containing vitamin E (~ 8.1 log₁₀ CFUs/cm²) (p > 0.4). The roughness of vitamin E-blended material surfaces (mean ± SD: 1.85 ± 0.46 µm) compared to that of materials without vitamin E (2.06 ± 1.24 µm) did not appear to influence biofilm formation.

Conclusions

Under physiologically relevant conditions, vitamin E-blended UHMWPE did not have the ability to reduce the formation of biofilms by MRSA.

Clinical Relevance

These data indicate that the addition of vitamin E to UHMWPE may not reduce clinically relevant rates of biofilm-related periprosthetic infections of total joint arthroplasty devices.     

Rifamycin Derivatives Are Effective Against Staphylococcal Biofilms In Vitro and Elutable From PMMA

Background

Local antimicrobial delivery through polymethylmethacrylate beads (PMMA), commonly vancomycin, is used for the treatment of contaminated open fractures but has limited activity against Staphylococcus aureus biofilms, which occur commonly in such fractures. Rifamycins have activity against biofilms and are an effective treatment for osteoarticular infections involving staphylococcal biofilms, but there are limited studies evaluating the activity of rifamycin derivatives, other than rifampin, against biofilms of S. aureus and evaluating incorporation of these drugs into PMMA for treatment of contaminated open fractures.

Questions/purposes

(1) Are rifamycin derivatives effective against established biofilms of clinical isolates of S. aureus? (2) Can PMMA be used as a carrier for rifamycin derivatives?

Methods

Biofilms were developed and evaluated for susceptibility to a panel of antimicrobials in vitro using the minimum biofilm eradication concentration high-throughput model. Susceptibility was assessed by measuring bacterial recovery at 6 and 24 hours after antimicrobial treatment. Activity of rifamycin derivatives against intracellular bacteria was also evaluated using a gentamicin protection assay. Evaluation of PMMA as a carrier for rifampin and rifamycin derivatives was determined by assessing the curing time subsequent to loading of rifamycins and characterizing the release kinetics of rifamycins at daily intervals for 14 days from PMMA by performing bioassays.

Results

Rifamycin derivatives between 1 and 8 µg/mL reduced bacteria within biofilms 5- to 9-logs and prevented bacterial recovery up to 24 hours post-treatment, indicating near to complete eradication of biofilms. Rifamycin derivatives at 32 µg/mL had activity against intracellular staphylococci, significantly reducing the number of internalized bacteria with limited effects on osteoblast viability. Rifampin was the only rifamycin observed to have a suitable release profile from PMMA, releasing 49% of the total antibiotic and maintaining a sustained released profile up to 14 days at a mean 28 ± 6 μg/mL.

Conclusions

Rifampin can be incorporated into PMMA and eluted at concentrations effective against biofilms and intracellular staphylococci.

Clinical Relevance

Our in vitro findings suggest that local delivery of rifampin may be an effective strategy for the prevention and/or treatment of open fractures where S. aureus biofilms might develop. Clinical studies are needed to characterize what role this approach might have in the prevention and treatment of infections involving biofilms.

Electronic supplementary material

The online version of this article (doi:10.1007/s11999-015-4300-3) contains supplementary material, which is available to authorized users.     

Can Near-infrared Spectroscopy Detect and Differentiate Implant-associated Biofilms?

Background

Established bacterial diagnostic techniques for orthopaedic-related infections rely on a combination of imperfect tests that often can lead to negative culture results. Spectroscopy is a tool that potentially could aid in rapid detection and differentiation of bacteria in implant-associated infections.

Questions/purposes

We asked: (1) Can principal component analysis explain variation in spectral curves for biofilm obtained from Staphylococcus aureus, Staphylococcus epidermidis, and Pseudomonas aeruginosa? (2) What is the accuracy of Fourier transformed-near infrared (FT-NIR)/multivariate data analysis in identifying the specific species associated with biofilm?

Methods

Three clinical isolates, S aureus, S epidermidis, and P aeruginosa were cultured to create biofilm on surgical grade stainless steel. At least 52 samples were analyzed per group using a FT-NIR spectrometer. Multivariate and principal component analyses were performed on the spectral data to allow for modeling and identification of the bacterial species.

Results

Spectral analysis was able to correctly identify 86% (37/43) of S aureus, 89% (16/18) of S epidermidis, and 70% (28/40) of P aeruginosa samples with minimal error. Overall, models developed using spectral data preprocessed using a combination of standard normal variant and first-derivative transformations performed much better than models developed with the raw spectral data in discriminating between the three classes of bacteria because of its low Type 1 error and large intermodel distinction.

Conclusions

The use of spectroscopic methods to identify and classify bacterial biofilms on orthopaedic implant material is possible and improves with advanced modeling that can be obtained rapidly with little error. The sensitivity for identification was 97% for S aureus (95% CI, 88-99%), 100% for S epidermidis (95% CI, 95–100%), and 77% for P aeruginosa (95% CI, 65–86%). The specificity of the S aureus was 86% (95% CI, 3–93%), S epidermidis was 89% (95% CI, 67–97%), and P aeruginosa was 70% (95% CI, 55–82%).

Clinical Relevance

This technique of spectral data acquisition and advanced modeling should continue to be explored as a method for bacterial biofilm identification. A spectral databank of bacterial and potentially contaminating tissues should be acquired initially through an in vivo animal model and quickly transition to explanted devices and the clinical arena.     

Biofilm Growth Has a Threshold Response to Glucose in Vitro

Background

Hyperglycemia is a risk factor for nosocomial infections with known host effects. Increased glucose levels also increase pathogenicity of infecting microbes through greater biofilm formation. The dose response of biofilm formation to glucose concentration is not known.

Questions/purposes

We asked: What is the relationship between the amount of biofilm formed by Staphylococcus epidermidis and Staphylococcus aureus and change in glucose concentration in the clinically important range of 20 to 300 mg/dL?

Methods

This experiment studied biofilm formation by S epidermidis and S aureus in Lennox broth medium supplemented with increasing glucose concentrations from 0 to 320 mg/dL in 20 mg/dL intervals. Biofilm was grown for 24 hours for S epidermidis and 48 hours for S aureus. Biofilms were heat fixed, stained with 0.1% crystal violet, and washed with deionized water. The dye was then extracted with 30% acetic acid. Visual light absorption of the extracted crystal violet dye at 600 nm was used to quantify the biofilm biomass. The effect of glucose concentration on the amount of biofilm mass produced was analyzed using ANOVA and Tukey’s test.

Results

Biofilm mass was increased at higher glucose concentration for both species with a threshold response at 0 to 20 and 160 to 200 mg/dL for S epidermidis and 200 to 240 mg/dL for S aureus.

Conclusions

Increased biofilm growth by S aureus and S epidermidis has a threshold response at clinically important concentrations.

Clinical Relevance

Postoperative hyperglycemia may increase the risk for implant infection through increased pathogenicity of intraoperative wound contaminants in addition to compromising host immune status.     

Twenty Percent of Patients May Remain Colonized With Methicillin-resistant Staphylococcus aureus Despite a Decolonization Protocol in Patients Undergoing Elective Total Joint Arthroplasty

Background

Staphylococcus aureus is the most commonly isolated organism in periprosthetic joint infection (PJI). Resistant strains such as methicillin-resistant S aureus (MRSA) are on the rise, and many programs have instituted decolonization protocols. There are limited data on the success of S aureus nasal decolonization programs and their impact on PJI.

Questions/purposes

The purposes of this study were to (1) determine the proportion of patients successfully decolonized using a 2-week protocol; (2) compare infection risks between our surveillance and decolonization protocol group against a historical control cohort to evaluate changes in proportions of S aureus infections; and (3) assess infection risk based on carrier type, comparing S aureus carriers with noncarrier controls.

Methods

We retrospectively evaluated a group of 3434 patients who underwent elective primary and revision hip and knee arthroplasty over a 2-year period; each patient in the treatment group underwent a surveillance protocol, and a therapeutic regimen of mupurocin and chlorhexidine was instituted when colonization criteria were met. A 2009 to 2010 comparative historical cohort was chosen as the control group. We compared risks of infection between our treatment group and the historical control cohort. Furthermore, in patients who developed surgical site infections (SSIs), we compared the proportions of each S aureus type between the two cohorts. Finally, we compared infection rates based on carrier status. Surveillance for infection was carried out by the hospital infection control coordinator using the Centers for Disease Control and Prevention (CDC) criteria. During the time period of this study, the CDC defined hospital-acquired infection related to a surgical procedure as any infection diagnosed within 1 year of the procedure. With the numbers available, we had 41% power to detect a difference of 0.3% in infection rate between the treatment and control groups. To achieve 80% power, a total of 72,033 patients would be needed.

Results

Despite the protocol, 22% (26 of 121) of patients remained colonized with MRSA. With the numbers available, there were no differences in infection risk between the protocoled group (27 of 3434 [0.8%]) and the historical control group (33 of 3080 [1.1%]; relative risk [RR], 0.74; 95% confidence interval [CI], 0.44–1.22; p = 0.28). In terms of infecting organism in those who developed SSI, S aureus risk decreased slightly (treatment: 13 of 3434 patients [0.38%]; control: 21 of 3080 patients [0.68%]; RR, 0.56; CI, 0.28–1.11; p = 0.11). Within the protocoled group, carriers had a slightly higher risk of developing SSI (carrier: seven of 644 [1.1%]; noncarrier: 18 of 2763 [0.65%]; RR, 1.77; CI, 0.74–4.24; p = 0.20).

Conclusions

The screening and decolonization protocol enabled a substantial reduction in nasal carriage of MRSA, but some patients remained colonized. However, our nasal decolonization protocol before elective total joint arthroplasty did not demonstrate a decrease in the proportion of patients developing SSI. Future meta-analyses and systematic reviews will be needed to pool the results of studies like these to ascertain whether small improvements in infection risk are achieved by protocols like ours and to determine whether any such improvements warrant the costs and potential risks of surveillance and intervention.

Level of Evidence

Level III, therapeutic study.     

Underestimation of Bone Loss of the Spine With Posterior-Anterior Dual-Energy X-Ray Absorptiometry in Patients With Spinal Cord Injury

Background:

Bone mineral density (BMD) of the lumbar spine (L-spine) has been reported to be normal by routine posterior-anterior (PA) bone density imaging in patients with chronic spinal cord injury (SCI).

Objective:

To determine BMD of the L-spine by PA and lateral (LAT) dual-energy radiographic absorptiometry (DXA) in patients with chronic SCI.

Design:

Prospective study.

Setting:

Veterans Affairs Medical Center and a private rehabilitation facility.

Methods:

Measurements of the PA and LAT L-spine and hip were performed in 15 patients with SCI: 9 with tetraplegia and 6 with paraplegia. The DXA (GE Lunar Advance DXA) images were obtained using standard software. Results are reported as mean ± SD.

Results:

The mean age was 35 ± 15 years (range  =  20–62 years), and the duration of injury was 57 ± 74 months (range  =  3–240 months). T- and Z-scores were lower for the LAT L-spine than those for PA L-spine (T-scores L2: −0.7 ± 1.2 vs 0.0 ± 1.4, P < 0.01; L3: −0.9 ± 1.6 vs 0.3 ± 1.3, P < 0.002; L2-L3: −0.8 ± 1.3 vs 0.2 ± 1.3, P < 0.001; Z-scores L2: −0.3 ± 1.1 vs 0.2 ± 1.2, P < 0.05; L3: −0.6 ± 1.3 vs 0.5 ± 1.3, P < 0.01; L2-L3: −0.4 ± 1.1 vs 0.4 ± 1.2, P < 0.005). The T- and Z-scores for the total hip (−1.1 ± 1.0 and −1.0 ± 1.0, respectively) and L2-L3 LAT L-spine demonstrated remarkable similarity, whereas the L2-L3 PA L-spine scores were not reduced. Bone mineral density of the LAT L-spine, but not the PA L-spine, was significantly reduced with increasing duration of injury.

Conclusions:

Individuals with SCI may have bone loss of the L-spine that is evident on LAT DXA that may be misdiagnosed by PA DXA, underestimating the potential risk of fracture.     

Effects of underwater treadmill training on leg strength,balance, and walking performance in adults with incomplete spinal cord injury

Objective

To document the effects of underwater treadmill training (UTT) on leg strength, balance, and walking performance in adults with incomplete spinal cord injury (iSCI).

Design

Pre-test and post-test design.

Setting

Exercise physiology laboratory.

Participants

Adult volunteers with iSCI (n = 11).

Intervention

Participants completed 8 weeks (3 × /week) of UTT. Each training session consisted of three walks performed at a personalized speed, with adequate rest between walks. Body weight support remained constant for each participant and ranged from 29 to 47% of land body weight. Increases in walking speed and duration were staggered and imposed in a gradual and systematic fashion.

Outcome measures

Lower-extremity strength (LS), balance (BL), preferred and rapid walking speeds (PWS and RWS), 6-minute walk distance (6MWD), and daily step activity (DSA).

Results

Significant (P < 0.05) increases were observed in LS (13.1 ± 3.1 to 20.6 ± 5.1 N·kg⁻¹), BL (23 ± 11 to 32 ± 13), PWS (0.41 ± 0.27 to 0.55 ± 0.28 m·s⁻¹), RWS (0.44 ± 0.31 to 0.71 ± 0.40 m·s⁻¹), 6MWD (97 ± 80 to 177 ± 122 m), and DSA (593 ± 782 to 1310 ± 1258 steps) following UTT.

Conclusion

Physical function and walking ability were improved in adults with iSCI following a structured program of UTT featuring individualized levels of body weight support and carefully staged increases in speed and duration. From a clinical perspective, these findings highlight the potential of UTT in persons with physical disabilities and diseases that would benefit from weight-supported exercise.     

How Are Dysplastic Hips Different? A Three-dimensional CT Study

Background

Surgical correction of acetabular dysplasia can postpone or prevent joint degeneration. The specific abnormalities that make up the dysplastic hip are controversial.

Questions/purposes

(1) What are the relative size, shape, and orientations of the typical nondysplastic hip? (2) How do these variables differ in the developmentally dysplastic hip? (3) Are there version differences between the acetabuli of dysplastic and nondysplastic hips? (4) Are there pairs of variables in which the change in one is always accompanied by a change in the other for both nondysplastic and dysplastic acetabuli?

Methods

Of 117 consecutive three-dimensional (3-D) CT scans performed for hip dysplasia between March 1988 and October 1995, 48 met criteria of developmentally dysplastic hips by plain radiography. These were retrospectively compared with 55 pelvic 3-D CT scans culled from 81 consecutive scans performed for reasons other than hip dysplasia (ie, hip pain, trauma, infection) that did not affect the hip or pelvic landmarks. The 3-D reconstructions were orientated anatomically for standardization of the measurements to be compared. Representative 3-D volumes of the acetabular space were constructed from which we could measure anatomic positions and dimensional information. One author performed all image orientation and measurements.

Results

Nondysplastic acetabuli are essentially hemispheric with height equal to width and twice the depth. The dysplastic acetabuli were elongated in females (52.4 ± 6.2 mm for dysplastic versus 46.5 ± 4.6 mm for nondysplastic (mean difference, 5.0; 95% confidence interval [CI], 1.9–8.0; p = 0.002) and shallower in both females (18.7 ± 4.9 mm for dysplastic versus 23.6 ± 4.0 mm for nondysplastic; mean difference, 6.5; 95% CI, 4.4–8.5; p < 0.0001) and males (21.1 ± 4.8 mm for dysplastic versus 25.0 ± 4.3 mm for nondysplastic, mean difference, 5.3; 95% CI, 2.6–8.1; p = 0.0002); width was similar to that of nondysplastic hips. Acetabular openings were slightly more vertical than nondysplastic hips in females (5°; 95% CI, 1.9–8.1; p = 0.002) but not in male subjects. The dysplastic acetabuli were smaller in volume (18% in females, p = 0.002, and 19% in males, p = 0.0012) and had less space occupied by the femoral head compared with nondysplastic hips (p < 0.0001 for females, p < 0.0001 for males). Dysplastic hip midacetabulum was 4° more anteverted in females (95% CI, 0.5–6.8; p = 0.022) but not for males (p = 0.538). The upper dysplastic acetabulum was more retroverted in females and males (10.2°; 95% CI, 5.5–15; p < 0.0001, and 7.0°; 95% CI, 0.6–13.4; p = 0.032, respectively). Acetabular volumes in nondysplastic and dysplastic hips were related to acetabular width but not to length.

Conclusions

Developmentally dysplastic acetabuli are not deficient in merely a single dimension but are globally deficient. The subluxated femoral head lies in the elongated and retroverted superior acetabulum, which becomes progressively shallower as the acetabulum increases in length. Focally deficient anterior or posterior femoral head coverage is uncommon. Current procedures that redirect the acetabulum, no matter how technically successful, cannot fully compensate for the incongruence of a spherical femoral head within a shallow and elongated acetabulum unless corrected at an early age when acetabular remodeling is possible. Early detection and treatment of acetabular dysplasia should be emphasized.

Level of Evidence

Level III, prognostic study.     

Botulinum Toxin-induced Muscle Paralysis Inhibits Heterotopic Bone Formation

Background

Short-term muscle atrophy induced by botulinum toxin A (BTxA) has been observed to impair osteogenesis in a rat closed femur fracture model. However, it is unclear whether the underlying mechanism is a direct effect of BTxA on muscle-bone interactions or an indirect effect that is driven by skeletal unloading. Because skeletal trauma in the closed fracture model also leads to disuse atrophy, we sought to mitigate this confounding variable by examining BTxA effects on muscle-bone interactions in two complementary in vivo models in which osteogenesis is induced in the absence of skeletal unloading. The overall aim of this study was to identify a potential strategy to inhibit pathological bone formation and heterotopic ossification (HO).

Questions/purposes

(1) Does muscle paralysis inhibit periosteal osteogenesis induced by a transcortical defect? (2) Does muscle paralysis inhibit heterotopic bone formation stimulated by intramuscular bone morphogenetic protein (BMP) injection?

Methods

Focal osteogenesis was induced in the right hindlimb of mice through surgical initiation of a small transcortical defect in the tibia (fracture callus; n = 7/group) or intramuscular injection of BMP-2 (HO lesion; n = 6/group), both in the presence/absence of adjacent calf paralysis. High-resolution micro-CT images were obtained in all experimental groups 21 days postinduction and total volume (ie, perimeter of periosteal callus or HO lesion) and bone volume (calcified tissue within the total volume) were quantified as primary outcome measures. Finally, these outcome measures were compared to determine the effect of muscle paralysis on inhibition of local osteogenesis in both studies.

Results

After a transcortical defect, BTxA-treated mice showed profound inhibition of osteogenesis in the periosteal fracture callus 21 days postsurgery compared with saline-treated mice (total volume: 0.08 ± 0.06 versus 0.42 ± 0.11 mm³, p < 0.001; bone volume: 0.07 ± 0.05 versus 0.32 ± 0.07 mm³, p < 0.001). Similarly, BMP-2-induced HO formation was inhibited by adjacent muscle paralysis at the same time point (total volume: 1.42 ± 0.31 versus 3.42 ± 2.11 mm³, p = 0.034; bone volume: 0.68 ± 0.18 versus 1.36 ± 0.79 mm³, p = 0.045).

Conclusions

Our data indicate that BTxA-induced neuromuscular inhibition mitigated osteogenesis associated with both a transcortical defect and BMP-2-induced HO.

Clinical Relevance

Focal neuromuscular inhibition represents a promising new approach that may lead to a new clinical intervention to mitigate trauma-induced HO, a healthcare challenge that is severely debilitating for civilian and war-wounded populations, is costly to both the patient and the healthcare system, and currently lacks effective treatments.     

Addition of Vancomycin to Cefazolin Prophylaxis Is Associated With Acute Kidney Injury After Primary Joint Arthroplasty

Background

With increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in patients undergoing hip and knee arthroplasty, some have advocated a dual-antibiotic regimen including vancomycin as prophylaxis against surgical site infections. However, routine administration of vancomycin may result in impaired renal functions in susceptible patients.

Questions/purposes

The purpose of this study was to determine whether patients receiving antibiotic prophylaxis with cefazolin and vancomycin have a higher risk of postoperative acute kidney injury (AKI) compared with patients receiving cefazolin alone before elective primary hip and knee arthroplasty. We also aimed to compare severity and recovery of AKI in these two cohorts and to determine independent risk factors for AKI.

Methods

We retrospectively evaluated a series of 1828 patients undergoing primary hip and knee arthroplasty over a 2-year period who received either cefazolin (n = 500) or cefazolin and vancomycin (n = 1328) as perioperative antibiotic prophylaxis. During the study period, a perceived high prevalence of MRSA infections at our institution led some surgeons to add vancomycin to the prophylactic antibiotic regimen. The patient characteristics, case mix, and preoperative renal function and baseline creatinine clearance were similar between the two groups. We defined AKI according to the published Acute Kidney Injury Network (AKIN) criteria, and the risk of AKI in both groups was compared. We also compared the proportions of patients by AKIN severity stage and assessed recovery as defined by creatinine levels showing kidney function reaching 50% baseline. The American Society of Anesthesiologists (ASA) classification, preoperative chronic kidney disease, intraoperative fluid requirements, and estimated blood loss were recorded. We analyzed the data using a multivariate logistic regression model to identify potential independent risk factors, including dual antibiotic therapy.

Results

Patients receiving dual antibiotics were more likely to develop AKI compared with those receiving cefazolin alone (13% versus 8%, p = 0.002). Dual-antibiotic prophylaxis also was associated with greater severity; patients in the dual antibiotic group had higher rates of Grade II and III acute kidney injury (3% versus 0%, p = 0.003). There was no difference in the rate of return to baseline renal function (2 ± 1.4 days versus 3 ± 3.4 days; mean difference, 0.5 days; 95% confidence interval [CI], −0.2 to 1.2 days; p = 0.155). Controlling for confounding variables, dual antibiotic prophylaxis (adjusted odds ratio [OR], 1.82; 95% CI, 1.25–2.64; p = 0.002), ASA class (adjusted OR, 1.64; 95% CI, 1.24–2.17; p = 0.001), and preoperative kidney disease (adjusted OR, 1.81; 95% CI, 1.30–2.52; p = 0.001) were independent risk factors for AKI after primary total joint arthroplasty.

Conclusions

Without a clear advantage in reducing surgical site infections, the utility and safety of routine addition of vancomycin to the prophylactic regimen in all patients undergoing primary hip and knee arthroplasty should be avoided. Further prospective studies should look at the efficacy of preoperative MRSA screening, decolonization, and selective use of vancomycin in high-risk patients.

Level of Evidence

Level III, therapeutic study.     

Sex Differences in Arm Muscle Fatigability With Cognitive Demand in Older Adults

Background

Muscle fatigability can increase when a stressful, cognitively demanding task is imposed during a low-force fatiguing contraction with the arm muscles, especially in women. Whether this occurs among older adults (> 60 years) is currently unknown.

Questions/purposes

We aimed to determine if higher cognitive demands, stratified by sex, increased fatigability in older adults (> 60 years). Secondarily, we assessed if varying cognitive demand resulted in decreased steadiness and was explained by anxiety or cortisol levels.

Methods

Seventeen older women (70 ± 6 years) and 13 older men (71 ± 5 years) performed a sustained, isometric, fatiguing contraction at 20% of maximal voluntary contraction until task failure during three sessions: high cognitive demand (high CD = mental subtraction by 13); low cognitive demand (low CD = mental subtraction by 1); and control (no subtraction).

Results

Fatigability was greater when high and low CD were performed during the fatiguing contraction for the women but not for the men. In women, time to failure with high CD was 16 ± 8 minutes and with low CD was 17 ± 4 minutes, both of which were shorter than time to failure in control contractions (21 ± 7 minutes; high CD mean difference: 5 minutes [95% confidence interval {CI}, 0.78–9.89], p = 0.02; low CD mean difference: 4 minutes [95% CI, 0.57–7.31], p = 0.03). However, in men, no differences were detected in time to failure with cognitive demand (control: 13 ± 5 minutes; high CD mean difference: −0.09 minutes [95% CI, −2.8 to 2.7], p = 1.00; low CD mean difference: 0.75 minutes [95% CI, −1.1 to 2.6], p = 0.85). Steadiness decreased (force fluctuations increased) more during high CD than control. Elevated anxiety, mean arterial pressure, and salivary cortisol levels in both men and women did not explain the greater fatigability during high CD.

Conclusions

Older women but not men showed marked increases in fatigability when low or high CD was imposed during sustained static contractions with the elbow flexor muscles and contrasts with previous findings for the lower limb. Steadiness decreased in both sexes when high CD was imposed.

Clinical Relevance

Older women are susceptible to greater fatigability of the upper limb with heightened mental activity during sustained postural contractions, which are the foundation of many work-related tasks.     

Can High-friction Intraannular Material Increase Screw Pullout Strength in Osteoporotic Bone?

Background

Osteoporotic bone brings unique challenges to orthopaedic surgery, including a higher likelihood of problematic screw stripping in cancellous bone. Currently, there are limited options to satisfactorily repair stripped screws. Additionally, nonstripped screws hold with less purchase in osteoporotic bone.

Questions/purposes

This study attempts to answer the following questions: (1) Does high-friction intraannular (HFIA) augmentation increase pullout strength in osteoporotic and in severely osteoporotic bone; and (2) can HFIA repair stripped bone thread in osteoporotic and severely osteoporotic bone?

Methods

We measured screw pullout strength using a synthetic bone model in three groups: (1) predrilled nonstripped control holes as controls; (2) predrilled nonstripped augmented with HFIA; and (3) predrilled stripped holes repaired with HFIA. We tested this in osteoporotic and severely osteoporotic synthetic bone for a total of six test groups. We measured screw pullout force using an electromechanical tensile-testing machine comparing pullout force between the test groups and controls.

Results

HFIA augmentation did not increase pullout force compared with the control group in the osteoporotic bone model (489 ± 175 versus 607 ± 76, respectively; effect size = 0.94 [95% confidence interval {CI}, −1.75 to 0.08], p = 0.06). However, in severely osteoporotic cancellous bone that was augmented, the HFIA material generated more pullout force than the control (51 ± 18 versus 35 ± 16, respectively; effect size = 0.94 [95% CI, −0.02 to 1.82], p = 0.05). In stripped holes, HFIA partially restored pullout strength but remained weaker than controls in both osteoporotic and severely osteoporotic bone models (osteoporotic: 320 ± 59 versus 607 ± 76, respectively; effect size = −4.28 [95% CI, −5.57 to −2.51], p < 0.001; severely osteoporotic: 21 ± 8 versus 35 ± 16, respectively; effect size = −1.13 [95% CI, −2.0 to 0.12], p = 0.027).

Conclusions

HFIA effectively augmented severely osteoporotic bone for screw purchase, but this effect was not seen for osteoporotic bone. In a model simulating both osteoporotic and severely osteoporotic bone, we found that HFIA can be used to repair stripped screw holes, but the resulting construct remains weaker than nonstripped controls.

Clinical Relevance

The HFIA material looks promising as a potential solution to stripped screws in osteoporotic bone. However, this material has yet to be tested in human bone. Furthermore, the fine mesh material could be damaged by autoclaving and could break off in vivo causing unknown tissue reactions. We recommend additional testing in a living animal model to better understand how living bone will react to the HFIA material.     

A Study of Microbial Colonisation of Orthopaedic Tourniquets

INTRODUCTION

Tourniquets are employed widely in orthopaedic surgery. The use of the same tourniquet on a repetitive basis without a standard protocol for cleaning may be a source of cross-infection. This study examines the contamination of the tourniquets in our institution.

MATERIALS AND METHODS

Agar plates were used to take samples from 20 tourniquets employed in orthopaedic procedures. Four sites on each tourniquet were cultured and incubated at 37°C for 48 h.

RESULTS

All sampled tourniquets were contaminated with colony counts varying from 9 to > 385. Coagulase-negative Staphylococcus spp. were the most commonly grown organisms from the tourniquets (96%).Some tourniquets had growths of important pathogens including methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas spp., and S. aureus. On cleaning five tourniquets with Clinell (detergent and disinfectant) wipes (GAMA Healthcare Ltd, London, UK), there was a 99.2% reduction in contamination of the tourniquets 5 min after cleaning.

CONCLUSIONS

In addition to the manufacturers'' guidelines, we recommend the cleaning of tourniquets with a disinfectant wipe before every case.     

Assessment of passive knee stiffness and viscosity in individuals with spinal cord injury using pendulum test

Objective

Stiffness and viscosity represent passive resistances to joint motion related with the structural properties of the joint tissue and of the musculotendinous complex. Both parameters can be affected in patients with spinal cord injury (SCI). The purpose of this study was to measure passive knee stiffness and viscosity in patients with SCI with paraplegia and healthy subjects using Wartenberg pendulum test.

Design

Non-experimental, cross-sectional, case–control design.

Setting

An outpatient physical therapy clinic, University of social welfare and Rehabilitation Science, Iran.

Patients

A sample of convenience sample of 30 subjects participated in the study. Subjects were categorized into two groups: individuals with paraplegic SCI (n = 15, age: 34.60 ± 9.18 years) and 15 able-bodied individuals as control group (n = 15, age: 30.66 ± 11.13 years).

Interventions

Not applicable.

Main measures

Passive pendulum test of Wartenberg was used to measure passive viscous-elastic parameters of the knee (stiffness, viscosity) in all subjects.

Results

Statistical analysis (independent t-test) revealed significant difference in the joint stiffness between healthy subjects and those with paraplegic SCI (P = 0.01). However, no significant difference was found in the viscosity between two groups (P = 0.17). Except for first peak flexion angle, all other displacement kinematic parameters exhibited no statistically significant difference between normal subjects and subjects with SCI.

Conclusions

Patients with SCI have significantly greater joint stiffness compared to able-bodied subjects.