The lack of an accurate, rapid diagnostic test for mycobacterium tuberculosis (TB) is a major handicap in the management of spinal TB. GeneXpert, a new, rapid molecular diagnostic test is recommended as the first line investigation for suspected pulmonary TB in areas with a high prevalence of HIV or drug resistance, yet it has not been validated for the diagnosis of musculoskeletal TB.

The aim of this study was to assess the accuracy of GeneXpert in diagnosing spinal TB.

A prospective clinical study of 69 consecutive adults with suspected spinal TB was conducted at a tertiary hospital in an area with the highest incidence and prevalence of TB in the world. GeneXpert was used on tissue samples of the enrolled patients and its diagnostic accuracy compared with a reference standard of tissue in liquid culture. A total of 71 spine samples from 69 patients (two re-biopsies) were included in the study.

The GeneXpert test showed a sensitivity of 95.6% and specificity of 96.2% for spinal TB. The results of the GeneXpert test were available within 48 hours compared with a median of 35 days (IQR 15 to 43) for cultures. All cases of multi-drug resistant TB (MDR TB) were diagnosed accurately with the GeneXpert test. The MDR TB rate was 5.8%.

Cite this article: Bone Joint J 2014;96-B:1366–9.

Aims. The preoperative diagnosis of periprosthetic joint infection (PJI) remains a challenge due to a lack of biomarkers that are both sensitive and specific. We investigated the performance characteristics of polymerase chain reaction (PCR), interleukin-6 (IL6), and calprotectin of synovial fluid in the diagnosis of PJI. Methods. We performed systematic search of PubMed, Embase, The Cochrane Library, Web of Science, and Science Direct from the date of inception of each database through to 31 May 2021. Studies which described the diagnostic accuracy of synovial fluid PCR, IL6, and calprotectin using the Musculoskeletal Infection Society criteria as the reference standard were identified. Results. Overall, 31 studies were identified: 20 described PCR, six described IL6, and five calprotectin. The sensitivity and specificity were 0.78 (95% confidence interval (CI) 0.67 to 0.86) and 0.97 (95% CI 0.94 to 0.99), respectively, for synovial PCR;, 0.86 (95% CI 0.74 to 0.92), and 0.94 (95% CI 0.90 to 0.96), respectively, for synovial IL6; and 0.94 (95% CI 0.82 to 0.98) and 0.93 (95% CI 0.85 to 0.97), respectively, for synovial calprotectin. Likelihood ratio scattergram analyses recommended clinical utility of synovial fluid PCR and IL6 as a confirmatory test only. Synovial calprotectin had utility in the exclusion and confirmation of PJI. Conclusion. Synovial fluid PCR and IL6 had low sensitivity and high specificity in the diagnosis of PJI, and is recommended to be used as confirmatory test. In contrast, synovial fluid calprotectin had both high sensitivity and specificity with utility in both the exclusion and confirmation of PJI. We recommend use of synovial fluid calprotectin studies in the preoperative workup of PJI. Cite this article: Bone Joint J 2022;104-B(3):311–320

Aims. Use of molecular sequencing methods in periprosthetic joint infection (PJI) diagnosis and organism identification have gained popularity. Next-generation sequencing (NGS) is a potentially powerful tool that is now commercially available. The purpose of this study was to compare the diagnostic accuracy of NGS, polymerase chain reaction (PCR), conventional culture, the Musculoskeletal Infection Society (MSIS) criteria, and the recently proposed criteria by Parvizi et al in the diagnosis of PJI. Methods. In this retrospective study, aspirates or tissue samples were collected in 30 revision and 86 primary arthroplasties for routine diagnostic investigation for PJI and sent to the laboratory for NGS and PCR. Concordance along with statistical differences between diagnostic studies were calculated. Results. Using the MSIS criteria to diagnose PJI as the reference standard, the sensitivity and specificity of NGS were 60.9% and 89.9%, respectively, while culture resulted in sensitivity of 76.9% and specificity of 95.3%. PCR had a low sensitivity of 18.4%. There was no significant difference based on sample collection method (tissue swab or synovial fluid) (p = 0.760). There were 11 samples that were culture-positive and NGS-negative, of which eight met MSIS criteria for diagnosing infection. Conclusion. In our series, NGS did not provide superior sensitivity or specificity results compared to culture. PCR has little utility as a standalone test for PJI diagnosis with a sensitivity of only 18.4%. Currently, several laboratory tests for PJI diagnosis should be obtained along with the overall clinical picture to help guide decision-making for PJI treatment. Cite this article: Bone Joint J 2021;103-B(1):26–31

Aims. The aim of this study was to determine the extent to which patient demographics, clinical presentation, and blood parameters vary in Kingella kingae septic arthritis when compared with those of other organisms, and whether this difference needs to be considered when assessing children in whom a diagnosis of septic arthritis is suspected. Methods. A prospective case series was undertaken at a single UK paediatric institution between October 2012 and November 2018 of all patients referred with suspected septic arthritis. We recorded the clinical, biochemical, and microbiological findings in all patients. Results. A total of 160 patients underwent arthrotomy for a presumed septic arthritis. Of these, no organism was identified in 61 and only 25 of these were both culture- and polymerase chain reaction (PCR)-negative. A total of 36 patients did not undergo PCR analysis. Of the remaining 99 culture- and PCR-positive patients, K. kingae was the most commonly isolated organism (42%, n = 42). The knee (n = 21), shoulder (n = 9), and hip (n = 5) were the three most commonly affected joints. A total of 28 cases (66%) of K. kingae infection were detected only on PCR. The mean age of K. kingae-positive cases (16.1 months) was significantly lower than that of those whose septic arthitis was due to other organisms (49.4 months; p < 0.001). The mean CRP was significantly lower in the K. kingae group than in the other organism group (p < 0.001). The mean ESR/CRP ratio was significantly higher in K. kingae (2.84) than in other infections (1.55; p < 0.008). The mean ESR and ESR/CRP were not significantly different from those in the 'no organism identified' group. Conclusion. K. kingae was the most commonly isolated organism from paediatric culture- and/or PCR-positive confirmed septic arthritis, with only one third of cases detected on routine cultures. It is important to develop and maintain a clinical suspicion for K. kingae infection in young patients presenting atypically. Routine PCR testing is recommended in these patients. Cite this article: Bone Joint J 2021;103-B(3):584–588

Aims. The aim of this study was to compare the results of 16S/28S rRNA sequencing with the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and synovial fluid analysis in the diagnosis of prosthetic joint infection (PJI). Patients and Methods. Between September 2015 and August 2016, 214 consecutive patients were enrolled. In the study population, there were 25 patients with a PJI and 189 controls. Of the PJI patients, 14 (56%) were women, and the mean age at the time of diagnosis was 65 years (38 to 83). The ESR and CRP levels were measured, and synovial fluid specimens were collected prospectively. Synovial fluid was subjected to reverse transcription polymerase chain reaction (RT-PCR)/sequence analysis targeting the 16S/28S rRNA, and to conventional culture. Laboratory personnel who were blind to the clinical information performed all tests. The diagnosis of PJI was based on the criteria of the Musculoskeletal Infection Society. Results. A total of 25 patients had a confirmed PJI. In 20 cases of monomicrobial PJI, the PCR products could be perfectly matched with the 16S/28S rRNA genes specific for different species of bacteria provided by sequence analysis. Of the five polymicrobial cases of PJI, 16S/28S rRNA PCR sequence analysis failed to identify the concordant bacteria species. In the 189 control patients, there was one false-positive RT-PCR result. The sensitivity and specificity of the molecular diagnosis method were 100% (95% confidence interval (CI) 85.7 to 100) and 99.5% (95% CI 97.1 to 99.9), respectively, whereas the positive and negative predictive values of PCR were 96.1% (95% CI 79.6 to 99.9) and 100% (95% CI 98.1 to 100), respectively. The PCR results were significantly better than serological diagnostic methods (p = 0.004 and p = 0.010 for ESR and CRP, respectively), the synovial fluid white blood cell (WBC) count (p = 0.036), and percentage of polymorphonuclear cells (PMN%) (p = 0.014). Conclusion. Stepwise RT-PCR and sequence analysis of the 16S/28S rRNA carried out under stringent laboratory conditions achieved highly sensitive and specific results for the differentiation between aseptic and septic joints undergoing arthroplasty. Sequence analysis successfully identified bacterial strains in monomicrobial infections but failed to identify molecular targets in polymicrobial infections. Further refinement of the protocols to identify the bacteria in polymicrobial infections is needed. Cite this article: Bone Joint J 2018;100-B:1345–51

MicroRNAs (miRNAs ) are small non-coding RNAs that regulate gene expression. We hypothesised that the functions of certain miRNAs and changes to their patterns of expression may be crucial in the pathogenesis of nonunion. Healing fractures and atrophic nonunions produced by periosteal cauterisation were created in the femora of 94 rats, with 1:1 group allocation. At post-fracture days three, seven, ten, 14, 21 and 28, miRNAs were extracted from the newly generated tissue at the fracture site. Microarray and real-time polymerase chain reaction (PCR) analyses of day 14 samples revealed that five miRNAs, miR-31a-3p, miR-31a-5p, miR-146a-5p, miR-146b-5p and miR-223-3p, were highly upregulated in nonunion. Real-time PCR analysis further revealed that, in nonunion, the expression levels of all five of these miRNAs peaked on day 14 and declined thereafter. . Our results suggest that miR-31a-3p, miR-31a-5p, miR-146a-5p, miR-146b-5p and miR-223-3p may play an important role in the development of nonunion. These findings add to the understanding of the molecular mechanism for nonunion formation and may lead to the development of novel therapeutic strategies for its treatment. Cite this article: Bone Joint J 2015; 97-B:1144–51

Infection of human cartilage with HIV in vivo has not previously been reported. Specimens of articular cartilage taken at postmortem from ten patients who were HIV-positive were examined. Two had AIDS and eight were believed to have stage-2 disease. The standard polymerase chain reaction (PCR) protocol was modified to allow semiquantitative analysis of the samples. Oligonucleotide primers labelled with . 32. P gamma-ATP were used to detect a segment of HIV DNA and a control DNA gene segment (HLA genome) to estimate the ratio of infected cells. The . 32. P-labelled PCR products were separated on acrylamide gels and visualised directly by autoradiography and computer densitometry. Infection of human cartilage in vivo was demonstrated in nine of the ten samples in which the PCR analysis was positive. The other did not react sufficiently to produce detectable radiolabelled PCR product despite repeated DNA digestion and extraction. Cartilage infected with HIV could be a potential source of HIV when used in operations

Aims

This study aimed to investigate the clinical characteristics and outcomes associated with culture-negative limb osteomyelitis patients.

We carried out weight-bearing video radiological studies on 40 patients with a total knee arthroplasty (TKA), to determine the presence and magnitude of femoral condylar lift-off. Half (20) had posterior-cruciate-retaining (PCR) and half (20) posterior-cruciate-substituting (PS) prostheses. The selected patients had successful arthroplasties with no pain or instability. Each carried out successive weight-bearing knee bends to maximum flexion, and the radiological video tapes were analysed using an interactive model-fitting technique. Femoral lift-off was seen at some increment of knee flexion in 75% of patients (PCR TKA 70%; PS TKA 80%). The mean values for lift-off were 1.2 mm with a PCR TKA and 1.4 mm with a PS TKA. Lift-off occurred mostly laterally with the PCR TKA, and both medially and laterally with the PS TKA. Separation between the femoral condyles and the articular surface of the tibia was recorded at 0°, 30°, 60° and 90° of flexion. Femoral condylar lift-off may contribute to eccentric polyethylene wear, particularly in designs of TKA which have flatter condyles. Coronal conformity is an important consideration in the design of a TKA

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.

Aims

This study aimed to answer two questions: what are the best diagnostic methods for diagnosing bacterial arthritis of a native joint?; and what are the most commonly used definitions for bacterial arthritis of a native joint?

Aims

The primary aim was to determine the influence of COVID-19 on 30-day mortality following hip fracture. Secondary aims were to determine predictors of COVID-19 status on presentation and later in the admission; the rate of hospital acquired COVID-19; and the predictive value of negative swabs on admission.

Aims

We aimed to describe the epidemiological, biological, and bacteriological characteristics of osteoarticular infections (OAIs) caused by Kingella kingae.

We evaluated the rates of survival and cause of revision of seven different brands of cemented primary total knee replacement (TKR) in the Norwegian Arthroplasty Register during the years 1994 to 2009. Revision for any cause, including resurfacing of the patella, was the primary endpoint. Specific causes of revision were secondary outcomes. Three posterior cruciate-retaining (PCR) fixed modular-bearing TKRs, two fixed non-modular bearing PCR TKRs and two mobile-bearing posterior cruciate-sacrificing TKRs were investigated in a total of 17 782 primary TKRs. The median follow-up for the implants ranged from 1.8 to 6.9 years. Kaplan-Meier 10-year survival ranged from 89.5% to 95.3%. Cox’s relative risk (RR) was calculated relative to the fixed modular-bearing Profix knee (the most frequently used TKR in Norway), and ranged from 1.1 to 2.6. The risk of revision for aseptic tibial loosening was higher in the mobile-bearing LCS Classic (RR 6.8 (95% confidence interval (CI) 3.8 to 12.1)), the LCS Complete (RR 7.7 (95% CI 4.1 to 14.4)), the fixed modular-bearing Duracon (RR 4.5 (95% CI 1.8 to 11.1)) and the fixed non-modular bearing AGC Universal TKR (RR 2.5 (95% CI 1.3 to 5.1)), compared with the Profix. These implants (except AGC Universal) also had an increased risk of revision for femoral loosening (RR 2.3 (95% CI 1.1 to 4.8), RR 3.7 (95% CI 1.6 to 8.9), and RR 3.4 (95% CI 1.1 to 11.0), respectively). These results suggest that aseptic loosening is related to design in TKR. Cite this article: Bone Joint J 2013;95-B:636–42

Aims

The primary aim was to assess the rate of postoperative COVID-19 following hip and knee arthroplasty performed in March 2020 in the UK. The secondary aims were to assess whether there were clinical factors associated with COVID-19 status, the mortality rate of patients with COVID-19, and the rate of potential COVID-19 in patients not presenting to healthcare services.

Cryopreserved patellar tendon allografts are often recommended for reconstruction of anterior cruciate ligaments (ACLs) because living donor fibroblasts are thought to promote repair. Animal studies, however, indicate that ligaments regenerate from recipient rather than donor cells. If applicable to man, these observations suggest that allograft cell viability is unimportant. We therefore used short tandem repeat analysis with polymerase chain reaction (PCR) amplification to determine the source of cells in nine human ACLs reconstructed with cryopreserved patellar tendon allografts. PCR amplification of donor and recipient DNA obtained before operation and DNA from the graft obtained two to ten months after transplantation revealed the genotype of cells and showed only recipient cells in the graft area. Rather than preserve the viability of donor cells, a technique is required which will facilitate the introduction of recipient cells into patellar tendon allografts

We used fluoroscopy to study the kinematics of the knee in 47 patients with total knee arthroplasty (TKA) and four control subjects with normal knees while performing a single-leg deep-knee bend. The videos were analysed using still photographs taken at 5 degrees increments of flexion. Femorotibial contact points, patellar ligament rotation, and patellar rotation were calculated from each image. Maximum weight-bearing flexion was determined for each knee. Compared with the control group, posterior-cruciate-retaining TKA did not reproduce normal knee kinematics in any case, but showed a starting point posterior to the tibial midline which translated anteriorly with flexion. The curves from successive knee bends could not be consistently reproduced. Under weight-bearing conditions, the maximum flexion for any PCR TKA was 98 degrees and several patients could not flex beyond 70 degrees

We compared the changes in the ratio of type-I and type-II collagen in monolayer cultures of human articular chondrocytes (HAC). HAC were isolated from samples of cartilage from normal joints and cultivated in monolayer for up to 46 days. Expression of collagen type-I and type-II was determined by immunocytochemistry, Western blotting, and the nested reverse transcription polymerase chain reaction (RT-PCR), and quantified by real-time PCR. The transition from a spherical morphology to the flattened morphology of an anchorage-dependent culture was accompanied by a rapid change in the collagen phenotype with the replacement of collagen type II by collagen type I. This was confirmed by immunocytochemistry and Western blotting between days 21 and 28. Using techniques for the analysis of gene transcription (nested RT-PCR and real-time PCR), a complete switch of collagen gene expression was not observed. Expression of collagen type I increased 100-fold during the culture time. That of collagen type II was found during the entire period and decreased more than 100-fold. The main finding was that expression of the genes encoding collagen type I and II was highly time-dependent and the ratio of collagen type II to I (CII/CI), defined as an index of cell differentiation, was significantly higher (215- to 480-fold) at the beginning of the culture. At the end of the experimental culture time, ratios between 0.1 and 1 were reached

Aims

Calprotectin (CLP) is produced in neutrophils and monocytes and released into body fluids as a result of inflammation or infection. The aim of this study was to evaluate the utility of blood and synovial CLP in the diagnosis of chronic periprosthetic joint infection (PJI).