Lateral wall fixation with bone pegs for advanced osteochondritis dissecans of the humeral capitellum.

BACKGROUND AND HYPOTHESIS: It is generally considered that fragment fixation with bone pegs (FFBP) for osteochondritis dissecans (OCD) of the humeral capitellum can be indicated for stages I and II according to the International Cartilage Repair Society (ICRS) classification of OCD and it is difficult to obtain complete bone union for advanced lesions. However, the clinical and radiologic results of FFBP with cancellous bone graft for ICRS-OCD stage III with lateral wall involvement have not been described in detail. Good bone union can be achieved with the lateral wall fragment of the capitellum by FFBP in combination with refreshing the sclerotic surface at the base of the lesion and cancellous bone grafting even in ICRS-OCD stage III lesions. METHODS: In total, 10 adolescent baseball players with a diagnosis of OCD, a median age of 13.5 years at the time of surgery, and 26.7 months of postoperative follow-up were included. Preoperative imaging showed that all patients had lesions in the late detached stage and of the lateral-widespread type based on the site of the focal lesion. The intraoperative ICRS-OCD classification was stage III. We aimed to preserve and fix the lateral wall fragment with cancellous bone grafting if the condition of the articular cartilage was good and the size and thickness of the segment could withstand fixation. RESULTS: Bone union of the lateral wall fragment was achieved in all cases. The elbow extension range of motion was -3.9° ± 9.7° before surgery and was eventually -0.4° ± 6.7° at the final assessment. Flexion range of motion ranged from 138.1° ± 10.5° to 142.4° ± 6.2°. The Timmerman and Andrews score significantly improved from 165.5 ± 10.9 points before surgery to 197.0 ± 6.3 points after surgery, demonstrating excellent results in all patients. All patients were able to return to competitive baseball. CONCLUSION: The radiographic and clinical outcomes of FFBP for lateral wall fragments with cancellous bone graft were satisfactory, showing that the indications for this procedure could be extended to ICRS-OCD stage III.

Conservative treatment of severe clubfoot using a novel functional dynamic splint.

Forty-six severe clubfeet in 29 patients were treated by serial castings, followed by a newly developed dynamic splint. The mean period of splint usage was 59.9 months and the mean period of follow-up was 81.5 months. Of the patients, 76.1% were satisfied, 87.0% had no functional deficit, and 84.8% had no pain. Radiographical evaluation showed good correction. The mean dorsiflexion angle was -0.8° at the end of cast treatment and 13.6° at the time of the final follow-up. This study clearly showed the effectiveness of a functional dynamic splint for the correction of equinus in cases of severe clubfoot.

Strong adhesiveness of a new biodegradable hydrogel glue, LYDEX, for use on articular cartilage.

AIM: Until recently, only fibrin glue has been available for clinical usage to repair articular cartilage, although its adhesiveness is not strong enough for use with articular cartilage, and it is derived from human blood and thus carries the risk of contamination. Recently, LYDEX, a new biodegradable hydrogel glue, has come onto the market. The purpose of this study was to evaluate the adhesive strength and cytotoxicity of LYDEX when used on articular cartilage. MATERIALS AND METHODS: The differing adhesive strengths of collagen membrane and articular cartilage with LYDEX versus with fibrin glue were measured using a tensile tester. In addition, the cytotoxicity of LYDEX in vitro was evaluated. The cytotoxicity of LYDEX for the articular cartilage of rats was evaluated histopathologically. RESULTS: The adhesive strength of LYDEX was significantly stronger than that of fibrin glue, giving values about 3.8 times higher. LYDEX has no discernible effect on normal articular cartilage. CONCLUSIONS: Our study is the first to assess the usefulness and safety of LYDEX for use on articular cartilage.

Articular cartilage repair with magnetic mesenchymal stem cells.

BACKGROUND: Cell therapies are hampered by the difficulty of delivering cells to and retaining them in target tissues long enough to repair or regenerate local tissues. HYPOTHESIS: Magnetic-assisted delivery of magnetically labeled mesenchymal stem cells (m-MSCs) would be rapid, allowing for chondrogenic differentiation and functional joint repair without replacement. STUDY DESIGN: Controlled laboratory study. METHODS: Sixteen mini-pigs aged 6 to 7 months were used. A full-thickness cartilage defect was created in the center of the patella with a cylindrical punch (diameter, 6 mm). At 4 weeks after creation of the cartilage defects, the animals were divided into 3 treatment groups: In the M group, m-MSCs (5 × 10(6) cells) were injected and accumulated to the cartilage defect using an external magnetic force (1.5 T) for 10 minutes; in the G group, the patella was faced upward, filled with MSCs (5 × 10(6) cells), and held for 10 minutes; and in the C group, only phosphate-buffered saline was injected. The regenerated cartilage was evaluated in 5 knees in each of the 3 groups by arthroscopic surgery at 6 and 12 weeks and histological and ultrasound evaluation at 12 and 24 weeks. RESULTS: The mean arthroscopic scores at 6 weeks were 10.4 ± 1.10 in the M group, 8.8 ± 0.84 in the G group, and 7.4 ± 0.89 in the C group. There was a statistically significant difference between the M group and the other 2 groups. The mean arthroscopic scores at 12 weeks were 12.8 ± 1.30 (M group), 10.5 ± 1.30 (G group), and 9.5 ± 0.58 (C group), with a statistically significant difference between the M and C groups. The mean histological scores using the Wakitani scoring system at 12 weeks were 2.8 ± 0.96 (M group), 5.4 ± 0.55 (G group), and 6.0 ± 2.20 (C group), and the mean histological scores at 24 weeks were 2.4 ± 1.50 (M group), 3.5 ± 0.56 (G group), and 5.3 ± 1.50 (C group). The mean histological scores at 12 weeks were significantly better in the M group than in the other groups, and the M group maintained a significantly better histological score than did the C group at 24 weeks. CONCLUSION: The m-MSCs had no adverse effect on chondrogenic differentiation, and m-MSCs delivered by magnetic field application repaired cartilage defects. CLINICAL RELEVANCE: The clinical application of this novel stem cell delivery system is a potential therapeutic option for treating cartilage defects and may be more applicable throughout the body than traditional methods.

Evaluation of joint position sense measured by inversion angle replication error in patients with an osteochondral lesion of the talus.

The etiology of the osteochondral lesion of the talar dome (OLT) remains unclear. A joint position sense deficit of the ankle is reported to be a possible cause of ankle disorder. Repeated contact of the articular surface of the talar dome with the plafond during inversion might be a cause of OLT. The aim of the present study was to evaluate the joint position sense deficit by measuring the replication error of the inversion angle in patients with OLT. The replication error, which is the difference between the index angle and replication angle in inversion, was measured in 15 patients with OLT. The replication error in 15 healthy volunteers was evaluated as a control group. The side to side differences of the replication errors between the patients with OLT and healthy volunteers and the replication errors in each angle between the involved and uninvolved ankle in the patients with OLT were investigated. Finally, the side to side differences of the replication errors between the patients with OLT with a traumatic and nontraumatic history were compared. The side to side difference in the patients with OLT (1.3° ± 0.2°) was significantly greater than that in the healthy subjects (0.4° ± 0.7°) (p ≤ .05). Significant differences were found between the involved and uninvolved sides at 10°, 15°, 20°, and 25° in the patients with OLT. No significant difference (p > .05) was found between the patients with traumatic and nontraumatic OLT. The present study found that the patients with OLT have a joint position sense deficit during inversion movement, regardless of a traumatic history. Although various factors for the etiology of OLT have been reported, the joint position sense deficit in inversion might be a cause of OLT.

Overexpression of microRNA-223 in rheumatoid arthritis synovium controls osteoclast differentiation.

OBJECTIVES: MicroRNAs, a class of noncoding RNAs, play roles in human diseases. MicroRNA-223 (miR-223) is reported to play critical roles in osteoclastogenesis. The purpose of this study was to analyze the expression pattern of miR-223 in rheumatoid arthritis (RA) synovium and examine the suppression of osteoclastogenesis from human peripheral blood mononuclear cells (PBMC) by overexpression of miR-223. METHODS: Expression of miR-223 in synovium from RA patients was analyzed by quantitative reverse transcription polymerase chain reaction (RT-PCR) and section in situ hybridization. MiR-223 was overexpressed in an osteoclastogenesis coculture system with PBMC and RA synovial fibroblast. At 3 weeks after transfection of double-stranded miR-223, the formation of tartrate-resistant acid phosphatase (TRAP)-stained multinucleated cells was analyzed to evaluate the inhibitory effect of miR-223 on osteoclastogenesis. RESULTS: MiR-223 was more highly expressed in RA synovium than in osteoarthritis (OA) synovium due to the increased number of miR-223-positive cells in RA synovium. MiR-223 was expressed in the superficial and sublining layers, and macrophages, monocytes, and CD4 T cells also expressed miR-223. The number of TRAP-positive multinucleated cells was significantly decreased by overexpression of miR-223 in a dose-dependent manner. The expression of osteoclastogenesis marker genes was significantly down-regulated by miR-223 overexpression. CONCLUSION: MiR-223 is intensely expressed in RA synovium, and overexpression of miR-223 suppresses osteoclastogenesis in vitro. This study demonstrates the possibility of gene therapy with miR-223 to treat bone destruction in RA patients.

Characteristic shape of the lateral femoral condyle in patients with osteochondritis dissecans accompanied by a discoid lateral meniscus.

BACKGROUND: There are various indirect signs of a discoid lateral meniscus in radiographs, for example lateral joint space widening, hypoplasia of the LFC, etc. There has, however, been no previous report of the characteristic shape of the lateral femoral condyle (LFC) in patients with osteochondritis dissecans (OCD) accompanied by a discoid lateral meniscus. The purpose of this study was to evaluate the characteristic shape of the LFC in patients with OCD accompanied by a discoid lateral meniscus, and sex differences associated with the shape of the LFC in those patients. METHODS: This study included 29 males (31 knees) and 29 females (32 knees) of average age 17.7 years. There were 15 knees in 15 patients that were accompanied by OCD of the LFC (9 males, 9 knees; 6 females, 6 knees; average age 14.9 years; OCD group). There were 48 knees in 43 patients that were not accompanied by OCD of the LFC (20 males, 22 knees; 23 females, 26 knees; average age 17.6 years; non-OCD group). Standardized Rosenberg view radiographs of the knee were obtained for all patients. We evaluated the shape of LFC using the Rosenberg view and measured the condylar prominence ratio of the medial and lateral condyles adjacent to the intercondylar notch, in accordance with Ha's procedure. RESULTS: The OCD group had a significantly larger prominence ratio than the non-OCD group. The prominence ratio for males was significantly larger than that for females. CONCLUSION: We clearly demonstrated that the prominence ratio in the OCD group was significantly larger than that in the non-OCD group, indicating that the shape of the LFC and OCD in the LFC may be associated with the development of these lesions.

Changes in microRNA expression in peripheral mononuclear cells according to the progression of osteoarthritis.

MicroRNAs (miRNAs) are a family of non-coding RNAs that play an important role in human diseases, including osteoarthritis (OA). The objective of this study was to investigate the expression patterns of miRNAs in the peripheral blood mononuclear cells (PBMCs) of OA patients. PBMCs were isolated from 36 patients with OA, 6 RA patients, and 36 healthy controls. The expression patterns of miR-146a, 155, 181a, and 223 in PBMCs were analyzed using quantitative reverse transcription-polymerase chain reaction (qPCR). We investigated the expression patterns of the miRNAs in OA progression, and their relationships with the parameters of age, body mass index (BMI), the femorotibial angle (FTA), and serum keratan sulfate (KS). The relative expression levels of miR-146a, 155, 181a, and 223 in the OA patients were significantly higher than those found in healthy controls. In the early stages of OA, miR-146a and 223 expressions were significantly higher than they were at later stages. There was a significant correlation between the expression of miR-223 and KS. This study demonstrated that high expression levels of miR-146a, 155, 181a, and 223 in the PBMCs of OA patients might be related to the pathogenesis of OA. This evidence could lead to the elucidation of the mechanism underlying OA pathogenesis and hence to a novel therapeutic strategy for OA.

Determination of the safe penetration depth during all-inside meniscal repair of the posterior part of the lateral meniscus using the FasT-Fix suture repair system.

PURPOSE: The objective of this study was to determine the safe penetration depth of the FasT-Fix meniscal suture repair system during all-inside repair of the posterior part of the lateral meniscus. METHODS: Thirty-one knees from 17 embalmed and formalin-fixed cadavers (11 women, 6 men) were used. In each case, the circumference of the cadaver knee was measured before dissection. After dissection, 41 Fast-Fix meniscal repair devices were used in different predetermined penetration depths ranging from 8 to 16 mm. In this study, non-involvement of the popliteal neurovascular bundle, common peroneal nerve or the inferior lateral genicular vessels by either needle penetration or affixment by the suture bar anchors was considered to be a safe trial. RESULTS: Out of the 41 FasT-Fix devices used in this study, only one device bent during introduction and was excluded from the study. For the remaining 40 trials, 27 of them were considered safe, while 13 trials were considered unsafe. The ratio of the average penetration depth to the average circumference of the cadaver knee was found to be >0.05 for the unsafe penetrations, and this was statistically significant P < 0.05. Additionally, for the first point, which is more central, there was a trend for the straight needles through the direct lateral approach to be less safe, and this was found to be statistically significant P < 0.05. CONCLUSIONS: Correlating the needle-penetration depth to the measured circumference of the cadaver knee may be an important clinical predictor of safety whereby a ratio of less than 0.05 might be useful as a guide to determine the safe penetration depth of the FasT-Fix suture repair needle during repair of the posterior horn lateral meniscus. Also, it is better to avoid using straight needles through the direct lateral approach during repair of the more central portion of the posterior horn lateral meniscus.

The inhibitory effect of microRNA-146a expression on bone destruction in collagen-induced arthritis.

OBJECTIVE: MicroRNA, a class of noncoding RNA, play a role in human diseases. MicroRNA-146a (miR-146a) is a negative regulator of immune and inflammatory responses, and is strongly expressed in rheumatoid arthritis (RA) synovium and peripheral blood mononuclear cells (PBMCs). This study was undertaken to examine whether miR-146a expression inhibits osteoclastogenesis, and whether administration of miR-146a prevents joint destruction in mice with collagen-induced arthritis (CIA). METHODS: PBMCs from healthy volunteers were isolated and seeded in culture plates. The following day, double-stranded miR-146a was transfected and cultured in the presence of macrophage colony-stimulating factor and either tumor necrosis factor α or RANKL. After 3 weeks, tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells were counted. Three days after miR-146a culture, the expression of c-Jun, nuclear factor of activated T cells c1 (NF-ATc1), PU.1, and TRAP was evaluated by quantitative reverse transcriptase-polymerase chain reaction. After the onset of distinct arthritis in mice with CIA, double-stranded miR-146a or nonspecific double-stranded RNA was administered twice by intravenous injection. Radiographic and histologic examinations were performed at 4 weeks. RESULTS: The number of TRAP-positive multinucleated cells in human PBMCs was significantly reduced by miR-146a in a dose-dependent manner. The expression of c-Jun, NF-ATc1, PU.1, and TRAP in PBMCs was significantly down-regulated by miR-146a. Administration of miR-146a prevented joint destruction in mice with CIA, although it did not completely ameliorate inflammation. CONCLUSION: Our findings indicate that expression of miR-146a inhibits osteoclastogenesis and that administration of double-stranded miR-146a prevents joint destruction in arthritic mice. Administration of miR-146a has potential as a novel therapeutic target for bone destruction in RA.

Effects of unloading bracing on knee and hip joints for patients with medial compartment knee osteoarthritis.

BACKGROUND: Osteoarthritis affects the whole body, thus biomechanical effects on other joints should be considered. Unloading knee braces could be effective for knee osteoarthritis, but their effects on the contralateral knee and bilateral hip joints remain unknown. This study investigated the effects of bracing on the kinematics and kinetics of involved and contralateral joints during gait. METHODS: Nineteen patients with medial compartment knee osteoarthritis were analysed. Kinematics and kinetics of the knee and hip joints in frontal and sagittal planes were measured during walking without and with bracing on the more symptomatic knee. FINDINGS: The ipsilateral hip in the braced condition showed a lower adduction angle by an average of 2.58° (range, 1.05°-4.16°) during 1%-49% of the stance phase, and a lower abduction moment at the second peak during the stance phase than the hip in the unbraced condition (P<0.05 and P<0.005, respectively). With bracing, the contralateral hip showed a more marked peak extension moment and lower abduction moment at the first peak (P<0.05), and the contralateral knee adduction angle increased by an average of 0.32° (range, 0.21°-0.45°) during 46%-55% of the stance phase (P<0.05), compared to no bracing. INTERPRETATION: Unloading bracing modified the contralateral knee adduction angle pattern at a specific time point during gait. It also affected the frontal plane on the ipsilateral hip and the frontal and sagittal planes on the contralateral hip joint. Consideration should be provided to other joints when treating knee osteoarthritis.

Medial patellofemoral ligament reconstruction fixed with a cylindrical bone plug and a grafted semitendinosus tendon at the original femoral site for recurrent patellar dislocation.

BACKGROUND: The medial patellofemoral ligament (MPFL) is the most important factor for stabilizing the patella and preventing lateral patellar dislocation. Medial patellofemoral ligament reconstruction is an accepted surgical technique to restore patellofemoral stability after lateral patellar dislocation. The authors recently developed a new anatomical MPFL reconstruction method using a cylindrical bone plug and grafted semitendinosus tendon at the anatomical femoral attachment site to mimic the native MPFL. This study evaluated the new technique for stabilizing recurrent patellar dislocation. HYPOTHESIS: This new MPFL reconstruction technique will improve knee symptoms and function with excellent clinical results. STUDY DESIGN: Case series; Level of evidence, 4. METHOD: Thirty-one knees were evaluated from 29 cases of recurrent patellar dislocation that were surgically treated using the anatomical MPFL reconstruction technique. The average patient age was 22.2 years (range, 12-34 years); postsurgery follow-up was 2 to 5 years (average, 3.2 years). The patients were clinically evaluated based on the Kujala score, range of motion, and signs of apprehension. The Merchant view was used to measure congruence and tilting angles. RESULTS: Of the 31 knees, 30 showed good clinical results after surgery, while 1 patient showed remaining signs of apprehension. The Kujala score improved from an average of 64 points (range, 35-70) initially to an average of 94.5 points (range, 79-100) at the final follow-up. Range of motion improved for all patients, with an average knee extension of 0° ± 2° and knee flexion of 145° ± 3° at final follow-up. No patellar redislocation was reported. Radiological assessment indicated significant improvement to the congruence angle from 13° ± 4° before surgery to -5° ± 5° at the final follow-up, while the tilting angle went from 8° ± 7° before surgery to 7° ± 4° at the final follow-up. CONCLUSION: This study demonstrated excellent results using the new procedure for recurrent dislocation of the patella, with instability in only 1 of 31 knees (3.2%).

Silencing microRNA-34a inhibits chondrocyte apoptosis in a rat osteoarthritis model in vitro.

OBJECTIVE: miRNAs, which are non-coding RNAs, play a role in the pathogenesis of disease including OA. miRNA (miR)-34a is induced by p53, subsequently leading to cell apoptosis, which is one of the major factors in the pathogenesis of OA. The purpose of this study is to investigate the effect of silencing miR-34a on IL-1ß-induced chondrocyte apoptosis in a rat OA model in vitro. METHODS: Locked nucleotide analogue (LNA)-modified miR-34a-specific anti-sense was transfected into rat chondrocyte monolayer culture. After that, IL-1ß was added to the chondrocytes to create an OA model in vitro. The effect of silencing miR-34a on the prevention of chondrocyte apoptosis was analysed by assessment of the expression levels of Col2a1 and iNOS, also through assessment of cell viability and TUNEL staining. RESULTS: The expression of miR-34a was significantly up-regulated by IL-1ß. Silencing of miR-34a significantly prevented IL-1ß-induced down-regulation of Col2a1, as well as IL-1ß-induced up-regulation of iNOS. Finally, MiR-34a inhibitor could also reduce TUNEL-positive cells. CONCLUSION: Silencing of miR-34a by LNA-modified anti-sense could effectively reduce rat chondrocyte apoptosis induced by IL-1ß. This present study revealed that silencing of miR-34a might develop a novel intervention for OA treatment through the prevention of cartilage degradation.

Acceleration of muscle regeneration by local injection of muscle-specific microRNAs in rat skeletal muscle injury model.

MicroRNA (miRNA)s are a class of non-coding RNAs that regulate gene expression post-transcriptionally. Muscle-specific miRNA, miRNA (miR)-1, miR-133 and miR-206 play a crucial role in the regulation of muscle development and homeostasis. Muscle injuries are a common musculoskeletal disorder, and the most effective treatment has not been established yet. The purpose of this study was to demonstrate that a local injection of double-stranded (ds) miR-1, miR-133 and 206 can accelerate muscle regeneration in a rat skeletal muscle injury model. After the laceration of the rat tibialis anterior muscle, ds miR-1, 133 and 206 mixture mediated atelocollagen was injected into the injured site. The control group was injected with control siRNA. At 1 week after injury, an injection of miRNAs could enhance muscle regeneration morphologically and physiologically, and prevent fibrosis effectively compared to the control siRNA. Administration of exogenous miR-1, 133 and 206 can induce expression of myogenic markers, MyoD1, myogenin and Pax7 in mRNA and expression in the protein level at 3 and 7 days after injury. The combination of miR-1, 133 and 206 can promote myotube differentiation, and the expression of MyoD1, myogenin and Pax7 were up-regulated in C2C12 cells in vitro. Local injection of miR-1, 133 and 206 could be a novel therapeutic strategy in the treatment of skeletal muscle injury.

Induction of apoptosis in the synovium of mice with autoantibody-mediated arthritis by the intraarticular injection of double-stranded MicroRNA-15a.

OBJECTIVE: MicroRNA is a family of noncoding RNAs that exhibit tissue-specific or developmental stage-specific expression patterns and are associated with human diseases. MicroRNA-15a (miR-15a) is reported to induce cell apoptosis by negatively regulating the expression of Bcl-2, which suppresses the apoptotic processes. The purpose of this study was to investigate whether double-stranded miR-15a administered by intraarticular injection could be taken up by cells and could induce Bcl-2 dysfunction and cell apoptosis in the synovium of arthritic mice in vivo. METHODS: Autoantibody-mediated arthritis was induced in male DBA/1J mice. In the experimental group, double-stranded miR-15a labeled with FAM-atelocollagen complex was injected into the knee joint. In the control group, control small interfering RNA-atelocollagen complex was injected into the knee joint. Synovial expression of miR-15a was analyzed by quantitative polymerase chain reaction, FAM by fluorescence microscopy, Bcl-2 by Western blotting, and Bcl-2 and caspase 3 by immunohistochemistry. RESULTS: The expression of miR-15a in the synovium of the experimental group was significantly higher than that in the control group. Green fluorescence emission of FAM was observed in the synovium of the experimental group. Bcl-2 protein was down-regulated and the expression of caspase 3 was increased as compared with that in the control group. CONCLUSION: These results indicate that the induction of cell apoptosis after intraarticular injection of double-stranded miR-15a occurs through inhibition of the translation of Bcl-2 protein in arthritic synovium.

Potential risks of femoral tunnel drilling through the far anteromedial portal: a cadaveric study.

PURPOSE: The purpose of this study was to estimate the potential risks when drilling femoral tunnels through the far anteromedial portal in double-bundle anterior cruciate ligament reconstruction in cadaveric knees. METHODS: Ten cadaveric knees were used. We drilled the anteromedial bundle (AMB) and posterolateral bundle (PLB) through the far anteromedial portal at 3 different knee flexion angles: 70 degrees, 90 degrees, and 110 degrees. We measured the shortest distance to the common peroneal nerve and the posterior articular cartilage of the lateral femoral condyle and the femoral tunnel length. RESULTS: At 70 degrees, the distance to the nerve was less than 10 mm in 7 AMB cases and in 9 PLB cases, and the distance to the cartilage was less than 10 mm in all the AMB and PLB cases. At 90 degrees, the distance to the nerve was less than 10 mm in 1 AMB and 5 PLBs, and the distance to the cartilage was less than 10 mm in 2 AMBs and all the PLBs. On the other hand, at 110 degrees , the distance to the nerve was greater than 10 mm in all the AMBs and PLBs, and the distance to the cartilage did not exceed 10 mm in just 2 of the PLBs. CONCLUSIONS: In our cadaveric study we found that the low knee flexion angles when drilling femoral tunnels through the far anteromedial portal might have the potential risks of damage to the common peroneal nerve and the posterior articular cartilage, and the risks would be decreased at higher degrees of knee flexion. However, we found there was a 20% risk of damage to the cartilage while drilling the PLB at 110 degrees. CLINICAL RELEVANCE: High knee flexion angles are recommended to avoid damage to the nerve and the cartilage when drilling femoral tunnels through the far anteromedial portal in double-bundle anterior cruciate ligament reconstruction.