Ryosuke Nakagawa

Association of Anxiety and Depression With Pain and Quality of Life in Patients With Chronic Foot and Ankle Diseases

Background: The purposes of this study were to clarify the incidence of anxiety and depression among patients with chronic foot and ankle diseases and to examine the independent association of anxiety and depression with pain and quality of life. Methods: Patients who visited the foot and ankle clinic from April 2015 to November 2016 were recruited. Anxiety and depression in patients were assessed using the Hospital Anxiety and Depression Scale. Pain and quality of life were evaluated using the visual analog scale (VAS) and Self-Administered Foot Evaluation Questionnaire (SAFE-Q), respectively. Furthermore, patient characteristics, including age, sex, body mass index, pain in other body areas, social support, employment, and household income, were surveyed. A multiple regression analysis was performed to examine the independent association of anxiety and depression with pain and quality of life. A total of 250 patients were included in the analysis. Results: The prevalence of anxiety and depression was 30% and 27%, respectively. The VAS and all SAFE-Q subscale scores were significantly worse in patients with anxiety or depression than in patients without the same (median VAS 63 vs 49 for anxiety, P = .005; 68 vs 47 for depression, P < .001). Furthermore, the multiple regression analyses showed that the presence of anxiety (P = .02) and depression (P < .001) was independently associated with increased pain, and it led to low scores on all SAFE-Q subscales (P < .001 for all subscales). Conclusion: About 30% of patients with chronic foot and ankle disease had anxiety or depression. The presence of these psychological symptoms was independently associated with worse pain and impaired quality of life after controlling for patient characteristics. Clinicians need to recognize the possibility of concurrent anxiety and depression to provide a more holistic treatment for chronic foot and ankle disease. Level of Evidence: Level IV, case series.

Evaluating different closed loop graft preparation technique for tibial suspensory fixation in ACL reconstruction using TightRope

In most anterior cruciate ligament (ACL) reconstructions, grafts are fixed to the femoral side first followed by the tibial side. Various techniques have been reported to achieve optimal tension on the grafts, but once the grafts are fixed it is difficult to adjust graft tension further. To enable post fixation tension control we have invented a new graft configuration using an adjustable loop-device (TightRopeTM, Arthrex, FL, USA) on the tibial side. In this paper, biomechanical properties of this configuration using soft tissue were examined in terms of graft diameter and various suture techniques (referred to as base suture) to make a closed circle to support TightRopeTM. Two experiments were conducted under different conditions. In each experiment, cyclic load, followed by a pull-to-failure load, was applied to the grafts and elongation and failure mode were recorded. (1) To evaluate the effects of diameter, 5.0 or 6.0 mm grafts were prepared by a single locking loop stitch as the base suture (SLL5, SLL6). (2) To evaluate different base sutures, 5.0 mm tendons were used, and grafts were prepared using five kinds of base sutures (SLL, ZLL: zigzag locking loop, DZLL: double zigzag locking loop, DK: double Krackow, DK w/o TR: double Krackow without TightRopeTM). In the first experiment, tearing was observed in 2 of 6 cases in the SLL5 test group, whereas no tearing was observed with SLL6. In the second experiment, no tearing was observed with DZLL or DK. Elongation was smaller in these two groups compared to the other groups. Mechanical strength decreases with a smaller graft diameter. Biomechanical properties differed with different base sutures and, among them, the double-zigzag-suture stitch and double Krackow provided less elongation and higher ultimate load in this graft configuration.

The effect of systemic administration of G-CSF on a full-thickness cartilage defect in a rabbit model MSC proliferation as presumed mechanism: G-CSF for cartilage repair

Objectives The aim of this study was to investigate the effect of granulocyte-colony stimulating factor (G-CSF) on mesenchymal stem cell (MSC) proliferation in vitro and to determine whether pre-microfracture systemic administration of G-CSF (a bone marrow stimulant) could improve the quality of repaired tissue of a full-thickness cartilage defect in a rabbit model. Methods MSCs from rabbits were cultured in a control medium and medium with G-CSF (low-dose: 4 μg, high-dose: 40 μg). At one, three, and five days after culturing, cells were counted. Differential potential of cultured cells were examined by stimulating them with a osteogenic, adipogenic and chondrogenic medium. A total of 30 rabbits were divided into three groups. The low-dose group (n = 10) received 10 μg/kg of G-CSF daily, the high-dose group (n = 10) received 50 μg/kg daily by subcutaneous injection for three days prior to creating cartilage defects. The control group (n = 10) was administered saline for three days. At 48 hours after the first injection, a 5.2 mm diameter cylindrical osteochondral defect was created in the femoral trochlea. At four and 12 weeks post-operatively, repaired tissue was evaluated macroscopically and microscopically. Results The cell count in the low-dose G-CSF medium was significantly higher than that in the control medium. The differentiation potential of MSCs was preserved after culturing them with G-CSF. Macroscopically, defects were filled and surfaces were smoother in the G-CSF groups than in the control group at four weeks. At 12 weeks, the quality of repaired cartilage improved further, and defects were almost completely filled in all groups. Microscopically, at four weeks, defects were partially filled with hyaline-like cartilage in the G-CSF groups. At 12 weeks, defects were repaired with hyaline-like cartilage in all groups. Conclusions G-CSF promoted proliferation of MSCs in vitro. The systemic administration of G-CSF promoted the repair of damaged cartilage possibly through increasing the number of MSCs in a rabbit model. Cite this article: T. Sasaki, R. Akagi, Y. Akatsu, T. Fukawa, H. Hoshi, Y. Yamamoto, T. Enomoto, Y. Sato, R. Nakagawa, K. Takahashi, S. Yamaguchi, T. Sasho. The effect of systemic administration of G-CSF on a full-thickness cartilage defect in a rabbit model MSC proliferation as presumed mechanism: G-CSF for cartilage repair. Bone Joint Res 2017;6:123–131. DOI: 10.1302/2046-3758.63.BJR-2016-0083.

Association between avulsion fracture of the distal fibula and recurrent sprain in children with ankle sprain

Category: Sports Introduction/Purpose: The incidence of ankle sprain is higher in children than in adolescents and adults. Avulsion fractures of the distal fibula, where the anterior tibiofibular ligament attaches, commonly occur with lateral ankle sprain in children. If the avulsion fracture remains ununited, it will become a subfibular ossicle (Figure), and can cause pain, instability, and recurrent sprain. However, the incidence and radiographic result of avulsion fracture, as well as the impact of the fracture on clinical outcomes, are not well-studied. The purposes of this study were 1) to clarify the incidence and union rate of distal fibular avulsion fracture with lateral ankle sprain in children, and 2) to assess the association between avulsion fracture and recurrent sprain. Methods: Patients who presented to four orthopaedic clinics were prospectively examined. Patients with a first-time inversion ankle sprain, aged from 6 to 12 years, and visiting the clinics within 48 hours after injury, were included. Patients underwent anteroposterior and lateral radiographs, and the ATFL view (Figure) at the first visit, and the incidence of avulsion fracture was assessed. The patients with avulsion fractures underwent follow-up radiographs after 8 weeks, and fracture union was assessed. Treatment was not standardized, and ranged from an elastic bandage to a non-weightbearing cast for 6 weeks. Recurrent sprain of the ipsilateral ankle was surveyed by a review of the medical record and the questionnaire that was sent to the patients regularly. Furthermore, patients were divided into 3 groups: patients with no avulsion fracture, fracture union, and fracture nonunion. The rates of recurrent sprain were compared among the groups using the chi-square test and multiple comparisons. Results: From April 2014 to August 2015, 144 ankles of 144 patients (53 female and 91 male) with a mean age of 8.8 years underwent the radiographs at the first visit. Recurrent sprain was assessed in 105 (73%) patients with a mean follow-up of 23months. The incidence of distal fibular avulsion fracture was 62% (89/144 patients). The union rate of avulsion fracture was only 17%. The overall rate of recurrent sprain was 32% (34/105 patients). The rates were 45% (5/11) in patients with fracture union and 39% (20/51) in patients with nonunion. These rates were significantly higher than that in patients with no avulsion fracture (21%, 9/43) (P=0.02). However, the rates were similar between patients with fracture union and nonunion. Conclusion: Avulsion fractures of the distal fibula were surprisingly common with ankle sprain in children, and the most of the fractures remained ununited. The rate of recurrent sprain was relatively high at a 23 month follow-up. The presence of avulsion fracture was associated with a higher risk of recurrent sprain, however achieving fracture union did not reduce the risk.

Single vs. repeated matrix metalloproteinase-13 knockdown with intra-articular short interfering RNA administration in a murine osteoarthritis model

ABSTRACT Purpose: Our aims were 1) to estimate the duration of short interfering RNA (siRNA) effect on matrix metalloproteinase-13 (Mmp-13) levels by a single intra-articular injection using a mouse knee osteoarthritis (OA) model and 2) to test whether repeated injections results in any additional suppressive effect on cartilage degradation compared to a single injection. Materials and Methods: OA was induced in 9 weeks old male C57BL/6 mice by destabilization of medial meniscus (DMM). Chemically modified siRNA targeted for Mmp-13 was injected into the knee joint at 1 week post-DMM surgery. Control group of knees received that for non-targeted genes. Synovial tissue was collected to measure Mmp-13 expression levels by quantitative polymerase chain reaction (qPCR) at 2, 3, and 6 weeks after surgery in each group. To test the effect of multiple injections, we created four experiment groups according to the number of injections. Histological assessment of articular cartilage was performed at 8 weeks post-DMM surgery. Results: In the Mmp-13 siRNA-treated group, expression levels of Mmp-13 mRNA were decreased by 40% compared to the control group at 2 weeks after surgery (p = 0.04), before returning to baseline at 3 weeks after surgery. A significant improvement in the histological score was observed in all Mmp-13 siRNA-treated groups compared to the control group (p < 0.05). However, no significant differences were seen between the single and multiple injection group. Conclusions: Our results suggested that the duration of siRNA effect in the knee joint lasts for at least 1 week, and that no further benefit is achieved by multiple injections.

Timing of Intra-Articular Injection of Synovial Mesenchymal Stem Cells Affects Cartilage Restoration in a Partial Thickness Cartilage Defect Model in Rats

Objective We investigated the effect of administration of intra-articular mesenchymal stem cells (MSCs) on cartilage repair at different timings, and the distribution of MSCs in the knee. Design A partial thickness cartilage defect (PTCD) was created on the medial femoral condyle in 14-week-old Sprague-Dawley rats. Intra-articular injection of 1 × 106 MSCs was performed at 3 time points, namely at the time of surgery (0w group), at 1 week after surgery (1w group), and at 2 weeks after surgery (2w group). For the control, 50 μL phosphate-buffered saline was injected at the time of surgery. The femoral condyles were collected at 6 weeks after creation of PTCD and assessed histologically. To investigate the distribution of MSCs, fluorescent-labeled MSCs were injected into the knee joint. Results In the control group, the cartilage lesion was distinguishable from surrounding cartilage. In the 0w group, hypocellularity and a slight decrease in safranin O stainability were observed around the injured area, but cartilage was restored to a nearly normal condition. In contrast, in the 1w and 2w groups, the cartilage surface was irregular and safranin O stainability in the injured and surrounding areas was poor. Histological score in the 0w group was significantly better than in the control, 1w, and 2w groups. At 1 day postinjection, fluorescent-labeled MSCs were mostly distributed in synovium. However, no migration into the PTCD was observed. Conclusions Early intra-articular injection of MSCs was effective in enhancing cartilage healing in a rat PTCD model. Injected MSCs were distributed in synovium, not in cartilage surrounding the PTCD.

The effect of femoral bone tunnel configuration on tendon-bone healing in an anterior cruciate ligament reconstruction

Objectives To compare the effect of femoral bone tunnel configuration on tendon-bone healing in an anterior cruciate ligament (ACL) reconstruction animal model. Methods Anterior cruciate ligament reconstruction using the plantaris tendon as graft material was performed on both knees of 24 rabbits (48 knees) to mimic ACL reconstruction by two different suspensory fixation devices for graft fixation. For the adjustable fixation device model (Socket group; group S), a 5 mm deep socket was created in the lateral femoral condyle (LFC) of the right knee. For the fixed-loop model (Tunnel group; group T), a femoral tunnel penetrating the LFC was created in the left knee. Animals were sacrificed at four and eight weeks after surgery for histological evaluation and biomechanical testing. Results Histologically, both groups showed a mixture of direct and indirect healing patterns at four weeks, whereas only indirect healing patterns were observed in both groups at eight weeks. No significant histological differences were seen between the two groups at four and eight weeks in the roof zone (four weeks, S: mean 4.8 sd 1.7, T: mean 4.5 sd 0.5, p = 0.14; eight weeks, S: mean 5.8 sd 0.8, T: mean 4.8 sd 1.8, p = 0.88, Mann-Whitney U test) or side zone (four weeks, S: mean 5.0 sd 1.2, T: mean 4.8 sd 0.4, p = 0.43; eight weeks, S: mean 5.3 sd 0.8,T: mean 5.5 sd 0.8, p = 0.61, Mann-Whitney U test) . Similarly, no significant difference was seen in the maximum failure load between group S and group T at four (15.6 sd 9.0N and 13.1 sd 5.6N) or eight weeks (12.6 sd 3.6N and 17.1 sd 6.4N, respectively). Conclusion Regardless of bone tunnel configuration, tendon-bone healing after ACL reconstruction primarily occurred through indirect healing. No significant histological or mechanical differences were observed between adjustable and fixed-loop femoral cortical suspension methods. Cite this article: Y. Sato, R. Akagi, Y. Akatsu, Y. Matsuura, S. Takahashi, S. Yamaguchi, T. Enomoto, R. Nakagawa, H. Hoshi, T. Sasaki, S. Kimura, Y. Ogawa, A. Sadamasu, S. Ohtori, T. Sasho. The effect of femoral bone tunnel configuration on tendon-bone healing in an anterior cruciate ligament reconstruction: An animal study. Bone Joint Res 2018;7:327–335. DOI: 10.1302/2046-3758.75.BJR-2017-0238.R2.

The recognition and incidence of peroneal tendon dislocation associated with a fracture of the talus

Aims The purposes of this study were to clarify first, the incidence of peroneal tendon dislocation in patients with a fracture of the talus and second the factors associated with peroneal tendon dislocation. Patients and Methods We retrospectively examined 30 patients (30 ankles) with a mean age of 37.5 years, who had undergone internal fixation for a fracture of the talus. Independent examiners assessed for peroneal tendon dislocation using the pre‐operative CT images. The medical records were also reviewed for the presence of peroneal tendon dislocation. The associations between the presence of dislocation with the patient characteristics or radiological findings, including age, mechanism of injury, severity of fracture, and fleck sign, were assessed using Fishers exact tests. Results The pre‐operative CT images showed peroneal tendon dislocation in eight out of 30 patients. Dislocation was found later in one patient whose pre‐operative CT image had not shown dislocation. The overall incidence of peroneal tendon dislocation was 30% (9/30). The presence of dislocation was associated with the presence of a fleck sign (p = 0.03). Conclusions Surprisingly, approximately one‐third of the patients who underwent internal fixation for a fracture of the talus had peroneal tendon dislocation. This was associated with a fleck sign.

Incidence and Union Rate of Avulsion Fracture at the Tip of the Fibula for Ankle Sprain in Children Prospective Study

Category: Sports. Introduction/Purpose: Although ankle sprain in children is traditionally diagnosed as Salter-Harris type 1 epiphyseal injury because of negative radiographic findings, recent studies have reported that avulsion fracture at the tip of the fibula may be common. If the fracture remains ununited, it will become os subfibulare, and can cause pain and instability. Therefore recognition of the avulsion fracture is clinically important. However, incidence and radiographic result of the fracture is not well studied. The purposes of this study was 1)to clarify the incidence of avulsion fracture at the tip of the fibula for ankle sprain in children, 2)to assess the utility of the ATFL view proposed by Haraguchi for detection of the avulsion fracture, and 3)to clarify the union rate of the fracture. Methods: Patients who presented four local orthopaedic clinics were prospectively examined. Patients with a first-time inversion sprain, aged from six to twelve years, and visiting to the clinics within forty-eight hours after injury, were included. Patients underwent anteroposterior and lateral radiographs, and the ATFL view (Figure) proposed by Haraguchi at the first visit. Patients with avulsion fracture underwent follow-up radiographs 8 weeks after injury. Incidence of avulsion fracture was assessed using the radiographs at the first visit. If the fracture is visible in at least one of the three images, we diagnosed as fracture. Sensitivity of fracture detection for the standard anteroposterior and lateral view, as well as that of the ATFL view, were also evaluated. Union rate of the avulsion fracture was assessed using the radiographs at 8 weeks. The treatment was not standardized, and ranged from elastic bandage to non-weightbearing cast for 6 weeks. Results: From April 2014 to August 2015, 98 ankles of 98 patients (35 female and 63 male) with a mean age of 8.7 years were included. Overall incidence of avulsion fracture at the tip of the fibula was 61% (61/98 ankles). Fifty-nine avulsion fractures out of 61 were visible in the ATFL view (sensitivity, 98%), while only 28 fractures were visible in the anteroposterior and/or lateral views (sensitivity, 46%). Of the 61 ankles with fractures, 50 ankles underwent radiographs at 8 weeks. The overall union rate was 20% (10/50 ankles). When the patients received casting for 4 weeks or more, the union rate was 40%. When the patients received casting less than 4 weeks the union rate was lower, and 10%. Conclusion: Avulsion fracture at the tip of the fibula was surprisingly common after ankle sprain in children. More than half of the fractures were not detected in standard radiographs of the ankle, and the ATFL view should be taken routinely to detect avulsion fracture. Otherwise the fracture can be overlooked, and a misdiagnosis of Salter-Harris I injury will result. Only 20% of the fractures united after 8 weeks of injury. Although clinical significance of the avulsion fracture is yet to be determined further, the results of this study provide baseline data with which optimal treatment can be studied.

Clinical and Radiographic Outcomes of Foot Orthosis for Hallux Valgus: A Prospective One-Year Follow-Up Study

Category: Bunion Introduction/Purpose: Nonoperative care, which is safer and costs less than operative treatment, is the first-line treatment for hallux valgus. Despite numerous studies have reported results of operative treatments, little information is available on the efficacy of nonoperative treatments for hallux valgus. Foot orthosis, or shoe insole, is one of the most widely used nonoperative treatments. Torkki et al. compared orthotic treatment with operative treatment in a randomized controlled trial, however the subjects were patients who planned to undergo hallux valgus surgery, and thus the patient background was different from clinical setting. It is also controversial whether orthotic treatment can prevent the progression of toe deformity. This prospective one- year follow-up study was conducted to evaluate clinical and radiographic outcomes of foot orthosis for painful hallux valgus. Methods: Patients were recruited prospectively at the foot and ankle clinic of our university hospital from 2011 to 2014. Inclusion criteria were patients over 20 years old, with hallux valgus angle (HVA) greater than 20 degrees, and having a painful hallux and/or forefoot. Patients were informed of both surgical and orthotic treatments regardless of the severity of deformity, and those who selected orthotic treatment were included. One certified orthotist made custom-made total contact insoles, and patients were instructed to wear them as long as possible. Clinical evaluations were performed at baseline, 6 and 12 months. The evaluations included visual analog scale (VAS) for pain, American Academy of Orthopaedic Surgeons (AAOS) foot and ankle score, and SF-36. Patients also reported mean hours a day to wear the orthosis, and treatment satisfaction using VAS at 6 and 12 months. HVA and intermetatarsal angle were measured with the radiographs at baseline and 12 months. Results: Of 158 patients visiting the clinic, 65 patients selected orthotic treatment, and thus included in this study. Mean pain VAS was 48.1 at baseline, and it decreased significantly at 6 months (27.7, p < 0.001). However, it increased slightly at 12 months, although it was still lower than the baseline value (30.6, p=0.002). The AAOS Core Scale was 36.1 at baseline, and it improved significantly at 6 months (42.3, p < 0.001). However the effect of orthosis diminished at 12 month (39.8, p=0.2). The same trend was found for the bodily pain of the SF-36. Patient satisfactions were 54.1 and 54.7 at 6 and 12 months, respectively. The mean HVA and intermetatarsal angle were 41.1 degrees and 17.4 degrees at baseline, and they did not change at 12 months. Conclusion: Wearing total contact shoe insole improved pain and functional outcomes for patients with painful hallux valgus, and the treatment effect lasted for at least 12 months. However, the effect was maximal at 6 months, and diminished slightly at 12 months. Therefore a longer follow-up study is necessary to assess how long the effect will continue. Additionally, the orthotic treatment in this study had no effect on hallux valgus deformity over a 12 month period.