Risk factors influencing fracture characteristics in postoperative periprosthetic femoral fractures around cemented stems in total hip arthroplasty : a multicentre observational cohort study on 584 fractures.

AIMS: This study evaluates risk factors influencing fracture characteristics for postoperative periprosthetic femoral fractures (PFFs) around cemented stems in total hip arthroplasty. METHODS: Data were collected for PFF patients admitted to eight UK centres between 25 May 2006 and 1 March 2020. Radiographs were assessed for Unified Classification System (UCS) grade and AO/OTA type. Statistical comparisons investigated relationships by age, gender, and stem fixation philosophy (polished taper-slip (PTS) vs composite beam (CB)). The effect of multiple variables was estimated using multinomial logistic regression to estimate odds ratios (ORs) with 95% confidence intervals (CIs). Surgical treatment (revision vs fixation) was compared by UCS grade and AO/OTA type. RESULTS: A total of 584 cases were included. Median age was 79.1 years (interquartile range 72.0 to 86.0), 312 (53.6%) patients were female, and 495 (85.1%) stems were PTS. The commonest UCS grade was type B1 (278, 47.6%). The most common AO/OTA type was spiral (352, 60.3%). Metaphyseal split fractures occurred only with PTS stems with an incidence of 10.1%. Male sex was associated with a five-fold reduction in odds of a type C fracture (OR 0.22 (95% CI 0.12 to 0.41); p < 0.001) compared to a type B fracture. CB stems were associated with significantly increased odds of transverse fracture (OR 9.51 (95% CI 3.72 to 24.34); p < 0.001) and wedge fracture (OR 3.72 (95% CI 1.16 to 11.95); p = 0.027) compared to PTS stems. Both UCS grade and AO/OTA type differed significantly (p < 0.001 and p = 0.001, respectively) between the revision and fixation groups but a similar proportion of B1 fractures underwent revision compared to fixation (45.3% vs 50.6%). CONCLUSION: The commonest fracture types are B1 and spiral fractures. PTS stems are exclusively associated with metaphyseal split fractures, but their incidence is low. Males have lower odds of UCS grade C fractures compared to females. CB stems have higher odds of bending type fractures (transverse and wedge) compared to PTS stems. There is considerable variation in practice when treating B1 fractures around cemented stems. Cite this article: Bone Jt Open 2021;2(7):466-475.

Prolonged Antimicrobial Activity of PMMA Bone Cement with Embedded Gentamicin-Releasing Silica Nanocarriers.

Antibiotic laden bone cements are regularly employed to prevent infections after joint replacement surgeries. We have developed silica nanocarriers loaded with gentamicin as a drug delivery system to be dispersed in poly methyl-methacrylate (PMMA) bone cement for controlling and extending the release of the antibiotic from bone cements, thus proving a prolonged antimicrobial activity. Layer-by-layer self-assembly was used to deposit gentamicin between alginate layers and two different poly ß-amino esters on the silica nanoparticles. The release of gentamicin from PMMA bone cement containing silica nanocarriers continued for about 30 days compared to 6 days when the same amount of antibiotic was added as a pure powder (as in commercial formulations); moreover, the medium containing the released antimicrobial drug was capable of preventing the growth of numerous bacteria species responsible for prosthetic joint infections (both catalogue strains and clinical isolates) for longer periods of time than in the case of commercial formulations, thus confirming the extended antimicrobial properties of the drug once released from the carrier. No detrimental effects toward human osteoblasts were also observed; moreover, bone cement material characteristics such as curing time, water uptake, and mechanical properties were unaffected when the silica nanocarriers were added.

LbL-assembled gentamicin delivery system for PMMA bone cements to prolong antimicrobial activity.

INTRODUCTION: Antibiotic-loaded poly(methyl methacrylate) bone cements (ALBCs) are widely used in total joint replacement (TJR), for local delivery of antibiotics to provide prophylaxis against prosthetic joint infections (PJI). One of the shortcomings of the current generation of ALBCs is that the antibiotic release profile is characterized by a burst over the first few hours followed by a sharp decrease in rate for the following several days (often below minimum inhibitory concentration (MIC)), and, finally, exhaustion (after, typically, ~ 20 d). This profile means that the ALBCs provide only short-term antimicrobial action against bacterial strains involved PJI. RATIONALE: The purpose of the present study was to develop an improved antibiotic delivery system for an ALBC. This system involved using a layer-by-layer technique to load the antibiotic (gentamicin sulphate) (GEN) on silica nanoparticles, which are then blended with the powder of the cement. Then, the powder was mixed with the liquid of the cement (NP-GEN cement). For controls, two GEN-loaded brands were used (Cemex Genta and Palacos R+G). Gentamicin release and a host of other relevant properties were determined for all the cements studied. RESULTS: Compared to control cement specimens, improved GEN release, longer antimicrobial activity (against clinically-relevant bacterial strains), and comparable setting time, cytocompatibility, compressive strength (both prior to and after aging in PBS at 37 oC for 30 d), 4-point bend strength and modulus, fracture toughness, and PBS uptake. CONCLUSIONS: NP-GEN cement may have a role in preventing or treating PJI.

Validation and application of a liquid chromatography-tandem mass spectrometric method for the determination of GDC-0152 in human plasma using solid-phase extraction.

A liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the determination of GDC-0152 in human plasma to support clinical development. The method consisted of a solid-phase extraction for sample preparation and LC-MS/MS analysis in the positive ion mode using TurboIonSpray(TM) for analysis. d(7) -GDC-0152 was used as the internal standard. A linear regression (weighted 1/concentration(2) ) was used to fit calibration curves over the concentration range of 0.02-10.0 ng/mL for GDC-0152. There were no endogenous interference components in the blank human plasma tested. The accuracy at the lower limit of quantitation was 99.3% with a precision (%CV) of 13.9%. For quality control samples at 0.0600, 2.00 and 8.00 ng/mL, the between-run %CV was ≤8.64. Between-run percentage accuracy ranged from 98.2 to 99.6%. GDC-0152 was stable in human plasma for 363 days at -20°C and for 659 days at -70°C storage. GDC-0152 was stable in human plasma at room temperature for up to 25 h and through three freeze-thaw cycles. In whole blood, GDC-0152 was stable for 12 h at 4°C and at ambient temperature. This validated LC-MS/MS method for determination of GDC-0152 was used to support clinical studies.

Validation and application of a liquid chromatography-tandem mass spectrometric method for the determination of GDC-0834 and its metabolite in human plasma using semi-automated 96-well protein precipitation.

A liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the determination of GDC-0834 and its amide hydrolysis metabolite (M1) in human plasma to support clinical development. The method consisted of semi-automated 96-well protein precipitation extraction for sample preparation and LC-MS/MS analysis in positive ion mode using TurboIonSpray® for analysis. D6-GDC-0834 and D6-M1 metabolite were used as internal standards. A linear regression (weighted 1/concentration(2) ) was used to fit calibration curves over the concentration range of 1 - 500 ng/mL for both GDC-0834 and M1 metabolite. The accuracy (percentage bias) at the lower limit of quantitation (LLOQ) was 5.20 and 0.100% for GDC-0834 and M1 metabolite, respectively. The precision (CV) for samples at the LLOQ was 3.13-8.84 and 5.20-8.93% for GDC-0834 and M1 metabolite, respectively. For quality control samples at 3, 200 and 400 ng/mL, the between-run CV was ≤ 7.38% for GDC-0834 and ≤ 8.20% for M1 metabolite. Between run percentage bias ranged from -2.76 to 6.98% for GDC-0834 and from -6.73 to 2.21% for M1 metabolite. GDC-0834 and M1 metabolite were stable in human plasma for 31 days at -20 and -70°C. This method was successfully applied to support a GDC-0834 human pharmacokinetic-based study.