Corridor-diameter-dependent angular tolerance for safe transiliosacral screw placement: an anatomic study of 433 pelves.

BACKGROUND: The purpose of this study was to determine the angular tolerance of the S1 and S2 segments to accommodate a transiliosacral screw across both sacroiliac joints. HYPOTHESIS: We hypothesized that the angular tolerance for transiliosacral screw placement would be more constrained than the angular tolerance for iliosacral fixation in pelves where a safe osseous corridor was measured. MATERIALS AND METHODS: The cortical boundaries of the S1 and S2 sacral segments in 433 pelvic CTs were digitally mapped. A straight-line path was placed within each osseous corridor and extended across both SI joints past the outer iliac cortices. The diameter of the path was increased until it breached the cortex, geometrically determining maximum diameter (Dmax). Angular tolerance for screw placement was calculated with trigonometric analysis of the Dmax value of the corridor, and the average distance from the termination of the osseous corridor to the site of percutaneous insertion. Gender, age, and BMI were evaluated as independent predictors using binomial logistic regression. RESULTS: The transiliosacral angular tolerance for the S1 and S2 osseous corridors was 1.53 ± 0.57 degrees and 1.02 ± 0.33 degrees, respectively. 68.9% of S1 corridors and 81.1% of S2 corridors had a safe zone (corridor diameter ≥ 10 mm) for transiliosacral placement, 48.3% of the pelves had a safe zone for both corridors, while 5.1% had no safe zones. Females had a less frequent Dmax ≥ 10 mm at S1, 52% vs 67% (p = 0.001), and at S2, 64% vs 86% (p < 0.001). DISCUSSION: In conclusion, the angular tolerance of 1.53 and 1.03 degrees for the S1 and S2 segments, respectively, creating a narrow interval for safe passage of the trans-iliac and trans-sacral, with approximately 31.1% of patients not having a viable corridor for screw passage. A correlation exist between S1 and S2 corridors with Dmax ≥ 10 mm and the resulting increase in angular tolerance for safe passage of a transilioscral screw. LEVEL OF EVIDENCE IV: Level Retrospective Cohort.

Immediate weight bearing as tolerated (WBAT) correlates with a decreased length of stay post intramedullary fixation for subtrochanteric fractures: a multicenter retrospective cohort study.

BACKGROUND: Subtrochanteric femur fractures associate with a relatively high complication rate and are traditionally treated operatively with a period of limited weight bearing. Transitioning from extramedullary to intramedullary implants, there are increasing biomechanical and clinical data to support early weight bearing. This multicenter retrospective study examines the effect of postoperative weight bearing as tolerated (WBAT) for subtrochanteric femur fractures. We hypothesize that WBAT will result in a decreased length of stay (LOS) without increasing the incidence of re-operation. METHODS: This study assesses total LOS and postoperative LOS after intramedullary fixation for subtrochanteric fractures between postoperative weight bearing protocols across 6 level I trauma centers (n = 441). Analysis techniques consisted of multivariable linear regression and nonparametric comparative tests. Additional subanalyses were performed, targeting mechanism of injury (MOI), Winquist-Hansen fracture comminution, 20-year age strata, and injury severity score (ISS). RESULTS: Total LOS was shorter in WBAT protocol within the overall sample (7.4 vs 9.7 days; p < 0.01). Rates of re-operation were similar between the two groups (10.6% vs 10.5%; p = 0.99). Stratified analysis identified patients between ages 41-80, WH comminution 2-3, high MOI, and ISS between 6-15 and 21-25 to demonstrate a significant reduction in LOS as a response to WBAT. CONCLUSION: An immediate postoperative weight bearing as tolerated protocol in patients with subtrochanteric fractures reduced length of hospital stay with no significant difference in reoperation and complication rates. If no contraindication exists, immediate weight bearing as tolerated should be considered for patients with subtrochanteric femur fractures treated with statically locked intramedullary nails. LEVEL OF EVIDENCE: Therapeutic Level III.

Multicenter experience using simeprevir and sofosbuvir with or without ribavirin to treat hepatitis C genotype 1 in patients with cirrhosis.

UNLABELLED: Interferon (IFN)-free regimens are needed to treat hepatitis C virus (HCV) infection. Combined simeprevir (SMV) and sofosbuvir (SOF) with or without ribavirin (RBV) results in high sustained virological response (SVR) rates along with minimal adverse events (AEs) in patients with hepatitis C genotype 1 (HCV GT1). The aim of this study was to report on the virological response, safety, and tolerability of SOF and SMV with or without RBV in compensated and decompensated patients with cirrhosis with HCV GT1 infection. Patients treated with standardized clinical protocol utilizing SMV+SOF with or without RBV at three transplant centers were retrospectively reviewed. A total of 119 patients (61% male, 87% white, 69% subtype 1a, 30% Child-Pugh-Turcott [CPT]-B liver cirrhosis [LC], and 82% were treatment experienced) received treatment and were followed for a median of 38 weeks (range, 12-58). Sustained virological response (SVR) at week 12 (SVR12) was achieved in 78% (92 of 118) of patients (95% confidence interval: 69-85). Lower pretreatment Model for End Stage Liver Disease (MELD) score was a predictor of SVR12 (P = 0.018). Baseline viral load, previous treatment status, RBV use, or GT1 subtype did not impact SVR 12. The majority of patients with SVR12 showed stability or improvement in MELD score. Treatment was very well tolerated with mild degrees of AEs. CONCLUSIONS: The regimen of SMV+SOF with or without RBV for 12 weeks was very well tolerated and resulted in high SVR12 rates (78%) in HCV GT1 patients with LC. SVR12 was inversely related to pretreatment MELD. SVR12 had favorable short-term impact on MELD score. Long-term impact on disease stability is yet to be determined. Longer treatment duration or the use of different regimen may still be needed in this population.

Correction: Biophysical separation of Staphylococcus epidermidis strains based on antibiotic resistance.

Correction for 'Biophysical separation of Staphylococcus epidermidis strains based on antibiotic resistance' by Paul V. Jones et al., Analyst, 2015, 140, 5152-5161.

Infectious complications associated with the use of temporary prostatic urethral stents in patients with benign prostatic hyperplasia.

INTRODUCTION: To examine the infectious outcomes after the insertion of the temporary prostatic urethral stent (TPUS) in benign prostatic hyperplasia (BPH) patients. MATERIAL AND METHODS: Between November 2007 and September 2012, ninety TPUS were used in 33 patients with BPH at our institution. All patients had negative urine cultures prior to the first stent insertion. TPUS were sent for cultures at time of removal or exchange. Stents were removed at the time of definite surgical intervention, at 4-6 weeks, or when patients elected another course of treatment. Colonization was defined as asymptomatic positive stent culture. Infection was defined as symptomatic positive stent culture requiring treatment. Infection and colonization rates are reported. Logistic regression was used to examine the predictors of infection at any point. Predictors examined were age, body mass index, history of prostate cancer, diabetes mellitus, hyperlipidemia, coronary artery disease, neurologic disorder, erectile dysfunction and the sequence of stent placement. RESULTS: The majority of the subjects, 72% (24/33) had 1-2 stents, 9.0% (3/33) had 3-4 stents, 6.0% (2/33) had 5-6 stents, and 12% (4/33) of patients had more than 6 stents. From the 69 available culture results, the symptomatic infection rate was 16% (11/69) (95% CI: 8.2%-26.7%). The colonization rate was 58% (40/69) (95% CI: 45.5%-69.7%). None of the predictors examined were identified as a predictor of infection. There was no colonization detected when stents were removed in the first 20 days. CONCLUSION: Infection rates with TPUS in BPH patients are acceptable and early removal may prevent colonization.

Tranexamic acid decreases blood loss in total shoulder arthroplasty and reverse total shoulder arthroplasty.

BACKGROUND: Efficacy of tranexamic acid (TXA) remains unproven in the setting of shoulder arthroplasty. The purpose of this study was to determine the effects of TXA on perioperative blood loss and drain output in patients undergoing primary total shoulder arthroplasty (TSA) and reverse total shoulder arthroplasty (RTSA). METHODS: We conducted a retrospective comparison of 77 TSAs and 94 RTSAs performed in 168 patients. TXA was administered intravenously in 35 TSA and 42 RTSA patients. Changes in hemoglobin (Hgb), hematocrit (Hct), drain output, and total blood loss were reviewed with univariate analysis and additional multivariate regression examining the cofactors of age, body mass index, American Society of Anesthesiologists status, and gender of each patient. RESULTS: Use of TXA in TSA led to a significant decrease in total blood loss (679 mL vs. 910 mL; P < .001), change in Hgb (1.8 mg/dL vs. 2.6 mg/dL; P < .001), and drop in Hct (5.2 vs. 7.0; P < .001). Similarly, RTSA also had significantly less total blood loss with the use of TXA (791 mL vs. 959 mL; P < .001), change in Hgb (2.3 mg/dL vs. 2.9 mg/dL; P < .001), and change in Hct (6.4 vs. 8.3; P < .001). TXA also significantly decreased drain output in both TSA (99 mL vs. 235 mL; P < .001) and RTSA (180 mL vs. 370 mL; P < .001). CONCLUSIONS: Use of TXA perioperatively among patients undergoing primary shoulder arthroplasty can decrease perioperative blood loss, change in Hgb and Hct, and postoperative drain output.

Biophysical separation of Staphylococcus epidermidis strains based on antibiotic resistance.

Electrophoretic and dielectrophoretic approaches to separations can provide unique capabilities. In the past, capillary and microchip-based approaches to electrophoresis have demonstrated extremely high-resolution separations. More recently, dielectrophoretic systems have shown excellent results for the separation of bioparticles. Here we demonstrate resolution of a difficult pair of targets: gentamicin resistant and susceptible strains of Staphylococcus epidermidis. This separation has significant potential implications for healthcare. This establishes a foundation for biophysical separations as a direct diagnostic tool, potentially improving nearly every figure of merit for diagnostics and antibiotic stewardship. The separations are performed on a modified gradient insulator-based dielectrophoresis (g-iDEP) system and demonstrate that the presence of antibiotic resistance enzymes (or secondary effects) produces a sufficient degree of electrophysical difference to allow separation. The differentiating factor is the ratio of electrophoretic to dielectrophoretic mobilities. This factor is 4.6 ± 0.6 × 10(9) V m(-2) for the resistant strain, versus 9.2 ± 0.4 × 10(9) V m(-2) for the susceptible strain. Using g-iDEP separation, this difference produces clear and easily discerned differentiation of the two strains.

Antimicrobial Release From Prefabricated Spacers Is Variable and the Dose Is Low.

BACKGROUND: High-dose antimicrobial-loaded bone cement (ALBC) is recommended to treat orthopaedic infections. Elution characteristics from prefabricated ALBC spacers and how they compare with hand-mixed ALBC are not well described. QUESTIONS/PURPOSES: (1) How does antimicrobial release from prefabricated spacers compare with release from hand-mixed ALBC over time? (2) Is antimicrobial release uniform across the surface of prefabricated ALBC spacers? (3) Do variations exist between different prefabricated spacer components? (4) Do textured surfaces release more antimicrobial than smooth surfaces? METHODS: Six prefabricated ALBC spacer components, two hip and four knee, and three hand-mixed ALBC formulations were studied in this comparative laboratory study. Gentamicin was eluted from 41 discrete sites over the surfaces of six spacer components and compared with elution from 15 ALBC specimens, five from each of three hand-mixed formulations. Elution was compared between spacer sites, components, and surface texture. Statistical analysis was performed by analysis of variance and Tukey's multiple-comparison test or t-test. RESULTS: Gentamicin release was highest in the first 24 hours for both prefabricated ALBC spacers and hand-mixed ALBC. Elution decreased over 7 days similarly for both. At Day 7, prefabricated ALBC spacers eluted more than hand-mixed 1 g ALBC (1 g ALBC: 1.49 ± 0.34, prefabricated: 3.59 ± 1.48, mean difference = 2.1 [0.2-4.0], p = 0.04) but eluted less than 5 g ALBC (9.21 ± 1.31, mean difference = -5.6 [-3.5 to -7.7], p < 0.001) and less than 10 g ALBC (35.8 ± 1.69, mean difference = -32.2 [-29.8 to -34.6], p < 0.001). Release varied from 2.7 to 9.9 µg/mm(2) over the surface of the spacers and from 3.5 to 5.5 µg/mm(2) between components with no component different than the others (Tukey). Release from textured surfaces was inconsistent. CONCLUSIONS: Antimicrobial release from prefabricated ALBC spacers is consistent with low-dose ALBC. Variation across the surface and between components is small compared with changes in antimicrobial load. CLINICAL RELEVANCE: Antimicrobial release from prefabricated ALBC spacers is consistent with local antimicrobial delivered from other low-dose ALBC formulations.

Liposomal Formulation Decreases Toxicity of Amphotericin B In Vitro and In Vivo.

BACKGROUND: Liposomal amphotericin B is locally delivered to treat fungal orthopaedic infections but little is known about local tissue toxicity, if any, that might be associated with local delivery. QUESTIONS/PURPOSES: (1) Is liposomal amphotericin B cytotoxic in vitro? (2) Is locally delivered liposomal amphotericin B toxic to tissue in vivo? METHODS: Mouse fibroblasts (BA LB/3T3 A31) and osteoblasts (MC3T3) were exposed to two formulations of amphotericin B (liposomal and deoxycholate) at concentrations of 0, 1, 5, 10, 100, 500, and 1000 µg/mL. Cell viability was determined by MTT assay after 1, 3, and 5 hours of exposure and a proliferation assay after 1, 4, and 7 days of exposure and then after 3 recovery days without drug. Tissue exposure occurred by local delivery of liposomal amphotericin B, 200 or 800 mg/batch antifungal-loaded bone cement (ALBC), or amphotericin B deoxycholate, 800 mg/batch ALBC in rat paraspinal muscles. White blood cell count (WBC) and serum amphotericin B levels were obtained on Days 1 and 3. Rats were euthanized at 2 and 4 weeks and semiqualitative histopathology was performed. RESULTS: Liposomal amphotericin B is cytotoxic in vitro but not toxic to tissues in vivo. All cells survived concentrations up to 1000 µg/mL for 5 hours, 100% ± 0%, but none survived ≥ 100 µg/mL for 7 days, 0% ± 0%. Fibrosis was seen adjacent to ALBC without inflammation or necrosis, indistinguishable from controls for both liposomal amphotericin B doses. Amphotericin B serum levels were all less than 1 µg/mL and WBC counts were all normal. CONCLUSIONS: In vitro cytotoxicity to liposomal amphotericin B occurred but no adverse tissue reaction was seen in vivo. CLINICAL RELEVANCE: Local delivery of liposomal amphotericin B in ALBC was well tolerated by mouse tissue; however, clinical studies are needed to confirm this finding in humans.

Local gentamicin delivery from resorbable viscous hydrogels is therapeutically effective.

BACKGROUND: Local delivery can achieve the high antimicrobial concentrations necessary to kill biofilm-related microbes. Degradation times for resorbable carriers are too long. Hydrogels (gels of hydrophilic polymer in water) can degrade faster but release antimicrobials too quickly. We previously developed hydrogels based on the copolymer poly(N-isopropylacrylamide-co-dimethyl-γ-butyrolactone acrylate-co-Jeffamine® M-1000 acrylamide) (PNDJ) with delivery times of several days with complete degradation in less than 6 weeks. QUESTIONS/PURPOSES: We asked: (1) What is the elution profile of gentamicin from PNDJ hydrogels? (2) Is gentamicin released from gentamicin-loaded PNDJ (G-PNDJ) hydrogel effective for treatment of orthopaedic infection? (3) Does local gentamicin delivery from G-PNDJ hydrogel cause renal dysfunction? METHODS: (1) Two formulations of G-PNDJ, lower dose (1.61 wt%) and higher dose (3.14 wt%), five samples each, were eluted in buffered saline under infinite sink conditions. (2) Infections were induced in 16 New Zealand White rabbits by inserting a Kirschner wire in a devascularized radius segment and inoculating with 7.5×10(6) colony-forming units Staphylococcus aureus. At 3 weeks, débridement was performed and a new Kirschner wire was placed in the dead space. Treatment was randomized to higher-dose G-PNDJ or no hydrogel. No systemic antimicrobials were used. Positive culture and acute inflammation on histology were used to determine the presence of infection 4 weeks postdébridement. (3) 3.14 wt% G-PNDJ, 0.75, 1.5, or 3.0 mL, was injected subcutaneously in nine Sprague-Dawley rats, three of each dose. Serum gentamicin, blood urea nitrogen, and creatinine were measured on Days 1, 3, 7, 14, and 28. RESULTS: (1) Gentamicin release was sustained over 7 days with the higher-dose formulation release profile similar to release from high-dose antimicrobial-loaded bone cement. (2) Four weeks postdébridement, infection was present in eight of eight no-hydrogel rabbits but zero of eight rabbits treated with G-PNDJ hydrogel (p<0.001). (3) Blood urea nitrogen and creatinine were transiently elevated (p<0.05) only for the two of three rats receiving the 3.0-mL dose on Days 3 and 7. CONCLUSIONS: Gentamicin is delivered from PNDJ hydrogel with low systemic exposure and decreased treatment failure for orthopaedic infection. Transient renal dysfunction occurs at high doses. Biodistribution and toxicity testing are needed for G-PNDJ to be clinically usable. CLINICAL RELEVANCE: Resorbable viscous hydrogels for local antimicrobial delivery may improve outcomes for one-stage management of implant infections when uncemented reconstructions are performed.

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.

Antimicrobial distribution from local delivery depends on dose : a pilot study with MRI.

BACKGROUND: Tissue distribution after local delivery has been quantified over a period of 5 hours on 7-T MRI in a rabbit model using gadolinium-labeled diethylenetriamine pentaacetic acid (Gd-DTPA) as an antimicrobial surrogate; however, it is unknown how the Gd-DTPA load in a local depot will affect the duration of high-concentration Gd-DTPA in local tissues after surgical débridement. QUESTIONS/PURPOSES: We determined whether the Gd-DTPA load in bone cement affected its local tissue distribution over a period of 1 month after local delivery. METHODS: A 1-cm3 soft tissue dead space was created in the quadriceps of seven rabbits and filled with gadolinium-loaded bone cement. At 7, 14, and 33 days, the volume of tissue with a Gd-DTPA concentration of more than 14 µg/mL was calculated from T1-weighted images using 7-T MRI. Differences in volumes of distribution were analyzed with ANOVA. RESULTS: The volume of tissue with more than 14 µg/mL Gd-DTPA was much larger from higher gadolinium loads on Day 7 (p=0.02) (2121 mm3 for 10 g and 665 mm3 for 1 g) and smaller with time for the 10-g formulation (2121 mm3 on Day 7 and 1241 mm3 on Day 14). CONCLUSIONS: Volume of distribution and duration of Gd-DTPA after local delivery increased with increasing load in the cement and decreased with time. CLINICAL RELEVANCE: For local delivery, high antimicrobial concentrations would be expected in greater volumes of tissue, for longer durations, when higher antimicrobial loads are used.

Distribution of locally delivered antimicrobials is limited by cortical bone: a pilot study.

BACKGROUND: Local delivery is required to achieve the high antimicrobial concentrations needed to treat biofilm-forming infections. The delivery site is commonly either in the intramedullary canal or at the periosteal surface. It is unknown whether locally delivered antimicrobials are transported transcortically between the endosteal and periosteal surfaces when the infection involves the opposite surface. QUESTIONS/PURPOSES: (1) Are antimicrobials transported transcortically between the endosteal and periosteal surfaces over time? And (2) are transcortical antimicrobials transported uniformly over the cortical surface? METHODS: To study transcortical antimicrobial transport, 12 human cadaveric femoral segments obtained from two women aged 63 and 64 years and one man aged 64 years were filled with antimicrobials. Three diaphyseal segments were filled with 5 wt% vancomycin in an N-isopropylacrylamide-based hydrogel and eluted in phosphate-buffered saline under infinite-sink conditions for 5 days; vancomycin was assayed by high-performance liquid chromatography. Nine segments (three infraisthmal diaphysis, three metaphysis, three epiphysis) embedded in 0.1% agarose gel were filled with aqueous doxycycline (400 µg/mL) and imaged under ultraviolet light for fluorescence on the periosteal surface at 15-minute intervals for 3 days. RESULTS: Transcortical vancomycin elution occurred: 8.65 mg during Day 1 and 26.5 mg by Day 5. Fluorescence from transcortical doxycycline transport was only visualized at focal locations corresponding to vascular foramina, appearing first at 5 to 10 minutes, with none over the majority of the periosteal surface for up to 24 hours. CONCLUSIONS: Transcortical transport of locally delivered antimicrobials occurs primarily through vascular foramina. CLINICAL RELEVANCE: Transcortical antimicrobial transported may not be adequate to achieve therapeutic levels for infection on the far side of an intact cortex.

Voriconazole is cytotoxic at locally delivered concentrations: a pilot study.

BACKGROUND: Fungal infections are rare but major problems when they involve orthopaedic implants. Preferred treatment in North America is two-staged: resection and then delayed reconstruction, with local delivery of an antifungal between stages. The effect of voriconazole, a hydrophobic antifungal, on local tissues and wound healing is unclear. QUESTIONS/PURPOSES: We asked: (1) Is voriconazole cytotoxic to fibroblasts or osteoblasts at target concentrations for local delivery? And (2) if cytotoxic, can fibroblasts or osteoblasts resume proliferation after voriconazole is removed? METHODS: We exposed 5000 fibroblasts or osteoblasts/well to voriconazole concentrations of 0, 1, 5, 10, 25, 100, 500, 1000, 5000, 10,000, and 20,000 µg/mL (n=4 wells/concentration) in 24-well plates. At 3 and 7 days, cell growth was assessed with alamarBlue® and light microscopy. After Day 7, exposure to voriconazole was stopped and incubation continued for 4 days in medium with no voriconazole. On Day 11, cell growth (recovery) was assessed with alamarBlue® and light microscopy. RESULTS: Increasing voriconazole concentration to more than 100 µg/mL decreased osteoblast and fibroblast growth. Cell growth recovered after 7 days' exposure to 1000 µg/mL or less. CONCLUSIONS: Voriconazole is cytotoxic to osteoblasts and fibroblasts, but cell growth recovers over 4 days after exposure to 1000 µg/mL or less. CLINICAL RELEVANCE: Cytotoxicity seen from voriconazole to mouse osteoblasts and fibroblasts occurs at concentrations achievable clinically from local delivery. It may be prudent to limit the dose of voriconazole in antibiotic-loaded bone cement.

Have levels of evidence improved the quality of orthopaedic research?

BACKGROUND: Since 2003 many orthopaedic journals have adopted grading systems for levels of evidence (LOE). It is unclear if the quality of orthopaedic literature has changed since LOE was introduced. QUESTIONS/PURPOSES: We asked three questions: (1) Have the overall number and proportion of Level I and II studies increased in the orthopaedic literature since the introduction of LOE? (2) Is a similar pattern seen in individual orthopaedic subspecialty journals? (3) What is the interobserver reliability of grading LOE? METHODS: We assigned LOE to therapeutic studies published in 2000, 2005, and 2010 in eight major orthopaedic subspecialty journals. Number and proportion of Level I and II publications were determined. Data were evaluated using log-linear models. Twenty-six reviewers (13 residents and 13 attendings) graded LOE of 20 blinded therapeutic articles from the Journal of Bone and Joint Surgery for 2009. Interobserver agreement relative to the Journal of Bone and Joint Surgery was assessed using a weighted kappa. RESULTS: The total number of Level I and II publications in subspecialty journals increased from 150 in 2000 to 239 in 2010. The proportion of high-quality publications increased with time (p < 0.001). All subspecialty journals other than the Journal of Pediatric Orthopaedics and the Journal of Orthopaedic Trauma showed a similar behavior. Average weighted kappa was 0.791 for residents and 0.842 for faculty (p = 0.209). CONCLUSIONS: The number and proportion of Level I and II publications have increased. LOE can be graded reliably with high interobserver agreement. The number and proportion of high-level studies should continue to increase.

Voriconazole is delivered from antifungal-loaded bone cement.

BACKGROUND: Local delivery of antifungals is an important modality in managing orthopaedic fungal infection. Voriconazole is a powder antifungal suitable for addition to bone cement that is released from bone cement but the mechanical properties of antimicrobial-loaded bone cement (ALBC) made with voriconazole are unknown. QUESTIONS/PURPOSES: (1) Is voriconazole release dose-dependent? (2) Is released voriconazole active? (3) Is the loss of ALBC's compressive strength caused by voriconazole dose- and elution-dependent? METHODS: Sixty standard test cylinders were fabricated with ALBC: 300 or 600 mg voriconazole per batch eluted for 30 days in deionized water. Voriconizole concentration in the eluate was measured using high-performance liquid chromatography. Cumulative-released voriconizole was calculated. Biologic activity was tested. Compressive strength was measured before and after elution. The effect of dose and time on release and compressive strength were analyzed using repeated-measure analysis of variance. RESULTS: Fifty-seven percent and 63% of the loaded voriconazole were released by Day 30 for the 300-mg and 600-mg formulations, respectively. The released voriconazole was active on bioassay. Compressive strength was reduced from 79 MPa to 53 MPa and 69 MPa to 31 MPa by 30 days for the 300-mg and 600-mg formulations, respectively. CONCLUSIONS: Voriconazole release from ALBC increases with dose and is bioactive. Loss in compressive strength is greater after elution and with higher dose. CLINICAL RELEVANCE: Three hundred milligrams of voriconazole in ALBC would be expected to deliver meaningful amounts of active drug in vivo. The compressive strength of ALBC with 600 mg voriconazole is less than expected compared to commonly used antibacterials.

Effect of body mass index on limb alignment after total knee arthroplasty.

Prior studies have reported increased failure rates in obese patients with postoperative limb mal-alignment. This study was undertaken to determine if a relationship exists between postoperative limb alignment and BMI in patients undergoing primary TKA performed with mechanical instruments. An IRB-approved retrospective review of 196 knees was undertaken. Limb alignment was determined on full-length, standing, hip-to-ankle x-rays, preoperatively and postoperatively. The effects of gender, side, preoperative mechanical alignment and BMI on postoperative alignment were analyzed via multivariate regression analysis. Both preoperative mechanical limb alignment (P<0.001) and BMI (P=0.009) had a significant effect on postoperative limb alignment following TKA performed with mechanical instruments.