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Bone & Joint Research
Vol. 8, Issue 2 | Pages 49 - 54
1 Feb 2019
Stravinskas M Nilsson M Vitkauskiene A Tarasevicius S Lidgren L

Objectives. The aim of this study was to analyze drain fluid, blood, and urine simultaneously to follow the long-term release of vancomycin from a biphasic ceramic carrier in major hip surgery. Our hypothesis was that there would be high local vancomycin concentrations during the first week with safe low systemic trough levels and a complete antibiotic release during the first month. Methods. Nine patients (six female, three male; mean age 75.3 years (sd 12.3; 44 to 84)) with trochanteric hip fractures had internal fixations. An injectable ceramic bone substitute, with hydroxyapatite in a calcium sulphate matrix, containing 66 mg of vancomycin per millilitre, was inserted to augment the fixation. The vancomycin elution was followed by simultaneously collecting drain fluid, blood, and urine. Results. The antibiotic concentration in the drain reached a peak during the first six hours post-surgery (mean 966.1 mg/l), which decreased linearly to a mean value of 88.3 mg/l at 2.5 days. In the urine, the vancomycin concentration reached 99.8 mg/l during the first two days, followed by a logarithmic decrease over the next two weeks to reach 0 mg/l at 20 days. The systemic concentration of vancomycin measured in blood serum was low and decreased linearly from 2.17 mg/l at one hour post-surgery to 0 mg/l at four days postoperatively. Conclusion. This is the first long-term pharmacokinetic study that reports vancomycin release from a biphasic injectable ceramic bone substitute. The study shows initial high targeted local vancomycin levels, sustained and complete release at three weeks, and systemic concentrations well below toxic levels. The plain ceramic bone substitute has been proven to regenerate bone but should also be useful in preventing bone infection. Cite this article: M. Stravinskas, M. Nilsson, A. Vitkauskiene, S. Tarasevicius, L. Lidgren. Vancomycin elution from a biphasic ceramic bone substitute. Bone Joint Res 2019;8:49–54. DOI: 10.1302/2046-3758.82.BJR-2018-0174.R2


Aims

This study intended to investigate the effect of vericiguat (VIT) on titanium rod osseointegration in aged rats with iron overload, and also explore the role of VIT in osteoblast and osteoclast differentiation.

Methods

In this study, 60 rats were included in a titanium rod implantation model and underwent subsequent guanylate cyclase treatment. Imaging, histology, and biomechanics were used to evaluate the osseointegration of rats in each group. First, the impact of VIT on bone integration in aged rats with iron overload was investigated. Subsequently, VIT was employed to modulate the differentiation of MC3T3-E1 cells and RAW264.7 cells under conditions of iron overload.


Bone & Joint Research
Vol. 12, Issue 9 | Pages 580 - 589
20 Sep 2023
Dai X Liu B Hou Q Dai Q Wang D Xie B Sun Y Wang B

Aims

The aim of this study was to investigate the global and local impact of fat on bone in obesity by using the diet-induced obese (DIO) mouse model.

Methods

In this study, we generated a diet-induced mouse model of obesity to conduct lipidomic and 3D imaging assessments of bone marrow fat, and evaluated the correlated bone adaptation indices and bone mechanical properties.


The Bone & Joint Journal
Vol. 106-B, Issue 10 | Pages 1044 - 1049
1 Oct 2024
Abelleyra Lastoria DA Ogbolu C Olatigbe O Beni R Iftikhar A Hing CB

Aims

To determine whether obesity and malnutrition have a synergistic effect on outcomes from skeletal trauma or elective orthopaedic surgery.

Methods

Electronic databases including MEDLINE, Global Health, Embase, Web of Science, ScienceDirect, and PEDRo were searched up to 14 April 2024, as well as conference proceedings and the reference lists of included studies. Studies were appraised using tools according to study design, including the Oxford Levels of Evidence, the Institute of Health Economics case series quality appraisal checklist, and the CLARITY checklist for cohort studies. Studies were eligible if they reported the effects of combined malnutrition and obesity on outcomes from skeletal trauma or elective orthopaedic surgery.


The Bone & Joint Journal
Vol. 106-B, Issue 6 | Pages 555 - 564
1 Jun 2024
Leal J Holland CT Cochrane NH Seyler TM Jiranek WA Wellman SS Bolognesi MP Ryan SP

Aims

This study aims to assess the relationship between history of pseudotumour formation secondary to metal-on-metal (MoM) implants and periprosthetic joint infection (PJI) rate, as well as establish ESR and CRP thresholds that are suggestive of infection in these patients. We hypothesized that patients with a pseudotumour were at increased risk of infection.

Methods

A total of 1,171 total hip arthroplasty (THA) patients with MoM articulations from August 2000 to March 2014 were retrospectively identified. Of those, 328 patients underwent metal artefact reduction sequence MRI and had minimum two years’ clinical follow-up, and met our inclusion criteria. Data collected included demographic details, surgical indication, laterality, implants used, history of pseudotumour, and their corresponding preoperative ESR (mm/hr) and CRP (mg/dl) levels. Multivariate logistic regression modelling was used to evaluate PJI and history of pseudotumour, and receiver operating characteristic curves were created to assess the diagnostic capabilities of ESR and CRP to determine the presence of infection in patients undergoing revision surgery.


Bone & Joint 360
Vol. 12, Issue 5 | Pages 45 - 47
1 Oct 2023

The October 2023 Research Roundup360 looks at: Gut microbiota in high-risk individuals for rheumatoid arthritis associated with disturbed metabolome and initiates arthritis by triggering mucosal immunity imbalance; International Consensus on Anaemia Management in Surgical Patients (ICCAMS); Sleep disturbance trends in the short-term postoperative period for patients undergoing total joint replacement; Achilles tendon tissue turnover before and immediately after an acute rupture; Quadriceps or hip exercises for patellofemoral pain? A randomized controlled equivalence trial; Total-body MRI for screening in patients with multiple osteochondromas.


The Bone & Joint Journal
Vol. 106-B, Issue 5 | Pages 492 - 500
1 May 2024
Miwa S Yamamoto N Hayashi K Takeuchi A Igarashi K Tada K Taniguchi Y Morinaga S Asano Y Tsuchiya H

Aims

Surgical site infection (SSI) after soft-tissue sarcoma (STS) resection is a serious complication. The purpose of this retrospective study was to investigate the risk factors for SSI after STS resection, and to develop a nomogram that allows patient-specific risk assessment.

Methods

A total of 547 patients with STS who underwent tumour resection between 2005 and 2021 were divided into a development cohort and a validation cohort. In the development cohort of 402 patients, the least absolute shrinkage and selection operator (LASSO) regression model was used to screen possible risk factors of SSI. To select risk factors and construct the prediction nomogram, multivariate logistic regression was used. The predictive power of the nomogram was evaluated by receiver operating curve (ROC) analysis in the validation cohort of 145 patients.


Bone & Joint Research
Vol. 11, Issue 11 | Pages 835 - 842
17 Nov 2022
Wiesli MG Livio F Achermann Y Gautier E Wahl P

Aims

There is a considerable challenge in treating bone infections and orthopaedic device-associated infection (ODAI), partly due to impaired penetration of systemically administrated antibiotics at the site of infection. This may be circumvented by local drug administration. Knowledge of the release kinetics from any carrier material is essential for proper application. Ceftriaxone shows a particular constant release from calcium sulphate (CaSO4) in vitro, and is particularly effective against streptococci and a large portion of Gram-negative bacteria. We present the clinical release kinetics of ceftriaxone-loaded CaSO4 applied locally to treat ODAI.

Methods

A total of 30 operations with ceftriaxone-loaded CaSO4 had been performed in 28 patients. Ceftriaxone was applied as a single local antibiotic in 21 operations and combined with vancomycin in eight operations, and in an additional operation with vancomycin and amphotericin B. Sampling of wound fluid was performed from drains or aspirations. Ceftriaxone concentrations were measured by liquid chromatography with tandem mass spectrometry (LC-MS/MS).


Bone & Joint Research
Vol. 13, Issue 1 | Pages 28 - 39
10 Jan 2024
Toya M Kushioka J Shen H Utsunomiya T Hirata H Tsubosaka M Gao Q Chow SK Zhang N Goodman SB

Aims

Transcription factor nuclear factor kappa B (NF-κB) plays a major role in the pathogenesis of chronic inflammatory diseases in all organ systems. Despite its importance, NF-κB targeted drug therapy to mitigate chronic inflammation has had limited success in preclinical studies. We hypothesized that sex differences affect the response to NF-κB treatment during chronic inflammation in bone. This study investigated the therapeutic effects of NF-κB decoy oligodeoxynucleotides (ODN) during chronic inflammation in male and female mice.

Methods

We used a murine model of chronic inflammation induced by continuous intramedullary delivery of lipopolysaccharide-contaminated polyethylene particles (cPE) using an osmotic pump. Specimens were evaluated using micro-CT and histomorphometric analyses. Sex-specific osteogenic and osteoclastic differentiation potentials were also investigated in vitro, including alkaline phosphatase, Alizarin Red, tartrate-resistant acid phosphatase staining, and gene expression using reverse transcription polymerase chain reaction (RT-PCR).


Bone & Joint Open
Vol. 5, Issue 10 | Pages 832 - 836
4 Oct 2024
Kayani B Mancino F Baawa-Ameyaw J Roussot MA Haddad FS

Aims

The outcomes of patients with unexpected positive cultures (UPCs) during revision total hip arthroplasty (THA) and total knee arthroplasty (TKA) remain unknown. The objectives of this study were to establish the prevalence and infection-free implant survival in UPCs during presumed aseptic single-stage revision THA and TKA at mid-term follow-up.

Methods

This study included 297 patients undergoing presumed aseptic single-stage revision THA or TKA at a single treatment centre. All patients with at least three UPCs obtained during revision surgery were treated with minimum three months of oral antibiotics following revision surgery. The prevalence of UPCs and causative microorganisms, the recurrence of periprosthetic joint infections (PJIs), and the infection-free implant survival were established at minimum five years’ follow-up (5.1 to 12.3).


Bone & Joint Research
Vol. 11, Issue 12 | Pages 854 - 861
1 Dec 2022
Park TJ Park SY Cho W Oh H Lee HJ Abd El-Aty AM Bayram C Jeong JH Jung TW

Aims

Myokine developmental endothelial locus-1 (DEL-1) has been documented to alleviate inflammation and endoplasmic reticulum (ER) stress in various cell types. However, the effects of DEL-1 on inflammation, ER stress, and apoptosis in tenocytes remain unclear.

Methods

Human primary tenocytes were cultured in palmitate (400 μM) and palmitate plus DEL-1 (0 to 2 μg/ml) conditions for 24 hours. The expression levels of ER stress markers and cleaved caspase 3, as well as phosphorylated 5' adenosine monophosphate-activated protein kinase (AMPK) and autophagy markers, were assessed by Western blotting. Autophagosome formation was measured by staining with monodansylcadaverine, and apoptosis was determined by cell viability assay and caspase 3 activity assay.


Bone & Joint Research
Vol. 13, Issue 1 | Pages 4 - 18
2 Jan 2024
Wang Y Wu Z Yan G Li S Zhang Y Li G Wu C

Aims

cAMP response element binding protein (CREB1) is involved in the progression of osteoarthritis (OA). However, available findings about the role of CREB1 in OA are inconsistent. 666-15 is a potent and selective CREB1 inhibitor, but its role in OA is unclear. This study aimed to investigate the precise role of CREB1 in OA, and whether 666-15 exerts an anti-OA effect.

Methods

CREB1 activity and expression of a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4) in cells and tissues were measured by immunoblotting and immunohistochemical (IHC) staining. The effect of 666-15 on chondrocyte viability and apoptosis was examined by cell counting kit-8 (CCK-8) assay, JC-10, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) staining. The effect of 666-15 on the microstructure of subchondral bone, and the synthesis and catabolism of cartilage, in anterior cruciate ligament transection mice were detected by micro-CT, safranin O and fast green (S/F), immunohistochemical staining, and enzyme-linked immunosorbent assay (ELISA).


The Bone & Joint Journal
Vol. 106-B, Issue 4 | Pages 372 - 379
1 Apr 2024
Straub J Staats K Vertesich K Kowalscheck L Windhager R Böhler C

Aims

Histology is widely used for diagnosis of persistent infection during reimplantation in two-stage revision hip and knee arthroplasty, although data on its utility remain scarce. Therefore, this study aims to assess the predictive value of permanent sections at reimplantation in relation to reinfection risk, and to compare results of permanent and frozen sections.

Methods

We retrospectively collected data from 226 patients (90 hips, 136 knees) with periprosthetic joint infection who underwent two-stage revision between August 2011 and September 2021, with a minimum follow-up of one year. Histology was assessed via the SLIM classification. First, we analyzed whether patients with positive permanent sections at reimplantation had higher reinfection rates than patients with negative histology. Further, we compared permanent and frozen section results, and assessed the influence of anatomical regions (knee versus hip), low- versus high-grade infections, as well as first revision versus multiple prior revisions on the histological result at reimplantation. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), chi-squared tests, and Kaplan-Meier estimates were calculated.


Bone & Joint Research
Vol. 11, Issue 10 | Pages 700 - 714
4 Oct 2022
Li J Cheung W Chow SK Ip M Leung SYS Wong RMY

Aims

Biofilm-related infection is a major complication that occurs in orthopaedic surgery. Various treatments are available but efficacy to eradicate infections varies significantly. A systematic review was performed to evaluate therapeutic interventions combating biofilm-related infections on in vivo animal models.

Methods

Literature research was performed on PubMed and Embase databases. Keywords used for search criteria were “bone AND biofilm”. Information on the species of the animal model, bacterial strain, evaluation of biofilm and bone infection, complications, key findings on observations, prevention, and treatment of biofilm were extracted.


Bone & Joint Research
Vol. 13, Issue 7 | Pages 362 - 371
17 Jul 2024
Chang H Liu L Zhang Q Xu G Wang J Chen P Li C Guo X Yang Z Zhang F

Aims

The metabolic variations between the cartilage of osteoarthritis (OA) and Kashin-Beck disease (KBD) remain largely unknown. Our study aimed to address this by conducting a comparative analysis of the metabolic profiles present in the cartilage of KBD and OA.

Methods

Cartilage samples from patients with KBD (n = 10) and patients with OA (n = 10) were collected during total knee arthroplasty surgery. An untargeted metabolomics approach using liquid chromatography coupled with mass spectrometry (LC-MS) was conducted to investigate the metabolomics profiles of KBD and OA. LC-MS raw data files were converted into mzXML format and then processed by the XCMS, CAMERA, and metaX toolbox implemented with R software. The online Kyoto Encyclopedia of Genes and Genomes (KEGG) database was used to annotate the metabolites by matching the exact molecular mass data of samples with those from the database.


Bone & Joint Research
Vol. 12, Issue 2 | Pages 91 - 102
1 Feb 2023
Li Z Chen M Wang Z Fan Q Lin Z Tao X Wu J Liu Z Lin R Zhao C

Aims

Rheumatoid arthritis (RA) is a common chronic immune disease. Berberine, as its main active ingredient, was also contained in a variety of medicinal plants such as Berberaceae, Buttercup, and Rutaceae, which are widely used in digestive system diseases in traditional Chinese medicine with anti-inflammatory and antibacterial effects. The aims of this article were to explore the therapeutic effect and mechanism of berberine on rheumatoid arthritis.

Methods

Cell Counting Kit-8 was used to evaluate the effect of berberine on the proliferation of RA fibroblast-like synoviocyte (RA-FLS) cells. The effect of berberine on matrix metalloproteinase (MMP)-1, MMP-3, receptor activator of nuclear factor kappa-Β ligand (RANKL), tumour necrosis factor alpha (TNF-α), and other factors was determined by enzyme-linked immunoassay (ELISA) kit. Transcriptome technology was used to screen related pathways and the potential targets after berberine treatment, which were verified by reverse transcription-polymerase chain reaction (RT-qPCR) and Western blot (WB) technology.


Bone & Joint Research
Vol. 13, Issue 10 | Pages 535 - 545
2 Oct 2024
Zou C Guo W Mu W Wahafu T Li Y Hua L Xu B Cao L

Aims

We aimed to determine the concentrations of synovial vancomycin and meropenem in patients treated by single-stage revision combined with intra-articular infusion following periprosthetic joint infection (PJI), thereby validating this drug delivery approach.

Methods

We included 14 patients with PJI as noted in their medical records between November 2021 and August 2022, comprising eight hip and seven knee joint infections, with one patient experiencing bilateral knee infections. The patients underwent single-stage revision surgery, followed by intra-articular infusion of vancomycin and meropenem (50,000 µg/ml). Synovial fluid samples were collected to assess antibiotic concentrations using high-performance liquid chromatography.


Bone & Joint Research
Vol. 12, Issue 4 | Pages 259 - 273
6 Apr 2023
Lu R Wang Y Qu Y Wang S Peng C You H Zhu W Chen A

Aims

Osteoarthritis (OA) is a prevalent joint disorder with inflammatory response and cartilage deterioration as its main features. Dihydrocaffeic acid (DHCA), a bioactive component extracted from natural plant (gynura bicolor), has demonstrated anti-inflammatory properties in various diseases. We aimed to explore the chondroprotective effect of DHCA on OA and its potential mechanism.

Methods

In vitro, interleukin-1 beta (IL-1β) was used to establish the mice OA chondrocytes. Cell counting kit-8 evaluated chondrocyte viability. Western blotting analyzed the expression levels of collagen II, aggrecan, SOX9, inducible nitric oxide synthase (iNOS), IL-6, matrix metalloproteinases (MMPs: MMP1, MMP3, and MMP13), and signalling molecules associated with nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. Immunofluorescence analysis assessed the expression of aggrecan, collagen II, MMP13, and p-P65. In vivo, a destabilized medial meniscus (DMM) surgery was used to induce mice OA knee joints. After injection of DHCA or a vehicle into the injured joints, histological staining gauged the severity of cartilage damage.


The Bone & Joint Journal
Vol. 105-B, Issue 4 | Pages 439 - 448
15 Mar 2023
Hong H Pan X Song J Fang N Yang R Xiang L Wang X Huang C

Aims

The prevalence of scoliosis is not known in patients with idiopathic short stature, and the impact of treatment with recombinant human growth hormone on those with scoliosis remains controversial. We investigated the prevalence of scoliosis radiologically in children with idiopathic short stature, and the impact of treatment with growth hormone in a cross-sectional and retrospective cohort study.

Methods

A total of 2,053 children with idiopathic short stature and 4,106 age- and sex-matched (1:2) children without short stature with available whole-spine radiographs were enrolled in the cross-sectional study. Among them, 1,056 with idiopathic short stature and 790 controls who had radiographs more than twice were recruited to assess the development and progression of scoliosis, and the need for bracing and surgery.


The Bone & Joint Journal
Vol. 106-B, Issue 9 | Pages 1021 - 1030
1 Sep 2024
Oto J Herranz R Fuertes M Plana E Verger P Baixauli F Amaya JV Medina P

Aims

Bacterial infection activates neutrophils to release neutrophil extracellular traps (NETs) in bacterial biofilms of periprosthetic joint infections (PJIs). The aim of this study was to evaluate the increase in NET activation and release (NETosis) and haemostasis markers in the plasma of patients with PJI, to evaluate whether such plasma induces the activation of neutrophils, to ascertain whether increased NETosis is also mediated by reduced DNaseI activity, to explore novel therapeutic interventions for NETosis in PJI in vitro, and to evaluate the potential diagnostic use of these markers.

Methods

We prospectively recruited 107 patients in the preoperative period of prosthetic surgery, 71 with a suspicion of PJI and 36 who underwent arthroplasty for non-septic indications as controls, and obtained citrated plasma. PJI was confirmed in 50 patients. We measured NET markers, inflammation markers, DNaseI activity, haemostatic markers, and the thrombin generation test (TGT). We analyzed the ability of plasma from confirmed PJI and controls to induce NETosis and to degrade in vitro-generated NETs, and explored the therapeutic restoration of the impairment to degrade NETs of PJI plasma with recombinant human DNaseI. Finally, we assessed the contribution of these markers to the diagnosis of PJI.