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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. Results. Patients with confirmed PJI had significantly increased levels of NET markers (cfDNA (p < 0.001), calprotectin (p < 0.001), and neutrophil elastase (p = 0.022)) and inflammation markers (IL-6; p < 0.001) in plasma. Moreover, the plasma of patients with PJI induced significantly more neutrophil activation than the plasma of the controls (p < 0.001) independently of tumour necrosis factor alpha. Patients with PJI also had a reduced DNaseI activity in plasma (p < 0.001), leading to a significantly impaired degradation of NETs (p < 0.001). This could be therapeutically restored with recombinant human DNaseI to the level in the controls. We developed a model to improve the diagnosis of PJI with cfDNA, calprotectin, and the start tail of TGT as predictors, though cfDNA alone achieved a good prediction and is simpler to measure. Conclusion. We confirmed that patients with PJI have an increased level of NETosis in plasma. Their plasma both induced NET release and had an impaired ability to degrade NETs mediated by a reduced DNaseI activity. This can be therapeutically restored in vitro with the approved Dornase alfa, Pulmozyme, which may allow novel methods of treatment. A combination of NETs and haemostatic biomarkers could improve the diagnosis of PJI, especially those patients in whom this diagnosis is uncertain. Cite this article: Bone Joint J 2024;106-B(9):1021–1030


Bone & Joint Research
Vol. 13, Issue 8 | Pages 411 - 426
28 Aug 2024
Liu D Wang K Wang J Cao F Tao L

Aims

This study explored the shared genetic traits and molecular interactions between postmenopausal osteoporosis (POMP) and sarcopenia, both of which substantially degrade elderly health and quality of life. We hypothesized that these motor system diseases overlap in pathophysiology and regulatory mechanisms.

Methods

We analyzed microarray data from the Gene Expression Omnibus (GEO) database using weighted gene co-expression network analysis (WGCNA), machine learning, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to identify common genetic factors between POMP and sarcopenia. Further validation was done via differential gene expression in a new cohort. Single-cell analysis identified high expression cell subsets, with mononuclear macrophages in osteoporosis and muscle stem cells in sarcopenia, among others. A competitive endogenous RNA network suggested regulatory elements for these genes.


Bone & Joint Open
Vol. 4, Issue 7 | Pages 539 - 550
21 Jul 2023
Banducci E Al Muderis M Lu W Bested SR

Aims

Safety concerns surrounding osseointegration are a significant barrier to replacing socket prosthesis as the standard of care following limb amputation. While implanted osseointegrated prostheses traditionally occur in two stages, a one-stage approach has emerged. Currently, there is no existing comparison of the outcomes of these different approaches. To address safety concerns, this study sought to determine whether a one-stage osseointegration procedure is associated with fewer adverse events than the two-staged approach.

Methods

A comprehensive electronic search and quantitative data analysis from eligible studies were performed. Inclusion criteria were adults with a limb amputation managed with a one- or two-stage osseointegration procedure with follow-up reporting of complications.


Bone & Joint Open
Vol. 4, Issue 3 | Pages 146 - 157
7 Mar 2023
Camilleri-Brennan J James S McDaid C Adamson J Jones K O'Carroll G Akhter Z Eltayeb M Sharma H

Aims

Chronic osteomyelitis (COM) of the lower limb in adults can be surgically managed by either limb reconstruction or amputation. This scoping review aims to map the outcomes used in studies surgically managing COM in order to aid future development of a core outcome set.

Methods

A total of 11 databases were searched. A subset of studies published between 1 October 2020 and 1 January 2011 from a larger review mapping research on limb reconstruction and limb amputation for the management of lower limb COM were eligible. All outcomes were extracted and recorded verbatim. Outcomes were grouped and categorized as per the revised Williamson and Clarke taxonomy.


Bone & Joint Open
Vol. 2, Issue 9 | Pages 721 - 727
1 Sep 2021
Zargaran A Zargaran D Trompeter AJ

Aims

Orthopaedic infection is a potentially serious complication of elective and emergency trauma and orthopaedic procedures, with a high associated burden of morbidity and cost. Optimization of vitamin D levels has been postulated to be beneficial in the prevention of orthopaedic infection. This study explores the role of vitamin D in orthopaedic infection through a systematic review of available evidence.

Methods

A comprehensive search was conducted on databases including Medline and Embase, as well as grey literature such as Google Scholar and The World Health Organization Database. Pooled analysis with weighted means was undertaken.


Bone & Joint Open
Vol. 2, Issue 8 | Pages 599 - 610
1 Aug 2021
Hothi H Bergiers S Henckel J Iliadis AD Goodier WD Wright J Skinner J Calder P Hart AJ

Aims

The aim of this study was to present the first retrieval analysis findings of PRECICE STRYDE intermedullary nails removed from patients, providing useful information in the post-market surveillance of these recently introduced devices.

Methods

We collected ten nails removed from six patients, together with patient clinical data and plain radiograph imaging. We performed macro- and microscopic analysis of all surfaces and graded the presence of corrosion using validated semiquantitative scoring methods. We determined the elemental composition of surface debris using energy dispersive x-ray spectroscopy (EDS) and used metrology analysis to characterize the surface adjacent to the extendable junctions.


Bone & Joint Research
Vol. 10, Issue 7 | Pages 425 - 436
16 Jul 2021
Frommer A Roedl R Gosheger G Hasselmann J Fuest C Toporowski G Laufer A Tretow H Schulze M Vogt B

Aims

This study aims to enhance understanding of clinical and radiological consequences and involved mechanisms that led to corrosion of the Precice Stryde (Stryde) intramedullary lengthening nail in the post market surveillance era of the device. Between 2018 and 2021 more than 2,000 Stryde nails have been implanted worldwide. However, the outcome of treatment with the Stryde system is insufficiently reported.

Methods

This is a retrospective single-centre study analyzing outcome of 57 consecutive lengthening procedures performed with the Stryde nail at the authors’ institution from February 2019 until November 2020. Macro- and microscopic metallographic analysis of four retrieved nails was conducted. To investigate observed corrosion at telescoping junction, scanning electron microscopy (SEM) and energy dispersive x-ray spectroscopy (EDX) were performed.


Bone & Joint Open
Vol. 1, Issue 10 | Pages 628 - 638
6 Oct 2020
Mott A Mitchell A McDaid C Harden M Grupping R Dean A Byrne A Doherty L Sharma H

Aims

Bone demonstrates good healing capacity, with a variety of strategies being utilized to enhance this healing. One potential strategy that has been suggested is the use of stem cells to accelerate healing.

Methods

The following databases were searched: MEDLINE, CENTRAL, EMBASE, Cochrane Database of Systematic Reviews, WHO-ICTRP, ClinicalTrials.gov, as well as reference checking of included studies. The inclusion criteria for the study were: population (any adults who have sustained a fracture, not including those with pre-existing bone defects); intervention (use of stem cells from any source in the fracture site by any mechanism); and control (fracture healing without the use of stem cells). Studies without a comparator were also included. The outcome was any reported outcomes. The study design was randomized controlled trials, non-randomized or observational studies, and case series.


The Bone & Joint Journal
Vol. 101-B, Issue 3 | Pages 288 - 296
1 Mar 2019
Sigmund IK Holinka J Sevelda F Staats K Heisinger S Kubista B McNally MA Windhager R

Aims

This study aimed to assess the performance of an automated multiplex polymerase chain reaction (mPCR) technique for rapid diagnosis of native joint septic arthritis

Patients and Methods

Consecutive patients with suspected septic arthritis undergoing aseptic diagnostic joint aspiration were included. The aspirate was used for analysis by mPCR and conventional microbiological analysis. A joint was classed as septic according to modified Newman criteria. Based on receiver operating characteristic (ROC) analysis, the area under the ROC curve (AUC) values of the mPCR and the synovial fluid culture were compared using the z-test. A total of 72 out of 76 consecutive patients (33 women, 39 men; mean age 64 years (22 to 92)) with suspected septic arthritis were included in this study.


The Bone & Joint Journal
Vol. 97-B, Issue 9 | Pages 1296 - 1300
1 Sep 2015
Jauregui JJ Bor N Thakral R Standard SC Paley D Herzenberg JE

External fixation is widely used in orthopaedic and trauma surgery. Infections around pin or wire sites, which are usually localised, non-invasive, and are easily managed, are common. Occasionally, more serious invasive complications such as necrotising fasciitis (NF) and toxic shock syndrome (TSS) may occur.

We retrospectively reviewed all patients who underwent external fixation between 1997 and 2012 in our limb lengthening and reconstruction programme. A total of eight patients (seven female and one male) with a mean age of 20 years (5 to 45) in which pin/wire track infections became limb- or life-threatening were identified. Of these, four were due to TSS and four to NF. Their management is described. A satisfactory outcome was obtained with early diagnosis and aggressive medical and surgical treatment.

Clinicians caring for patients who have external fixation and in whom infection has developed should be aware of the possibility of these more serious complications. Early diagnosis and aggressive treatment are required in order to obtain a satisfactory outcome.

Cite this article: Bone Joint J 2015;97-B:1296–1300.


The Bone & Joint Journal
Vol. 97-B, Issue 5 | Pages 582 - 589
1 May 2015
Brennan SA Ní Fhoghlú C Devitt BM O’Mahony FJ Brabazon D Walsh A

Implant-associated infection is a major source of morbidity in orthopaedic surgery. There has been extensive research into the development of materials that prevent biofilm formation, and hence, reduce the risk of infection. Silver nanoparticle technology is receiving much interest in the field of orthopaedics for its antimicrobial properties, and the results of studies to date are encouraging. Antimicrobial effects have been seen when silver nanoparticles are used in trauma implants, tumour prostheses, bone cement, and also when combined with hydroxyapatite coatings. Although there are promising results with in vitro and in vivo studies, the number of clinical studies remains small. Future studies will be required to explore further the possible side effects associated with silver nanoparticles, to ensure their use in an effective and biocompatible manner. Here we present a review of the current literature relating to the production of nanosilver for medical use, and its orthopaedic applications.

Cite this article: Bone Joint J 2015; 97-B:582–9.


Bone & Joint Research
Vol. 4, Issue 5 | Pages 84 - 92
1 May 2015
Hamamura K Nishimura A Iino T Takigawa S Sudo A Yokota H

Objectives

Salubrinal is a synthetic agent that elevates phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α) and alleviates stress to the endoplasmic reticulum. Previously, we reported that in chondrocytes, Salubrinal attenuates expression and activity of matrix metalloproteinase 13 (MMP13) through downregulating nuclear factor kappa B (NFκB) signalling. We herein examine whether Salubrinal prevents the degradation of articular cartilage in a mouse model of osteoarthritis (OA).

Methods

OA was surgically induced in the left knee of female mice. Animal groups included age-matched sham control, OA placebo, and OA treated with Salubrinal or Guanabenz. Three weeks after the induction of OA, immunoblotting was performed for NFκB p65 and p-NFκB p65. At three and six weeks, the femora and tibiae were isolated and the sagittal sections were stained with Safranin O.


Bone & Joint Research
Vol. 4, Issue 5 | Pages 70 - 77
1 May 2015
Gupta A Liberati TA Verhulst SJ Main BJ Roberts MH Potty AGR Pylawka TK El-Amin III SF

Objectives

The purpose of this study was to evaluate in vivo biocompatibility of novel single-walled carbon nanotubes (SWCNT)/poly(lactic-co-glycolic acid) (PLAGA) composites for applications in bone and tissue regeneration.

Methods

A total of 60 Sprague-Dawley rats (125 g to 149 g) were implanted subcutaneously with SWCNT/PLAGA composites (10 mg SWCNT and 1gm PLAGA 12 mm diameter two-dimensional disks), and at two, four, eight and 12 weeks post-implantation were compared with control (Sham) and PLAGA (five rats per group/point in time). Rats were observed for signs of morbidity, overt toxicity, weight gain and food consumption, while haematology, urinalysis and histopathology were completed when the animals were killed.


The Bone & Joint Journal
Vol. 97-B, Issue 4 | Pages 572 - 576
1 Apr 2015
Polfer EM Hope DN Elster EA Qureshi AT Davis TA Golden D Potter BK Forsberg JA

Currently, there is no animal model in which to evaluate the underlying physiological processes leading to the heterotopic ossification (HO) which forms in most combat-related and blast wounds. We sought to reproduce the ossification that forms under these circumstances in a rat by emulating patterns of injury seen in patients with severe injuries resulting from blasts. We investigated whether exposure to blast overpressure increased the prevalence of HO after transfemoral amputation performed within the zone of injury. We exposed rats to a blast overpressure alone (BOP-CTL), crush injury and femoral fracture followed by amputation through the zone of injury (AMP-CTL) or a combination of these (BOP-AMP). The presence of HO was evaluated using radiographs, micro-CT and histology. HO developed in none of nine BOP-CTL, six of nine AMP-CTL, and in all 20 BOP-AMP rats. Exposure to blast overpressure increased the prevalence of HO.

This model may thus be used to elucidate cellular and molecular pathways of HO, the effect of varying intensities of blast overpressure, and to evaluate new means of prophylaxis and treatment of heterotopic ossification.

Cite this article: Bone Joint J 2015;97-B:572–6


The Bone & Joint Journal
Vol. 96-B, Issue 11 | Pages 1561 - 1565
1 Nov 2014
Park JW Kim YS Yoon JO Kim JS Chang JS Kim JM Chun JM Jeon IH

Non-tuberculous mycobacterial (NTM) infection of the musculoskeletal tissue is a rare disease. An early and accurate diagnosis is often difficult because of the indolent clinical course and difficulty of isolating pathogens. Our goal was to determine the clinical features of musculoskeletal NTM infection and to present the treatment outcomes. A total of 29 patients (nine females, 20 males between 34 and 85 years old, mean age 61.7 years; 34 to 85) with NTM infection of the musculoskeletal system between 1998 to 2011 were identified and their treatment retrospectively analysed. Microbiological studies demonstrated NTM in 29 patients: the isolates were Mycobacterium intracellulare in six patients, M. fortuitum in three, M. abscessus in two and M. marinum in one. In the remaining patients we failed to identify the species. The involved sites were the hand/wrist in nine patients the knee in five patients, spine in four patients, foot in two patients, elbow in two patients, shoulder in one, ankle in two patients, leg in three patients and multiple in one patient. The mean interval between the appearance of symptoms and diagnosis was 20.8 months (1.5 to 180). All patients underwent surgical treatment and antimicrobial medication according to our protocol for chronic musculoskeletal infection: 20 patients had NTM-specific medication and nine had conventional antimicrobial therapy. At the final follow-up 22 patients were cured, three failed to respond to treatment and four were lost to follow-up. Identifying these diseases due the initial non-specific presentation can be difficult. Treatment consists of surgical intervention and adequate antimicrobial therapy, which can result in satisfactory outcomes.

Cite this article: Bone Joint J 2014;96-B:1561–5.


The Bone & Joint Journal
Vol. 96-B, Issue 10 | Pages 1287 - 1289
1 Oct 2014
Nikiphorou E Konan S MacGregor AJ Haddad FS Young A

There has been an in increase in the availability of effective biological agents for the treatment of rheumatoid arthritis as well as a shift towards early diagnosis and management of the inflammatory process. This article explores the impact this may have on the place of orthopaedic surgery in the management of patients with rheumatoid arthritis.

Cite this article: Bone Joint J 2014;96-B:1287–9


The Bone & Joint Journal
Vol. 96-B, Issue 6 | Pages 829 - 836
1 Jun 2014
Ferguson JY Dudareva M Riley ND Stubbs D Atkins BL McNally MA

We report our experience using a biodegradable calcium sulphate antibiotic carrier containing tobramycin in the surgical management of patients with chronic osteomyelitis. The patients were reviewed to determine the rate of recurrent infection, the filling of bony defects, and any problems with wound healing. A total of 193 patients (195 cases) with a mean age of 46.1 years (16.1 to 82.0) underwent surgery. According to the Cierny–Mader classification of osteomyelitis there were 12 type I, 1 type II, 144 type III and 38 type IV cases. The mean follow-up was 3.7 years (1.3 to 7.1) with recurrent infection occurring in 18 cases (9.2%) at a mean of 10.3 months post-operatively (1 to 25.0). After further treatment the infection resolved in 191 cases (97.9%). Prolonged wound ooze (longer than two weeks post-operatively) occurred in 30 cases (15.4%) in which there were no recurrent infection. Radiographic assessment at final follow-up showed no filling of the defect with bone in 67 (36.6%), partial filling in 108 (59.0%) and complete filling in eight (4.4%). A fracture occurred in nine (4.6%) of the treated osteomyelitic segments at a mean of 1.9 years (0.4 to 4.9) after operation.

We conclude that Osteoset T is helpful in the management of patients with chronic osteomyelitis, but the filling of the defect in bone is variable. Prolonged wound ooze is usually self-limiting and not associated with recurrent infection.

Cite this article: Bone Joint J 2014; 96-B:829–36


Bone & Joint Research
Vol. 3, Issue 6 | Pages 193 - 202
1 Jun 2014
Hast MW Zuskov A Soslowsky LJ

Tendinopathy is a debilitating musculoskeletal condition which can cause significant pain and lead to complete rupture of the tendon, which often requires surgical repair. Due in part to the large spectrum of tendon pathologies, these disorders continue to be a clinical challenge. Animal models are often used in this field of research as they offer an attractive framework to examine the cascade of processes that occur throughout both tendon pathology and repair. This review discusses the structural, mechanical, and biological changes that occur throughout tendon pathology in animal models, as well as strategies for the improvement of tendon healing.

Cite this article: Bone Joint Res 2014;3:193–202.


The Bone & Joint Journal
Vol. 96-B, Issue 5 | Pages 569 - 573
1 May 2014
Sullivan MP McHale KJ Parvizi J Mehta S

Nanotechnology is the study, production and controlled manipulation of materials with a grain size < 100 nm. At this level, the laws of classical mechanics fall away and those of quantum mechanics take over, resulting in unique behaviour of matter in terms of melting point, conductivity and reactivity. Additionally, and likely more significant, as grain size decreases, the ratio of surface area to volume drastically increases, allowing for greater interaction between implants and the surrounding cellular environment. This favourable increase in surface area plays an important role in mesenchymal cell differentiation and ultimately bone–implant interactions. Basic science and translational research have revealed important potential applications for nanotechnology in orthopaedic surgery, particularly with regard to improving the interaction between implants and host bone. Nanophase materials more closely match the architecture of native trabecular bone, thereby greatly improving the osseo-integration of orthopaedic implants. Nanophase-coated prostheses can also reduce bacterial adhesion more than conventionally surfaced prostheses. Nanophase selenium has shown great promise when used for tumour reconstructions, as has nanophase silver in the management of traumatic wounds. Nanophase silver may significantly improve healing of peripheral nerve injuries, and nanophase gold has powerful anti-inflammatory effects on tendon inflammation. . Considerable advances must be made in our understanding of the potential health risks of production, implantation and wear patterns of nanophase devices before they are approved for clinical use. Their potential, however, is considerable, and is likely to benefit us all in the future. Cite this article: Bone Joint J 2014; 96-B: 569–73


The Bone & Joint Journal
Vol. 96-B, Issue 3 | Pages 420 - 425
1 Mar 2014
Fahal AH Shaheen S Jones DHA

This article presents an overview of mycetoma and offers guidelines for orthopaedic surgeons who may be involved in the care of patients with this condition.

Cite this article: Bone Joint J 2014;96-B:420–5.