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Bone & Joint Research
Vol. 13, Issue 4 | Pages 157 - 168
4 Apr 2024
Lin M Chen G Yu H Hsu P Lee C Cheng C Wu S Pan B Su B

Aims

Osteosarcoma is the most common primary bone malignancy among children and adolescents. We investigated whether benzamil, an amiloride analogue and sodium-calcium exchange blocker, may exhibit therapeutic potential for osteosarcoma in vitro.

Methods

MG63 and U2OS cells were treated with benzamil for 24 hours. Cell viability was evaluated with the MTS/PMS assay, colony formation assay, and flow cytometry (forward/side scatter). Chromosome condensation, the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay, cleavage of poly-ADP ribose polymerase (PARP) and caspase-7, and FITC annexin V/PI double staining were monitored as indicators of apoptosis. Intracellular calcium was detected by flow cytometry with Fluo-4 AM. The phosphorylation and activation of focal adhesion kinase (FAK) and signal transducer and activator of transcription 3 (STAT3) were measured by western blot. The expression levels of X-linked inhibitor of apoptosis protein (XIAP), B-cell lymphoma 2 (Bcl-2), B-cell lymphoma-extra large (Bcl-xL), SOD1, and SOD2 were also assessed by western blot. Mitochondrial status was assessed with tetramethylrhodamine, ethyl ester (TMRE), and intracellular adenosine triphosphate (ATP) was measured with BioTracker ATP-Red Live Cell Dye. Total cellular integrin levels were evaluated by western blot, and the expression of cell surface integrins was assessed using fluorescent-labelled antibodies and flow cytometry.


The Bone & Joint Journal
Vol. 101-B, Issue 9 | Pages 1093 - 1099
1 Sep 2019
Bradley KE Ryan SP Penrose CT Grant SA Wellman SS Attarian DE Green CL Risoli T Bolognesi MP

Aims. Antifibrinolytic agents, including tranexamic acid (TXA) and epsilon-aminocaproic acid (EACA), have been shown to be safe and effective for decreasing perioperative blood loss and transfusion following total hip arthroplasty (THA) and total knee arthroplasty (TKA). However, there are few prospective studies that directly compare these agents. The purpose of this study was to compare the benefits of intraoperative intravenous TXA with EACA. Patients and Methods. A total of 235 patients (90 THA and 145 TKA) were enrolled in this prospective, randomized controlled trial at a single tertiary-care referral centre. In the THA cohort, 53.3% of the patients were female with a median age of 59.8 years (interquartile range (IQR) 53.3 to 68.1). In the TKA cohort, 63.4% of the patients were female with a median age of 65.1 years (IQR 59.4 to 69.5). Patients received either TXA (n = 119) or EACA (n = 116) in two doses intraoperatively. The primary outcome measures included change in haemoglobin level and blood volume, postoperative drainage, and rate of transfusion. Secondary outcome measures included postoperative complications, cost, and length of stay (LOS). Results. TKA patients who received EACA had greater drainage (median 320 ml (IQR 185 to 420) vs 158 ml (IQR 110 to 238); p < 0.001), increased loss of blood volume (891 ml (IQR 612 to 1203) vs 661 ml (IQR 514 to 980); p = 0.014), and increased haemoglobin change from the preoperative level (2.1 ml (IQR 1.7 to 2.8) vs 1.9 ml (IQR 1.2 to 2.4); p = 0.016) compared with patients who received TXA. For the THA cohort, no statistically significant differences were observed in any haematological outcome measure. One patient in the EACA group required transfusion. No patient in the TXA group required transfusion. There were no statistically significant differences in number or type of postoperative complications or LOS for either THA or TKA patients regardless of whether they received TXA or EACA. Conclusion. For hip and knee arthroplasty procedures, EACA is associated with increased perioperative blood loss compared with TXA. However, there is no significant difference in transfusion rate. While further prospective studies are needed to compare the efficacy of each agent, we currently recommend orthopaedic surgeons to select their antifibrinolytic based on cost and regional availability. Cite this article: Bone Joint J 2019;101-B:1093–1099


Bone & Joint Research
Vol. 5, Issue 2 | Pages 37 - 45
1 Feb 2016
Roh YH Kim W Park KU Oh JH

Objectives. This study was conducted to evaluate the cytokine-release kinetics of platelet-rich plasma (PRP) according to different activation protocols. Methods. Two manual preparation procedures (single-spin (SS) at 900 g for five minutes; double-spin (DS) at 900 g for five minutes and then 1500 g for 15 minutes) were performed for each of 14 healthy subjects. Both preparations were tested for platelet activation by one of three activation protocols: no activation, activation with calcium (Ca) only, or calcium with a low dose (50 IU per 1 ml PRP) of thrombin. Each preparation was divided into four aliquots and incubated for one hour, 24 hours, 72 hours, and seven days. The cytokine-release kinetics were evaluated by assessing PDGF, TGF, VEGF, FGF, IL-1, and MMP-9 concentrations with bead-based sandwich immunoassay. Results. The concentration of cytokine released from PRP varied over time and was influenced by various activation protocols. Ca-only activation had a significant effect on the DS PRPs (where the VEGF, FGF, and IL-1 concentrations were sustained) while Ca/thrombin activation had effects on both SS and DS PRPs (where the PDGF and VEGF concentrations were sustained and the TGF and FGF concentrations were short). The IL-1 content showed a significant increase with Ca-only or Ca/thrombin activation while these activations did not increase the MMP-9 concentration. Conclusion. The SS and DS methods differed in their effect on cytokine release, and this effect varied among the cytokines analysed. In addition, low dose of thrombin/calcium activation increased the overall cytokine release of the PRP preparations over seven days, relative to that with a calcium-only supplement or non-activation. Cite this article: Professor J. H. Oh. Cytokine-release kinetics of platelet-rich plasma according to various activation protocols. Bone Joint Res 2016;5:37–45. doi: 10.1302/2046-3758.52.2000540


Bone & Joint Research
Vol. 4, Issue 9 | Pages 154 - 162
1 Sep 2015

Objective. Clinical studies of patients with bone sarcomas have been challenged by insufficient numbers at individual centres to draw valid conclusions. Our objective was to assess the feasibility of conducting a definitive multi-centre randomised controlled trial (RCT) to determine whether a five-day regimen of post-operative antibiotics, in comparison to a 24-hour regimen, decreases surgical site infections in patients undergoing endoprosthetic reconstruction for lower extremity primary bone tumours. . Methods. We performed a pilot international multi-centre RCT. We used central randomisation to conceal treatment allocation and sham antibiotics to blind participants, surgeons, and data collectors. We determined feasibility by measuring patient enrolment, completeness of follow-up, and protocol deviations for the antibiotic regimens. . Results. We screened 96 patients and enrolled 60 participants (44 men and 16 women) across 21 sites from four countries over 24 months (mean 2.13 participants per site per year, standard deviation 2.14). One participant was lost to follow-up and one withdrew consent. Complete data were obtained for 98% of eligible patients at two weeks, 83% at six months, and 73% at one year (the remainder with partial data or pending queries). In total, 18 participants missed at least one dose of antibiotics or placebo post-operatively, but 93% of all post-operative doses were administered per protocol. . Conclusions. It is feasible to conduct a definitive multi-centre RCT of post-operative antibiotic regimens in patients with bone sarcomas, but further expansion of our collaborative network will be critical. We have demonstrated an ability to coordinate in multiple countries, enrol participants, maintain protocol adherence, and minimise losses to follow-up. Cite this article: Bone Joint Res;4:154–162


The Bone & Joint Journal
Vol. 106-B, Issue 8 | Pages 849 - 857
1 Aug 2024
Hatano M Sasabuchi Y Ishikura H Watanabe H Tanaka T Tanaka S Yasunaga H

Aims

The use of multimodal non-opioid analgesia in hip fractures, specifically acetaminophen combined with non-steroidal anti-inflammatory drugs (NSAIDs), has been increasing. However, the effectiveness and safety of this approach remain unclear. This study aimed to compare postoperative outcomes among patients with hip fractures who preoperatively received either acetaminophen combined with NSAIDs, NSAIDs alone, or acetaminophen alone.

Methods

This nationwide retrospective cohort study used data from the Diagnosis Procedure Combination database. We included patients aged ≥ 18 years who underwent surgery for hip fractures and received acetaminophen combined with NSAIDs (combination group), NSAIDs alone (NSAIDs group), or acetaminophen alone (acetaminophen group) preoperatively, between April 2010 and March 2022. Primary outcomes were in-hospital mortality and complications. Secondary outcomes were opioid use postoperatively; readmission within 90 days, one year, and two years; and total hospitalization costs. We used propensity score overlap weighting models, with the acetaminophen group as the reference group.


The Bone & Joint Journal
Vol. 106-B, Issue 7 | Pages 642 - 645
1 Jul 2024
Harris IA Sidhu VS MacDessi SJ Solomon M Haddad FS


The Bone & Joint Journal
Vol. 104-B, Issue 12 | Pages 1362 - 1368
1 Dec 2022
Rashid F Mahmood A Hawkes DH Harrison WJ

Aims

Prior to the availability of vaccines, mortality for hip fracture patients with concomitant COVID-19 infection was three times higher than pre-pandemic rates. The primary aim of this study was to determine the 30-day mortality rate of hip fracture patients in the post-vaccine era.

Methods

A multicentre observational study was carried out at 19 NHS Trusts in England. The study period for the data collection was 1 February 2021 until 28 February 2022, with mortality tracing until 28 March 2022. Data collection included demographic details, data points to calculate the Nottingham Hip Fracture Score, COVID-19 status, 30-day mortality, and vaccination status.


Bone & Joint Research
Vol. 13, Issue 10 | Pages 525 - 534
1 Oct 2024
Mu W Xu B Wang F Maimaitiaimaier Y Zou C Cao L

Aims

This study aimed to assess the risk of acute kidney injury (AKI) associated with combined intravenous (IV) and topical antibiotic therapy in patients undergoing treatment for periprosthetic joint infections (PJIs) following total knee arthroplasty (TKA), utilizing the Kidney Disease: Improving Global Outcomes (KDIGO) criteria for classification.

Methods

We conducted a retrospective analysis of 162 knees (162 patients) that received treatment for PJI post-TKA with combined IV and topical antibiotic infusions at a single academic hospital from 1 January 2010 to 31 December 2022. The incidence of AKI was evaluated using the KDIGO criteria, focussing on the identification of significant predictors and the temporal pattern of AKI development.



The Bone & Joint Journal
Vol. 105-B, Issue 11 | Pages 1135 - 1139
1 Nov 2023
Young SW Chen W Clarke HD Spangehl MJ

Prophylactic antibiotics are important in reducing the risk of periprosthetic joint infection (PJI) following total knee arthroplasty. Their effectiveness depends on the choice of antibiotic and the optimum timing of their administration, to ensure adequate tissue concentrations. Cephalosporins are typically used, but an increasing number of resistant organisms are causing PJI, leading to the additional use of vancomycin. There are difficulties, however, with the systemic administration of vancomycin including its optimal timing, due to the need for prolonged administration, and potential adverse reactions. Intraosseous regional administration distal to a tourniquet is an alternative and attractive mode of delivery due to the ease of obtaining intraosseous access. Many authors have reported the effectiveness of intraosseous prophylaxis in achieving higher concentrations of antibiotic in the tissues compared with intravenous administration, providing equal or enhanced prophylaxis while minimizing adverse effects. This annotation describes the technique of intraosseous administration of antibiotics and summarizes the relevant clinical literature to date.

Cite this article: Bone Joint J 2023;105-B(11):1135–1139.


Bone & Joint Research
Vol. 13, Issue 4 | Pages 169 - 183
15 Apr 2024
Gil-Melgosa L Llombart-Blanco R Extramiana L Lacave I Abizanda G Miranda E Agirre X Prósper F Pineda-Lucena A Pons-Villanueva J Pérez-Ruiz A

Aims

Rotator cuff (RC) injuries are characterized by tendon rupture, muscle atrophy, retraction, and fatty infiltration, which increase injury severity and jeopardize adequate tendon repair. Epigenetic drugs, such as histone deacetylase inhibitors (HDACis), possess the capacity to redefine the molecular signature of cells, and they may have the potential to inhibit the transformation of the fibro-adipogenic progenitors (FAPs) within the skeletal muscle into adipocyte-like cells, concurrently enhancing the myogenic potential of the satellite cells.

Methods

HDACis were added to FAPs and satellite cell cultures isolated from mice. The HDACi vorinostat was additionally administered into a RC injury animal model. Histological analysis was carried out on the isolated supra- and infraspinatus muscles to assess vorinostat anti-muscle degeneration potential.


The Bone & Joint Journal
Vol. 106-B, Issue 9 | Pages 892 - 897
1 Sep 2024
Mancino F Fontalis A Kayani B Magan A Plastow R Haddad FS

Advanced 3D imaging and CT-based navigation have emerged as valuable tools to use in total knee arthroplasty (TKA), for both preoperative planning and the intraoperative execution of different philosophies of alignment. Preoperative planning using CT-based 3D imaging enables more accurate prediction of the size of components, enhancing surgical workflow and optimizing the precision of the positioning of components. Surgeons can assess alignment, osteophytes, and arthritic changes better. These scans provide improved insights into the patellofemoral joint and facilitate tibial sizing and the evaluation of implant-bone contact area in cementless TKA. Preoperative CT imaging is also required for the development of patient-specific instrumentation cutting guides, aiming to reduce intraoperative blood loss and improve the surgical technique in complex cases. Intraoperative CT-based navigation and haptic guidance facilitates precise execution of the preoperative plan, aiming for optimal positioning of the components and accurate alignment, as determined by the surgeon’s philosophy. It also helps reduce iatrogenic injury to the periarticular soft-tissue structures with subsequent reduction in the local and systemic inflammatory response, enhancing early outcomes. Despite the increased costs and radiation exposure associated with CT-based navigation, these many benefits have facilitated the adoption of imaged based robotic surgery into routine practice. Further research on ultra-low-dose CT scans and exploration of the possible translation of the use of 3D imaging into improved clinical outcomes are required to justify its broader implementation.

Cite this article: Bone Joint J 2024;106-B(9):892–897.


Bone & Joint Research
Vol. 7, Issue 10 | Pages 548 - 560
1 Oct 2018
Qayoom I Raina DB Širka A Tarasevičius Š Tägil M Kumar A Lidgren L

During the last decades, several research groups have used bisphosphonates for local application to counteract secondary bone resorption after bone grafting, to improve implant fixation or to control bone resorption caused by bone morphogenetic proteins (BMPs). We focused on zoledronate (a bisphosphonate) due to its greater antiresorptive potential over other bisphosphonates. Recently, it has become obvious that the carrier is of importance to modulate the concentration and elution profile of the zoledronic acid locally. Incorporating one fifth of the recommended systemic dose of zoledronate with different apatite matrices and types of bone defects has been shown to enhance bone regeneration significantly in vivo. We expect the local delivery of zoledronate to overcome the limitations and side effects associated with systemic usage; however, we need to know more about the bioavailability and the biological effects. The local use of BMP-2 and zoledronate as a combination has a proven additional effect on bone regeneration. This review focuses primarily on the local use of zoledronate alone, or in combination with bone anabolic factors, in various preclinical models mimicking different orthopaedic conditions. Cite this article: I. Qayoom, D. B. Raina, A. Širka, Š. Tarasevičius, M. Tägil, A. Kumar, L. Lidgren. Anabolic and antiresorptive actions of locally delivered bisphosphonates for bone repair: A review. Bone Joint Res 2018;7:548–560. DOI: 10.1302/2046-3758.710.BJR-2018-0015.R2


Aims

The aim of this study was to evaluate the healthcare costs and benefits of enoxaparin compared to aspirin in the prevention of symptomatic venous thromboembolism (VTE) after total hip arthroplasty (THA) or total knee arthroplasty (TKA) using data from the CRISTAL trial.

Methods

This trial-based economic analysis reports value for money as incremental cost per quality-adjusted life-year (QALY) gained in 2022 Australian dollars, compared to a single threshold value of AUD$70,000 per QALY. Event costs were estimated based on occurrence of VTEs and bleeds, and on published guidelines for treatment. Unit costs were taken from Australian sources. QALYs were estimated using CRISTAL six-month follow-up data. Sensitivity analyses are presented that vary the cost of VTE treatment, and extend the analyses to two years.


The Bone & Joint Journal
Vol. 97-B, Issue 2 | Pages 177 - 184
1 Feb 2015
Felden A Vaz G Kreps S Anract P Hamadouche M Biau DJ

Conventional cemented acetabular components are reported to have a high rate of failure when implanted into previously irradiated bone. We recommend the use of a cemented reconstruction with the addition of an acetabular reinforcement cross to improve fixation. We reviewed a cohort of 45 patients (49 hips) who had undergone irradiation of the pelvis and a cemented total hip arthroplasty (THA) with an acetabular reinforcement cross. All hips had received a minimum dose of 30 Gray (Gy) to treat a primary nearby tumour or metastasis. The median dose of radiation was 50 Gy (Q1 to Q3: 45 to 60; mean: 49.57, 32 to 72). . The mean follow-up after THA was 51 months (17 to 137). The cumulative probability of revision of the acetabular component for a mechanical reason was 0% (0 to 0%) at 24 months, 2.9% (0.2 to 13.3%) at 60 months and 2.9% (0.2% to 13.3%) at 120 months, respectively. One hip was revised for mechanical failure and three for infection. Cemented acetabular components with a reinforcement cross provide good medium-term fixation after pelvic irradiation. These patients are at a higher risk of developing infection of their THA. . Cite this article: Bone Joint J 2015;97-B:177–84


Bone & Joint 360
Vol. 13, Issue 5 | Pages 39 - 42
1 Oct 2024

The October 2024 Trauma Roundup360 looks at: Early versus delayed weightbearing following operatively treated ankle fracture (WAX): a non-inferiority, multicentre, randomized controlled trial; The effect of early weightbearing and later weightbearing rehabilitation interventions on outcomes after ankle fracture surgery; Is intramedullary nailing of femoral diaphyseal fractures in the lateral decubitus position as safe and effective as on a traction table?; Periprosthetic fractures of the hip: Back to the Future, Groundhog Day, and horses for courses; Two big bones, one big decision: when to fix bilateral femur fractures; Comparison of ankle fracture fixation using intramedullary fibular nailing versus plate fixation; Unclassified acetabular fractures: do they really exist?


Bone & Joint Research
Vol. 11, Issue 11 | Pages 787 - 802
1 Nov 2022
Sebastian S Tandberg F Liu Y Raina DB Tägil M Collin M Lidgren L

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.


Bone & Joint 360
Vol. 11, Issue 6 | Pages 45 - 47
1 Dec 2022

The December 2022 Research Roundup360 looks at: Halicin is effective against Staphylococcus aureus biofilms in vitro; Synovial fluid and serum neutrophil-to-lymphocyte ratio: useful in septic arthritis?; Transcutaneous oximetry and wound healing; Orthopaedic surgery causes gut microbiome dysbiosis and intestinal barrier dysfunction; Mortality in alcohol-related cirrhosis: a nationwide population-based cohort study; Self-reported resistance training is associated with better bone microarchitecture in vegan people.


Bone & Joint 360
Vol. 13, Issue 3 | Pages 35 - 36
3 Jun 2024

The June 2024 Spine Roundup360 looks at: Intraoperative navigation increases the projected lifetime cancer risk in patients undergoing surgery for adolescent idiopathic scoliosis; Intrawound vancomycin powder reduces delayed deep surgical site infections following posterior spinal fusion for adolescent idiopathic scoliosis; Characterizing negative online reviews of spine surgeons; Proximal junctional failure after surgical instrumentation in adult spinal deformity: biomechanical assessment of proximal instrumentation stiffness; Nutritional supplementation and wound healing: a randomized controlled trial.


Bone & Joint Research
Vol. 13, Issue 10 | Pages 546 - 558
4 Oct 2024
Li Y Wuermanbieke S Wang F Mu W Ji B Guo X Zou C Chen Y Zhang X Cao L

Aims

The optimum type of antibiotics and their administration route for treating Gram-negative (GN) periprosthetic joint infection (PJI) remain controversial. This study aimed to determine the GN bacterial species and antibacterial resistance rates related to clinical GN-PJI, and to determine the efficacy and safety of intra-articular (IA) antibiotic injection after one-stage revision in a GN pathogen-induced PJI rat model of total knee arthroplasty.

Methods

A total of 36 consecutive PJI patients who had been infected with GN bacteria between February 2015 and December 2021 were retrospectively recruited in order to analyze the GN bacterial species involvement and antibacterial resistance rates. Antibiotic susceptibility assays of the GN bacterial species were performed to screen for the most sensitive antibiotic, which was then used to treat the most common GN pathogen-induced PJI rat model. The rats were randomized either to a PJI control group or to three meropenem groups (intraperitoneal (IP), IA, and IP + IA groups). After two weeks of treatment, infection control level, the side effects, and the volume of antibiotic use were evaluated.