Outcomes of Joint-Preserving Surgery for Forefoot Deformities in Patients With Rheumatoid Arthritis.

BACKGROUND: With the advent of effective disease-modifying medications, the surgical treatment of forefoot deformities in patients with rheumatoid arthritis (RA) has evolved from joint-sacrificing to joint-preserving surgery. However, it is unclear whether joint-preserving surgery is effective for the full range of metatarsophalangeal joint involvement. Hence, this study investigated the postoperative outcomes of joint-preserving surgery for rheumatoid forefoot deformities with a wide range of joint destruction. METHODS: This retrospective observational study included 68 feet from 68 patients with RA who underwent joint-preserving surgery for forefoot deformities between 2014 and 2020. The Larsen grade classification was used to assess the first metatarsophalangeal joint destruction and classify patients into 4 groups as follows: 0 and 1 (n = 14), 2 (n = 21), 3 (n = 19), and 4 and 5 (n = 14). The Self-Administered Foot and Ankle Evaluation Questionnaire (SAFE-Q) score, hallux valgus angle (HVA), and intermetatarsal angle (IMA) were determined before surgery and at the last follow-up visit. RESULTS: The median observation duration was 40 (range, 24-78) months. SAFE-Q scores of all groups significantly improved in all subscales at the last observation, with no significant differences among the study groups. Radiographic evaluations of all groups revealed significant improvements in HVA and IMA after surgery, with no significant differences among the groups. CONCLUSION: In patients using the surgical approaches described in this study, joint-preserving surgery for rheumatoid forefoot deformities led to satisfactory clinical and radiographic improvements, regardless of the severity of joint destruction. LEVEL OF EVIDENCE: Level III, case-control study.

Hindfoot Alignment and Ankle Stability Following Arthroscopic Lateral Ankle Ligament Repair.

BACKGROUND: Hindfoot varus deformity is a known risk factor for chronic lateral ankle instability (CLAI). The impact of this deformity on clinical results following arthroscopic lateral ankle ligament repair (ALLR) for CLAI has not been studied. METHODS: Sixty-three ankles from 62 patients who received ALLR for CLAI were retrospectively examined. Preoperative plain radiographs were used to measure tibial articular surface (TAS) angles, and long axial hindfoot alignment radiographs were used to measure tibiocalcaneal angles (TCAs) pre- and postoperatively. Results included ratings on the Self-Administered Foot Evaluation Questionnaire (SAFE-Q) and recurrent ankle instability (respraining of the operated ankle following surgery). RESULTS: Recurrent ankle instability, defined as incidence of any new ankle sprain after surgery reported in the follow-up period, occurred in 13 ankles. The TAS angles of these patients were significantly low, and their preoperative TCA was significantly high. Multivariate analysis showed that preoperative TCA was an independent risk factor for recurrent ankle instability. The threshold values for preoperative TCA for recurrent instability were determined via the receiver operating characteristic curve analysis to be 3.4 degrees. Patients were assigned to a low- or high-TCA group based on the reported average TCA (2.7 degrees) of healthy patients. In the high-TCA group, recurrent instability was significantly more frequent, and the scores on the pain subscale of the postoperative SAFE-Q were significantly lower. CONCLUSION: Hindfoot varus alignment was associated with pooreroutcomes after ALLR. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Nonresponder Considerations for Romosozumab Treatment.

Romosozumab can increase bone mineral density (BMD) in patients with osteoporosis, but some patients do not respond to it. This study aimed to identify risk factors for being a nonresponder to romosozumab treatment. This retrospective observational study included 92 patients. Romosozumab (210 mg) was subcutaneously administered to the participants every 4 weeks over 12 months. We excluded patients who previously underwent treatment for osteoporosis to assess the impact of romosozumab alone. We evaluated the proportion of patients who did not respond to romosozumab treatment to the lumbar spine and hip with increased BMD. Nonresponders were defined as those with a bone density change of < 3% after 12 months of treatment. We compared demographics and biochemical markers between responders and nonresponders. We found that 11.5% of patients were nonresponders at the lumbar spine, and 56.8% were nonresponders at the hip. A risk factor for nonresponse at the spine was low type I procollagen N-terminal propeptide (P1NP) values at 1 month. The cutoff value for P1NP at month 1 was 50 ng/ml. We found that 11.5% and 56.8% of patients experienced no significant improvement in the lumbar spine and hip BMD, respectively. Clinicians should use nonresponse risk factors to inform decisions about romosozumab treatment for patients with osteoporosis.

Surgical intervention for patients with rheumatoid arthritis is declining except for foot and ankle surgery: A single-centre, 20-year observational cohort study.

OBJECTIVES: A global downward trend in the number of rheumatoid arthritis (RA)-related surgeries has been reported. The purpose of our study was to investigate the latest trends in RA-related surgeries in a single-centre Japanese RA cohort. METHODS: This study was a retrospective analysis of RA-related surgeries between 2001 and 2020 in the Institute of Rheumatology Rheumatoid Arthritis cohort. An average of 4944 patients per semi-annual survey was included in the study. The primary goal was to analyse the half-year period prevalence proportion (HPP) of RA-related surgeries in a 20-year period, and the secondary goal was to analyse the HPP of surgeries by site or by categories of disease activity. RESULTS: There has been a downward trend in the HPP of RA-related surgeries in the 20-year study period. The total HPP of RA-related surgeries decreased by 50.3% during the 20-year study period. There was a significant decrease in knee, hip, shoulder/elbow, and hand procedures. Only foot/ankle joint surgeries significantly increased in volume during this period (p = .001). The HPP of RA-related surgeries remained unchanged in patients with remission or low disease activity. CONCLUSIONS: The number of RA-related surgeries decreased over a 20-year period, but foot/ankle joint surgeries increased in the site-specific evaluation.

Anterior talofibular ligament remnant quality is important for achieving a stable ankle after arthroscopic lateral ankle ligament repair.

PURPOSE: The relationship between ligament remnant quality and postoperative outcomes after arthroscopic lateral ankle ligament repair for chronic lateral ankle instability is controversial. This study aimed to determine whether the signal intensity of the anterior talofibular ligament on preoperative magnetic resonance imaging and ligament remnant quality identified on arthroscopy are associated with recurrent ankle instability after arthroscopic lateral ankle ligament repair. METHODS: A total of 68 ankles from 67 patients with chronic lateral ankle instability who underwent arthroscopic lateral ankle ligament repair were retrospectively studied. The signal intensity of the anterior talofibular ligament was evaluated using T2-weighted magnetic resonance imaging. Arthroscopy was used to evaluate the thickness and mechanical resistance of the anterior talofibular ligament by hook palpation and to classify ankles into two groups: the present anterior talofibular ligament group with adequate mechanical resistance and the absent anterior talofibular ligament group with no mechanical resistance. The outcomes included recurrent ankle instability (respraining of the operated ankle after surgery) and Self-Administered Foot Evaluation Questionnaire scores. RESULTS: Thirteen ankles were diagnosed with recurrent ankle instability. Patients with a high anterior talofibular ligament T2 signal intensity experienced more recurrent ankle instability than those with a low intensity. As determined via arthroscopy, the absent anterior talofibular ligament group had a higher rate of recurrent ankle instability than the present anterior talofibular ligament group. There were no significant differences in Self-Administered Foot Evaluation Questionnaire scores between patients with high and low anterior talofibular ligament T2 signal intensity, as well as between absent and present anterior talofibular ligament groups based on arthroscopy. CONCLUSION: Poor quality of the anterior talofibular ligament remnant could result in recurrent ankle instability after arthroscopic lateral ankle ligament repair. Therefore, when treating chronic lateral ankle instability, surgeons should consider ligament quality. LEVEL OF EVIDENCE: IV.

Varus-Tilted Distal Tibial Plafond Is a Risk Factor for Recurrent Ankle Instability After Arthroscopic Lateral Ankle Ligament Repair.

BACKGROUND: Although varus-tilted distal tibial deformity is an established risk factor for chronic lateral ankle instability (CLAI), no studies have reported whether this deformity influences ankle instability after arthroscopic lateral ankle ligament repair (ALLR) for CLAI. METHODS: A total of 57 ankles from 57 patients who underwent ALLR for CLAI were retrospectively analyzed. Tibial articular surface (TAS) angles were measured on preoperative plain radiograph. After 12 months of follow-up, recurrent ankle instability and talar tilt angles on stress radiograph were evaluated as outcomes. Relationships between the TAS angle and these outcomes were assessed. RESULTS: Recurrent ankle instability was observed in 10 ankles. The TAS angles of patients with recurrent instability were significantly lower (85.2 degrees vs 87.9 degrees). The receiver operating characteristic curve analysis revealed that the cutoff value of TAS angle for recurrent instability was 86.2 degrees. Based on this cutoff value, our patients were divided into 2 groups: low-TAS and high-TAS group. Univariate and multivariate analysis revealed that low TAS was an independent risk factor for recurrent ankle instability and greater postoperative talar tilt angles. CONCLUSION: Varus-tilted distal tibial plafond appears to be a risk factor for recurrent ankle instability after ALLR.

O-Arm Assisted Cervicothoracic Spine Pedicle Screw Placement Accuracy Is Higher Than C-Arm Fluoroscopy.

OBJECTIVE: We compared the accuracy of C-arm fluoroscopy versus O-arm-assisted pedicle screw (PS) placement in the cervicothoracic spinal junction (CTSJ). METHODS: Patients who underwent PS placement in the CTSJ (C7-T4) at our hospital were included in this study. Of 37 patients who underwent PS placement in the CTSJ, 20 underwent intraoperative C-arm fluoroscopy-assisted surgery (C Group) and 17 underwent intraoperative O-arm-assisted surgery (O Group). In total, 159 PSs were placed-73 in the C Group and 86 in the O Group. The accuracy of PS placement was compared between the C Group and O Group using the classification proposed by Gertzbein and Robbins to analyze pedicle violation. RESULTS: PS accuracy was higher in the O Group than C Group; PS placement evaluated as grade A, representing no perforation, was 95.3% (82/86) for the O Group, whereas it was 78.1% (57/73) for the C Group. There was a clear statistically significant difference in accuracy of PS placement between the groups (P = 0.0013). CONCLUSIONS: O-arm-assisted surgery improved the accuracy of PS placement in the CTSJ.

Joint-Preserving Surgery for Forefoot Deformities in Patients with Rheumatoid Arthritis: A Literature Review.

The combination of first metatarsophalangeal joint arthrodesis and resection arthroplasty of all lesser metatarsal heads has been historically considered the golden standard treatment for rheumatoid forefoot deformities. However, as recent improved management of rheumatoid arthritis have reduced progression of joint destruction, the surgical treatments for rheumatoid forefoot deformities have gradually changed from joint-sacrificing surgery, such as arthrodesis and resection arthroplasty, to joint-preserving surgery. The aim of this literature review was to provide current evidence for joint-preserving surgery for rheumatoid forefoot deformities. We focused on the indications, specific outcomes, and postsurgical complications of joint-preserving surgery in this review.

Regenerative effects of human chondrocyte sheets in a xenogeneic transplantation model using immune-deficient rats.

Although cell transplantation has attracted much attention in regenerative medicine, animal models continue to be used in translational research to evaluate safety and efficacy because cell sources and transplantation modalities are so diverse. In the present study, we investigated the regenerative effects of human chondrocyte sheets on articular cartilage in a xenogeneic transplantation model using immune-deficient rats. Osteochondral defects were created in the knee joints of immune-deficient rats that were treated as Group A, untreated (without transplantation); Group B, transplantation of a layered chondrocyte sheet containing 5.0 × 105 cells (layered chondrocyte sheet transplantation); Group C, transplantation of a synoviocyte sheet containing 5.0 × 105 cells (synoviocyte sheet transplantation); or Group D, transplantation of both a synoviocyte sheet plus a layered chondrocyte sheet, each containing 5.0 × 105 cells (synoviocyte sheet plus layered chondrocyte sheet transplantation). Histological evaluation demonstrated that Group B showed cartilage regeneration with hyaline cartilage and fibrocartilage. In Groups C and D, the defect was filled with fibrous tissue but no hyaline cartilage. Transplanted cells were detected at 4 and 12 weeks after transplantation, but the number of cells had decreased at 12 weeks. Our results indicate that layered chondrocyte sheet transplantation contributes to articular cartilage regeneration; this model proved useful for evaluating these regenerative effects.

Rabbit xenogeneic transplantation model for evaluating human chondrocyte sheets used in articular cartilage repair.

Research on cartilage regeneration has developed novel sources for human chondrocytes and new regenerative therapies, but appropriate animal models for translational research are needed. Although rabbit models are frequently used in such studies, the availability of immunocompromised rabbits is limited. Here, we investigated the usefulness of an immunosuppressed rabbit model to evaluate directly the efficacy of human chondrocyte sheets through xenogeneic transplantation. Human chondrocyte sheets were transplanted into knee osteochondral defects in Japanese white rabbits administered with immunosuppressant tacrolimus at a dosage of 0.8 or 1.6 mg/kg/day for 4 weeks. Histological evaluation at 4 weeks after transplantation in rabbits administered 1.6 mg/kg/day showed successful engraftment of human chondrocytes and cartilage regeneration involving a mixture of hyaline cartilage and fibrocartilage. No human chondrocytes were detected in rabbits administered 0.8 mg/kg/day, although regeneration of hyaline cartilage was confirmed. Histological evaluation at 12 weeks after transplantation (i.e., 8 weeks after termination of immunosuppression) showed strong immune rejection of human chondrocytes, which indicated that, even after engraftment, articular cartilage is not particularly immune privileged in xenogeneic transplantation. Our results suggest that Japanese white rabbits administered tacrolimus at 1.6 mg/kg/day and evaluated at 4 weeks may be useful as a preclinical model for the direct evaluation of human cell-based therapies.

Quality assessment of cellular and tissue-based products using liquid chromatography-tandem mass spectrometry.

We are currently conducting clinical research on cell sheets for cartilage regeneration. One issue with the future use of chondrocyte sheets as cellular and tissue-based products is quality assessment. Currently, chondrocyte sheets are evaluated using invasive methods that cannot be performed on every sheet produced. We report here on our liquid chromatography-tandem mass spectrometry (LC-MS/MS) technique that allows the noninvasive assessment of every sheet using only 50 µl of culture medium. We found that LC-MS/MS could be used to confirm cell sheet viability through the measurement of glucose and glutamine uptake, to estimate extracellular matrix production by measuring serine consumption, to estimate cell kinetics by measuring cytidine and uracil concentrations, and to estimate melanoma inhibitory activity level by measuring pyridoxal concentration. LC-MS/MS may be useful for the noninvasive assessment of products to be used in regenerative medicine.

DNA Methylation Suppresses Leptin Gene in 3T3-L1 Adipocytes.

Leptin is a key regulator of energy intake and expenditure. This peptide hormone is expressed in mouse white adipose tissue, but hardly expressed in 3T3-L1 adipocytes. Using bisulfite sequencing, we found that CpG islands in the leptin promoter are highly methylated in 3T3-L1cells. 5-azacytidine, an inhibitor of DNA methyltransferase, markedly increased leptin expression as pre-adipocytes matured into adipocytes. Remarkably, leptin expression was stimulated by insulin in adipocytes derived from precursor cells exposed to 5-azacytidine, but suppressed by thiazolidinedione and dexamethasone. In contrast, adipocytes derived from untreated precursor cells were unresponsive to both 5-azacytidine and hormonal stimuli, although lipid accumulation was sufficient to boost leptin expression in the absence of demethylation. Taken together, the results suggest that leptin expression in 3T3-L1 cells requires DNA demethylation prior to adipogenesis, transcriptional activation during adipogenesis, and lipid accumulation after adipogenesis.