[Enhancement of Pesticide Peak Response in GC-MS in the Presence of Multiple Co-Existing Reference Pesticides].

We carried out a collaborative study in six laboratories to confirm the universality of the enhancing effect of co-existing reference pesticides on the GC-MS peak response to a target pesticide (malathion, procymidone, or flucythrinate). First, we confirmed the response enhancement of the target pesticides with increasing numbers of co-existing reference pesticides in solution. Then, using diluted green soybean matrix, we analyzed the target pesticides with two types of matrix-matched calibration, containing the target pesticides or 166 other pesticides. In both cases, the response-enhancing effect of co-existing pesticides was confirmed in all laboratories. The enhancement was reduced by addition of green soybean matrix to the sample and calibration solutions. Our results show that it is necessary to estimate the peak response-enhancing effect of co-existing pesticides in the calibration solution to obtain accurate results with GC-MS determination. The enhancing effect could be reduced by addition of food matrix to the sample and calibration solutions.

Risk factors for failure of revision total hip arthroplasty using a Kerboull-type acetabular reinforcement device.

BACKGROUND: The present study aimed to identify the risk factors associated with revision total hip arthroplasty (THA) failure using a Kerboull-type (KT) plate. METHODS: We analyzed 77 revision THAs using cemented acetabular components with a KT plate for aseptic loosening between May 2000 and March 2012. We examined the association of bone graft type, acetabular bone defects, age at the time of surgery, preoperative Japanese Orthopaedic Association (JOA) score, postoperative JOA hip score, and body mass index, with radiographic failure as the outcome. RESULTS: The 7.4-year radiographic failure survival rate was 81.6%. The survival rate was significantly different between the beta-tricalcium phosphate (ß-TCP) group and the bulk allograft group (p = 0.019). The survival curves were also significantly different between the ß-TCP group and bulk allograft group (p = 0.036). American Academy of Orthopaedic Surgeons type IV was significantly associated with radiographic failure (odds ratio [OR]: 15.5, 95% confidence interval [CI]: 1.4-175.4; p = 0.032). CONCLUSIONS: The midterm outcomes of revision THA indicate that type of bone graft and bone defect size may affect radiographic survival rate when using a KT plate.

Clinical importance of impingement deformities for hip osteoarthritis progression in a Japanese population.

PURPOSE: Femoroacetabular impingement is a new disease concept for hip disorders in young adults suggested as a major cause of primary hip osteoarthritis in Western countries. However, significant controversy exists regarding the prevalence and contribution of impingement deformities to osteoarthritis in Japan, owing to the higher prevalence of developmental dysplasia of the hip. Therefore, the aims of this study were to: (1) determine the prevalence of structural abnormalities associated with hip disorders in patients undergoing total hip replacement and (2) analyse the contribution of impingement deformities to osteoarthritis. METHODS: We analysed 250 patients from two different medical centres who underwent primary total hip replacement except those which were due to femoral head necrosis, posttraumatic osteoarthritis and systemic inflammatory disease. The average patient age at surgery was 64 years (range, 40-89 years), with 35 men and 215 women. RESULTS: Radiographic abnormality related to developmental dysplasia of the hip was associated with the majority of osteoarthritic hips (62%). Hips with femoroacetabular impingement deformities were present within the cases categorized as unknown etiology. Cam impingement deformity was present in 22% of unknown aetiology cases when cases with reactive osteophytes were excluded from all cam deformity cases (pistol grip deformity and aspherical femoral heads). CONCLUSIONS: The prevalence of femoroacetabular impingement within primary osteoarthritis cases and gender predominance of impingement deformities are relatively similar to those reported previously in Western populations. This finding indicates that femoroacetabular impingement deformities are associated with osteoarthritis in the Japanese population, although it has a lower frequency among all hip failure patients.

Time elapsed from definitive diagnosis to surgery for osteonecrosis of the femoral head: a nationwide observational study in Japan.

OBJECTIVES: This study documents the time elapsed from the diagnosis of osteonecrosis of the femoral head (ONFH) to surgery, exploring the factors that influence ONFH severity. DESIGN: Retrospective observational study of a nationwide database. SETTING: The Kaplan-Meier method with log-rank tests was applied to examine the period from definitive diagnosis of ONFH to surgery using any surgery as the end point. For bilateral cases, the date of the first surgery was the endpoint. PARTICIPANTS: This study included 2074 ONFH cases registered in 34 university hospitals and highly specialised hospitals of the multicentre sentinel monitoring system of the Japanese Investigation Committee between 1997 and 2018. MAIN OUTCOME MEASURE: The primary outcome was the time from diagnosis to surgery. The secondary outcome was the proportion of subjects remaining without surgery at 3, 6 and 9 months, and at 1, 2 and 5 years after diagnosis. RESULTS: The median time to surgery was 9 months (IQR 4-22 months) after diagnosis of ONFH. The time to surgery was significantly shorter in the alcohol alone group and the combined corticosteroid and alcohol group than in the corticosteroid alone group (p=0.018 and p<0.001, respectively), in early stage ONFH with no or mild joint destruction (stages II and III, p<0.001), and with joint preserving surgery (p<0.001). The proportion without surgery was 75.8% at 3 months, 59.6% at 6 months, 48.2% at 9 months, 40.5% at 1 year, 22.2% at 2 years and 8.3% at 5 years. CONCLUSION: ONFH has been considered to be an intractable disease that often requires surgical treatment, but the fact that surgery was performed in more than half of the patients within 9 months from diagnosis suggests severe disease with a significant clinical impact. TRIAL REGISTRATION NUMBER: Chiba University ID1049.

Leg edema due to a mass in the pelvis after a large-diameter metal-on-metal total hip arthroplasty.

We report the case of a patient with leg edema after large-diameter metal-on-metal total hip arthroplasty. At 1 year and 2 months after primary left large-diameter metal-on-metal total hip arthroplasty, the patient complained of left leg edema. At first, we suspected deep venous thrombosis. However, deep venous thrombosis was not detected by venous ultrasonographic examination. Computed tomography imaging revealed a mass in front of the iliac fossa. The mass compressed the left iliac artery and vein. We therefore believed that this lesion was the cause of the leg edema and performed resection of the mass. The resected mass consisted of necrotic tissue infiltrating inflammation cells, so it was diagnosed as pseudotumor. Unilateral leg edema disappeared gradually after the resection.

Evaluation of the accuracy of femoral component orientation by the CT-based fluoro-matched navigation system.

PURPOSE: Accurate orientation of acetabular and femoral components are important during THA. However, no study has assessed the use of the CT-based fluoro-matched navigation system during THA. Therefore, we have evaluated the accuracy of stem orientation by CT-based fluoro-matched navigation. METHODS: The accuracy of stem orientation by CT-based fluoro-matched navigation was assessed by postoperative CT data. Furthermore, we compared the postoperative stem orientation with the intraoperative registration errors. RESULTS: The average antetorsion error of the stem (navigation records - postoperative CT) was -0.5° ± 5.2°. The stem valgus error was 0.4° ± 2.7°. The accuracy of the navigation record for the orientation of the stem valgus was dependent on the intraoperative registration errors. CONCLUSIONS: The clinical accuracy of CT-based fluoro-matched navigation is adequate for stem alignment orientation, and the intraoperative verification of registration errors is valuable for checking the accuracy of stem orientation by navigation.

Excessive femoral offset does not affect the range of motion after total hip arthroplasty.

PURPOSE: Implant dislocations are often caused by implant or bone impingement, and less impingement is critical to prevent dislocations. The aim of this study was to clarify the effect of the femoral offset in avoiding component or bony impingement after total hip arthroplasty (THA). METHODS: Seventy-eight patients underwent THA with a Pinnacle cup and Summit stem (DePuy). Intraoperative kinematic analysis was performed with a navigation system, which was used to obtain intraoperative range of motion (ROM) measurements during trial insertion of stems of two different offset lengths with the same head size. Further, ROM was also measured after actual component insertion. RESULTS: Maximal ROM was independent of the femoral offset of the stem in each patient. However, the range of external rotation was significantly greater in patients with a greater femoral offset. CONCLUSIONS: The Summit stem has enough offset length to avoid implant/bone impingement, even when the standard offset stem is used. Nevertheless, selection of the offset stem should be performed carefully to prevent offset complications.

Leg length change in total hip arthroplasty with subtrochanteric femoral shortening osteotomy for Crowe type IV developmental hip dysplasia.

Primary total hip arthroplasties were performed in 70 hips for the treatment of Crowe type IV developmental dysplasia of the hip. The patients were subdivided into 2 groups with or without iliofemoral osteoarthritis. Leg length change was measured radiographically. Preoperative hip motion was reviewed from medical records and defined as either higher or lower motion groups. The leg length change in patients without iliofemoral osteoarthritis was significantly greater than that in patients with iliofemoral osteoarthritis, and the higher hip motion group had greater leg length change in total hip arthroplasty than the lower motion group. The current study identifies several features that might help predict leg length change during the preoperative planning of total hip arthroplasty for Crowe type IV developmental hip dysplasia.

Obese patients may have more soft tissue impingement following primary total hip arthroplasty.

PURPOSE: Several studies have reported a risk of dislocation in obese patients after total hip arthroplasty. In this study, we evaluated the interaction between obesity and dislocation by kinematic analysis using a navigation system. METHODS: The intraoperative range of motion (ROM) and postoperative impingement-free ROM were measured in 38 patients, and we compared the impingement-free ROM in obese and non obese patients. RESULTS: The postoperatively simulated ROM was similar in the obese and non obese groups. The intraoperative ROM was smaller in the obese group. The difference values between the intraoperative ROM and postoperatively simulated ROM were larger in the obese group. These results indicate that obese patients have less ROM following primary total hip arthroplasty even when the implant positioning is performed correctly. CONCLUSIONS: Dislocations are multifactorial problems including soft tissue impingement. Therefore, the risk of dislocation caused by soft tissue impingement in obese patients may be increased.

Periprosthetic bone mineral density with a cementless triple tapered stem is dependent on daily activity.

PURPOSE: Periprosthetic bone loss around the femoral stem is frequently found after total hip arthroplasty. We have shown that periprosthetic bone mineral density (BMD) loss using the triple tapered stem is consistently much less in comparison with the straight type component. In this study, we compared periprosthetic BMD change with clinical factors. METHODS: Postoperative dual-energy X-ray absorptiometry was evaluated at follow-up. BMD was determined based on seven Gruen zones. We further compared BMD with clinical examination: body mass index (BMI), age, Harris hip score (HHS) or University of California at Los Angeles (UCLA) activity rating score. RESULTS: Periprosthetic BMD loss of the triple tapered stem was maintained. Especially, BMD in Gruen zone 1 which was maintained at 96% in comparison with the straight tapered stem. We compared the BMD change with clinical factors. There is no correlation between BMD and BMI, age or HHS. However, we found significant correlation between BMD and UCLA activity rating score in Gruen zones 1 and 2 of the triple tapered stem. Further, the correlation coefficient was increased at 48 months in comparison with 24 months. CONCLUSION: The cementless triple tapered stem maintains periprosthetic bone mineral density. Activity may reflect improving periprosthetic bone quality after THA using a triple tapered stem.

Comparison of outcomes of different osteotomy sites for hallux valgus: A systematic review and meta-analysis.

BACKGROUND: Hallux valgus (HV) is a common foot deformity for which several corrective surgical procedures, with different osteotomy sites, have been reported. The purpose of the present study was to systematically review randomized (RCTs) or controlled (CCTs) clinical trials and perform meta-analysis on outcomes of different osteotomy sites of the first metatarsal. METHODS: An extensive literature search was conducted in PubMed and the Cochrane Library from January 1983 to July 2020. Studies were identified using the terms "hallux valgus" and "osteotomy". We included RCTs or CCTs comparing different locations of osteotomy for the first metatarsal bone (distal vs. mid-shaft, distal vs. proximal, and mid-shaft vs. proximal). The surgical outcomes included postoperative hallux valgus angle (HVA), intermetatarsal angle (IMA), American Orthopaedic Foot and Ankle Society (AOFAS) score, pain visual analog scale (VAS) score, perioperative complications and recurrence of deformity. We enrolled 10 studies with a total of 793 feet in the qualitative synthesis following full-text screening. RESULTS: A majority of patients included in the enrolled trials showed mild to moderate deformity, with mean HVA <40°. Out of the 10 enrolled studies; six compared distal osteotomies with mid-shaft osteotomies and showed no significant differences in the surgical outcomes between the scarf and chevron groups; three RCTs compared distal osteotomies with proximal osteotomies with conflicting results, one RCT showed the superiority of proximal osteotomy while the other two RCTs showed equivalent outcomes; one study that compared between mid-shaft and proximal osteotomies showed equivalent outcomes between the groups. CONCLUSION: For the management of mild to moderate HV deformity, we found no significant clinical and radiological differences between patients treated with scarf and chevron osteotomies. Further controlled trials comparing different sites of osteotomies for moderate to severe HV deformity are needed.

Pregnancy associated plasma protein-A is necessary for expeditious fracture healing in mice.

Pregnancy-associated plasma protein A (PAPP-A), a metalloproteinase that regulates IGF bioavailability in vitro through cleavage of inhibitory IGF-binding protein-4 (IGFBP-4), has been implicated in skeletal development and injury repair responses. However, direct in vivo data are lacking. In this study, we used PAPP-A knock-out (KO) mice to determine the role of PAPP-A in fracture repair. Stabilized mid-shaft fractures were produced in femurs of 3-month-old mice. At 14 days post-fracture, complete bony bridging of the fracture callus was seen radiographically in wild-type but not in PAPP-A KO mice. Histological examination 5 to 28 days post-fracture showed reductions in the amount of intramembranous bone formation, cartilage production, endochondral ossification and remodeling in PAPP-A KO compared with wild-type mice. However, fracture healing appeared similar in both groups at 42 days post-fracture when analyzed by histology. A similar degree of healing strength in wild-type and PAPP-A KO femurs was demonstrated by mechanical testing at 28 and 42 days post-fracture. Untreated cultures of day 5 fracture calluses from wild-type mice showed robust IGFBP-4 protease activity and IGF receptor phosphorylation, whereas fracture calluses from PAPP-A KO mice had no IGFBP-4 protease activity and reduced IGF receptor phosphorylation. These data demonstrate a marked delay in fracture healing in PAPP-A KO compared with wild-type mice, and suggest that PAPP-A is necessary in the early phases of the process for expeditious fracture repair. The ability of PAPP-A to enhance local IGF action may be an important mechanism for optimizing the fracture repair response.

Reliability and validity of the Baecke physical activity questionnaire in adult women with hip disorders.

BACKGROUND: Although physical activity maintenance is important for OA management, it is not clear whether people with OA are more inactive or not. One possible reason is no simple monitoring tool to assess physical activity at the clinic. The aim of this study was to determine the reliability and validity of the Baecke Physical Activity Questionnaire (BQ) in adult women with hip disorders. METHODS: Sixty-four patients with unilateral or bilateral hip disorders were recruited from an outpatients clinic at a university hospital in Japan. BQ includes a total of 16 questions classified into three domains: work, sports, and non-sports leisure activity. For test-retest reliability, one BQ was administrated face-to-face, and a second was mailed to participants two weeks later. Test-retest reliability of BQ was assessed using intra-class correlation (ICC) and Bland and Altman method. To determine criterion validity, the correlation between BQ measurements and pedometer-measured step counts was assessed. Correlations between BQ measurements and step counts were assessed using Spearman rank correlation coefficient (rho). RESULTS: Analyses were restricted to the 61 patients (53.3 +/- 11.3 years old) who wore the pedometer continuously for 5 days or more. Twenty eight patients had unilateral hip osteoarthritis, 17 patients had unilateral total hip arthroplasty, and 16 patients had hip osteoarthritis and total hip arthroplasty. The mean step count was 6,309 +/- 2,392 steps/day. In analysis for reliability, the value of ICC was 0.84 for work, 0.83 for sports, 0.78 for non-sports leisure activity, and 0.87 total. Bland and Altman analysis showed the step count and BQ total did not differ significantly from 0 with most falling between 0 +/- 1.96 SD. In analysis for validity, there was a significant but low to moderate correlation between step counts and 3 BQ subscales (rho, 0.30-0.49) and a higher correlation between step counts and total score (rho, 0.49). CONCLUSION: BQ is a useful monitoring tool for assessing multiple domains of physical activity with acceptable reliability and validity in adult women with hip disorders.

Oxidative stress-induced apoptosis and matrix loss of chondrocytes is inhibited by eicosapentaenoic acid.

Eicosapentaenoic acid (EPA) is an antioxidant and n-3 polyunsaturated fatty acid that reduces the production of inflammatory cytokines. We evaluated the role of EPA in chondrocyte apoptosis and degeneration. Normal human chondrocytes were treated with EPA and sodium nitroprusside (SNP). Expression of metalloproteinases (MMPs) was detected by real-time polymerase chain reaction (PCR) and that of apoptosis-related proteins was detected by western blotting. Chondrocyte apoptosis was detected by flow cytometry. C57BL/6J mice were used for the detection of MMP expression by immunohistochemistry and for investigation of chondrocyte apoptosis. EPA inhibited SNP-induced chondrocyte apoptosis, caspase 3 and poly(ADP-ribose) polymerase cleavage, phosphorylation of p38 MAPK and p53, and expression of MMP3 and MMP13. Intra-articular injection of EPA prevented the progression of osteoarthritis (OA) by inhibiting MMP13 expression and chondrocyte apoptosis. EPA treatment can control oxidative stress-induced OA progression, and thus may be a new approach for OA therapy.

Cis-acting intronic elements that regulate cartilage-specific alternative splicing of the type II collagen (Col2) pre-mRNA lie at or near splice site junction sequences flanking exon 2 of the gene.

UNLABELLED: Knowledge of the cis-acting elements is required for identifying trans-acting splicing factors underlying cartilage-specific alternative splicing of Col2 pre-mRNA. By performing desired deletions in the mouse Col2 pre-mRNA, location of the intronic cis-acting elements was narrowed down to be at or near splice-junction sequences flanking exon 2 of the gene. INTRODUCTION: Type II collagen (Col2) pre-mRNA undergoes cartilage-specific alternative splicing involving exon 2 during chondrocyte differentiation. Thus, the trans-acting protein factors that regulate the splicing are associated with the differentiation of chondrocytes. Knowledge of the cognate cis-acting elements is necessary to eventually identify the trans-acting factors. MATERIALS AND METHODS: To localize the cis-acting sequences, we created several deletions within a minigene containing exon 1 to exon 4 of mouse Col 2 gene and evaluated alternative splicing of the resulting pre-mRNAs in ATDC5 cells, a model of insulin-stimulated chondrocyte differentiation. The first deletion reduced intron 1 from 3799 to 259 bp, the second reduced intron 2 from 1108 to 94 bp, the third combined the above two deletions, and the fourth was derived from the third by removing intron 3 and exon 4. ATDC5 cells harboring these constructs were cultured for up to 21 days with or without insulin. Alternative splicing was evaluated by determining the ratio of Col2B (lacks exon 2) to Col2A (has exon 2) RNAs by reverse transcription-polymerase chain reaction. RESULTS: The deletion in intron 1 had no effect on the alternative splicing while other deletions affected splicing (demonstrated by the presence of splicing intermediates) in cells cultured without insulin or with insulin for 1 week. The splicing intermediates were not seen from any construct when cells were cultured longer (14-21 days) with insulin. CONCLUSION: These results show that the 259-bp intron 1, the 94-bp intron 2, and exon 2 sequences retained in the fourth construct provide cis-acting signal sufficient for insulin-induced cartilage-specific alternative splicing of Col2 pre-mRNA.

Flexible hinge silicone implant with or without titanium grommets for arthroplasty of the first metatarsophalangeal joint.

PURPOSE: To review outcomes of 37 patients who underwent arthroplasty of the first metatarsophalangeal joint using flexible hinge silicone implants with or without titanium grommets. METHODS: 36 women and one man (63 feet) underwent arthroplasty of the first metatarsophalangeal joint for rheumatoid arthritis (RA) using Swanson flexible hinge silicone toe implants with or without titanium grommets. 20 women (35 feet) aged 31 to 72 (mean, 52) years with Steinbrocker grade II (n=4), grade III (n=6), and grade IV (n=10) RA of the feet were treated with the implant without grommets, whereas 16 women and one man (28 feet) aged 48 to 73 (mean, 60) years with Steinbrocker grade III (n=4) and grade IV (n=13) RA of the feet were treated with the implant with grommets. Pain levels were self-rated. Degenerative changes and the presence of osteophytes or deformity were recorded, as were breakage or deformation of the implants, radiolucencies around the implant, implant loosening, silicone-induced synovitis, and sclerosis around the implant. RESULTS: All patients reported pain relief from severe to mild or moderate. Respectively for the feet with and without grommets, the rates of implant deformation were 25% and 63% (p=0.031), whereas the rates of moderate-to-severe radiolucencies (>2 mm) were 4% and 34% (p=0.004). Sclerosis developed around the implant in all feet. CONCLUSION: Titanium grommets appear to protect the implant and improve clinical outcomes.

PTEN regulates matrix synthesis in adult human chondrocytes under oxidative stress.

Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) was identified as an important tumor suppressor gene. PTEN functions as a negative regulator of phosphoinositol-3-kinase (PI3K)-Akt and MEK/ERK signaling. The PI3K-Akt pathway is critical for cell survival, differentiation, and matrix synthesis. Oxidative stress is considered a critical factor in the onset and progression of osteoarthritis (OA). Therefore, we investigated the function of PTEN in OA chondrocytes under oxidative stress. Chondrocytes were treated with insulin-like growth factor-1 (IGF-1) and/or tert-butyl hydroperoxide (tBHP), which causes oxidative stress. The expression levels of type2 collagen (Col2a1) and aggrecan were analyzed by real-time PCR, and phosphorylation of Akt and ERK1/2 was analyzed by Western blotting. Chondrocytes were treated with PTEN-specific small interfering RNA (siRNA), as well as IGF-1 and/or tBHP. PTEN and IGF-1 expressions in OA chondrocytes were increased. The downregulation of PTEN expression increased the expression levels of Col2a1 and aggrecan, and increased proteoglycan synthesis under oxidative stress. Oxidative stress decreased the phosphorylation of Akt and increased that of ERK1/2. The downregulation of PTEN expression increased Akt phosphorylation, but did not increase that of ERK 1/2. Our results suggest that PTEN regulates matrix synthesis via the PI3K-Akt pathway under oxidative stress.

Automated pelvic anatomical coordinate system is reproducible for determination of anterior pelvic plane.

Most of computer-assisted planning systems need to determine the anatomical axis based on the anterior pelvic plane (APP). We analysed that our new system is more reproducible for determination of APP than previous methods. A pelvic model bone and two subjects suffering from hip osteoarthritis were evaluated. Multidetector-row computed tomography (MDCT) images were scanned with various rotations by MDCT scanner. The pelvic rotation was calibrated using silhouette images. APP was determined by an optimisation technique. The values of variation of APP caused by pelvic rotation were analysed with statistical analysis. APP determination with calibration and optimisation was most reproducible.The values of variance of APP were within 0.05° in model bone and 0.2° even in patient pelvis. Furthermore, the values of variance of APP with calibration/optimisation were significantly lower in comparison without calibration/optimisation. Both calibration and optimisation are actually required for determination of APP. This system could contribute to the evaluation of hip joint kinematics and computer-assisted surgery.