Flatfoot Surgery for Flexible Progressive Collapsing Foot Deformity With Inflammatory Joint Diseases: A Report of 3 Cases.

CASE: Three cases of inflammatory joint diseases (systemic lupus erythematosus and ongoing juvenile idiopathic arthritis) with painful flexible progressive collapsing foot deformity (PCFD) underwent flatfoot surgery. All cases maintained sufficient radiological correction and achieved good clinical condition at final follow-up. CONCLUSION: Although the prospect for recurrence of the deformity is not clear, even in inflammatory joint diseases, flat foot surgery such as flexor digitorum longs transfer, spring ligament reconstruction, and lateral column lengthening could have a possibility to be indicated against PCFD, as long as disease activity could be well suppressed by drug therapy, subsequently subtalar and talonavicular joints could be preserved.

Osteoporosis and Osteopenia in patients with psoriatic arthritis: a single-center retrospective study.

OBJECTIVE: It is known that fracture risk is increased in patients with psoriatic arthritis (PsA), however, there is no consensus on the association with osteoporosis. The purpose of this study was to elicit the rate of osteoporosis and the risk factors of osteoporosis in patients with PsA at our institution. METHODS: The data in this study were extracted from 163 patients with PsA. Osteoporosis and osteopenia were defined based on the WHO definition. Osteoporosis was also diagnosed when a fragility vertebral compression fracture was observed. RESULTS: The osteoporosis and osteopenia rates for PsA patients were 11.7% and 33.1%, respectively. The rates of osteoporosis and osteopenia in males were particularly high compared to previous reports, at 9.3% and 34.3%, respectively. Trabecular bone score (TBS) was considered age-appropriate for both males and females. Body mass index (BMI) and TBS were significantly lower in patients with osteoporosis. CONCLUSIONS: In patients with PsA, males are at elevated risk of osteoporosis and associated fragility fractures even if they are under 50 years old. BMI was significantly lower in osteoporotic cases, suggesting the importance of bone mineral density testing and treatment in such cases.

Iguratimod suppresses sclerostin and receptor activator of NF-κB ligand production via the extracellular signal-regulated kinase/early growth response protein 1/tumor necrosis factor alpha pathway in osteocytes and ameliorates disuse osteoporosis in mice.

Disuse osteoporosis is a prevalent complication among patients afflicted with rheumatoid arthritis (RA). Although reports have shown that the antirheumatic drug iguratimod (IGU) ameliorates osteoporosis in RA patients, details regarding its effects on osteocytes remain unclear. The current study examined the effects of IGU on osteocytes using a mouse model of disuse-induced osteoporosis, the pathology of which crucially involves osteocytes. A reduction in distal femur bone mass was achieved after 3 weeks of hindlimb unloading in mice, which was subsequently reversed by intraperitoneal IGU treatment (30 mg/kg; five times per week). Histology revealed that hindlimb-unloaded (HLU) mice had significantly increased osteoclast number and sclerostin-positive osteocyte rates, which were suppressed by IGU treatment. Moreover, HLU mice exhibited a significant decrease in osteocalcin-positive cells, which was attenuated by IGU treatment. In vitro, IGU suppressed the gene expression of receptor activator of NF-κB ligand (RANKL) and sclerostin in MLO-Y4 and Saos-2 cells, which inhibited osteoclast differentiation of mouse bone marrow cells in cocultures. Although IGU did not affect the nuclear translocation or transcriptional activity of NF-κB, RNA sequencing revealed that IGU downregulated the expression of early growth response protein 1 (EGR1) in osteocytes. HLU mice showed significantly increased EGR1- and tumor necrosis factor alpha (TNFα)-positive osteocyte rates, which were decreased by IGU treatment. EGR1 overexpression enhanced the gene expression of TNFα, RANKL, and sclerostin in osteocytes, which was suppressed by IGU. Contrarily, small interfering RNA-mediated suppression of EGR1 downregulated RANKL and sclerostin gene expression. These findings indicate that IGU inhibits the expression of EGR1, which may downregulate TNFα and consequently RANKL and sclerostin in osteocytes. These mechanisms suggest that IGU could potentially be used as a treatment option for disuse osteoporosis by targeting osteocytes.

Early full weight-bearing and gait exercise after cemented total ankle arthroplasty with modified antero-lateral approach.

BACKGROUND: According to the conventional postoperative procedure after total ankle arthroplasty (TAA) against end-stage osteoarthritis (OA) and rheumatoid arthritis (RA), mobilization and weight-bearing is currently started after completion of wound healing. Recently, early mobilization for dorsiflexion after TAA with modified antero-lateral approach was reported to be feasible and safe. To investigate the further possibility of expediting rehabilitation, this study evaluated the feasibility and safety of early full weight-bearing and gait exercise after cemented TAA utilizing a modified antero-lateral approach. MATERIALS AND METHODS: This retrospective, observational study investigated 23 consecutive ankles (OA: 14 ankles, RA: 9 ankles) that had received cemented TAA with a modified antero-lateral approach. These ankles were divided into three groups [1. conventional postoperative protocol: 8 ankles, 2. early dorsiflexion protocol: 7 ankles, 3. early dorsiflexion+full weight-bearing protocol: 8 ankles]. In group 3, after early dorsiflexion mobilization (day 3), full weight-bearing/gait exercise was started from 7 days after surgery (10 days after if malleolar osteotomy was added). Postoperative wound complications were observed and recorded. Number of days for hospitalization was also evaluated. Range of motion (ROM) of dorsiflexion/plantar flexion was measured. Patients also completed a self-administered foot evaluation questionnaire (SAFE-Q) and the scale of Japanese Society for Surgery of the Foot (JSSF) ankle/hindfoot score preoperatively and at final follow-up. RESULTS: No postoperative complications related to wound healing were observed even after early full weight-bearing and gait exercise. Days for hospitalization was significantly shortened in early full weight-bearing and gait exercise group (group 3) from 35-38 days to 24 days. ROM for both dorsiflexion and plantar flexion significantly increased in group 3, furthermore all indices of SAFE-Q score also showed stronger significant improvement in group 3. JSSF score improved significantly after TAA in all groups. CONCLUSION: Within this small number of cases, early full weight-bearing and gait exercise from 7 days after cemented TAA was feasible and safe with the modified antero-lateral approach. Combination of early dorsiflexion mobilization and weight-bearing/gait exercise contributed to shortening the hospitalization day, and improving ROM for both dorsiflexion and plantar flexion after surgery. Innovations in postoperative procedures for rehabilitation after TAA can be expected.

Long-term retention rates of anti-tumour necrosis factor and anti-interleukin-17 antibodies for patients with psoriatic arthritis.

OBJECTIVE: While biologics have been used for the patients with psoriatic arthritis, there remains to be unknown concerning long-term retention rates. This study aims to present real-world data about long-term retention rates of biologics for the patients with psoriatic arthritis, and to undertake an analysis of the contributing factors. METHODS: We examined retention rates and the reasons for discontinuation for biologics (adalimumab, certolizumab pegol, secukinumab, and ixekizumab) in 146 prescriptions (of which, 109 prescriptions were as naive) at our hospital since March 2010. RESULTS: Throughout the entire course of the study, the 10-year retention rates were approximately 70% for adalimumab, 50% for ixekizumab, and 40% for secukinumab. When evaluating retention rates in the biologic-naïve subgroups, the 10-year retention rates were all approximately 70%. Regarding certolizumab pegol, the 3-year retention rate was approximately 75%. For adalimumab, a higher degree of arthritis at the initiation of treatment was found to correlate with an increased likelihood of secondary inefficacy. The main reason for discontinuation was secondary inefficacy, except for ixekizumab. CONCLUSIONS: Each biologic exhibited a favourable long-term retention rate. The main reason for discontinuation was secondary inefficacy. Regarding adalimumab, secondary inefficacy was linked to the extent of arthritis upon treatment initiation.

Anti-NF-κB peptide derived from nuclear acidic protein attenuates ovariectomy-induced osteoporosis in mice.

NF-κB is a transcription factor that is activated with aging. It plays a key role in the development of osteoporosis by promoting osteoclast differentiation and inhibiting osteoblast differentiation. In this study, we developed a small anti-NF-κB peptide called 6A-8R from a nuclear acidic protein (also known as macromolecular translocation inhibitor II, Zn2+-binding protein, or parathymosin) that inhibits transcriptional activity of NF-κB without altering its nuclear translocation and binding to DNA. Intraperitoneal injection of 6A-8R attenuated ovariectomy-induced osteoporosis in mice by inhibiting osteoclast differentiation, promoting osteoblast differentiation, and inhibiting sclerostin production by osteocytes in vivo with no apparent side effects. Conversely, in vitro, 6A-8R inhibited osteoclast differentiation by inhibiting NF-κB transcriptional activity, promoted osteoblast differentiation by promoting Smad1 phosphorylation, and inhibited sclerostin expression in osteocytes by inhibiting myocyte enhancer factors 2C and 2D. These findings suggest that 6A-8R has the potential to be an antiosteoporotic therapeutic agent with uncoupling properties.

Preoperative degree of deformity and underlying disease affect the postoperative deformity of joint-preserving hallux valgus surgery.

BACKGROUND: The combination of distal osteotomy with lateral dissection in joint-preserving surgery for severe hallux valgus deformity has recently begun to yield encouraging results. We examined the frequency of complications and risk factors of those for joint-preserving surgery in patients with and without rheumatoid arthritis (RA). METHODS: A retrospective, observational study of 72 feet (27 patients with RA) was performed. The inclusion criteria were patients who underwent joint-preserving surgery for hallux valgus deformity at our hospital between January 2008 and March 2016 who could be followed up with for longer than 12 months. RESULTS: The mean preoperative and immediate postoperative hallux valgus angles (HVA) were 41.8 and 4.4, respectively. The mean preoperative and immediate postoperative intermetatarsal angles between the first and second metatarsal bones (M1-M2A) were 14.6 and 5.8, respectively. At the final postoperative evaluation, the mean HVA was 8.8 and the mean M1-M2A was 6.4.Data were compared among the patients with complications (recurrent valgus deformity, varus deformity), and those without complications (normal HVA) at the final postoperative evaluation. The rate of RA in the varus deformity group was 71.4%, which tended to be higher than in other groups (p = .058). The mean preoperative HVA were 48.2 and 52.6 in the group of recurrent valgus deformity and varus deformity, which was higher than the normal HVA group (p = .001). CONCLUSIONS: High preoperative HVA was a risk factor for the recurrence of valgus deformity. Most of the varus deformities were observed in the RA group with high preoperative HVA; therefore, caution should be exercised in operating on patients with severe deformity or those with RA. LEVEL OF EVIDENCE: III.

Basic fibroblast growth factor promotes meniscus regeneration through the cultivation of synovial mesenchymal stem cells via the CXCL6-CXCR2 pathway.

OBJECTIVE: To investigate the efficacy of basic fibroblast growth factor (bFGF) in promoting meniscus regeneration by cultivating synovial mesenchymal stem cells (SMSCs) and to validate the underlying mechanisms. METHODS: Human SMSCs were collected from patients with osteoarthritis. Eight-week-old nude rats underwent hemi-meniscectomy, and SMSCs in pellet form, either with or without bFGF (1.0 × 106 cells per pellet), were implanted at the site of meniscus defects. Rats were divided into the control (no transplantation), FGF (-) (pellet without bFGF), and FGF (+) (pellet with bFGF) groups. Different examinations, including assessment of the regenerated meniscus area, histological scoring of the regenerated meniscus and cartilage, meniscus indentation test, and immunohistochemistry analysis, were performed at 4 and 8 weeks after surgery. RESULTS: Transplanted SMSCs adhered to the regenerative meniscus. Compared with the control group, the FGF (+) group had larger regenerated meniscus areas, superior histological scores of the meniscus and cartilage, and better meniscus mechanical properties. RNA sequencing of SMSCs revealed that the gene expression of chemokines that bind to CXCR2 was upregulated by bFGF. Furthermore, conditioned medium derived from SMSCs cultivated with bFGF exhibited enhanced cell migration, proliferation, and chondrogenic differentiation, which were specifically inhibited by CXCR2 or CXCL6 inhibitors. CONCLUSION: SMSCs cultured with bFGF promoted the expression of CXCL6. This mechanism may enhance cell migration, proliferation, and chondrogenic differentiation, thereby resulting in superior meniscus regeneration and cartilage preservation.

Extensive subcutaneous emphysema of the thigh as a rare complication following total knee arthroplasty: A case report.

INTRODUCTION AND IMPORTANCE OF THE CASE: This is the first report of subcutaneous emphysema of the thigh as a complication after total knee arthroplasty (TKA). PRESENTATION OF CASE: A 78-year-old female patient with valgus knee arthropathy underwent TKA. Two days postoperatively, the patient experienced left thigh swelling and pain, and subcutaneous emphysema was detected upon palpation. Although the skin tone was comparable to the other side, the left thigh was tender and firm. The surgical wound did not exhibit erythema. Computed tomography imaging revealed emphysema in the subcutaneous and intermuscular regions of the left thigh. Gram stain and culture tests from arthrocentesis were negative, and blood culture results were also negative. As there was no fever or disturbance of consciousness, and the LRINEC score was 1, supportive care was provided to the patient. At 5 days postoperatively, there was an observable improvement in the emphysema, and by day 9 postoperatively, the emphysema had fully resolved. CLINICAL DISCUSSION: There is a lack of documented cases reporting extensive subcutaneous emphysema of the thigh following TKA, suggesting it to be an exceedingly rare complication. In this case, we conducted a thorough investigation to assess the potential association of infection. Subsequently, the symptoms were successfully alleviated with supportive care without antibiotics. CONCLUSION: The occurrence of subcutaneous emphysema in the thigh was identified as a postoperative complication following TKA. Blood tests, culture tests and LRINEC score can be valuable tools for differentiation.

Early mobilization of dorsiflexion from 3 days after cemented total ankle arthroplasty with modified antero-lateral approach.

BACKGROUND: According to the conventional postoperative procedure after total ankle arthroplasty (TAA), mobilization is currently started after completion of wound healing. To investigate the possibility of expediting rehabilitation, this study evaluated the feasibility and safety of early mobilization of dorsiflexion after cemented TAA utilizing a modified antero-lateral approach. MATERIALS AND METHODS: This retrospective, observational study investigated 14 consecutive ankles that had received cemented TAA. Mobilization of dorsiflexion was started from 3 days after surgery. Postoperative wound complications including blister formation, eschar formation, wound dehiscence, peri-incisional decreased sensation were observed and recorded. Range of motion (ROM) of dorsiflexion/plantar flexion was measured. Patients also completed a self-administered foot evaluation questionnaire (SAFE-Q) and the scale of Japanese Society for Surgery of the Foot (JSSF) ankle/hindfoot score preoperatively and at final follow-up. RESULTS: No postoperative complications related to wound healing were observed. ROM for dorsiflexion, SAFE-Q score, and JSSF score improved significantly after TAA. CONCLUSION: Within this small number of cases, early mobilization of dorsiflexion from 3 days after cemented TAA was feasible and safe with the modified antero-lateral approach. Innovations in postoperative procedures for rehabilitation after TAA can be expected.

Modified Scarf Osteotomy with Medial Capsular Interposition Combined with Metatarsal Shortening Offset Osteotomy: A Comparison of Patients with Noninflammatory Arthritis and Rheumatoid Arthritis of the Foot.

BACKGROUND: Patients who have noninflammatory arthritis of the feet may develop destructive changes on the first metatarsal head and painful dislocation of the metatarsophalangeal (MTP) joint of 1 or more lesser toes. This aim of this study was to compare feet with noninflammatory arthritis and those with rheumatoid arthritis (RA) with respect to the clinical and radiographic outcomes after treatment of these destructive deformities with a modified Scarf osteotomy with medial capsular interposition into the newly formed first MTP joint, combined with metatarsal shortening offset osteotomy. METHODS: A retrospective observational study of 93 feet (31 with noninflammatory arthritis and 62 with RA) was performed. Hallux and lesser-toe scores on the Japanese Society for Surgery of the Foot (JSSF) scoring system, a self-administered foot evaluation questionnaire (SAFE-Q), and preoperative and postoperative radiographic parameters were evaluated. RESULTS: There were significant improvements at the time of the final follow-up in the mean scores on the hallux and lesser-toe scales of the JSSF system and in the SAFE-Q score. The postoperative JSSF lesser-toes function score was better for the feet with noninflammatory arthritis feet than the feet with RA. There was no significant difference in the hallux valgus angle (HVA) between 1 month postoperatively and the final follow-up for both groups. Furthermore, the HVA showed a strong correlation between the 1-month and final follow-up values. CONCLUSIONS: The combination of the modified Scarf osteotomy with medial capsular interposition and shortening metatarsal offset osteotomy was useful and safe in feet with noninflammatory arthritis. The HVA at 1 month after surgery is useful to predict the HVA within 5 years after surgery. The postoperative clinical score for the lesser toes was better in the feet with noninflammatory arthritis. LEVEL OF EVIDENCE: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Effects of iguratimod on glucocorticoid-induced disorder of bone metabolism in vitro.

INTRODUCTION: Glucocorticoids are widely used to treat various diseases including rheumatoid arthritis (RA); however, one of the most frequent and severe adverse effects is glucocorticoid-induced osteoporosis (GIOP). Iguratimod (IGU) is a novel conventional synthetic disease-modifying anti-rheumatic drug developed in Japan. The aim of this study is to investigate the effects of IGU on glucocorticoid-induced disorder of bone metabolism in vitro. MATERIALS AND METHODS: In osteoclastogenesis of mouse bone marrow-derived cells, tartrate-resistant acid phosphatase staining, resorption pit assay, western blotting, real-time polymerase chain reaction (PCR), and mRNA sequencing were performed. In osteoblastogenesis of MC3T3-E1 cells, alkaline phosphatase (ALP) staining and activity, alizarin red staining, and mRNA sequencing were performed, and real-time PCR and western blotting were conducted in MC3T3-E1 cells and murine osteocyte-like cell line MLO-Y4 cells. RESULTS: IGU significantly suppressed a dexamethasone-induced increase in osteoclasts, differentiation, and bone resorption activity by inhibition of the receptor activator of the nuclear factor kappa-B (RANK)/tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6)/nuclear factor kappa-B (NFκB)-p52 pathway. In MC3T3-E1 cells, IGU significantly upregulated dexamethasone-induced downregulation of ALP activity, bone mineralization, and osteoblast-related gene and protein expression. In MLO-Y4 cells, IGU significantly upregulated dexamethasone-induced downregulation of the gene expression of ALP and osteocalcin, and also downregulated receptor activator of NFκB ligand (RANKL)/osteoprotegerin gene expression ratio without dexamethasone. CONCLUSION: These results suggest that IGU may improve glucocorticoid-induced disorder of bone metabolism and may exhibit positive effects against GIOP associated with RA.

A report of three cases which required tibialis anterior tendon resection to recover delayed wound healing after total ankle arthroplasty in patients with rheumatoid arthritis.

Delayed wound healing is one of the severe complications after total ankle arthroplasty (TAA). In particular, once tibialis anterior (TA) tendon is exposed from tendon sheath of extensor retinaculum, wound healing will be critically intractable. We report three cases (mean age: 75.3 years old) of delayed wound healing after TAA cured by resection of TA tendon in patients with rheumatoid arthritis (RA). All three cases underwent TAA through an anterior approach, with careful suture of extensor retinaculum in wound closure. Ankle joint was fixed with splint and avoid weight bearing for three weeks after surgery. Delayed wound healing with TA tendon exposure was observed, and initially treated by debridement, basic fibroblast growth factor spray, and negative pressure wound therapy, which all failed to obtain wound healing. Finally, complete resection of TA tendon led to rapid wound healing. In all cases, ankle dorsal flexion was compensated by other extensors, with maintained range of motion and muscle strength (manual muscle testing 3 to 4) compared to pre-operation at 1 year after TAA operation. Resection of TA tendon may be considered as one of the salvage treatment options of severe delayed wound healing in TAA with anterior approach, especially in elderly patients.

Combined effect of teriparatide and an anti-RANKL monoclonal antibody on bone defect regeneration in mice with glucocorticoid-induced osteoporosis.

OBJECTIVE: The purpose of this study was to examine the effect of single or combination therapy of teriparatide (TPTD) and a monoclonal antibody against the murine receptor activator of nuclear factor κB ligand (anti-RANKL Ab) on cancellous and cortical bone regeneration in a mouse model of glucocorticoid-induced osteoporosis (GIOP). METHODS: C57BL/6 J mice (24 weeks of age) were divided into five groups: (1) the SHAM group: sham operation + saline; (2) the prednisolone (PSL) group: PSL + saline; (3) the TPTD group: PSL + TPTD; (4) the Ab group: PSL + anti-RANKL Ab; and (5) the COMB group: PSL + TPTD + anti-RANKL Ab (n = 8 per group). With the exception of the SHAM group, 7.5 mg of PSL was inserted subcutaneously into mice, to generate a mouse model of GIOP. Four weeks after insertion, bone defects with a diameter of 0.9 mm were created to assess bone regeneration on both femoral metaphysis (cancellous bone) and diaphysis (cortical bone). After surgery, therapeutic intervention was continued for 4 weeks. Saline (200 µl) or TPTD (40 µg/kg) was injected subcutaneously five times per week, whereas the anti-RANKL Ab (5 mg/kg) was injected subcutaneously once on the day after surgery. Subsequently, the following analyses were performed: microstructural assessment of bone regeneration and bone mineral density (BMD) measurement via micro-computed tomography, and histological, histomorphometrical, and biomechanical analyses with nanoindentation. RESULTS: The COMB group showed the highest lumbar spine BMD increase (vs. the PSL, TPTD, and Ab groups). The volume of regenerated cancellous bone at the bone defect site was higher in the COMB group compared with the PSL, TPTD, and Ab group. The volume of the regenerated cortical bone was significantly higher in the COMB group compared with the PSL group, and its hardness was significantly higher in the COMB group compared with the PSL and TPTD groups. CONCLUSION: In a mouse model of glucocorticoid-induced osteoporosis, the combination therapy of TPTD plus the anti-RANKL Ab increased bone mineral density in the lumbar spine and regenerated cancellous bone volume compared with single administration of each agent, and also increased regenerated cortical bone strength compared with single administration of TPTD.

Promoting Effect of Basic Fibroblast Growth Factor in Synovial Mesenchymal Stem Cell-Based Cartilage Regeneration.

Synovial mesenchymal stem cell (SMSC) is the promising cell source of cartilage regeneration but has several issues to overcome such as limited cell proliferation and heterogeneity of cartilage regeneration ability. Previous reports demonstrated that basic fibroblast growth factor (bFGF) can promote proliferation and cartilage differentiation potential of MSCs in vitro, although no reports show its beneficial effect in vivo. The purpose of this study is to investigate the promoting effect of bFGF on cartilage regeneration using human SMSC in vivo. SMSCs were cultured with or without bFGF in a growth medium, and 2 × 105 cells were aggregated to form a synovial pellet. Synovial pellets were implanted into osteochondral defects induced in the femoral trochlea of severe combined immunodeficient mice, and histological evaluation was performed after eight weeks. The presence of implanted SMSCs was confirmed by the observation of human vimentin immunostaining-positive cells. Interestingly, broad lacunae structures and cartilage substrate stained by Safranin-O were observed only in the bFGF (+) group. The bFGF (+) group had significantly higher O'Driscoll scores in the cartilage repair than the bFGF (-) group. The addition of bFGF to SMSC growth culture may be a useful treatment option to promote cartilage regeneration in vivo.

Impact of combining medial capsule interposition with modified scarf osteotomy for hallux valgus.

Objectives: To clarify the effect of combining medial capsule interposition with modified scarf osteotomy for hallux valgus.Methods: A multicenter, retrospective study included 64 cases [59 osteoarthritis patients (excluding rheumatoid arthritis); age 68.8 years, range 40-93 years] of modified scarf osteotomy which were performed from 2013 to 2017 and followed for 26.6 (range, 13-50) months. Patients were treated by either (1) without medial capsule interposition (33 cases) or (2) combined with interposition (31 cases) at each senior surgeon's discretion. The Japanese Society for Surgery of the Foot (JSSF) hallux metatarsophalangeal (MTP)-interphalangeal scale was evaluated along with radiographic parameters (hallux valgus angle [HVA], first and second metatarsals intermetatarsal angles, and Hardy grade).Results: All JSSF scale and radiographic parameters were similar at baseline and significantly improved at final follow-up in both groups (pre-operation vs. final follow-up: p < .001). However, compared to without interposition group, interposition group showed significantly higher improvement in the JSSF scale (pre-operation to final follow-up: p value between the two groups at final follow-up) for pain (without interposition: 19.4-34.2, interposition: 18.4-37.1; p = .02), function (without interposition: 20.8-33.6, interposition: 18.3-36.6; p = .005), total score (without interposition: 41.5-81.8, interposition: 38.5-88.5; p < .001), and the MTP joint space (without interposition: 1.4-1.5 mm, interposition: 1.6-2.6 mm; p < .001) with significant correlation between the total JSSF score (r = .40; p = .001).Conclusion: Combining medial capsule interposition with modified scarf osteotomy significantly improved mid-term clinical outcomes.

Bone stock reconstruction for huge bone loss using allograft-bones, bone marrow, and teriparatide in an infected total knee arthroplasty.

Bone stock reconstruction using allograft-bones, bone marrow (BM), and teriparatide (TPTD) is reported. Huge and extensive bone losses occurred in the medullary cavity of the femur and tibia of a 55-year-old female rheumatoid arthritis patient with severe osteoporosis after debridement of her infected total knee arthroplasty. Because of the risks of unstable prosthetic fixation and intra-operation fracture, we first reconstructed the bone stock. Chipped allograft bones mixed with BM were implanted in the bone defects, and TPTD was administrated for the osteoporosis therapy. Good bone formation was found by computed tomography after 4 months. Bone turnover markers and bone mineral density (BMD) were increased at 6 months. We confirmed good bone formation at the re-implantation surgery. The newly formed bone harvested during the re-implantation surgery showed active osteoblast-like lining cells. TPTD is known to enhance allograft bone union, mesenchymal stem cell differentiation into osteoblasts, and BMD. This tissue engineering-based technique might be improved by the various effects of TPTD. This method without any laboratory cell culture might be a good option for bone stock reconstruction surgery in ordinary hospitals.

Albumin and apolipoprotein H mRNAs in human plasma as potential clinical biomarkers of liver injury: analyses of plasma liver-specific mRNAs in patients with liver injury.

CONTEXT: Plasma liver-specific mRNAs are useful biomarkers of hepatotoxicity in rats. OBJECTIVE: To investigate the potential application of liver-specific mRNAs as biomarkers for liver injury in humans. METHODS: We determined the plasma levels of liver-specific mRNAs by real-time qRT-PCR in healthy donors and patients with liver injury. RESULTS: Plasma levels of albumin (ALB) and apolipoprotein H (APOH) mRNAs increased in patients with elevated serum alanine aminotransferase. These mRNAs also increased in plasma after transcatheter arterial chemoembolization, which induces specific injury to liver. CONCLUSIONS: We demonstrated the potential application of plasma ALB and APOH mRNAs as clinical biomarkers for liver injury.

Improved toxicogenomic screening for drug-induced phospholipidosis using a multiplexed quantitative gene expression ArrayPlate assay.

We previously showed that a toxicogenomics analysis of drug-induced phospholipidosis enabled the identification of 12 specific gene markers and the establishment of an in vitro real-time PCR screening assay for the assessment of the phospholipidosis-inducing potential of compounds. The purpose of this study was to transfer our PCR-based assay into a 96-well microplate-based multiple mRNAs measuring assay (ArrayPlate assay) in order to increase throughput. Specifically, we determined the expression of the 12 marker genes using real-time PCR and ArrayPlate in human hepatoma HepG2 cells that were treated for 24h with each of amiodarone and 80 proprietary compounds. The following three performance criteria were satisfied in the ArrayPlate analysis: 1. Sensitivity-the expression of mRNA for all target genes was detected at quantifiable levels. 2. Repeatability-signal intensities and fold change values of each marker gene were highly repeatable. 3. Correlation-fold change values and their average values, which were used as indices of phospholipidosis induction potential, showed apparent correlation between the ArrayPlate and real-time PCR assays. Thus, the in vitro screening assay for compound-induced phospholipidosis should be transferable from a PCR-based assay to the higher-throughput ArrayPlate-based method.

A toxicogenomic approach to drug-induced phospholipidosis: analysis of its induction mechanism and establishment of a novel in vitro screening system.

Phospholipidosis is a lipid storage disorder in which excess phospholipids accumulate within cells. Some cationic amphiphilic compounds are known to have the potential to induce phospholipidosis. This study was undertaken to examine the molecular mechanisms that contribute to the development of phospholipidosis and to identify specific markers that might form the basis of an in vitro screening test. Specifically, we performed a large-scale gene expression analysis using DNA microarrays on human hepatoma HepG2 cells after they were treated with each of 12 compounds known to induce phospholipidosis. In electron microscopy, HepG2 cells developed lamellar myelin-like bodies in their lysosomes, the characteristic change of phospholipidosis, after treatment with these compounds for 72 h. DNA microarray analysis performed 6 and 24 h after treatment showed alterations in gene expression reflecting the inhibition of lysosomal phospholipase activity and lysosomal enzyme transport, and the induction of phospholipid and cholesterol biosynthesis. Seventeen genes that showed a similar expression profile following treatment were selected as candidate markers. Real-time PCR analysis confirmed that 12 gene markers showed significant concordance with lamellar myelin-like body formation. Furthermore, the average fold change values of these markers correlated well with the magnitude of this pathological change. In conclusion, microarray analysis revealed that factors such as alterations in lysosomal function and cholesterol metabolism were involved in the induction of phospholipidosis. Furthermore, comprehensive gene expression analysis enabled us to identify biomarkers of this condition that we then used to develop a rapid and sensitive in vitro screening test for drug-induced phospholipidosis.