Bead-beating assay during synovial fluid DNA extraction improves real-time PCR accuracy for periprosthetic joint infection.

Polymerase chain reaction (PCR)-based genetic diagnosis is a rapid and sensitive method to diagnose periprosthetic joint infection (PJI). DNA extraction using bead beating is an effective method for collecting bacterial genes in Gram-positive bacteria. We compared the detection accuracy between the conventional and bead-beating DNA extraction assay. The detection rate improved from 86.7% using the conventional method to 95.6% using the bead-beating. Our results suggest that bead-beating during DNA extraction can improve the accuracy of PCR-based genetic diagnosis of PJI.

Use of data-independent acquisition mass spectrometry to identify an objective serum indicator of the need for osteoporotic therapeutic intervention.

Osteoporosis is characterized by weakened bone microstructure and loss of bone mass. Current diagnostic criteria for osteoporosis are based on the T-score, which is a measure of bone mineral density. However, osteoporotic fragility fractures can occur regardless of the T-score, underscoring the need for additional criteria for the early detection of patients at fracture risk. To identify indicators of reduced bone strength, we performed serum proteomic analysis using data-independent acquisition mass spectrometry with serum samples from two patient groups, one with osteoporosis but no fractures and the other with osteopenia and fragility fractures. Collective evaluation of the results identified six serum proteins that changed to a similar extent in both patient groups compared with controls. Of these, extracellular matrix protein 1 (ECM1), which contributes to bone formation, showed the most significant increase in serum levels in both patient groups. An ELISA-based assay suggested that ECM1 could serve as a serum indicator of the need for therapeutic intervention; however, further prospective studies with a larger sample size are necessary to confirm these results. The present findings may contribute to the provision of early and appropriate therapeutic strategies for patients at risk of osteoporotic fractures. SIGNIFICANCE: This study aimed to identify objective serum indicators of the need for therapeutic intervention in individuals at risk of osteoporotic fracture. Comprehensive proteome analyses of serum collected from patients with osteoporosis but no fractures, patients with osteopenia and fragility fractures, and controls were performed by data-independent acquisition mass spectrometry. Collective evaluation of the proteome analysis data and ELISA-based assays identified serum ECM1 as a potential objective marker of the risk of fragility fractures in patients with osteoporosis or osteopenia. The findings are an important step toward the development of appropriate bone health management methods to improve well-being and maintain quality of life.

Identification of gravity-responsive serum proteins in spaceflight mice using a quantitative proteomic approach with data-independent acquisition mass spectrometry.

Physical inactivity associated with gravity unloading, such as microgravity during spaceflight and hindlimb unloading (HU), can cause various physiological changes. In this study, we attempted to identify serum proteins whose levels fluctuated in response to gravity unloading. First, we quantitatively assessed changes in the serum proteome profiles of spaceflight mice using mass spectrometry with data-independent acquisition. The serum levels of several proteins involved in the responses to estrogen and glucocorticoid, blood vessel maturation, osteoblast differentiation, and ossification were changed by microgravity exposure. Furthermore, a collective evaluation of serum proteomic data from spaceflight and HU mice identified 30 serum proteins, including Mmp2, Igfbp2, Tnc, Cdh5, and Pmel, whose levels varied to a similar extent in both gravity unloading models. These changes in serum levels could be involved in the physiological changes induced by gravity unloading. A collective evaluation of serum, femur, and soleus muscle proteome data of spaceflight mice also showed 24 serum proteins, including Igfbp5, Igfbp3, and Postn, whose levels could be associated with biological changes induced by microgravity. This study examined serum proteome profiles in response to gravity unloading, and may help deepen our understanding of microgravity adaptation mechanisms during prolonged spaceflight missions.

Increased Wnt5a/ROR2 signaling is associated with chondrogenesis in meniscal degeneration.

The aim of the present study was to investigate the association between chondrogenic differentiation and Wnt signal expression in the degenerative process of the human meniscus. Menisci were obtained from patients with and without knee osteoarthritis (OA), and degeneration was histologically assessed using a grading system. Immunohistochemistry, real-time polymerase chain reaction (PCR), and Western blot analysis were performed to examine the expressions of chondrogenic markers and of the components of Wnt signaling. Histological analyses showed that meniscal degeneration involved a transition from a fibroblastic to a chondrogenic phenotype with the upregulation of SOX9, collagen type II, collagen type XI, and aggrecan, which were associated with increased Wnt5a and ROR2 and decreased TCF7 expressions. OA menisci showed significantly higher expressions of Wnt5a and ROR2 and significantly lower expressions of AXIN2 and TCF7 than non-OA menisci on real-time PCR and Western blot analysis. These results potentially demonstrated that increased expression of Wnt5a/ROR2 signaling promoted chondrogenesis with decreased expression in downstream Wnt/ß-catenin signaling. This study provides insights into the role of Wnt signaling in the process of meniscal degeneration, shifting to a chondrogenic phenotype. The findings suggested that the increased expression of Wnt5a/ROR2 and decreased expression of the downstream target of Wnt/ß-catenin signaling are associated with chondrogenesis in meniscal degeneration.

Integrated analyses of the genetic and clinicopathological features of cholangiolocarcinoma: cholangiolocarcinoma may be characterized by mismatch-repair deficiency.

Cholangiolocarcinoma (CLC) is a primary liver carcinoma that resembles the canals of Hering and that has been reported to be associated with stem cell features. Due to its rarity, the nature of CLC remains unclear, and its pathological classification remains controversial. To clarify the positioning of CLC in primary liver cancers and identify characteristics that could distinguish CLC from other liver cancers, we performed integrated analyses using whole-exome sequencing (WES), immunohistochemistry, and a retrospective review of clinical information on eight CLC cases and two cases of recurrent CLC. WES demonstrated that CLC includes IDH1 and BAP1 mutations, which are characteristic of intrahepatic cholangiocarcinoma (iCCA). A mutational signature analysis showed a pattern similar to that of iCCA, which was different from that of hepatocellular carcinoma (HCC). CLC cells, including CK7, CK19, and EpCAM, were positive for cholangiocytic differentiation markers. However, the hepatocytic differentiation marker AFP and stem cell marker SALL4 were completely negative. The immunostaining patterns of CLC with CD56 and epithelial membrane antigen were similar to those of the noncancerous bile ductules. In contrast, mutational signature cluster analyses revealed that CLC formed a cluster associated with mismatch-repair deficiency (dMMR), which was separate from iCCA. Therefore, to evaluate MMR status, we performed immunostaining of four MMR proteins (PMS2, MSH6, MLH1, and MSH2) and detected dMMR in almost all CLCs. In conclusion, CLC had highly similar characteristics to iCCA but not to HCC. CLC can be categorized as a subtype of iCCA. In contrast, CLC has characteristics of dMMR tumors that are not found in iCCA, suggesting that it should be treated distinctly from iCCA. © 2024 The Pathological Society of Great Britain and Ireland.

Changes in the astronaut serum proteome during prolonged spaceflight.

The molecular mechanisms associated with spaceflight-induced biological adaptations that may affect many healthy tissue functions remain poorly understood. In this study, we analyzed temporal changes in the serum proteome of six astronauts during prolonged spaceflight missions using quantitative comprehensive proteome analysis performed with the data-independent acquisition method of mass spectrometry (DIA-MS). All six astronauts participated in a spaceflight mission for approximately 6 months and showed a decreasing trend in T-scores at almost all sites where dual-energy X-ray absorptiometry scans were performed. DIA-MS successfully identified 624 nonredundant proteins in sera and further quantitative analysis for each sampling point provided information on serum protein profiles closely related to several time points before (pre-), during (in-), and after (post-) spaceflight. Changes in serum protein levels between spaceflight and on the ground suggest that abnormalities in bone metabolism are induced in astronauts during spaceflight. Furthermore, changes in the proteomic profile occurring during spaceflight suggest that serum levels of bone metabolism-related proteins, namely ALPL, COL1A1, SPP1, and POSTN, could serve as highly responsive indicators of bone metabolism status in spaceflight missions. This study will allow us to accelerate research to improve our understanding of the molecular mechanisms of biological adaptations associated with prolonged spaceflight.

Shelf acetabuloplasty may inhibit range of motion: A computer simulation analysis.

Shelf acetabuloplasty has been performed in patients with developmental dysplasia of the hip (DDH); however, the appropriate position of the shelf has not been determined, particularly with respect to avoiding range of motion (ROM) loss. The aim of this study was to investigate the frequency of ROM inhibition and the influence of 3D position of the shelf following actual shelf acetabuloplasty and virtual surgery using computer simulation analysis. Computed tomography data from 15 patients with DDH who underwent shelf acetabuloplasty were collected between August 2019 and February 2022. The three-dimensional models of a hip joint were constructed using Zed Hip®. Maximal internal rotation (MIR) at 45° and 90° flexion was measured in each patient. The frequency and position of ROM inhibition was determined in a real postoperative model virtually. In addition, a second analysis using virtual acetabuloplasty was performed. Upon placing the shelf, three patterns were provided for the following four parameters: height, coronal inclination, center-edge angle (CEA), and anteroposterior position. The predictors for ROM inhibition were analyzed using a logistic regression model. In the actual postoperative model, a limitation of MIR at 90° and 45° of flexion occurred in 60% and 66.7% of patients, respectively. A higher CEA and anterior position are major factors limiting MIR. The analysis of the virtual shelf acetabuloplasty model revealed that anterior position and CEA were significant factors causing ROM inhibition. As for clinical significance, the results of the current study indicated the optimal location of the shelf to avoid iatrogenic impingement after shelf acetabuloplasty.

Comprehensive analyses of the clinicopathological features and genomic mutations of combined hepatocellular-cholangiocarcinoma.

AIM: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer that has two different tumor phenotypes in a single tumor nodule. The relationship between genetic mutations and clinicopathological features of cHCC-CCA remains to be elucidated. METHODS: Whole-exome sequencing analyses were carried out in 13 primary and 2 recurrent cHCC-CCAs. The whole-exome analyses and clinicopathological information were integrated. RESULTS: TP53 was the most frequently mutated gene in this cohort, followed by BAP1, IDH1/2, and NFE2L2 mutations in multiple cases. All tumors with diameters <3 cm had TP53 mutations. In contrast, six of seven tumors with diameters ≥3 cm did not have TP53 mutations, but all seven tumors had mutations in genes associated with various pathways, including Wnt, RAS/PI3K, and epigenetic modulators. In the signature analysis, the pattern of mutations shown in the TP53 mutation group tended to be more similar to HCC than the TP53 nonmutation group. Mutations in recurrent cHCC-CCA tumors were frequently identical to those in the primary tumor, suggesting that those tumors originated from identical clones of the primary cHCC-CCA tumors. Recurrent and co-occurrent HCC tumors in the same patients with cHCC-CCA had either common or different mutation patterns from the primary cHCC-CCA tumors in each case. CONCLUSIONS: The study suggested that there were two subtypes of cHCC-CCA, one involving TP53 mutations in the early stage of the carcinogenic process and the other not involving such mutations. The comparison of the variants between primary and recurrent tumors suggested that cHCC-CCA was derived from an identical clone.

Physical Therapy May Not Be Successful for Patients With Cam-Type Femoroacetabular Impingement Syndrome and May Result in Insufficient Hip Range of Motion When Femoral Anteversion Is Less Than 16° and α-Angle Is Greater Than 65°.

PURPOSE: To identify factors associated with insufficient range of motion (ROM) improvement after the posterior pelvic tilt change in cam-type femoroacetabular impingement syndrome. METHODS: Preoperative computed tomography images from 71 consecutive patients with femoroacetabular impingement syndrome treated with arthroscopic cam resection were evaluated. Using a dynamic computer simulation program, 3-dimensional models with a 10° posterior pelvic tilt from the supine functional pelvic plane (baseline) were created by computed tomography models. Patients were divided into 2 groups: those who experienced >10° (effective group) and ≤10° (ineffective group) improvements in internal rotation at 90° flexion after a 10° posterior pelvic tilt. Demographic characteristics; preoperative range of internal rotation at 90° flexion; and radiographic parameters, including Tönnis grade, lateral center-edge angle, acetabular roof obliquity angle, central acetabular anteversion, cranial acetabular anteversion, femoral anteversion, and α angle, were compared in the 2 groups. Univariate and multivariable logistic regression analyses were performed to evaluate factors associated with insufficient ROM improvement following a 10° posterior pelvic tilt. RESULTS: The 71 patients included 58 men and 13 women, of mean age 41.4 ± 14.6 years. Posterior pelvic tilt was effective in 13 hips and ineffective in 58. Univariate analysis showed that preoperative range of internal rotation at 90°flexion, femoral anteversion, and α angle differed significantly in the 2 groups. Multivariable analysis showed that femoral anteversion <16° (odds ratio 7.4; 95% confidence interval 1.6-35; P = .012) and α angle >65° (odds ratio 6.7; 95% confidence interval 1.2-37; P = .027) were significant factors associated with insufficient ROM improvement after posterior pelvic tilt. CONCLUSIONS: Physical therapy may not be successful for patients with cam-type femoroacetabular impingement syndrome and may result in insufficient hip ROM when femoral anteversion is less than 16° and α-angle is greater than 65°. CLINICAL RELEVANCE: Patients with a prominent cam-type deformity and lower anterior femoral anteversion are at high risk of clinical failure following improvement in pelvic mobility by conservative treatment alone and are likely to benefit from surgery for cam deformity.

Accuracy of Albumin, Globulin, and Albumin-Globulin Ratio for Diagnosing Periprosthetic Joint Infection: A Systematic Review and Meta-Analysis.

Periprosthetic joint infection (PJI) is one of the most intractable orthopedic diseases, partly because of the difficulty in differentiating septic from aseptic conditions. We aimed to evaluate and consolidate the diagnostic accuracy of the quantitative assessment of serum albumin (Alb), globulin (Glb), and albumin-globulin ratio (AGR), alone or in combination with the inflammatory marker, C-reactive protein (CRP), for PJI. We searched the PubMed, CINAHL, and Cochrane Library databases for studies that quantitatively measured Alb, Glb, or AGR for the diagnosis of PJI up until the 30 April 2023. A total of 2339 patients were included from 10 studies, including 845 patients with a definitive diagnosis of PJI and 1494 with non-PJI. The pooled sensitivity, specificity, and area under the curve (AUC) in the summary receiver-operating characteristic curve were as follows: 0.625, 0.732, and 0.715 for Alb; 0.815, 0.857, and 0.887 for Glb; 0.753, 0.757, and 0.875 for AGR; 0.788, 0.837, and 0.876 for CRP; 0.879, 0.890, and 0.917 for the CRP-Alb ratio; and 0.845, 0.855, and 0.908 for the CRP-AGR ratio. Serum Alb, Glb, and AGR levels are feasible and accurate diagnostic markers for PJI, and the combination of these markers with CRP levels may potentially improve preoperative serum diagnostic accuracy. Future prospective studies are required to verify these findings because of the small numbers of included studies.

A Comparison of the Minimum Inhibitory Concentration of Antibiotics in Staphylococcus Species Isolated From Orthopedic and Respiratory Medicine Infections.

INTRODUCTION: Antibiotic susceptibility is very important for the successful treatment of orthopedic infections, particularly for implant-related infections. While the minimum inhibitory concentrations (MICs) of Staphylococcus species were well investigated for the isolates from the respiratory tract, investigations for orthopedic pathogens are very limited. We investigated the antibiotic MIC values of Staphylococcus species isolated from orthopedic infections and compared them with those of respiratory medicine isolates used as a control. METHODS: The MICs of vancomycin (VCM), arbekacin (ABK), teicoplanin (TEIC), linezolid (LZD), and rifampicin (RFP) of a total of consecutive 259 (89 orthopedic and 170 respiratory) Staphylococcus speciesisolated in our laboratory from January 2013 to July 2016 were retrospectively reviewed. Differences between the MICs of each antibiotic in orthopedic and respiratory samples were determined. RESULTS: The number of methicillin-sensitive Staphylococcus aureus (MSSA) with a VCM MIC of <0.5 µg/mL among respiratory isolates was significantly higher than that among orthopedic isolates, while those with a MIC of 2 µg/mL were significantly lower (P = 0.0078). The proportion of methicillin-resistant coagulase-negative staphylococci (MRCNS) isolates with a VCM MIC of 2 µg/mL was significantly higher in orthopedic samples than that of methicillin-resistant Staphylococcus aureus (MRSA) (P < 0.001) in respiratory isolates. The proportion of MRCNS orthopedic isolates with an RFP MIC of >2 µg/mL was significantly higher (P = 0.0058) than that of other orthopedic staphylococci. CONCLUSIONS: The VCM MICs of Staphylococcus species from orthopedic infections were higher than those of respiratory samples, particularly MRCNS from implant-related samples.

Novel Local Antifungal Treatment for Fungal Periprosthetic Joint Infection With Continuous Local Antibiotic Perfusion: A Surgical Technique.

Fungal periprosthetic joint infections are one of the most intractable orthopedic disorders. Continuous local antibiotic perfusion allows direct administration of the antifungal agent micafungin into the local infection area at biofilm-disruptive concentrations, while controlling the dead space in addition to conventional treatment. Although the appropriate use of continuous local antibiotic perfusion requires familiarity with the characteristics of local antibiotic perfusion, it is a versatile treatment modality that can improve the clinical outcomes of fungal periprosthetic joint infection in combination with conventional treatment methods.

Bevacizumab promotes tenogenic differentiation and maturation of rat tendon-derived cells in vitro.

Previous work suggested that tenogenic differentiation of tendon stem/progenitor cells (TSPCs) was suppressed by upregulated expression of the angiogenic marker vascular endothelial growth factor (VEGF). The purpose of this study was to test the hypothesis that anti-VEGF antibody, bevacizumab, promotes in vitro tenogenic differentiation and maturation of two distinct types of TSPCs, tendon proper-derived cells (TDCs), and paratenon-derived cells (PDCs) originating from rat Achilles tendon. TDCs and PDCs were isolated from the tendon proper and the paratenon of rat Achilles tendons. TDCs and PDCs were cultured for 3 days on plates with or without VEGF. TDCs and PDCs were also cultured in collagen gel matrix, and the blocking effect of VEGF was examined by the addition of 100 ng/mL of bevacizumab. Effects of bevacizumab on tenogenic differentiation were assessed using real-time PCR, immunofluorescent staining, and western blotting. VEGF significantly attenuated expression of the Tnmd gene in both PDCs and TDCs (P<0.05). Expressions of the Scx, Tnmd, and Col1a1 genes were significantly upregulated by the addition of bevacizumab (P<0.05). Immunofluorescent staining showed that the percentage of tenomodulin-positive PDCs and TDCs was significantly higher with bevacizumab treatment than in control cultures (P<0.05). Western blotting showed that bevacizumab suppressed pVEGFR-2 protein expression in both PDCs and TDCs. Bevacizumab promoted the in vitro tenogenic differentiation and maturation of two distinct TSPCs derived from rat Achilles tendon. Since the previous studies demonstrated that TSPCs have a potential to contribute to tendon repair, attenuating VEGF levels in TSPCs by administration of bevacizumab is a novel candidate therapeutic option for promoting tendon repair.

Identification of mouse soleus muscle proteins altered in response to changes in gravity loading.

Gravity-dependent physical processes strongly affect the ability of elderly people to maintain musculoskeletal health by reducing muscle atrophy and increasing bone mineral density, thereby increasing quality of life. A need therefore exists to identify molecules in the musculoskeletal system that are responsive to gravitational loading and to establish an objective indicator for the maintenance of healthy musculoskeletal systems. Here, we performed an integrated assessment of the results of soleus muscle proteomic analyses in three model mouse experiments under different gravity environments (hypergravity, hindlimb unloading, and spaceflight). Myl6b, Gpd1, Fbp2, Pvalb, and Actn3 were shown to be gravity-responsive muscle proteins, and alterations in the levels of these proteins indicated changes in muscle fiber type to slow-twitch type due to gravity loading. In addition, immunoblotting and enzyme-linked immunosorbent assays revealed that Pvalb levels in the sera of hindlimb-unloaded mice and osteoporosis patients were higher than in control subjects, suggesting that Pvalb levels might be useful to objectively evaluate soleus muscle atrophy and bone loss.

Radiologic simulation of leg length change after double level osteotomy in preoperative surgical planning.

BACKGROUND: To evaluate the expected postoperative total leg length change using preoperative radiographs during surgical planning of four different methods of double level osteotomy (DLO). METHODS: This study included 34 patients (44 knees) who underwent DLO for varus knee osteoarthritis. Surgical planning was performed so that the postoperative weight bearing line ratio was 62.5%. In DLO, lateral closed or medial open wedge distal femoral osteotomy (LCWDFO, MOWDFO) was performed so that the postoperative mechanical lateral distal femoral angle was 85°, and residual deformity was corrected with medial open or lateral closed wedge high tibial osteotomy (MOWHTO, LCWHTO). Pre- and surgical planning X-rays in the one-leg standing position were compared to assess the change in leg length, and the factors affecting it, in the various surgical groups. The proportion of cases in which Δ total leg length was greater than 6 mm (symptomatic change) was investigated. RESULTS: The mean postoperative total leg length increased significantly with LCWDFO + MOWHTO, MOWDFO + MOWHTO, and MOWDFO + LCWHTO, while it decreased with LCWDFO + LCWHTO. The proportion of cases with a postoperative total leg length change > 6 mm was 72.7%, 2.3%, 100%, and 6.8% in LCWDFO + MOWHTO, LCWDFO + LCWHTO, MOWDFO + MOWHTO, and MOWDFO + LCWHTO, respectively. In addition, the preoperative hip-knee-ankle angle correlated negatively with the postoperative total leg length change in LCWDFO + MOWHTO, MOWDFO + MOWHTO, and MOWDFO + LCWHTO, but not in LCWDFO + LCWHTO. CONCLUSIONS: MOWDFO + MOWHTO had the largest postoperative leg length change and MOWDFO + LCWHTO had the smallest. Symptomatic leg length change (> 6 mm) should be considered in MOWDFO + MOWHTO and LCWDFO + MOWHTO.

Identification of gravity-responsive proteins in the femur of spaceflight mice using a quantitative proteomic approach.

Although the microgravity (µ-g) environment that astronauts encounter during spaceflight can cause severe acute bone loss, the molecular mechanism of this bone loss remains unclear. To investigate the gravity-response proteins involved in bone metabolism, it is important to comprehensively determine which proteins exhibit differential abundance associated with mechanical stimuli. However, comprehensive proteomic analysis using small bone samples is difficult because protein extraction in mineralized bone tissue is inefficient. Here, we established a high-sensitivity analysis system for mouse bone proteins using data-independent acquisition mass spectrometry. This system successfully detected 40 proteins in the femoral diaphysis showing differential abundance between mice raised in a µ-g environment, where the bone mass was reduced by gravity unloading, and mice raised in an artificial 1-gravity environment on the International Space Station. Additionally, 22 proteins, including noncollagenous bone matrix proteins, showed similar abundance between the two groups in the mandible, where bone mass was unaltered due to mastication stimuli, suggesting that these proteins are responsive to mechanical stimuli. One of these proteins, SPARCL1, is suggested to promote osteoclastogenesis induced by receptor activator of nuclear factor-κB ligand. We expect these findings to lead to new insights into the mechanisms of bone metabolism induced by mechanical stimuli. SIGNIFICANCE: We aimed to investigate the gravity-response proteins involved in bone metabolism. To this end, we established a comprehensive analysis system for mouse bone proteins using data-independent acquisition mass spectrometry, which is particularly useful in comprehensively analyzing the bone proteome using small sample volumes. In addition, a comprehensive proteomic analysis of the femoral diaphysis and mandible, which exhibit different degrees of bone loss in mice raised on the International Space Station, identified proteins that respond to mechanical stimuli. SPARCL1, a mechanical stimulus-responsive protein, was consequently suggested to be involved in osteoclast differentiation associated with bone remodeling. Our findings represent an important step toward elucidating the molecular mechanism of bone metabolism induced by mechanical stimuli.

Tranexamic acid administration for the prevention of periprosthetic joint infection and surgical site infection: a systematic review and meta-analysis.

INTRODUCTION: Tranexamic acid (TXA) has been widely utilized to reduce blood loss and allogeneic transfusions in patients who undergo lower limb arthroplasty. In recent years, there have been several articles reporting the incidence of periprosthetic joint infection (PJI) as a primary outcome of TXA administration, but no meta-analysis has been conducted to date. The present systematic review and meta-analysis evaluated the efficacy of TXA administration in preventing PJI and surgical site infection (SSI). MATERIALS AND METHODS: Pubmed, CINAHL, and the Cochrane Library bibliographic databases were searched for studies published by May 24, 2022, that evaluated the effects of TXA on PJI and SSI. Two researchers screened the identified studies based on the PRISMA flow diagram. The quality of each randomized clinical trial was assessed using Version 2 of the Cochrane risk-of-bias tool for randomized trials (ROB2.0), and the quality of cohort and case-control studies was assessed by risk of bias for nonrandomized studies (ROBANS-I). RESULTS: Of the 2259 articles identified from the database search, 31 were screened and selected. Treatment with TXA significantly reduced the incidence of overall infection, including PJI, SSI, and other infections (OR 0.55; 95% CI 0.49-0.62) (P < 0.00001), and that of PJI alone (OR 0.53; 95% CI 0.47-0.59) (P < 0.00001). TXA reduced the incidence of overall infection in patients who underwent total hip arthroplasty (THA; OR 0.51; 95% CI: 0.35-0.75) (P = 0.0005) and total knee arthroplasty (TKA; OR 0.55; 95% CI: 0.43-0.71) (P < 0.00001). Intravenous administration of TXA reduced the incidence of overall infection (OR 0.59; 95% CI 0.47-0.75) (P < 0.0001), whereas topical administration did not. CONCLUSIONS: Intravenous administration of TXA reduces the incidence of overall infection in patients undergoing both THA and TKA. LEVEL OF EVIDENCE: Level III.

Targeting of Periprosthetic Muscles for the Ultrasonographic Screening of Hip Abnormalities in Hip Resurfacing Arthroplasty Patients.

BACKGROUND: Hip resurfacing arthroplasty (HRA) patients require subsequent annual screening for postoperative complications. Ultrasonography may be useful for this purpose but lacks a screening protocol for hips. The purpose of this study was to evaluate the accuracy of ultrasonography for detecting postoperative complications in HRA patients using a screening protocol that specifically targets periprosthetic muscles. METHODS: We enrolled 45 hips from 40 HRA patients with a mean follow-up period of 8.2 years. MRI and ultrasonography scans were simultaneously conducted at follow-up. The ultrasonography assessments were conducted on the anterior part of the hip that targets iliopsoas, sartorius, rectus femoris, lateral with anterior superior and inferior iliac spine (ASIS and AIIS) as bony landmarks, and the lateral and posterior parts that target fascia tensor, short rotators, and gluteus minimus, medius, and maximus with greater trochanter and ischial tuberosity as bony landmarks. The accuracy of diagnosing postoperative abnormalities and the visibility of periprosthetic muscles were compared between these two modalities. RESULTS: Both MRI and ultrasonography detected an abnormal region in eight cases comprising two infections, two pseudotumors, and four patients with greater trochanteric bursitis. Among these cases, four hips required implant removal. The increase in anterior space, measured as the distance between the iliopsoas and resurfacing head, was a good indicator for the abnormal mass in these four HRA cases. In the assessment of periprosthetic muscles, MRI showed a much lower visibility than ultrasonography in the iliopsoas (6.7% vs. 100%), gluteus minimus (6.7% vs. 88.9%), and short rotators (8.8% vs. 71.4%) due to implant halation. CONCLUSIONS: By targeting periprosthetic muscles, ultrasonography can detect postoperative complications as effectively as MRI assessments in HRA patients. Ultrasonography has superior visibility in the periprosthetic muscles of HRA patients, indicating its utility for the screening of small legions in these cases which may not be visible by MRI.

Cartilage Degeneration of the Lateral Compartment of the Knee at Second-Look Arthroscopy Is Associated With Deterioration of 10-Year Clinical Outcomes After Opening-Wedge High Tibial Osteotomy.

PURPOSE: To identify the arthroscopic findings associated with deterioration of 10-year clinical outcomes after opening-wedge high tibial osteotomy (OWHTO) in patients with knee osteoarthritis. METHODS: A total of 114 consecutive knees of 91 patients with knee osteoarthritis who underwent OWHTO between 2007 and 2011 were retrospectively reviewed. Of these patients, those who underwent second-look arthroscopy and were followed up for a minimum of 10 years were enrolled. The Knee Society Score (KSS) and hip-knee-ankle angle were assessed. Cartilage status was graded at the time of osteotomy (first look) and plate removal (second look) according to the International Cartilage Repair Society (ICRS) grading system. The KSS knee subscale score and function subscale score were assessed separately, and on the basis of the changes in each of these scores from 1 to 10 years postoperatively and the minimal clinically important difference (MCID), the patients were divided into 2 groups: deteriorated (deterioration of score ≥ MCID) and non-deteriorated (deterioration of score < MCID). RESULTS: Sixty-nine knees were included in this study. The mean knee score improved continuously from 48.7 ± 11.3 preoperatively to 86.8 ± 10.3 at 1 year (P < .001), 87.5 ± 9.9 at 5 years (P < .001), and 86.5 ± 10.5 at 10 years (P < .001) postoperatively. The mean function score also improved continuously from 62.5 ± 12.1 preoperatively to 90.7 ± 12.9 at 1 year (P < .001), 91.6 ± 12.1 at 5 years (P < .001), and 88.5 ± 13.1 at 10 years (P < .001) postoperatively. Three knees underwent conversion to total knee arthroplasty within 10 years postoperatively. The deteriorated KSS group showed significantly progressed ICRS grades in the lateral compartment compared with the non-deteriorated KSS group. The ICRS grade in the lateral compartment at second-look arthroscopy was identified as the only significant factor associated with both knee score deterioration (odds ratio, 4.89; P = .03) and function score deterioration (odds ratio, 3.91; P = .03) on multivariable logistic regression analysis. CONCLUSIONS: The presence of cartilage degeneration of the lateral compartment of the knee at second-look arthroscopy is associated with deterioration of long-term clinical outcomes after OWHTO. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Bevacizumab suppressed degenerative changes in articular cartilage explants from patients with osteoarthritis of the knee.

BACKGROUND: This study was designed to test the hypothesis that blockade of vascular endothelial growth factor (VEGF) suppresses degenerative changes in articular cartilage from patients with osteoarthritis (OA). METHODS: Articular cartilage from eight OA patients was subjected to explant culture for 2 days in the presence or absence of 10 ng/ml recombinant interleukin (IL)-1ß. The blocking effect of VEGF was examined by the addition of 10 or 100 ng/ml of bevacizumab. The culture media were harvested, and markers for cartilage degradation were measured by sandwich enzyme-linked immunoassay. Total RNA was isolated from cartilage tissues, and gene expressions associated with the anabolic response were examined by the quantitative real-time polymerase chain reaction. RESULTS: Bevacizumab significantly reduced concentrations of matrix metalloproteinase (MMP)-2, MMP-3, and cartilage oligomeric matrix protein in the culture media with and without IL-1ß. Significant suppressive effects of bevacizumab on MMP-9 and MMP-13 were shown only in the presence of IL-1ß. Gene expression of Col2a1 was significantly increased by the addition of bevacizumab in the absence of IL-1ß. CONCLUSION: Bevacizumab inhibits catabolic reactions and stimulates anabolic function in articular cartilage derived from OA patients directly, suggesting a protective effect on articular cartilage from OA progression.