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

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.

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)

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

Aim. Prosthetic joint infection (PJI) presents the second most common complication of total joint arthroplasty (TJA). Accumulating evidence suggests that up to 20% of aseptic failures are low-grade PJI. However, there is still no single test to reliably diagnose all PJI. In his thesis, Mazzucco emphasized the viscosity differences between normal, osteoarthritic, and rheumatic synovial fluid. Similarly, a recent study by Fu et al. reported significantly lower viscosity in patients with PJI compared to the aseptic failure cohort. The primary aim of our study was to determine whether synovial fluid viscosity is a more reliable diagnostic criterion for PJI compared to the synovial fluid cell count with differential and serum C-reactive protein (CRP) levels. Method. We prospectively analyzed the viscosity of synovial fluid samples obtained during TJA of hip and knee joint revision procedures. We sampled 2.5–5 mL of synovial fluid for viscosity measurement. The samples were centrifuged (4 min at 7000 rpm) and the resulting supernatant was immediately transferred into the Ostwald viscometer. Viscosity was derived from the time required for a given volume of synovial fluid to pass the viscometer at 20 °C. The synovial fluid samples were also analysed for their cell count with differential and serum CRP was measured. The definite diagnosis of PJI was established on basis of EBJIS criteria. For the viscosity, the threshold for detecting PJI was set at 65 seconds. Results. Between December 2020 and March 2021, we analyzed 12 knee and 11 hip TJA revision samples. These included 14 septic and 9 aseptic synovial fluid samples. The average viscometer time in the PJI group was 31s (range 20–48s) compared to 247s (range 68–616s) in the group of aseptic revision procedures. The specificity and sensitivity of our viscosity measurements were 100%. The sensitivity and specificity of cell count was 100% and 85.7%, for the synovial fluid differential they were 100% and 85.7%, and for the CRP they were 88.9% and 71.4%, respectively. Conclusions. Our study is the first to report a significant difference in synovial fluid viscosity between the PJI and the aseptic cohort. It points towards the diagnostic superiority of viscosity measurements over conventional synovial fluid cell count, synovial fluid differential, and serum CRP levels. Albeit currently limited by small sample size, the study remains ongoing

Aim. D-dimer is a widely available serum test that detects fibrinolytic activities that occur during infection. Prior studies have explored its utility for diagnosis of chronic periprosthetic joint infections (PJI), but not explored its prognostic value for prediction of subsequent treatment failure. The purpose of this study was to: (1) assess the ability of serum D-dimer and other standard-of-care serum biomarkers to predict failure following reimplantation, and (2) establish a new cutoff value for serum D-dimer for prognostic use prior to reimplantation. Method. This prospective study enrolled 92 patients undergoing reimplantation between April 2015 and March 2019 who had previously undergone total hip/knee resection arthroplasty with placement of an antibiotic spacer for treatment of chronic PJI. Serum D-dimer level, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels were measured preoperatively for all patients. Failure following implantation was defined per the Delphi consensus criteria. Optimal cutoffs for D-dimer, ESR, and CRP were calculated based on ROC curves and compared in their association with failure following reimplantation criteria at minimum 1-year follow-up. Results. 15/92(16.3%) patients failed reimplantation surgery at mean follow up of 2.9 years (range 1.0–4.8). Optimal thresholds for D-Dimer, ESR and CRP were determined to be 1300ng/mL, 30mm/hr, and 1mg/L, respectively. The failure rate in patient with positive D-dimer was significantly higher at 32.0% (8/25) compared to those with negative D-dimer 10.6% (7/66); p=0.024. In comparison, 17.8% (8/45) of patients with ESR above threshold failed, compared to 13.89% (5/41) below (p=0.555) and 16.0% (4/25) of patients with CRP above threshold failed, compared to 16.1% (10/62) below (p=1.000). Conclusions. Patients with elevated D-Dimer appear to be at higher risk of failure after reimplantation surgery. This serum marker may be used to generate an additional data point in patients undergoing reimplantation surgery, especially in circumstances when optimal timing of reimplantation cannot be determined based on clinical circumstances

Endoscopic spine surgery is a promising and minimally invasive technique for the treatment of disc herniation and spinal stenosis. However, the literature on the outcome of interlaminar endoscopic decompression (IED) versus conventional microsurgical technique (CMT) in patients with lumbar spinal stenosis is scarce. We analyzed 88 patients (IED: 36/88, 40.9%; CMT: 52/88, 59.1%) presenting with lumbar central spinal stenosis between 2018–2020. Surgery-related (operation time, complications, time to hospital release (THR), ASA score, C-reactive protein (CRP), white blood cell count (WBC), side (unilateral/bilateral), patient-reported (ODI, NRS (leg-, back pain), eQ5D, COMI), and radiological (preoperative dural sack cross-sectional area (DSCA), Shizas score (SC), left (LRH) and right (RRH) lateral recess heights, left (LFA) and right (RFA) facet angle) parameters were extracted. Complication (most often re-stenosis due to hematoma and/or residual sensorimotor deficits) rates were higher in the endoscopic (38.9%) than microsurgical (13.5%) treatment group (p<0.01). Age, THR, SC, CRP, and DSCA revealed significant correlations with 3 weeks and 1 year postoperatively evaluated ODI, COMI, eQ5D, NRS leg, or NRS back values in our cohort. We did not observe significant differences in the endoscopic versus microsurgical group for the patient-reported outcomes. Age, THR, SC, CRP, and DSCA revealed significant correlations with patient-centered outcomes and should be considered in future studies. Endoscopic treatment of lumbar spinal stenosis was similarly successful as the conventional microsurgical approach, although it was associated with higher complication rates in our single-center study experience. This was probably because of the surgeons' lack of experience with this method and the resulting different learning curve compared with the conventional technique

Aim. Debridement, antibiotic, and implant retention (DAIR) is an accepted treatment of early and late acute Total Knee Arthroplasty (TKA) infections. DAIR failure may adversely affect the outcome of a subsequent two-stage exchange arthroplasty. Controversy exists on risk factors that can affect DAIR's results. The aim of the study is to review presurgical, intrasurgical and postsurgical variables that could affect DAIR's result. Method. A retrospective study of 27 DAIRs performed between 2015–2019 to treat late acute TKA infections was carried out. Patients were divided into two groups depending on DAIR's outcome [Healing (H) vs non-healing group (NH)] according on the Delphi-based multidisciplinary consensus criteria on success after treatment of periprosthetic joint infection. We reviewed presurgical variables, including epidemiological variables (Age, Sex, comorbidities, ASA, Charlson, BMI, alcohol dependency), prosthesis variables (prosthesis type, primary cause of operation, primary TKA surgery center), infection variables (concomitant infection, previous antibiotic treatment, c-reactive protein, synovial WBC count, synovial % PMN, pathogen), KLIC score and CRIME 80 score. Surgical variables such as surgery duration and type of surgery (elective vs urgent). Post-surgical variables like antibiotic treatment duration and destination at discharge. Normal distribution was assessed by Shapiro-Wilk test. Mann Whitney U test was used to compare the two independent sample variables. Chi-squared test was used for qualitative variables. P-value was established at 0.05 and statistical power at 80%. Results. Infection Healing was achieved in 63% of patients. In presurgical variables, alcohol dependency, hypertension, liver disease, previous surgery performed in another institution were more frequent in NH group (p< 0.05). KLIC score value equal or greater than 4 had a higher risk of surgical failure (p < 0.05). Regarding surgical variables, the healing group had more negative cultures than de non-healing one (p<0.05). Regarding post-surgical variables, long term antibiotic treatment (six months) achieved more healing after DAIR (p<0.05). Conclusions. Alcohol dependency, hypertension, liver disease and KLIC score values equal or greater than 4, may increases the risk of DAIR failure. Finally, we observed that the long-term antibiotic treatment (6 months) favors healing after DAIR

Aim. The diagnosis of septic arthritis mostly relies on clinical examination, several blood parameters including white blood cell count, C-reactive protein, sedimentation, and the analysis of the joint aspiration. However, the diagnosis can be difficult when the symptoms are vague and the information obtained from laboratory might be insufficient for definitive diagnosis. This study aimed to evaluate several ratios obtained from routine blood tests for a possible use in the diagnosis of septic arthritis. Method. The adult patients who were operated in our clinic due to septic arthritis between 2014–2020 were identified and retrospectively evaluated. The patients with any blood disorders or missing file information were excluded. A total of 36 patients were found to be eligible for inclusion. The control group included 40 patients without any sign of infection who underwent total knee arthroplasty due to knee osteoarthritis. Preoperative blood tests of each patients were examined. In addition to CRP and sedimentation values, neutrophil-lymphocyte, monocyte-lymphocyte, platelet-lymphocyte, and platelet count-mean platelet volume were calculated and receiving operating characteristics (ROC) curve analysis was made to determine the sensitivity, specificity and area under curve (AUC) values of these parameters. Results. The distribution of affected joint in septic arthritis group was as follow; 22 knees, 6 hips, 4 shoulders, 2 elbows, 1 wrist and 1 ankle. The cultures of joint aspiration yielded positive result in 19 patients while the cultures were negative in 17 patients. All of the analyzed parameters were significantly different between the groups (p<0.001). ROC curve analysis results are given in detail, in Table 1 and Figure 1. The AUC value was 97.3 when only CRP and sedimentation values were used but increased to 98.6 when neutrophile/ lymphocyte ratio was added and increased to 100 when all analyzed parameters were included. Conclusions. The analyzed parameters were found to increase the overall sensitivity and specificity when used together with acute phase reactants. However, when evaluated separately, CRP and sedimentation were still found as the most valuable parameters in the diagnosis of septic arthritis. In the diagnosis of septic arthritis, 35 mm/hr cut-off value for sedimentation and 10 mg/L cut-off value for CRP were found more sensitive and specific compared to standard laboratory cut-off values of 20 mm/hr and 5 mg/L. For any tables or figures, please contact the authors directly

Aim. The liver is the major source of acute phase proteins (APPs) and serum concentrations of several APPs are widely used as markers of inflammation and infection. The aim of the present study was to explore if a local extra hepatic osseous acute phase response occurs during osteomyelitis. Method. The systemic (liver tissue and serum) and local (bone tissue) expression of several APPs during osteomyelitis was investigated with qPCR and ELISA in a porcine model of implant associated osteomyelitis (IAO) at 5, 10 and 15 days after inoculation with S. aureus or saline, respectively. Additionally, samples were also collected from normal heathy pigs and pigs with spontaneous, chronic, haematogenous osteomyelitis. Afterwards, immunohistochemistry towards different upregulated APPs was performed on the porcine osteomyelitis lesions and on bone biopsies from human patients with chronic osteomyelitis. Results. All infected porcine bone lesions (apart from Day 5 in the IAO model) were made up by necrosis, pus, and various degree of fibrotic encapsulation. A local, highly significant upregulation of Serum Amyloid A (SAA, up to 4000-fold upregulation), Complement component C3 (C3), and Inter-Alpha-Trypsin Inhibitor Heavy Chain 4 (ITIH4) were present in infected pigs compared to sterile controls. For the experimental IAO animals, the upregulation of C3 and ITIH4 increased over time, i.e., the highest expression was seen on day 15 after bacterial inoculation. In the liver, only C-reactive protein (CRP) and ITIH4 (not SAA or C3) were slightly upregulated in infected pigs. Serum concentrations of CRP, SAA and haptoglobin were only upregulated at day 5 in IAO infected animals. Immunohistochemically, comparable numbers of APP positive cells (leucocytes and bone cells) were found in human and porcine bone samples with chronic osteomyelitis. Conclusions. This is to our knowledge the first description of local APP up-regulation during chronic bone infection. Only small changes in the expression of APPs were found in the liver and serum samples. Thus, the presence of an osseous upregulation of APPs appears to be part of a predominantly local response that will be difficult to measure systemically. The importance of a local immune response in bone infections seems logical as the blood supply is severely impaired during osteomyelitis. There is a real need for supportive diagnostic bone infection criteria which should be based on a comprehensive understanding of the local inflammatory response. As seen from the present study, staining for SAA or C3 could potentially improve the diagnostic performance of histopathology

Aim. Our goal is to increase diagnostic accuracy of synovial fluid testing in differentiating prosthetic joint infection(PJI) by more exhaustively studying simple and inexpensive biomarkers. For that purpose, we sought to determine: 1) if synovial fluid C-reactive protein(CRP), alpha-2-macrogloblulin(A2M), procalcitonin and adenosine deaminase(ADA) concentrations are different between infected and aseptic cases; 2) performance and optimal cutoff values of each marker; 3) whether any such test may help improve diagnostic performance of traditional leukocyte count. Method. Between January/2013 and December/2015 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 as infection or aseptic on the basis of the recent International Consensus Meeting definition of PJI. Using receiver operating characteristic curves, we determined cutoff values as well as sensitivity and specificity for each marker. Results. Fifty-five out of 143 revision arthroplasties fully respected the inclusion criteria. Two supposedly aseptic cases were ultimately classified as infected resulting in 32 aseptic and 23 infected cases available for analysis. Total leukocyte count, proportion of PMN, C-reactive protein, ADA and alpha-2-macroglobulin but not procalcitonin were significantly different between both groups. Cutoff values for optimal performance in the diagnosis of infection were: total leukocyte count >1,463 cells/μL; proportion of PMN >81%; CRP >6.7mg/L and ADA >61U/L. Conclusions. Synovial fluid leukocyte count offers great negative predictive value and interpreting it together with other more specific markers such as C-reactive protein and ADA is helpful in improving its positive predictive value. These simple and inexpensive markers may reduce the number of equivocal synovial fluid results requiring more expensive investigation

Drainage from the knee wound after TKA is an obvious concern for the arthroplasty surgeon. One of the inherent problems with a total knee arthroplasty is there is a focus on obtaining maximum range of motion but at the same time the wound needs to heal in a timely fashion. Consistent knee drainage after a TKA is a source of concern. The quantity and quality of drainage needs to be assessed and there are certain questions that need to be answered including: 1) Is there bloody drainage which suggests fascial dehiscence?; 2) Is the patient too active?; 3) Is the drainage in some way related to DVT prophylaxis?; 4) Is the patient obese and could the drainage be secondary to fat necrosis or seroma? and 5) Is the drainage suggestive of an infection? The work-up can include C-reactive protein and sed rate, and possibly a knee aspiration. In general, C-reactive protein >100mg/L within the first six weeks after surgery suggests the presence of an infection. The sed rate is generally not useful in the early post-operative period. In the first six weeks after surgery if the number of white cells in the aspiration is >10,000 this suggests infection especially if there are 80–90% polymorphonuclear cells. Each day of prolonged wound drainage is noted to increase the risk of infection by 29%. Morbid obesity has been shown to be an independent risk factor for infection. Some anticoagulants (i.e. low molecular weight heparin) have been associated with increased wound drainage. In a retrospective review of 11,785 total joint arthroplasties, 2.9% of joints developed wound drainage, and of these patients, 28% required further surgery. It was noted that patients that were malnourished had a 35% failure rate with respect to controlling the drainage and preventing infection versus 5% in patients that were healthy. The International Consensus Conference on Infection concluded that a wound that has been persistently draining for greater than 5–7 days requires surgical intervention. The available literature provides little guidance regarding the specifics of this procedure. In general, if the wound is draining or is red, rest the leg for a day or two. In some instances a bulky Jones dressing can be helpful. If the drainage persists one could consider using a negative pressure dressing (wound vac) but there is little data on efficacy after TKA. If there is persistent drainage or cellulitis, then operative intervention is probably necessary. Evaluation of CRP and a knee joint aspiration can be helpful. The decision to return to the OR should be made within the first 7 days after the surgery. At the time of the procedure one will need to decide to perform either a superficial washout versus a washout and polyethylene exchange

Aims. To evaluate the effectiveness of an institutionally developed algorithm for evaluation and diagnosis of prosthetic joint injection and to determine the impact of this protocol on overall hospital re-admissions.p. Patients and Methods. We retrospectively evaluated 2685 total hip arthroplasty (THA) and total knee arthroplasty (TKA) patients prior to (1263) and following (1422) the introduction of an infection detection protocol. The protocol used conservative thresholds for C-reactive protein to direct the medical attendant to aspirate the joint. The protocol incorporated a clear set of laboratory and clinical criteria that allowed a patient to be discharged home if all were met. Patients were included if they presented to our emergency department within 120 days post-operatively with concerns for swelling, pain or infection and were excluded if they had an unambiguous infection or if their chief complaint was non-orthopaedic in nature. Results. Concern for infection was the single most common (32%) reason for presentation. A total of 296 patients made an emergency visit and were included following THA or TKA. In the pre-protocol cohort, 11 of 27 patients were formally re-admitted to the hospital with concern for infection but only five (45%) patients had actual infections and received additional treatment. In comparison, in the post-protocol cohort, 11 patients were admitted for suspected infection, nine (82%) of whom were truly infected (p = 0.04). Sensitivity increased from 83% to 100% and specificity increased from 71% to 96%. Implementation of this protocol did not miss any infections. Conclusion. A standardised protocol for evaluation of THA and TKA infections significantly reduced unnecessary hospital re-admissions. The protocol was both sensitive and specific and did not compromise quality of care. Cite this article: Bone Joint J 2017;99-B:1603–10

Drainage from the knee wound after TKA is an obvious concern for the arthroplasty surgeon. One of the inherent problems with a total knee arthroplasty is there is a focus on obtaining maximum range of motion but at the same time the wound needs to heal in a timely fashion. Consistent knee drainage after a TKA is a source of concern. The quantity and quality of drainage needs to be assessed and there are certain questions that need to be answered including: 1) Is there bloody drainage which suggests fascial dehiscence?; 2) Is the patient too active?; 3) Is the drainage in some way related to DVT prophylaxis?; 4) Is the patient obese and could the drainage be secondary to fat necrosis or seroma? and 5) Is the drainage suggestive of an infection? The work up can include C-reactive protein and sed rate, and possibly a knee aspiration. In general, C-reactive protein >100 mg/L within the first six weeks after surgery suggests the presence of an infection. The sed rate is generally not useful in the early post-operative period. In the first six weeks after surgery if the number of white cells in the aspiration is >10,000 this suggests infection especially if there are 80–90% polymorphonuclear cells. Each day of prolonged wound drainage is noted to increase the risk of infection by 29%. Morbid obesity has been shown to be an independent risk factor for infection. Some anticoagulants (i.e. low molecular weight heparin) have been associated with increased wound drainage. In a retrospective review of 11,785 total joint arthroplasties, 2.9% of joints developed wound drainage, and of these patients, 28% required further surgery. It was noted that patients that were malnourished had a 35% failure rate with respect to controlling the drainage and preventing infection versus 5% in patients that were healthy. The International Consensus Conference on Infection concluded that a wound that has been persistently draining for greater than 5–7 days requires surgical intervention. The available literature provides little guidance regarding the specifics of this procedure. In general, if the wound is draining or is red, rest the leg for a day or two. In some instances a bulky Jones dressing can be helpful. If there is persistent drainage or cellulitis, then operative intervention is probably necessary. Evaluation of CRP and a knee joint aspiration can be helpful. The decision to return to the OR should be made within the first 7 days after the surgery. At the time of the procedure one will need to decide to perform either a superficial washout versus a washout and polyethylene exchange

Aim. Although established serum inflammatory biomarkers, such as serum C-reactive protein (CRP) and serum white blood cell count (WBC), showed low accuracies in the literature, they are still commonly used in diagnosing periprosthetic joint infections (PJI). For a sufficient preoperative diagnosis novel more accurate serum parameters are needed. The aim of our study was to evaluate the performances of the established and novel routinely available serum parameters in diagnosing periprosthetic joint infections when using the proposed European Bone and Joint Infection Society (pEBJIS) criteria. Method. In this retrospective study, 177 patients with an indicated revision surgery after a total joint replacement were included from 2015 to 2019. The easily accessible and routinely available serum parameters CRP, WBC, the percentage of neutrophils (%N), the neutrophils to lymphocytes ratio (NLR), fibrinogen and the platelet count to mean platelet volume ratio (PC/mPV) were evaluated preoperatively. The performances were examined via receiver operating characteristic (ROC) curve analysis (AUC). The curves were compared using the z-test. Seventy-five cases (42%) showed a PJI based on the pEBJIS-criteria. Results. The sensitivities of serum CRP (cut-off: ≥10mg/L), WBC (≥10×10^9 cells/L), %N (≥69.3%), NLR(≥ 3.82), fibrinogen (≥ 457 mg/dL), and PC/mPV (≥ 29.4) were calculated with 68% (95% CI: 57–78), 36% (26 – 47), 66% (54 – 76), 63% (51 – 73), 69% (57 – 78), and 43% (32 – 54), respectively. Specificities were 87% (79 – 93), 89% (81 – 94), 67% (57 76), 73% (63 – 81), 89% (80 – 93), and 81% (72 – 88), respectively. Serum CRP and fibrinogen showed better performances than the other evaluated serum parameters (p<0.0001). The median serum CRP (17.6 mg/L) in patients with PJI caused by a low virulence microorganism was lower compared with infections caused by high virulence organisms (49.2 mg/L; p=0.044). Synovial fluid leucocyte count and histology showed better accuracies than serum CRP, serum WBC, %N, NLR, serum fibrinogen, and PC/mPV (p<0.0001). Conclusions. Although serum CRP and fibrinogen showed the best performances among the evaluated serum inflammatory markers, their results should be interpreted with caution in clinical practice. Serum parameters may remain normal in chronic infections or may be elevated in patients with other inflammatory conditions. In addition, they also correlated poorly with synovial fluid leukocyte count and histology. Therefore, serum parameters are still insufficient to confirm or exclude a periprosthetic joint infection. Hence, they can only be recommended as suggestive criteria in diagnosing PJI

Post operative prosthetic joint infection (PJI) is the most common cause of failure of total joint arthroplasty, requiring revision surgery, but a gold standard for the diagnosis and the treatment of PIJ is still lacking [1]. SuPAR, the soluble urokinase plasminogen activation receptor, has been recently described as a powerful diagnostic and prognostic tool, able not only to detect sepsis but also to discriminate different grade of sepsis severity [2,3]. This study aimed to examine the diagnostic value of SuPAR in post operative PJI, in order to explore the possible application of this new biomarker in the early diagnosis of PJI. The level of SuPAR have been measured in PJI patients and controls (patients undergoing prosthesis revision without infection), and correlated with pro and anti inflammatory markers (CRP C-reactive protein, IL-6, IL-1 TNFα, IL-10, IL-12, IL-8, IL1ra and the chemokine CCL2). Statistical analysis of Receiver Operating Characteristic (ROC) curves and Area Under the Curve (AUC) was performed. As described in Figure 1, serum SuPAR displayed a strongly significative increase in PJI patients compared to not infected controls, and a significative positive correlation with C-reactive protein, IL-6, IL-1 and TNFα and the chemokine CCL2. SuPAR displayed a very good AUC, significantly higher than CRP and IL-6 AUC. This study clearly show that the measure of Serum level of SuPAR provide a extremely important benefit because it is a precise indicator of bacterial infection, and the addition of SuPAR serum level measurement to classical inflammatory markers can strongly improve the diagnosis of prosthesis joint infection. The authors acknowledge ViroGates, Denmark for providing suPARNOSTIC Standard Kit. The authors would also acknowledge the Italian Ministero dell’ Istruzione, Università e Ricerca (MIUR) and Italian Ministero della Salute for providing funds for this research project

Background. Although tourniquets are widely used in total knee arthroplasty (TKA), their influence on the postoperative course is still unclear. In addition, tourniquet-related soft tissue damage is a major concern in daily practice. We performed a prospective, randomized controlled trial to clarify the role of tourniquets in TKA. Methods. Seventy-two patients undergoing TKA were randomly allocated to a tourniquet or non-tourniquet group. Changes in C-reactive protein, creatine phosphokinase, and other indicators of soft tissue damage were monitored preoperatively and postoperatively on days 1, 2, and 4. Rehabilitation progress was also recorded for comparison. Results. Patients in the tourniquet group showed smaller increases in C-reactive protein (peak values: 175 ± 55 versus 139 ± 75 mg/dl) and creatine phosphokinase (peak values: 214 ± 89 versus 162 ± 104 U/l) compared those in the non-tourniquet group. There was slightly less postoperative pain in the non-tourniquet group, and no significant differences in swelling, or rehabilitation progress. Conclusions. Using tourniquets in TKA was effective for reducing blood loss and avoiding excessive postoperative inflammation and muscle damage. Tourniquets caused slightly more postoperative pain but did not affect postoperative recovery

Periprosthetic joint infection (PPJI) following shoulder arthroplasty is uncommon, with an overall rate of 0.98%. However, the rates following revision arthroplasty and reverse arthroplasty are much higher. Given the rapid increase in the prevalence of shoulder arthroplasty and the increasing revision burden, the cost of PPJI to society will likely increase substantially. The most common organisms found in PPJI following shoulder arthroplasty are Staphylococcus aureus, coagulase-negative Staphylococcus, and Propionibacterium acnes (P. acnes). P. acnes is especially common in males. Traditional testing for PPJI includes aspiration, white blood cell count (WBC), erythrocyte sedimentation rate (ESR), and c-reactive protein (CRP). Aspiration often yields a dry tap and when fluid is obtained for culture, a positive result is helpful but a negative result does not rule out PPJI. Although WBC, ESR, and CRP are often positive with PPJI in the lower extremity, they are most often negative in shoulder PPJI. Although bone scans and WBC labeled scans are used, they are expensive and have low sensitivity and specificity. New testing and techniques have been reported in an attempt to improve sensitivity and specificity for PPJI. These techniques can be divided into tests on serum, synovial fluid, and tissue. Serum Interleukin-6 (IL-6) is highly specific (94%) for shoulder PPJI but has low sensitivity (14%). Synovial fluid can be tested for leukocyte esterase using a simple and cheap technique. In lower extremity PPJI it has shown to be helpful. It is not as helpful in shoulder PPJI with 30% sensitivity and 67% specificity. Alpha defensin has been reported to be more sensitive (63%) and as specific (95%) as traditional techniques but still lacks predictive value. Testing for specific cytokines (IL-2, IL-6, TNF- α) within synovial fluid is not widely used as yet but has shown promise with 80% sensitivity and 90% specificity. Obtaining tissue for culture and other testing is probably the most reliable way of confirming PPJI for the shoulder. Frozen sections taken at the time of revision can be helpful but is very pathologist dependent and institution specific. With a dedicated musculoskeletal pathologist, the finding of 10 or more WBCs per high powered field has been reported to be 72% sensitive and 100% specific for P. acnes and 63% sensitive and 100% specific for other organisms. Cultures from arthroscopic tissue biopsy have also been found to have high sensitivity (100%) and specificity (100%). Genetic testing of tissue biopsy specimens (PCR/NGS) has recently been reported and shows great promise. The significance of positive cultures and other tests, especially for P. acnes is unclear. There is a high rate of positive intra-operative cultures in primary cases of shoulder arthroplasty. In addition, intra-operative cultures taken at the time of revision, even in cases in which infection is not suspected, are frequently positive for P. acnes with weak correlation with rates of post-operative clinical infection. In conclusion, shoulder PPJI is a difficult problem to deal with. The definition of shoulder PPJI is currently unclear and further study is needed. There is no ideal test to confirm it. A reasonable approach is to aspirate for culture, and perform serum tests for WBC, ESR, and C-reactive protein. If any of these is positive in the setting of a painful arthroplasty, PPJI should be assumed until proven otherwise. Operative tissue cultures are probably the most reliable test but the clinical significance is not always obvious. Synovial fluid cytokine profiles and tissue PCR/NGS show promise for the future

Background: Several studies have shown that uncomplicated hip or knee arthroplasties induce an abrupt rise in serum C-reactive protein (CRP) concentration for a few days, falling thereafter to preoperative level within a couple of weeks, if no infection is present. Aim: To evaluate the computer-aided CRP levels analysis in a primary hospital care setting. Material and Methods: 300 patients undergoing total knee and hip replacements were screened before and for 5 days after arthroplasty. The data were recorded in a database and mathematical algorithm to obtain integral and progressive field surface of the CRP curve. Results: An elevated C-reactive protein level on the fifth postoperative day correlated positively with the development of acute periprosthetic infection in the first three months postoperatively. Conclusions: The patient’s individual pattern not following one of the four normal patterns can be argued to necessitate introduction of any infection treatment (whether debridement with retention or antimicrobial therapy alone) within the first three months after the operation

The aim of our study was to describe the characteristics, treatment, and outcomes of patients with periprosthetic joint infection (PJI) and normal inflammatory markers after total knee arthroplasty (TKA) and total hip arthroplasty (THA). . In total 538 TKAs and 414 THAs underwent surgical treatment for PJI and met the inclusion criteria. Pre-operative erythrocyte sedimentation rate (ESR) and C-reactive protein level (CRP) were reviewed to identify the seronegative cohort. An age- and gender-matched cohort was identified from the remaining patients for comparison. Overall, 4% of confirmed infections were seronegative (21 TKA and 17 THA). Of those who underwent pre-operative aspiration, cultures were positive in 76% of TKAs (n = 13) and 64% of THAs (n = 7). Cell count and differential were suggestive of infection in 85% of TKA (n = 11) and all THA aspirates (n = 5). The most common organism was coagulase-negative Staphylococcus. Seronegative infections were associated with a lower aspirate cell count and a lower incidence of Staphylococcus aureus infection. Two-stage revision was performed in 35 cases (95%). At a mean of five years (14 to 162 months) following revision, re-operation for infection occurred in two TKAs, and one THA. From our study we estimate around 4% of patients with PJI may present with normal ESR and CRP. When performed, pre-operative aspirate is useful in delivering a definitive diagnosis. When treated, similar outcomes can be obtained compared with patients with positive serology. Cite this article: Bone Joint J 2015;97-B:939–44

Osteoarthritis is a slowly progressive disease which includes the intervention of several cytokines and macrophage metalleinoproteinases reaction, leading to the degradation of the local cartilage but also having an impact on the serum acute phase proteins (APPs). Subsequently, biomarkers seem to be essential to estimate its progression and the need for any surgical intervention such as total arthroplasty, but also can be used as therapeutic agents. Recently, among APPs, fetuin-A drew attention regarding its possible anti-inflammatory role in animal models but also as a therapeutic agent in the inflammatory joint disease in clinical trials. The purpose of this study is to investigate the possible attenuating role of the intra-articular administration of Fetuin-A in post-traumatic induced secondary osteoarthritis in rats, and also its effect on the systematic levels of IL-2,4,7, BMPs 2,4,7, CRP and Fetuin-A. 30 male Sprague Dawley rats were separated in two groups where post-traumatic osteoarthritis was induced surgically by Anterior Cruciate Ligament Transection and the transection of the Medial Collateral Ligament of the right knee. In the Control Group, only surgical intervention took place. In Fetuin Group, along with the induction of osteoarthritis, a single dose of bovine fetuin was administrated intra-articularly intra-operatively in 5 and 8 weeks of the experimental protocol. Both groups were examined for 8 weeks. The levels of interleukins, bone morphogenetic proteins, Fetuin-A and C-Reactive Protein were evaluated by ELISA of peripheral blood in three time periods: preoperatively, 5 and 8 weeks post-operatively. Knee osteoarthritic lesions were classified according to Osteoarthritis Research Society International Grading System and Modified Mankin Score, by histologic examination. IL-2 levels were significantly decreased in the Fetuin Group. No statistical difference was signed on the levels of IL-7, BMP-2,4,7 and Fetuin-A between the two groups. CRP levels were significantly increased in the Fetuin Group in 5 weeks of the experiment. Fetuin Group signed better scores according to the OARSI classification system and Modified Mankin Score, without any statistical significance. Intra-articular administration of Fetuin-A restrictively affected the progression of post-traumatic arthritis in rats, as only the levels of IL-2 were decreased as well as limited osteoarthritic lesions were observed on the Fetuin Group

Inflammatory markers such as the C-reactive protein (CRP), white blood cell count and body temperature are easy to measure and are used as indicators of infection. The way in which they change in the early post-operative period after instrumented spinal surgery has not been reported in any depth. We measured these markers pre-operatively and at one, four, seven and 14 days postoperatively in 143 patients who had undergone an instrumented posterior lumbar interbody fusion. The CRP proved to be the only sensitive marker and had returned to its normal level in 48% of patients after 14 days. The CRP on day 7 was never higher than that on day 4. Age, gender, body temperature, operating time and blood loss were not related to the CRP level. A high CRP does not in itself suggest infection, but any increase after four days may presage infection

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.

We evaluated the effects on infection control and clinical feasibility of a prosthesis with antibiotic-loaded acrylic cement(PROSTALAC) which was designed for treatment of infected total hip arthroplasty. Thirty patients underwent two-staged exchange arthroplasty using the PROSTALAC for treatment of the infected total hip arthroplasty were analysed from March 1995 to February 2007. For shaping of the stem spacer, cement containing antibiotics were appropriately coated on stem spacer and push and pull movement was carried out within the medullary cavity of proximal femur until cement hardened. Also, for prevent of post surgical dislocation, a specially designed polyethylene liner was used. Postoperatively, antibiotics were administered for at least 6 weeks according to the results of erythrocyte sedimentation rate and C-reactive protein assessment. Infection cure rated 83.3% (20 cases) and C-reactive protein normalized in an average of 5.6weeks (2wks~26wks) but ESR showed very variable score. Partial weight bearing with crutch was possible after 2 weeks postoperatively and lower-limb shortening averaged to 1.43 cm (0.5~3) with a mean bending range of 63.6 degrees (40~90). There were neither dislocations nor fractures during patient mobilization and 5 cases, especially in old age showed satisfactory results even without second staged revision. Recurred infection after PROSTALAC insertion occurred in 5 cases (15%). Appropriate techniques of PROSTALAC insertion for stability allows us to adjust the reimplantation timing to the course of infection control

Introduction. The objectives of this study were to compare the systemic inflammatory reaction, localised thermal response and macroscopic soft tissue injury outcomes in conventional jig-based total knee arthroplasty (conventional TKA) versus robotic total knee arthroplasty (robotic TKA). Methods. This prospective randomised controlled trial included 30 patients with symptomatic knee osteoarthritis undergoing conventional TKA versus robotic TKA. Predefined serum markers of inflammation and localised knee temperature were collected preoperatively and postoperatively at 6 hours, day 1, day 2, day 7, and day 28 following TKA. Blinded observers used the Macroscopic Soft Tissue Injury (MASTI) classification system to grade intraoperative periarticular soft tissue injury and bone trauma. Plain radiographs were used to assess the accuracy of achieving the planned limb alignment and implant positioning in both treatment groups. Results. Conventional TKA and robotic TKA had comparable changes in the postoperative systemic inflammatory reaction and localised thermal response at 6 hours, day 1, day 2 and day 28 after surgery. Robotic TKA had reduced levels of interleukin-6 (p<0.001), tumour necrosis factor-α (p=0.021), erythrocyte sedimentation rate (p=0.001), C-reactive protein (p=0.004), and creatine kinase (p=0.004) at day 7 after surgery compared to conventional TKA. Robotic TKA was associated with improved intraoperative preservation of the periarticular soft tissue envelope (p<0.001) and reduced bone trauma (p=0.015) compared to conventional TKA. Robotic TKA improved accuracy of achieving the planned limb alignment (p<0.001), femoral component positioning (<0.001), and tibial component positioning (<0.001) compared to conventional TKA. Conclusion. Robotic TKA was associated with a transient reduction in the early (day 7) postoperative inflammatory response but there was no difference in the immediate (<48 hours) or late (day 28) postoperative systemic inflammatory responses compared to conventional TKA. Robotic TKA was associated with decreased iatrogenic periarticular soft tissue injury, reduced bone trauma and improved accuracy of implant positioning compared to conventional TKA

Background. The anterior approach for total hip arthroplasty has recently been hypothesized to result in less muscle damage. While clinical outcome studies are essential, they are subject to patient and surgeon bias. We prospectively analyzed biochemical markers of muscle damage and inflammation in patients receiving anterior and posterior minimally-invasive total hip arthroplasty to provide objective evidence of the surgical insult. Methods. 29 patients receiving an anterior and 28 patients receiving a posterior total hip arthroplasty were analyzed. Peri-operative and radiographic data were collected to ensure similar cohorts. Creatine kinase, C-reactive protein, Interleukin-6, Interleukin-1beta, and Tumor necrosis factor-alpha were collected pre-operatively, post-operatively, and on post-operative days 1 and 2. Comparisons between the groups were made using the Student's t-test and Fisher's Exact test. Independent predictors of elevation in markers of inflammation and muscle damage were determined using multivariate logistic regression analysis. Results. Markers of inflammation were slightly decreased in direct anterior group (mean differences in C-reactive protein 27.5 [95% confidence interval −24.7–79.6] mg/dL, Interleukin-6 13.5 [95% confidence interval −11.5–38.4] pg/ml, Interleukin-1beta 42.6 [95% confidence interval −10.4–95.6], and Tumor necrosis factor-alpha 148.6 [95% confidence interval −69.3–366.6] pg/ml). The rise in creatine kinase was 5.5 times higher in the post anesthesia care unit (mean difference 150.3 [95% confidence interval 70.4–230.2] units/L, p < 0.05) and nearly twice as high cumulatively in the miniposterior approach group (305.0 [95% confidence interval −46.7–656.8] units/L, p < 0.05). Conclusion. Anterior total hip arthroplasty caused significantly less muscle damage compared to traditional posterior surgery as indicated by creatine kinase levels. The clinical importance of this rise needs to be delineated by further clinical studies. The overall physiologic burden as measured by markers of inflammation, however, appears to be similar. Objective measurement of muscle damage and inflammation provides an unbiased way of determining the immediate effects of surgical intervention in total hip arthroplasty patients

Aim. In the diagnosis of prosthetic joint infection (PJI), many biomarkers have shown a sound performance in terms of accuracy, sensitivity and specificity. In this study we aimed to test the frequently used serum biomarkers C-reactive Protein (CRP), Fibrinogen, Leukocytes, Interleukin-6 (IL-6), Interferon alpha (IF-alpha) and Procalcitonin (PCT) regarding these qualities. Following that, the optimal multi-biomarker combination was calculated to further improve the diagnostic performance. Method. 124 knee or hip revision arthroplasty procedures were prospectively investigated focusing on preoperative serum blood levels of CRP, Fibrinogen, Leukocytes, IL-6, IF-alpha and PCT. The presence of PJI was determined by a blinded researcher. Logistic regression with lasso-regularization was used for the biomarkers and all their ratios. Following cross-validation on a training sample set to get optimal performance estimates, we performed the final model on a test set (25% of all samples). Results. Out of all evaluated biomarkers, CRP (AUC 0.91, p-value 0.03) and Fibrinogen (AUC 0.93, p-value 0.02) had the best performances. The optimal combination when testing multiple biomarkers in 32 cross-validation runs was calculated including Fibrinogen, CRP, the ratio of Fibrinogen to CRP and the ratio of serum Thrombocytes to CRP (AUC 0.92, accuracy 0.77, specificity 0.92, sensitivity 0.68, cut-off 0.63, p-value 0.04). Conclusions. It was not possible to increase the diagnostic performance by combining multiple biomarkers using sophisticated statistical methods. The calculated Multi-biomarker models did not improve the AUC, accuracy, sensitivity and specificity when compared to single biomarkers

Objective. Mortality rates reported by the National Joint Registry for England and Wales (NJR) were higher following cemented total knee replacement (TKR) compared with uncemented procedures. The aim of this study is to examine and compare the effects of cemented and uncemented TKR on the activation of selected markers of inflammation, endothelium, and coagulation, and on the activation of selected cytokines involved in the various aspects of the systemic response following surgery. Methods. This was a single centre, prospective, case-control study. Following enrolment, blood samples were taken pre-operatively, and further samples were collected at day one and day seven post-operatively. One patient in the cemented group developed a deep-vein thrombosis confirmed on ultrasonography and was excluded, leaving 19 patients in this cohort (mean age 67.4, (. sd. 10.62)), and one patient in the uncemented group developed a post-operative wound infection and was excluded, leaving 19 patients (mean age 66.5, (. sd. 7.82)). Results. Both groups had a similar response with regards to the levels of C-reactive protein (CRP), interleukin 6 (IL-6) and tumour necrosis factor-alpha (TNFα). CD40 levels rose significantly on the cemented group over day one to day seven compared with that of the uncemented group, which occurred over the first 24 hours. The CD14/42a levels demonstrated a statistically significant increase in the cemented group (p < 0.001 first 24 hours and p = 0.02 between days one and seven). . Conclusions. The uncemented and cemented groups demonstrated significant changes in the various parameters measured at various time points but apart from CD14/42a levels, there was no significant difference in the serum markers of inflammation, coagulation and endothelial dysfunction following cemented TKR. Cite this article: Bone Joint Res 2014;3:108–16

The keys to revision total knee arthroplasty start with understanding the nature of the problem. Revision TKR is a major undertaking and should be focused on problem solving. Know the problem and remember pain is not a diagnosis. Review history of the problem and think of the possibilities: infection, loosening, instability, stiffness, malalignment, and poor kinematics. Ensure an adequate workup including an adequate history, exam and imaging including radiographs, MRI for soft tissue issues, and CT scans to assess rotational alignment. Labs should include CBC, ESR, C-reactive protein, and an aspiration including cell count and culture. Synthesise a working diagnosis and formulate a provisional plan to include what is to be revised, how will you get there remembering old incisions, and how will get the parts out? Think about equipment: what tools do you need and implant specific tools. Finally, once everything is out, think about what you have left (soft tissue defects and bone defects) to “rebuild”? This involves pondering constraint for soft tissue defects, stems for mechanical stability, cones, augments, bone graft for osseous defects and fixation

Adverse reaction to wear and corrosion debris is a cause for concern in total hip arthroplasty (THA). Modular junctions are a potential source of such wear products and are associated with secondary pseudotumour formation. . We present a consecutive series of 17 patients treated at our unit for this complication following metal-on-highly cross-linked polyethylene (MoP) THA. We emphasise the risk of misdiagnosis as infection, and present the aggregate laboratory results and pathological findings in this series. The clinical presentation was pain, swelling or instability. Solid, cystic and mixed soft-tissue lesions were noted on imaging and confirmed intra-operatively. Corrosion at the head–neck junction was noted in all cases. No bacteria were isolated on multiple pre- and intra-operative samples yet the mean erythrocyte sedimentation rate was 49 (9 to 100) and C-reactive protein 32 (0.6 to 106) and stromal polymorphonuclear cell counts were noted in nine cases. . Adverse soft–tissue reactions can occur in MoP THA owing to corrosion products released from the head–neck junction. The diagnosis should be carefully considered when investigating pain after THA. This may avoid the misdiagnosis of periprosthetic infection with an unidentified organism and mitigate the unnecessary management of these cases with complete single- or two-stage exchange. Cite this article: Bone Joint J 2015;97-B:1024–1030

Background. About 85% of the patients with low back pain seeking medical care have nonspecific low back pain (NsLBP), implying that no definitive cause can be identified. Many pain conditions are linked with elevated serum levels of (pro-)inflammatory biomarkers. Purpose. To unravel the etiology and get better insight in the prognosis of NsLBP, the aim of this study was to assess the association between (pro-)inflammatory biomarkers and the presence and severity of NsLBP. Methods. A systematic literature search was made in Embase, Medline, Cinahl, Web-of-science, and Google scholar up to January 19th 2017. Included were studies reporting on patients >18 years with NsLBP, in which one or more pro-inflammatory biomarkers were measured in blood plasma. The methodological quality of the included studies was assessed using the Newcastle Ottawa Scale (NOS). A best-evidence synthesis was used to summarize the results from the individual studies. Results. Included were 10 studies which assessed 4 different (pro-)inflammatory biomarkers. For the association between the presence of NsLBP and C-reactive protein (CRP), interleukin 6 (IL-6) and tumor necrosis factor (TNF)-α limited, conflicting and moderate evidence, respectively, was found. For the association between the severity of NsLBP and CRP and IL-6, moderate evidence was found. For the association between the severity of NsLBP and TNF-α and RANTES conflicting and limited evidence, respectively, was found. Conclusions. This study found moderate evidence for i) a positive association between the (pro-)inflammatory biomarkers CRP and IL-6 and the severity of NsLBP, and ii) a positive association between TNF-α and the presence of NsLBP. No conflicts of interest. No funding obtained

Rapidly progressive osteoarthritis of the hip (RPOH) is an unusual subset of osteoarthritis. It is characterized by rapid joint space loss, chondroly­sis, and sometimes marked femoral head and acetabular destruction as a late finding. The exact pathogenetic mechanism is unknown. Potential causes of RPOH include subchondral insufficiency fracture resulting from osteoporosis, increasing posterior pelvic tilt as a mechanical factor, and high serum levels of matrix metalloproteinase (MMP)-3 as biological factors. This study was aimed to identify some markers that associate with the destructive process of RPOH by analyzing the proposed pathological factors of the disease, MMP-3, pelvic tilt, and osteoporosis. Of female patients who visited our hospital with hip pain from 2012 through 2018, this study enrolled female patients with sufficient clinical records including the onset of hip pain, age and body mass index (BMI) at the onset, a series of radiographs during the period of >12 months from the onset of hip pain, and hematological data of MMP-3 and C-reactive protein (CRP). We found the hip joints of 31 patients meet the diagnostic criteria of RPOH, chondrolysis >two mm in one year, or 50% joint space narrowing in one year. Those patients were classified into two groups, 17 and 14 patients with and without subsequent femoral head destruction in one year shown by computed tomography, respectively. Serum MMP-3 and CRP were measured with blood samples within one year after the hip pain onset. The cortical thickness index (CTI) as an indicator of osteoporosis and pelvic tilt parameters were evaluated on the initial anteroposterior radiograph of the hip. These factors were statistically compared between the two groups. This study excluded male patients because RPOH occurs mainly in elderly females and the reference intervals of MMP-3 are different between males and females. There was no difference in age at onset or bone mass index between the RPOH patients with and without subsequent femoral head destruction. Serum levels of MMP-3 were significantly higher in the RPOH patients with the destruction (152.1 ± 108.9 ng/ml) than those without the destruction (66.8 ± 27.9 ng/ml) (P = 0.005 by Mann-Whitney test). We also found increased CRP in the patients with femoral head destruction (0.725 ± 1.44 mg/dl) compared with those without the destruction (0.178 ± 0.187 mg/dl) (P = 0.032 by Mann-Whitney test). No difference in the duration between the hip pain onset and the blood examination was found between the two groups. There was no significant difference in CTI or pelvic tilt between the two groups. The pathological condition that may increase serum MMP-3 and CRP could be involved in femoral head destruction after chondrolysis of the hip in patients with RPOH

Aims. The aim of this study was to examine the efficacy and safety of multiple boluses of intravenous (IV) tranexamic acid (TXA) on the hidden blood loss (HBL) and inflammatory response following primary total hip arthroplasty (THA). Patients and Methods. A total of 150 patients were allocated randomly to receive a single bolus of 20 mg/kg IV TXA before the incision (group A), a single bolus followed by a second bolus of 1 g IV-TXA three hours later (group B) or a single bolus followed by two boluses of 1 g IV-TXA three and six hours later (group C). All patients were treated using a standard peri-operative enhanced recovery protocol. Primary outcomes were HBL and the level of haemoglobin (Hb) as well as the levels of C-reactive protein (CRP) and interleukin-6 (IL-6) as markers of inflammation. Secondary outcomes included the length of stay in hospital and the incidence of venous thromboembolism (VTE). Results. The mean HBL was significantly lower in group C (402.13 ml standard deviation (. sd). 225.97) than group A (679.28 ml. sd. 277.16, p < 0.001) or B (560.62 ml . sd. 295.22, p = 0.010). The decrease in the level of Hb between the pre-operative baseline and the level on the third post-operative day was 30.82 g/L (. sd. 6.31 g/L) in group A, 27.16 g/L (. sd. 6.83) in group B and 21.98 g/L (. sd. 3.72) in group C. This decrease differed significantly among the three groups (p < 0.01). The mean level of CRP was significantly lower in group C than in the other two groups on the second (p ≤ 0.034) and third post-operative days (p ≤ 0.014). The levels of IL-6 were significantly lower in group C than group A on the first three post-operative days (p = 0.023). The mean length of stay was significantly lower in group C than group A (p = 0.023). No VTE or other adverse events occurred. Conclusion. Multiple boluses of IV-TXA can effectively reduce HBL following primary THA. A regime of three boluses leads to a smaller decrease in the level of Hb, less post-operative inflammation and a shorter length of stay in hospital than a single bolus. Cite this article: Bone Joint J 2017;99-B:1442–9

Purpose of the study: Joint puncture-wash-out is generally recommended for septic arthritis in children, but the debate is still open concerning the proper attitude for the hip joint. The purpose of this work was to examine our failure cases after treatment of septic hip arthritis using the puncture-wash-out option. We wanted to know whether first-intention primary arthrotomy might be a valid option. Material and methods: We reviewed retrospective 29 cases of septic hip arthritis treated initially by puncture-wash-out between January 1996 and June 2003. We excluded all cases of first intention arthrotomy. The series included 19 boys and ten girls aged four years three months on average at time of diagnosis (age range 8 months to 9 years). Mean follow-up was one year five months (range 1 month the 4 years). Mean delay to diagnosis was two days (range 0–6 days). In addition to intravenous antibiotics, the 29 hips were drained and washed out with saline solution under general anesthesia until a clear wash-out was obtained. Surgical revision (arthrotomy) was required for seven patients within 3 to 21 days. Results: Outcome was assessed at days 2, 5, and 10. Assessment variables were pain relief, normal blood tests, and apyrexia. Seven children required surgical revision for arthrotomy due to persistent clinical or biological disorders. Cure was achieved after all seven arthrotomies. At last follow-up, there was no difference, clinically or radiographically, between the children treated by puncture-wash-out or by arthrotomy. The factors which appeared to be the most significant to distinguish the two groups were, at admission: time to diagnosis and management greater than four days and C-reactive protein > 100. On day 5, the most significant factors were persistent joint pain and C-reactive protein > 100. Discussion: These results suggest that puncture-wash-out remains a simple and reliable treatment but that it has its limitations: a synovial biopsy cannot be obtained, visual examination of the joint cartilage is not possible, trepanation of the metaphysis is not possible. Our factors favoring poorer outcome are similar to those reported in the literature to which can be added age less than one year. When these factors are present, first-intention arthrotomy should be discussed

In the case of a complete dislocated hip or a severe deformity of the proximal femur, total hip arthroplasty (THA) can still be combined with a proximal femoral osteotomy for shortening femur or correcting the deformity if needed. Subtrochanteric femoral shortening and a corrective osteotomy are considered to be an integral part of THA for such cases. A precise osteotomy is mandatory to achieve good results. Although, the freehand excision of V-shaped subtrochanteric osteotomy used to be performed frequently, this procedure was also subject to some pitfalls, such as poor coaptation of the osteotomy surface. A new device was thus developed to perform a V-shaped osteotomy in an identical central axis between the distal and proximal femur. The purpose of this study was to evaluate the efficacy of the device by comparing the perioperative results with those of a free-hand subtrochanteric osteotomy. From 1999 to 2002, THA combined with a double-chevron subtrochanteric osteotomy was performed by free hand (free hand group). From 2003 to 2007, THA combined with a double-chevron subtrochanteric osteotomy was performed using a new device (device group). The free hand group included 27 hips in 21 patients. The mean age of the patients (23 females and 3 males) at the time of the operation was 58 years. Fourteen were completely dislocated hips and 13 followed various proximal femoral osteotomies. The device group included 102 hips in 79 patients. The mean age of thepatients (70 females and 9 males) at the time of the operation was 62 years. Seventy two were completely dislocated hips and 26 followed various proximal femoral osteotomies. Four parameters were used to evaluate the efficacy of the device:. operation time,. total blood loss,. C-reactive protein at postoperative 1 day and. early complications at the osteotomy site. The mean operation time, total blood loss, and C-reactive protein in the device group all significantly decreased in comparison to the free hand group. The decreases ranged from; 132 to 96 minutes (p< 0.01), 1346 to 999 g (p< 0.01), 4.9 to 3.0 mg/dl (p< 0.05), respectively. Two types of complications were observed at the osteotomy site. Pseudoarthrosis at the osteotomy site was observed one case in each group and both of these cases underwent a stem revision (4% in the freehand group and 1% in the device group). A femoral shaft split was observed in 3 cases in the freehand group (11%) and 3 cases in the device group (3%) and all 6 cases were treated conservatively. There were no instances of nerve palsy, infections, or thromboembolic events resulting from these procedures. The above described new device allowed for the easy and accurate performance of a subtrochanteric V-shaped osteotomy with THA for either a completely dislocated hip or a severely deformed proximal femur

There have been few reports regarding the efficacy of posterior instrumentation alone as surgical treatment for patients with pyogenic spondylitis, thus avoiding the morbidity of anterior surgery. We report the clinical outcomes of six patients with pyogenic spondylitis treated effectively with a single-stage posterior fusion without anterior debridement at a mean follow-up of 2.8 years (2 to 5). Haematological data, including white cell count and level of C-reactive protein, returned to normal in all patients at a mean of 8.2 weeks (7 to 9) after the posterior fusion. Rigid bony fusion between the infected vertebrae was observed in five patients at a mean of 6.3 months (4.5 to 8) post-operatively, with the remaining patient having partial union. Severe back pain was immediately reduced following surgery and the activities of daily living showed a marked improvement. Methicillin-resistant Staphylococcus aureus was detected as the causative organism in four patients. Single-stage posterior fusion may be effective in patients with pyogenic spondylitis who have relatively minor bony destruction

Since 1996 more than one million metal-on-metal articulations have been implanted worldwide. Adverse reactions to metal debris are escalating. Here we present an algorithmic approach to patient management. The general approach to all arthroplasty patients returning for follow-up begins with a detailed history, querying for pain, discomfort or compromise of function. Symptomatic patients should be evaluated for intra-articular and extra-articular causes of pain. In large head MoM arthroplasty, aseptic loosening may be the source of pain and is frequently difficult to diagnose. Sepsis should be ruled out as a source of pain. Plain radiographs are evaluated to rule out loosening and osteolysis, and assess component position. Laboratory evaluation commences with erythrocyte sedimentation rate and C-reactive protein, which may be elevated. Serum metal ions should be assessed by an approved facility. Aspiration, with manual cell count and culture/sensitivity should be performed, with cloudy to creamy fluid with predominance of monocytes often indicative of failure. Imaging should include ultrasound or metal artifact reduction sequence MRI, specifically evaluating for fluid collections and/or masses about the hip. If adverse reaction to metal debris is suspected then revision to metal or ceramic-on-polyethylene is indicated and can be successful. Delay may be associated with extensive soft-tissue damage and hence poor clinical outcome

Introduction: The results of total hip arthroplasty are in general very good. One of the factors with a negative influence on the outcome is an infection of the prosthesis. The prevalence of an acute post-operative infection is in the Netherlands in the range of 0.5 up to 2.0%. Different types of treatment are advised in the literature. Methods and Material: In 1997 we started to treat all the acute infected THA according a protocol of open surgical debridement, pulsative irrigation, application of several gentamicin loaded sponges and starting directly post-operative an antibiotic combination therapy of flucloxacillin and rifampin. The antibiotic therapy was adjusted to the cultures taken during the operation and continued till 3 months after the debridement. From Mars 1997 till July 2003 we subsequent included 32 patients, 26 with a minimal follow-up of 2 years are presented in this study. We evaluated the results of the treatment prospectively. The inflammatory parameters; C-reactive protein, erythrocyte sedimentation rate and white blood cell count (before and after debridement) The Harris Hip Score and radiograms were monitored multiple times. Results: The mean onset of infection symptoms till surgical debridement was ldays (range 0–15). All had high-elevated infection parameters and in all cases we found positive tissue cultures. 15 Times a Staphylococcus aureus was found, 5 times a Enterobacter cloacae, twice a Streptococcus, once a Pseudomonas, once a Klebsiella and once a peptostreptococcus. The average follow-up was 46 months (range 24–74). In 23 patients the infection did not re-appear. The C-reactive protein normalised from a mean of 103 (2–320) to lower than 5 at 2 years, the erythrocyte sedimentation rate from 72 (14–120) to lower than 10. The white blood cell count was not elevated. In none of the cases radiological signs of loosening was found and the mean HHS was 88 (75–96) points. However in 3 patients the infection did re-occur: once after 2.5 months with the same bacterium as the first infection, a Streptococcus, again treated with a surgical debridement. At present she is clinical free of infection at a follow up of 2 years. The 2 other re-infections occurred respectively after 9 and 10 months, once after a surgical treatment of a jaw abscess and once after an episode of diverticulitis. The cultures derived other bacteria, a streptococcus and an E. coli, than the first infection, both a Staphylococcus aureus. In both cases a two-stage revision was the choice of treatment. Conclusion: Finally 24 of the 26 acute infected hip arthroplasties were free of infection at 2 years follow-up. Surgical debridement and three months of antibiotics gave a good clinical result and a very low recurrent rate of the infection

Aim. Treatment of complicated wound healing after total joint arthroplasty is controversial. What exactly constitutes prolonged wound drainage is matter of debate and recommendations to manage it vary considerably. Nonoperative measures are often recommended. If drainage persists, surgery may be indicated. To further intricate decision-making, differentiating superficial from deep surgical site infection is also controversial and inherently complex. Specific cutoffs for synovial fluid leukocyte count and blood C-reactive protein (CRP) in the acute stage have been suggested as a way to superficial infection requiring superficial wound washout from deep infection requiring a formal debridement, antibiotics and implant retention (DAIR) procedure. The goal of this study is to analyze clinical and laboratory findings of an institutional protocol of “aggressively” proceeding with formal DAIR in all patients with complicated wound healing. Method. Our indications for DAIR in suspected acute postoperative periprosthetic joint infection (PJI) are: 1)prolonged wound drainage and CRP upward trend after day-3; 2)persistent wound drainage by day-10 regardless of CRP; 3)wound healing disturbance (e.g. “superficial” infection, “superficial” skin necrosis) anytime in early postoperative weeks. We retrospectively evaluated patients undergoing DAIR in the first 60 postoperative days between 2014–2018. Patients without multiple deep tissue cultures obtained intraoperative were excluded. Deep infection was defined by at least two positive deep tissue cultures or one positive deep culture and positive leukocyte count (>10,000 cells/mL or >90% PMN). Results. A total of 44 DAIR procedures were included. Deep infection was confirmed in 79.5%(35/44) of cases. Mean CRP in infected cases was 93mg/L with 63%(19/30) of them below the 100 mg/L threshold. Unfortunately, only a small proportion of cases (10/44) had synovial fluid leukocyte counts available. Mean leukocyte count was 15,558 cells/mL and mean proportion of PMN was 65.3%. Of these ten, six confirmed deep infections were below the proposed >10,000 cells/mL or >90% PMN cutoff. Conclusions. Early diagnosis of acute postoperative PJI is often hampered by its very subtle presentation. This study confirms that more often than not, deep infection is present when facing complicated wound healing after total joint arthroplasty, supporting our institutional “aggressive” protocol. We have been surprised by the number of confirmed acute PJI with low blood CRP levels and low synovial leukocyte counts. We hypothesize that the proposed acute PJI specific thresholds may lead to misinterpret a significant proportion of cases as superficial infections thus compromising timely intervention. The findings of this study lack confirmation in larger cohorts

Aim. Traditionally, serum white blood count (WBC), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) have been utilized as markers to evaluate septic arthritis (SA). Recently, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been identified as prognostic factors for treatment failure, mortality and morbidity in various clinical settings. To date, these markers have not been utilized for evaluating outcomes after hip and knee SA. Thus, the purpose of this study was to determine the ability of admission NLR and PLR to predict treatment failure and postoperative 90-day mortality in hip and knee SA. Method. A retrospective study was performed using our institutional research patient database to identify 235 patients with native hip and knee septic arthritis from 2000–2018. Patient demographics, comorbidities and social factors (alcohol intake, smoking and intravenous drug use) were obtained, and NLR and PLR were calculated based on complete blood count values (absolute neutrophil, lymphocyte and platelet count) on admission. Treatment failure was defined as any reoperation or readmission within 90 days after surgery. Receiver operating curves were analyzed, and optimal thresholds for NLR and PLR were determined using Youden's test. Univariate and multivariate analyses were performed to determine if these ratios were independent predictors of treatment failure and 90-day mortality after surgery. These ratios were compared to serum WBC, CRP, and ESR. Results. Optimal thresholds for NLR was 9.49 (sensitivity=60%, specificity=84%) and PLR was 303 (sensitivity=54%, specificity=77%). With univariate analysis, NLR>9.49 was associated with failure (odds ratio [OR]=7.64, 95%. Confidence Interval [CI]=4.10–14.21) and 90-day mortality (OR=9.83, 95% CI=2.74–35.25). PLR>303 was associated with increased failure (OR=3.85, 95% CI=2.12–7.00). In multivariate analysis controlling for patient demographics, comorbidities and social factors, elevated NLR remained an independent predictor of failure (OR=7.04, 95% CI=3.78–13.14) and 90-day mortality (OR=5.98, 95% CI=1.60–22.32), whereas PLR remained a predictor of failure (OR=3.58, 95% CI=1.95–6.58). NLR was a better predictor of failure and 90- day mortality compared to serum WBC, CRP, and ESR. Conclusions. This study demonstrates that NLR is a good estimate of SA and performs better than serum WBC, CRP and. ESR to predict treatment failure and 90-day mortality. Elevated NLR is a reliable novel biomarker that may be utilized when evaluating SA patients, and this accessible test could be utilized in the musculoskeletal infection field

Aim. Debridement, antibiotics and implant retention (DAIR) is the recommended treatment for all acute prosthetic joint infections (PJI). However, the efficacy of DAIR and identification of risk factors for failure in patients with late acute PJI, is not well described. Method. Patients diagnosed with late acute PJI between 2005 and 2015 were retrospectively evaluated. Late acute PJI was defined as the development of acute symptoms (≤ 3 weeks) occurring ≥ 3 months after arthroplasty. Failure was defined as: i) the need for implant removal, ii) infection related death, iii) the need for suppressive antibiotic therapy due to persistent signs of infection and/or iv) relapse or reinfection during follow-up. Results. 340 patients from 27 centers were included. The overall failure rate was 45.0% (153/340). Failure was dominated by Staphylococcus aureus PJI (54.7%, 76/139). Preoperative risk factors for failure according to the multivariate analysis were: fracture as indication for the prosthesis (odds ratio (OR) 5.4), rheumatoid arthritis (OR 5.1), COPD (OR 2.9), age above 80 years (OR 2.6), male gender (OR 2.0) and C-reactive protein >150 mg/L (OR 2.0). Exchanging the mobile components during DAIR was the strongest predictor for treatment success (OR 0.35). Conclusions. Late acute PJIs have a high failure rate. Treatment strategies should be individualized according to patients' age, comorbidity, clinical presentation and microorganism causing the infection

Early mortality in patients with hip fractures due to bony metastases is unknown. The aim was to quantify 30 and 90-day mortality in patients with metastatic hip fractures and identify markers associated with early death. Consecutive patients referred to orthopaedics with a metastatic proximal femoral fracture/impending fracture over a six-year period were compared to a matched control group of non-malignant hip fractures. Minimum follow-up was 1 year and data was analysed using the student´s t-test (significance p<0.05). From Jan 2010-Dec 2015, 163 patients were referred with metastatic proximal femoral lesions. 90-day mortality was three times higher than controls (44% 71/163 vs. 12% 4/33, p<0.01). Mean time from referral to surgery was longer in impending versus completed fractures (11 and 4 days respectively, p<0.05). Multiple biochemical markers were associated with early mortality in the metastatic group. Patients who died early were more likely to demonstrate low haemoglobin and albumin, and high c-reactive protein, platelets, urea, alkaline phosphatase and calcium (p<0.05). Several biochemical markers associated with early mortality reached clinical and statistical significance. These markers were combined into a score out of 7 and indicated a higher early mortality in metastatic patients compared to controls. Patients with a score of 5–6/7 were 31 times more likely to die within 90 days versus controls. This scoring system could be utilised to predict early mortality and guide management. The average delay to surgery of 4 days (completed) and 11 days (impending fractures) identifies a window to intervene and correct these abnormalities to improve survival

Aim. The increasing incidence of orthopaedic methicillin-resistant Staphylococcus aureus (MRSA) infections represents a significant therapeutic challenge. Being effective against MRSA, the role of vancomycin may become more important in the orthopaedic setting in the years to come. Nonetheless, vancomycin bone and soft tissue penetration during infection remains unclear. We assessed the effect of a traumatically induced, implant-associated acute osteomyelitis on vancomycin bone penetration in a porcine model. Method. In eight pigs, implant-associated osteomyelitis was induced on day 0, using a Staphylococcus aureus strain. Following administration of 1,000 mg of vancomycin on day 5, vancomycin concentrations were obtained with microdialysis for eight hours in the implant bone cavity, in cancellous bone adjacent to the implant cavity, in subcutaneous adipose tissue (SCT) adjacent to the implant cavity, and in healthy cancellous bone and healthy SCT in the contralateral leg. Venous blood samples were also obtained. The extent of infection and inflammation was evaluated by post-mortem computed tomography scans, C-reactive protein serum levels and cultures of blood and swabs. Results. In relation to all the implant cavities, bone destruction was found. Ranging from 0.20 to 0.74, tissue penetration, expressed as the ratio of tissue to plasma area under the concentration-time curve from 0 to the last measured value, was incomplete for all compartments except for healthy SCT. The lowest penetration was found in the implant cavity. Conclusions. Staphylococcus aureus implant-associated osteomyelitis was found to reduce vancomycin bone penetration, especially in the implant cavity. These findings suggest that it may be unsafe to rely solely on vancomycin therapy when treating acute osteomyelitis. Particularly when metaphyseal cavities are present, surgical debridement seems necessary

Aim. Cutibacterium acnes is a significant cause of late-onset spinal implant infection (SII). In addition, usual preoperative prophylactic measures may be insufficient to prevent C. acnes operating site colonisation and infection, as demonstrated for prosthetic shoulder surgery. However, little information is available regarding risk factors for SII due to this microorganism. The aims of this study were to determine the characteristics of and risk factors for C. acnes SII. Method. we conducted a retrospective unmatched case-control study including all adult patients treated for mono and polymicrobial C. acnes SII during 2010–2015. Controls were randomly selected among patients diagnosed with SII due to other microorganisms during the same period. Results. Fifty-nine patients with C. acnes SII were compared with 59 controls. There was no difference in sex distribution (39% vs 53% men). Patients with C. acnes SII were younger (median age 42 vs. 65, p< 0.001), thinner (median body mass index (BMI) 21 vs. 25 kg/m. 2. , p< 0.001), and presented a better health status (ASA score≤ 2, 83% vs. 65%, p= 0.015; and presence of immunosuppression, 3% vs. 27%, p= 0.002). Patients with C. acnes SII were more likely to experience delayed/late infections (i.e. diagnosed >3 months post-instrumentation, 66% vs. 22%, p< 0.001) and to be instrumented for scoliosis (83% vs. 27%, p< 0.001) with an extended osteosynthesis (median number of fused vertebrae 12 vs. 5, p< 0.001). However, 20 C. acnes SII (34%) developed early (≤3 months) after instrumentation. The clinical presentation was significantly more indolent in the C. acnes group (presence of fever, 27% vs. 61%, p= 0.001; wound inflammation 39% vs. 61%, p< 0.001 and median C-reactive protein level 38 vs. 146 mg/L). Mixed C. acnes SII were diagnosed on 24 occasions (41%), 22 of which involving both C. acnes and staphylococcal strains. In the multivariate logistic regression model, factors independently associated with the development of SII involving C. acnes were age less than 65 (adjusted odds ratio [aOR] 7.13, 95% CI [2.44–24.4], p= 0.001), BMI< 22kg/m. 2. (aOR 3.71 [1.34–10.7], p= 0.012) and a number of fused vertebrae >10 (aOR 3.90 IC 95% [1.51–10.4], p= 0.005). Conclusions. There were significant differences between SII involving C. acnes and those involving other microorganisms. We identified a specific profile of patients at increased risk of developing C. acnes SII. These findings could contribute to improve both the prevention and treatment of such infections

Aim. Debridement, antibiotics and implant retention (DAIR) is a widely used treatment modality for early acute prosthetic joint infection (PJI). A preoperative risk score was previously designed for predicting DAIR failure, consisting of chronic renal failure (K), liver cirrhosis (L), index surgery (I), cemented prosthesis (C) and C-reactive protein >115mg/L (KLIC). The aim of this study was to validate the KLIC score in an external cohort. Method. We retrospectively evaluated patients with early acute PJI treated with DAIR between 2006 and 2016 in three Dutch hospitals. Early acute PJI was defined as less than 21 days of symptoms and DAIR performed within 90 days after index surgery. Failure was defined as the need for 1) second DAIR, 2) implant removal, 3) suppressive antimicrobial treatment or 4) infection-related death within 60 days after debridement. Results. A total of 386 patients were included. Failure occurred in 148 patients (38.3%). Patients with KLIC scores of ≤2, 2.5–3.5, 4–5, 5.5–6.5 and ≥7 had failure rates of 27.9%, 37.1%, 49.3%, 54.5% and 85.7% respectively (p<0.001, OR 1.33), in which one point increase in the KLIC score represents a 1.33 times higher risk of failure. The ROC curve showed an area under the curve of 0.64 (95% CI 0.59–0.69). A KLIC score higher than 6 points showed a specificity of 97.9%. Conclusions. The KLIC score is a relatively good preoperative risk score for DAIR failure in patients with early acute PJI and appears to be most useful in clinical practice for patients with low or high KLIC scores

Aim. The aim of this study was to compare outcomes between patients with diabetic foot soft-tissue infection and osteomyelitis. Methods. Medical records of patients with diabetic foot infection involving either soft-tissue (STI) or bone (OM) were retrospectively reviewed. Diagnosis was determined by bone culture, bone histopathology or imaging with magnetic resonance imaging (MRI) or single-photon emission computed tomography (SPECT/CT). Patient outcomes were recorded up to 1 year after admission. Results. Out of 294 patients included in the study, 137 were diagnosed with STI and 157 had OM. No differences in age (p=.40), sex (p=.79), race (p=.83), body-mass index (p=.79) or type of diabetes (p=.77) were appreciated between groups. Frequency of comorbidities (neuropathy, chronic kidney disease, peripheral arterial disease) also did not differ except for increased prevalence of cardiac disease in patients with STI (86.9%) compared to those with OM (31.8%) (p<.00001) and decreased prevalence of retinopathy (24.8% vs. 35.7%) (p=.04). Patients with OM had greater C-reactive protein (p<.00001), erythrocyte sedimentation rate (p<.00001) and white blood cell count (p<.00001). Among 1-year outcomes, patients with OM more often underwent surgery (p<.00001), had lower limb amputations (p<.00001), became reinfected (p=.0007), were readmitted for the initial problem (p=.008), had longer time to healing (p=.03) and had longer hospital length of stay (p=.00002). However, no differences in 1-year mortality (p=1.000), overall 1-year readmission (p=.06) or healing within 1-year (p=.64) were appreciated. Conclusion. In our study, OM was associated with more aggressive treatment, reinfection and longer time to healing than STI. However, despite being associated with more aggressive care and readmissions, patients with diabetic foot OM has similar 1-year mortality and healing rates to those with diabetic foot STI

Aim. Diagnosing fracture related infections (FRI) based on clinical symptoms alone can be challenging and additional diagnostic tools such as serum inflammatory markers are often utilized. The aims of this study were 1) to determine the individual diagnostic performance of three commonly used serum inflammatory markers: C-Reactive Protein (CRP), Leukocyte Count (LC) and Erythrocyte Sedimentation Rate (ESR), and 2) to determine the diagnostic performance of a combination of these markers and their value additionally to clinical predictors for FRI. Method. This cohort study included patients who presented with a suspected FRI at two level I academic trauma centers between February 1. st. 2009 and December 31. st. 2017. The parameters CRP, LC and ESR, were obtained from hospital records when FRI was suspected. The gold standard for diagnosing or ruling out FRI was defined as: positive microbiology results of surgically obtained tissue samples, or absence of FRI at a clinical follow-up of at least six months. Separate markers were analysed using hospital thresholds, to determine current diagnostic performance, and continuously, to determine maximum possible diagnostic performance. Multivariable logistic regression analyses were performed to obtain the discriminative performance (Area Under the Receiver Operating Characteristic, AUROC) of (1) the combined inflammatory markers, and (2) the value of these markers additional to clinical parameters. Results. A total of 168 patients met the inclusion criteria and were included for analysis. CRP had a 38% sensitivity, 34% specificity, 42% positive predictive value (PPV) and 78% negative predictive value (NPV). For LC this was 39%, 74%, 46% and 67% and for ESR 62%, 64%, 45% and 76% respectively. The diagnostic accuracy was 52%, 61% and 80% respectively. The AUROC was 0.64 for CRP, 0.60 for LC and 0.58 for ESR. The AUROC of the combined inflammatory markers was 0.63. Serum inflammatory markers combined with clinical parameters resulted in AUROC of 0.66 as opposed to 0.62 for clinical parameters alone. Conclusions. The added diagnostic value of CRP, LC and ESR for diagnosing FRI is limited. Clinicians should be aware of this finding in the diagnostic work-up of suspected FRI

Aim. Prosthetic Joint Infection (PJI) remains one of the leading cause for revision arthroplasty. 1,2. Early recognition and appropriate initial treatment of early PJI with debridement, antibiotics and implant retention (DAIR) can eradicate infection on first attempt and prevent implant failure. We evaluated the outcome after one year of patients who were treated for an early PJI after primary total knee arthroplasty (TKA) or total hip arthroplasty (THA) with DAIR. Furthermore, we determined preoperative infection markers, microbiology, and treatment factors related to treatment failure after DAIR procedure. Method. A retrospective cohort study was assembled with 91 patients undergoing DAIR after primary TKA or THP with a high suspicion of an early PJI. For all patients intraoperative cultures were obtained. Records were reviewed for demographic details, preoperative laboratory results, microbiological data, given treatment and postoperative follow-up. The primary outcome measure was infection-free implant survival at one year. Repeated DAIR was not considered as treatment failure. Results. Following DAIR in early PJI the rate of infection-free implant survival was 83% (95% confidence intervals (CI) 79 to 91) at one year follow-up, including patients with multiple DAIR procedures. Univariate analysis indicate a higher failure rate in early PJI caused by Enterococcus faecalis (p=0.04). Multivariate analysis showed that a high C-reactive protein level (CRP >100) (odds ratio 7.5, 95% CI [1.4–39.7]) and multiple debridement procedures (≥2) (p=0.004, odds ratio 8.5, 95%CI [2.1–34.3]) were independently associated with treatment failure. Conclusions. Significantly elevated preoperative serum inflammatory markers may indicate difficult-to-treat, fulminant infections. The winning team in the eradication of an early PJI on first attempt and prevent implant failure is adequate debridement and appropriate empiric antibiotics. To improve treatment success and prevent the need for multiple debridement procedures it is important to use the adequate debridement technique and to have knowledge about local bacterial resistance patterns. Inadequate use of debridement and/or antibiotics can contribute to treatment failure in early PJIs and consequently in saving the affected joint arthroplasty

Purpose. Various approaches have been reported for the total hip replacement (THR). In recent years, a muscle sparing approach with low postoperative muscle weakness and low dislocation risk has been frequently selected. However, such surgery has a learning curve. Thus, at the time of switching from the conventional approach to such approaches, invasion or infection risk may increase with the operation time extension. The purpose of this study is to clarify the change of invasiveness or latent infection rate with the change in approach in order to select the cases safely at the beginning of introducing a new approach in THR. Methods. In facility A, THR was performed with Dall's approach (Dall), but 1 surgeon changed Dall to anterolateral modified Watson-Jones approach (OCM) and another surgeon changed Dall to direct anterior approach (DAA). In facility B, all 3 surgeons changed posterolateral (PL) approach to OCM. The subjects are 150 cases in total, including the each last 25 cases operated with the conventional approach and the each first 25 cases operated with a new approach (Dall to OCM: 25 + 25, Dall to DAA: 25 + 25, PL to OCM: 25 +25 cases). And, differences in operative time, intraoperative bleeding volume, postoperative hospital stay, and postoperative hemoglobin, white blood cell count, lymphocyte count, creatine kinase (CK), C-reactive protein (CRP) were investigated. Results. The average age of subjects was 64 years (31–87 years old), and there were 27 male subjects and 123 female subjects. In the change from Dall to OCM, only the postoperative hospital stay decreased significantly. In the change from Dall to DAA, the length of hospital stay and postoperative CRP significantly decreased, but the intraoperative bleeding volume increased. In the change from PL to OCM, the operation time, postoperative CRP and CK decreased, but postoperative Hb decreased. Cases with lymphocytes less than 1000/µL or less than 10% after surgery on day 4 are latent infection cases, and in such cases the operation time was significantly longer, the postoperative Hb was significantly lower, and the postoperative CK was significantly higher. However, such cases were not significantly increased by the change of operation approach. Conclusion. Introduction of the muscle sparing approach improved many items on surgical invasion, but some items deteriorated especially at the beginning of a new approach. In the early stages of introduction of the new approach, choosing cases without obesity and without lots of muscle volume may reduce latent infection

Cutibacterium species (formerly Propionibacterium species) are increasingly recognized as causative pathogens of low-grade periprosthetic joint infections (PJI). The clinical manifestation of infections caused by this low virulent microorganism is nonspecific and the interpretation remains challenging. In this prospective cohort study from 01/2012 to 07/2017 we analyzed the clinical and diagnostic characteristics of microbiologically proven hip PJI caused by Cutibacterium species. PJI was defined by growth of Cutibacteria in ≥2 periprosthetic tissue samples or in sonication fluid of the removed implant (>50 CFU/ml) at revision surgery. If Cutibacteria grew only in synovial fluid at least one other positive microbiological specimen or non-microbiological criterion was required. We included 26 patients suffering from Cutibacterium hip PJI, among them 19 were males (73%). The majority of PJI (24, 92%) presented delayed (3–24 months) or late (>24 months) after implantation. Sinus tract was present in 4 patients (16%) and radiological implant loosening in 16 patients (62%). Among non-microbiological diagnostic tests, increased synovial fluid leukocyte count showed the highest sensitivity (82%), followed by tissue histology (71%) and serum C-reactive protein (58%). After 7 days of incubation Cutibacterium grew in synovial fluid, periprosthetic tissue and sonication fluid culture in 20%, 42% and 32%, respectively, and in 43%, 76% and 83%, respectively, after 14 days of incubation. We conclude that Cutibacterium PJI was diagnosed late in the disease course and presented with subtle clinical signs. Prolonged culture incubation and implant sonication improved the poor performance of conventional microbiological tests. Due to lack of reliable diagnostic tests, Cutibacterium remains difficult to detect making the diagnosis challenging

Understand the nature of the problem. Revision TKR is a major undertaking and should be focused on problem solving. Know the problem!- Pain is not a diagnosis. Review history of problem. Think of possibilities: Infection, loosening, instability, stiffness, malalignment, poor kinematics. Ensure an adequate workup - History, Exam; Imaging: Radiographs: consider long alignment films, MR for soft tissue issues: Clunk, recurrent hemarthroses; CT scan: Remains gold standard for rotational alignment. Labs: CBC, ESR, C-reactive protein. Aspiration: Cell count, Culture. Assessment of where the patient is currently!. Synthesise a working diagnosis and formulate a provisional plan. Revise “part of knee”: you better know what's in there! Revise “all of knee”. How will you get there? Think old incisions. How will get the parts out? What tools do you need? High speed burrs / diamond tip wheel /long thin saw blades; Osteotomes; Implant specific tools. Once everything is out: What do you have left? Soft tissue defects, Bone defects. How to “rebuild”: Constraint for soft tissue defects, Stems for mechanical stability, Cones / augments / bone graft for osseous defects; Fixation: Cement, Cementless

Aim. Fracture related infection (FRI) remains a challenging diagnosis in orthopedic and trauma surgery. In addition to clinical signs and imaging, serum inflammatory markers are often used to estimate the probability of FRI. To what extent serum inflammatory markers can be used to rule out and diagnose FRI remains unclear. The aim of this systematic review was to assess the diagnostic value of the serum inflammatory markers C-reactive protein (CRP), leukocyte count (LC) and erythrocyte sedimentation rate (ESR) in suspected fracture related infection. Method. PubMed, Embase and Cochrane databases were searched for all articles focusing on the diagnostic value of CRP, LC and ESR in FRI. Studies on other inflammatory markers or other types of orthopedic infection, such as periprosthetic and diabetic foot infections, were excluded. For each serum inflammatory marker, all reported sensitivity and specificity combinations were extracted and graphically visualized. Average estimates were obtained using bivariate mixed effects models. This study utilized the QUADAS-2 criteria and was reported following the PRISMA statement. Results. The search resulted in 8280 articles, of which seven were eligible for inclusion. One study was excluded after quality assessment. CRP was reported in all included studies, with sensitivity ranging from 60.0 to 100.0% and specificity from 34.3 to 85.7%. Five of these studies were pooled. The average pooled sensitivity and specificity of CRP were, respectively, 77.0% (95% CI 66.5–85.0%) and 67.9% (95% CI 38.7–87.6%). LC was reported in five studies. Sensitivity ranged from 22.9 to 72.6% and specificity from 73.5 to 85.7%. The results of four of these studies were pooled, resulting in a 51.7% (95% CI 27.2–75.5%) sensitivity and 67.1% (95% CI 19.3–50.2%) specificity. ESR was reported in five studies. Sensitivity and specificity ranged from 37.1 to 100.0% and 59.0 to 85.0% respectively. Three of these studies were pooled, showing a 45.1% (95% CI 37.8–52.6%) sensitivity and 79.3% (95% CI 71.7–85.2%) specificity of ESR. Four studies analyzed the combined value of inflammatory markers, reporting an increased diagnostic accuracy. These results could not be pooled due to heterogeneity. Conclusions. The serum inflammatory markers CRP, LC and ESR are insufficiently accurate to diagnose FRI. These markers cannot rule out the presence of FRI, but they may be used as a suggestive sign in the diagnosis of FRI

While advances in laboratory and imaging modalities facilitate the diagnosis of periprosthetic joint infection (PJI), clinical suspicion and a thorough history and physical remain the basis of evaluation. If clinical suspicion is high, the evaluation should be more vigorous, and vice versa. The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are inexpensive as well as ubiquitous, and should be obtained as a preliminary screening tool. These tests have been found to be cost-effective and highly sensitive. If both tests are negative, there is a low risk of periprosthetic joint infection (i.e., good negative predictive value). Positive results on both tests, in contrast, are not as specific but again raise suspicion. When either the ESR or CRP is elevated, or if the clinical suspicion for infection is high, aspiration of the knee joint is suggested. Synovial fluid should be sent for a synovial fluid white blood cell count (WBC), differential and culture. Given the ability to get three data points from one intervention, arthrocentesis, is the best single maneuver the physician can perform to rule in or out PJI. The synovial fluid WBC count has demonstrated in multiple studies excellent specificity and sensitivity in the diagnosis of infection. Based on multiple recent studies, the proceedings of the International Consensus on PJI recommend cut-offs for the synovial fluid WBC count as >3000 cells/mL and > 80% neutrophils for the differential. Synovial fluid biomarkers represent an expanding area of clinical interests based on the unique cascade of gene expression that occurs in white blood cells in response to pathogens. Deirmegian et al. described the unique gene expression and biomarker production by neutrophils in response to bacteria that are detectable in synovial fluid. Specifically, alpha-defensin is one such antimicrobial peptide. Along with synovial CRP, alpha-defensin can be measured in a currently commercially-available immunoassays. The diagnosis of PJI can be difficult to make in spite of the variety of tests available. That being said, the diagnosis is easily made in our experience in 90% of patients by getting an ESR and CRP followed by selective aspiration of the joint if these values are elevated or if the clinical suspicion is high. Synovial fluid obtained should be sent for a synovial fluid WBC count, differential and cultures

The AAOS clinical practice guideline for diagnosis of periprosthetic joint infection (PJI) and the MSIS definition of PJI were both “game changers” in terms of diagnosing PJI and the reporting of outcomes for research. However, the introduction of new diagnostic modalities, including biomarkers, prompted a re-look at the diagnostic criteria for PJI. Further there was a desire to develop an evidence-based, validated algorithm for the diagnosis of PJI. This multi-institutional study led by Dr. Jay Parvizi examined revision total joint arthroplasty patients from three academic institutions. For development of the algorithm, infected and aseptic cohorts were defined. PJI cases were defined using only the major criteria from the Musculoskeletal Infection Society (MSIS) definition (n=684). Aseptic cases underwent revision for a non-infective indication and did not show evidence of PJI or undergo a reoperation for any reason within 2 years (n=820). Risk factors, clinical findings, serum and synovial markers as well as intraoperative findings were assessed. A stepwise approach using random forest analysis and multivariate regression was used to generate relative weights for each of the various variables assessed at each stage to create an algorithm for diagnosing PJI using the 3 most important tests from each step. The algorithm was formally validated on a separate cohort of 422 patients, 222 who were treated with a 2-stage exchange for PJI who subsequently failed secondary to PJI within one year and 200 patients who underwent revision surgery for an aseptic diagnosis and had no evidence of PJI within two years and did not undergo a reoperation for any reason. The first step in evaluating PJI should include a physical examination to identify a sinus tract, followed by serum testing for C-reactive protein (cut-off value 1mg/dl), D-dimer (cut-off value 860ng/mL) and/or erythrocyte sedimentation rate (cut-off value 30mm/hr) in that order of importance. If at least one of these are elevated, or if there is a high clinical suspicion, joint aspiration should be performed, sending the fluid obtained for a synovial fluid white blood-cell (cut-off value 3,000 wbc/uL) or leukocyte esterase strip testing, polymorphonuclear percentage (cut-off value 80%) and culture. Alpha defensin did not show added benefit as a routine diagnostic test. Major diagnostic criteria are the same whereby the presence of a sinus tract or (2) positive cultures showing the same organism defines PJI. Special care should be taken in cases of ALTR (failed metal-on-metal bearing), crystalline deposition disease, inflammatory arthritis flares or slow growing organisms. In the rare cases where no fluid is obtained at the time of an attempted aspiration and revision surgery is not planned, then this is the rare scenario where nuclear imaging (my preference is an indium labeled white blood cell scan) or a biopsy can be performed. The updated definition of PJI demonstrated a higher sensitivity of 97.7% when compared to the MSIS criteria (79.3%) and the ICM definition (86.9%), with a similar specificity of 99.5%. However, just over 2% of patients examined do fall into the “inconclusive” category. The proposed diagnostic algorithm demonstrated a high overall sensitivity (96.9%) and specificity (99.5%)