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

The aim of this study was to determine whether the level of circulating C-reactive protein (CRP) before treatment predicted overall disease-specific survival and local tumour control in patients with a sarcoma of bone. We retrospectively reviewed 318 patients who presented with a primary sarcoma of bone between 2003 and 2010. Those who presented with metastases and/or local recurrence were excluded. Elevated CRP levels were seen in 84 patients before treatment; these patients had a poorer disease-specific survival (57% at five years) than patients with a normal CRP (79% at five years) (p < 0.0001). They were also less likely to be free of recurrence (71% at five years) than patients with a normal CRP (79% at five years) (p = 0.04). Multivariate analysis showed the pre-operative CRP level to be an independent predictor of survival and local control. Patients with a Ewing’s sarcoma or chondrosarcoma who had an elevated CRP before their treatment started had a significantly poorer disease-specific survival than patients with a normal CRP (p = 0.02 and p < 0.0001, respectively). Patients with a conventional osteosarcoma and a raised CRP were at an increased risk of poorer local control. We recommend that CRP levels are measured routinely in patients with a suspected sarcoma of bone as a further prognostic indicator of survival. Cite this article: Bone Joint J 2013;95-B:411–18

Aims. The aim of this study was to determine the prevalence and characteristics of C-reactive protein (CRP)-negative prosthetic joint infection (PJI) and evaluate the influence of the type of infecting organism on the CRP level. Patients and Methods. A retrospective analysis of all PJIs affecting the hip or knee that were diagnosed in our institution between March 2013 and December 2016 was performed. A total of 215 patients were included. Their mean age was 71 years (. sd. 11) and there were 118 women (55%). The median serum CRP levels were calculated for various species of organism and for patients with acute postoperative, acute haematogenous, and chronic infections. These were compared using the Kruskal–Wallis test, adjusting for multiple comparisons with Dunn’s test. The correlation between the number of positive cultures and serum CRP levels was estimated using Spearman correlation coefficient. Results. Preoperative CRP levels were normal (< 10 mg/l) in 77 patients (35.8%) with positive cultures. Low-virulent organisms were isolated in 66 PJIs (85.7%) with normal CRP levels. When grouping organisms by species, patients with an infection caused by Propionibacterium spp., coagulase-negative staphylococci (CNS), and Enterococcus faecalis had significantly lower median serum CRP levels (5.4 mg/l, 12.2 mg/l, and 23.7 mg/l, respectively), compared with those with infections caused by Staphylococcus aureus and Streptococcus spp. (194 mg/l and 89.3 mg/l, respectively; p < 0.001). Those with a chronic PJI had statistically lower median serum CRP levels (10.6 mg/l) than those with acute postoperative and acute haematogenous infections (83.7 mg/l and 149.4 mg/l, respectively; p < 0.001). There was a significant correlation between the number of positive cultures and serum CRP levels (Spearman correlation coefficient, 0.456; p < 0.001). Conclusion. The CRP level alone is not accurate as a screening tool for PJI and may yield high false-negative rates, especially if the causative organism has low virulence. Aspiration of the joint should be used for the diagnosis of PJI in patients with a chronic painful arthroplasty, irrespective of CRP level. Cite this article: Bone Joint J 2018;100-B:1482–86

We analysed the serum C-reactive protein level, synovial fluid obtained by joint aspiration and five synovial biopsies from 145 knee replacements prior to revision to assess the value of these parameters in diagnosing late peri-prosthetic infection. Five further synovial biopsies were used for histological analysis. Samples were also obtained during the revision and incubated and analysed in an identical manner for 14 days. A total of 40 total knee replacements were found to be infected (prevalence 27.6%). The aspiration technique had a sensitivity of 72.5% (95% confidence interval (CI) 58.7 to 86.3), a specificity of 95.2% (95% CI 91.2 to 99.2), a positive predictive value of 85.3% (95% CI 73.4 to 100), a negative predictive value of 90.1% (95% CI 84.5 to 95.7) and an accuracy of 89%. The biopsy technique had a sensitivity of 100%, a specificity of 98.1% (95% CI 95.5 to 100), a positive predictive value of 95.2% (95% CI 88.8 to 100), a negative predictive value of 100% and an accuracy of 98.6%. C-reactive protein with a cut-off-point of 13.5 mg/l had a sensitivity of 72.5% (95% CI 58.7 to 86.3), a specificity of 80.9% (95% CI 73.4 to 88.4), a positive predictive value of 59.2% (95% CI 45.4 to 73.0), a negative predictive value of 88.5% (95% 81.0 to 96.0 CI) and an accuracy of 78.1%. We found that biopsy was superior to joint aspiration and C-reactive protein in the diagnosis of late peri-prosthetic infection of total knee replacements

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

78 patients (41 male and 37 female) with a revision total knee or hip arthroplasty were enrolled in this prospective study to evaluate the role of new laboratory markers in the diagnostic of deep implant infection. The average age at the time of surgery was 64 years. Based on intraoperative cultures, 21 patients had a septic and 57 patients had an aseptic revision total joint arthroplasty. White blood cell counts, erythrocyte sedimentation rate, C-reactive protein levels, interleukin-6, procalcito-nin and TNF-alpha were measured in preoperative blood samples. Diagnostic cut of values were determined by Receiver Operating Characteristic curve analysis. If patients with rheumatoid arthritis and other concomitant infections are excluded the C-reactive protein (> 3.2md/dl) and interleukin 6 (> 12 pg/ml) have the highest sensitivity (0.95). Interleukin 6 is less specific than the C-reactive protein (0.87 versus 0.96). Combining C-reactive protein and interleukin identifies all patients with deep implant infection. Procalcitonin (> 0.3 ng/ml) and TNF-alpha (> 40 ng/ml) are very specific (0.98 versus 0.94)) but have a low sensitivity (0.33 versus 0.43). The combination of C-reactive protein and interleu-kin 6 is an excellent screening tests for deep implant infection. Highly specific marker like procalcitoninn as well as preoperative joint aspiration might be useful to identify patients with true positive CRP and/or interleu-kin 6 levels

We studied the changes in plasma viscosity and C-reactive protein to establish normal values after total hip or knee arthroplasty. Viscosity decreased from 1.68 (+/- 0.017) to 1.57 (+/- 0.014) on the first postoperative day and thereafter rose to 1.60 (+/- 0.019), 1.75 (+/- 0.015), and 1.74 (+/- 0.011) on the third, seventh and fourteenth days respectively. Six to eight weeks after operation it had returned to pre-operative levels. A viscosity above the upper limit of the laboratory range, obtained more than two months after operation, may be considered as abnormal. The C-reactive protein level increased significantly on the first postoperative day and then decreased from a peak on the second day, attaining nearly normal levels at six to eight weeks after operation. It may be a more sensitive indicator of deep postoperative infection than plasma viscosity

Successfully treatment of acute shoulder arthroplasty infections strongly depends on the timing of treatment. The objective of this study is to determine the normalization curve of C-reactive protein (CRP) after shoulder arthroplasty. Prospective study including 63 patients undergoing shoulder arthroplasty (46 reverse shoulder arthroplasty (RSA) and 17 total shoulder (TSA)). Mean age 74.1 years old. 25 cuff deficient shoulders, 14 acute fractures, 19 primary gleno-humeral arthritis and 5 fracture sequel were included. Blood samples to determine CRP were obtained before surgery the day of surgery, 24 and 48 hours after surgery and then 6, 8 and 14 days after surgery (data of blood samples was determined based on a previous limited study). Co-morbidities that could interfere CRP were also recorded. Normal value of CRP before surgery (mean 1.28) slightly increases 24 hours after surgery (mean 3.92), reach maximum value at 48 hours after surgery (mean 6.91) and then slowly decreases to normalize at 14 days (6th day mean 3.80, 8th day 2.33 and 14th day 1.08). Normalization curve is not affected by age, diagnosis or type of arthroplasty. CRP after shoulder arthroplasty reaches maximum value at 48h and then slowly decreases to become normal at 14 days. Any deviation from this normalization curve may help in diagnosis and early treatment of acute shoulder arthroplasty infections

Background. The diagnosis of Periprosthetic Joint Infection (PJI) is a considerable challenge in total joint arthroplasty. The mainstay for diagnosis of PJI is a combination of serological markers, including C-reactive protein (CRP), along with joint aspirate for white cell count, differential and culture. The aim of this study was to examine the use of synovial fluid CRP in the diagnosis of PJI. Material & Methods. Synovial fluid samples were collected prospectively from patients undergoing primary and revision knee arthroplasty. Samples were assessed for CRP, cell count and differential. Three groups were analyzed; those undergoing primary knee arthroplasty, aseptic knee arthroplasties and infected arthroplasties. Demographic data, along with associated medical co-morbidities, were collected,. Statistical analysis was performed. Synovial fluid CRP was correlated with serum CRP values. Sensitivity and specificity were calculated. Results. 50 synovial fluid samples were collected from 50 patients. Synovial fluid CRP was 0.3 +/− 0.4 in native knees, 0.2 +/− 0.5 in aseptic knee arthroplasties, 4.3+/−4.1 in patients with infected knee arthroplasties. Synovial fluid CRP was significantly higher in septic total knee arthroplasties by comparison to both aseptic total knees (p< 0.001) and native knees (p=0.006). The specificity was 100% and the sensitivity was 89% at a CRP of 1. Conclusion. While this is preliminary data, synovial fluid CRP was found to be significantly elevated in patients with infected total knee arthroplasties. This test is easily performed under routine hospital laboratory conditions without specific, expensive assays. We believe synovial CRP assay holds great promise as a new, potentially low-cost, diagnostic marker for PJI

Our study has determined the response of C-reactive protein (CRP) after total knee replacement (TKR). The peak level occurs on the second postoperative day and is significantly greater than that after total hip replacement (THR). The level returns to normal at similar times after both procedures. The physiological response to TKR as measured by the area under the CRP/ time curve is significantly greater than that after THR. Rising CRP levels after the third postoperative day may indicate a complication of surgery such as infection

C-reactive protein (CRP) level is used at our tertiary paediatric hospital in the diagnosis, management, and discharge evaluation of paediatric septic arthritis patients. The purpose of this study was to evaluate the efficacy of a discharge criterion of CRP less than 2 mg/dL for patients with septic arthritis in preventing reoperation and readmission. We also aimed to identify other risk factors of treatment failure. Patients diagnosed with septic arthritis between January 1, 2007 and December 31, 2017 were reviewed retrospectively. The diagnosis of septic arthritis was made based on clinical presentation, laboratory results and the finding of purulent material on joint aspiration or the isolation of a bacterial pathogen from joint fluid or tissue. Bivariate tests of associations between patient or infection factors and readmission and reoperation were performed. Quantitative variables were analyzed using Mann-Whitney tests and categorical variables were analyzed using Chi-square tests. One hundred eighty-three children were included in the study. Seven (3.8%) were readmitted after hospital discharge for further management, including additional advanced imaging, and IV antibiotics. Six (85.7%) of the readmitted patients underwent reoperation. Mean CRP values on presentation were similar between the two groups: 8.26 mg/dL (± 7.87) in the single-admission group and 7.94 mg/dL (± 11.26) in the readmission group (p = 0.430). Mean CRP on discharge for single-admission patients was 1.71 mg/dL (± 1.07), while it was 1.96 mg/dL (± 1.19) for the readmission group (p = 0.664), with a range of < 0 .8 to 6.5 mg/dL and a median of 1.5 mg/dL for the two groups combined. A total of 48 children (25.9%) had CRP values greater than the recommended 2 mg/dL at discharge, though only three of these patients (6.2%) were later readmitted. The only common variable in the readmitted children was either a negative culture result at time of discharge or atypical causative bacteria. CRP values are useful in monitoring treatment efficacy but not as reliable as a discharge criterion to prevent readmission or reoperation in children with septic arthritis. We recommend determining discharge readiness on the basis of clinical improvement and downtrending CRP values. There was a higher risk of readmission in children with an atypical causative bacteria and when culture results were negative at discharge. Close monitoring of these patients after discharge is suggested to identify signs of persistent infection

Any operation induces an elevation in the level of serum C-reactive protein (CRP). After hip and knee arthroplasty the maximal values are seen on the second and third postoperative days, after which the CRP decreases rapidly. There is no difference between patients with cemented or uncemented prostheses. Major postoperative complications may cause a further increase in CRP levels at one and two weeks

Aim. Diagnosing periprosthetic joint infection after total joint arthroplasty is often challenging. The alpha defensin test has been recently reported as a promising diagnostic test for periprosthetic joint infection. The goal of this study was to determine the diagnostic accuracy of alpha defensin testing. Method. One hundred and eighty-three synovial alpha defensin and synovial fluid C-reactive protein (CRP) tests performed in 183 patients undergoing evaluation for periprosthetic joint infection were reviewed. Results were compared with the Musculoskeletal Infection Society (MSIS) criteria for periprosthetic joint infection. Results. Alpha defensin tests were performed prior to surgical treatment for infection, and 37 of these patients who had these tests were diagnosed by MSIS criteria as having infections. Among this group, the alpha defensin test had a sensitivity of 81.1% (95% confidence interval [CI], 64.8% to 92.0%) and a specificity of 95.9% (95% CI, 91.3% to 98.5%). There were 6 false-positive results, 4 of which were associated with metallosis. There were 7 false negatives, all of which were associated with either draining sinuses (n = 3) or low-virulence organisms (n = 4). A combined analysis of alpha defensin and synovial fluid CRP tests was performed in which a positive result was represented by a positive alpha defensin test and a positive synovial fluid CRP test (n = 28). Among this group, the sensitivity was calculated to be 73.0% (95% CI, 55.9% to 86.2%) and the specificity was calculated to be 99.3% (95% CI, 96.2% to 99.9%). An additional combined analysis was performed where a positive result was represented by a positive alpha defensin test or positive synovial fluid CRP test (n = 64). Among this group, the sensitivity was calculated tobe91.9%(95%CI, 78.1%to98.3%) andthe specificitywas calculated tobe79.5%(95%CI, 72.0%to85.7%). Conclusions. Alpha defensin in combination with synovial fluid CRP demonstrates very high sensitivity for diagnosing periprosthetic joint infection, but may yield false-positive results in the presence of metallosis or false-negative results in the presence of low-virulence organisms. When both alpha defensin and synovial fluid CRP tests are positive, there is a very high specificity for diagnosing periprosthetic joint infection

We measured the serum concentration of C-reactive protein (CRP) by a high-sensitive method in patients with lumbar disc herniation. There were 48 patients in the study group and 53 normal controls. The level and type of herniation were evaluated. The clinical data including the neurological findings, the angle of straight leg raising and post-operative recovery as measured by the Japanese Orthopaedic Association (JOA) score, were recorded. The high-sensitive CRP (hs-CRP) was measured by an ultrasensitive latex-enhanced immunoassay. The mean hs-CRP concentration was 0.056 ± 0.076 mg/dl in the patient group and 0.017 ± 0.021 mg/dl in the control group. The difference was statistically significant (p = 0.006). There was no other correlation between the hs-CRP concentration and the level and type of herniation, or the pre-operative clinical data. A positive correlation was found between the concentration of hs-CRP before operation and the JOA score after. Those with a higher concentration of hs-CRP before operation showed a poorer recovery after. The significantly high concentration of serum hs-CRP might indicate a systemic inflammatory response to impingement of the nerve root caused by disc herniation and might be a predictor of recovery after operation

Serial serum C-reactive protein (CRP) measurements were made, for three weeks, in 42 consecutive patients with solitary tibial fractures. The CRP response was related to the treatment: lower values were observed in 27 patients treated conservatively than in 15 operated patients. Open reduction and plating resulted in a greater response than closed intramedullary nailing. The timing of the CRP response was related to the timing of the treatment: the highest values were usually recorded two days after admission or operation. The timing of the operation did not affect the degree of CRP response. Neither the site, nor the type of fracture, nor the age of the patient played any role. Awareness of these natural CRP responses after fractures may help in the diagnosis of early post-traumatic and postoperative complications, especially infections

Culture examination is still considered the gold standard for diagnosis of bone and joint infections, including prosthetic ones, even if in up to 20–30% of cases, particularly prosthetic joint infections, it fails to yield microbial growth. To overcome this limitation, determination of markers of inflammation and or infection directly in joint fluid has been proposed. Aim of this study was to evaluate the applicability of measurement of lecukocyte esterase (LE), C-reactive protein (CRP) and glucose in synovial fluid for diagnosis of bone and joint infections. Synovial fluids from 80 patients were aseptically collected and sent to laboratory for microbiological cultures. After centrifugation at 3000 rpm for 10 minutes, pellet was used for cultures, while the surnatant was used for determination of LE, CRP and glucose. LE and glucose were evaluated by means of enzymatic colorimetric strips developed for urinanalysis. One drop of synovial fluid was placed on the LE and on the glucose pads and the results were read after about 120 seconds. A LE test graded + or ++, and a glucose test equal to trace or negative were considered suggestive for infection. CRP was measured by an automated turbidimetric method. On the basis of clinical findings, microbiological, haematological and histological analyses patients were retrospectively divided into 2 groups. Group 1 comprised 19 infected patients (12 males, 7 females age: 70.6 ± 10.3 yrs, range: 47 – 88 yrs) while Group 2 included 61 aseptic patients (32 males and 29 females, age: 61.5 ± 16.3 yrs, range: 15 – 84). Sensitivity of the three tests was 89.5%. 84% and 73,7% for LE, CRP and glucose, respectively. Specificity was 98.4%, 88.5% and 70% for LE, CRP and glucose, respectively. Positive and negative predictive values were 94.4% and 96.8% for LE, 69.6% and 94.6% for CRP and 77.8% and 89.6% for glucose test. When LE was combined with CRP, sensitivity increased to 94.7%, while no differences were observed for LE combined with glucose. Leukocyte esterase has proven to be a rapid, simple and inexpensive test to rule in or out bone and joint infections. Combination of its measurement with that of CRP increased sensitivity. In conclusion, the combination of leukocyte esterase and CRP may represent a simple and useful tool for diagnosis of bone and joint infections

Over 13 months we prospectively monitored C-Reactive Protein (CRP) to assess surgical site infection (SSI) in 148 patients undergoing hip arthroplasty, including 34 hemiprostheses for femoral neck fracture, 35 hemiprostheses for osteosynthesis failure, 17 primary total hip arthroplasties (THAs) and 62 revisions of hemi-arthroplasty or THA. Ten patients who had probably had interaction with CRP were included. In four out of seven patients with SSI, CRP values peaked three days after the operation, compared to eight out of 131 without SSI (p =0.0001). This gives a 60% sensitivity for detecting SSI by the CRP curve, with a specificity of 94%. The positive predictive value was 33%, and the negative predictive value 98%. Previous studies have established the normal CRP curve after major joint replacement surgery. This study shows that a peak in CRP after day three may indicate SSI, or point to other deep infections such as pneumonia

Monomeric C reactive protein (mCRP) presents important proinflammatory effects in endothelial cells, leukocytes, or chondrocytes. However, CRP in its pentameric form exhibits weak anti-inflammatory activity. It is used as a biomarker to follow severity and progression in infectious or inflammatory diseases, such as intervertebral disc degeneration (IVDD). This work assesses for the first time the mCRP effects in human intervertebral disc cells, trying to verify the pathophysiological relevance and mechanism of action of mCRP in the etiology and progression of IVD degeneration.

We demonstrated that mCRP induces the expression of multiple proinflammatory and catabolic factors, like nitric oxide synthase 2 (NOS2), cyclooxygenase 2 (COX2), matrix metalloproteinase 13 (MMP13), vascular cell adhesion molecule 1 (VCAM1), interleukin (IL)-6, IL-8, and lipocalin 2 (LCN2), in human annulus fibrosus (AF) and nucleus pulposus (NP) cells. We also showed that nuclear factor-κβ (NF-κβ), extracellular signal-regulated kinase 1/2 (ERK1/2), and phosphoinositide 3-kinase (PI3K) are at play in the intracellular signaling of mCRP.

Our results indicate that the effect of mCRP is persistent and sustained, regardless of the proinflammatory environment, as it was similar in healthy and degenerative human primary AF cells. This is the first article that demonstrates the localization of mCRP in intravertebral disc cells of the AF and NP and that provides evidence for the functional activity of mCRP in healthy and degenerative human AF and NP disc cells.

Background. The majority of adults will experience an episode of low back pain during their life. Patients with non-specific low back pain and lumbar disc degeneration (LDD) may experience spinal pain and morning stiffness because of a comparable inflammatory process as in patients with osteoarthritis of the knee and/or hip. Therefore, this study assessed the association between spinal morning stiffness, LDD and systemic inflammation in middle aged and elderly patients with low back pain. Methods. This cross-sectional study used the baseline data of the BACE study, including patients aged ≥55 years visiting a general practitioner with a new episode of back pain. The association between spinal morning stiffness, the radiographic features of lumbar disc degeneration and systemic inflammation measured with serum C-reactive protein was assessed with multivariable logistic regression models. Results. At baseline, a total of 661 back pain patients were included. Mean age was 66 years (SD 8), 416 (63%) reported spinal morning stiffness and 108 (16%) showed signs of systemic inflammation measured with CRP. Both LDD definitions were significantly associated with spinal morning stiffness (osteophytes OR=1.5 95% CI 1.1–2.1, narrowing OR=1.7 95% CI 1.2–2.4) and spinal morning stiffness >30 minutes (osteophytes OR=1.9 95% CI 1.2–3.0, narrowing OR=3.0 95% CI 1.7–5.2) For severity of disc space narrowing we found a clear dose response relationship with spinal morning stiffness. We found no associations between spinal morning stiffness and the features of LDD with systemic inflammation. Conclusions. This study demonstrated an association between the presence and duration of spinal morning stiffness and radiographic LDD features. No conflicts of interest. No funding obtained

Aim: In patients without infections following primary total hip (PTHA) and knee (PTKA) arthroplasty, the natural course of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were evaluated. The effects of gender, anesthesia type, cementing, and tourniquet use on the natural course of CRP and ESR were determined. Understanding the natural course of plasma ESR and CRP is helpful in terms of the diagnosis and follow-up of infections, especially in the early postoperative period. Methods: A total of 82 patients with normal preoperative CRP and ESR, both in accordance with gender and age; without any chronic condition, infection, or inflammatory disease; and with no intra–and post-operative complications were included. PTHA was performed on 38 (Groups I–II) and PTKA on 44 patients (Groups III-IV). CRP and ESR measurements were performed on the 1st preoperative day; 1st, 2nd, 3rd, 5th, 7th, 14th, and 21st postoperative days; and the 1st, 2nd, 3rd, 6th, 9th, and 12th months. CRP measurements were performed with the nephelometric (Dade Behring S.p.A., Italy) and quantitative Methods: Westergren method was used for ESR measurements. The PTHA group was further classified as femoral component fixed with (Group I; 28 patients) and with-out cement (Group II; 10 patients), while PTKA as with (Group III; 32 patients) and without tourniquet (Group IV; 12 patients). Furthermore, epidural (Group IIIa) and general anesthesia (Group IIIb), and gender differences (Group Ia; female and Group Ib; male) were compared. Wilcoxon test, paired-t test, Students’-t test, ANOVA, and chi-square tests were used for statistical analysis. Results: After the operation, separate peak CRP and ESR levels of each patient and days of reaching peak and normalization were evaluated. When the mean of peak CRP levels were compared, groups III and IV had significantly higher levels with regard to groups I and II (p=0.037), However, the days of reaching peak levels were statistically similar between PTHA and PTKA groups (p=0.245). The same comparison was repeated for the mean of peak ESR levels, the results were similar (p=0.547). In cemented PTHA, CRP normalized earlier than cementless PTHA and PTKA (p=0.035) and ESR also normalized earlier, but this was not significant (p= 0.074). Among groups comparing gender and anesthesia type, mean values of CRP and ESR peaks, distribution of these two levels on the days controlled, and days of reaching peaks and normalization were statistically similar (p> 0.05). Conclusions: In the PTKA group, the mean CRP peak was higher than PTHA. CRP levels normalized earlier in cemented PTHA cases. Anesthesia type, gender differences, and use of tourniquet in PTKA did not affect the course of CRP and ESR following arthroplasty

INTRODUCTION

This study is to determine the response of CRP after TKR surgery, both unilateral and simultaneous bilateral TKR. According to the previously published literature from North America and Europe CRP value peaks on the 1^st and 2^nd post-operative day and then gradually comes down to normal by 6–8 weeks post-operatively.

Aim

C-reactive protein(CRP) and erythrocyte sedimentation rate(ESR) are non-specific markers with variable reported accuracy in the diagnosis of prosthetic joint infection(PJI). They are often used as a part of the initial diagnostics as they are widely available and inexpensive. Given its high false-negative rate, CRP is an insufficient screening tool for PJI especially in low virulence microorganisms. Nevertheless, many advocate ESR offers no added advantage and is useless in this setting. Our goal is to determine if the combined measurement of ESR and CRP offers increased sensitivity for the preliminary screening of PJI over isolated CRP measurement.

Objectives

C-reactive protein(CRP) Used as screening test for acute periprosthetic joint infection has high sensitivity and low specificity. So there are many reasons except acute infection after total knee arthroplasty to elevate CRP level but it is unclear what reasons exactly were concerned. We therefore performed this study to determine the Causes of elevated CRP level in the early-postoperative period after primary total knee arthroplasty.

Aim

Preoperative serum CRP has been identified as an independent predictor in various malignancies. For osteosarcoma, however, the value of serological markers is unreliable. Aim of this study was to evaluate the prognostic power of preoperative CRP in patients with osteosarcoma.

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. 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

Serum inflammatory parameters are widely used to aid in diagnosing a periprosthetic joint infection (PJI). Due to their limited performances in the literature, novel and more accurate biomarkers are needed. Serum albumin-to-globulin ratio (AGR) and serum CRP-to-albumin ratio (CAR) have previously been proposed as potential new parameters, but results were mixed. The aim of this study was to assess the diagnostic accuracy of AGR and CAR in diagnosing PJI and to compare them to the established and widely used marker CRP.

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

To determine risk factors of infection in total knee arthroplasty. This descriptive study was conducted in the Department of Orthopedics for a duration of three years from January 2016 to January 2019. All patients undergoing primary total knee replacement were included in the study. Exclusion criteria were all patients operated in another hospital and revision total knee replacement. All patients were followed up at 2, 4, 8, 12 and 24 weeks post-operatively. Signs of inflammation and inflammatory markers such as total leukocyte count (TLC), C-reactive protein (CRP) and ESR were measured. Risk factors like age, body mass index (BMI), ASA, co-morbid conditions were also noted. A total of 78 patients underwent primary unilateral Total Knee Replacement (TKR) during the study period. Of these, 30 (34.09%) were male and 48 (61.54%) female patients. Mean age of patients was 68.32 ± 8.54 years. Average BMI 25.89 Kg/m2 .Osteoarthritis was the pre-dominant cause of total knee replacement (94.87%). Among co-morbid factors 33.33% were diabetic, 28.20% having ischemic heart disease and 12.82% with chronic lung disease. Upon anaesthesia fitness pre-operatively, 91.02% patients had an American society of anaesthesiologist score (ASA) between 0–2 while 07 (8.97%) between 3- 5. Average duration of surgery was 85.62± 4.11 minutes. 6.41% cases got infected. In majority of the infected cases (60%), Staphylococcus aureus was the infective organism. Diabetes Mellitus (p=0.01) and Obesity (p=0.02) had a significant relation to post-operative infection. Pre-operative risk evaluation and prevention strategies along with early recognition of infection and control can greatly reduce the risk of joint infection post-TKR which will not only improve the mobility of patient but also its morbidity and mortality as well. Key Words:. C-reactive protein (CRP), Erythrocyte Sedimentation Rate (ESR), Staphylococcus aureus, Total Knee Arthroplasty (TKA)

The aim of this study was to determine whether the high-sensitivity modified Glasgow prognostic score (Hs-mGPS) could predict the disease-specific survival and oncological outcome in adult patients with non-metastatic soft-tissue sarcoma before treatment. A total of 139 patients treated between 2001 and 2012 were retrospectively reviewed. The Hs-mGPS varied between 0 and 2. Patients with a score of 2 had a poorer disease-specific survival than patients with a score of 0 (p < 0.001). The estimated five-year rate of disease-specific survival for those with a score of 2 was 0%, compared with 85.4% (95% CI 77.3 to 93.5) for those with a score of 0. Those with a score of 2 also had a poorer disease-specific survival than those with a score of 1 (75.3%, 95% CI 55.8 to 94.8; p < 0.001). Patients with a score of 2 also had a poorer event-free rate than those with a score of 0 (p < 0.001). Those with a score of 2 also had a poorer event-free survival than did those with a score of 1 (p = 0.03). A multivariate analysis showed that the Hs-mGPS remained an independent predictor of survival and recurrence. The Hs-mGPS could be a useful prognostic marker in patients with a soft-tissue sarcoma.

Cite this article: Bone Joint J 2015; 97-B:847–52.

Acute Haematogenous Osteomyelitis (AHO) remains a cause of severe illness among children. Contemporary research aims to identify predictors of acute and chronic complications. Trends in C-reactive protein (CRP) following treatment initiation may predict disease course. We have sought to identify factors associated with acute and chronic complications in the New Zealand population. A retrospective review of all patients <16 years with presumed AHO presenting to a tertiary referral centre between 2008–2018 was performed. Multivariate was analysis used to identify factors associated with an acute or chronic complication. An “acute” complication was defined as need for two or more surgical procedures, hospital stay longer than 14-days, or recurrence despite IV antibiotics. A “chronic” complication was defined as growth or limb length discrepancy, avascular necrosis, chronic osteomyelitis, pathological fracture, frozen joint or dislocation. 151 cases met inclusion criteria. The median age was 8 years (69.5% male). Within this cohort, 53 (34%) experienced an acute complication and 18 (12%) a chronic complication. Regression analysis showed that contiguous disease, delayed presentation, and failure to reduce CRP by 50% at day 4/5 predicted an acutely complicated disease course. Chronic complication was predicted by need for surgical management and failed CRP reduction by 50% at day 4/5. We conclude that CRP trends over 96 hours following commencement of treatment differentiate patients with AHO likely to experience severe disease

Abstract. Background. Distinction between foot and ankle wound healing complications as opposed to infection is crucial for appropriate allocation of antibiotic therapy. Our aim was to evaluate the diagnostic accuracy of white cell count (WCC) and C-reactive protein (CRP) as diagnostic tools for this distinction in the non-diabetic cohort. Methods. Data were reviewed from a prospectively maintained Infectious Diseases Unit database of 216 patients admitted at Leicester University Hospitals – United Kingdom between July 2014 and February 2020 (68 months). All diabetic patients were excluded. For the infected non-diabetic included patients, we retrospectively retrieved the inflammatory markers (WCCs and CRP) at the time of presentation. Values of CRP 0–10 mg/L and WCC 4.0–11.0 ×109 /L were considered normal. Results. 25 patients met our inclusion criteria. Infections were confirmed microbiologically with positive intra-operative culture results. 7 (28%) patients with foot osteomyelitis (OM), 11 (44%) with ankle OM, 5 (20%) with ankle septic arthritis, and 2 (8%) patients with post-surgical wound infection were identified. Previous bony surgery was identified in 13 (52%) patients. 21 (84%) patients did have raised inflammatory markers while 4 (16%) patients failed to mount an inflammatory response even with subsequent debridement and removal of metalwork. CRP sensitivity was 84%, while WCC sensitivity was only 28%. Conclusion. CRP had good sensitivity, whereas WCC is a poor inflammatory marker in the detection of such cases. In presence of a clinically high level of suspicion of foot or ankle infection, a normal CRP should not rule out the diagnosis of OM

High doses of intra-articular (IA) antibiotics has been shown to effectively achieve a minimal biofilm eradication concentration which could mitigate the need for removal of infected but well-ingrown cementless components of a total hip arthroplasty (THA). However, there are concerns that percutaneous catheters could lead to multi-resistance or multi-organism peri-prosthetic joint infections (PJI) following single stage THA revisions for PJI. Eighteen single-stage revision procedures were performed for acute (N=9) or chronic (N=9) PJI following a primary (N=12) or revision (N=6) cementless THA. Modular and loosened components were replaced. All well ingrown components were retained. Two Hickmann catheters were placed in the joint space. Along with intravenous antibiotics, IA antibiotics were injected twice a day for two weeks, followed by 3 months of oral antibiotics. Per-operative cultures demonstrated 4 multi-bacterial PJIs. None of the patients developed post-operatively an AB related renal or systemic dysfunction. At a mean follow-up of 38 months [range, 8–72] all patients had normal erythrocyte sedimentation rate and white blood cell count. Four had a slightly elevated C-reactive protein but were completely symptom free and did not show any sign of loosening at a mean of 27 months [range, 16–59]. Addition of high doses of IA antibiotics following single-stage revision for PJI in cementless THA, is an effective and safe treatment option that allows for retention of well-ingrown components. We found no evidence for residual implant infection or catheter induced multi-resistance. Total hip arthroplasty, revision surgery, Periprosthetic Joint Infection, Intra-articular antibiotics. Level 4 (Case series)

Periprosthetic joint infection is a serious complication of primary total hip replacement (THR) with significant associated morbidity. In acute infection, Debridement, Antibiotics and Implant Retention (DAIR) may be considered. Current national guidelines recommend a DAIR should be performed by “an experienced arthroplasty surgeon┕ but do not specify the need for this to be a revision arthroplasty surgeon. We investigated outcomes in our NHS Trust of DAIR procedures performed by revision and non-revision arthroplasty surgeons. Infection registry data and patient records were analysed for all DAIR procedures of infected primary THRs between 2017 and 2021. Data collected included details of the primary surgery, the presentation with infection, the DAIR procedure and any subsequent complications including return to theatre at any time point. Routinely collected pre- and post-operative patient reported outcome measures (PROMs) were reviewed. 54 periprosthetic joint infections of primary THRs received a DAIR procedure. 41 DAIRs were performed by a revision surgeon and 13 by non-revision surgeons. There was no significant difference in time from primary THR to presentation with infection, time from presentation to DAIR or pre-operative C-reactive protein between the two groups. In 21 (38.9%) patients the DAIR procedure was classed as a treatment failure; 17 patients (31.5%) returned to theatre for further revision surgery, one (2.4%) died related to infection and three (5.6%) had persistent infection but did not receive further surgery. Treatment failure was significantly higher in the non-revision surgeon group (9/13 (69.2%)) than in the revision surgeon group (12/41 (29.3%)) (p = 0.02). Overall, improvement in PROMs after DAIR was seen at both six and 12 months. The overall success rate of DAIR was 61.1% and there was a sustained improvement in PROMs after surgery. However, there was a significant difference in failure rates between revision surgeons and non-revision surgeons

Shoulder septic arthritis is uncommon and frequently misdiagnosed, resulting in severe consequences. This study evaluated the demographics, bacteriological profile, antibiotic susceptibility, treatment regimens, and clinical outcomes. This is a 10-year retrospective observational analysis of 30 patients (20 males and 10 females) who were treated for septic arthritis of the shoulder. The data collecting process utilised clinical records, laboratory archives, and x-ray archives. We gathered demographic information, pre- and post-intervention clinical data, serum biochemical markers, and the results of imaging examinations. All patients had a surgical arthrotomy and joint debridement in the operating room, and specimens were taken for culture and sensitivity testing. The specimens were cultivated for at least seventy-two hours. Shoulder joint ranges of motion, comorbidities, and the presence of osteomyelitis were assessed clinically to determine the outcome. All statistical analyses were conducted using the STATA 17 statistical software. Analysis of correlation between categorical variables was performed using the chi-squared test. The majority of the study patients were black Africans (97%). The age range of the group was from 8 days to 17 years. At presentation, 33% of patients had a low-grade fever, whereas the majority (60%) had normal body temperature. The average length of symptoms was 3.9 days (ranged from 1 day to 15 days), and the majority of patients had an increased white cell count (83%) and C-reactive protein (98%). There was accumulation of fluid in the joint of all individuals who received shoulder ultrasound imaging. We noted a significant incidence of gram-positive cocci, which were mostly susceptible to first-line antibiotics. Shoulder stiffness affected 63% of patients and chronic osteomyelitis affected 50% of individuals. Neither the severity nor the duration of the symptoms was related to an increased risk of osteomyelitis. The results of this study revealed that the clinical characteristics and bacterial profile of septic arthritis of the shoulder conform to typical patterns. The likelihood of osteomyelitis and an unfavourable prognosis is considerable

Introduction: The water soluble vitamins B1, B2 and B6 are essential precursors for a wide variety of coenzymes involved in intermediary metabolism. Recent evidence suggests that the systemic inflammatory response associated with disease, injury and infection may lower micronutrient concentrations in plasma independent of tissue stores. Elective knee arthroplasty surgery has been shown to induce a significant and reproducible systemic inflammatory response and therefore provides an ideal model with which to examine the relationship between plasma and erythrocyte (intracellular) concentrations of B-vitamins and the evolution of the systemic inflammatory response. Methods: The study was approved by the local ethics committee. All subjects were informed of the purpose and procedure of the study and all gave consent. Venous blood samples (EDTA) were withdrawn pre-operatively from 12 primary knee arthroplasty patients and at 12, 24, 48, 72 and 168 hours after the start of surgery. Analysis of plasma and red cell vitamins B1, B2, B6, C-reactive protein and albumin. Data presented as median and range. Data from different time periods were tested for statistical significance using the Freidman test and where appropriate comparisons of data from different time periods were carried out using the Wilcoxon signed rank test. Results: All patients were over the age of 60 years and had circulating concentrations of B vitamins in the normal range (B1 275–675ng TDP/g Hb; B2 220–410nmol/l; B6 17–135nmol/l). On analysis of serial postoperative values over the study period 0–168hrs there were significant increases in C-reactive protein and significant decreases in albumin concentrations peaking/troughing at 48hrs returning towards normal concentrations at 7 days (p< 0.001). In contrast, during this period plasma albumin (p< 0.001), B2 (p< 0.001) and B6 (p< 0.001) concentrations fell transiently by as much as 50% returning towards normal in parallel with the fall in C-reactive protein concentrations. In contrast, neither red cell B2 nor B6 concentrations fell during the study period. Conclusions: In this study red blood cell B2 and B6 remained stable over the period of study. In contrast, plasma concentrations of B2 and B6 fell and were outwith the normal range, the trough coinciding with the peak of C-reactive protein before returning to baseline values. These results are consistent with the concept that plasma concentrations of vitamins are unlikely to be a reliable measure of status in patients with evidence of a systemic inflammatory response. Red cell B1, B2 and B6 concentrations more accurately reflect status in patients with evidence of a systemic inflammatory response

Aim. Culture negative (CN) prosthetic joint infections (PJI) account for approximately 10% of all PJIs and present significant challenges for clinicians. We aimed to explore the significance of CN PJI within a large prospective cohort study, and to compare their characteristics and outcomes with culture positive cases. Methods. The Prosthetic joint Infection in Australia and New Zealand Observational (PIANO) study is a prospective, binational, multicentre observational cohort study conducted at 27 hospitals between July 2014 and December 2017. We compared baseline characteristics and outcomes of all patients with culture negative (CN) prosthetic joint infection (PJI) from the PIANO cohort with culture positive (CP) cases. “Treatment success” was defined as absence of clinical or microbiological signs of infection, no need for ongoing antibiotics, and no need for revision or resection arthroplasty since the end of the initial treatment. We also describe PJI diagnostic criteria in the CN cohort and apply internationally recognised PJI diagnostic guidelines. Results. Of the 650 patients eligible for inclusion, 55 (8.5%) were CN and 595 were CP. Compared with the CP cohort, CN patients were more likely to be female [32 (58.2%) vs 245 (41.2%); p=0.02], involve the shoulder joint [5 (9.1%) vs. 16 (2.7%); p=0.03] and have a lower mean C-reactive protein (142 mg/L vs. 187 mg/L; p=0.02). Overall, outcomes were superior in CN patients, with culture negativity an independent predictor of treatment success at 24 months (aOR 3.78; 95%CI 1.65 – 8.67). Of the 55 CN cases meeting Infectious Diseases Society of America (IDSA) diagnostic criteria, 45 (82%) met European Bone and Joint Infection Society (EBJIS) criteria (probable or definite) and 39 (71%) met the 2013 Musculoskeletal Infection Society (MSIS) criteria. Conclusions. Culture negativity is an independent predictor of treatment success in PJI. It is unclear whether this is because some of them are not actually infections, or for other reasons such as lower bacterial load or earlier effective antibiotic treatment. Diagnostic criteria for PJI vary substantially in their sensitivity, with MSIS criteria being the least sensitive. Acknowledgements. This work is being presented on behalf of the broader PIANO investigators and the Australasian Society for Infectious Diseases Clinical Research Network. The PIANO study received seed funding from Heraeus Medical and the John Hunter Hospital Charitable Trust Fund

Aim. Serum parameters continue to be a focus of research in diagnosing periprosthetic joint infections (PJI). Several workgroups have recently proposed serum Albumin-Globulin-Ratio (AGR) as a potential new biomarker. Due to controversies in the literature, its usability in clinical practice remains uncertain. The aim of this study was to assess the value of serum AGR in diagnosing PJI preoperatively, especially in comparison with the well-established marker C-reactive Protein (CRP). Method. From January 2015 to June 2022, patients with indicated revision hip (rTHA) and knee (rTKA) arthroplasty were included in this retrospective cohort study of prospectively collected data. A standardized diagnostic workup was performed using the 2021 European Bone and Joint Infection Society (EBJIS) definition of PJI, excluding CRP. Diagnostic accuracies of serum AGR and CRP were calculated by receiver operating characteristic curve (ROC) analysis. A z-test was used to compare the area under the curves (AUC). Results. A total of 275 patients with rTHA and rTKA were included, 144 joints (52.4%) were identified as septic. Decreased AGR and elevated CRP were strongly associated with PJI, optimal diagnostic thresholds were calculated with 1.253 and 9.4 mg/L, respectively. Sensitivities were 62.5% (95%-confidence interval: 54.3–70.0) and 73.6% (65.8–80.1), and specificities 84.7% (77.5–89.9) and 87.8% (80.9–92.4), respectively. CRP showed a significantly higher AUC than AGR (0.807 (0.761–0.853) and 0.736 (0.686–0.786); p<0.0001). Subgroup analysis of acute versus chronic infections yielded significantly higher diagnostic accuracies in acute PJI for both parameters (p<0.0001). Similar results were observed when focusing on the causative microorganism; a better diagnostic performance was observed in high-virulence PJI compared to low-virulence PJI (p≤0.005). Furthermore, higher AUCs were calculated in knee PJI compared with hip PJI, with a significant difference for AGR (p=0.043). Conclusions. Due to its limited diagnostic accuracy, serum AGR cannot be recommended as an additional marker for diagnosing PJI. Serum parameters are generally unspecific and can be influenced by comorbidities and other foci of infection. Additionally, parameters may remain within normal levels in low-grade PJI. Evaluating AGR, further possible pitfalls must be considered, for example an increased latency until bottom values are reached and the impact of malnutrition

Aim. Treatment algorithms for fracture-related nonunion depend on the presence or absence of bacterial infection. However, the manifestation of septic nonunion varies. Low-grade infections, unlike manifest infections, lack clinical signs of infection and present similarly to aseptic nonunion. The clinical importance of low-grade infection in nonunion is not entirely clear. Therefore, the aim of this study was to evaluate the clinical relevance of low-grade infection in the development and management of femoral or tibial nonunion. Method. A prospective, multicenter clinical study enrolled patients with nonunion and regular healed fractures. Preoperatively, complete blood count without differential, C-reactive protein (CRP), and procalcitonin were obtained, clinical signs of infection were recorded, and a suspected septic or aseptic diagnosis was made based on history and clinical examination. During surgical nonunion revision or routine implant removal, tissue samples were collected for microbiology and histopathology, and osteosynthesis material for sonication. Nonunion patients were followed for 12 months. Definitive diagnosis of “septic” or “aseptic” nonunion was made according to diagnostic criteria for fracture-related infection, considering the results of any further revision surgery during follow-up. Results. 34 patients with regular healed fractures were included. 62 nonunion patients were diagnosed as aseptic, 22 with manifest, and 23 with low-grade infection. The positive predictive value was 88% and the negative predictive value 72% for the suspected diagnosis. The nonunion groups had significantly higher CRP levels than the regular healer group. Differentiation between septic and aseptic nonunion based on blood values was not possible. Low-grade infection demonstrated less frequently histopathologic signs of infection than manifest infection (22% vs. 50%, p=0.048), with 15% of regular healers having histopathologic signs of infection. Cutibacterium acnes was less present in manifest compared to low-grade infection (p=0.042). Healing rates for septic nonunion involving C. acnes were significantly lower for manifest infection (20%) than for low-grade infection (100%, p=0.002). Patients with low-grade infection were treated with systemic antibiotics less frequently than patients with manifest infection (p=0.026), with no significant difference in healing rate (83% vs. 64%), which was slightly lower for low-grade infection than for aseptic nonunion (90%). Conclusions. Low-grade infections play a significant role in nonunion development and are difficult to diagnose preoperatively due to the lack of clinical signs of infection and unremarkable blood counts. However, our results imply that for low-grade infections, antibiotic therapy may not always be mandatory to heal the nonunion. This study was supported by the German Social Accident Insurance (FF-FR0276)

After a hip fracture, infections are common, but signs of infection resemble those of systemic inflammatory response to trauma and surgery, and conventional infection markers lack specificity. Plasma-calprotectin, a novel marker of neutrophil activation, has shown potential as an infection marker in ER and ICU settings. To investigate if plasma-calprotectin is superior compared to conventional infection biomarkers after hip fracture. Prospective cohort study of hip fracture patients admitted to our department. Calprotectin, procalcitonin (PCT), C-reactive protein (CRP), and white blood cell (WBC) count were measured in blood plasma upon admission and on day 3 post-surgery. Patients with infection (pneumonia, UTI, sepsis, SSI, other soft tissue infections) pre- or post-surgery were compared to a control group without infection within 30 days. Statistics: Wilcoxon rank-sum test, medians with interquartile range, and area under the curve (AUC) with 95% confidence intervals. Pilot study comprises calprotectin obtained at least once for 60 patients at admission and 48 on day 3. Mean age 84 years (SD 8.4), 65% women. 9/60 patients (23%) were admitted with infections. They had higher levels of CRP (median 111 [73-149]) and PCT (0.35 [0.18–0.86]) compared to the control group (29 [16-64], p=0.037; 0.10 [0.07–0.17], p=0.007). Calprotectin (2.67 vs 2.51) and WBC (12.2 vs 9.3) did not differ significantly. AUC was highest for PCT (0.79 [CI 0.60–0.97]), followed by CRP (0.71 [0.46–0.96]), WBC (0.60 [0.35–0.84]), and calprotectin (0.58, [0.33–0.83]). Day 3, 6/48 (13%) had infections, without significant differences between groups in any marker. The median levels were: calprotectin 3.5 vs 3.1, CRP 172 vs 104, WBC 12 vs 9, PCT 0.16 vs 0.17. Calprotectin had highest AUC 0.68 (0.41–0.93, n.s.). AUC for WBC was 0.67 (0.31–1.00), CRP 0.66 (0.38–0.94), PCT 0.56 (0.29–0.82). Preliminary data show no significant associations with postoperative infection for any of the studied biomarkers. However, plasma-calprotectin might perform slightly better compared to conventional markers

Aim. Differentiation of infected (INF) nonunion from aseptic (AS) nonunion is crucial for the choice of intra- and postoperative treatment. Preoperative diagnosis of infected nonunion is challenging, especially in case of low-grade infection lacking clinical signs of infection. Standard blood markers such as C-reactive protein or leucocyte count do not aid in preoperative diagnosis. Proteomic profiling has shown promising results for differentiation of numerous chronic disease states, and in this study was applied to preoperative blood samples of patients with nonunion in an attempt to identify potential biomarkers. Method. This prospective multicenter study enrolled patients undergoing revision surgery of femur or tibia nonunion. Patients with implant removal after regular fracture healing (HEAL) were included as a control-group. Preoperative blood samples, intraoperative tissue samples, sonication of osteosynthesis material and 1-year-follow-up questionnaire were taken. Nonunion patients were grouped into INF or AS after assessing bacterial culture and histopathology of retrieved samples. Diagnosis of infection followed the fracture related infection consensus group criteria, with additional consideration of healing one year after revision surgery. Targeted proteomics was used to investigate a predefined panel of 45 cytokines in preoperative blood samples. Statistical differences were calculated with Kruskal Wallis and Dunn's post hoc test. Cytokines with less than 80% of samples being above the lower limit of detection range (LLDR) were excluded for this study. Results. We recruited 62 AS, 43 INF and 32 HEAL patients. Patients in the two nonunion groups (INF and AS) did not differ concerning smoking, diabetes or initial open or closed fracture. Thirty-two cytokines were above LLDR in >80% of patients. INF patients showed a significant difference in expression of 8 cytokines compared to AS, with greatest differences observed for Macrophage Colony Stimulating Factor 1 (MCSF-1) and Hepatocyte Growth Factor (HGF) (p<0.01). In comparing AS with HEAL patients, 9 cytokines displayed significant differences, including interleukin (IL)-6, Vascular Endothelial Growth Factor A (VEGFA), Matrix Metalloproteinase 1 (MMP-1). Comparison of INF with HEAL patients revealed significantly different expression of 20 cytokines, including. IL-6, IL-18, VEGFA or MMP-1. Conclusions. Our study revealed differences in plasma cytokine profile of blood samples from INF and AS patients. Although no single biomarker is sufficient to differentiate these patients preoperatively in isolation, future multivariant analysis of this cytokine data in combination with clinical characteristics may provide valuable diagnostic insights. Funded by German Social Accident Insurance (FF-FR 0276) and AO Trauma (AR2021_04)

Objectives. Prosthetic joint infection (PJI) diagnosis is a major challenge in orthopaedics, and no reliable parameters have been established for accurate, preoperative predictions in the differential diagnosis of aseptic loosening or PJI. This study surveyed factors in synovial fluid (SF) for improving PJI diagnosis. Methods. We enrolled 48 patients (including 39 PJI and nine aseptic loosening cases) who required knee/hip revision surgery between January 2016 and December 2017. The PJI diagnosis was established according to the Musculoskeletal Infection Society (MSIS) criteria. SF was used to survey factors by protein array and enzyme-linked immunosorbent assay to compare protein expression patterns in SF among three groups (aseptic loosening and first- and second-stage surgery). We compared routine clinical test data, such as C-reactive protein level and leucocyte number, with potential biomarker data to assess the diagnostic ability for PJI within the same patient groups. Results. Cut-off values of 1473 pg/ml, 359 pg/ml, and 8.45 pg/ml were established for interleukin (IL)-16, IL-18, and cysteine-rich with EGF-like domains 2 (CRELD2), respectively. Receiver operating characteristic curve analysis showed that these factors exhibited an accuracy of 1 as predictors of PJI. These factors represent potential biomarkers for decisions associated with prosthesis reimplantation based on their ability to return to baseline values following the completion of debridement. Conclusion. IL-16, IL-18, and CRELD2 were found to be potential biomarkers for PJI diagnosis, with SF tests outperforming blood tests in accuracy. These factors could be useful for assessing successful debridement based on their ability to return to baseline values following the completion of debridement. Cite this article: M-F. Chen, C-H. Chang, L-Y. Yang, P-H. Hsieh, H-N. Shih, S. W. N. Ueng, Y. Chang. Synovial fluid interleukin-16, interleukin-18, and CRELD2 as novel biomarkers of prosthetic joint infections. Bone Joint Res 2019;8:179–188. DOI: 10.1302/2046-3758.84.BJR-2018-0291.R1

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

Introduction. Chronic recurrent multifocal osteomyelitis (CRMO) is a rare condition characterised by bony pain and swelling which may be initially mistaken for bacterial osteomyelitis. The episodic course of the disease may confound the diagnosis and potentially be mistaken for a partial response to antimicrobial therapy. It is an orphan disease and consequently results in many unclear aspects of diagnosis, treatment and follow up for patients. The aim of this study is to evaluate a national tertiary centre's experience with the clinical condition and present one of the largest cohorts to date, emphasizing the vast array of clinical spectrum, course and response to treatment. Methods. We retrospectively evaluated all children identified with CRMO from the period 2000–2022 within Wales. Demographic data and clinical parameters were selectively identified through the utilisation of a national clinical platform (Welsh Clinical Portal). The diagnosis was based on clinical findings, radiological images, histopathological and microbiological studies. Results. A total of 21 patients were identified as suitable for inclusion. The mean age of diagnosis was 9.4 ±2 years. The age range of children being diagnosed was 6–14 years. Of the 21 patients, only 2 reported feeling unwell prior to their first presentation with generalized coryzal illness reported. The most common presenting site for CRMO was knee (33%) followed by back pain (28%). 19% of the included cases at initial presentation had localised warmth and had nocturnal pain. 4 of the patients went on to have dermatological conditions of which psoriasis was the most common (14%). Bilateral symptoms developed in 38% of the included patients. Biochemical investigations revealed only 19% of patients had a raised C-reactive protein level and erythrocyte sedimentation rate whilst 9/21 patients went on to have a bone biopsy to aid diagnosis. 100% of patients had MRI whilst whole body MRI was utilised in 8/21 patients. NSAID's were utilised for 81%, Pamidronate for 33% and methotrexate for 14%. Biologics were utilised for a further 24% of the total population in failed medical therapy. Surgical intervention was utilised for a single individual in this cohort of patients in the form of posterior spinal stabilisation. The most common referring speciality for these patients was Rheumatology (71%) followed by Orthopaedics (33%). Discussion. CRMO represents a challenging diagnosis to make with such varied clinical and biochemical presentations for this condition. The absence of diagnostic Radiological features on X-ray could argue over early MRI imaging. The utilisation of whole body-MRI can now identify multifocal disease burden which may facilitate a timely diagnosis and ensure that effective medical treatment is started promptly without delay. This study is the largest cohort of CRMO patients conducted in this country. Future work will serve to build upon a framework and national referral pathway so that these patients can be seen by the appropriate specialist in a timely manner

Aims. The aims of this study were to report the efficacy of revision surgery for patients with co-infective bacterial and fungal prosthetic joint infections (PJIs) presenting to a single institution, and to identify prognostic factors that would guide management. Patients and Methods. A total of 1189 patients with a PJI were managed in our bone infection service between 2006 and 2015; 22 (1.85%) with co-infective bacterial and fungal PJI were included in the study. There were nine women and 13 men, with a mean age at the time of diagnosis of 64.5 years (47 to 83). Their mean BMI was 30.9 kg/m. 2. (24 to 42). We retrospectively reviewed the outcomes of these PJIs, after eight total hip arthroplasties and 14 total knee arthroplasties. The mean clinical follow-up was 4.1 years (1.4 to 8.8). Results. The median number of risk factors for PJI was 5.5 (interquartile range (IQR) 3.25 to 7.25). All seven patients who initially underwent debridement and implant retention (DAIR) had a recurrent infection that led to a staged revision. All 22 patients underwent the first of a two-stage revision. None of the nine patients with negative tissue cultures at the second stage had a recurrent infection. The rate of recurrent infection was significantly higher in the presence of multidrug-resistant bacteria (p = 0.007), a higher C-reactive protein (CRP) at the time of presentation (p = 0.032), and a higher number of co-infective bacterial organisms (p = 0.041). The overall rate of eradication of infection after two and five years was 50% (95% confidence interval (CI) 32.9 to 75.9) and 38.9% (95% CI 22.6 to 67), respectively. Conclusion. The risk of failure to eradicate infection with the requirement of amputation associated with this diagnosis is much higher than in patients with PJI without bacterial and fungal co-infection, and this risk is heightened when the fungal organism is joined by polymicrobial and multidrug-resistant bacterial organisms. Cite this article: Bone Joint J 2019;101-B:582–588

Aim. Low-grade infections are difficult to diagnose. As the presence of a chronic infection requires extensive surgical debridement and antibiotic treatment, it is important to diagnose a SII prior to surgery, especially when the hardware is revised. We investigated whether serum inflammatory markers or nuclear imaging can accurately diagnose a chronic spinal instrumentation infection (SII) prior to surgery. Method. All patients who underwent revision spinal surgery after a scoliosis correction between 2017 and 2019 were retrospectively evaluated. The diagnostic accuracy of serum C-reactive protein (CRP) and Erythrocyte Sedimentation Rate (ESR), . 18. F-fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT) and Technetium-99m-methylene diphosphonate (99mTc-MDP) 3-phase bone scintigraphy (TPBS) to diagnose infection were studied. Patients with an acute infection or inadequate culture sampling were excluded. SII was diagnosed if ≥ 2 of the same microorganism(s) were isolated from intra-operative tissue cultures. Results. 31 patients were included. The indication for hardware extraction was pseudoarthrosis in the majority of patients (n = 15). 22 patients (71%) were diagnosed with SII. In all infected cases, Cutibacterium acnes was isolated, including 5 cases with a polymicrobial infection. Sensitivity, specificity, PPV and NPV was: 4.5%, 100%, 100% and 30.0% for CRP >10.0 mg/L, 5.5%, 100%, 100% and 29% for ESR > 30 mm/h; 56%, 80%, 83% and 50% for FDG-PET/CT and 50%, 100%, 100% and 20% for TPBS, respectively. Conclusions. The prevalence of SII in patients undergoing revision spinal surgery is high, with Cutibacterium acnes as the main pathogen. No diagnostic tests could be identified that could accurately diagnose or exclude SII prior to surgery. Future studies should aim to find more sensitive diagnostic modalities to detect low-grade inflammation

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

Aim. This study aims to define the normal postoperative presepsin kinetics in patients undergoing primary cementless total hip replacement (THR). Methods. Patients undergoing primary cementless THR at our Institute were recruited. At enrollment anthropometric data, smocking status, osteoarthritis stage according to Kellgren and. Lawrence, Harris Hip Score (HHS), drugs assumption and comorbidities were recorded. All the patients underwent serial blood tests, including complete blood count, presepsin (PS) and C-Reactive Protein (CRP) 24 hours before arthroplasty and at 24-, 48-, 72- and 96-hours postoperatively and at 3-, 6- and 12-months follow-up. Statistical analysis was performed with SPSS v25.0 (SPSS Inc, Chicago, IL, USA). The Wilcoxon and Kruskal-Wallis tests followed by the Dunn multiple comparison post hoc tests were carried out. Correlations between PS, CRP and TOT were assessed using the Spearman rank correlation coefficient. P values below 0.05 were considered significant. Results and conclusion. A total of 96 patients were recruited (51 female; 45 male; mean age= 65.74±5.58) were recruited. The mean PS values were: 137.54 pg/ml at baseline, 192.08 pg/ml at 24-hours post-op; 254.85 pg/ml at 48-hours post-op; 259 pg/ml at 72-hours post-op; 248.6 pg/ml at 96-hour post-op; 140.52 pg/ml at 3-months follow-up; 135.55 pg/ml at 6-months follow-up and 130.11 pg/ml at 12-months follow-up. In two patients (2.08%) a soft-tissue infection was observed; in these patients higher levels (>350pg/mL) were recorded at 3-months follow-up. The lack of a presepsin decrease at 96 hours post-operatively should be a predictive factor of infection

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

Aim. Our goal is to assess diagnostic accuracy of synovial fluid testing in diagnosing prosthetic joint infection (PJI) as defined by the European Bone and Joint Infection Society (EBJIS). In addition to differential leukocyte count, simples and inexpensive biomarkers such as synovial fluid C-reactive protein (CRP), adenosine deaminase (ADA) and alpha-2-macrogloblulin(A2M) were also investigated and its possible role in increasing accuracy assessed. Method. Between January/2013 and December/2019 total hip or knee arthroplasty revision cases (regardless of preoperative diagnosis) were prospectively included provided enough synovial fluid for biomarker analysis was collected and at least four tissue samples, as well as the implant for sonication, were gathered for microbiological study. Definitive diagnosis was classified according to the new EBJIS PJI definition. Using receiver operating characteristic curves, we determined cutoff values as well as diagnostic accuracy for each marker. Results. Out of 364 revision arthroplasties performed, 102 fully respected inclusion criteria. There were 58 unlikely, 8 likely and 36 confirmed infections. Synovial fluid total leukocyte count, proportion of polymorphonuclear neutrophils (PMN), CRP, ADA and A2M were significantly different between groups. Area under the curve was 0.94 for total leucocyte count, 0.91 for proportion of PMN, 0.90 for CRP, 0.82 for ADA and 0.76 for A2M. Sensitivity, specificity, and predictive values for statistically optimal but also selected rule-in and rule-out cutoffs values are shown in Table 1. Interpreting a raised level of CRP(>2.7mg/L) or ADA(>60U/L) together with high leukocyte count (>1470 cells/μL) or proportion of PMN (>62.5%) significantly increases specificity and positive predictive value for affirming PJI. Conclusions. Differential leukocyte count cutoffs proposed by the EBJIS PJI definition are shown to perform well in ruling out (<1,500 cells/μL) and ruling in (>3,000 cells/μL) PJI. Adding simple and inexpensive biomarkers such synovial CRP or ADA is helpful in interpreting inconclusive results. For any tables or figures, please contact the authors directly