Aim. Aseptic loosening is the leading cause of revision of total hip arthroplasty (THA). It is well recognized that an occult infection is the underlying cause of some aseptic revisions. Intraoperative cultures are central to the diagnosis of prosthetic joint infection (PJI). However, the diagnostic and prognostic value of unexpected positive intraoperative cultures remains unclear. The aim was to study whether first-time aseptic revision of a total hip arthroplasty with unexpected bacterial growth in cultures of intraoperatively taken biopsies have an increased risk of secondary revision due to all causes and increased risk of PJI revision, specifically. Method. Cases reported as first-time aseptic loosening revisions to the Danish Hip Arthroplasty Register (DHR) performed during January 1. st. , 2010, to May 15. th. , 2016, were included. DHR data were merged with the Danish Microbiology Database, which contains data from all intraoperatively obtained cultures in Denmark. Included first-time revisions were grouped based on the number of positive cultures growing the same bacteria genus: ≥2, 1 and 0 cultures. Revisions were followed until secondary revision, death, or end of follow-up period after one year. Relative risk for secondary revision due to all causes and PJI was estimated. Results. We included 2,305 first-time aseptic revisions. Unexpected growth was found in 282 (12%) of which 170 (60%) cases showed growth of the same bacteria in only one culture. Coagulase-negative staphylococcus accounted for 121 (71%). Secondary revision was performed in 163 (7%) cases, with PJI being the indication for revision in 43 (26%) cases. The relative risk of secondary revision was significantly higher for cases of one positive culture growing the same bacteria compared to culture negative cases, both for revision due to all causes; 1.73 (95%CI 1.07; 2.80) and PJI exclusively; 2.63 (1.16; 5.96). Cases of 2 or more biopsies culturing the same bacteria had a relative risk of all cause revision of 1.52 (0.82; 2.80). Conclusions. First-time aseptic loosening THA revisions with unexpected growth in only one biopsy culture had an increased risk of secondary revision, both due to all causes and PJI. Our findings indicate that some cases of unexpected growth of bacteria should likely be regarded as clinically significant and not sample contamination, underlining the need for more awareness and better strategies when treating patients with unexpected positive intraoperative cultures. The improved diagnosis of occult PJI in clinically aseptic THA is of great importance for future care of this large and growing patient group

Aim. Our aim was to evaluate the prevalence and impact of unexpected intraoperative cultures on the outcome of total presumed aseptic knee and hip revision surgery. Method. Data regarding patients prospectively recruited in our center, who had undergone elective complete hip and knee revision surgery from January 2003 to July 2017 with a preoperative diagnosis of aseptic loosening was retrospectively reviewed. Partial revisions and patients with follow up below 60 months were excluded from the study. The protocol of revision included at least 3 intraoperative cultures. Failure was defined as the need for re-revision due to any-cause at 5 years and/or the need for antibiotic suppressive therapy. Results. A total of 608 cases were initially included in the study, 53 patients were excluded. 123 hip and 432 knee revision surgeries were included. 420 cases (75.7%) had all cultures negative, 114 (20.5%) a single positive culture or two of different microorganisms and 21 (3.8%) had at least 2 positive cultures for the same microorganism. Early failure was found in 4.8% (1/21) of the patients with missed low grade infection. The presence of positive cultures during total exchange was not associated with a higher failure rate than in those with negative cultures (44 of 420, 10.5%). In contrast, patients revised before 24 months had a significant higher rate of re-revision, 18% (15/83) vs. 8.4%. Conclusions. Total hip and knee revisions with unexpected positive cultures were not significantly associated with a higher re-revision risk at 5 years of follow-up. Representing an overall good prognosis. However, revision surgeries performed within the first 24 months have a higher rate of failure

Aim. The prevalence of unexpected positive cultures (UPC) in aseptic revision surgery of the joint with a prior septic revision procedure in the same joint remain unknown. The purpose of this study was to determine the prevalence of UPC in aseptic revisions performed in patients with a previous septic revision in the same joint. As secondary outcome measure, we explore possible risk factors associated with UPC and the re-revision rates. Method. This retrospective single-center study includes all patients between January 2016 and October 2018 with an aseptic revision total hip or knee arthroplasty procedure with a prior septic revision in the same joint. Patients with less than three microbiology samples, without joint aspiration or with aseptic revision surgery performed <3 weeks after a septic revision were excluded. UPC was defined as a single positive culture in a revision that the surgeon had classified as aseptic according to the 2018 International Consensus Meeting. Results. A total of 139 revision total hip/knee arthroplasties in patients with a previous septic revision were performed during the study period. After excluding 47 cases with insufficient information, a total of 92 patients were recruited for final analysis. The patient cohort consist of 52 males and 40 females with a mean age of 70 years (±10.6). There were 66 (71.7%) hips and 26 (28.3%) knees. The mean time between the septic and the aseptic revision was 83 months (±89). The two main causes for the aseptic revision were aseptic loosening (n=57, 62%) followed by instability (n=21, 22.9%). We identified 11 (12%) UPC in the entire cohort, while in 3 cases there was a concordance of the germ compared to the previous septic surgery. There were no differences for the presence of UPC between hips and knees (p=0.282), diabetes (p=0.701), immunosuppression (p= 0.252), previous one-stage or two-stages septic revision (p=0.316), or between the causes for the aseptic revision ((p=0.429). There was no correlation between the UPC and time after the septic revision (p=0.773). Conclusions. The prevalence of UPC in this specific group was similar to those reported in the literature for aseptic revisons. More studies, regarding this patient group are necessitated to better understand and more securely interprete the results in those high-risk aseptic revisions

Aim. Synovial calprotectin point-of-care test (POC) has shown promising clinical value in diagnosing periprosthetic joint infections (PJIs). However, limited data are available in unclear cases. Moreover, cut-off values for calprotectin lateral flow assay (LFA) and enzyme-linked immunosorbent assay (ELISA) need to be adapted. The aim of this study was to evaluate the performance of an upgraded and more sensitive version of a synovial calprotectin LFA along with ELISA immunoassay in patients with septic, aseptic, and unclear cases. Methods. Overall, 206 prospectively collected periprosthetic synovial fluid samples from 169 patients (106f/63m; 38 hip/131 knee) who underwent revision surgeries were retrospectively evaluated for calprotectin concentration. The following groups were analyzed: unexpected negative cultures (UNC; 32/206), unexpected positive cultures (UPC; 28/206), and unclear cases (65/206) with conflicting clinical results. In addition, we added a true aseptic (40/206), and true septic (41/206) control groups according to the international consensus meeting (ICM) 2018 PJI classification. Calprotectin concentration was determined by a rapid quantitative LFA (n=206) (Lyfstone®, Norway), and compared to calprotectin ELISA immunoassay (171/206). For the determination of a new calprotectin cut-off value, analysis of the area under the curve (AUC) followed by Youden's J statistic were performed using the calproctectin values from clear septic and aseptic cases. Sensitivity and specificity for calprotectin were calculated. All statistical analyses were performed using IBM-SPSS® version 25 (Armonk, NY, USA). Results. An absolute calprotectin value of 43 mg/ml, and 40.15 mg/ml was determined to be the optimal cut-off for PJI diagnosis using the new version of the LFA and ELISA, respectively. With this cut-off, the sensitivity and specificity of synovial calprotectin concentration for PJI were 88.1% (95% CI 77.8 to 94.7) and 76.6% (95% CI 61.9 to 87.7) for LFA, and 97.06% (95% CI 89.8 to 99.64) and 93.6% (95% CI 82.5 to 98.66) for ELISA, respectively. Of the evaluated groups, UNC 30/32 (93.8%) vs 26/27 (96.3%), UPC 6/28 (21.4%) vs 4/21 (19%), and unclear samples 45/65 (69.2%) vs 30/56 (53.6%) displayed a high likelihood of infection by using LFA, and ELISA, respectively. Conclusion. The upgraded version of the calprotectin quantitative LFA with a new suggested cut-off for infected samples showed additional clinical value in identifying cases at high risk of infection in unclear PJI revisions. Additionally, calprotectin ELISA immunoassay had a better performance than LFA. Further large sample-size validation studies are warranted

Aim. Currently, despite a thorough diagnostic work up, around ten percent of the presumed aseptic revisions turn out to have unexpected positive cultures during the revision procedure. The purpose of this study was to evaluate the negative predictive value (ruling out) of the automated multiplex PCR Unyvero i60 implant and tissue infection (ITI) cartridge (U-ITI) system for the detection of microorganisms in synovial fluid obtained intraoperatively. Methods. A prospective study was conducted with 200 patients undergoing a one-stage knee or hip revision. In all patients six intraoperative tissue cultures were taken and a sample of synovial fluid which was analyzed as a culture and with the multiplex PCR U-ITI system. The primary outcome measure was the negative predictive value (NPV) of the multiplex PCR U-ITI system compared to the intraoperative tissue cultures to reliable rule out an infection. Results. The NPV of the multiplex PCR U-ITI system of synovial fluid compared to tissue cultures in knee and hip revisions was 96.8% and 92.5%, respectively. In addition, cultures require several days for growth whereas the automated mPCR U-ITI system provides results within five hours. Conclusions. The multiplex PCR U-ITI system is a quick additional test to conventional cultures in presumed aseptic knee and hip revisions for reliable ruling out of an underlying infective cause. With this simple test antibiotic overtreatment as well as undertreatment after one-stage revision arthroplasty can be avoided which can directly result in a reduction in length of hospital stay, hospital costs and possible antibiotic resistance development

Aim. Unexpected positive infections are distinct entity in prosthetic revision surgery. The prevalence and characteristics of unexpected positive cultures in internal fixation are however less established. The aim of this study was to describe the prevalence and characteristics of unexpected diagnosis of infection in a prospective cohort of revision surgeries following internal fixation. Method. We reviewed the microbiological results following 356 surgeries that included partial or complete removal of internal fixation, performed in 328 patients (54% male, mean age 53 ± 17 years), in which infection was not initially suspected. This prospective study was performed in a large single center for musculoskeletal surgery from 2013–2017. The implants most commonly removed were plate and/or screws (281 cases, 78,9%), followed by intramedullary nails (64 cases, 18,0%). The main indications for surgery were nonunion (89 cases, 25%) and symptomatic hardware (70 cases, 19,7%). All removed implants were sonicated, and tissue cultures were obtained depending on the surgeon's criteria. Diagnosis of infection was established by the presence of 2 or more positive tissue cultures (1 with a highly virulent microorganism), or ≥ 50 colony-forming units found in the sonication fluid. Results. Infection was confirmed in 47 cases (13,2%); diagnosis was obtained with tissue cultures in 5 cases (1,4%), sonication in 14 cases (3,9%) and a combination of both sonication and tissue samples in 28 cases (7,9%). In another 24 cases (6,7%), ≥ 50 CFU of low-virulence microorganisms were isolated in the sonication fluid, but no tissue samples were available to confirm the diagnosis. Low-virulent microorganisms such as Propionibacterium acnes (22 cases / 46,8%) or coagulase-negative Staphycoccci (13 cases, 27,7%) were most commonly isolated. Sonication was key for the diagnosis of 61,7% of unexpected-positive surgeries. Nearly half of the patients received a new implant (internal fixation in 40,4%; arthroplasty in 6,4%), but only 34% of the patients were treated with antibiotics on discharge. Conclusions. Unexpected diagnosis of infection occurs in approximately 13,2% of revision surgeries following internal fixation, most commonly due to low-virulent microorganisms. Sonication was key for the diagnosis of the majority of these infections. The clinical relevance of these infections remains unclear, though the insertion of new implants raises concern. We recommend sonication of all internal fixation devices removed, especially if new implants are inserted in the revision surgery

The number of shoulder arthroplasty procedures performed in the United States continues to rise. Currently, the number of procedures performed per year ranges from 55,000–80,000 and is expected to increase more than 300% in the coming years. Periprosthetic joint infection (PJI) is one of the most serious complications associated with arthroplasty surgery, leading to poor outcomes, increased cost, and technically difficult revision surgery. The incidence of infection following primary shoulder arthroplasty has been reported between 0.7% and 4%, representing 2.9–4.6% of all complications. Prosthetic shoulder joint infections are unlike prosthetic joint infections of the hip and knee. Shoulder PJIs are primarily indolent in nature and difficult to diagnose using traditional methods that have been shown to be accurate for periprosthetic infections of the hip and knee. The majority of infected revision shoulder arthroplasties are associated with growth of Propionibacterium acnes (P. Acnes). This slow-growing, anaerobic organism requires longer than normal incubation times for culture (7–21 days), and typically demonstrates a subtle, non-specific clinical presentation that can make the presence of infection difficult to identify. In the reported literature, P. Acnes accounts for about 70% of cases with positive cultures associated with revision for treatment of a painful shoulder arthroplasty and due to the bacteria's slow growing nature and virulence profile, the rate of infection following shoulder arthroplasty may often be underestimated. A more recent and promising tool for evaluation of periprosthetic infection has been analysis of synovial fluid. Synovial fluid biomarkers have been identified as part of the innate response to pathogens, and include pro-inflammatory cytokines and anti-microbial peptides, and marker levels have shown promise for improved diagnostic efficacy in hip and knee PJI. Currently, no highly predictive clinical test for diagnosis of PJI in the shoulder exists, however, several of these synovial biomarkers have recently been analyzed for their diagnostic capacity in the setting of periprosthetic shoulder infection. Synovial fluid cytokine analysis shows the potential to improve diagnosis of infection in revision shoulder arthroplasty. This information can help to guide decision-making in the management of PJI of the shoulder, including the decision to perform a single- vs. two-stage revision surgery, and the need for post-operative antibiotics following an unexpected positive culture result after revision surgery. However, there are still challenges to broader use of these synovial biomarkers. Synovial α-defensin (Synovsure, CD Diagnostic) is the only marker currently available as a commercial test, and no point-of-care test is currently available for any of the biomarkers to allow for intraoperative decision-making. While a preoperative synovial aspirate is possible to send for α-defensin analysis currently, with results back in approximately 24 hours, dry fluid aspirations are frequent in the shoulder because of the predominance of indolent pathogens and may limit utility of the test. In summary, indolent infection associated with P. acnes is a common cause for the painful total shoulder arthroplasty. Pre-operative diagnosis of infection is difficult as a result of the poor diagnostic accuracy of traditional methods of testing. Synovial biomarker testing may ultimately improve our ability to more accurately diagnosis and treat prosthetic shoulder joint infections

Aim. Despite a preoperative workup with no evidence to suspect a prosthetic joint infection (PJI) before revision surgery, routinely obtained intraoperative cultures still can be unexpectedly positive. The purpose of this study was (1) to assess the incidence of unexpected positive intraoperative cultures in presumed aseptic knee and hip revisions and (2) to determine whether a difference exists between the infection-free implant survival rate of patients with and without unexpected positive intraoperative cultures. Method. We selected patients who underwent a one-stage revision total knee arthroplasty (TKA) or total hip arthroplasty (THA) for different reasons. Three or more separate intraoperative cultures were obtained during each procedure. A negative result was defined as less than two positive cultures with the same microorganism. An unsuspected PJI was defined as having two or more positive cultures with the same microorganism. Patients’ medical records were reviewed to collect demographics, preoperative laboratory results, culture results, and the occurrence of infection during follow-up. Results. A total of 340 and 339 patients with a presumed aseptic knee and hip revision, respectively, were analyzed. The incidence of unsuspected PJIs was 7.9% and 12.1% in the knees and hips, respectively. Of these unsuspected PJIs, the infection-free prosthetic survival rate at 2 year follow-up was 88% (95%CI 59–97) and 92% (95%CI 73–98) in knees and hips, respectively. In the knee group, the infection-free prosthetic survival rate of patients with an unsuspected PJI was significantly lower compared to that of patients with negative intraoperative culture results (88% (95%CI 59–97) versus 97% (95%CI 93–99) with p=0.01). In the hip group, there was no such a difference (92% (95%CI 73–98) versus 93% (95%CI 88–96) with p=0.41). Conclusions. We found incidences of unsuspected PJI and infection-free prosthetic survival rates that are comparable with previous studies. During follow-up after one-stage revision TKA, a higher incidence of infection was observed in patients with an unsuspected PJI. This difference was not observed in the hip revisions