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1.  Local Transplantation of Granulocyte Colony Stimulating Factor-Mobilized CD34+ Cells for Patients With Femoral and Tibial Nonunion: Pilot Clinical Trial 
This paper reports a phase I/IIa clinical trial regarding transplantation of autologous, granulocyte colony stimulating factor-mobilized CD34+ cells with atelocollagen scaffold for patients with femoral or tibial fracture nonunion. The results suggest feasibility, safety, and potential effectiveness of CD34+ cell therapy in patients with nonunion.
Most bone fractures typically heal, although a significant proportion (5%–10%) of fractures fail to heal, resulting in delayed union or persistent nonunion. Some preclinical evidence shows the therapeutic potential of peripheral blood CD34+ cells, a hematopoietic/endothelial progenitor cell-enriched population, for bone fracture healing; however, clinical outcome following transplantation of CD34+ cells in patients with fracture has never been reported. We report a phase I/IIa clinical trial regarding transplantation of autologous, granulocyte colony stimulating factor-mobilized CD34+ cells with atelocollagen scaffold for patients with femoral or tibial fracture nonunion (n = 7). The primary endpoint of this study is radiological fracture healing (union) by evaluating anteroposterior and lateral views at week 12 following cell therapy. For the safety evaluation, incidence, severity, and outcome of all adverse events were recorded. Radiological fracture healing at week 12 was achieved in five of seven cases (71.4%), which was greater than the threshold (18.1%) predefined by the historical outcome of the standard of care. The interval between cell transplantation and union, the secondary endpoint, was 12.6 ± 5.4 weeks (range, 8–24 weeks) for clinical healing and 16.1 ± 10.2 weeks (range, 8–36 weeks) for radiological healing. Neither deaths nor life-threatening adverse events were observed during the 1-year follow-up after the cell therapy. These results suggest feasibility, safety, and potential effectiveness of CD34+ cell therapy in patients with nonunion.
PMCID: PMC3902290  PMID: 24307697
CD34+ cells; Clinical trial; G-CSF; Nonunion; Peripheral blood
2.  Local intra-articular injection of rapamycin delays articular cartilage degeneration in a murine model of osteoarthritis 
Recent studies have revealed that rapamycin activates autophagy in human chondrocytes preventing the development of osteoarthritis (OA) like changes in vitro, while the systemic injection of rapamycin reduces the severity of experimental osteoarthritis in a murine model of OA in vivo. Since the systemic use of rapamycin is associated with numerous side effects, the goal of the current study was to examine the beneficial effect of local intra-articular injection of rapamycin in a murine model of OA and to elucidate the mechanism of action of rapamycin on articular cartilage.
Destabilization of the medial meniscus (DMM) was performed on 10-week-old male mice to induce OA. Intra-articular injections of 10 μl of rapamycin (10 μM) were administered twice weekly for 8 weeks. Articular cartilage damage was analyzed by histology using a semi-quantitative scoring system at 8 and 12 weeks after surgery. Mammalian target of rapamycin (mTOR), light chain 3 (LC3), vascular endothelial growth factor (VEGF), collagen, type X alpha 1 (COL10A1), and matrix metallopeptidase 13 (MMP13) expressions were analyzed by immunohistochemistry. VEGF, COL10A1, and MMP13 expressions were further examined via quantitative RT-PCR (qPCR).
Intra-articular injection of rapamycin significantly reduced the severity of articular cartilage degradation at 8 and 12 weeks after DMM surgery. A reduction in mTOR expression and the activation of LC3 (an autophagy marker) in the chondrocytes was observed in the rapamycin treated mice. Rapamycin treatment also reduced VEGF, COL10A1, and MMP13 expressions at 8 and 12 weeks after DMM surgery.
These results demonstrate that the intra-articular injection of rapamycin could reduce mTOR expression, leading to a delay in articular cartilage degradation in our OA murine model. Our observations suggest that local intra-articular injection of rapamycin could represent a potential therapeutic approach to prevent OA.
PMCID: PMC4269094  PMID: 25403236
3.  Cyclin-dependent kinase inhibitor p21 does not impact embryonic endochondral ossification in mice 
Molecular Medicine Reports  2014;11(3):1601-1608.
Endochondral ossification at the growth plate is regulated by a number of factors and hormones. The cyclin-dependent kinase inhibitor p21 has been identified as a cell cycle regulator and its expression has been reported to be essential for endochondral ossification in vitro. However, to the best of our knowledge, the function of p21 in endochondral ossification has not been evaluated in vivo. Therefore, the aim of this study was to investigate the function of p21 in embryonic endochondral ossification in vivo. Wild-type (WT) and p21 knockout (KO) pregnant heterozygous mice were sacrificed on embryonic days E13.5, E15.5 and E18.5. Sagittal histological sections of the forearms of the embryos were collected and stained with Safranin O and 5-bromo-2′-deoxyuridine (BrdU). Additionally, the expression levels of cyclin D1, type II collagen, type X collagen, Sox9, and p16 were examined using immunohistochemistry, and the expression levels of p27 were examined using immunofluorescence. Safranin O staining revealed no structural change between the cartilage tissues of the WT and p21KO mice at any time point. Type II collagen was expressed ubiquitously, while type X collagen was only expressed in the hypertrophic zone of the cartilage tissues. No differences in the levels of Sox9 expression were observed between the two groups at any time point. The levels of cyclin D1 expression and BrdU uptake were higher in the E13.5 cartilage tissue compared with those observed in the embryonic cartilage tissue at subsequent time points. Expression of p16 and p27 was ubiquitous throughout the tissue sections. These results indicate that p21 may not be essential for embryonic endochondral ossification in articular cartilage of mice and that other signaling networks may compensate for p21 deletion.
PMCID: PMC4270329  PMID: 25376471
endochondral ossification; cell cycle; p21; p27; mouse embryo
4.  Influence of intra-operative parameters on postoperative early recovery of active knee flexion in posterior-stabilized total knee arthroplasty 
International Orthopaedics  2013;37(11):2153-2157.
Active knee flexion is more important for daily activities than passive knee flexion. The hypothesis is that the intra-operative parameters such as osteotomized bone thickness and soft tissue balance affect the postoperative active flexion angle in total knee arthroplasty (TKA). Therefore, we evaluate the influence of intra-operative parameters on postoperative early recovery of active flexion after posterior-stabilized (PS) TKA.
The subjects were 45 osteoarthritic knees undergoing primary PS TKA with anterior-reference technique. Intra-operative soft tissue balance was measured using an offset type tensor, and each osteotomized bone thickness was also measured. Pre- and postoperative active knee flexion angles were measured using lateral radiographs. Liner regression analysis was used to determine the influence of these intra-operative parameters on postoperative active flexion angles or recovery of active flexion angles.
Pre-operative flexion angle was positively correlated with postoperative flexion angle (R = 0.52, P = 0.0002). Postoperative flexion angle was negatively correlated with the osteotomized bone thickness of femoral medial posterior condyle (R = −0.37, P = 0.012), and femoral lateral posterior condyle (R = −0.36, P = 0.015). Recovery of flexion angle was slightly negatively correlated with gap difference calculated by subtracting joint gap at extension from that at flexion between osteotomized surfaces (R = −0.30, P = 0.046).
The osteotomized bone thickness of the femoral posterior condyle is a significant independent factor of postoperative flexion angles. This indicates that the restoration of the posterior condyle offset may lead to larger postoperative active flexion angles in PS TKA.
PMCID: PMC3824896  PMID: 23877717
5.  Management of Intolerance to Casting the Upper Extremities in Claustrophobic Patients 
The Scientific World Journal  2014;2014:803047.
Introduction. Some patients showed unusual responses to the immobilization without any objective findings with casts in upper extremities. We hypothesized their that intolerance with excessive anxiety to casts is due to claustrophobia triggered by cast immobilization. The aim of this study is to analyze the relevance of cast immobilization to the feeling of claustrophobia and discover how to handle them. Methods. There were nine patients who showed the caustrophobic symptoms with their casts. They were assesed whether they were aware of their claustrophobis themselves. Further we investigated the alternative immobilization to casts. Results. Seven out of nine cases that were aware of their claustrophobic tendencies either were given removable splints initially or had the casts converted to removable splints when they exhibited symptoms. The two patients who were unaware of their latent claustrophobic tendencies were identified when they showed similar claustrophobic symptoms to the previous patients soon after short arm cast application. We replaced the casts with removable splints. This resolved the issue in all cases. Conclusions. We should be aware of the claustrophobia if patients showed unusual responses to the immobilization without any objective findings with casts in upper extremities, where removal splint is practical alternative to cast to continue the treatment successfully.
PMCID: PMC4213395  PMID: 25379544
6.  Arthroscopic Ankle Arthrodesis for Treating Osteoarthritis in a Patient with Kashin-Beck Disease 
Case Reports in Medicine  2014;2014:931278.
Kashin-Beck disease (KBD) is an endemic degenerative osteoarthritis. Death of cartilage and growth plate is the pathologic feature; therefore, KBD involves skeletal deformity and often results in osteoarthritis. Deficiency of selenium, high humic acid levels in water, and fungi on storage gains are considered the cause of KBD. The most frequently involved joints are ankles, knees, wrists, and elbows and symptoms are pain and limited motions of those joints. The main treatments for KBD are rehabilitation and osteotomy to correct the deformities because preventive treatment has not been established. In this report, we present a case of ankle osteoarthritis due to KBD and first describe arthroscopic ankle arthrodesis for treating osteoarthritis of KBD.
PMCID: PMC4202255  PMID: 25349619
7.  Long-term subjective outcomes of computer-assisted total knee arthroplasty 
International Orthopaedics  2013;37(10):1911-1915.
This study aimed to clarify the results of computer-assisted total knee arthroplasty (TKA) after ten years using patient-derived scores.
Thirty posterior-stabilised total knee prostheses implanted using a computed tomography-free navigation system were compared with 30 matched total knee prostheses of the same type implanted using a conventional, manual technique. At an average of ten years after surgery, we investigated patient-reported outcomes using the Knee Society’s new scoring system. The results of 27 patients (14 patients in the navigation group and 13 patients in the manual group) were assessed in this study.
There was no significant difference between the navigation and manual groups for any section of the questionnaire, which consisted of symptoms, patient satisfaction, patient expectation, walking/standing, standard activities, advanced activities, and discretionary activities.
After long-term follow-up, we found no subjective advantages of using a navigation system for patients who undergo TKA though the absolute number of patients was very small. Additional extensive studies are required to validate our result.
PMCID: PMC3779564  PMID: 23807729
8.  Involvement of ERCC1 in the Pathogenesis of Osteoarthritis Through the Modulation of Apoptosis and Cellular Senescence 
DNA damage is a cause of age related pathologies, including osteoarthritis (OA). Excision repair cross complementation group 1 (ERCC1) is an endonuclease required for DNA damage repair. In this study we investigated the function of ERCC1 in chondrocytes and its association with the pathophysiology of OA. ERCC1 expression in normal and osteoarthritic cartilage was assessed, as were changes in ERCC1 expression in chondrocytes under catabolic stress. Inhibiting ERCC1 in chondrocytes under interleukin-1β stimulation using small interfering RNA (siRNA) was also evaluated. Finally, cellular senescence and apoptosis were examined in relation to ERCC1 function. ERCC1 expression was decreased in OA cartilage and increased within 4 h of exposure to interleukin (IL)-1β, but decreased after 12 h. The inhibition of ERCC1 by siRNA increased the expression of matrix metallopeptidase 13 and decreased collagen type II. ERCC1 inhibition also increased the number of apoptotic and senescent cells. The inhibition of ERCC1 in chondrocytes increased their expression of OA related proteins, apoptosis, cellular senescence, and hypertrophic-like changes which suggest that ERCC1 is critical for protecting human chondrocytes (HCs) from catabolic stresses and provides insights into the pathophysiology of OA and a potential target for its treatment.
PMCID: PMC4134687  PMID: 24964749
ERCC1; osteoarthritis; apoptosis; senescence; interleukin (IL)-1β
9.  Bicondylar Hoffa Fracture Successfully Treated with Headless Compression Screws 
Case Reports in Orthopedics  2014;2014:139897.
Bicondylar coronal plane fracture, eponymically named Hoffa fractures, is an extremely rare injury. We present a case of isolated unilateral bicondylar Hoffa fracture that was successfully treated with open reduction and internal fixation using headless compression screws with satisfactory results. We inserted posteroanteriorly oriented Acutrak screws perpendicular to the fracture plane via lateral parapatellar arthrotomy, which provided excellent compression across the fracture.
PMCID: PMC4124765  PMID: 25140263
10.  Transcutaneous Carbon Dioxide Induces Mitochondrial Apoptosis and Suppresses Metastasis of Oral Squamous Cell Carcinoma In Vivo 
PLoS ONE  2014;9(7):e100530.
Squamous cell carcinoma (SCC) is the main histological type of oral cancer. Its growth rate and incidence of metastasis to regional lymph nodes is influenced by various factors, including hypoxic conditions. We have previously reported that transcutaneous CO2 induces mitochondrial apoptosis and decreases lung metastasis by reoxygenating sarcoma cells. However, previous studies have not determined the sequential mechanism by which transcutaneous CO2 suppresses growth of epithelial tumors, including SCCs. Moreover, there is no report that transcutaneous CO2 suppresses lymphogenous metastasis using human cell lines xenografts. In this study, we examined the effects of transcutaneous CO2 on cancer apoptosis and lymphogenous metastasis using human SCC xenografts. Our results showed that transcutaneous CO2 affects expressions of PGC-1α and TFAM and protein levels of cleavage products of caspase-3, caspase-9 and PARP, which relatives mitochondrial apoptosis. They also showed that transcutaneous CO2 significantly inhibits SCC tumor growth and affects expressions of HIF-1α, VEGF, MMP-2 and MMP-9, which play essential roles in tumor angiogenesis, invasion and metastasis. In conclusion, transcutaneous CO2 suppressed tumor growth, increased mitochondrial apoptosis and decreased the number of lymph node metastasis in human SCC by decreasing intra-tumoral hypoxia and suppressing metastatic potential with no observable effect in vivo. Our findings indicate that transcutaneous CO2 could be a novel therapeutic tool for treating human SCC.
PMCID: PMC4079455  PMID: 24988190
11.  Excessive femoral offset does not affect the range of motion after total hip arthroplasty 
International Orthopaedics  2013;37(7):1233-1237.
Implant dislocations are often caused by implant or bone impingement, and less impingement is critical to prevent dislocations. The aim of this study was to clarify the effect of the femoral offset in avoiding component or bony impingement after total hip arthroplasty (THA).
Seventy-eight patients underwent THA with a Pinnacle cup and Summit stem (DePuy). Intraoperative kinematic analysis was performed with a navigation system, which was used to obtain intraoperative range of motion (ROM) measurements during trial insertion of stems of two different offset lengths with the same head size. Further, ROM was also measured after actual component insertion.
Maximal ROM was independent of the femoral offset of the stem in each patient. However, the range of external rotation was significantly greater in patients with a greater femoral offset.
The Summit stem has enough offset length to avoid implant/bone impingement, even when the standard offset stem is used. Nevertheless, selection of the offset stem should be performed carefully to prevent offset complications.
PMCID: PMC3685658  PMID: 23553118
12.  Concurrent Rotator Cuff Tear and Axillary Nerve Palsy Associated with Anterior Dislocation of the Shoulder and Large Glenoid Rim Fracture: A “Terrible Tetrad” 
Case Reports in Orthopedics  2014;2014:312968.
We present a case of concurrent rotator cuff tear and axillary nerve palsy resulting from anterior dislocation of the shoulder and a large glenoid rim fracture—a “terrible tetrad.” A 61-year-old woman fell on her right shoulder. Radiographs showed anterior dislocation of the shoulder with a glenoid rim fracture, and an MRI two months after injury revealed a rotator cuff tear. Upon referral to our hospital, physical and electrophysiological examinations revealed axillary nerve palsy. The axillary nerve palsy was incomplete and recovering, and displacement of the glenoid rim fracture was minimal and already united; therefore, we surgically repaired only the rotator cuff tear three months after injury. The patient recovered satisfactorily following the operation. In patients whose axillary nerve palsy is recovering, surgeons should consider operating on rotator cuff tears in an attempt to prevent rotator cuff degeneration.
PMCID: PMC4082929  PMID: 25024858
13.  Evaluation of the accuracy of femoral component orientation by the CT-based fluoro-matched navigation system 
International Orthopaedics  2013;37(6):1063-1068.
Accurate orientation of acetabular and femoral components are important during THA. However, no study has assessed the use of the CT-based fluoro-matched navigation system during THA. Therefore, we have evaluated the accuracy of stem orientation by CT-based fluoro-matched navigation.
The accuracy of stem orientation by CT-based fluoro-matched navigation was assessed by postoperative CT data. Furthermore, we compared the postoperative stem orientation with the intraoperative registration errors.
The average antetorsion error of the stem (navigation records − postoperative CT) was −0.5° ± 5.2°. The stem valgus error was 0.4° ± 2.7°. The accuracy of the navigation record for the orientation of the stem valgus was dependent on the intraoperative registration errors.
The clinical accuracy of CT-based fluoro-matched navigation is adequate for stem alignment orientation, and the intraoperative verification of registration errors is valuable for checking the accuracy of stem orientation by navigation.
PMCID: PMC3664150  PMID: 23512603
14.  Treatment Results of a Periprosthetic Femoral Fracture Case Series: Treatment Method for Vancouver Type B2 Fractures Can Be Customized 
Clinics in Orthopedic Surgery  2014;6(2):138-145.
Currently, an algorithmic approach for deciding treatment options according to the Vancouver classification is widely used for treatment of periprosthetic femoral fractures after hip arthroplasty. However, this treatment algorithm based on the Vancouver classification lacks consideration of patient physiology and surgeon's experience (judgment), which are also important for deciding treatment options. The purpose of this study was to assess the treatment results and discuss the treatment options using a case series.
Eighteen consecutive cases with periprosthetic femoral fractures after total hip arthroplasty and hemiarthroplasty were retrospectively reviewed. A locking compression plate system was used for osteosynthesis during the study period. The fracture type was determined by the Vancouver classification. The treatment algorithm based on the Vancouver classification was generally applied, but was modified in some cases according to the surgeon's judgment. The reasons for modification of the treatment algorithm were investigated. Mobility status, ambulatory status, and social status were assessed before the fracture and at the latest follow-up. Radiological results including bony union and stem stability were also evaluated.
Thirteen cases were treated by osteosynthesis, two by revision arthroplasty and three by conservative treatment. Four cases of type B2 fractures with a loose stem, in which revision arthroplasty is recommended according to the Vancouver classification, were treated by other options. Of these, three were treated by osteosynthesis and one was treated conservatively. The reasons why the three cases were treated by osteosynthesis were technical difficulty associated with performance of revision arthroplasty owing to severe central migration of an Austin-Moore implant in one case and subsequent severe hip contracture and low activity in two cases. The reasons for the conservative treatment in the remaining case were low activity, low-grade pain, previous wiring around the fracture and light weight. All patients obtained primary bony union and almost fully regained their prior activities.
We suggest reaching a decision regarding treatment methods of periprosthetic femoral fractures by following the algorithmic approach of the Vancouver classification in addition to the assessment of each patient's hip joint pathology, physical status and activity, especially for type B2 fractures. The customized treatments demonstrated favorable overall results.
PMCID: PMC4040372  PMID: 24900893
Femur; Periprosthetic fracture; Hip arthroplasty; Vancouver classification
15.  Kinematic factors affecting postoperative knee flexion after cruciate-retaining total knee arthroplasty 
International Orthopaedics  2013;37(5):803-808.
The purpose of this study was to investigate kinematic factors affecting postoperative knee flexion after cruciate-retaining (CR) total knee arthroplasty (TKA) by analysing pre- and postoperative knee kinematics.
We retrospectively analysed 58 patients with osteoarthritis who received the same implant series. Pre- and postoperative kinematics were measured intraoperatively using a navigation system. As a clinical outcome, we measured the knee flexion angle before and one year after surgery. Correlations among pre- and postoperative kinematics and postoperative flexion were analysed using simple linear regression analyses.
Preoperative knee kinematics, including tibial internal rotation and anterior translation (R = 0.87, P < 0.001; R = 0.53, P < 0.001, respectively), were significantly correlated with postoperative kinematics. Preoperative varus–valgus movements improved significantly postoperatively; however, tibial internal rotation remained unchanged. Furthermore, postoperative knee flexion angle was significantly correlated with postoperative tibial internal rotation (R = 0.45, P < 0.001).
Preoperative knee kinematics were unchanged even after CR-TKA. Postoperative tibial internal rotation is one of the most important factors affecting postoperative knee flexion.
PMCID: PMC3631492  PMID: 23460410
16.  In vitro hypertrophy and calcification of human fracture haematoma-derived cells in chondrogenic differentiation 
International Orthopaedics  2013;37(5):961-967.
The haematoma at a fracture site plays an important role in fracture healing. Previously, we demonstrated that a fracture haematoma contains multilineage mesenchymal progenitor cells. We postulated that the haematoma provided a source of chondrogenic cells for endochondral ossification during fracture healing and preservation of the cells contributed to biological fracture healing. In this study, we investigated whether haematoma-derived cells (HCs) could differentiate into hypertrophic chondrocytes and finally induce calcification of the extracellular matrix in vitro.
Fracture haematomas were obtained from four patients. HCs were cultured for five weeks under conditions that induce chondrogenic differentiation, followed by two weeks of hypertrophic induction using a pellet culture system. The pellets were analysed histologically and immunohistochemically. The gene expression levels of chondrogenic, hypertrophic, osteogenic, and angiogenic markers were measured by real-time PCR.
The histological and immunohistochemical analyses revealed that HCs differentiated into chondrocytes and hypertrophic chondrocytes, followed by calcification of the extracellular matrix. This sequential differentiation was also reflected in the gene expression profiles. After chondrogenic induction, expression of osteogenic and angiogenic markers was not significantly upregulated. However, the expression of these markers was significantly upregulated following hypertrophic induction. These in vitro observations mimicked the process of endochondral ossification during fracture healing.
Our results suggest that the fracture haematoma may offer a source of cells with chondrogenic potential that play key roles in endochondral ossification during fracture healing. These findings support the opinion that the haematoma should be preserved for biological fracture healing.
PMCID: PMC3631505  PMID: 23446329
17.  C1 laminectomy for retro-odontoid pseudotumor without atlantoaxial subluxation: review of seven consecutive cases 
European Spine Journal  2013;22(5):1119-1126.
A retro-odontoid pseudotumor is usually a reactive fibrocartilaginous mass associated with atlantoaxial subluxation (AAS). However, a retro-odontoid pseudotumor not associated with AAS, which undergoes spontaneous regression following C1 laminoplasty, has been reported. The purpose of this study was to report surgical outcomes of C1 laminectomy for retro-odontoid pseudotumor without AAS.
Materials and methods
The cases of seven patients (mean age 75.6 ± 7.6 years-old) with retro-odontoid pseudotumor without AAS were reviewed. The mean follow up time was 52.3 ± 25.5 months. Each patient underwent a C1 laminectomy with an additional C3–6 expansion laminoplasty in three patients. The Japanese Orthopaedic Association score (JOA score) was used for neurological assessment. Pseudotumor size and additional AAS were analyzed using MRI and radiography.
All patients exhibited neurological improvement following surgery, the JOA score improved from 7.2 ± 3.2 to 14.1 ± 2.6. The mean O-C2 and C2–7 angle decreased from −3.2 ± 2.1° to −3.9 ± 1.7°, showing a slight kyphotic change. Postoperative AAS was not observed. All pseudotumors spontaneously resolved, and recurrence and regrowth were not observed. Five patients had MRIs after gadolinium administration; four patients who showed enhancement of the pseudotumor had almost complete reduction within 1 year following surgery.
Our study, assessing the outcome of C1 laminectomy for retro-odontoid pseudotumor, found neurological improvement in all cases. Since all pseudotumors were reduced and additional AAS was not observed, C1 laminectomy for retro-odontoid pseudotumor, in the absence of AAS, is recommended as a therapeutic strategy.
PMCID: PMC3657042  PMID: 23386281
Retro-odontoid pseudotumor; Spontaneous regression; C1 laminectomy
18.  Missed Massive Morel-Lavallee Lesion 
Case Reports in Orthopedics  2014;2014:920317.
A Morel-Lavallee lesion (MLL) involves posttraumatic fluid collection around the greater trochanter. Many cases of MLL are missed at the initial evaluation, and the treatment of MLL is not well established. We present two cases in which MLL was missed at the initial evaluation. Case 1. A 65-year-old man was run over by a parade float. There was subcutaneous hematoma around the left greater trochanter, and no fracture was found. We diagnosed this injury as MLL on the 7th day after the trauma. Although we performed percutaneous drainage, the injured area was infected. Case 2. A 57-year-old man was hit by a train in a factory. There was an iliac wing fracture, but an MLL was not initially recognized. On the 6th day after the trauma, when performing open reduction and internal fixation for the iliac fracture, we recognized the lesion and performed percutaneous drainage simultaneously. This lesion also became infected. In these two cases, the wounds finally healed after a long duration of treatment. We suggest that it is important to keep this injury in mind and debride the lesion early and completely in the treatment course.
PMCID: PMC3985225  PMID: 24800092
19.  Dreams come true: the soul and spirit of orthopaedics 
Journal of Orthopaedic Science  2014;19(2):205-206.
PMCID: PMC3960481  PMID: 24595646
20.  The influence of patella height on soft tissue balance in cruciate-retaining and posterior-stabilised total knee arthroplasty 
International Orthopaedics  2012;37(3):421-425.
Although the patella reduced or everted position has recently been recognised as an important factor influencing soft tissue balance during assessment in total knee arthroplasty (TKA), the influence of patella height on soft tissue balance has not been well addressed. Therefore, the relationship between soft tissue balance and patella height was investigated and differences between cruciate-retaining (CR) and posterior-stabilised (PS) TKA were compared.
Forty consecutive patients blinded to the type of implant received, were randomised prospectively. Using lateral radiographs, pre-operative patella height was measured. Using an offset-type tensor designed to measure the soft tissue balance with a reduced patellofemoral (PF) joint and femoral component in place, soft tissue balance was intra-operatively assessed in CR TKA (n = 20) and PS TKA (n = 20) in osteoarthritic patients. The joint component gap and varus ligament balance at zero, ten, 45, 90 and 135° of knee flexion with the patella reduced were measured.
In PS TKA, the joint component gap positively correlated with patella height at 90 and 135° of knee flexion. However, there was no correlation between joint component gap and patella height at other flexion angles in PS TKA and any flexion angle in CR TKA. Varus ligament balance showed no significant correlation with patella height in either CR or PS TKA.
Analysis of soft tissue balance and patella height only showed a positive correlation in joint component gap at a high flexion angle (90 and 135°) in PS TKA but not in other parameters examined. Pre-operative measurement of patella height may be an important factor for predicting an intra-operative flexion gap in PS TKA.
PMCID: PMC3580105  PMID: 23275081
21.  Notochordal cell disappearance and modes of apoptotic cell death in a rat tail static compression-induced disc degeneration model 
The intervertebral disc has a complex structure originating developmentally from both the mesenchyme and notochord. Notochordal cells disappear during adolescence, which is also when human discs begin to show degenerative signs. During degeneration later in life, disc cells decline because of apoptosis. Although many animal models have been developed to simulate human disc degeneration, few studies have explored the long-term changes in cell population and phenotype. Our objective was to elucidate the time-dependent notochordal cell disappearance and apoptotic cell death in a rat tail static compression-induced disc degeneration model.
Twenty-four 12-week-old male Sprague–Dawley rat tails were instrumented with an Ilizarov-type device and loaded statically at 1.3 MPa for up to 56 days. Loaded and distal-unloaded discs were harvested. Changes in cell number and phenotype were assessed with histomorphology and immunofluorescence. Apoptosis involvement was determined with terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining and immunohistochemistry.
The number of disc nucleus pulposus and annulus fibrosus cells decreased with the loading period; particularly, the decrease was notable at day 7 in larger, vacuolated, cytokeratin-8- and galectin-3-co-positive cells, indicating notochordal origin. Subsequently, the proportion of cells positive for TUNEL and cleaved caspase-3, markers of apoptosis induction, increased from day 7 through day 56. Although the percentage of cells immunopositive for cleaved caspase-8, a marker of apoptosis initiation through the death-receptor pathway, increased only at day 7, the percentage of cells immunopositive for cleaved caspase-9 and p53-regulated apoptosis-inducing protein 1 (p53AIP1), markers of apoptosis initiation through the p53-mediated mitochondrial pathway, increased from day 7 through day 56. The percentage of cells immunopositive for B-cell lymphoma 2 (Bcl-2) and silent mating type information regulation 2 homolog 1 (SIRT1), antiapoptotic proteins, decreased consistently with compression.
This rat tail model mimics notochordal cell disappearance and apoptotic cell death in human disc aging and degeneration. Sustained static compression induces transient activation of apoptosis through the death-receptor pathway and persistent activation of apoptosis through the p53-mediated mitochondrial pathway in disc cells. The increased proapoptotic and decreased antiapoptotic proteins observed at all time points signify static compression-induced disc cell death and degeneration.
PMCID: PMC3979117  PMID: 24472667
22.  Obese patients may have more soft tissue impingement following primary total hip arthroplasty 
International Orthopaedics  2012;36(12):2419-2423.
Several studies have reported a risk of dislocation in obese patients after total hip arthroplasty. In this study, we evaluated the interaction between obesity and dislocation by kinematic analysis using a navigation system.
The intraoperative range of motion (ROM) and postoperative impingement-free ROM were measured in 38 patients, and we compared the impingement-free ROM in obese and non obese patients.
The postoperatively simulated ROM was similar in the obese and non obese groups. The intraoperative ROM was smaller in the obese group. The difference values between the intraoperative ROM and postoperatively simulated ROM were larger in the obese group. These results indicate that obese patients have less ROM following primary total hip arthroplasty even when the implant positioning is performed correctly.
Dislocations are multifactorial problems including soft tissue impingement. Therefore, the risk of dislocation caused by soft tissue impingement in obese patients may be increased.
PMCID: PMC3508038  PMID: 23135350
23.  Osteochondral autograft transplantation for juvenile osteochondritis dissecans of the knee: a series of twelve cases 
International Orthopaedics  2012;36(11):2243-2248.
The purpose of this study was to evaluate the clinical outcomes of osteochondral autograft transplantation (OAT) for juvenile osteochondritis dissecans (JOCD) lesions of the knee, especially time to return to sports.
Twelve knee JOCD lesions with OCD grade 3 and 4 categorised by magnetic resonance imaging (MRI) were treated with OAT. Nine male and two female skeletally immature patients averaging 13.7 years old were included. The OCD lesions were assessed arthroscopically and then fixed in situ using multiple osteochondral plugs harvested under fluoroscopy from the distal femoral condyle without damaging the physis. International Cartilage Repair Society (ICRS) score and Lysholm score were assessed pre- and postoperatively.
After a mean follow-up of 26.2 ± 15.1 months, the International Knee Documentation Committee (IKDC) subjective score significantly improved (p < 0.01). According to the IKDC score, objective assessment showed that ten of 12 (83 %) had excellent results (score: A) after OAT and significantly improved (p < 0.01). Based on ICRS criteria, results were satisfactory in all patients. No patients experienced complications at the graft harvest site. All patients returned to their previous level of athletic activity at an average of 5.7 months after the surgery.
OAT for JOCD of the knee provided satisfactory results in all patients at a mean follow-up of 26.2 months.
PMCID: PMC3479294  PMID: 22955675
24.  Ligament regeneration using an absorbable stent-shaped poly-l-lactic acid scaffold in a rabbit model 
International Orthopaedics  2012;36(11):2379-2386.
Ligaments are frequently damaged in sports activities and trauma, and severe ligament injury can lead to joint instability and osteoarthritis. In this study, we aimed to regenerate the medial collateral ligament (MCL) using an absorbable stent-shaped poly-l-lactic acid (PLLA) scaffold in a rabbit model to examine the biocompatibility and mechanical properties.
Twenty-three Japanese white rabbits were used in this study. MCL defects were surgically created in the knee joints and then reconstructed using stent-shaped PLLA scaffolds. As controls, flexor digitorum longus (FDL) tendons were implanted into the contralateral knees. Seven rabbits were sacrificed at three time points, conducted four, eight and 16 weeks after the operation. The regenerated tissues were histologically evaluated using fibre alignment scoring, morphology of fibroblast scoring and immunohistochemical analysis of types I and III collagen. The regenerated tissues were also biomechanically evaluated by measuring the ultimate failure load and stiffness.
At four weeks post-operation, spindle-shaped cells were observed on the inside of the scaffolds. At eight weeks, maturation of the regenerated tissues and collagen fibre alignment parallel to the ligaments was observed. At 16 weeks, the fibre alignment had become denser. The fibre alignment and morphology of fibroblast scores significantly increased in a time-dependent manner. Expression of type I collagen was more strongly observed in the scaffold group at eight and 16 weeks post-operation than at four weeks. Type III collagen was also observed at four, eight and 16 weeks post-operation. A thin layer of fibrocartilage was observed at the ligament-bone junction at eight and 16 weeks. The ultimate failure load of the scaffold group was 46.7 ± 20.7 N, 66.5 ± 11.0 N and 74.3 ± 11.5 N at four, eight and 16 weeks post-operation, respectively. There was no statistical difference between the normal MCL and the scaffold group at 16 weeks post-operation.
The stent-shaped PLLA scaffold allowed for MCL regeneration with type I collagen expression and fibrocartilage formation and resulted in sufficient mechanical function.
PMCID: PMC3479301  PMID: 22976595
25.  In vivo comparisons of patellofemoral kinematics before and after ADVANCE® Medial-Pivot total knee arthroplasty 
International Orthopaedics  2012;36(10):2073-2077.
ADVANCE® Medial-Pivot (MP) (Wright Medical Technology, Arlington, TN, USA) total knee arthroplasty (TKA) was developed to replicate normal tibiofemoral knee joint kinematics, allowing medial-pivot knee motion. The design concept of the prosthesis is unique; therefore, the influence on the patellofemoral knee joint remains unclear at present. The purpose of this study was to determine the in vivo patellofemoral kinematics with ADVANCE® MP TKA and compare them with the pre-operative conditions.
ADVANCE® MP TKA was performed in ten subjects with osteoarthritis (OA). At before and one month after surgery, lateral radiographs with weight-bearing at maximum extension, 30, 60 and 90° were taken, and patella flexion angle (PF), tibiopatellar angle (TP) and estimated patellofemoral contact point (PC) were evaluated, according to a previously reported method.
In PF and TP, there was no statistically significant change between pre-operative and postoperative values. Pre-operative PC reached its peak at 90°; however, its peak was at 60° at one month after surgery. Postoperative PC at maximum extension was significantly higher compared to before surgery.
The results in this study indicated that ADVANCE® MP TKA changed patellofemoral joint kinematics compared to before surgery. Early postoperative evaluation is the limitation of this study; however, we consider that the results in this study might be one of the keys to resolving the kinematic features of this prosthesis, helping clinicians to comprehend this prosthesis.
PMCID: PMC3460083  PMID: 22885803

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