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Purpose: To identify parameters associated with deterioration of patellofemoral (PF) cartilage after open-wedge high tibial osteotomy (OWHTO) and determine predictive values. It was hypothesized that cartilage injuries in PF joints would progress after OWHTO in patients who need a large alignment correction., Methods: Fifty-two knees in 47 patients who underwent bi-planer OWHTO for the treatment of medial compartment osteoarthritis from 2012 to 2017 and received a second-look arthroscopy at the time of plate removal (mean 14 months post-OWHTO) were assessed. Clinical outcomes were evaluated by the Knee Society Scores. Cartilage status in PF joints were evaluated arthroscopically using the International Cartilage Repair Society (ICRS) grading system. Patients were divided into two groups and patients who had progressed PF cartilage injury (progressed group) were compared with those who did not have progressed PF cartilage injuries (non-progressed group) using various parameters. The relationships between medial opening gap or change in the medial proximal tibial angle (ΔmPTA) and progression of PF cartilage injuries were examined by receiver operating characteristic (ROC) curve analysis., Results: The mean Knee Society Scores were significantly improved after surgery (P < 0.01). The grades for the patella and trochlea progressed in 12 (23.0%) and 16 knees (30.8%), respectively. The mean preoperative hip-knee-ankle (HKA) angle, mechanical axis, and mPTA in the progressed group were significantly smaller than those in the non-progressed group (P < 0.01). The mean medial opening gap and ΔmPTA in the progressed group were significantly larger than those in the non-progressed group (P < 0.01). ROC curve analysis showed that the cut-off values of the medial opening gap and ΔmPTA for progression of PF cartilage injuries were 13 mm and 9°, respectively. Progression of PF cartilage injuries was more frequently observed in knees with a medial opening gap ≥ 13 mm (P = 0.019, odds ratio = 4.60) or a ΔmPTA ≥ 9° (P = 0.003, odds ratio 6.93) than knees with those of < 13 mm or 9°, respectively., Conclusions: Cartilage injuries in PF joints tended to progress after OWHTO in patients with medial opening gap ≥ 13 mm or ΔmPTA ≥ 9°. If medial opening gap is ≥ 13 mm or ΔmPTA is ≥ 9° in planning for OWHTO, other type of surgery may need to be considered to avoid early progression of PF cartilage injuries., Level of Evidence: Level IV, therapeutic case series.

Simvastatin is clinically used for the treatment of hypercholesterolaemia. This study investigated the effects of the intra-articular administration of a simvastatin-conjugated gelatin hydrogel on osteoarthritis (OA) progression in a murine model. The medial meniscus of the knee joint was de-stabilized to induce OA in 10-week-old mice. Mice were then intra-articularly injected with dimethyl sulfoxide (control), drug-free gelatin hydrogel, simvastatin, or simvastatin-conjugated gelatin hydrogel. At 8 weeks postsurgery, OA progression was significantly attenuated in the simvastatin-conjugated gelatin hydrogel-treated mice compared with the other three groups. Attenuation of OA in mice treated with simvastatin-conjugated gelatin hydrogel was associated with decreased expression of cartilage-degrading enzymes and interleukin (IL)-1β and increased expression of type II collagen and an autophagic marker, LC3, in the articular cartilage. The effects of simvastatin on gene expression and autophagy in the mouse primary chondrocytes were also examined in the presence or absence of IL-1β. Treatment with simvastatin down-regulated Mmp-13 and Il-1β and up-regulated Col2a1 and autophagic activity. Our findings suggest that the intra-articular administration of simvastatin-conjugated gelatin hydrogel could be used as a new potential therapy for OA., (© 2019 John Wiley & Sons, Ltd.)

Background: The wide variations in patient demographics and concomitant injuries make the prediction of which patients will regain strength quickly following anterior cruciate ligament (ACL) reconstruction challenging. This study aimed to identify the dominant factor affecting quadriceps strength recovery after ACL reconstruction with a hamstring tendon autograft and to construct a predictive model for quadriceps strength recovery using decision tree analysis., Methods: Three hundred and eighty-six patients who underwent ACL reconstruction with a hamstring tendon autograft were included in this study. The isokinetic quadriceps strength at 60°/s was measured preoperatively and at 6 months after surgery. The quadriceps strength index (QSI) was calculated by normalising the peak torque of the involved leg with the uninvolved leg and multiplying it by 100. A stepwise multiple linear regression and a decision tree analysis were performed to assess whether or not the following parameters affect quadriceps strength recovery at 6 months: socio-demographic data and maximum isokinetic quadriceps strength., Results: The preoperative QSI, age, and pre-injury Tegner activity scale were independently correlated with quadriceps strength recovery at 6 month after surgery. The decision tree analysis demonstrated that patients were expected to have a QSI ≥85% at 6 months after surgery if they met one of the following conditions: (1) age <23 years with a preoperative QSI ≥78.8%, (2) age ≥29 years with a preoperative QSI ≥98.0%, or (3) age <16 years with a preoperative QSI <58.5% and pre-injury Tegner activity scale ≥9. By contrast, patients ≥29 years with a preoperative QSI <98.0% were likely to achieve a quadriceps strength index <70% at 6 months after surgery., Conclusions: Based on the results of the decision tree analysis, younger patients could achieve good quadriceps recovery even if they have a lower preoperative QSI, whereas patients ≥29 years need a higher preoperative QSI to obtain good muscle recovery., (Copyright © 2018 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Purpose: Concomitant meniscus injuries in the anterior cruciate ligament (ACL) have been suggested to exacerbate rotational laxity. However, the effect is supposed to be so small, if any, that some quantitative pivot-shift measurement is needed. The purpose of this prospective study was to determine the effect of meniscus tear on rotational laxity in ACL-deficient knees by an quantitative measurement. It was hypothesized that a concomitant meniscus tear, especially a lateral one, would induce greater pivot shift., Methods: Fifty-seven unilateral ACL-injured patients (26 men and 31 women, mean age: 24 ± 10 years) were included. The pivot-shift test was performed prior to ACL reconstruction, while a quantitative evaluation using an electromagnetic system to determine tibial acceleration and a clinical grading according to the IKDC were performed. Meniscus injuries were diagnosed arthroscopically, and concomitant meniscus tear was confirmed in 32 knees., Results: The clinical grade was not different between the ACL-injured knees of patients with and without meniscus tear (n.s.). Tibial acceleration did not show a statistical significant difference (meniscus-injured knees: 1.6 ± 1.1 m/s 2 versus meniscus-intact knees: 1.2 ± 0.7 m/s 2 , n.s.). However, the subgroup analysis demonstrated that there was increased tibial acceleration in ACL-deficient knees with lateral meniscus tear (2.1 ± 1.1 m/s 2 , n = 13) compared with meniscus-intact knees (p < 0.05), whereas rotational laxity did not increase in the medial meniscus-injured and bilateral-injured knees (1.2 ± 0.9 m/s 2 , n = 12, n.s. and 1.4 ± 1.1 m/s 2 , n = 7, n.s., respectively)., Conclusion: A concomitant meniscus tear, especially a lateral meniscus tear, has a significant impact on rotational laxity in ACL-injured knees. When a large pivot shift is observed in the ACL-injured knee, a concomitant meniscus tear should be suspected and an aggressive treatment would be considered. Meniscus injuries should be inspected carefully when substantial pivot shift is encountered in ACL-injured knees., Level of Evidence: Diagnostic study, Level III.

Purpose: The factors affecting anterior tibial subluxation (ATS) have not yet been well examined. To assess the factors affecting ATS in anterior cruciate ligament (ACL)-deficient knees., Methods: One hundred twenty-four patients with unilateral ACL injuries were included. True lateral views of the ACL-deficient knee and contralateral normal knee were obtained during maximum extension using fluoroscopy under general anesthesia, and ATS was calculated as the side-to-side difference in the tibial position relative to the femur. Patients were divided into four groups according to the time from injury to surgery. To identify the factors affecting ATS, the following possible factors were assessed: (1) the time from injury to surgery, (2) presence of a medial meniscal injury, and (3) posterior tibial slope angle., Results: There was a positive correlation between the ATS ratio and the time from injury to surgery ( r = 0.52). The ratio of the presence of a medial meniscus injury was significantly higher in patients who underwent anterior tibial subluxation reconstruction (ACL-R) more than 12 months after an injury than in other patients who underwent ACL-R within 12 months after an injury. The ATS ratio was significantly higher in patients with a medial meniscus injury than in those without a medial meniscus injury (5.6% vs. 4.1%)., Conclusions: Our results suggested that ACL-R should be performed within 6 months after injury if surgeons prefer to avoid an increase in ATS in maximum knee extension and at the latest within 12 months to avoid medial meniscal injury at the time of ACL-R.

Purpose: Several non-invasive devices have been developed to obtain quantitative assessment of the pivot-shift test in clinical setting using similar but diverse measurement parameters. However, the clinical usability of those measurements has yet to be closely investigated and compared. The purpose of this study was to compare the diagnostic accuracy of three non-invasive measurement devices for the pivot-shift test., Methods: Thirty patients with unilateral anterior cruciate ligament (ACL) injury were enrolled. The pivot-shift test was performed under general anaesthesia. Three devices, an accelerometer system (KiRA), an image analysis iPad application (iPad), and electromagnetic measurement system (EMS), were used simultaneously to provide two parameters, namely tibial acceleration monitored using KiRA and EMS, and tibial translation recorded using iPad and EMS. Side-to-side differences in each parameter and correlation between the measurements were tested, and a receiver-operating characteristic (ROC) curve analysis was conducted to compare their measurement accuracy., Results: Significant side-to-side differences were successfully detected using any of the measurements (all p < 0.01). KiRA demonstrated moderate correlation with the EMS for tibial acceleration (r = 0.54; p < 0.01), while poor correlation was observed between iPad and the EMS for the translation (r = 0.28; p < 0.01). The ROC curve analysis demonstrated better accuracy for the detection of ACL insufficiency in the EMS than KiRA and iPad for tibial acceleration and translation, respectively., Conclusions: Although all three measurements were similarly capable of detecting ACL deficiency, the EMS has the advantage of comprehensive evaluation of the pivot-shift test by evaluating both tibial acceleration and translation with higher accuracy than those of KiRA and iPad. It could be suggested that any of those measurement tools might improve the clinical diagnosis of ACL insufficiency., Level of Evidence: Diagnostic study of consecutive patients with a universally applied gold standard, Level Ib.

Purpose: This study quantified the error in anterior cruciate ligament (ACL) insertion site location and area estimated from three-dimensional (3D) isotropic magnetic resonance imaging (MRI) by comparing to native insertion sites determined via 3D laser scanning., Methods: Isotropic 3D DESS MRI was acquired from twelve fresh-frozen, ACL-intact cadaver knees. ACL insertion sites were manually outlined in each MRI slice, and the resulting contours combined to determine the 3D insertion site shape. Specimens were then disarticulated, and the boundaries of the ACL insertion sites were digitized using a high-accuracy laser scanner. MRI and laser scan insertion sites were co-registered to determine the percent overlapping area and difference in insertion centroid location., Results: Femoral ACL insertion site area averaged 112.7 ± 17.9 mm 2 from MRI and 109.7 ± 10.9 mm 2 from laser scan (p = 0.345). Tibial insertion area was 134.7 ± 22.9 mm 2 from MRI and 135.2 ± 15.1 mm 2 from laser scan (p = 0.881). Percentages of overlapping area between modalities were 82.2 ± 10.2% for femurs and 81.0 ± 9.0% for tibias. The root-mean-square differences for ACL insertion site centroids were 1.87 mm for femurs and 2.49 mm for tibias. The MRI-estimated ACL insertion site centroids were biased on average 0.6 ± 1.6 mm proximally and 0.3 ± 1.9 mm posteriorly for femurs, and 0.3 ± 1.1 mm laterally and 0.5 ± 1.5 mm anteriorly for tibias., Conclusion: Errors in ACL insertion site location and area estimated from 3D-MRI were determined via comparison with a high-accuracy 3D laser scanning. Results indicate that MRI can provide estimates of ACL insertion site area and centroid location with clinically applicable accuracy. MRI-based assessment can provide a reliable estimate of the native ACL anatomy, which can be helpful for surgical planning as well as assessment of graft tunnel placement.

The Short Time Exposure (STE) test method is an alternative method for assessing eye irritation potential using Statens Seruminstitut Rabbit Cornea cells and has been adopted as test guideline 491 by the Organisation for Economic Co-operation and Development. Its good predictive performance in identifying the Globally Harmonized System (GHS) No Category (NC) or Irritant Category has been demonstrated in evaluations of water-soluble substances, oil-soluble substances, and water-soluble mixtures. However, the predictive performance for oil-soluble mixtures was not evaluated. Twenty-four oil-soluble mixtures were evaluated using the STE test method. The GHS NC or Irritant Category of 22 oil-soluble mixtures were consistent with that of a Reconstructed human Cornea-like Epithelium (RhCE) test method. Inter-laboratory reproducibility was then confirmed using 20 water- and oil-soluble mixtures blind-coded. The concordance in GHS NC or Irritant Category among four laboratories was 90%-100%. In conclusion, the concordance in comparison with the results of RhCE test method using 24 oil-soluble mixtures and inter-laboratory reproducibility using 20 water- and oil-soluble mixtures blind-coded were good, indicating that the STE test method is a suitable alternative for predicting the eye irritation potential of both substances and mixtures., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: A fluoroscopic guidance method for medial patellofemoral ligament (MPFL) reconstruction has been widely used to determine the anatomic femoral attachment site., Purpose: To examine the graft length change patterns in MPFL reconstruction with a fluoroscopic guidance method., Study Design: Cross-sectional study; Level of evidence, 3., Methods: Forty-four knees of 42 patients who underwent MPFL reconstruction for the treatment of recurrent patellar dislocation were examined prospectively. During surgery, suture anchors were inserted into the proximal one-third and center of the patella. A guide pin for the femoral tunnel was inserted into the position reported by Schöttle et al based on the true lateral view of the knee under fluoroscopic control. Changes in graft length patterns of the proximal and center anchors were examined through 0° to 120° of knee flexion. Favorable changes in length patterns were defined as meeting 2 of 3 criteria: (1) not long during flexion (≤3 mm between 30° and 120° of flexion) and either (2) nearly isometric during flexion between 0° and 90° or (3) slightly long during maximum extension (≤3 mm). Other patterns were considered unfavorable. If the change in length pattern was unfavorable, then the pin for the femoral tunnel was moved to different positions until it was favorable. Knees were separated into the favorable group and the unfavorable group. Differences between the groups regarding radiographic parameters were assessed. Student t test or chi-square test was used for statistical analysis., Results: Of the 44 knees, 31 (70.5%) showed favorable patterns. However, 13 knees (29.5%) showed unfavorable patterns; therefore, the position of the pin was changed. The mean ± SD distance from the original position to the final position was 5.3 ± 1.1 mm distal for 7 patients and 5.2 ± 0.4 mm posterodistal for 6 patients. Technical errors, including a nontrue lateral view and the tip of the wire not being in the determined area, were found for 4 of 13 knees in the unfavorable group. There was no statistical difference in radiographic parameters between the groups., Conclusion: The graft length change pattern could be nonphysiologic at the position determined through the fluoroscopic guidance method; thus, caution may be necessary. The change in length pattern should be checked before graft fixation. If the length change pattern is unfavorable, then it is advisable to move it approximately 5 to 7 mm distally or posterodistally from the first position.

Purpose: Final tunnel location in the anterior cruciate ligament (ACL) reconstruction is unpredictable due to tunnel widening and/or transposition. The mechanical stress around the tunnel aperture seems to be a major factor but is not fully investigated. The purpose of this study was to measure the stress from the ACL graft around the tunnel aperture when the ACL graft tension reaches its peak., Methods: Six cadaveric knees were used. Single-bundle ACL reconstruction was performed using a hamstrings graft. Both femoral and tibial tunnels were created at the centre of the original ACL footprint. A 7-mm-internal-diameter aluminium cylinder with pressure sensors was placed in the femoral tunnel. Hamstrings graft with a microtension sensor was inserted. After fixation, passive extension-flexion was performed while monitoring the tunnel aperture pressure and the graft tension simultaneously. The pressure on the femoral tunnel aperture when the ACL graft tension reach its peak was compared between four directions., Results: The ACL graft tension peaked (67 ± 49 N) at full extension (-5.8 ± 4.1°). Pressure at the femoral tunnel aperture was different between different directions (p < 0.01). Distal part had significantly larger pressure (1.7 ± 1.3 MPa) than the other directions (p < 0.01). Second largest pressure was carried in the anterior part (0.6 ± 0.5 MPa), followed by proximal and posterior parts (0.4 ± 0.3, 0.2 ± 0.2 MPa respectively)., Conclusion: The stress distribution at the femoral tunnel aperture is not equal in different directions, while the distal part dominantly bears the stress from the ACL graft. Surgeons should pay close attention to the distal edge of the femoral tunnel which should be inside the anatomic ACL footprint eventually.

The Short Time Exposure (STE) test method is an in vitro method for assessing the eye irritation potential of chemicals and is used to classify the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) Category 1 and No Category (NC). The method has been adopted by the Organisation for Economic Co-operation and Development (OECD) as test guideline (TG) 491 since 2015. While this method can be used to classify GHS NC, it is not suitable for testing highly volatile substances and solids other than surfactants. Here we evaluated highly volatile substances to expand the applicability domain. According to TG 491, acetone, ethanol, iso-propanol, and methyl acetate as highly volatile substances resulted in false negatives. Saline was selected as a solvent of these false negatives. In this study, mineral oil was used as the solvent, because these false negatives were amphiphilic. Based on this change, four highly volatile substances were correctly evaluated. The predictive performance for classifying GHS NC was then verified using a substance dataset constructed in reference to the Draize eye test Reference Database and STE Summary Review Document. The accuracy and false-negative rate were 86.6% (194/224) and 3.8% (3/80), respectively. Collectively, the applicability domain was expanded by changing the solvent to mineral oil for highly volatile substances, and the predictive performance for the new applicability domain including highly volatile substances was excellent. The STE test method is suitable to classify GHS NC, indicating its applicability as a test method in a bottom-up approach.

Purpose: Patients typically return to sports activities 6-12 months after anterior cruciate ligament (ACL) reconstruction, and quadriceps strength has been used as one of the criteria to return to sports activities. The purpose of this study is to identify the factors that affect quadriceps strength recovery after ACL reconstruction with a hamstring tendon autograft 6 months after surgery., Methods: Isokinetic quadriceps strength at 60°/s was measured preoperatively and 6 months after surgery in 193 athletes who underwent ACL reconstruction with a hamstring tendon autograft. The quadriceps strength index was calculated by normalizing the peak torque of the involved leg with the uninvolved leg. The subjects were divided into two groups according to the quadriceps strength index 6 months after surgery: at least 85 % (n = 84) or less than 85 % (n = 109). Multivariate logistic regression analysis and a receiver operating curve analysis were performed., Results: The preoperative quadriceps strength index [odds ratio (OR) 1.02; 95 % confidence interval (CI) 1.01-1.03], age (OR 0.92; 95 % CI 0.86-0.98), sex (OR 2.45; 95 % CI 1.19-5.18), and knee pain (OR 0.17; 95 % CI 0.04-0.52) were independently associated with quadriceps strength recovery. The cut-off value of the preoperative quadriceps strength index was 70.2 % to obtain at least 85 % quadriceps strength index 6 months after surgery., Conclusion: To achieve sufficient quadriceps strength recovery at the timing of return to sports activities following ACL reconstruction using a hamstring tendon autograft, preoperative quadriceps strength, age, sex, and knee pain should be considered., Level of Evidence: III.

Purpose: To evaluate the tension deprivation through the tunnels with and without preconditioning at the time of fixation, and the influences of cyclic loading and pretensioning on graft tension in anatomic single bundle anterior cruciate ligament (ACL) reconstruction using a hamstring tendon., Methods: Nine fresh-frozen cadaveric knees underwent anatomic ACL reconstruction using hamstring grafts. Each specimen was examined to ensure that there was no severe osteoarthritic change, ligament insufficiency, or torn menisci by manual and arthroscopic evaluation. Applied graft tension was measured at the tibial tunnel outlet using a graft tensor with a load cell. Intra-articular graft tension was evaluated by using an originally developed microforce sensor, which was sutured into the graft. Both tensions were simultaneously measured just after initial tensioning under 3 different conditions: condition 1, just after initial tensioning of 20 N at 20° of knee flexion without preconditioning; condition 2, after the same initial tensioning following 5 rounds of passive cyclic flexion-extension movement; and condition 3, after the same initial tensioning following 5 minutes of static pretensioning of 20 N., Results: The intra-articular tension was 12.7 ± 5.3 N in condition 1, 12.0 ± 4.8 N in condition 2, and 13.5 ± 4.8 N in condition 3. In these 3 conditions, intra-articular graft tension was significantly lower than the applied tension of around 20 N (no pretension: P = .009, cyclic pretension: P = .004, static pretension: P = .008), with no difference among the 3 conditions (P = .82)., Conclusions: The intra-articular graft tension was significantly lower than the applied tension from the outside of the joint, even after cyclic loading and pretensioning., Clinical Relevance: It is difficult to evaluate the intra-articular graft tension precisely on the basis of the extra-articular tension at time zero in ACL reconstruction., (Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to evaluate subjective outcomes after medial patellofemoral ligament (MPFL) reconstructions., Methods: Fifty-four knees of 46 patients who received MPFL reconstruction for recurrent patellar dislocations were examined with a minimum follow-up of two years. To assess patient-based outcomes, the Knee Injury and Osteoarthritis Outcome Score (KOOS) and the Kujala score were assessed., Results: The mean Kujala score was significantly improved from 64.6 ± 22.1 pre-operatively to 84.7 ± 11.8 post-operatively (P < 0.001). The mean KOOS was also significantly improved post-operatively in all five subscales. Further, the mean scores of 41 out of the 42 questions for the KOOS were significantly improved after surgery, except those of the question about "grinding and clicking". When the KOOS was assessed individually, the scores on one or more subscales out of the five were worsened post-operatively in eight patients, and seven of the eight patients had decreased post-operative pain subscale scores. Furthermore, those eight patients (worse group) were compared with patients without any worsened scores on any of the subscales (better group). The mean pre-operative pain and sports/recreation function subscale scores were significantly higher in the worse group whereas the mean post-operative pain and symptoms subscale scores were significantly lower in the worse group than in the better group., Conclusions: Overall, satisfactory patient-based outcomes were obtained after MPFL reconstruction in most of the patients. However, patients who only have mild pain pre-operatively tend to have worse subjective outcomes, and a caution may be needed when performing MPFL reconstruction on these patients.

Background: Vascular CD34+ cells in anterior cruciate ligament (ACL) tissue have the potential for high proliferation and multilineage differentiation that can accelerate tendon-bone healing. While patient characteristics, such as age, can affect tendon-bone healing, the influence of elapsed time after injury on the healing process is unclear., Hypothesis: Cells obtained during the early phase after injury will exhibit a greater tendon-bone healing potential compared with chronic phase counterparts when applied to an immunodeficient rat model of ACL reconstruction., Study Design: Controlled laboratory study., Methods: Adult human ACL-ruptured tissue was harvested from patients undergoing arthroscopic primary ACL reconstruction and classified into 2 groups based on the time elapsed between injury and surgery: (1) early group (≤3 months from injury) and (2) chronic group (>3 months from injury). In addition, 76 ten-week-old female immunodeficient rats underwent ACL reconstruction, followed by intracapsular administration of one of the following: (1) ACL-derived cells from the early group (n = 5), (2) ACL-derived cells from the chronic group (n = 5), or (3) phosphate-buffered saline (PBS) only (n = 5). During the 8 weeks after surgery, histological (weeks 2, 4, 8), immunohistochemical (week 2), radiographic (weeks 0, 2, 4, 8), and biomechanical (week 8) analyses were performed to evaluate tendon-bone healing., Results: In the early group, the histological evaluation showed early healing, induction of endochondral ossification-like integration, and mature bone ingrowth. Micro-computed tomography showed that the tibial bone tunnels at week 4 and week 8 were significantly reduced in the early group compared with those in the chronic group and PBS group ( P < .05). Moreover, biomechanical tensile strength was significantly greater in the early group than in the other groups ( P < .05). An accelerated healing potential in the early group was further demonstrated by the enhancement of intrinsic angiogenesis/osteogenesis and human-derived vasculogenesis/osteogenesis., Conclusion: Compared with human ACL-derived cells obtained during the chronic phase, cells obtained during the early phase after injury have a greater tendon-bone healing potential when used in an immunodeficient rat model of ACL reconstruction., Clinical Relevance: During ACL reconstruction surgery, transplanting ACL remnant tissue in the early phase after injury could accelerate and enhance tendon-bone healing.

Purpose: Anterior cruciate ligament (ACL) injuries are often accompanied by meniscal tears. Meniscal repair is typically performed during ACL reconstruction. However, retear of the meniscus after repair is frequent. The purpose of this study was to analyze the factors associated with meniscal healing after meniscal repair concomitant with ACL reconstruction., Materials and Methods: Eighty-seven meniscal repairs in 87 patients who received meniscal repair combined with ACL reconstruction and received second-look arthroscopy at a mean of postoperatively 15.7 months were examined retrospectively. The menisci were divided into three groups (complete heal, incomplete heal, and retear), and factors thought to affect the healing status of repaired menisci were analyzed using multivariate logistic regression analysis., Results: Meniscal healing was judged to be complete in 49 knees (56%), incomplete in 19 knees, (22%), and retear in 19 knees (22%). There were no significant differences among the three groups in age, sex, time from injury to operation, mean Tegner activity scale, tear location, or mean postoperative anteroposterior tibial translation on KT-1000. The mean length of the tear was significantly higher in the retear group. Additionally, the proportion patients with complete tear and the proportion with postoperative positive pivot shift test were significantly higher in the retear group than in the other groups. Multivariate logistic regression analysis showed that complete tear and positive pivot shift test were associated with retear., Conclusions: These findings suggest that complete tears and residual instability are associated with retears after meniscal repair concomitant with ACL reconstruction.

Purpose: To examine the clinical and biomechanical results of posterolateral (PL) augmentation to reconstruct damaged PL bundle while preserving the less-damaged anteromedial bundle for partial anterior cruciate ligament (ACL) tears in comparison with double-bundle ACL reconstruction., Methods: Sixteen patients who underwent PL augmentation for partial ACL tears (Group P) and 37 patients who underwent double-bundle ACL reconstructions for complete ACL tears were examined (Group D). Anterior tibial translation (ATT) was evaluated using the KT-1000 arthrometer. ATT during the Lachman test and acceleration of posterior tibial translation (APT) during the pivot shift test were evaluated using an electromagnetic measurement system (EMS). Clinical outcomes were evaluated using the Lysholm score. Second-look arthroscopy was performed 1 year after surgery., Results: The mean postoperative Lysholm scores were 91.7 ± 12.2 and 94.6 ± 7.2 in Groups P and D, respectively, and there was no statistically significant difference between the two groups. The mean side-to-side difference of ATT on the KT-1000 was significantly improved in both Groups P and D. In the EMS analysis, the mean side-to-side difference of ATT and the mean APT were significantly improved in both Groups P and D. There was no significant difference in the second-look evaluation between the two groups., Conclusions: The clinical and biomechanical outcomes of PL augmentation were satisfactorily comparable to those of double-bundle ACL reconstruction. PL augmentation could be a useful treatment option for patients with partial ACL tears., Level of Evidence: IV.

Safety assessments of cosmetics are carried out by identifying possible harmful effects of substances in cosmetic products and assessing the exposure to products containing these substances. The present study provided data on the amounts of cosmetic products consumed in Japan to enhance and complement the existing data from Europe and the United States, i.e., the West. The outcomes of this study increase the accuracy of exposure assessments and enable more sophisticated risk assessment as a part of the safety assessment of cosmetic products. Actual amounts of products applied were calculated by determining the difference in the weight of products before and after use by approximately 300 subjects. The results of the study of skincare products revealed that in comparison with the West, large amounts of lotions and emulsions were applied, whereas lower amounts of cream and essence were applied in Japan. In the study of sunscreen products, actual measured values during outdoor leisure use were obtained, and these were lower than the values from the West. The study of the use of facial mask packs yielded data on typical Japanese sheet-type impregnated masks and revealed that high amounts were applied. Furthermore, data were obtained on cleansing foams, makeup removers and makeup products. The data from the present study enhance and complement existing information and will facilitate more sophisticated risk assessments. The present results should be extremely useful in safety assessments of newly developed cosmetic products and to regulatory authorities in Japan and around the world.

Purpose: Patellar width ratio, a new measurement of anterior-posterior patellar width, was developed using lateral radiographs. The hypothesis was that patellar width ratio would increase with increasing patellar tilt angle and that patients with patellar instability would have larger patellar width ratio compared to controls., Methods: Fifty knees who underwent surgery for patellar instability were enrolled as Group P. The fifty knees without patellar instability were enrolled as controls (Group C). Patellar width ratio was measured using preoperative lateral radiographs. The width between proximal and distal apexes of patella was defined as A. The width between anterior and posterior margins of patella was defined as B. Patellar width ratio was defined as the ratio B/A. Patellar tilt angle was measured on preoperative computed tomography images. Values were compared between groups and their correlation examined, and a receiver operating characteristic (ROC) curve was generated to identify the threshold value., Results: Mean patellar width ratio in Groups C and P was 0.54 ± 0.04 and 0.66 ± 0.11 (P < 0.01). Mean patellar tilt angle in Groups C and P was 12.8° ± 4.9° and 32.0° ± 10.3° (P < 0.01). Patellar width ratio was strongly correlated with patellar tilt angle (R = 0.83, P < 0.01). For patellar width ratio, the area under ROC curve was 0.86, and the cut-off value was 0.59 (sensitivity 76.0 %, specificity 90.0 %)., Conclusion: Patellar width ratio in Group P was significantly larger than in Group C. Patellar width ratio would allow clinicians to evaluate patellar tilt on lateral radiographs., Level of Evidence: III.

We report a case of concurrent bilateral hip arthroscopy for symptomatic bilateral femoroacetabular impingement (FAI) performed under the single anesthesia on an elite rugby player. A 27-year-old rugby player who played for a top league had bilateral hip joint pain. Physical examination revealed bilateral tenderness in the anterior area of the hips, with positive impingement signs. Based on the findings of hip radiography and magnetic resonance imaging, the patient's symptoms were diagnosed as bilateral FAI with hip labral tears. Bilateral hip arthroscopy under the single anesthesia was performed due to refractory symptoms. He returned to regular rugby games without any symptoms in either hip. Bilateral hip arthroscopic surgery under the single anesthesia should be an effective treatment for typical and symptomatic FAI, even in elite athletes.

Treatment of massive osteochondral defects of the medial femoral condyle is challenging. A 46-year-old man who had a medial femoral condyle fracture on his left knee underwent osteosynthesis in a hospital, but the pain remained and the patient was referred to our hospital 8 months after the surgery. Radiographs showed a varus alignment of the leg, and magnetic resonance image showed a massive necrotic area in the medial femoral condyle. The patient received high tibial osteotomy (HTO) combined with iliac cancellous bone graft and an osteochondral autograft transplantation. Pain and the knee function markedly improved 2 years after the surgery. A second look arthroscopy showed a well-covered bone graft site with cartilaginous tissue and a well-integrated osteochondral plug. HTO combined with cancellous bone autograft and osteochondral autograft transplantation could be an effective treatment for patients presenting with a varus knee deformity associated with massive osteochondral defects in the medial femoral condyle.

Mesenchymal stem/stromal cells (MSCs) reside in the bone marrow and maintain their stemness under hypoxic conditions. However, the mechanism underlying the effects of hypoxia on MSCs remains to be elucidated. This study attempted to uncover the signaling pathway of MSC proliferation. Under low-oxygen culture conditions, MSCs maintained their proliferation and differentiation abilities for a long term. The Notch2 receptor was up-regulated in MSCs under hypoxic conditions. Notch2-knockdown (Notch2-KD) MSCs lost their cellular proliferation ability and showed reduced gene expression of hypoxia-inducible transcription factor (HIF)-1α, HIF-2α, and c-Myc. Overexpression of the c-Myc gene in Notch2-KD MSCs allowed the cells to regain their proliferation capacity. These results suggested that Notch2 signaling is linked to c-Myc expression and plays a key role in the regulation of MSC proliferation. Our findings provide important knowledge for elucidating the self-replication competence of MSCs in the bone marrow microenvironment., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To compare the effect of graft fixation angle and tension in double-bundle anterior cruciate ligament (ACL) reconstruction on knee biomechanics., Methods: Fourteen cadaver knees were tested using a robotic system under two loadings: (1) an 89-N anterior tibial load (ATL) at full extension (FE), 15°, 30°, 45°, 60°, and 90°, and (2) combined 7 N m valgus and 5 N m internal tibial torques (simulated pivot-shift test) at FE, 15° and 30°. Four graft fixation angles and tensions were used for the anteromedial (AM) and posterolateral (PL) bundles, respectively: (Recon 1) 30°/20N and FE/20N, (Recon 2) 30°/30N and FE/10N, (Recon 3) 45°/20N and 15°/20N, and (Recon 4) 45°/30N and 15°/10N., Results: All fixation protocols closely restored the intact knee kinematics under ATL and simulated pivot-shift loading. For the AM bundle under ATL, the in situ force (ISF) with Recon 3 at the FE was significantly lower than that of the intact knee. For the PL bundle under ATL, the ISF with Recon 3 at the FE, 15° and 30° was significantly higher than that of the intact knee. In PL bundle under simulated pivot-shift loading, the ISF with Recon 1 and Recon 2 at FE was lower and the ISF of the PL bundle with Recon 3 at the 15° was higher than that of the intact knee., Conclusion: The AM-45°/30N and PL-15°/10N fixation most closely matched intact knee kinematics; however, stabilizing the knee during anterior tibial translation may risk an imbalance of the AM and the PL bundle loading. The results indicate that ACL bundle forces may not be restored even if the clinical assessment shows good results with the Lachman test and pivot-shift test. This may alter the loading on other structures of the knee.

Purpose: The purpose of this study was to measure the semitendinosus tendon graft shift at the tunnel aperture with graft bending using a simulated femoral bone tunnel., Methods: Eight semitendinosus tendon grafts were used in this study. The median age of the specimen was 53 years (range 46-63). After stripping excess soft tissue, the semitendinosus tendon was doubled over the loop of the EndoButton CL (Smith and Nephew Inc.). The diameter of the graft was measured using a graft-sizing tube (Smith and Nephew Inc.) and verified to be 7.0 mm. A custom-made aluminium fixture, the size was 40.0 mm(3), with 7.0-mm-diameter hole was used as a simulated femoral bone tunnel. The graft was inserted to the tunnel, and EndoButton was positioned to the outside of the tunnel on the fixture. The distal end of the graft was tensioned with 30 N at an angle of 15°, 30°, 45°, 60°, 75° that reproduced the graft bending angle during knee range of motion. The photograph of the tunnel aperture was taken at each graft bending angle using a digital camera, and the graft shift amount in the simulated tunnel was analysed using the computer software (ImageJ)., Results: The amount of the graft shift significantly increased when the graft bending angle was increased (P < 0.05). The biggest shift was observed when the graft bending angle was 75° in all specimens, and the value was 1.10 mm ± 0.12., Conclusion: The present study suggests that even if the femoral tunnel was created in the centre of the ACL insertion site, the graft shifted within the tunnel in the direction of the tension applied to the graft during knee range of motion. Surgeons may have to consider the graft shift within the bone tunnel as well as the tunnel position in the restoration of the native ACL anatomy.

Background: Postoperative cisplatin and radiation is the standard of care for high-risk squamous cell carcinoma of the head and neck (SCCHN). We have used cetuximab and radiation in the postoperative setting for patients deemed poor candidates for cisplatin., Methods: We retrospectively identified 40 patients who received cetuximab and radiation for resected locoregionally advanced SCCHN between 2006 and 2013 at our institution., Results: The 2-year Kaplan-Meier estimates were: overall survival (OS) 41%, recurrence-free survival (RFS) 34%, locoregional control 63%, and distant metastatic control 59%. Eastern Cooperative Oncology Group (ECOG) performance status ≥1 predicted for inferior OS (hazard ratio [HR] = 5.43; p = .003), RFS (HR = 4.07; p = .007), and locoregional control (HR = 4.92; p = .04) in multivariate analysis., Conclusion: Patients with resected high-risk SCCHN treated with postoperative cetuximab and radiation have suboptimal therapeutic outcomes. Further study of the efficacy and cost-effectiveness compared to radiation alone is warranted. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1318-1323, 2016., (© 2016 Wiley Periodicals, Inc.)

Purpose: To evaluate quantitatively the biomechanical function of anterior cruciate ligament (ACL) remnants in patients with ACL injuries. Anterior tibial translation (ATT) with KT-1000 and during the Lachman test with an electromagnetic measurement system (EMS) and tibial acceleration during the pivot shift test with EMS were measured., Methods: A total of 121 unilateral ACL injuries were examined. ACL remnants were morphologically classified as being attached to the posterior cruciate ligament (PCL group), to the roof of the intercondylar notch (RIN group), to the lateral wall of the intercondylar notch (LWIN group), or as having no substantial remnants (NONE group). Partial ACL tears were excluded. ATT was measured using KT-1000. ATT during the Lachman test and tibial acceleration during the pivot shift test were measured using EMS., Results: ACL remnant patterns were as follows: PCL group, 27 knees; RIN group, 34 knees; LWIN group, 27 knees; and NONE group, 33 knees. The ATT side-to-side difference in LWIN group (3.4 ± 0.7 mm) by KT-1000 was significantly smaller than the RIN (5.7 ± 1.0 mm) and NONE groups (5.9 ± 1.0 mm) (P < .05). The ATT side-to-side difference during the Lachman test was significantly smaller in the LWIN group (5.3 ± 1.2 mm) than the PCL (8.6 ± 1.4 mm), RIN (8.5 ± 1.2 mm), and NONE groups (7.6 ± 1.0 mm) (P < .05). Tibial accelerations were 2.0 ± 0.4, 1.7 ± 0.2, 1.9 ± 0.2, and 1.8 ± 0.3 m/s(2) in the PCL, RIN, LWIN, and NONE groups, respectively. There were no significant differences among groups., Conclusions: ACL remnants attached to the lateral wall of the intercondylar notch partially contributed to anterior-posterior stability but did not contribute to dynamic knee stability. These findings suggest that ACL remnants attached to nonanatomic insertion sites do not contribute significantly to knee stabilization., Level of Evidence: Level III, diagnostic study of nonconsecutive patients., (Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Background: The effect of posterior slope on joint gap in unicompartmental knee arthroplasty (UKA) has yet to be quantified. The purpose of this study was to quantify the effect of the tibial slope on the joint component gap and postoperative range of motion in UKA., Methods: Forty consecutive patients were prospectively enrolled. The correlation between the tibial slope changes and the component gap, the component gap difference between flexion angles, the postoperative extension or flexion angles was examined. The correlation of joint looseness with tibial slope changes and postoperative extension angle was also examined., Results: Increased tibial slope positively correlated with the differences between the component gap at 90° and 10°, 120° and 10°, or 135° and 10° knee flexion angle. Although tibial slope change did not affect postoperative flexion angle, increased tibial slope reduced postoperative extension angle. Moreover, increased tibial slope resulted in decreased joint looseness during 10° of knee flexion and decreased joint looseness during 10° of knee flexion resulted in reduced postoperative extension angle., Conclusions: Increased tibial slope resulted in tight component gap at knee extension compared with that at knee flexion. Furthermore, tight component gap at extension lead to decreased postoperative extension angle. These results indicate that an individual anatomical tibial slope should be considered when tibial sagittal osteotomy was performed and increasing tibial slope should be avoided to achieve full extension angle after UKA., Level of Evidence: II., (Copyright © 2016. Published by Elsevier B.V.)

Background: This study aimed to resolve uncertainty regarding sex differences in alignment changes with age., Methods: We measured various parameters of weight-bearing long leg radiographs of 797 legs without osteoarthritic changes, which were classified according to sex and age (young [15-39 years], middle-aged [40-54 years], aged [55-69 years], and elderly [≥70 years]), and performed morphological analysis of the lower extremities. The mean measurements in each group were calculated and compared among the groups., Results: In the young and middle-aged populations, the femorotibial angle was significantly more varus in male than in female participants (p<0.001). In addition, medial femoral bowing was seen both in male and female participants, but it was more significant in male participants (p<0.005). This was due to greater femoral condylar orientation (p<0.01) and tibial plateau inclination (p<0.01) in male participants compared to female participants with nearly identical joint space narrowing. In aged and elderly populations, on the contrary, lateral femoral bowing was seen in both male and female participants, and there were no differences in any measured values, including the femorotibial angle, between male and female participants., Conclusions: In relatively young Japanese individuals, male participants' femorotibial angles were more varus and had more medial femoral bowing than female participants, while there was no difference in any measured values between male and female participants in older adults by a radiographic analysis on the alignment of the lower extremities., Level of Evidence: Level 2., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Purpose: Patients with acute myeloid leukemia (AML) who are in morphologic complete remission are typically considered separately from patients with active disease (ie, ≥ 5% marrow blasts by morphology) in treatment algorithms for allogeneic hematopoietic cell transplantation (HCT), which implies distinct outcomes for these two groups. It is well recognized that the presence of minimal residual disease (MRD) at the time of transplantation is associated with adverse post-HCT outcome for those patients in morphologic remission. This effect of pre-HCT MRD prompted us to compare outcomes in consecutive patients in MRD-positive remission with patients with active AML who underwent myeloablative allogeneic HCT at our institution., Patients and Methods: We retrospectively studied 359 consecutive adults with AML who underwent myeloablative allogeneic HCT from a peripheral blood or bone marrow donor between 2006 and 2014. Pre-HCT disease staging included 10-color multiparametric flow cytometry on bone marrow aspirates in all patients. Any level of residual disease was considered to be MRD positive., Results: Three-year relapse estimates were 67% in 76 patients in MRD-positive morphologic remission and 65% in 48 patients with active AML compared with 22% in 235 patients in MRD-negative remission. Three-year overall survival estimates were 26%, 23%, and 73% in these three groups, respectively. After multivariable adjustment, MRD-negative remission status remained statistically significantly associated with longer overall and progression-free survival as well as lower risk of relapse compared with MRD-positive morphologic remission status or having active disease, with similar outcomes between the latter two groups., Conclusion: The similarities in outcomes between patients in MRD-positive morphologic remission and those with active disease at the time of HCT support the use of treatment algorithms that use MRD- rather than morphology-based disease assessments., Competing Interests: Authors' disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article., (© 2015 by American Society of Clinical Oncology.)

The pivot shift test is a commonly used clinical examination by orthopedic surgeons to evaluate knee function following injury. However, the test can only be graded subjectively by the examiner. Therefore, the purpose of this study is to develop software for a computer tablet to quantify anterior translation of the lateral knee compartment during the pivot shift test. Based on the simple image analysis method, software for a computer tablet was developed with the following primary design constraint - the software should be easy to use in a clinical setting and it should not slow down an outpatient visit. Translation of the lateral compartment of the intact knee was 2.0 ± 0.2 mm and for the anterior cruciate ligament-deficient knee was 8.9 ± 0.9 mm (p < 0.001). Intra-tester (ICC range = 0.913 to 0.999) and inter-tester (ICC = 0.949) reliability were excellent for the repeatability assessments. Overall, the average percent error of measuring simulated translation of the lateral knee compartment with the tablet parallel to the monitor increased from 2.8% at 50 cm distance to 7.7% at 200 cm. Deviation from the parallel position of the tablet did not have a significant effect until a tablet angle of 45°. Average percent error during anterior translation of the lateral knee compartment of 6mm was 2.2% compared to 6.2% for 2 mm of translation. The software provides reliable, objective, and quantitative data on translation of the lateral knee compartment during the pivot shift test and meets the design constraints posed by the clinical setting.

Background: No study has examined the possible factors associated with different characteristics of stem-like cells derived from anterior cruciate ligament (ACL) remnants. And the purpose of the study is to elucidate whether demographic factors are associated with healing potential of stem-like cells derived from the ACL remnants tissue., Methods: Thirty-six ACL remnants were harvested from patients who received primary arthroscopic ACL reconstruction. Interval from injury to surgery, age, sex, and combined meniscal or chondral injuries were analyzed. Cells were isolated from remnant tissues and their healing potential was evaluated by: 1) characterization of surface markers (CD34, CD44, CD45, CD146, CD29, and Stro-1), 2) cell expansion, 3) osteogenic differentiation, and 4) endothelial differentiation. Finally, using multivariable logistic regression to evaluate the relation between demographic factors and healing potential parameters. Adjusted odds ratios (OR) were calculated, and the significant difference was set at p < 0.05., Results: ACL remnant tissue harvested less than 90 days after injury predicted higher fractions of stem-like cells [CD34+ (OR = 6.043, p = 0.025), CD44 + (OR = 8.440, p = 0.011), CD45+ (OR = 16.144, p = 0.015), and CD146+ (OR = 9.246, p = 0.015)] and higher expansion potential (passage 3: OR = 9.755, p = 0.034; passage 10: OR = 33.245, p = 0.003). Regarding osteogenic differentiation, higher gene expression of Osteocalcin (OR = 22.579, p = 0.009), Alkaline phosphatase (OR = 6.527, p = 0.022), and Runt-related transcription factor 2 (OR = 5.247, p = 0.047) can also be predicted. Younger age predicted higher CD34+ levels (20 ≤ age < 30 years, OR = 2.020, p = 0.027) and higher expansion potential at passage 10 (10 ≤ age < 20 years, OR = 25.141, p = 0.026). There was no significant relation found between meniscal or chondral injuries and ACL healing potential., Conclusion: Our results indicated that the ACL remnant tissue harvested within 3-months after injury yields higher healing potential, suggesting early surgical intervention may achieve better clinical results.

Purpose: Tibial acceleration during the pivot shift test is a potential quantitative parameter to evaluate rotational laxity of anterior cruciate ligament (ACL) insufficiency. However, clinical application of this measurement has not been fully examined. This study aimed to measure and compare tibial acceleration before and after ACL reconstruction (ACLR) in ACL-injured patients. We hypothesized tibial acceleration would be reduced by ACLR and tibial acceleration would be consistent in the same knee at different time points., Methods: Seventy ACL-injured patients who underwent ACLR were enrolled. Tibial acceleration during the pivot shift test was measured using an electromagnetic measurement system before ALCR and at the second-look arthroscopy 1 year post-operatively. Tibial acceleration was compared to clinical grading and between ACL-injured/ACL-reconstructed and contralateral knees., Results: Pre-operative tibial acceleration was increased stepwise with the increase in clinical grading (P < 0.01). Tibial acceleration in ACL-injured knee (1.9 ± 1.2 m/s(2)) was larger than that in the contralateral knee (0.8 ± 0.3 m/s(2), P < 0.01), and reduced to 0.9 ± 0.3 m/s(2) post-operatively (P < 0.01). There was no difference between ACL-reconstructed and contralateral knee (n.s.). Tibial acceleration in contralateral knees was consistent pre- and post-operatively (n.s.)., Conclusion: Tibial acceleration measurement demonstrated increased rotational laxity in ACL-injured knees and its reduction by ALCR. Additionally, consistent measurements were obtained in ACL-intact knees at different time points. Therefore, tibial acceleration during the pivot shift test could provide quantitative evaluation of rotational stability before and after ACL reconstruction., Level of Evidence: III.

For single colloidal Ag nanoaggregates, covered with either large or small amounts of citrate anions, blinking surface-enhanced Raman scattering (SERS) of anionic thiacyanine was measured and analyzed by a truncated power law. The power law without and with an exponential function reproduces a probability distribution for bright and dark SERS events versus their duration times, respectively. On the Ag surface, except for junctions of the nanoaggregate with a large or small amount of the citrate anions, two-dimensional fast or one-dimensional slow random walk of the anionic thiacyanine, respectively, was estimated by the exponents and the truncation times in the power law for the dark SERS events. In addition, the power law exponents for the bright SERS events were derived to be of similar values, indicating a similar molecular random walk near the junction, which may be dominated evenly by a surface-plasmon-enhanced electromagnetic field on the same-sized Ag nanoaggregate. Thus, not only the bright SERS, but also the dark SERS molecular behaviour on the Ag surface was investigated by the truncated power law analysis.

Purpose: The tibia first technique in unicompartmental knee arthroplasty (UKA) may have the advantage that surgeons can obtain a balanced flexion-extension gap. However, changes of the soft tissue tension during UKA have not been elucidated yet. The purpose of this study was to examine the correlation between the soft tissue tension before the femoral osteotomy and after the femoral component is in place using the tibia first technique in UKA., Methods: Thirty UKAs for isolated medial compartmental osteoarthritis or idiopathic osteonecrosis were assessed. The actual values of the proximal and posterior femoral osteotomy were calculated by adding the thickness of the bone saw blades to the thickness of the bony cut. Using a UKA tensor designed to facilitate intra-operative soft tissue tension throughout the range of motion (ROM), the original gap before the femoral osteotomy, the component gap after the femoral osteotomy, and component placement were assessed under 20-lb distraction forces., Results: The mean actual thickness of the distal femoral osteotomy was 6.5 ± 1.3 mm and the posterior femoral osteotomy was 7.4 ± 1.3 mm. The distal thickness of the prosthesis was set to 6.5 mm and the mean posterior thickness of the prosthesis used in this study was 5.8 ± 0.3 mm. There is a positive correlation between the original and component gap throughout the ROM (R > 0.5). The original and component gap showed the same kinematic pattern from full extension to 90° of knee flexion. However, the component gap was significantly higher compared to the original gap after 120° of knee flexion (P < 0.001)., Conclusions: Despite the fact that the component gap values were significantly higher compared to the original gap value in deep flexion, there is a positive correlation between the original and component gap throughout the ROM. The discrepancy during deep flexion was due to the posterior design of the prosthesis that is designed to be thinner than the actual thickness of the posterior osteotomy. These results suggest that the tibia first technique with the tensor have the advantage that surgeons can predict final soft tissue tension before femoral osteotomies with the prosthetic design and help restore natural knee kinematics, potentially improving implant survival and functional outcomes.

New schemes on the cost-effectiveness acceptability curve (CEAC) were developed, which can make the CEAC augmented to be more informative regarding the types of acceptance and statistical inference. Theoretical approaches have been undertaken to address two questions: 1) how the area under the curve (AUC) can be zoned by different types of acceptance displayed on the incremental cost-effectiveness plane, and 2) how the accepted dataset of incremental cost-effectiveness ratios (ICERs), which are generated by simulation runs, can be statistically associated with a threshold of ICER for acceptance. To address the first question, the AUC of a typically sigmoid-shaped CEAC was divided into three zones according to the three segmentations of the scattered plots accepted at South-east, North-east and South-west quadrants on the incremental cost-effectiveness plane. A solution for the second question was "a new CEAC of the mean" (mCEAC), which is defined by plotting a pair of the mean and its occurrence probability of ICER accepted at North-east quadrant on the incremental cost-effectiveness plane. All those schemes were graphically illustrated based on hypothetical examples using the bootstrapping simulation. Our new schemes on CEAC will provide decision makers with useful information on cost-effectiveness assessment beyond the standard presentation of CEAC.

Background: The anterior cruciate ligament (ACL) does not heal spontaneously after injury, and ACL patients of different ages respond differently to treatment. Although ACL-derived CD34-positive cells contribute to bone-tendon healing after ACL reconstruction, the relationship between the healing potential of ACL-derived cells and a patient's age is unknown., Hypothesis: ACL-derived cells from young patients will have a greater effect on the maturation of bone-tendon integration in an immunodeficient rat model of ACL reconstruction compared with cells derived from older patients., Study Design: Controlled laboratory study., Methods: Sixty 10-week-old female immunodeficient rats underwent ACL reconstruction (using the autologous flexor digitorum longus tendon as a graft) followed by intracapsular administration of ACL-derived cells from patients aged 10 to 19 years (younger group) or patients aged 30 to 39 years (older group), or they were given phosphate-buffered saline (PBS; PBS group). Histologic, radiographic, and biomechanical examinations were performed 2 to 8 weeks after surgery. In addition, intrinsic and human cell-derived angiogenesis and osteogenesis were examined by immunohistochemistry., Results: In the younger group, histologic assessment demonstrated early bone-tendon healing, which induced endochondral ossification-like integration. Micro-computed tomography showed a statistically significant reduction in the area of tibial bone tunnel in the younger group (week 4, 20.0% ± 11.2% reduction; week 8, 25.7% ± 5.6% reduction) compared with the older group (week 4, 1.8% ± 3.0% reduction; week 8, 4.0% ± 5.9% reduction) and the PBS group (week 4, -0.5% ± 3.2% reduction; week 8, 3.3% ± 5.2% reduction) (week 4, P < .05; week 8, P < .01). Failure loads during tensile testing demonstrated a significantly higher ultimate load to failure in the younger group (17.52 ± 4.01 N) compared with the older (8.05 ± 2.91 N) and PBS (7.01 ± 3.16 N) groups (P < .05), and isolectin B4 and rat osteocalcin immunostaining indicated enhanced intrinsic angiogenesis and osteogenesis in the younger group. There was no statistically significant difference in the results of radiographic and biomechanical examinations between the older and PBS groups. Double immunohistochemistry for human-specific endothelial cell and osteoblast markers demonstrated a greater ability of differentiation into endothelial cells and osteoblasts in the younger group., Conclusion: ACL-derived cells from younger patients enhanced early bone-tendon healing in an immunodeficient rat model of ACL reconstruction., Clinical Relevance: Surgeons should consider a patient's age when performing ACL reconstruction with remnant preservation or ruptured tissue incorporation, as this can predict healing ability., (© 2015 The Author(s).)

Background: The morphology of the supraspinatus tendon may affect tear propagation. It was hypothesized that tears located in the anterior third of the supraspinatus tendon would propagate more readily and would require lower loads to reach critical amounts of tear propagation than those located in the middle third of the supraspinatus tendon., Methods: Twenty-three fresh-frozen human cadaveric shoulders were tested under increasing levels of cyclic loading. Tears were created in the anterior third (Group A, n=10) or the middle third (Group M, n=13) of the supraspinatus tendon. The maximum load at which a critical tear retraction was reached and the tear area for the final loading set were compared between groups. A correlation analysis was also performed for age compared with maximum load., Results: No significant differences were found between the anterior-third tear group (Group A) and the middle-third tear group (Group M) in maximum load (p=0.09) or tear area (p=0.6). However, Group A first reached a 100% increase in tear size at a significantly lower load than Group M (p=0.03). Strong negative correlations were detected between age and maximum load in Group A (τ=-0.82) and Group M (r=-0.63)., Conclusions: Other factors being equal, tears in the anterior supraspinatus tendon may propagate more readily than tears in the tendon's middle part. Age may be a factor for tear propagation., Clinical Relevance: Older patients and patients with tears in the anterior supraspinatus should be followed especially carefully., (Copyright © 2015 by The Journal of Bone and Joint Surgery, Incorporated.)

Rotator cuff tears are a significant clinical problem. Tears in the anterior supraspinatus might behave differently compared to central tears due to differences in regional structural properties. The objective of this study was to determine strain distributions for anterior supraspinatus tendon tears and the relationship to tear propagation during cyclic loading. It was hypothesized that highest maximum principal strain would be posterior to the tear, and tears would propagate in the direction of the maximum principal strain. Eight human cadaveric supraspinatus tendons with surgically created small tears in the anterior third were tested with increasing levels of cyclic loads. The position of strain markers was recorded on the bursal surface of the tendon to calculate strain. Tendons reached a 2 cm critical tendon retraction at 580 ± 181 N. Largest strains were found medial and posterior to the tear (26.1 ± 9.4%). In five tendons, the strain direction for the initial (114 ± 28°) and final loading sets (86 ± 20°) indicated the strain direction shifted from an anterior to posterior orientation (p < 0.01), corresponding to the direction of tear propagation. Based on the results, anterior supraspinatus tears would remain isolated to the supraspinatus tendon during activities of daily living., (© 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Background: The femoral and tibial bone tunnel enlargement after anatomic double-bundle anterior cruciate ligament reconstruction (ACL-R) has not been fully documented., Purpose: To evaluate the region-specific bone tunnel volume changes and those transpositions using 3-dimensional multidetector-row computed tomography (MDCT) after anatomic double-bundle ACL-R., Study Design: Case series; Level of evidence, 4., Methods: Eleven patients who underwent unilateral double-bundle ACL-R with hamstring tendon autografts were included in this study. MDCT scanning of their knees was performed at 3 weeks and 1 year after surgery. The bone tunnel regions were extracted from the MDCT images, and the longitudinal axis of each bone tunnel was divided into 3 equal sections. The centroids of the outside and the articular thirds were then extracted from the bone tunnel position. Changes in the bone tunnel volume and the transposition of the articular third were calculated and compared., Results: At 1 year postoperatively, as compared with the 3-week postoperative value (set at 100%), the femoral bone tunnel volume of the anteromedial bundle (AMB) and posterolateral bundle (PLB) changed to 77.4% ± 15.3% and 102.3% ± 19.2% in the outside third and 122.3% ± 31.8% and 112.5% ± 34.4% in the articular third, respectively. The tibial bone tunnel volume of the AMB and the PLB changed to 108.6% ± 28.7% and 105.4% ± 22.6% in the tibial articular third and 54.9% ± 25.8% and 52.5% ± 26.9% in the outside third, respectively. The femoral outside third of the AMB and the tibial outside third of both the AMB and PLB were significantly reduced in bone tunnel volume. The centroid of the femoral articular third of the AMB moved 13°, 1.1 ± 0.6 mm posterodistally, and that of the PLB moved 35°, 0.8 ± 0.4 mm anterodistally. Furthermore, the centroid of the tibial articular third of the AMB moved 14°, 2.0 ± 1.6 mm posterolaterally, and that of the PLB moved 72°, 1.0 ± 1.3 mm posterolaterally., Conclusion: Compared with 3 weeks postoperatively, the articular side outlets of the femoral and tibial bone tunnels at 1 year postoperatively had enlarged slightly but statistically maintained their volume, and they had moved a little in the direction that the grafts were pulled., (© 2014 The Author(s).)

Purpose: To compare the tunnel enlargement of double-bundle (DB) anterior cruciate ligament reconstruction (ACLR) with and without suturing of autologous ruptured tissue to hamstring graft in patients with subacute anterior cruciate ligament injury., Methods: Ten patients with subacute (≤3 months after injury) anterior cruciate ligament rupture were randomly allocated to undergo DB ACLR with suturing of the ruptured tissue to hamstring graft (n = 5) or conventional DB ACLR (n = 5). When autologous ruptured tissue was used, remnant ruptured tissue was then harvested, divided into 4 pieces, placed between the loops at the distal and proximal portions of the graft, and secured with the suture. As the primary endpoint, tunnel volume assessment by 3-dimensional multi-detector row computed tomography (MDCT) was performed 1 year after ACLR. To assess the efficacy of these procedures, the Lysholm score, anterior tibial translation (measured with a KT-1000 arthrometer [MEDmetric, San Diego, CA]), and rotational instability (measured by the pivot-shift test) were evaluated after 2 years., Results: Tunnel volume enlargement between 3 weeks and 1 year after ACLR as assessed by 3-dimensional MDCT was significantly less for ACLR using ruptured tissue than for conventional ACLR, especially at the femoral site (P < .05). However, the postoperative Lysholm score, anterior stability of the knee measured with the KT-1000 arthrometer, and rate of negative manual pivot-shift test results did not differ significantly between the 2 groups. There was no correlation to the clinical outcomes in terms of tunnel size., Conclusions: The Lysholm score, anterior laxity measured with the KT-1000 arthrometer, and rotational instability according to the pivot-shift test did not differ significantly between ACLR using ruptured tissue and the conventional technique. However, ACLR using ruptured tissue produced less femoral tunnel enlargement as assessed by MDCT, warranting further long-term follow-up to elucidate its effectiveness., Level of Evidence: Level II, prospective comparative study., (Copyright © 2014 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Background: Autogenous osteochondral grafting has been widely performed as a treatment for focal osteochondral defects. In this procedure, it is important to match the shape of the articular surface between the donor site and recipient site to reproduce the original articular surface of the femur., Purpose: To investigate the ideal matching patterns of articular surface profiles of donor and recipient sites for autogenous osteochondral grafting of the femur using a 3-dimensional laser scanning method., Study Design: Descriptive laboratory study., Methods: The donor and recipient sites in 11 cadaveric knees were examined, and each of the sites was divided into 12 areas. In the donor sites, the contours of the articular surface of the medial and lateral femoral trochleae were determined. In the recipient sites, the contours of the articular surface of the medial and lateral femoral condyles were assessed. Vertical intervals (VIs) were then calculated as the parameter for the height of the articular surface. The VI was the height difference from the highest and lowest points in the contours of the articular surface within the area of the donor and recipient sites. Finally, assessments were made on whether the articular surface of the donor and recipient sites matched properly for cylindrical osteochondral grafts with diameters of 6, 8, and 10 mm., Results: For the donor site, the VIs of the middle area of the femoral trochlea were significantly smaller than those of the peripheral area. For the recipient site, the VIs of the anterior area of the femoral condyle were significantly smaller than those of the posterior area., Conclusion: These results indicated in aging specimens that the articular surface profile of the middle area of the donor site matched that of the anterior area of the recipient site. On the other hand, the shape of the articular surface of the peripheral area of the donor site was congruent with that of the posterior area of the recipient site., Clinical Relevance: This study will be useful for improving donor site selection during preoperative planning. The authors recommend selection of the middle area of the femoral trochlea for cartilage defects in the anterior area of the femoral condyle and of the peripheral area of the femoral trochlea for cartilage defects in the posterior area of the femoral condyle.

Objectives: The present study aimed to identify the effect of memory-related genes on male rats tested for spatial memory with either molar teeth extraction or its restoration by occlusal support using experimental dentures., Design: Memory-related genes were detected from hippocampi of male Wistar rats (exposed to teeth extraction with or without dentures, or no extraction (control)) (7-week old) after behavioural testing (via the radial maze task) using a DNA microarray. The time course of the expression of these genes was evaluated by quantitative real-time polymerase chain reaction (PCR) (on 49-week-old rats)., Results: In preliminary experiments, to determine which memory genes are affected by spatial memory training, DNA microarray analysis revealed that thyrotropin-releasing hormone (Trh) and tenascin XA (Tnxa) were up-regulated and neuronatin (Nnat) and S100a9 were down-regulated after the maze training. The expression of Tnxa, Nnat and S100a9 of 49-week-old rats (during the time course) via quantitative real-time PCR was consistent with the results of microarrays of the preliminary experiment. Expression of Trh that was evaluated by quantitative real-time PCR did not agree with the results for this gene from the microarray for all groups. Therefore, expression of Trh may have increased in only young, trained rats. The expression of S100a9 prior to the maze task was down-regulated in only the extraction group., Conclusion: These results demonstrated that Trh, Tnxa and Nnat genes were affected according to the degree of memory in male rats. This study also indicated that S100a9 is a memory-related gene, which is affected by the presence of occlusal support., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

We report herein a 53-year-old Japanese female case of polypoid adenomyoma of endocervical type. A sessile 16 mm sized cervical polyp, hard in consistency, was surgically removed. Histologically, the polypoid lesion was composed of smooth muscle bundles and scattered benign-looking endocervical glands. The mucin was diffusely alcianophilic. Immunohistochemically, some mucous glands were positive for MUC1 (CA15-3) and MUC5AC, and the other small glands were immunoreactive for MUC6. MUC2 and mucin characteristic of gastric gland mucous cells (M-GGMC-1 or HIK1083) were negative. Carcinoembryonic antigen was consistently expressed along the apical surface. Estrogen receptor was positive, while progesterone receptor was negative. Ki-67 labeling index was low. These findings were consistent with the endocervical nature of the mucin-producing columnar cells. This is the 18th case of adenomyoma of endocervical type reported in the English literature.

Purpose: To investigate the congruency of the articular cartilage surface of the knee between the recipient and donor site during autogenous osteochondral grafting using a three-dimensional (3D) laser scanning., Methods: Six cadaveric knees were included in this study. The 3D profiles of the articular surface were obtained by a 3D laser scanner (FastSCAN(®), Polhemus). We divided each of the donor and recipient sites into 6 areas in each. The 2 central areas of the donor site were excluded from evaluation because of the trochlear groove. In the donor site, the peripheral and the middle one-third of the femoral articular surface in the medial and lateral patellofemoral joint were extracted. In the recipient site, the peripheral and the middle one-third of the articular surface in the medial and lateral femoral condyle were assessed. In each recipient area, vertical intervals (VIs) of grafts of 6, 8, and 10 mm diameter, showing the distance between highest and lowest point of articular surface were calculated from the data obtained and to the donor sites for matching., Results: ϕ6- and ϕ8-mm grafts The VI of the middle area of the donor site did not differ significantly from that of either the peripheral or the middle area of the recipient site. The VI of the peripheral area of the donor site was significantly higher than that of the peripheral area of the recipient site (p < 0.01). ϕ10-mm grafts The VI of the middle area of the donor site was significantly lower than that of the peripheral area of the recipient site. The VI of the peripheral area of the donor site was significantly higher than that of the middle area of the recipient site (p < 0.01)., Conclusions: An osteochondral graft harvested from the peripheral area of the patellofemoral joint might protrude into the middle area in the recipient site, whereas a ϕ10-mm osteochondral graft harvested from the middle area might be depressed from the peripheral area into the recipient site.

Anatomic anterior cruciate ligament (ACL) reconstruction is common procedure performed by orthopedic surgeons, particularly in association with sports-related injuries. Whereas traditional reconstruction techniques used a single bundle graft that was typically placed in a non-anatomic position, a renewed interest in anatomy has facilitated the popularization of anatomic reconstruction techniques. Recently, a focus has been placed on individualizing ACL surgery based on each patient's native anatomical characteristics (e.g., insertion site size, notch size, and shape), thereby dictating the ultimate procedure of choice. As subjective outcome measurements have demonstrated varying outcomes with respect to single- versus double-bundle ACL reconstruction, investigators have turned to more objective techniques, such as in vivo kinematics, as a means of evaluating joint motion and cartilage contact mechanics. Further investigation in this area may yield important information with regard to the potential progression to osteoarthritis after ACL reconstruction, including factors affecting or preventing it.