Yohei Yukizawa

New application of 18F-fluoride PET for the detection of bone remodeling in early-stage osteoarthritis of the hip.

PurposeRecent studies have reported the acceleration of subchondral bone remodeling during the development of osteoarthritis (OA). However, it is not possible to evaluate such molecular abnormalities using conventional radiographic techniques. We have applied 18F-fluoride PET to the analysis of painful or dysplastic hips at various stages of OA and then compared this with radiographic findings and clinical findings. MethodsA consecutive series of 65 joints from 48 patients (average age, 40 years; range, 19–72 years) with a hip joint complaint or radiographic dysplastic hip were enrolled in this study. Twenty-five contralateral joints without any evidence of OA or clinical symptoms were assigned as a normal control group. Radiographic evaluations were performed on the basis of Kellgren and Lawrence grade and the minimum joint space. Clinical evaluations were performed using the grading scale for pain severity and the SUVmax was measured for each joint. The association between SUVmax and the radiographic or clinical findings was evaluated. Results18F-fluoride PET shows a significantly higher uptake value for progressive-stage OA cases than for early-stage cases and also shows a significantly higher uptake value in cases with severe pain. Even in early-OA-stage patients who do not show joint space narrowing on a plain x-ray, cases with severe pain show a significantly higher uptake value. Conclusions18F-fluoride PET has great potential as an imaging method for diagnosing early-stage OA without any marked radiographic changes.

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.

A comparison of the effects of alendronate and alfacalcidol on bone mineral density around the femoral implant and in the lumbar spine after total hip arthroplasty.

BACKGROUND Several previous studies have demonstrated that bone mineral density loss around femoral implants is common, particularly in the proximal part of the femur, soon after total hip arthroplasty. The purpose of the present study was to compare the effects of alendronate and alfacalcidol on bone mineral density loss around the femoral implant and in the lumbar spine after total hip arthroplasty. METHODS The present study included sixty patients with osteoarthritis of the hip who had undergone a primary cementless total hip arthroplasty. We assigned these individuals to treatment with alendronate (n = 20), alfacalcidol (n = 18), or no medication (n = 22). Periprosthetic and lumbar spine bone mineral density was measured one week after surgery, and biochemical markers (bone-specific alkaline phosphatase and serum N-terminal telopeptides of type-1 collagen) were measured before surgery as a reference baseline. Subsequent measurements were performed at twelve, twenty-four, and forty-eight weeks after surgery. The periprosthetic measurement area in the femur was defined as Regions 1 to 7, which are consecutively located around the implant from the greater trochanter to the lesser trochanter and calcar. RESULTS Bone mineral density in the alendronate group was maintained in all regions. In the alfacalcidol and no-medication groups, bone mineral density in Region 7 was lower than in Regions 3 to 6 throughout the study period (p < 0.0001 as a result of repeated measures analysis of variance). Bone mineral density in the lumbar spine in the alendronate and alfacalcidol groups was higher than in the no-medication group at forty-eight weeks. The serum level of N-terminal telopeptides of type-1 collagen in the alendronate group was lower than that in the no-medication group throughout the study period (p = 0.003, 0.02 and 0.005). CONCLUSIONS Alendronate prevented bone mineral density loss around femoral implants, particularly in Region 7 (calcar), but alfacalcidol did not show any effects in any regions. However, bone mineral density losses in the lumbar spine were effectively prevented by either alendronate or alfacalcidol.

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.

Little Clinical Advantage of Modified Watson-Jones Approach Over Modified Mini-Incision Direct Lateral Approach in Primary Total Hip Arthroplasty

This study compared the clinical outcomes of total hip arthroplasty using a minimally invasive anterolateral approach with a muscle-sparing technique (modified Watson-Jones approach) and the modified mini-incision direct lateral approach. We randomly assigned 102 patients to the muscle-sparing group (n = 52) or the mini-incision direct lateral group (n = 50). Muscle strength recovery of hip abduction at 6 weeks after surgery was better, and creatine kinase level at 1 day after surgery was lower in the muscle-sparing group than in the mini-incision direct lateral group (P < .01). However, there was no difference in the Harris hip score, pain visual analog scale, the Western Ontario and McMaster Universities Osteoarthritis Index, and Medical Outcomes Study Short Form 36 score between the 2 groups throughout the 1-year study period.

Effects of rotational acetabular osteotomy on the mechanical stress within the hip joint in patients with developmental dysplasia of the hip: a subject-specific finite element analysis.

In this study we used subject-specific finite element analysis to investigate the mechanical effects of rotational acetabular osteotomy (RAO) on the hip joint and analysed the correlation between various radiological measurements and mechanical stress in the hip joint. We evaluated 13 hips in 12 patients (two men and ten women, mean age at surgery 32.0 years; 19 to 46) with developmental dysplasia of the hip (DDH) who were treated by RAO. Subject-specific finite element models were constructed from CT data. The centre-edge (CE) angle, acetabular head index (AHI), acetabular angle and acetabular roof angle (ARA) were measured on anteroposterior pelvic radiographs taken before and after RAO. The relationship between equivalent stress in the hip joint and radiological measurements was analysed. The equivalent stress in the acetabulum decreased from 4.1 MPa (2.7 to 6.5) pre-operatively to 2.8 MPa (1.8 to 3.6) post-operatively (p < 0.01). There was a moderate correlation between equivalent stress in the acetabulum and the radiological measurements: CE angle (R = -0.645, p < 0.01); AHI (R = -0.603, p < 0.01); acetabular angle (R = 0.484, p = 0.02); and ARA (R = 0.572, p < 0.01). The equivalent stress in the acetabulum of patients with DDH decreased after RAO. Correction of the CE angle, AHI and ARA was considered to be important in reducing the mechanical stress in the hip joint.

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.