Modulation of WNT, Activin/Nodal, and MAPK Signaling Pathways Increases Arterial Hemogenic Endothelium and Hematopoietic Stem/Progenitor Cell Formation During Human iPSC Differentiation.

Several differentiation protocols enable the emergence of hematopoietic stem and progenitor cells (HSPCs) from human-induced pluripotent stem cells (iPSCs), yet optimized schemes to promote the development of HSPCs with self-renewal, multilineage differentiation, and engraftment potential are lacking. To improve human iPSC differentiation methods, we modulated WNT, Activin/Nodal, and MAPK signaling pathways by stage-specific addition of small-molecule regulators CHIR99021, SB431542, and LY294002, respectively, and measured the impact on hematoendothelial formation in culture. Manipulation of these pathways provided a synergy sufficient to enhance formation of arterial hemogenic endothelium (HE) relative to control culture conditions. Importantly, this approach significantly increased production of human HSPCs with self-renewal and multilineage differentiation properties, as well as phenotypic and molecular evidence of progressive maturation in culture. Together, these findings provide a stepwise improvement in human iPSC differentiation protocols and offer a framework for manipulating intrinsic cellular cues to enable de novo generation of human HSPCs with functionality in vivo.

Ex vivo culture resting time impacts transplantation outcomes of genome-edited human hematopoietic stem and progenitor cells in xenograft mouse models.

Ex vivo resting culture is a standard procedure following genome editing in hematopoietic stem and progenitor cells (HSPCs). However, prolonged culture may critically affect cell viability and stem cell function. We investigated whether varying durations of culture resting times impact the engraftment efficiency of human CD34+ HSPCs edited at the BCL11A enhancer, a key regulator in the expression of fetal hemoglobin. We employed electroporation to introduce CRISPR-Cas9 components for BCL11A enhancer editing and compared outcomes with nonelectroporated (NEP) and electroporated-only (EP) control groups. Post-electroporation, we monitored cell viability, death rates, and the frequency of enriched hematopoietic stem cell (HSC) fractions (CD34+CD90+CD45RA- cells) over a 48-hour period. Our findings reveal that while the NEP group showed an increase in cell numbers 24 hours post-electroporation, both EP and BCL11A-edited groups experienced significant cell loss. Although CD34+ cell frequency remained high in all groups for up to 48 hours post-electroporation, the frequency of the HSC-enriched fraction was significantly lower in the EP and edited groups compared to the NEP group. In NBSGW xenograft mouse models, both conditioned with busulfan and nonconditioned, we found that immediate transplantation post-electroporation led to enhanced engraftment without compromising editing efficiency. Human glycophorin A+ (GPA+) red blood cells (RBCs) sorted from bone marrow of all BCL11A edited mice exhibited similar levels of γ-globin expression, regardless of infusion time. Our findings underscore the critical importance of optimizing the culture duration between genome editing and transplantation. Minimizing this interval may significantly enhance engraftment success and minimize cell loss without compromising editing efficiency. These insights offer a pathway to improve the success rates of genome editing in HSPCs, particularly for conditions like sickle cell disease.

Influence of the menstrual cycle on static and dynamic kinematics of the foot medial longitudinal arch.

BACKGROUND: In women, the laxity of the plantar fascia increases during the ovulation phase of the menstrual cycle. Although it is possible that this increased laxity results in a decreased height of the foot in the medial longitudinal arch and exacerbates symptoms of several overuse injuries of the lower extremity, the influence of the menstrual cycle on static and dynamic kinematics of the medial longitudinal arch is unclear. The purpose of this study was to confirm that the medial longitudinal arch height during static standing, gait, and landing decrease during the menstrual cycle ovulation phase. METHODS: Participants in this study were 16 female college students with normal menstrual cycles and 16 male college students. Navicular height in the static standing position was measured using a three-dimensional foot scanner. Kinematics of the medial longitudinal arch during gait and landing were measured using a three-dimensional motion capture system to determine the navicular height at initial contact, minimal navicular height, and dynamic navicular drop. In all measurements, female participants were tested twice during the course of one complete menstrual cycle: once during the follicular phase and once during the ovulation phase. Male participants were tested twice with an interval of ≥1 week and <2 weeks. RESULTS: In women, navicular height in the static standing position significantly decreased during the ovulation phase compared with follicular phase (mean difference [95% confidence interval] = 2.1 [0.9-3.4] mm; p = 0.002), whereas men showed no statistical difference between the first and second measurements. In both men and women, no statistical differences were identified for the dynamic medial longitudinal arch kinematics measured during gait and landing. CONCLUSIONS: Navicular height in the static standing position slightly decreased during the ovulation phase.

Risk factors of residual pivot-shift after anatomic double-bundle anterior cruciate ligament reconstruction.

INTRODUCTION: Although anterior cruciate ligament reconstruction (ACLR) is considered a successful procedure, residual pivot-shift after surgery remains to be solved. The purpose of this study was to comprehensively evaluate the risk factors of residual pivot-shift after anatomic double-bundle (DB) ACLR. MATERIALS AND METHODS: A total of 164 patients who underwent primary anatomic DB-ACLR between January 2014 and December 2019 and screw removal after the index ACLR in our hospital were included in this retrospective case-control study. The manual pivot-shift test was performed under general anesthesia during screw removal surgery, and patients with grade 1 or higher pivot-shift were classified as the positive pivot-shift group, and those with grade 0 were defined as the negative pivot-shift group. Univariate and logistic regression analyses were performed to identify the factors associated with postoperative residual pivot-shift. Assessment included sex, age, time to surgery, preoperative Tegner activity scale, preoperative pivot-shift grade, preoperative anterior tibial translation by the KT-2000 arthrometer measurement, meniscus injury and its surgical procedure, knee hyperextension, cartilage damage, Segond fracture, medial and lateral posterior tibial slope, lateral-medial slope asymmetry, participation in pivoting sport/activity at the time of injury, and return to sports at postoperative one year line. RESULTS: Postoperative positive pivot-shift was observed in 14 (8.5%) of 164 patients. The KT-2000 measurement at 1-year postoperatively was significantly higher in the residual pivot-shift-positive group than in the negative group (P < 0.05). Logistic regression analysis revealed that age of patients < 20 years [P < 0.05, odds ratio (OR): 6.1)], preoperative pivot-shift grade (P < 0.05, OR: 4.4), and hyperextended knee (P < 0.05, OR: 11.8) were risk factors of postoperative pivot-shift. There were no statistically significant differences between other variables. CONCLUSIONS: Patients < 20 years of age, with high-grade preoperative pivot-shift, or hyperextended knees had a higher risk of residual postoperative pivot-shift.

Talar component subsidence correlates with periprosthetic osteolysis after total ankle arthroplasty.

PURPOSE: This study aimed to investigate the relationship between periprosthetic osteolysis around the talar component and the amount of talar component subsidence after total ankle arthroplasty (TAA). METHODS: This study included forty patients who underwent TAA with a mean follow-up of 67.5 ± 17.0 months. The patients were divided into two groups based on the amount of osteolysis around the talar component, as measured by computed tomography at the latest clinic visit: none to 2 mm (N group, n = 20) and greater than or equal to 2 mm (O group, n = 20). The average amount of talar component subsidence, clinical outcomes, and complications were compared between the two groups. In the O group, the correlation between osteolysis and talar component subsidence was evaluated. RESULTS: The average talar component subsidence was significantly different between the N (0.22 ± 0.94 mm) and O groups (2.12 ± 2.28 mm). Five out of 20 ankles in the O group required revision surgery owing to talar component subsidence. The Japanese Society for Surgery of the Foot scores in the N and O groups were significantly different: 93.5 ± 7.7 and 85.3 ± 15.4, respectively. In the O group, we found that osteolysis tended to develop on the lateral side, and the amount of osteolysis was positively correlated with the talar component subsidence (r = 0.59, P = .007). CONCLUSION: In the O group, a positive correlation between osteolysis and talar component subsidence was found, and five patients required revision surgery.

FZD5 regulates cellular senescence in human mesenchymal stem/stromal cells.

Human mesenchymal stem/stromal cells (hMSCs) have garnered enormous interest as a potential resource for cell-based therapies. However, the molecular mechanisms regulating senescence in hMSCs remain unclear. To elucidate these mechanisms, we performed gene expression profiling to compare clonal immature MSCs exhibiting multipotency with less potent MSCs. We found that the transcription factor Frizzled 5 (FZD5) is expressed specifically in immature hMSCs. The FZD5 cell surface antigen was also highly expressed in the primary MSC fraction (LNGFR+ THY-1+ ) and cultured MSCs. Treatment of cells with the FZD5 ligand WNT5A promoted their proliferation. Upon FZD5 knockdown, hMSCs exhibited markedly attenuated proliferation and differentiation ability. The observed increase in the levels of senescence markers suggested that FZD5 knockdown promotes cellular senescence by regulating the noncanonical Wnt pathway. Conversely, FZD5 overexpression delayed cell cycle arrest during the continued culture of hMSCs. These results indicated that the intrinsic activation of FZD5 plays an essential role in negatively regulating senescence in hMSCs and suggested that controlling FZD5 signaling offers the potential to regulate hMSC quality and improve the efficacy of cell-replacement therapies using hMSCs.

Direct suturing quadriceps tendon to a continuous loop with a suspensory button provides biomechanically superior fixation in ACL reconstruction.

PURPOSE: To compare the biomechanical strength of different fixation configurations using suspensory buttons in a soft-tissue quadriceps tendon (QT) grafts in anterior cruciate ligament (ACL) reconstruction. METHODS: Forty bovine QTs, 6-cm long and 10-mm wide, were allocated into four groups with different suture configurations using suspensory buttons (n = 10 in each group): Group A, a baseball suture with a knot tied to the continuous loop with a suspensory button; Group B, same configuration as in Group A but with the knot tied at the opposite end of the baseball suture; Group C, a continuous loop with a suspensory button stitched directly to the QT with simple sutures, and Group D, a baseball suture tied directly to a suspensory button. Biomechanical testing was performed by preloading followed by cyclic loading for 500 cycles between 10 and 100 N. The length of elongation (mm) and maximum load to failure (N) were recorded, and compared among the four groups. RESULTS: Group C showed significantly smaller elongation (4.1 mm [95% CI 3.1-5.2]) than Group A (8.2 mm [95% CI 7.0-9.4]), Group B (10.5 mm [95% CI 7.7-13.3]), and Group D (8.5 mm [95% CI 7.0-9.9]) (A-C; P = 0.004, B-C; P = 0.0001, C-D; P = 0.0018). The maximum load to failure in Group C (386 N [95%CI 306-466]) was significantly higher than that in Group A (196 N [95% CI 141-251]), Group B (226 N [95% CI 164-289]), and Group D (212 N [95%CI 171-253]) (A-C; P = 0.0001, B-C; P = 0.0009, C-D; P = 0.0002). No significant differences were observed between Group A, B, and D in terms of elongation and maximum load to failure. CONCLUSION: The soft-tissue QT graft fixation configuration stitched directly to a continuous loop with suspensory button using simple sutures exhibits small elongation and high maximum load to failure among the four configurations. Regarding clinical relevance, direct suturing of the soft-tissue QT to a continuous loop with a suspensory button may be advantageous for femoral fixation in ACL reconstruction from a biomechanical perspective, and warrant future development of a novel fixation device using this principle.

Anatomic double-bundle anterior cruciate ligament reconstruction could not achieve sufficient control of pivot-shift when accompanying tibial tunnel coalition.

PURPOSE: To evaluate the effect of tibial tunnel coalition on knee rotatory laxity and clinical outcomes after double-bundle (DB) anterior cruciate ligament (ACL) reconstruction. METHODS: Forty-one patients who underwent anatomic DB ACL reconstruction were included prospectively. Three-dimensional computed tomography of the knee joint was obtained at approximately 1 year postoperatively to determine if tunnel coalition occurred. After excluding seven cases of femoral tunnel coalition, two groups were established based on the existence of a tibial tunnel coalition. The pivot-shift test was quantitatively evaluated on the basis of tibial acceleration preoperatively and at 1 year postoperatively. Two subjective scores, the International Knee Documentation Committee (IKDC) subjective and Lysholm scores, were also collected. The pivot-shift measurement and subjective scores were compared between the ACL-reconstructed knees with and without tibial tunnel coalition. The independent t test, Pearson's chi-square test, and Student t tests were used in data analysis. RESULTS: Twenty-one knees had tibial tunnel coalition (group C), whereas 13 knees did not have tunnel coalition(group N). Pivot-shift was significantly diminished postoperatively in both groups on the basis of the clinical examination and quantitative evaluations (p < 0.05). However, there was a small but significant difference in tibial acceleration demonstrating larger pivot-shift in group C (1.0 ± 0.6 m/s2) than in group N (0.5 ± 0.3 m/s2, p < 0.05). No significant difference was observed in the IKDC subjective and Lysholm scores (both n.s.). CONCLUSION: When the tibial tunnel coalition occurs after DB ACL reconstruction, knee rotatory laxity may not be restored in ACL-reconstructed knees, as expected in those without tunnel coalition. It is recommended that two tibial tunnels should be created separately when performing DB-ACL reconstruction to achieve better control of rotatory knee laxity. LEVEL OF EVIDENCE: III.

The sagittal cutting plane affects evaluation of the femoral bone tunnel position on three-dimensional computed tomography after anterior cruciate ligament reconstruction.

PURPOSE: To investigate how the femoral sagittal cutting plane affects evaluation of the bone tunnel position after anterior cruciate ligament (ACL) reconstruction using the quadrant method in three-dimensional computed tomography (CT) imaging. METHODS: Thirty patients who underwent primary anatomic double-bundle ACL reconstruction and CT 2 weeks after surgery were enrolled. Three sagittal cutting planes with respect to the condylar axis were created using the CT images: at the top of the intercondylar notch (C-plane), 5% medial (M-plane), and 5% lateral (L-plane). The center of the bone tunnel position regarding depth and height of the anteromedial (AMB) and posterolateral bundle (PLB) were quantitatively evaluated using the quadrant method on the three different planes. RESULTS: The mean depths of AMB and PLB were 27.4 ± 4.4% and 39.7 ± 5.1%, 27.0 ± 4.2% and 37.6 ± 4.9%, and 27.4 ± 4.5% and 38.5 ± 6.0%, at the M, C and L planes, respectively. The mean heights of AMB and PLB were 30.8 ± 6.3% and 56.2 ± 5.6%, 30.4 ± 6.2% and 56.6 ± 5.6%, and 25.4 ± 7.0% and 52.9 ± 6.9% at the M, C, and L planes, respectively. Both AMB and PLB bone tunnels were evaluated as higher positions in the L-plane than the C-plane (p < 0.01, p = 0.02, respectively) and M-plane (p < 0.01, p = 0.04, respectively), but there were no significant differences between the C-plane and M-plane (n.s.). There was no significant difference in the anteroposterior direction for all planes. CONCLUSION: In evaluations of the bone tunnel position with the quadrant method using three-dimensional CT, the bone tunnel position depends on the femoral sagittal cutting plane. A consistent evaluation method should be used when evaluating the bone tunnel position after ACL reconstruction to enable correct evaluation clinically. LEVEL OF EVIDENCE: Case-control study, Level III.

Anterior placement of the talar component in total ankle arthroplasty: A risk factor for talar component subsidence.

BACKGROUND: Component subsidence is considered as a cause of revision surgery. The talar component subsidence may be a risk factor for revision surgery; however, there are no reports regarding talar component placement and subsidence amount following total ankle arthroplasty (TAA). We therefore investigated the relationship between talar component placement and subsidence amount. METHODS: Fifty-two ankles from 49 patients (age: 71 years [range 62-83], 13 male/ 36 female), who underwent TAA with mean follow-up of 36 months (range 12-83), were included. The subjects were divided into two groups based on talar component placement: anterior placement (n = 20, group A) and posterior placement (n = 32, group P) using weight-bearing lateral plain radiographs. The amount of the talar component subsidence and clinical outcomes, which included the Japanese Society for Surgery of the Foot (JSSF) scale, range of the motion (ROM) and the revision rate, were compared between the groups. RESULTS: Talar component subsidence was significantly higher in group A (2.1 ± 2.0 mm) than in group P (0.6 ± 1.4 mm, P = .017). There was no significant difference in the JSSF scale and ROM between group A and group P. The revision rate was 10.0% in group A and 6.3% in group P, albeit not statistically significant. CONCLUSION: Greater talar component subsidence was observed when the talar component was placed more anteriorly, suggesting that anterior placement of the talar component may need to be avoided during the surgery in order to minimize the postoperative talar component subsidence.

The Influences of Chronicity and Meniscal Injuries on Pivot Shift in Anterior Cruciate Ligament-Deficient Knees: Quantitative Evaluation Using an Electromagnetic Measurement System.

PURPOSE: To investigate the influences of time from injury to surgery and meniscal injuries on knee rotational laxity in anterior cruciate ligament (ACL)-deficient knees using the electromagnetic system retrospectively. METHODS: Ninety-four unilateral ACL-injured patients (44 male and 50 female, mean age: 27.3 ± 11.8 years) were included. The pivot-shift test was performed before ACL reconstruction, as was a quantitative evaluation using the electromagnetic system to determine tibial acceleration. Patients were divided into 4 groups according to the chronicity: group 1, within 3 months (22 patients); group 2, between 3 and 6 months (29 patients); group 3, between 6 and 12 months (23 patients); and group 4, more than 12 months (20 patients). The presence of meniscal injuries was examined arthroscopically. RESULTS: The tibial acceleration was significantly greater in group 4. There was a positive correlation between tibial acceleration and the time from injury to surgery (r = 0.47, P = .02). In groups 1, 2 and 3, the tibial acceleration in patients with a lateral meniscal injury was significantly greater than in patients with a medial meniscal injury and without meniscal injury. When patients with lateral meniscal injury were excluded (leaving those with medial meniscus injury or without meniscal injury), group 4 had significantly greater accelerations than other groups. CONCLUSIONS: In ACL-deficient knees, rotational laxity increased with time and the increased rotational laxity was evident more than 1 year after injury whereas it increased with concomitant lateral meniscal injuries within 1 year after injury. LEVEL OF EVIDENCE: Ⅳ, diagnostic study of nonconsecutive patients.

No difference in postoperative rotational laxity after ACL reconstruction in patients with and without anterolateral capsule injury: quantitative evaluation of the pivot-shift test at 1-year follow-up.

PURPOSE: To compare rotational laxity in anterior cruciate ligament (ACL)-reconstructed knees retrospectively with and without concomitant anterolateral capsule (ALC) injury confirmed by magnetic resonance imaging (MRI) prior to ACL reconstruction. METHODS: Sixty-two ACL-reconstructed knees (26 men, 36 women; median age 20 (range 13-59)) were included. Pivot-shift test was performed before ACL reconstruction and 1 year postoperatively under anesthesia with both clinical grading and quantitative measurement simultaneously. Clinical grading was determined according to the International Knee Documentation Committee (IKDC) criteria (none, glide, clunk, or gross), and an electromagnetic measurement system was used to provide tibial acceleration as a quantitative parameter. The resence of concomitant ALC injury was confirmed retrospectively by MRI. The pivot-shift test was compared between ACL-reconstructed knees with and without ALC injury test for clinical grading and the independent t test for quantitative evaluation. RESULTS: ALC injury was identified in 26 of 62 (42%) knees. Before ACL reconstruction, there was no difference in the pivot-shift test results between the ACL-deficient knees with and without ALC injury in IKDC grading (n.s.) or tibial acceleration (1.1 ± 0.7 m/s2 and 1.4 ± 1.1 m/s2, respectively, n.s.). At 1 year postoperatively, no difference was observed between groups (IKDC, p = 0.90; tibial acceleration, 0.6 ± 0.3 m/s2 and 0.8 ± 0.6 m/s2, n.s.). CONCLUSIONS: Concomitant ALC injury at the time of ACL injury had no effect on the rotational laxity of the knee in the postoperative course after ACL reconstruction. Therefore, additional treatment for ALC injury may not be warranted. LEVEL OF EVIDENCE: IV.

Greater knee joint laxity remains in teenagers after anatomical double-bundle anterior cruciate ligament reconstruction compared to young adults.

PURPOSE: There is paucity in studies regarding double-bundle anterior cruciate ligament reconstruction (DB-ACLR) in teenagers. The purpose of this study is to investigate clinical outcome after DB-ACLR and analyze whether any differences exist between teenagers and young adults. METHODS: A retrospective study was performed between 2009 and 2017. Teenagers were defined as patients between 15 and 19 years and young adults between 20 and 25 years old. Isolated anterior cruciate ligament (ACL) injuries with DB-ACLR with minimum two-year follow up were included. Pre and post-operative Lysholm score, Tegner activity scale, KT-2000 arthrometer, manual pivot-shift grade, were assessed with post-operative one-leg hop test, isokinetic knee extensor strength test at 60°/sec, International Knee Documentation Committee Score (IKDC score), and re-injury rate. RESULTS: One-hundred and thirty-one patients, 75 patients in the teenage group (Group A) and 56 patients in the young adult group (Group B), were enrolled. Lysholm score was significantly lower in Group A (89.6 ± 21.1) compared to Group B (95.9 ± 4.6) (p = 0.04). Side to side difference in KT-2000 arthrometer (2.3 ± 2.2 mm vs 1.0 ± 2.3 mm, Group A vs Group B, respectively, p < 0.01) and ratio of post-operative positive pivot shift was significantly greater in Group A (30.7%) compared to Group B (7.1%) (p < 0.01). No significant difference was seen in re-injury rate (n.s.). CONCLUSION: Teenage patients have a greater tendency for residual knee joint laxity after DB-ACLR. Although teenagers and patients in the early twenties are close in age, characteristic in knee joint laxity may be different and, therefore, may require attention upon surgery and post-operative follow-up. LEVEL OF EVIDENCE: III.

Unrepaired lateral meniscus tears lead to remaining pivot-shift in ACL-reconstructed knees.

PURPOSE: To compare the postoperative rotatory knee laxity between ACL-reconstructed knees with different meniscus treatments using an electromagnetic pivot-shift measurement. METHODS: Forty-six patients with unilateral ACL reconstructions were enrolled (21 males/25 females, 25 ± 12 y.o.). Concomitant meniscus tears, if any, were repaired whenever possible during primary ACL reconstruction. At 1 year postoperatively, pivot-shift test was performed under anaesthesia during screw removal surgery and quantitatively evaluated by tibial acceleration using an electromagnetic system. The acceleration was compared between ACL-reconstructed knees with different meniscal treatments: intact, repaired and unrepaired. RESULTS: A concomitant meniscus tear was found in 28 knees preoperatively: lateral tears in 11 knees, medial tears in 11 knees and both medial and lateral tears in 6 knees. Postoperatively, 19 ACL-reconstructed knees had a repaired meniscus for either medial, lateral or bilateral menisci tears, and 18 knees had intact menisci pre- and post-operatively. Meanwhile, nine lateral meniscus tears were irreparable and treated by partial meniscectomy or left in situ. ACL-reconstructed knees with unrepaired lateral menisci had significantly larger pivot-shift acceleration (0.9 ± 0.7 m/s2) than those with intact menisci (0.5 ± 0.2 m/s2, p < 0.05), whereas rotatory knee laxity was similar between the knees with fully repaired menisci (0.6 ± 0.3 m/s2) and intact menisci (n.s.). CONCLUSION: An unrepaired lateral meniscus tear in an ACL-reconstructed knee could lead to remaining pivot-shift postoperatively. A concomitant meniscus tear should be repaired during ACL reconstruction to restore normal rotational laxity. LEVEL OF EVIDENCE: Therapeutic Study, Level III.

Longitudinal Quadriceps Strength Recovery After Anterior Cruciate Ligament Reconstruction With Hamstring Autograft: Patients Stratified by Preoperative Quadriceps Strength Deficit.

CONTEXT: Some studies have discussed postoperative quadriceps strength recovery after anterior cruciate ligament reconstruction (ACLR). However, the effect of preoperative quadriceps strength deficit on longitudinal postoperative quadriceps strength recovery after ACLR with hamstring autograft is unknown. OBJECTIVE: To reveal the longitudinal postoperative quadriceps strength recovery after ACLR with hamstring autograft among patient groups stratified by preoperative quadriceps strength deficit. DESIGN: Retrospective cohort study. SETTING: Single center. PATIENTS: In total, 420 patients (222 men and 218 women; age at the time of surgery 23.1 [8.9] y) who underwent ipsilateral ACLR with hamstring autograft and completed knee function tests preoperatively and 3, 6, and 12 months postoperatively were included in this study. INTERVENTION: The authors measured quadriceps strength at 60°/s, tested 1-leg hop performance (distance and anxiety), and calculated the quadriceps strength index (QSI) and limb symmetry index for 1-leg hop distance. Patients were divided into the following 4 groups according to their preoperative QSI: >80% (Excellent group), 80% to 60% (Good group), 60% to 40% (Moderate group), and ≤40% (Poor group). MAIN OUTCOME MEASURES: Postoperative QSI at 3, 6, and 12 months and 1-leg hop performance at 12 months after the surgery. RESULTS: The Excellent group had the highest postoperative QSI at all periods. Based on the 1-leg hop performance, the Poor group had the lowest limb symmetry index and significantly greater anxiety during jump performance in comparison with the Excellent and Good groups. CONCLUSION: The present study shows a longitudinal recovery process and the average postoperative quadriceps strength after ACLR with hamstring autograft in patient groups stratified by preoperative QSI. The results indicate that the difference in preoperative QSI affects not only the longitudinal postoperative QSI recovery but also high-level 1-leg hop performance after ACLR using hamstring autograft.

MRI-determined anterolateral capsule injury did not affect the pivot-shift in anterior cruciate ligament-injured knees.

PURPOSE: The purpose of this study was to quantitatively compare the results of pivot-shift test between knees with anterior cruciate ligament (ACL) injury with and without anterolateral capsule (ALC) injury detected on MRI. ALC injury was hypothesized to worsen rotatory knee laxity. METHODS: 82 patients with unilateral ACL injury were enrolled in this study. The pivot-shift test was performed under anesthesia before ACL reconstruction. Two evaluations were conducted simultaneously: IKDC clinical grading and the quantitative evaluation using an electromagnetic measurement system that determined tibial acceleration (m/s2). Two examiners identified the ALC injury on magnetic resonance imaging (MRI) and stratified patients into two groups: ALC-injured (ALC+) and ALC-intact (ALC-). ALC injury was diagnosed if the signal intensity on coronal T2-weighted sequences is increased. After confirming the reliability of the MRI, the difference in the pivot-shift between two groups was assessed. RESULTS: Because of the poor agreement between examiners with respect to the ALC evaluations (κ coefficient of 0.25 and 58.5% concordance), the result from each examiner was analyzed separately. Examiner 1 found ALC injury in 42/82 knees (51%). The two groups had similar clinical grading (glide/clunk/gross: ALC+ group 21/18/3cases vs. ALC- group 21/16/3cases) (n.s.). Tibial acceleration during pivot-shift was also similar in the ALC+ (1.4 ± 1.2 m/s2) and ALC- (1.7 ± 1.3 m/s2) groups (n.s.). Examiner 2 found ALC injury in 28/82 knees (34%). Differences in clinical grading were not observed (glide/clunk/gross: ALC+ group 16/9/3 vs. ALC- group 26/25/3) (n.s.). However, the tibial acceleration in the ALC+ group (1.2 ± 0.8 m/s2) was significantly lower than that in the ALC- group (1.7 ± 1.3 m/s2, p = 0.03). CONCLUSION: Concomitant ALC injury in knees with ACL injury was not consistently detected on MRI and did not affect rotatory knee laxity. LEVEL OF EVIDENCE: Case-control study, level III.

The concomitant lateral meniscus injury increased the pivot shift in the anterior cruciate ligament-injured knee.

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/s2 versus meniscus-intact knees: 1.2 ± 0.7 m/s2, 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/s2, 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/s2, n = 12, n.s. and 1.4 ± 1.1 m/s2, 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.

Deterioration of patellofemoral cartilage status after medial open-wedge high tibial osteotomy.

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.

Prediction of quadriceps strength recovery after anterior cruciate ligament reconstruction with a hamstring autograft: Decision tree analysis.

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.

Three-dimensional isotropic magnetic resonance imaging can provide a reliable estimate of the native anterior cruciate ligament insertion site anatomy.

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 mm2 from MRI and 109.7 ± 10.9 mm2 from laser scan (p = 0.345). Tibial insertion area was 134.7 ± 22.9 mm2 from MRI and 135.2 ± 15.1 mm2 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.