Aims. To assess the diagnostic value of C-reactive protein (CRP), leucocyte count (LC), and erythrocyte sedimentation rate (ESR) in late fracture-related infection (FRI). Materials and Methods. PubMed, Embase, and Cochrane databases were searched focusing on the diagnostic value of CRP, LC, and ESR in late FRI. Sensitivity and specificity combinations were extracted for each marker. Average estimates were obtained using bivariate mixed effects models. Results. A total of 8284 articles were identified but only six were suitable for inclusion. Sensitivity of CRP ranged from 60.0% to 100.0% and specificity from 34.3% to 85.7% in all publications considered. Five articles were pooled for meta-analysis, showing a sensitivity and specificity of 77.0% and 67.9%, respectively. For LC, this was 22.9% to 72.6%, and 73.5% to 85.7%, respectively, in five articles. Four articles were pooled for meta-analysis, resulting in a 51.7% sensitivity and 67.1% specificity. For ESR, sensitivity and specificity ranged from 37.1% to 100.0% and 59.0% to 85.0%, respectively, in five articles. Three articles were pooled in meta-analysis, showing a 45.1% sensitivity and 79.3% specificity. Four articles analyzed the value of combined inflammatory markers, reporting an increased diagnostic accuracy. These results could not be pooled due to heterogeneity. Conclusion. The serum inflammatory markers CRP, LC, and ESR are insufficiently accurate to diagnose late FRI, but they may be used as a suggestive sign in its diagnosis

Aims. Spinal tuberculosis (TB) remains an important concern. Although spinal TB often has sequelae such as myelopathy after treatment, the predictive factors affecting such unfavourable outcomes are not yet established. We investigated the clinical manifestations and predictors of unfavourable treatment outcomes in patients with spinal TB. Patients and Methods. We performed a multicentre retrospective cohort study of patients with spinal TB. Unfavourable outcome was defined according to previous studies. The prognostic factors for unfavourable outcomes as the primary outcome were determined using multivariable logistic regression analysis and a linear mixed model was used to compare time course of inflammatory markers during treatment. A total of 185 patients were included, of whom 59 patients had unfavourable outcomes. Results. In multivariate regression analysis, the factors associated with unfavourable outcome were old age (odds ratio (OR) 2.51; 95% confidence interval (CI) 1.07 to 5.86; p = 0.034), acid-fast bacilli (AFB) smear positivity in specimens obtained through biopsy (OR 3.05; 95% CI 1.06 to 8.80; p = 0.039), and elevated erythrocyte sedimentation rate (ESR) at the end of treatment (OR 3.85; 95% CI 1.62 to 9.13; p = 0.002). Patients with unfavourable outcomes had a significant trend toward higher ESR during treatment compared with patients with favourable outcome (p = 0.009). Duration of anti-TB and surgical treatment did not affect prognosis. Conclusion. Elevated ESR at the end of treatment could be used as a marker to identify spinal TB patients with a poor prognosis. Patients whose ESR is not normalized during treatment, as well as those with old age and AFB smear positivity, should be aware of unfavourable outcomes. Cite this article: Bone Joint J 2019;101-B:1542–1549

Aims. Prosthetic joint infection (PJI) and aseptic loosening in total hip arthroplasty (THA) can present with pain and osteolysis. The Musculoskeletal Infection Society (MSIS) has provided criteria for the diagnosis of PJI. The aim of our study was to analyze the utility of F18-fluorodeoxyglucose (FDG) positron emission tomography (PET) CT scan in the preoperative diagnosis of septic loosening in THA, based on the current MSIS definition of prosthetic joint infection. Patients and Methods. A total of 130 painful unilateral cemented THAs with a mean follow-up of 5.17 years (. sd. 1.12) were included in this prospective study. The mean patient age was 67.5 years (. sd. 4.85). Preoperative evaluation with inflammatory markers, aspiration, and an F18 FDG PET scan were performed. Diagnostic utility tests were also performed, based on the MSIS criteria for PJI and three samples positive on culture alone. Results. The mean erythrocyte sedimentation rate, C-reactive protein, and white cell count were 47.83 mm/hr, 25.21 mg/l, and 11.05 × 10. 9. /l, respectively. The sensitivity, specificity, accuracy, negative predictive value, and false-positive rate of FDG PET compared with MSIS criteria were 94.87%, 38.46 %, 56.38%, 94.59 %, and 60.21%, respectively. The false-positive rate of FDG PET compared with culture alone was 77.4%. Conclusion. FDG PET has a definitive role in the preoperative evaluation of suspected PJI. This the first study to evaluate its utility based on MSIS criteria and compare it with microbiology results alone. However, FDG PET has a high false-positive rate. Therefore, we suggest that F18 FDG PET is useful in confirming the absence of infection, but if positive, may not be confirmatory of PJI. Cite this article: Bone Joint J 2019;101-B:910–914

Objectives. The diagnosis of periprosthetic joint infection (PJI) is difficult and requires a battery of tests and clinical findings. The purpose of this review is to summarize all current evidence for common and new serum biomarkers utilized in the diagnosis of PJI. Methods. We searched two literature databases, using terms that encompass all hip and knee arthroplasty procedures, as well as PJI and statistical terms reflecting diagnostic parameters. The findings are summarized as a narrative review. Results. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were the two most commonly published serum biomarkers. Most evidence did not identify other serum biomarkers that are clearly superior to ESR and CRP. Other serum biomarkers have not demonstrated superior sensitivity and have failed to replace CRP and ESR as first-line screening tests. D-dimer appears to be a promising biomarker, but more research is necessary. Factors that influence serum biomarkers include temporal trends, stage of revision, and implant-related factors (metallosis). Conclusion. Our review helped to identify factors that can influence serum biomarkers’ level changes; the recognition of such factors can help improve their diagnostic utility. As such, we cannot rely on ESR and CRP alone for the diagnosis of PJI prior to second-stage reimplantation, or in metal-on-metal or corrosion cases. The future of serum biomarkers will likely shift towards using genomics and proteomics to identify proteins transcribed via messenger RNA in response to infection and sepsis. Cite this article: A. Saleh, J. George, M. Faour, A. K. Klika, C. A. Higuera. Serum biomarkers in periprosthetic joint infections. Bone Joint Res 2018;7:85–93. DOI: 10.1302/2046-3758.71.BJR-2017-0323

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

This prospective study evaluates the role of new laboratory markers in the diagnosis of deep implant infection in 78 patients (41 men and 37 women) with a revision total knee or hip replacement. The mean age at the time of operation was 64.0 years (19 to 90). Intra-operative cultures showed that 21 patients had a septic and 57 an aseptic total joint replacement. The white blood cell count, the erythrocyte sedimentation rate and levels of C-reactive protein, interleukin-6, procalcitonin and tumour necrosis factor (TNF)-α were measured in blood samples before operation. The diagnostic cut-off values were determined by Received Operating Characteristic curve analysis. C-reactive protein (> 3.2 md/dl) and interleukin-6 (> 12 pg/ml) have the highest sensitivity (0.95). Interleukin-6 is less specific than C-reactive protein (0.87 vs 0.96). Combining C-reactive protein and interleukin-6 identifies all patients with deep infection of the implant. Procalcitonin (> 0.3 ng/ml) and TNF-α (> 40 ng/ml) are very specific (0.98 vs 0.94) but have a low sensitivity (0.33 vs 0.43). The combination of C-reactive protein and interleukin-6 measurement provide excellent screening tests for infection of a deep implant. A highly specific marker such as procalcitonin and pre-operative aspiration of the joint might be useful in identifying patients with true positive C-reactive protein and/or interleukin-6 levels

The aim of this study was to assess the role of synovial C-reactive protein (CRP) in the diagnosis of chronic periprosthetic hip infection. We prospectively collected synovial fluid from 89 patients undergoing revision hip arthroplasty and measured synovial CRP, serum CRP, erythrocyte sedimentation rate (ESR), synovial white blood cell (WBC) count and synovial percentages of polymorphonuclear neutrophils (PMN). Patients were classified as septic or aseptic by means of clinical, microbiological, serum and synovial fluid findings. The high viscosity of the synovial fluid precluded the analyses in nine patients permitting the results in 80 patients to be studied. There was a significant difference in synovial CRP levels between the septic (n = 21) and the aseptic (n = 59) cohort. According to the receiver operating characteristic curve, a synovial CRP threshold of 2.5 mg/l had a sensitivity of 95.5% and specificity of 93.3%. The area under the curve was 0.96. Compared with serum CRP and ESR, synovial CRP showed a high diagnostic value. According to these preliminary results, synovial CRP may be a useful parameter in diagnosing chronic periprosthetic hip infection. Cite this article: Bone Joint J 2015; 97-B:173–6

Thirty patients with non-tuberculous pyogenic osteomyelitis of the spine are reported in all of whom the diagnosis was confirmed bacteriologically, histologically or serologically. The clinical and radiological features and investigations are analysed. Back pain, localised to the level involved, was the predominant symptom. The erythrocyte sedimentation rate was raised in all cases, and a characteristic sequence of radiological features is described

In the literature 21 children have been reported with haematogenous osteomyelitis involving only the epiphyses of long bones; in 20 the epiphyses of the knee were involved and the radiographs showed a lytic lesion. Most patients gave a history of pain, limp or refusal to walk for weeks or months without general illness. The erythrocyte sedimentation rate and white cell count were of little diagnostic value, but a bone scan was usually positive. All the patients were cured by antibiotics alone or in combination with curettage

We have reviewed 60 patients with primary bone infections; 21 of these (35%) had subacute osteomyelitis, a figure which supports other recent observations that this variant of bone infection is becoming more widespread. In this group open culture and biopsy were necessary in order to exclude bony malignancy, and a raised erythrocyte sedimentation rate proved a useful diagnostic aid. All the patients with acute osteomyelitis or with vertebral infection responded to primary treatment, but five of those with subacute osteomyelitis had recurrences

A study of cadaveric vertebral biopsy and a review of 100 clinical biopsies has shown that needles and trephines producing tissue specimens of two millimetres or more in diameter can be expected to give a high degree of diagnostic accuracy. The erythrocyte sedimentation rate was a more useful screening investigation than were estimations of serum alkaline phosphatase. The complications are described. It is suggested that patients with painful thoracic metastases and evidence of progressive cord compression should have early decompression after open biopsy if further neurological compromise is to be prevented

An unusual form of chronic osteomyelitis in children is described. Three children presented with clinical signs of acute infection and radiographs revealed a pre-existing destructive bone lesion. Exploration of the lesions did not release pus, and cultures for pathogens were negative. The lesions healed but the symptoms returned intermittently over many years with the development of sclerosis and disturbance of bone growth. The lesions did not respond to antibiotics or operative treatment. All the patients were fully investigated and although the erythrocyte sedimentation rate was increased the white blood count was seldom abnormal. There were no neurological abnormalities. Two of the three cases required an osteotomy to correct malalignment. A comparison is made between the findings in these three patients with similar cases reported recently and possible causes are discussed

The British Orthopaedic Association assessment questionnaire for knee replacements was adapted to allow comparison of the severity of underlying polyarthritis with the benefits of geometric knee replacement in a retrospective study of 150 knees between six months and six years after operation. Total or partial relief of pain was achieved in 81 per cent of the operation, and changes in mobility occurred in fewer patients. Late sepsis remained a serious complication of nine per cent of the operations and one patient died from septicaemia. Late sepsis was associated with previous synovectomy or osteotomy. Retropatellar pain rarely interfered with the mobility of the patient. There was no association of operations that failed with a high erythrocyte sedimentation rate, a high platelet count, a low haemoglobin level or with a strongly positive rheumatoid factor but pain in the contralateral knee was associated with a diminished functional capacity

Infection of the intervertebral space is a rare complication of operation on the disc (Ford and Key 1955). It occurred in five cases in a series of 650 operations for lumbar disc protrusion done by two of the authors of this paper--an incidence of 0-8%. Symptoms began between seven and twelve days after operation. After initial relief of the original sciatic pain, the patients developed severe back pain and muscle cramps in the legs. Straight-leg raising became much more limited than before operation. The erythrocyte sedimentation rate was raised in all cases. The diagnosis was confirmed by rescreening the Myodil, when an indentation was seen opposite the intervertebral space from which the disc had been excised. Early removal of infected material from the disc space resulted in complete relief of pain and cure of the infection

In 50 patients with non-infected total hip arthroplasties (THA), 233 C-reactive protein (CRP) values were obtained over a three-year period. Six of these 50 patients occasionally had CRP values of over 20 mg/l. The erythrocyte sedimentation rate (ESR) and CRP concentration were measured in 23 patients with deep infections of THA before revision. In 11 patients the infections were caused by coagulase-negative staphylococci. CRP exceeded 20 mg/l in 18 patients and the ESR was more than 30 mm/hr in 14. In only one infected patient were both CRP and ESR below these levels. All of 33 patients with non-septic loosening had CRP less than 20 mg/l and ESR less than 30 mm/hr before revision. C-reactive protein seems to be a valuable supplement to the ESR in the monitoring of infection after THA

From 1981 to 1986 we treated 413 patients for acute spinal-cord injuries. We reviewed 356 patients followed for a minimum of two years of whom 71 (20%) developed heterotopic ossification around one or more joints. Heterotopic ossification occurred more often in male patients (23%) than in female (10%), and was most frequent in the 20- to 30-year age group. It was also more common after injuries of the lower cervical or thoracic spine than after those of the lumbar spine. Patients with severe neurological deficits (Frankel grades A and B) showed significantly more heterotopic ossification but there was no correlation with the number or severity of associated head and limb injuries. Serum calcium levels did not change significantly in either group for 30 weeks after injury, but the erythrocyte sedimentation rate and the alkaline phosphatase level were significantly increased at six weeks in patients with heterotopic ossification

1. Forty patients with solitary eosinophilic granuloma of bone from the Hospital for Sick Children, Toronto, have been reviewed. They had clinical and laboratory findings similar to those reported by others except for the erythrocyte sedimentation rate, which was raised in nearly half the patients tested. 2. Radiographs in all cases showed the lesion to be osteolytic. In the skull and cervical spine there was no bony reaction ; in the thoracic and lumbar spine the typical picture of Calvés disease was produced; in long bones the cortex commonly showed endosteal erosion and periosteal reaction. 3. In one patient the lesion progressed so rapidly that the body of a cervical vertebra was destroyed within ten days. 4. The differential diagnosis includes sarcoma. Biopsy is essential. 5. All the patients improved regardless of the treatment they received. Complications were due either to the site of the lesion or to its treatment. 6. Expansion of the lesion after biopsy indicates a more widespread manifestation of histiocytosis X

Clinical prediction algorithms are used to differentiate transient synovitis from septic arthritis. These algorithms typically include the erythrocyte sedimentation rate (ESR), although in clinical practice measurement of the C-reactive protein (CRP) has largely replaced the ESR. We evaluated the use of CRP in a predictive algorithm. The records of 311 children with an effusion of the hip, which was confirmed on ultrasound, were reviewed (mean age 5.3 years (0.2 to 15.1)). Of these, 269 resolved without intervention and without long-term sequelae and were considered to have had transient synovitis. The remaining 42 underwent arthrotomy because of suspicion of septic arthritis. Infection was confirmed in 29 (18 had micro-organisms isolated and 11 had a high synovial fluid white cell count). In the remaining 13 no evidence of infection was found and they were also considered to have had transient synovitis. In total 29 hips were categorised as septic arthritis and 282 as transient synovitis. The temperature, weight-bearing status, peripheral white blood cell count and CRP was reviewed in each patient. A CRP > 20 mg/l was the strongest independent risk factor for septic arthritis (odds ratio 81.9, p < 0.001). A multivariable prediction model revealed that only two determinants (weight-bearing status and CRP > 20 mg/l) were independent in differentiating septic arthritis from transient synovitis. Individuals with neither predictor had a < 1% probability of septic arthritis, but those with both had a 74% probability of septic arthritis. A two-variable algorithm can therefore quantify the risk of septic arthritis, and is an excellent negative predictor.

1. A primary subacute type of staphylococcal osteomyelitis has been described. It is the commonest form of osteomyelitis seen in East Africa, and the incidence appears to be increasing in Great Britain. 2. A review of the literature indicates that this is not a new disease but that in the past there has been some confusion in terminology. 3. The causative organism is a coagulase positive staphylococcus, but in a few instances a coagulase negative one has been isolated. The staphylococcus is thought to be of reduced virulence and in East Africa it is likely that the population has acquired an increased resistance to the staphylococcus. 4. Two radiologically distinct groups are recognised, depending on whether a bone abscess is present or not. In the first group there are two types of localised abscesses: the familiar Brodie's lesion and the less well recognised large bone abscess that occurs in the metaphysis of a long bone. While the pathology of the two types is similar, the radiological features are quite distinct. The lesions in the second group are characterised by extensive diaphysial changes, with or without metaphysial involvement, and an obvious abscess cannot usually be demonstrated. 5. The main clinical features are the long history, often weeks or months, before diagnosis; insignificant or absent general reaction to the infection and minimum physical signs. 6. Vertebral body osteomyelitis in adults is included because it generally presents as a subacute infection; the difficulties in distinguishing it from a tuberculous infection are outlined. 7. The most useful diagnostic aids are the staphylococcal antibody titres (especially in vertebral infections) and the erythrocyte sedimentation rate. A limited surgical exposure is usually required if the causative organism is to be isolated and empirical antibiotic therapy is to be avoided. The total and differential white blood count are so often normal in these patients that they are considered to be of no diagnostic value. 8. Curettage and local antibiotics together will cure the localised bone abscess. Other lesions may be effectively treated by systemic antibiotics alone, but in the later stages removal of sequestra and infected granulation tissue may be necessary. In this instance it is essential to make a planned incision and to cut a window in the bone large enough to expose the whole of the lesion; primary suture of the wound is advocated

Aims

There is a lack of evidence about the risk factors for local recurrence of a giant cell tumour (GCT) of the sacrum treated with nerve-sparing surgery, probably because of the rarity of the disease. This study aimed to answer two questions: first, what is the rate of local recurrence of sacral GCT treated with nerve-sparing surgery and second, what are the risk factors for its local recurrence?