Hyonmin Choe

Use of F-18 Fluoride Pet to Differentiate Septic From Aseptic Loosening in Total Hip Arthroplasty Patients

Purpose: The preoperative differentiation of aseptic and septic loosening following a total hip arthroplasty (THA) remains a challenging issue for clinicians to which several molecular imaging techniques have been applied. In our current study, we used F-18 fluoride positron emission tomography (PET) to evaluate THA cases with stable, septic or septic loosened implants to assess the possibility of differentiating these clinical settings using a novel uptake-type classification approach. Materials and Methods: A total of 65 joints were enrolled in this prospective study comprising 27 asymptomatic stable hips (control group), 11 painful hips conservatively treated after THA due to a suspicion of loosening, and 27 painful hips surgically treated after THA. PET imaging was classified into 3 types according to the uptake pattern. The maximum standardized uptake value (SUVmax) was then measured for each joint. A final diagnosis was made via tissue examinations of surgically treated cases, and by serological and radiographic findings in conservatively treated cases. Results: There were significant differences found between the SUVmax values for the aseptic and septic loosening THA cases. In the diagnosis of infection with type 3 pattern, the sensitivity and specificity were measured at 0.95 and 0.98 for all cases, and 0.95 and 0.88 for surgically treated cases, respectively. Conclusions: The results of our current study demonstrate that F-18 fluoride PET has considerable potential as a method for differentiating septic from aseptic loosening following a THA. The type classification of the uptake pattern can be performed relatively simply, and quantifications using the SUVmax values can then provide an objective evaluation.

Simultaneous intraoperative detection of methicillin-resistant Staphylococcus and pan-bacterial infection during revision surgery: use of simple DNA release by ultrasonication and real-time polymerase chain reaction.

BACKGROUND Periprosthetic infection is one of the most serious complications of arthroplasty, and low-grade infections are particularly difficult to diagnose with use of conventional culture methods. Real-time polymerase chain reaction is a potentially viable way to overcome this detection problem as it is a more rapid and sensitive technique. In the current study, we used intraoperative polymerase chain reaction identification combined with a simple DNA-release method with ultrasonication to diagnose periprosthetic infections during revision surgery. METHODS Thirty revision arthroplasty procedures were included in this prospective study. Surgical specimens were obtained intraoperatively, treated with ultrasonication, and then analyzed with real-time polymerase chain reaction. Methicillin-resistant Staphylococcus-specific polymerase chain reaction and 16S rRNA gene universal polymerase chain reaction were performed simultaneously to facilitate both specific and broad-range detection. Specimens obtained from the same sites were also analyzed with microbiologic culture and histopathological evaluation. RESULTS The specific polymerase chain reaction revealed methicillin-resistant Staphylococcus infection in specimens from six of the thirty operations analyzed in the present study, and the 16S rRNA gene universal polymerase chain reaction analysis was positive for specimens from thirteen operations. Conventional cultures revealed six methicillin-resistant Staphylococcus infections, two Staphylococcus aureus infections, one infection with another Staphylococcus species, and two Streptococcus infections. The sensitivity of the polymerase chain reaction method was 0.87 and the specificity was 0.8 when compared with the combined results of microbiologic culture and histopathological evaluation. CONCLUSIONS The ultrasonication method that we developed for accelerated DNA sample preparation as a replacement for conventional extraction made possible the potential intraoperative identification of periprosthetic infection during revision surgery. The simultaneous detection of methicillin-resistant Staphylococcus and broad-range bacterial infections would be invaluable for the informed selection of antibiotics and also for the formulation of the subsequent treatment strategy (a one-stage or two-stage revision) for the patient.

Rapid and sensitive detection of methicillin-resistant Staphylococcus periprosthetic infections using real-time polymerase chain reaction.

The aim of this study was to validate the accuracy, sensitivity, and specificity of a methicillin-resistant Staphylococcus (MRS) real-time polymerase chain reaction (PCR) assay in clinical periprosthetic infection cases. A total of 36 cases of revision arthroplasty were enrolled in this prospective study, and the primer and probe set of a methicillin-resistant Staphylococcus aureus detection kit were used for the specific detection of the MecA gene with a LightCycler system. The specimens were also tested in microbiologic cultures and histopathologic evaluations. Of the 36 cases tested, 14 were found to be PCR positive for MRS infection. Of these 14 cases, however, only 8 were also found to be MRS infected using the culture method, whereas 3 were culture negative and 3 samples showed growth of another organism. The accuracy, sensitivity, and specificity were 0.83, 1.00, and 0.79, respectively. We conclude that the use of this approach will improve the diagnosis of MRS having a direct impact in the management of cases of periprosthetic infections.

Association between venous thromboembolism and plasma levels of both soluble fibrin and plasminogen-activator inhibitor 1 in 170 patients undergoing total hip arthroplasty

Background and purpose Markers of coagulation and fibrinolysis, such as soluble fibrin (SF), D-dimer, and plasminogen activator inhibitor 1 (PAI-1), have been developed in order to determine thrombotic tendency. We investigated whether these markers could be used to diagnose venous thromboembolism (VTE) in the early phase after primary total hip arthroplasty (THA). Methods This prospective study involved 2 groups: an intermittent pneumatic compression (IPC) group (67 patients who underwent IPC only as prophylaxis for VTE) and a fondaparinux (FPX) group (103 patients who received IPC and FPX postoperatively). Plasma levels of SF and PAI-1 were measured on postoperative day 1. To diagnose postoperative VTE, multi-detector row computed tomography (MDCT) and duplex ultrasonography (US) were performed on postoperative day 7. Results VTE was detected postoperatively in 17 cases in the IPC group (25%) and in 8 cases in the FPX group (6%). In the IPC group, plasma levels of SF and PAI-1 were higher in patients with VTE (p < 0.01) than in those without VTE. On the other hand, in the FPX group there were no differences in the levels of SF or PAI-1 measured before administration of FPX on postoperative day 1. The diagnostic criterion of an increase in SF or PAI-1 above the cutoff level (19.8 µg/mL and 53.5 ng/mL, respectively) provided a sensitivity of 100% and a specificity of 67% in the IPC group. In addition, when this criterion was applied to FPX patients, 7 of the 8 patients with VTE met the criterion, and there was a negative agreement rate of 48/49. Interpretation Screening using the cutoff levels of SF and PAI-1 may be useful and shows high sensitivity in predicting postoperative VTE in the early phase after THA.

Use of real-time polymerase chain reaction for the diagnosis of infection and differentiation between gram-positive and gram-negative septic arthritis in children.

Background: Diagnosis and identification of the etiological agent of septic arthritis (SA) in children is an important issue, as early treatment based on accurate diagnosis of joint infections can prevent potentially disabling complications. The purpose of this study was to evaluate the efficacy of real-time polymerase chain reaction (PCR) for the diagnosis of SA in children. Patients and Methods: Twenty children with suspected SA who had joint pain and underwent surgical treatment were enrolled in this study. Their preoperative clinical and laboratory findings were investigated. Tissues obtained during operation were subjected to microbiological culture and real-time PCR, including methicillin-resistant Staphylococcus (MRS)-specific PCR and broad range universal PCR. Infection was confirmed if the result of microbiological culture was positive. Furthermore, abnormal clinical and laboratory findings and improvement in the symptoms and posttreatment data were also defined as the final diagnosis of infection. Results: Out of the 20 patients, 19 were diagnosed with the infection. The remaining patient was postoperatively diagnosed with juvenile idiopathic arthritis. Abnormal preoperative body temperatures, white blood cell counts, C-reactive protein levels, and erythrocyte sedimentation rates were observed in 6, 9, 15, and 12 cases, respectively. The results of microbiological culture, MRS-PCR, and universal PCR were positive in 9, 2, and 15 cases, respectively. Analysis of the melting peak in universal PCR revealed that of the 15 cases, 10 had gram-positive and 5 had gram-negative infections. The sensitivity and specificity for the diagnosis of SA were, respectively, 0.47 and 1.00 in microbiological culture and 0.79 and 1.00 in real-time PCR. Conclusions: Successful diagnosis of infection and differentiation between gram-positive and gram-negative bacteria were achieved using MRS-PCR and universal PCR. Hence, real-time PCR is useful and has greater sensitivity than microbial culture for diagnosing SA in children. Level of Evidence: Level II diagnostic study investigating a diagnostic test.

Use of 18F-fluoride PET to determine the appropriate tissue sampling region for improved sensitivity of tissue examinations in cases of suspected periprosthetic infection after total hip arthroplasty

Background and purpose The accurate diagnosis of periprosthetic infection requires assessment of intraoperative tissues. These must be sampled from the appropriate sites. We used 18F-fluoride positron emission tomography (PET) to identify sites of inflammation in order to improve the sensitivity of histopathology, microbiological culture, and real-time PCR in total hip arthroplasty (THA) patients. Patients and methods 23 THA patients (23 hips) scheduled for revision surgery (the revision group) and 17 uninfected THA patients (23 hips; control group) were enrolled. Uptake was classified into major, minor, and no uptake. To evaluate the association between the 18F-fluoride uptake and intraoperative tissue results in the revision group, we calculated their sensitivity on each of the major, minor, and no-uptake sides. Results 17 revision patients showed major uptake and all were diagnosed as having septic loosening from intraoperative tissue results. Minor uptake was observed in the other 6 revision patients and all were diagnosed as having aseptic loosening. Apart from 3 cases that showed minor uptake regions, control subjects showed no uptake. In the revision group, the sensitivities of histopathology, microbiological culture, real-time PCR separately and also in combination were 0.78, 0.58, 0.96, and 0.96, respectively, on the major 18F-fluoride uptake sides, 0.0, 0.0, 0.1, and 0.1 on the minor-uptake sides, and 0, 0, 0.18, and 0.18 on the no-uptake sides. Interpretation Our findings suggest that preoperative assessment of major uptake of 18F-fluoride markedly improves the accuracy of tissue sampling, and thus the sensitivity of subsequent tissue examinations. More definitive diagnosis of periprosthetic infection is therefore possible.

Different diagnostic properties of C-reactive protein, real-time PCR, and histopathology of frozen and permanent sections in diagnosis of periprosthetic joint infection

Background and purpose There are several diagnostic tests for periprosthetic joint infection (PJI). We evaluated the properties of preoperative serum C-reactive protein (CRP), real-time polymerase chain reaction (PCR), and histopathological evaluation of frozen and permanent sections in clinical cases with culture-positive PJI. Patients and methods 63 joints involving 86 operations were analyzed using serum CRP measurement prior to operation and tissue samples were collected intraoperatively for real-time PCR and histopathology. We calculated the sensitivity, specificity, likelihood ratio of positive test results (PLR), and likelihood ratio of negative test results (NLR) for each test in relation to positive microbiological culture results as the gold standard. Results The sensitivity and specificity of diagnosis with serum CRP were 90% and 85%, respectively. The corresponding values for real-time PCR and histopathology of frozen and paraffin tissue sections were 90% and 45%, 71% and 89%, and 90% and 87%, respectively. Serum CRP had a PLR of 5.8 and an NLR of 0.12, and real-time PCR had a PLR of 1.6 and an NLR of 0.18. The corresponding figures for frozen tissue sections were 6.6 and 0.32, and those for paraffin sections were 7.1 and 0.11, respectively. Interpretation The results suggest that real-time PCR and histopathology of frozen sections is a good combination. The former is suitable for screening, with its high sensitivity and good NLR, while the latter is suitable for definitive diagnosis of infection, with its excellent specificity and good PLR.

Comparison between mechanical stress and bone mineral density in the femur after total hip arthroplasty by using subject-specific finite element analyses

The mechanism underling bone mineral density (BMD) loss that occurs in the femur after total hip arthroplasty (THA) remains unknown. We compared the equivalent stress and strain energy density (SED) to BMD in the femur after THA using subject-specific finite element analyses. Twenty-four patients who had undergone primary cementless THA were analysed. BMD was measured using dual-energy X-ray absorptiometry (DEXA) at 1 week and 3, 6 and 12 months after THA. Seven regions of interest (ROIs) were defined in accordance with Gruens system (ROIs 1–7). Computed tomography images of the femurs were acquired pre- and postoperatively, and the images were converted into three-dimensional finite element (FE) models. Equivalent stress and SED were analysed and compared with DEXA data. BMD was maintained 1 year after THA in ROIs 3, 4, 5 and 6, whereas BMD decreased in ROIs 1, 2 and 7. FE analysis revealed that equivalent stress in ROIs 3, 4, 5 and 6 was much higher than that in ROIs 1, 2 and 7. A significant correlation was observed between the rate of changes in BMD and equivalent stress. Reduction of equivalent stress may contribute to decrease in BMD in the femur after THA.

Discrepancy Between Clinical and Radiological Responses to Tocilizumab Treatment in Patients with Systemic-onset Juvenile Idiopathic Arthritis

Objective. Tocilizumab (TCZ), an antiinterleukin-6 receptor monoclonal antibody, is clinically beneficial in patients with systemic-onset juvenile idiopathic arthritis (sJIA). We investigated the clinical and radiological outcomes of TCZ therapy in patients with sJIA. Methods. We retrospectively evaluated 2 clinical trials (NCT00144599 and NCT00144612) involving 40 patients with sJIA who received intravenous TCZ (8 mg/kg) every 2 weeks. Clinical data and radiographs of the hands and large joints were assessed before and during TCZ treatment. The Poznanski score, modified Larsen scores of the hands and large joints, and Childhood Arthritis Radiographic Score of the Hip (CARSH) were recorded. Results. After a mean duration of 4.5 years of TCZ treatment, clinical data had improved significantly, the mean Poznanski score improved from −1.5 to −1.1, the mean Larsen score of the hands deteriorated from 7.0 to 10.0, the mean Larsen score for the large joints deteriorated from 5.9 to 6.8, and the CARSH worsened from 3.9 to 6.2. The Larsen score for the large joints improved in 11 cases (28%), remained unchanged in 8 cases (20%), and worsened in 21 cases (52%). Matrix metalloproteinase 3 (MMP-3) levels remained significantly higher (278 mg/dl) in patients with worsened Larsen scores than in patients with improved or unchanged scores (65 mg/dl). Logistic regression analysis showed that older age at disease onset was a significant risk factor for radiographic progression. Conclusion. The modified Larsen score of the large joints deteriorated in half the patients who had high MMP-3 levels during TCZ treatment and who were significantly older at disease onset.

Quantitative evaluation of periprosthetic infection by real-time polymerase chain reaction: a comparison with conventional methods

Several recent studies have demonstrated the limited accuracy of conventional culture methods for diagnosing periprosthetic infections. We have applied real-time polymerase chain reaction (PCR) assays for the rapid identification of bacteria around implants and reported its utility. However, the capability of quantification is also a useful feature of this type of assay. The aim of our study was to validate the usefulness of quantitative analyses using real-time PCR of cases with clinical periprosthetic infections in comparison with more established tests, such as C-reactive protein (CRP) levels, microbiologic cultures, and histopathology. Fifty-six joints with suspected infections were reviewed retrospectively. A universal PCR assay was used to perform the quantitative analyses. The differences in the threshold cycles between clinical samples and a negative control (∆Ct) in each case were calculated. The results of the quantitative PCR assay were compared with CRP levels, microbiologic cultures, and histopathology. There was a significant correlation found between the CRP and ∆Ct values. There were also significant differences found in the ∆Ct values according to CRP levels, with higher CRP levels showing higher ∆Ct values. Similarly, there were significant differences in the ∆Ct measurements in our culture results and among our pathologic evaluations. We confirmed that quantification by universal PCR based on the ∆Ct correlated with preoperative CRP levels and was associated with the microbiologic culture results and pathologic severity. This quantification method may be valuable for assessing infection severity.