Different microbial and resistance patterns in primary total knee arthroplasty infections - a report on 283 patients from Lithuania and Sweden.

BACKGROUND: The microbiology and the susceptibility patterns of infected total knee arthroplasties (TKAs) vary depending on demographic, local antimicrobial stewardship, and surgical factors. We wanted to compare the recent microbial profile and antimicrobial resistance pattern in revisions due to infections after primary TKAs in Sweden and Lithuania. Our hypothesis was that there is a difference in bacteriology and resistance pattern based on patient related, societal and local hospital factors as almost similar praxis have been applied for TKA surgery, short term systemic prophylaxis and routine use of local gentamicin containing bone cement. METHODS: Primary TKAs revised for the first time due to verified or suspected infection were collected nationwide in Sweden during 2018, and in Lithuania between 2011 and 2020 from a single major TKA revision centre in Kaunas. We identified 202 TKAs in Sweden from the Swedish Knee Arthroplasty Register and 84 from Kaunas revised due to infection. We collected available culture reports and evaluated the type of microorganisms with antimicrobial resistance pattern at revision. RESULTS: The majority of the infected cases in Sweden were early-type prosthetic joint infection (PJI) (44%), whereas late-type PJI (52%) were more common in the Kaunas cases. Gram-positive bacteria prevailed in both Sweden (55%) and Lithuania (80%). Staphylococcus aureus was the most frequent organism identified in both countries (33% in Sweden and 34% in Lithuania). More polymicrobial infections were observed in Sweden than in Lithuania (16 and 6% respectively). Methicillin resistance in Staphylococcus aureus and coagulase-negative staphylococci were higher in Lithuania (4/28 and 19/29) than in Sweden (1/42 and 9/41). CONCLUSIONS: The type of infections, microbial profile, and drug resistance pattern differed between Sweden and Lithuania. Societal and local hospitals factors with emerging resistance in Lithuania are the most plausible explanation for the difference. Lack of complete data on a national level in Lithuania underlines the importance of adding microbiology of PJIs in implant registers for national aggregation and allow cross country comparisons.

Higher Risk of Loosening for a Four-Pegged TKA Tibial Baseplate Than for a Stemmed One: A Register-based Study.

BACKGROUND: Modern modular implants allow surgeons to mix different combinations of components within the same brand. From 1999 to 2012, the NexGen®-CR Option femoral component, together with a NexGen® Option Stemmed tibial plate (stemmed baseplate), which uses a short central stem, was the most-frequently used NexGen® combination in the Swedish Knee Arthroplasty Register. However, from 1999 to 2012, the same femoral component was also used along with the NexGen® Precoat four-pegged tibial baseplate (pegged baseplate). Considering the difference in the fixation concepts for these two tibial baseplates, we wanted to study whether their revision rates differed. QUESTIONS/PURPOSES: To investigate the difference in (1) all-cause revision and (2) the risk of revision for aseptic loosening between the NexGen® pegged and stemmed baseplates when used with the NG-CR Option femoral component and the same two types of inserts. METHODS: The Swedish Knee Arthroplasty Register provided data. The register, which was started in 1975, has since 1999 registered part numbers for individual implant components, allowing it to assess the combinations of components used in each patient. It has been shown to have high completeness (97%) and validity [12, 15]. The inclusion period was 1999 to 2012; during that time, 137,143 primary knee arthroplasties were registered, of which 125,094 were TKAs. Only TKAs performed for osteoarthritis and without patellar resurfacing were included, since not resurfacing the patella is the standard procedure in Sweden. This left 15,287 knees with the stemmed baseplate and 2479 with the pegged baseplate, or 12% and 2% of the total number of TKAs, respectively. Two general hospitals used the pegged baseplate exclusively during that period. Thus, specific patients were not selected for having the pegged plate. The mean age, mortality, and length of followup were similar for the two groups.We used the Kaplan-Meier statistics to calculate the cumulative revision rate (CRR) and Cox regression to compare risk ratios after adjusting for age and sex. The end point was a knee revision for respective all causes or aseptic loosening. The study ended on December 31, 2016. Due to the free healthcare system in Sweden it is highly unusual for patients to seek elective revision abroad, and by use of the extensive Swedish census register, we estimate the level of followup approximately 97%. RESULTS: Knees with the pegged baseplate had a higher risk for all-cause revision than did those with the stemmed baseplate (5.8% [95% confidence interval {CI}, 4-8.3] and 3% [95% CI, 2.6-3.5] at 15 years; p = 0.003). After controlling for age and sex, the aseptic loosening risk in the pegged baseplate group was still higher than that in the stemmed group (relative risk, 5.40; 95% CI, 3.64-8.02; p < 0.001). CONCLUSIONS: In this Swedish registry study, we observed a higher loosening risk with the pegged baseplate than the stemmed one, even after controlling for age and sex. Because this was only a comparison of implants from one vendor, and because there may have been other between-group differences for which we could not fully control, this concerning finding should be explored using data from other registries. LEVEL OF EVIDENCE: Level III, therapeutic study.

Weight and height separated provide better understanding than BMI on the risk of revision after total knee arthroplasty: report of 107,228 primary total knee arthroplasties from the Swedish Knee Arthroplasty Register 2009-2017.

Background and purpose - Obesity defined as increased BMI is commonly associated with higher revision rates following total knee arthroplasty (TKA). We examined the effect of BMI on the rate of revision after TKA, for both infection and other reasons, and analyzed weight and height separately to provide better understanding of the risk profile.Patients and methods - The Swedish national knee arthroplasty register was used to identify 107,228 patients operated with primary TKA for osteoarthritis between 2009 and 2017. Cox proportional hazards regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for BMI (categories: < 18.5, 18.5-24.9, 25-29.9, 30-34.9, 35-39.9, ≥ 40), weight (categories: < 65, 65-89, 90-114, ≥ 115 kg) and height (categories: < 160, 160-179, ≥ 180 cmResults - There were 2,503 revisions in the follow-up period; 1,036 for infection and 1,467 for other reasons. Higher BMI and weight categories were associated with a similar and statistically significantly increased risk of revision for all causes and for infection. The risk of revision for infection was almost twice in the highest BMI and highest weight group: HR = 3.4 (CI 2.3-4.7) and HR = 3.1 (CI 2.5-3.9) respectively. For BMI and weight categories there was no statistically significant association between revision for other reasons than infection, contrary to the tallest height category where it was statistically significant (HR = 1.3 [CI 1.1-1.5]).Interpretation - BMI, weight, and height may be associated with different types of risks for revision following TKA.

Synthetic hydroxyapatite: a recruiting platform for biologically active molecules.

Background and purpose - Targeted delivery of drugs is important to achieve efficient local concentrations and reduce systemic side effects. We hypothesized that locally implanted synthetic hydroxyapatite (HA) particles can act as a recruiting moiety for systemically administered drugs, leading to targeted drug accretion.Methods - Synthetic HA particles were implanted ectopically in a muscle pouch in rats, and the binding of systemically circulating drugs such as zoledronic acid (ZA), tetracycline and 18F-fluoride (18F) was studied. The local biological effect was verified in an implant integration model in rats, wherein a hollow implant was filled with synthetic HA particles and the animals were given systemic ZA, 2-weeks post-implantation. The effect of HA particle size on drug binding and the possibility of reloading HA particles were also evaluated in the muscle pouch.Results - The systemically administered biomolecules (ZA, tetracycline and 18F) all sought the HA moiety placed in the muscle pouch. Statistically significant higher peri-implant bone volume and peak force were observed in the implant containing HA particles compared with the empty implant. After a single injection of ZA at 2 weeks, micro HA particles showed a tendency to accumulate more 14C-zoledronic acid (14C-ZA) than nano-HA particles in the muscle pouch. HA particles could be reloaded when ZA was given again at 4 weeks, showing increased 14C-ZA accretion by 73% in microparticles and 77% in nanoparticles.Interpretation - We describe a novel method of systemic drug loading resulting in targeted accretion in locally implanted particulate HA, thereby biologically activating the material.

Patient-reported 1-year outcome not affected by body mass index in 3,327 total knee arthroplasty patients.

Background and purpose - Patient-reported outcome (PRO) in total knee arthroplasty (TKA) patients with high body mass index (BMI) is controversial. We compared pain, function, quality of life, general health, and satisfaction among different BMI categories preoperatively and 1 year after primary TKA. Patients and methods - 4,318 patients were operated with a TKA for knee osteoarthritis in the Region of Skane in 2013-2015. In all, 3,327 patients (77%) had complete PRO data and information on BMI and were included. Preoperatively the patients filled in the Knee injury and Osteoarthritis Outcome Score (KOOS) and EQ-VAS (general health). 1 year postoperatively the same questionnaires were filled in together with a question asking whether they were satisfied with the surgery. Information on age, sex, BMI, and ASA grade were obtained from the Swedish Knee Arthroplasty Register. Each patient was classified as Outcome Measures in Rheumatology- Osteoarthritis Research Society International (OMERACT-OARSI) responder or not based on a combination of absolute and relative changes in scores. Welch's t-test and a chi-square test were used in the statistical analysis. Results - Both preoperatively and 1 year postoperatively the obese patients reported somewhat worse scores than the normal weight and overweight. The differences were small with 1 exception, the KOOS sport- and recreation function postoperatively, where normal-weight and overweight patients reported fewer problems than obese patients with a BMI over 35 (40 and 39 points vs. 31 points, p < 0.001). Similar proportions of patients were satisfied and categorized as OMERACT-OARSI responders in the different BMI categories. Interpretation - The degree of improvement in PROs 1 year after TKA surgery does not seem to be affected by BMI.

Nonagenarians qualify for total knee arthroplasty: a report on 329 patients from the Swedish Knee Arthroplasty Register 2000-2016.

Background and purpose - The nonagenarian (those aged 90 years and older) population is expected to double in the next 20 years. This demographic age quake may have a significant impact on the incidence of total knee arthroplasty (TKA), although current literature provides limited data. We examined death and revision rates, patient-reported outcomes (PROs) and bias on patient selection of nonagenarian patients operated on with TKA for osteoarthritis (OA) between 2000 and 2016. Patients and methods - The Swedish national knee arthroplasty register was used to identify 329 nonagenarians (mean age, 92 years). Each patient was followed-up until death or the end of 2017. PRO data of 22 of these patients were compared with 65- to 74-year-old patients operated in 2015, from the same register. Results - 5 patients (1.5%) died within 90 days and 23 (7%) patients died within 365 days after TKA. 8 patients (2.4%) developed knee complications that needed revision. For patients followed for 5 and 10 years, more than 50% and 10%, respectively, lived without being revised. The patients had statistically significant improvements in PROs, not significantly different from the younger SKAR cohort. However, the material is small and this statistical finding does not preclude that there may be clinically relevant differences. TKA incidence was different amongst the 21 counties in the country (range, 0-5.1/10,000). Interpretation - Our study suggests that nonagenarians with knee OA qualify for TKA, having similar outcomes to younger patients. The data presented may help surgeons and patients assessing the risks and outcome associated with the procedure.

A ceramic bone substitute containing gentamicin gives good outcome in trochanteric hip fractures treated with dynamic hip screw and in revision of total hip arthroplasty: a case series.

BACKGROUND: The primary objective was to investigate the clinical and radiological outcome in patients undergoing major hip surgery using a novel antibiotic containing bone substitute for local augmentation in trochanteric fracture fixation or revision of total hip arthroplasty (THA). METHODS: We implanted a novel biphasic bone substitute CERAMENT™|G consisting of hydroxyapatite, calcium sulphate and gentamicin for bone regeneration and local antibiotic delivery in 20 patients treated surgically for trochanteric femoral fracture or uncemented hip revision. Preoperative, postoperative, 3 months and 1 year clinical and radiological assessment were performed including registration of any complications. In one trochanteric fracture patient, histological analyses were performed of bone biopsies taken at removal of hardware. RESULTS: None of the trochanteric fractures or revision of THA showed any large migration. No local wound disturbances were seen and no infection was observed at one year follow-up. All trochanteric fractures healed at 3 months with a minimal sliding screw displacement on average 3 mm. Radiological analysis showed signs of bone remodeling and new bone formation in the substitute, illustrated also by histology in the biopsies taken from one trochanteric fracture at one year post-op. CONCLUSIONS: Local CERAMENT™|G was shown to be safe in a limited prospective major hip surgery study. Remodeling of the bone graft substitute was observed in all patients. TRIAL REGISTRATION: EU-CTR2018-004414-18 Retrospectively registered on November 20, 2018.

Higher risk of revision for infection using systemic clindamycin prophylaxis than with cloxacillin.

Background and purpose - Clindamycin has not been compared with other antibiotics for prophylaxis in arthroplasty. Since 2009, the Swedish Knee Arthroplasty Register (SKAR) has been collecting information on the prophylactic antibiotic regime used at every individual operation. In Sweden, when there is allergy to penicillin, clindamycin has been the recommended alternative. We examined whether there were differences in the rate of revision due to infection depending on which antibiotic was used as systemic prophylaxis. Patients and methods - Patients who had a total knee arthroplasty (TKA) performed due to osteoarthritis (OA) during the years 2009-2015 were included in the study. Information on which antibiotic was used was available for 80,018 operations (55,530 patients). Survival statistics were used to calculate the rate of revision due to infection until the end of 2015, comparing the group of patients who received cloxacillin with those who received clindamycin as systemic prophylaxis. Results - Cloxacillin was used in 90% of the cases, clindamycin in 7%, and cephalosporins in 2%. The risk of being revised due to infection was higher when clindamycin was used than when cloxacillin was used (RR =1.5, 95% CI: 1.2-2.0; p = 0.001). There was no significant difference in the revision rate for other causes (p = 0.2). Interpretation - We advise that patients reporting allergic reaction to penicillin should have their allergic history explored. In the absence of a clear history of type-I allergic reaction (e.g. urticaria, anaphylaxis, or bronchospasm), we suggest the use of a third-generation cephalosporin instead of clindamycin as perioperative prophylaxis when undergoing a TKR. No recommendation can be given regarding patients with type-1 allergy.

Introducing prospective national registration of knee osteotomies. A report from the first year in Sweden.

PURPOSE: Knee osteotomy is a joint preserving surgery with new techniques and implants introduced during recent years. However the information of its use and outcome is scarce. A national knee osteotomy register was started in Sweden in 2013 from which we report here the information gathered during the first year of registration. METHODS: All patients having knee osteotomy (distal femur and proximal tibia), primaries and re-operations are intended to be included in the prospective registration. Reporting to the register is based on a paper form including information on the patient (ID, sex, age, American Society of Anesthesiologists classification [ASA], weight and height) surgical date, hospital, diagnosis, pre-operative alignment and grade of osteoarthritis (OA), part and LOT numbers of implants, surgical technique, prophylaxis (antithrombotic and antibiotic) and operating time. RESULTS: During the first year (April 2013 to March 2014), 34 clinics reported 220 primary knee osteotomies (209 proximal tibia and 11 distal femur). We estimate that this represents almost 80% of those performed on the adult population during the period. The majority of the patients were classified as healthy (60% ASA grade 1), were men (66%) and the median age was 51 years (range 19-67). Proximal tibia osteotomy for OA performed with open wedge osteotomy using internal fixation without bone transplantation was most commonly reported. CONCLUSIONS: As relatively few patients are being treated with different types of fixation and bone substitution in Sweden as well as the rapid development of techniques and new implants, a nationwide registration of knee osteotomies is relevant.

Co-delivery of rhBMP-2 and zoledronic acid using calcium sulfate/hydroxyapatite carrier as a bioactive bone substitute to enhance and accelerate spinal fusion.

Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been FDA-approved for lumbar fusion, but supraphysiologic initial burst release due to suboptimal carrier and late excess bone resorption caused by osteoclast activation have limited its clinical usage. One strategy to mitigate the pro-osteoclast side effect of rhBMP-2 is to give systemic bisphosphonates, but it presents challenges with systemic side effects and low local bioavailability. The aim of this in vivo study was to analyze if posterolateral spinal fusion (PLF) could be improved by utilizing a calcium sulfate/hydroxyapatite (CaS/HA) carrier co-delivering rhBMP-2 and zoledronic acid (ZA). Six groups were allocated (CaS/HA, CaS/HA + BMP-2, CaS/HA + systemic ZA, CaS/HA + local ZA, CaS/HA + BMP-2 + systemic ZA, and CaS/HA + BMP-2 + local ZA). 10-week-old male Wistar rats, were randomly assigned to undergo L4-L5 PLF with implantation of group-dependent scaffolds. At 3 and 6 weeks, the animals were euthanized for radiography, µCT, histological staining, or biomechanical testing to evaluate spinal fusion. The results demonstrated that the CaS/HA biomaterial alone or in combination with local or systemic ZA didn't support PLF. However, the delivery of rhBMP-2 significantly promoted PLF. Combining systemic ZA with BMP-2 didn't enhance spinal fusion. Notably, the co-delivery of rhBMP-2 and ZA using the CaS/HA carrier significantly enhanced and accelerated PLF, without inhibiting systemic bone turnover, and potentially reduced the dose of rhBMP-2. Together, the treatment regimen of CaS/HA biomaterial co-delivering rhBMP-2 and ZA could potentially be a safe and cost-effective off-the-shelf bioactive bone substitute to enhance spinal fusion.

Systemically administered zoledronic acid activates locally implanted synthetic hydroxyapatite particles enhancing peri-implant bone formation: A regenerative medicine approach to improve fracture fixation.

Fracture fixation in an ageing population is challenging and fixation failure increases mortality and societal costs. We report a novel fracture fixation treatment by applying a hydroxyapatite (HA) based biomaterial at the bone-implant interface and biologically activating the biomaterial by systemic administration of a bisphosphonate (zoledronic acid, ZA). We first used an animal model of implant integration and applied a calcium sulphate (CaS)/HA biomaterial around a metallic screw in the tibia of osteoporotic rats. Using systemic ZA administration at 2-weeks post-surgery, we demonstrated that the implant surrounded by HA particles showed significantly higher peri­implant bone formation compared to the unaugmented implants at 6-weeks. We then evaluated the optimal timing (day 1, 3, 7 and 14) of ZA administration to achieve a robust effect on peri­implant bone formation. Using fluorescent ZA, we demonstrated that the uptake of ZA in the CaS/HA material was the highest at 3- and 7-days post-implantation and the uptake kinetics had a profound effect on the eventual peri­implant bone formation. We furthered our concept in a feasibility study on trochanteric fracture patients randomized to either CaS/HA augmentation or no augmentation followed by systemic ZA treatment. Radiographically, the CaS/HA group showed signs of increased peri­implant bone formation compared with the controls. Finally, apart from HA, we demonstrated that the concept of biologically activating a ceramic material by ZA could also be applied to ß-tricalcium phosphate. This novel approach for fracture treatment that enhances immediate and long-term fracture fixation in osteoporotic bone could potentially reduce reoperations, morbidity and mortality. STATEMENT OF SIGNIFICANCE: • Fracture fixation in an ageing population is challenging. Biomaterial-based augmentation of fracture fixation devices has been attempted but lack of satisfactory biological response limits their widespread use. • We report the biological activation of locally implanted microparticulate hydroxyapatite (HA) particles placed around an implant by systemic administration of the bisphosphonate zoledronic acid (ZA). The biological activation of HA by ZA enhances peri­implant bone formation. •Timing of ZA administration after HA implantation is critical for optimal ZA uptake and consequently determines the extent of peri­implant bone formation. • We translate the developed concept from small animal models of implant integration to a proof-of-concept clinical study on osteoporotic trochanteric fracture patients. • ZA based biological activation can also be applied to other calcium phosphate biomaterials.

Bacterial colonization and resistance patterns in 133 patients undergoing a primary hip- or knee replacement in Southern Sweden.

BACKGROUND AND PURPOSE: Prosthetic joint infections can be caused by bacteria derived from the patient's skin. The aim of the study was: (1) to determine which bacteria colonize the nose and groin in patients planned for primary hip or knee arthroplasty, (2) to determine the antimicrobial resistance patterns, and (3) to monitor changes in bacterial colonization and resistance patterns connected to surgery. PATIENTS AND METHODS: 2 weeks before scheduled primary hip or knee arthroplasty, culture samples were taken from the anterior nares and from the groin of 133 consecutive patients. At surgery, cloxacillin was given prophylactically and cement with gentamicin was used. 2 weeks after surgery, another set of samples were taken from 120 of these patients. Bacterial findings and resistance patterns were analyzed. RESULTS: Preoperatively, 95% of the patients had coagulase-negative staphylococci (CNS) in the groin and 77% in the nose. The proportion of patients with a methicillin-resistant CNS in the groin increased from 20% preoperatively to 50% postoperatively (p < 0.001), and the proportion of patients with a gentamicin-resistant CNS in the groin increased from 5% to 45% (p < 0.001). 28% of the patients had Staphylococcus aureus in the nose preoperatively, and 7% in the groin. Methicillin-resistant Staphylococcus aureus (MRSA) was found in the nose of 1 patient. INTERPRETATION: In southern Sweden, beta-lactams were effective against 99% of the Staphylococcus aureus strains and 80% of the CNS strains colonizing the patients undergoing primary hip or knee arthroplasty. Gentamicin protects against most CNS strains in cemented primary joint replacements.

Systemic rifampicin shows accretion to locally implanted hydroxyapatite particles in a rat abdominal muscle pouch model.

Introduction: biomaterials combined with antibiotics are routinely used for the management of bone infections. After eluting high concentrations of antibiotics during the first week, sub-inhibitory concentrations of antibiotics may lead to late repopulation of recalcitrant bacteria. Recent studies have shown that systemically given antibiotics like tetracycline and rifampicin (RIF) could seek and bind to locally implanted hydroxyapatite (HA). The aim of this in vivo study was to test if systemically administered rifampicin could replenish HA-based biomaterials with or without prior antibiotic loading to protect the material from late bacterial repopulation. Methods: in vivo accretion of systemically administered RIF to three different types of HA-based materials was tested. In group 1, nano (n)- and micro (m)-sized HA particles were used, while group 2 consisted of a calcium sulfate / hydroxyapatite (CaS / HA) biomaterial without preloaded antibiotics gentamycin (GEN) or vancomycin (VAN), and in group 3, the CaS / HA material contained GEN (CaS / HA + GEN) or VAN (CaS / HA + VAN). The above materials were implanted in an abdominal muscle pouch model in rats, and at 7 d post-surgery, the animals were assigned to a control group (i.e., no systemic antibiotic) and a test group (i.e., animals receiving one single intraperitoneal injection of RIF each day (4 mg per rat) for 3 consecutive days). Twenty-four hours after the third injection, the animals were sacrificed and the implanted pellets were retrieved and tested against Staphylococcus aureus ATCC 25923 in an agar diffusion assay. After overnight incubation, the zone of inhibition (ZOI) around the pellets were measured. Results: in the control group, 2 / 6 CaS / HA + GEN pellets had a ZOI, while all other harvested pellets had no ZOI. No pellets from animals in test group 1 had a ZOI. In test group 2, 10 / 10 CaS / HA pellets showed a ZOI. In test group 3, 5 / 6 CaS / HA + GEN and 4 / 6 CaS / HA + VAN pellets showed a ZOI. Conclusions: in this proof-of-concept study, we have shown that a locally implanted biphasic CaS / HA carrier after 1 week can be loaded by systemic RIF administration and exert an antibacterial effect. Further in vivo infection models are necessary to validate our findings.

Metal-on-metal joint bearings and hematopoetic malignancy.

This is a review of the hip arthroplasty era. We concentrate on new metal bearings, surface replacements, and the lessons not learned, and we highlight recent reports on malignancies and joint implants. A low incidence of blood malignancies has been found in bone marrow taken at prosthetic surgery. The incidence is increased after replacement with knee implants that release very low systemic levels of metal ions. A carcinogenic effect of the high levels of metal ions released by large metal-on-metal implants cannot be excluded. Ongoing Swedish implant registry studies going back to 1975 can serve as a basis for evaluation of this risk.

Extended local release and improved bacterial eradication by adding rifampicin to a biphasic ceramic carrier containing gentamicin or vancomycin.

AIMS: There is a lack of biomaterial-based carriers for the local delivery of rifampicin (RIF), one of the cornerstone second defence antibiotics for bone infections. RIF is also known for causing rapid development of antibiotic resistance when given as monotherapy. This in vitro study evaluated a clinically used biphasic calcium sulphate/hydroxyapatite (CaS/HA) biomaterial as a carrier for dual delivery of RIF with vancomycin (VAN) or gentamicin (GEN). METHODS: The CaS/HA composites containing RIF/GEN/VAN, either alone or in combination, were first prepared and their injectability, setting time, and antibiotic elution profiles were assessed. Using a continuous disk diffusion assay, the antibacterial behaviour of the material was tested on both planktonic and biofilm-embedded forms of standard and clinical strains of Staphylococcus aureus for 28 days. Development of bacterial resistance to RIF was determined by exposing the biofilm-embedded bacteria continuously to released fractions of antibiotics from CaS/HA-antibiotic composites. RESULTS: Following the addition of RIF to CaS/HA-VAN/GEN, adequate injectability and setting of the CaS/HA composites were noted. Sustained release of RIF above the minimum inhibitory concentrations of S. aureus was observed until study endpoint (day 35). Only combinations of CaS/HA-VAN/GEN + RIF exhibited antibacterial and antibiofilm effects yielding no viable bacteria at study endpoint. The S. aureus strains developed resistance to RIF when biofilms were subjected to CaS/HA-RIF alone but not with CaS/HA-VAN/GEN + RIF. CONCLUSION: Our in vitro results indicate that biphasic CaS/HA loaded with VAN or GEN could be used as a carrier for RIF for local delivery in clinically demanding bone infections.Cite this article: Bone Joint Res 2022;11(11):787-802.

Comparative effectiveness research on proximal femoral nail versus dynamic hip screw in patients with trochanteric fractures: a systematic review and meta-analysis of randomized trials.

BACKGROUND: The treatments for trochanteric fractures try to regain early mobility and limit morbidity and risk of reoperations. The most currently used dynamic hip screw (DHS) and the proximal femoral nail (PFN) are both with pros and cons. We aimed to assess the comparative effectiveness of these interventions for trochanteric fractures by evaluating the surgical performance and postoperative outcomes. METHODS: PubMed, Web of Science and Cochrane Central Register were searched for RCTs comparing DHS and PFN for trochanteric fractures. All selected studies and the risk of bias were assessed. Clinical data including operative time, intraoperative blood loss, intraoperative fluoroscopy time, successful closed reduction and complications like nonunion, implant failure and reoperation were recorded. Random-effects models were used in Review Manager software, and GRADE was applied for the interpretation of the evidence. RESULTS: From 286 identified trials, twelve RCTs including 1889 patients were eligible for inclusion; six RCTs directly comparing DHS with PFN, while other six compared DHS with proximal femoral nail antirotation (PFNA). Compared to DHS, PFN had shorter operative time and led to less intraoperative blood loss. However, DHS need less intraoperative fluoroscopy time than PFN. No difference was seen for the achievement of closed reduction. For risk of postoperative complications, no difference was seen between PFN and DHS for non-union, risk of implant failure and revision surgery. CONCLUSIONS: PFN(A) resulted in a shorter operative time and less intraoperative blood loss compared to DHS. However, no difference was seen for postoperative complications. Trial registration PROSPERO: CRD42021239974.

Fracture behavior of a composite of bone and calcium sulfate/hydroxyapatite.

Calcium sulfate/hydroxyapatite (CaS/HA) biomaterials have been investigated for use in several orthopedic applications. However, the mechanical interactions between the composite of CaS/HA and bone at the microscale are still unknown. The aim of this study was to determine if and how augmentation with CaS/HA alters the fracture behavior of bone. Eleven cylinders of trabecular bone were drilled from human femoral heads and cleaned from bone marrow. Among them, five cylinders were injected with CaS/HA to generate composite specimens, while the others were kept intact. One extra specimen of pure CaS/HA was prepared. All specimens were compressed in situ using synchrotron X-ray tomography and imaged at ∼2% strain intervals. Structural properties were calculated from the images in unloaded state and mechanical properties were determined from the load-curves. CaS/HA alone displayed the highest peak force and stiffness and the lowest strain at fracture. All composite specimens had a higher peak force than the pure bone specimens and the composite specimens had higher toughness than the pure CaS/HA specimen. Furthermore, the fracture behavior was analyzed further to characterize the local deformations. The pure bone specimens presented damage in multiple trabeculae and the CaS/HA specimen displayed sharp transition in strains, with low strain in one load step and large cracks in the next. The composite specimens deformed uniformly, with the CaS/HA preventing tissue damage and the bone preventing cracks in the CaS/HA from propagating through the specimen. In conclusion, using tomography with in situ loading, it was possible to show how CaS/HA can help prevent bone tissue damage before global failure.