The Accuracy of a Portable Accelerometer-Based Navigation System for Tibial Alignment Can be Reliable during Total Knee Arthroplasty for Obese Patients.

A portable accelerometer-based navigation system can be useful for achieving the target alignment. Tibial registration is based on the medial and lateral malleoli; however, the identification of landmarks may be difficult in obese (body mass index [BMI] >30 kg/m2) patients whose bones are not easily palpable from the body surface. This study compared tibial component alignment achieved using a portable accelerometer-based navigation system (Knee Align 2 [KA2]) in obese and control groups and aimed to validate the accuracy of bone cutting in obese patients. A total of 210 knees that underwent primary total knee arthroplasty using the KA2 system were included. After 1:3 propensity score matching, there were 32 and 96 knees in the BMI >30 group (group O) and BMI ≤30 group (group C), respectively. The absolute deviations of the tibial implant from the intended alignment were evaluated in the coronal plane (hip-knee-ankle [HKA] angle and medial proximal tibial angle) and sagittal plane (posterior tibial slope [PTS]). The inlier rate of each cohort, which was defined as tibial component alignment within 2 degrees of the intended alignment, was investigated. In the coronal plane, the absolute deviations of the HKA and MPTA from the intended alignment were 2.2 ± 1.8 degrees and 1.8 ± 1.5 degrees in group C and 1.7 ± 1.5 degrees and 1.7 ± 1.0 degrees in group O (p = 1.26, and p = 0.532). In the sagittal plane, the absolute deviations of the tibial implant were 1.6 ± 1.2 degrees in group C and 1.5 ± 1.1 degrees in group O (p = 0.570). The inlier rate was not significantly different between group C and group O (HKA: 64.6 vs. 71.9%, p = 0.521; MPTA: 67.7 vs. 78.1%, p = 0.372; PTS: 82.2 vs. 77.8%, p = 0.667). The accuracy of tibial bone cutting for the obese group was comparable to that of the control group. An accelerometer-based portable navigation system can be useful when attempting to achieve the target tibial alignment in obese patients. LEVEL OF EVIDENCE: Level IV.

A case of prosthetic joint infection caused by Mycobacterium tuberculosis complicated secondary bacterial infection after knee joint replacement surgery.

Mycobacterium tuberculosis (M. tuberculosis) is a rare cause of prosthetic joint infection (PJI). Previous studies have reported that many cases of PJI caused by M. tuberculosis have no medical history of active tuberculosis (TB) or other localization, which contributes to diagnostic difficulties. Furthermore, owing to the limited number of studies on treatment, appropriate treatment strategies, such as the duration of anti-tuberculosis (anti-TB) drugs and surgical indications, remain unclear. We report a case of PJI caused by M. tuberculosis and secondary pyogenic arthritis caused by Staphylococcus aureus and Streptococcus dysgalactiae in a 67-year-old man after knee joint replacement surgery in Japan, which was a moderately endemic country until 2020 and a low endemic country since 2021. Although he had no past medical history or close contact with TB, he was diagnosed with PJI caused by M. tuberculosis, following the culture of a synovectomy specimen. He underwent two-stage surgery and was treated with anti-TB drugs for a total of 12 months and recovered without recurrence. Based on our case and previous studies, there are three points of clinical significance for PJI caused by M. tuberculosis. First, about one year of anti-TB drugs with two staged joint revision resulted in a good course of treatment. Second, surgical treatment might be considered in cases complicated by secondary bacterial infection. Third, because the diagnosis of PJI caused by M. tuberculosis is difficult, TB should be considered in the differential diagnosis of routine bacterial culture-negative PJI, especially in endemic areas.

Outcomes and component-positioning in total knee arthroplasty may be comparable between supervised trained surgeons and their supervisor.

PURPOSE: There are concerns that malalignment in total knee arthroplasty (TKA) occurs with less experienced surgeons. This study investigates the influence of surgical experience on TKA outcomes. MATERIALS AND METHODS: Nineteen patients (38 knees) who underwent bilateral TKA between 2011 and 2015 were included. A supervisor performed knee replacements associated with lower Knee Society Scores (KSS); trainee surgeons operated on the other knee. Knees were categorized into two groups: operations by the supervisor (group S) versus operations by trainee surgeons (group T). Range of motion (ROM), KSS, operative time, hip-knee-ankle angle, and femoral and tibial component angle were evaluated. RESULTS: The mean operative time was 92.5 min in group S and 124.2 min in group T (p < 0.01). The mean postoperative maximal flexion was 113.2° in group S and 114.2° in group T (not significant). The mean postoperative KSS was 92.9 in group S and 93.9 in group T (not significant). No significant differences between groups in terms of proportion of inliers for the hip-knee-ankle angle, femoral component angle, or tibial component angle were observed. CONCLUSIONS: Although operative time was significantly longer for trainee surgeons versus the supervisor, no significant differences in ROM, KSS, or component positioning between supervisor and trainee surgeons were observed. LEVEL OF EVIDENCE: IV (retrospective case series design).

Expression of minor cartilage collagens and small leucine rich proteoglycans may be relatively reduced in osteoarthritic cartilage.

BACKGROUND: In osteoarthritis (OA), cartilage matrix is lost despite vigorous chondrocyte anabolism. In this study, we attempted to determine whether altered matrix synthesis is involved in this paradox in disease progression through gene expression analysis and ultrastructural analysis of collagen fibrils within the cartilage matrix. METHODS: Cartilage tissues were obtained from 29 end-stage OA knees and 11 control knees. First, cDNA microarray analysis was performed and the expression of 9 genes involved in collagen fibrillogenesis was compared between OA and control cartilages. Then their expression was investigated in further detail by a quantitative polymerase chain reaction (qPCR) analysis combined with laser capture microdissection. Finally, collagen fibril formation was compared between OA and control cartilage by transmission electron microscopy. RESULTS: The result of the microarray analysis suggested that the expression of type IX and type XI collagens and fibrillogenesis-related small leucine-rich proteoglycans (SLRPs) may be reduced in OA cartilage relative to the type II collagen expression. The qPCR analysis confirmed these results and further indicated that the relative reduction in the minor collagen and SLRP expression may be more obvious in degenerated areas of OA cartilage. An ultrastructural analysis suggested that thicker collagen fibrils may be formed by OA chondrocytes possibly through reduction in the minor collagen and SLRP expression. CONCLUSIONS: This may be the first study to report the possibility of altered collagen fibrillogenesis in OA cartilage. Disturbance in collagen fibril formation may be a previously unidentified mechanism underlying the loss of cartilage matrix in OA.

Identification of DNA methylation changes associated with disease progression in subchondral bone with site-matched cartilage in knee osteoarthritis.

Subchondral bone plays a key role in the development of osteoarthritis, however, epigenetics of subchondral bone has not been extensively studied. In this study, we examined the genome-wide DNA methylation profiles of subchondral bone from three regions on tibial plateau representing disease progression using HumanMethylation450 BeadChip to identify progression associated DNA methylation alterations. Significant differential methylated probes (DMPs) and differential methylated genes (DMGs) were identified in the intermediate and late stages and during the transition from intermediate to late stage of OA in the subchondral bone. Over half of the DMPs were hyper-methylated. Genes associated with OA and bone remodeling were identified. DMGs were enriched in morphogenesis and development of skeletal system, and HOX transcription factors. Comparison of DMGs identified in subchondral bone and site-matched cartilage indicated that DNA methylation changes occurred earlier in subchondral bone and identified different methylation patterns at the late stage of OA. However, shared DMPs, DMGs and common pathways that implicated the tissue reparation were also identified. Methylation is one key mechanism to regulate the crosstalk between cartilage and subchondral bone.

αvß5 integrin promotes dedifferentiation of monolayer-cultured articular chondrocytes.

OBJECTIVE: When cultured in monolayers, articular chondrocytes undergo an obvious phenotypic change. Although the involvement of integrins has been suggested, the exact mechanisms of the change have not been determined. This study was undertaken to clarify the mechanisms underlying the loss of chondrocyte phenotype early after plating. METHODS: Primary cultured human articular chondrocytes were used for the experiments. Involvement of respective integrins in the phenotypic change was investigated in RNA interference (RNAi) experiments. A signaling pathway involved in the change was identified in experiments using specific inhibitors and adenoviruses encoding mutated genes involved in the pathway. Adenoviruses carrying mutated GTPases were used to determine the involvement of small GTPases in the process. RESULTS: In monolayer-cultured chondrocytes, suppression of αv or ß5 integrin expression by RNAi inhibited morphologic changes in the cells and increased (or prevented a reduction in) the expression of various cartilage matrix genes. Consistent results were obtained in experiments using a blocking antibody and a synthetic inhibitor of αvß5 integrin. The decrease in cartilage matrix gene expression in chondrocytes after plating was mediated by ERK signaling, which was promoted primarily by αvß5 integrin. In articular chondrocytes, the affinity of αvß5 integrin for ligands was regulated by the small GTPase R-Ras. R-Ras was gradually activated in monolayer-cultured chondrocytes after plating, which caused a gradual decline in cartilage matrix gene expression through enhanced αvß5 integrin activation and the subsequent increase in ERK signaling. CONCLUSION: Our findings indicate that αvß5 integrin may be involved in the change that occurs in monolayer-cultured chondrocytes after plating.

Relationship between radiographic changes and symptoms or physical examination findings in subjects with symptomatic medial knee osteoarthritis: a three-year prospective study.

BACKGROUND: Although osteoarthritis (OA) of the knee joints is the most common and debilitating joint disease in developed countries, the factors that determine the severity of symptoms are not yet understood well. Subjects with symptomatic medial knee OA were followed up prospectively to explore the relationship between radiographic changes and symptoms or physical examination findings. METHODS: One-hundred six OA knees in 68 subjects (mean age 71.1 years; 85% women) were followed up at 6-month intervals over 36 months. At each visit, knee radiographs were obtained, symptoms were assessed by a validated questionnaire, and the result of physical examination was recorded systematically using a specific chart. Correlations between the change of radiographs and clinical data were investigated in a longitudinal manner. RESULTS: During the study period, the narrowing of joint space width (JSW) was observed in 34 joints (32%). Although those knees were clinically or radiographically indistinguishable at baseline from those without JSW narrowing, differences became apparent at later visits during the follow-up. The subjects with knees that underwent JSW narrowing had severer symptoms, and the symptoms tended to be worse for those with higher rates of narrowing. A significant correlation was not found between the severity of symptoms and the growth of osteophytes. For the knees that did not undergo radiographic progression, the range of motion improved during the follow-up period, possibly due to the reduction of knee pain. Such improvement was not observed with the knees that underwent JSW narrowing or osteophyte growth. CONCLUSION: The result of this study indicates that the symptoms of knee OA patients tend to be worse when JSW narrowing is underway. This finding may explain, at least partly, a known dissociation between the radiographic stage of OA and the severity of symptoms.

Zonal gene expression of chondrocytes in osteoarthritic cartilage.

OBJECTIVE: To determine the chondrocyte metabolism in respective zones of osteoarthritic (OA) cartilage. METHODS: OA cartilage was obtained from macroscopically intact areas of 4 knee joints with end-stage OA. The cartilage was divided into 3 zones, and gene expression profiles were determined in the respective zones by a custom-designed microarray that focused on chondrocyte-related genes. For the genes whose expression was significantly different among the zones, the expression was compared between OA and control cartilage in the respective zones by an analysis using laser capture microdissection and real-time polymerase chain reaction (PCR). For some genes, the correlation of expression was investigated in specific cartilage zones. RESULTS: A total of 198 genes (approximately 40% of those investigated) were found to be expressed at significantly different levels among the zones. Expression of 26 of those genes was evaluated by laser capture microdissection and real-time PCR, which confirmed the validity of microarray analysis. The expression of cartilage matrix genes was mostly enhanced in OA cartilage, at similar levels across the zones but at different magnitudes among the genes. The expression of bone-related genes was induced either in the superficial zone or in the deep zone, and positive correlations were found among their expression in the respective zones. The expression of 5 proteinase genes was most enhanced in the superficial zone, where their expression was correlated, suggesting the presence of a common regulatory mechanism(s) for their expression. CONCLUSION: In OA cartilage, the metabolic activity of chondrocytes differed considerably among zones. Characteristic changes were observed in the superficial and deep zones.

Regional differences in chondrocyte metabolism in osteoarthritis: a detailed analysis by laser capture microdissection.

OBJECTIVE: To determine the change in metabolic activity of chondrocytes in osteoarthritic (OA) cartilage, considering regional difference and degree of cartilage degeneration. METHODS: OA cartilage was obtained from knee joints with end-stage OA, at both macroscopically intact areas and areas with various degrees of cartilage degeneration. Control cartilage was obtained from age-matched donors. Using laser capture microdissection, cartilage samples were separated into superficial, middle, and deep zones, and gene expression was compared quantitatively in the respective zones between OA and control cartilage. RESULTS: In OA cartilage, gene expression changed markedly with the site. The expression of cartilage matrix genes was highly enhanced in macroscopically intact areas, but the enhancement was less obvious in the degenerated areas, especially in the upper regions. In contrast, in those regions, the expression of type III collagen and fibronectin was most enhanced, suggesting that chondrocytes underwent a phenotypic change there. Within OA cartilage, the expression of cartilage matrix genes was significantly correlated with SOX9 expression, but not with SOX5 or SOX6 expression. In OA cartilage, the strongest correlation was observed between the expression of type III collagen and fibronectin, suggesting the presence of a certain link(s) between their expression. CONCLUSION: The results of this study revealed a comprehensive view of the metabolic change of the chondrocytes in OA cartilage. The change of gene expression profile was most obvious in the upper region of the degenerated cartilage. The altered gene expression at that region may be responsible for the loss of cartilage matrix associated with OA.

Rheumatoid arthritis fibroblast-like synoviocytes express BCMA and are stimulated by APRIL.

OBJECTIVE: Fibroblast-like synoviocytes (FLS) are among the principal effector cells in the pathogenesis of rheumatoid arthritis (RA). This study was undertaken to examine the variety of stimulating effects of APRIL and its specific effect on FLS in the affected RA synovium. METHODS: Synovium and serum samples were obtained from patients with RA, patients with osteoarthritis (OA), and healthy subjects. Soluble APRIL proteins were assayed by enzyme-linked immunosorbent assay. The relative gene expression of APRIL, BCMA, interleukin-6 (IL-6), tumor necrosis factor alpha (TNFalpha), IL-1beta, and RANKL was assessed in RA and OA FLS by polymerase chain reaction. Effects of APRIL on the production of proinflammatory cytokines and RANKL in RA FLS were investigated by flow cytometry and with the use of a BCMA-Fc fusion protein. RESULTS: A significantly higher level of soluble APRIL was detected in RA serum compared with normal serum. Among the 3 receptors of APRIL tested, RA FLS expressed only BCMA, whereas OA FLS expressed none of the receptors. APRIL stimulated RA FLS, but not OA FLS, to produce IL-6, TNFalpha, IL-1beta, and APRIL itself. In addition, APRIL increased RA FLS expression of RANKL and also enhanced progression of the cell cycle of RA FLS. Neutralization of APRIL by the BCMA-Fc fusion protein attenuated all of these stimulating effects of APRIL on RA FLS. CONCLUSION: RA FLS are stimulated by APRIL and express the APRIL receptor BCMA. These results provide evidence that APRIL is one of the main regulators in the pathogenesis of RA.