Objectives. Circulating exosomes represent novel biomarkers for multiple diseases. In this study, we investigated whether circulating exosome levels could be used as a diagnostic biomarker for steroid-induced osteonecrosis of the femoral head (ONFH). Methods. We assessed the serum exosome level of 85 patients with steroid-induced ONFH and 115 healthy donors by Nanosight detection. We then assessed the diagnostic accuracy of serum exosomes by receiver operating characteristic curve analysis. Results. The circulating exosome level of the ONFH group was significantly lower than that of control group. The area under the curve was 0.72, suggesting that the level of serum exosomes has moderate diagnostic accuracy for steroid-induced ONFH. Conclusion. Circulating exosome levels are valuable in the diagnosis of steroid-induced ONFH. Cite this article: H-Y. Zhu, Y-C. Gao, Y. Wang, C-Q. Zhang. Circulating exosome levels in the diagnosis of steroid-induced osteonecrosis of the femoral head. Bone Joint Res 2016;5:276–279. DOI: 10.1302/2046-3758.56.BJR-2015-0014.R1

Aims. The aim of this study was to determine the diagnostic accuracy of α defensin (AD) lateral flow assay (LFA) and enzyme-linked immunosorbent assay (ELISA) tests for periprosthetic joint infection (PJI) in comparison to conventional synovial white blood cell (WBC) count and polymorphonuclear neutrophil percentage (PMN%) analysis. Methods. Patients undergoing joint aspiration for evaluation of pain after total knee arthroplasty (TKA) or total hip arthroplasty (THA) were considered for inclusion. Synovial fluids from 99 patients (25 THA and 74 TKA) were analyzed by WBC count and PMN% analysis, AD LFA, and AD ELISA. WBC and PMN% cutoffs of ≥ 1,700 cells/mm. 3. and ≥ 65% for TKA and ≥ 3,000 cells/mm. 3. and ≥ 80% for THA were used, respectively. A panel of three physicians, all with expertise in orthopaedic infections and who were blinded to the results of AD tests, independently reviewed patient data to diagnose subjects as with or without PJI. Consensus PJI classification was used as the reference standard to evaluate test performances. Results were compared using McNemar’s test and area under the receiver operating characteristic curve (AUC) analysis. Results. Expert consensus classified 18 arthroplasies as having failed due to PJI and 81 due to aseptic failure. Using these classifications, the calculated sensitivity and specificity of AD LFA was 83.3% (95% confidence interval (CI) 58.6 to 96.4) and 93.8% (95% CI 86.2 to 98.0), respectively. Sensitivity and specificity of AD ELISA was 83.3% (95% CI 58.6 to 96.4) and 96.3% (95% CI 89.6 to 99.2), respectively. There was no statistically significant difference between sensitivity (p = 1.000) or specificity (p = 0.157) of the two AD assays. AUC for AD LFA was 0.891. In comparison, AUC for synovial WBC count, PMN%, and the combination of the two values was 0.821 (sensitivity p = 1.000, specificity p < 0.001), 0.886 (sensitivity p = 0.317, specificity p = 0.011), and 0.926 (sensitivity p = 0.317, specificity p = 0.317), respectively. Conclusion. The diagnostic accuracy of synovial AD for PJI diagnosis is comparable and not statistically superior to that of synovial WBC count plus PMN% combined. Cite this article: Bone Joint J 2021;103-B(6):1119–1126

Aims. The aims of this study were to increase the diagnostic accuracy of the analysis of synovial fluid in the differentiation of prosthetic joint infection (PJI) by the addition of inexpensive biomarkers such as the levels of C-reactive protein (CRP), adenosine deaminase (ADA), alpha-2-macrogloblulin (α2M) and procalcitonin. Patients and Methods. Between January 2013 and December 2015, synovial fluid and removed implants were requested from 143 revision total joint arthroplasties. A total of 55 patients met inclusion criteria of the receipt of sufficient synovial fluid, tissue samples and removed implants for analysis. The diagnosis of PJI followed the definition from a recent International Consensus Meeting to create two groups of patients; septic and aseptic. Using receiver operating characteristic curves we determined the cutoff values and diagnostic accuracy for each marker. Results. There were 23 PJIs and 32 patients with aseptic loosening. The levels of total leucocyte count, proportion of polymorphonuclear leucocytes (PMNs), CRP, ADA and α2M in the synovial fluid were all significantly higher in those with a PJI than in those with aseptic loosening. The levels of procalcitonin were comparable in the two groups. Cutoff values for the optimal performance in the diagnosis of infection were: total leucocyte count > 1463 cells/μL (sensitivity (Sens) 100%, specificity (Spec) 71.9%, positive predictive value (PPV) 71.9%, negative predictive value (NPV) 100%); proportion of PMNs > 81% (Sens 78.3%, Spec 75.0%, PPV 69.2%, NPV 82.8%); CRP > 6.7mg/L (Sens 78.3%, Spec 93.8%, PPV 90.0%, NPV 85.7%); ADA > 61U/L (Sens 78.3%, Spec 96.9%, PPV 94.7%, NPV 86.1%) and α2M > 958 mg/L (Sens 47.8%, Spec 96.9%, PPV 91.7%, NPV 72.1%). The addition of a raised level of CRP or ADA to the total leukocyte count increased the specificity: total leukocyte count > 1463 cells/μL and CRP > 6.7mg/L (Sens 78.3%, Spec 100%, PPV 100%, NPV 86.5%) or with ADA > 61U/L (Sens 78.3%, Spec 96.9%, PPV 94.7%, NPV 86.1%). . Conclusion. The total leucocyte count in the synovial fluid offers great negative predictive value in the diagnosis of PJI and the addition of more specific markers such as CRP and ADA improves the positive predictive value. Thus the addition of simple and inexpensive markers to the measurement of the leucocyte count in the synovial fluid may reduce the number of equivocal results which demand more expensive investigation. Cite this article: Bone Joint J 2017;99-B:351–7

Aims. The purpose of this study was to validate the diagnosis of periprosthetic joint infection (PJI) in the Danish Hip Arthroplasty Register (DHR). Patients and Methods. We identified a cohort of patients from the DHR who had undergone primary total hip arthroplasty (THA) since 1 January 2005 and followed them until first-time revision, death, emigration or until 31 December 2012. Revision for PJI, as registered in the DHR, was validated against a benchmark which included information from microbiology databases, prescription registers, clinical biochemistry registers and clinical records. We estimated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for PJI in the DHR alone and in the DHR when combined with microbiology databases. Results. In total, 1382 of the 37 826 primary THAs in the DHR were registered as having been revised for any cause once 26 patients with errors in registration had been excluded: 232 of these were for PJI. For this group, the sensitivity was 67%, specificity 95%, PPV 77%, and NPV 92%. Combining the data from the DHR with those from microbiology databases increased the sensitivity to 90% and also improved specificity (100%), PPV (98%) and NPV (98%). Conclusion. Only two thirds of revisions for PJI were captured in the DHR and only 77% of the PJI reported to the DHR could be confirmed to be infected. . Take home message: combining the data from the DHR with those from microbiology databases substantially improved the validity of the diagnosis of PJI and should enable future register-based studies. Cite this article: Bone Joint J 2016;98-B:320–5

We evaluated the diagnostic accuracy of fine-needle aspiration biopsy in a prospective study of 300 patients with previously undiagnosed bone lesions. Patients with suspected local recurrence of a primary bone tumour or a metastatic lesion of a previously diagnosed malignancy were excluded. Fine-needle aspiration biopsy was performed under radiological control as an outpatient procedure. The series was grouped into three major categories: 1) benign bone lesions including infections; 2) primary malignant bone tumours; and 3) metastases including lymphomas and myelomas. We compared the cytological diagnosis with the final diagnosis as assessed by histological examination and/or the clinical and radiological features. Material considered conclusive for cytological diagnosis was obtained from 251 of the 300 patients. Of the 49 failures, there were 24 aspirates with insufficient cellular yield and 25 in which a diagnosis could not be made although the cytological material was adequate in quantity. Most of the inconclusive aspirates (36/49) were obtained from benign bone lesions. The diagnosis was correct in 239 (95%) of the 251 cases providing adequate cytological material. There were eight (3%) falsely benign diagnoses, one (0.3%) falsely malignant, and three cases in which we were unable to differentiate between sarcoma and a metastasis. Chondrosarcoma (2/12) gave the greatest diagnostic difficulty and Ewing’s sarcoma the least (0/9). There were no decisive errors of treatment. All falsely benign or malignant diagnoses were questioned, and led to open biopsy since they did not correlate with the clinical and radiological features. Our study suggests that fine-needle aspiration biopsy is a valid option for the diagnosis of bone tumours. It is a simple outpatient procedure which gives sufficient cytological material for the correct diagnosis in 80% of cases. As with histological analysis of material from open biopsy, the cytological assessment must agree with the clinical and radiological findings

Aims. The diagnosis of periprosthetic joint infection (PJI) remains demanding due to limitations of all the available diagnostic tests. The synovial fluid marker, α-defensin, is a promising adjunct for the assessment of potential PJI. The purpose of this study was to investigate the qualitative assessment of α-defensin, using Synovasure to detect or exclude periprosthetic infection in total joint arthroplasty. Patients and Methods. We studied 50 patients (28 women, 22 men, mean age 65 years; 20 to 89) with a clinical indication for revision arthroplasty who met the inclusion criteria of this prospective diagnostic study. The presence of α-defensin was determined using the qualitative Synovasure test and compared with standard diagnostic methods for PJI. Based on modified Musculoskeletal Infection Society (MSIS) criteria, 13 cases were categorised as septic and 36 as aseptic revisions. One test was inconclusive. Results. The Synovasure test achieved a sensitivity of 69% and a specificity of 94%. The positive and negative likelihood ratios were 12.46 and 0.33, respectively. A good diagnostic accuracy for PJI, with an area under the curve of 0.82, was demonstrated. Adjusted p-values using the method of Hochberg showed that Synovasure is as good at diagnosing PJI as histology (p = 0.0042) and bacteriology with one positive culture (p = 0.0327). Conclusion. With its ease of use and rapid results after approximately ten minutes, Synovasure may be a useful adjunct in the diagnosis of PJI. Cite this article: Bone Joint J 2017;99-B:66–72

We investigated the eventual diagnosis in patients referred to a tertiary centre with a possible diagnosis of a primary bone malignancy. We reviewed our database from between 1986 and 2010, during which time 5922 patients referred with a suspicious bone lesion had a confirmed diagnosis. This included bone sarcoma in 2205 patients (37%), benign bone tumour in 1309 (22%), orthopaedic conditions in 992 (17%), metastatic disease in 533 (9%), infection in 289 (5%) and haematological disease in 303 (5%). There was a similar frequency of all diagnoses at different ages except for metastatic disease. Only 0.6% of patients (17 of 2913) under the age of 35 years had metastatic disease compared with 17.1% (516 of 3009) of those over 35 years (p < 0.0001). Of the 17 patients under 35 years with metastatic disease, only four presented with an isolated lesion, had no past history of cancer and were systematically well. Patients under the age of 35 years should have suitable focal imaging (plain radiography, CT or MRI) and simple systemic studies (blood tests and chest radiography). Reduction of the time to biopsy can be achieved by avoiding an unnecessary investigation for a primary tumour to rule out metastatic disease

In recent years, machine learning (ML) and artificial neural networks (ANNs), a particular subset of ML, have been adopted by various areas of healthcare. A number of diagnostic and prognostic algorithms have been designed and implemented across a range of orthopaedic sub-specialties to date, with many positive results. However, the methodology of many of these studies is flawed, and few compare the use of ML with the current approach in clinical practice. Spinal surgery has advanced rapidly over the past three decades, particularly in the areas of implant technology, advanced surgical techniques, biologics, and enhanced recovery protocols. It is therefore regarded an innovative field. Inevitably, spinal surgeons will wish to incorporate ML into their practice should models prove effective in diagnostic or prognostic terms. The purpose of this article is to review published studies that describe the application of neural networks to spinal surgery and which actively compare ANN models to contemporary clinical standards allowing evaluation of their efficacy, accuracy, and relatability. It also explores some of the limitations of the technology, which act to constrain the widespread adoption of neural networks for diagnostic and prognostic use in spinal care. Finally, it describes the necessary considerations should institutions wish to incorporate ANNs into their practices. In doing so, the aim of this review is to provide a practical approach for spinal surgeons to understand the relevant aspects of neural networks.

Cite this article: Bone Joint J 2021;103-B(9):1442–1448.

Aims

This study aimed to evaluate calprotectin in synovial fluid for diagnosing chronic prosthetic joint infection (PJI) .

Aims

Monocyte-lymphocyte ratio (MLR) or neutrophil-lymphocyte ratio (NLR) are useful for diagnosing periprosthetic joint infection (PJI), but their diagnostic values are unclear for screening fixation-related infection (FRI) in patients for whom conversion total hip arthroplasty (THA) is planned after failed internal fixation for femoral neck fracture.

In 52 patients we compared the accuracy of standard anteroposterior (AP) radiography, mortise radiography and MRI with arthroscopy of the ankle for the diagnosis of a tear of the tibiofibular syndesmosis. In comparison with arthroscopy, the sensitivity, specificity and accuracy were 44.1%, 100% and 63.5% for standard AP radiography and 58.3%, 100% and 71.2% for mortise radiography. For MRI they were 100%, 93.1% and 96.2% for a tear of the anterior inferior tibiofibular ligament and 100%, 100% and 100% for a tear of the posterior inferior tibiofibular ligament. Standard AP and mortise radiography did not always provide a correct diagnosis. MRI was useful although there were two-false positive cases. We suggest that arthroscopy of the ankle is indispensable for the accurate diagnosis of a tear of the tibiofibular syndesmosis

Aims. The aim of this study was to identify the association between asymmetrical skin creases of the thigh, buttock or inguinal region and pathological developmental dysplasia of the hip (DDH). Patients and Methods. Between 1 January 1996 and 31 December 2016, all patients referred to our unit from primary or secondary care with risk factors for DDH were assessed in a “one stop” clinic. All had clinical and sonographic assessment by the senior author (RWP) with the results being recorded prospectively. The inclusion criteria for this study were babies and children referred with asymmetrical skin creases. Those with a neurological cause of DDH were excluded. The positive predictive value (PPV) for pathological DDH was calculated. Results. A total of 105 patients met the inclusion criteria. There were 71 girls and 34 boys. Only two were found to have pathological DDH. Both also had unilateral limited abduction of the hip in flexion and a positive Galeazzi sign with apparent leg-length discrepancy. Thus, if the specialist examination of a patient with asymmetrical skin creases was normal, the PPV for DDH was 0%. Conclusion. Isolated asymmetrical skin creases are an unreliable clinical sign in the diagnosis of pathological DDH. Greater emphasis should be placed on the presence of additional clinical signs to guide radiological screening in babies and children. Cite this article: Bone Joint J 2018;100-B:675–9

A delay in the diagnosis of paediatric acute and subacute haematogenous osteomyelitis can lead to potentially devastating morbidity. There are no definitive guidelines for diagnosis, and recommendations in the literature are generally based on expert opinions, case series and cohort studies. All articles in the English literature on paediatric osteomyelitis were searched using MEDLINE, CINAHL, EMBASE, Google Scholar, the Cochrane Library and reference lists. A total of 1854 papers were identified, 132 of which were examined in detail. All aspects of osteomyelitis were investigated in order to formulate recommendations. On admission 40% of children are afebrile. The tibia and femur are the most commonly affected long bones. Clinical examination, blood and radiological tests are only reliable for diagnosis in combination. Staphylococcus aureus is the most common organism detected, but isolation of Kingella kingae is increasing. Antibiotic treatment is usually sufficient to eradicate the infection, with a short course intravenously and early conversion to oral treatment. Surgery is indicated only in specific situations. Most studies were retrospective and there is a need for large, multicentre, randomised, controlled trials to define protocols for diagnosis and treatment. Meanwhile, evidence-based algorithms are suggested for accurate and early diagnosis and effective treatment

We have previously shown that cytological diagnosis based on fine-needle aspiration biopsy (FNAB) is a safe and efficient method for the discrimination between benign, primary malignant and metastatic bony lesions. We have now studied metastatic lesions to assess the diagnostic accuracy and to ascertain whether FNAB allows identification of the primary lesion. Between 1990 and 1997, 447 patients were referred for diagnosis of skeletal lesions of unknown type. Of these 119 proved to have metastatic disease, either myeloma or lymphoma. Nine were excluded leaving 110 consecutive patients with metastatic carcinoma (80), myeloma (16) or lymphoma (14). FNAB gave a correct diagnosis in 102 of the 110 patients (93%). In eight it was inconclusive. It correctly diagnosed 15 of 16 patients with myeloma, 12 of 14 with lymphoma, and 75 of 80 with metastatic carcinoma. Furthermore, the site and type of malignancy were correctly suggested in two-thirds of patients with metastatic carcinoma. Overall, only seven open biopsies were carried out. We conclude that time-consuming and costly investigations can be reduced by choosing FNAB as the initial diagnostic method for skeletal lesions of unknown origin. The choice of radiological examinations, laboratory tests and surgical biopsies can be determined by using FNAB

Aims. The purpose of this current multicentre study is to analyse the presence of alpha-defensin proteins in synovial fluid using the Synovasure lateral flow device and to determine its diagnostic reliability and accuracy compared with the prosthetic joint infection (PJI) criteria produced by the Musculoskeletal Infection Society (MSIS). Patients and Methods. A cohort of 121 patients comprising 85 total knee arthroplasties and 36 total hip arthroplasties was prospectively evaluated between May 2015 and June 2016 in three different orthopaedic centres. The tests were performed on patients with a chronically painful prosthesis undergoing a joint aspiration in a diagnostic pathway or during revision surgery. Results. Based on the MSIS criteria, 34 patients (28%) would have had a PJI, and 87 patients had no PJI. Testing with the lateral flow device had a sensitivity of 97.1% (95% confidence intervals (CI) 84.5 to 99.9) and a specificity of 96.6% (95% CI 90.3 to 99.2). The positive predictive value was 91.7% (95% CI 77.7% to 98.3), and the negative predictive value was 98.8% (95% CI 93.6 to 99.9). Receiver operator characteristics analysis demonstrated an area under the curve for the Synovasure test of 0.97 (95% CI 0.93 to 1.00). Conclusion. Our findings suggest that the Synovasure test has an excellent diagnostic performance to confirm or reject the diagnosis of a PJI. The results are promising for the care of the painful or problematic knee and hip joint arthroplasty and the test should be considered as part of the diagnostic toolbox for PJIs. Cite this article: Bone Joint J 2017;99-B:1176–82

In many papers, the diagnosis of pincer-type femoroacetabular impingement (FAI) is attributed to the presence of coxa profunda. However, little is known about the prevalence of coxa profunda in the general population and its clinical relevance. In order to ascertain its prevalence in asymptomatic subjects and whether it is a reliable indicator of pincer-type FAI, we undertook a cross-sectional study between July and December 2013. A total of 226 subjects (452 hips) were initially screened. According to strict inclusion criteria, 129 asymptomatic patients (257 hips) were included in the study. The coxa profunda sign, the crossover sign, the acetabular index (AI) and lateral centre–edge (LCE) angle were measured on the radiographs. The median age of the patients was 36.5 years (28 to 50) and 138 (53.7%) were women. Coxa profunda was present in 199 hips (77.4%). There was a significantly increased prevalence of coxa profunda in women (p < 0.05) and a significant association between coxa profunda and female gender (p < 0.001) (92% vs 60.5%). The crossover sign was seen in 36 hips (14%), an LCE > 40° in 28 hips (10.9%) and an AI < 0º in 79 hips (30.7%). A total of 221 normal hips (79.2%) (normal considering the crossover) had coxa profunda, a total of 229 normal hips (75.5%) (normal considering the LCE) had coxa profunda and a total of 178 normal hips (75.3%) (normal considering AI) had coxa profunda. When the presence of all radiological signs in the same subject was considered, pincer-type FAI was found in only two hips (one subject). We therefore consider that the coxa profunda sign should not be used as a radiological indicator of pincer-type FAI. We consider profunda to be a benign alteration in the morphology of the hip with low prevalence and a lack of association with other radiological markers of FAI. We suggest that the diagnosis of pincer-type FAI should be based on objective measures, in association with clinical findings. Cite this article: Bone Joint J 2015; 97-B:478–83

The diagnosis of nerve injury using thermotropic liquid crystal temperature strips was compared blindly and prospectively against operative findings in 36 patients requiring surgical exploration for unilateral upper limb lacerations with suspected nerve injury. Thermotropic liquid crystal strips were applied to affected and non-affected segments in both hands in all subjects. A pilot study showed that a simple unilateral laceration without nerve injury results in a cutaneous temperature difference between limbs, but not within each limb. Thus, for detection of a nerve injury, comparison was made against the unaffected nerve distribution in the same hand. Receiver operating characteristic curve analysis showed that an absolute temperature difference ≥ 1.0°C was diagnostic of a nerve injury (area under the curve = 0.985, sensitivity = 100%, specificity = 93.8%). Thermotropic liquid crystal strip assessment is a new, reliable and objective method for the diagnosis of traumatic peripheral nerve injuries. If implemented in the acute setting, it could improve the reliability of clinical assessment and reduce the number of negative surgical explorations

The causes of persistent symptoms after meniscectomy have been assessed clinically, radiologically and arthroscopically in 174 knees. The commonest finding was early degenerative arthritis (chondromalacia) of the femoral condyle (40 per cent). Retained fragments of meniscus were less common than expected (13 per cent), and lesions of the other meniscus were rare (5 per cent). The clinical diagnosis was altered in 42 per cent by arthroscopic examination. Arthroscopy was found to be a valuable technique in this group of patients with problems of diagnosis

Although bone and soft-tissue sarcomas are rare, early diagnosis and prompt referral to a specialised unit offers the best chance of a successful outcome both in terms of survival and surgical resection. This paper highlights the clinical and radiological features that might suggest the possibility of a bone or soft-tissue sarcoma and suggests a succinct management pathway for establishing whether a suspicious bone or soft-tissue lesion could be malignant