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Purpose: The purpose of this study was to evaluate the effects of hamstring harvesting in patients after anterior cruciate ligament (ACL) reconstruction by comparing groups with and without hamstring harvesting. Methods: We evaluated the effect of hamstring harvesting in 73 consecutive patients who underwent ACL reconstruction: 39 patients whose hamstrings were harvested for autografts (group H) were compared with 34 patients who received allografts during the same time period (group C [control]). The cases and controls were compared by analyzing the following variables: age, height, weight, mean follow-up period, type of tissue used, and meniscal surgery. Outcomes were assessed by the Lysholm knee score, Tegner activity score, and KT-2000 side-to-side difference (MEDmetric, San Diego, CA), as well as functional performance tests. The flexor deficit and isokinetic peak torque for knee flexion were measured in the sitting position (0° to 90°), and the flexion torque at 90° was measured in the prone position (60° to 120°). Results: Although significant knee flexion weakness after ACL reconstruction was observed, a significantly greater knee flexor deficit was found in autograft patients than in allograft patients (P < .001). No differences were found between groups in terms of clinical and functional results regardless of hamstring harvesting. The performance of both study groups in all 4 functional tests were significantly correlated with flexor deficit in the sitting position (P < .05) but not in hyperflexion. Significant flexor deficits in both normal and hyperflexed positions were noted in both groups when compared with the unaffected knee (group H, P < .001; group C, P = .002). Conclusions: These results indicate significant knee flexion weakness compared with the unaffected knee after ACL reconstruction regardless of hamstring harvesting. Moreover, the greater increase in knee flexor deficit in the hamstring-harvested group compared with the allograft group was statistically significant. However, clinical and functional outcomes were similar between the groups. Level Of Evidence: Level III, case-control study. [ABSTRACT FROM AUTHOR]

The clinical application of collagen-based biomaterials is expanding rapidly, especially in tissue engineering and cosmetics. While oral supplements and injectable skin boosters are popular for enhancing skin health, clinical evidence supporting their effectiveness remains limited. Injectable products show potential in revitalizing skin, but safety concerns persist due to challenges in sterilization and the risk of biological contamination. Traditional methods of sterilization (heat and irradiation) can denature collagen. This study addresses these issues by introducing a novel technique: the double filtration and low-temperature steam sterilization of a collagen gel. In vitro tests documented the sterility and confirmed that the collagen did not show cytotoxicity, degradation, integrity, and viscosity characteristics changes after the processing and sterilization. The collagen gel induced new collagen expression and the proliferation of human dermal fibroblasts when the cells were cultured with the collagen gel. An in vivo study found no adverse effects in rats or significant lesions at the implantation site over 13 weeks. These results suggest that this novel method to process collagen gels is a safe and effective skin booster. Advanced processing methods are likely to mitigate the safety risks associated with injectable collagen products, though further research is needed to validate their biological effectiveness and clinical benefits.

Purpose: This study aimed to establish the normal values for knee patellofemoral alignment as measured using 3-dimensional computed tomography (3D CT), to standardize the technique, and to show the inter- and intra-observer reliability of this measurement., Methods: The present study included 62 asymptomatic volunteers (124 knees). 3D CT scanning was performed with each volunteer in the supine position with 15° of knee flexion, and consistent 3D axial images of the patellofemoral joint were obtained with alignment in the desired stereographic baseline direction in anterior-posterior, lateral, and axial rotations. Two independent observers measured patellofemoral alignment parameters, including the sulcus angle, congruence angle, lateral patellofemoral angle, condyle-patellar angle, and lateral trochlear inclination angle., Results: Based on 3D CT measurement, the mean values of the parameters were 145.9° ± 9.2° for the sulcus angle, 12.6° ± 22.6° for the congruence angle, 9.2° ± 4.6° for the lateral patellofemoral angle, 14.1° ± 6.4° for the condyle-patellar (lateral facets) angle, - 8.5° ± 8.4° for condyle-patellar (patellar axis) angle, and 16.5° ± 6.3° for the lateral trochlear inclination angle. A statistically significant difference was observed between men and women in the sulcus and condyle-patellar (patellar axis) angles (p = 0.045, 0.011, respectively). All parameters showed excellent inter- and intra-observer reliability., Conclusion: The normal values and ranges for patellofemoral alignment parameters were evaluated using 3D CT. The results of this study provide reference information that may facilitate diagnosis and treatment planning of patellofemoral disorders in skeletally mature non-pathologic patients., Level of Evidence: II., (© 2021. European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)

Aim: To mimic the ultrastructural morphology of the meniscus with nanofiber scaffolds coupled with controlled growth factor delivery to modulate cellular performance for tissue engineering of menisci. Methods: The authors functionalized collagen nanofibers by conjugating heparin to the following growth factors for sustained release: PDGF-BB, TGF-β1 and CTGF. Results: Incorporating growth factors increased human meniscal and synovial cell viability, proliferation and infiltration in vitro , ex vivo and in vivo ; upregulated key genes involved in meniscal extracellular matrix synthesis and enhanced generation of meniscus-like tissue. Conclusion: The authors' results indicate that functionalizing collagen nanofibers can create a cell-favorable micro- and nanoenvironment and can serve as a system for sustained release of bioactive factors.

Purpose: No studies have been conducted to determine long-term predictors of clinical failure after surgical root repair. This study identified long-term prognostic factors of clinical failure after pull-out repair of medial meniscus posterior root tears (MMPRTs) at a minimum of 10 year follow-up., Methods: A total of 37 patients who underwent MMPRT pull-out repair and had been observed for more than 10 years were recruited for this study. The mean follow-up period was 125.9 ± 21.2 months. Clinical failure of the procedures was defined as conversion to total knee arthroplasty (TKA). Participants were categorized into two groups: non-failure and failure groups. Various factors, including demographic features and radiologic findings, were analyzed and compared between the two groups. Meniscus extrusion was assessed at coronal magnetic resonance imaging preoperatively and 1 year postoperatively. Independent risk factors were determined by univariate analysis and logistic regression analysis. To determine the cut-off value for risk factors, the receiver-operating characteristic curve analysis was performed., Results: In total, eight patients (22%) were converted to TKA during the follow-up period. With univariate analysis, statistically significant differences between two groups were observed in mechanical varus alignment (P = 0.018), rate of the number of patient with more meniscal extrusion values after surgery (P = 0.024), and the difference between the preoperative and 1-year postoperative value of meniscus extrusion (mm) (P = 0.010). In a logistic analysis, OR of mechanical varus alignment and differences in meniscus extrusion value before and 1 year after surgery was 1.5 (P = 0.048) and 3.7 (P = 0.034). The cut-off values of mechanical varus alignment and differences in meniscus extrusion values were 5 degrees and 0.7 mm., Conclusion: Clinically, preoperative varus alignment and increased meniscal extrusion after surgery were found to be predictive for a clinical failure after meniscal root repair in a long-term perspective. Thus, these negative prognostic factors should be taken into consideration for performing root repair in MMPRTs., Level of Evidence: Level III., (© 2021. European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)

Background: Stiff knees, like completely ankylosed or arthrodesed knees, can be painless. Total knee arthroplasty (TKA) for these painless, stiff knees is technically demanding. However, it can correct the alignment and advance the range of motion to improve quality of life. So, we reviewed the preoperative and postoperative results of functional and pain scores, range of motion (ROM) and complications in painless, stiff knees treated by TKA., Methods: Fifteen painless, stiff knees underwent TKA from January 1998 to January 2017. The mean follow-up period was 15.4 (2.4-22.2) years. All the knees were completely ankylosed or arthrodesed. Clinical outcome and complications were evaluated using medical record review, serial plan radiography, ROM assessment, Knee Society score (KSS), Knee Society function score (FS), and a visual analog scale for pain (VAS)., Results: All patients were satisfied with their operated knees. Mean KSS and FS scores were improved from 36 and 50.9 to 76.9 and 67.2, respectively (P < 0.001 and P = 0.01). The mean ROM increased from 0º preoperatively to 77.6º (15-130) at the final follow-up (P < 0.001). The mean VAS had worsened from 0 preoperatively to 0.2 postoperatively, however it was not significant (P = 0.1). Major postoperative complications were reported in five of the knees (33.3%)., Conclusions: The results of TKA for painless, stiff knees were satisfactory with improved ROM and quality of life. Although some patients had mild pain and complications postoperatively, they were satisfied with the result. However, our study recommends that surgeons should consider the high rate of complications in the completely ankylosed or arthrodesed knees., Level of Evidence: A retrospective case series, Level IV.

Background: The importance of repair in medial meniscus posterior root tears (MMPRTs) has been increasingly recognized because it restores hoop tension. However, no study has compared the long-term outcomes between meniscectomy and repair., Hypothesis: Survivorship and clinical outcomes of repair would be better than those of meniscectomy after long-term follow-up., Study Design: Cohort study; Level of evidence, 3., Methods: Between 2005 and 2009, patients with MMPRTs who had been followed up for at least 10 years after partial meniscectomy (n = 18) or pullout repair (n = 37) were recruited. Clinical assessments, including the Lysholm score and International Knee Documentation Committee (IKDC) subjective score, were evaluated preoperatively and at the final follow-up. The final results in each group were compared with the preoperative results, and the final results of the groups were compared. Clinical failure was defined as conversion to total knee arthroplasty (TKA), and the final clinical scores were assessed just before TKA. Kaplan-Meier survival analysis was used to investigate the survival rates of surgical procedures., Results: Mean ± SD follow-up period was 101.4 ± 45.9 and 125.9 ± 21.2 months in the meniscectomy and repair groups, respectively ( P = .140). The mean Lysholm and IKDC scores, respectively, in the meniscectomy group were 50.8 ± 7.7 and 37.6 ± 7.0 preoperatively and 58.2 ± 22.1 and 44.4 ± 19.0 postoperatively ( P = .124; P = .240). In the repair group, the mean Lysholm score and IKDC score, respectively, significantly increased from 52.3 ± 10.9 and 41.0 ± 9.6 preoperatively to 77.1 ± 24.0 and 63.7 ± 20.6 postoperatively ( P < .001; P < .001). The final Lysholm and IKDC scores in the repair group were significantly better than those in the meniscectomy group ( P = .004; P = .003). In cases of clinical failure, 10 patients (56%) in the meniscectomy group and 8 patients (22%) in the repair group converted to TKA in the follow-up period ( P = .016). According to Kaplan-Meier analysis, the 10-year survival rates for the meniscectomy and repair groups were 44.4% and 79.6%, respectively ( P = .004)., Conclusion: In MMPRTs, root repair was superior to partial meniscectomy in terms of clinical results for at least 10 years of follow-up. From a long-term perspective, repair with restoration of hoop tension is more effective management than meniscectomy.

Background: Anterolateral augmentation procedures can be divided into traditional lateral extra-articular tenodesis (LET) and modern anterolateral ligament (ALL) reconstruction. Nevertheless, no studies have compared the clinical results between LET and ALL reconstruction, when combined with intra-articular ACL reconstruction. This study was therefore designed to compare the clinical results, including the anterior translation, rotational laxity, and patient-reported outcomes, in a group of patients who underwent ACL reconstruction combined with LET or ALL reconstruction., Methods: All studies systematically searched until March 2018 without any language restriction that reported the results of a lateral extra-articular stabilization procedure using either LET or ALL reconstruction methods combined with ACL reconstruction were evaluated. Two reviewers independently recorded data from each study, including the sample size, improvement in Lysholm score, and the number of patients with each grade of knee laxity using Lachman and pivot shift tests., Results: The pooled results of ten studies showed that the postoperative proportion of knees with grade 2 or 3 on the Lachman test was significantly higher following LET compared with ALL reconstruction in combination with ACL reconstruction (10.8%, 95% confidence interval [CI]: 6.6-17.1% vs. 1.5%, 95% CI 0.5-4.5%; p = 0.001). However, the pooled results of 12 studies showed that the proportion of knees that belonged to grade 2 or 3 on the pivot shift test, indicating poor rotational stability, was similar between these two techniques (4.9%, 95% CI 2.0-11.5% vs. 2.3%, 95% CI 1.1-4.5%; p = 0.101). The pooled improvements in Lysholm scores in these two groups were also similar (32.3, 95% CI 26.8-37.9 vs. 25.7, 95% CI 16.7-34.7, p = 0.218)., Conclusion: LET could lead to worse anterior instability than with ALL reconstruction when these two approaches were combined with single-bundle ACL reconstruction. However, rotational stability and patient-reported outcomes were similar between the techniques.

Background: Meniscus surgeries are frequently performed in orthopaedics. However, their current status is not well known in many countries, including Korea. This study aimed to investigate the national trends of meniscus surgery in Korea., Methods: Information from the national database was acquired through the Korean Health Insurance Review and Assessment Service from 2010 to 2017. All cases coded as meniscectomy or meniscus repair were included. The total number and incidence of cases of meniscus surgery per 100,000 persons were determined, and the results were stratified by age and gender. The meniscus repair ratio for the total number of meniscus surgeries was evaluated., Results: The total number and incidence of meniscectomy cases were 65,752 and 137, respectively, in 2010, which increased to 74,088 and 154, respectively, in 2017. The number of meniscectomies increased by 12.67% in 8 years. The total number and incidence of meniscus repair cases were 9,055 and 18, respectively, in 2010, which increased to 14,947 and 31 in 2017. The number of meniscus repairs increased by 65.04%. The meniscus repair ratio was 12.1% in 2010, which increased to 16.8% in 2017. The highest peak was noted for patients who underwent meniscus surgeries in their 50s and 60s. Meniscectomy was performed more frequently in women (57%) than in men (43%), whereas repair was performed more frequently in men (54%) than in women (46%) over the study period., Conclusion: The total number and incidence of meniscus surgeries increased from 2010 to 2017; the number and incidence of meniscus repair procedures increased more rapidly than those of meniscectomy, with the peak treatment age for both surgeries being in the 50s and 60s. The current study will contribute to understanding the epidemiology of meniscus surgery, its prevention, and cost-saving measures in Korea., Competing Interests: The authors have no potential conflict of interest to disclose., (© 2019 The Korean Academy of Medical Sciences.)

Data from mouse tumor models suggest that tumor-associated monocyte/macrophage lineage cells (MMLCs) dampen antitumor immune responses. However, given the fundamental differences between mice and humans in tumor evolution, genetic heterogeneity, and immunity, the function of MMLCs might be different in human tumors, especially during early stages of disease. Here, we studied MMLCs in early-stage human lung tumors and found that they consist of a mixture of classical tissue monocytes and tumor-associated macrophages (TAMs). The TAMs coexpressed M1/M2 markers, as well as T cell coinhibitory and costimulatory receptors. Functionally, TAMs did not primarily suppress tumor-specific effector T cell responses, whereas tumor monocytes tended to be more T cell inhibitory. TAMs expressing relevant MHC class I/tumor peptide complexes were able to activate cognate effector T cells. Mechanistically, programmed death-ligand 1 (PD-L1) expressed on bystander TAMs, as opposed to PD-L1 expressed on tumor cells, did not inhibit interactions between tumor-specific T cells and tumor targets. TAM-derived PD-L1 exerted a regulatory role only during the interaction of TAMs presenting relevant peptides with cognate effector T cells and thus may limit excessive activation of T cells and protect TAMs from killing by these T cells. These results suggest that the function of TAMs as primarily immunosuppressive cells might not fully apply to early-stage human lung cancer and might explain why some patients with strong PD-L1 positivity fail to respond to PD-L1 therapy., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Purpose: In anterior cruciate ligament (ACL) reconstruction, there is concern regarding the potential risk of femoral tunnel widening in the anteromedial portal (AMP) technique due to the acute graft-bending angle at the aperture and the more elliptical aperture shape of the femoral tunnel compared to the transtibial (TT) techniques. Therefore, the aim of the current systematic review and meta-analysis was to compare the femoral tunnel widening between the AMP and TT techniques in patients who underwent ACL reconstruction., Methods: It should be included the studies that reported on femoral tunnel widening in patients who underwent single-bundle ACL reconstruction, using soft-tissue tendon graft, with AMP and/or TT techniques. Two reviewers independently recorded data from each study, including the sample size and magnitude of tunnel widening after ACL reconstruction., Results: Twenty-one studies were finally included in this meta-analysis. The pooled changes of absolute millimeters of tunnel widening from the immediate postoperative status to the last follow-up did not differ significantly between the AMP and TT techniques at both the aperture [3.31 mm, 95% confidence interval (CI) 1.7-5.0. mm versus 2.9 mm, 95% CI 2.4-3.4 mm, P = n.s.] and the midportion (3.5 mm, 95% CI 0.8-6.3 mm versus 3.0 mm, 95% CI 2.2-3.9 mm, P = n.s.) of the femoral tunnel. No significant difference was observed between the two techniques in the relative percentage of femoral tunnel widening (AMP; 28.8%, 95% CI 14.8-42.9% vs. TT; 29.7%, 95% CI 15.6-43.7%, P = n.s.)., Conclusion: No significant difference in femoral tunnel widening was observed between the AMP and TT techniques, both in absolute millimeter and relative percentage, in patients who underwent single-bundle ACL reconstruction. This finding could alleviate the potential concerns associated with femoral tunnels being wider for the AMP than for the TT technique., Level of Evidence: III.

Purpose: This study investigated the outcomes of pullout fixation for medial meniscus posterior root tears (MMPRTs) in patients ≤ 60 years old versus patients > 60 years old. It was hypothesized that older patients would demonstrate results comparable with those of younger patients., Methods: Patients with pullout fixation who were followed-up for more than 5 years were included. Patients were categorized into two groups based on age (group A, ≤ 60 years; group B, > 60 years). The Lysholm score, Kellgren-Lawrence (K-L, 0/1/2/3/4) grade, and medial joint space width were evaluated retrospectively. Preoperative results were compared with the final results in each group, which were compared between groups., Results: Twenty-five patients in group A (mean age, 54.7 ± 3.8 years) and 22 patients in group B (mean age, 65.6 ± 4.4 years) were recruited. The mean follow-up duration was 70.9 months. The Lysholm score (group A, 53.0 ± 9.1 to 86.0 ± 12.1, P < 0.001; group B, 51.1 ± 7.1 to 82.9 ± 9.7, P < 0.001) improved significantly. However, the joint space width (group A, 4.7 ± 1.1 to 3.9 ± 1.1 mm, P < 0.001; group B, 4.7 ± 0.9 to 3.8 ± 0.9 mm, P < 0.001) and K-L grade (group A, 3/17/5/0/0 to 0/7/11/7/0, P < 0.001; group B, 2/14/6/0/0 to 0/3/14/5/0, P < 0.001) worsened significantly. No significant differences between groups were observed in final outcomes, including Lysholm score (n.s.), K-L grade (n.s.), and joint space narrowing (n.s.). No case with operation failure that require total knee arthroplasty was not observed., Conclusion: MMPRT fixation did not prevent the progression of arthrosis completely. However, clinical outcomes were not age-dependent. Thus, age may not be a critical factor to consider when applying fixation., Level of Evidence: Retrospective case-control study; Level of evidence, IV.

Eleven patients with bipolar clavicle injuries, including dislocation of both ends of the clavicle, dislocation of the sternoclavicular joint with distal clavicle fracture, dislocation of the acromioclavicular joint with medial clavicle fracture, and segmental fracture of the clavicle, were retrospectively reviewed. The purpose of this study was to report the clinical outcomes and a literature review of bipolar clavicle injury. Nonoperative treatment was performed for 5 patients and surgical treatment for 6 patients. The fracture or dislocation of the lateral end of the clavicle was fixed with a hook plate, and closed reduction of the medial end was performed; if the dislocation was still present, open reduction and anterior sternoclavicular ligament repair was performed. Visual analog scale pain score, Constant score, active range of motion, and radiological images were evaluated. The mean visual analog scale pain score for all patients was 0.7±0.9 (range, 0-2). The mean Constant score for all patients was 89.7±7.6 (range, 72-96). The mean Constant score was 84.2±8.5 (range, 72-96) for conservatively treated patients and 94.3±1.9 (range, 92-96) for surgically treated patients. The mean Constant score was 83.4±7.2 (range, 72-92) for patients in whom optimal reduction of 1 or both ends was not achieved. Residual pain or deformity was seen in 5 patients. The authors suggest operative treatment of bipolar clavicle injuries in younger, active patients when anatomical reduction cannot be achieved and residual deformity, pain, or functional limitations are unacceptable. [Orthopedics. 2018; 41(5):e681-e688.]., (Copyright 2018, SLACK Incorporated.)

Patient-derived xenotransplantation models of human myeloid diseases including acute myeloid leukemia, myelodysplastic syndromes and myeloproliferative neoplasms are essential for studying the biology of the diseases in pre-clinical studies. However, few studies have used these models for comparative purposes. Previous work has shown that acute myeloid leukemia blasts respond to human hematopoietic cytokines whereas myelodysplastic syndrome cells do not. We compared the engraftment of acute myeloid leukemia cells and myelodysplastic syndrome cells in NSG mice to that in NSG-S mice, which have transgene expression of human cytokines. We observed that only 50% of all primary acute myeloid leukemia samples (n=77) transplanted in NSG mice provided useful levels of engraftment (>0.5% human blasts in bone marrow). In contrast, 82% of primary acute myeloid leukemia samples engrafted in NSG-S mice with higher leukemic burden and shortened survival. Additionally, all of 5 injected samples from patients with myelodysplastic syndrome showed persistent engraftment on week 6; however, engraftment was mostly low (<2%), did not increase over time, and was only transiently affected by the use of NSG-S mice. Co-injection of mesenchymal stem cells did not enhance human myelodysplastic syndrome cell engraftment. Overall, we conclude that engraftment of acute myeloid leukemia samples is more robust compared to that of myelodysplastic syndrome samples and unlike those, acute myeloid leukemia cells respond positively to human cytokines, whereas myelodysplastic syndrome cells demonstrate a general unresponsiveness to them., (Copyright © 2018 Ferrata Storti Foundation.)

PRF001 is a fragmented DNA polymer extracted from the testes of salmon. The purpose of this study was to assess the anti-inflammatory effect of PRF001 in vitro as well as the protective effect of PRF001 intake against arthritis in a rat model. In vitro , cell survival and inflammatory markers after H 2 O 2 treatment to induce cell damage were investigated in CHON-001 cells treated with different concentrations of PRF001. In vivo , osteoarthritis was induced by intra-articular injection of monosodium iodoacetate (MIA) into the knee joints of rats. After consumption of PRF001 (10, 50, or 100 mg/kg) for 4 weeks, inflammatory mediators and cytokines in articular cartilage were investigated. In vitro, the levels of inflammatory markers, IL-1β, TNF-α, COX-2, iNOS, and PGE2, were significantly suppressed by PRF001 treatment. In vivo , the inflammatory mediators and cytokines, IL-1β, p-Erk1/2, NF-κB, TNF-α, COX-2, and PGE2, as well as MMP3 and MMP7, which have catabolic activity in chondrocytes, were decreased in the MIA-induced osteoarthritic rats following intake of PRF001. Histological analysis revealed that PRF001 had a protective effect on the articular cartilage. Altogether, these results demonstrated that the anti-inflammatory property of PRF001 contributes to its protective effects in osteoarthritis through deregulating IL-1β, TNF-α, and subsequent signals, such as p-Erk1/2, NF-κB, COX-2, PGE2, and MMPs., Competing Interests: CONFLICTS OF INTEREST: The authors declare no conflicts of interest.

Purpose: This study investigated the clinical outcomes and mid- to long-term survival rates in patients undergoing transtibial pullout repair of medial meniscus posterior root tears (MMPRTs) after a minimum follow-up of 5 years., Methods: Between 2005 and 2011, patients with MMPRTs who had been followed for at least 5 years after undergoing transtibial pullout repair were recruited. Participants were identified using medical records and information in a prospectively collected database. Clinical outcomes were assessed based on a comparison of patient preoperative Lysholm scores and their scores at the final follow-up. A Kaplan-Meier survival analysis was used to investigate the survival rates of repair procedures. Clinical failures were defined as cases requiring conversion to total knee arthroplasty (TKA) or having final Lysholm score <65 or less than their preoperative scores., Results: Overall, 91 patients (mean age, 58.7 ± 9.7 years) were included: the mean follow-up duration was 84.8 ± 13.8 months. Among these patients, the mean Lysholm score improved significantly from 51.8 ± 7.9 preoperatively to 83.0 ± 11.1 at the final follow-up (P < .001). Overall, 4 patients failed due to conversion to TKA (n = 1) or having final Lysholm scores <65 or less than the preoperative scores (n = 3). The overall Kaplan-Meier probabilities of survival after repair were 99% at 5 years, 98% at 6 years, 95% at 7 years, and 92% at 8 years., Conclusions: Among patients with MMPRTs, transtibial pullout repair demonstrated a high clinical survival rate and the patients demonstrated clinical improvement, based on mid- and long-term follow-up examinations., Level of Evidence: Level IV, retrospective uncontrolled case series., (Copyright © 2017 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Background: To investigate the effect of synovialization of graft following anterior cruciate ligament reconstruction (ACLR) on functional performance test (FPT) and clinical outcomes., Methods: Eighty-four male patients who underwent second-look arthroscopy at 2-year follow-up after unilateral ACLR using hamstring autograft were analyzed retrospectively. Patients were categorized by synovial coverage into A group (42 subjects, poor synovial coverage) and B group (42 subjects, good synovial coverage). FPT results, including those of single leg hop test (cm) of the involved limb, co-contraction test (s), shuttle run test (s), and carioca test (s), were compared between groups. Clinical scores, including Lysholm score, International Knee Documentation Committee (IKDC) subjective score, and Tegner activity score; stability assessments including Lachman test, Pivot-shift test, and side-to-side differences (cm) measured using a KT-2000 arthrometer were also compared between groups., Results: Based on FPT results, no difference was evident between groups. Single leg hop test results were 144.3 ± 25.5 in A group and 145.4 ± 24.7 in B group (P = 0.849). Co-contraction test results were 17.1 ± 2.9 in A group and 16.9 ± 3.6 in B group (P = 0.827). Shuttle run test results were 9.3 ± 1.9 in A group and 9.3 ± 1.9 in B group (P = 0.935). Carioca test results were 11.4 ± 2.9 in A group and 10.5 ± 2.5 in B group (P = 0.149). Clinical scores and stability assessments did not differ between groups (P > 0.05)., Conclusions: Based on functional performance results, well-synovialized grafts did not yield better functional performance outcomes following ACLR compared to poorly synovialized grafts at 2-year follow-up. The same was true of clinical outcomes. Thus, the success of synovialization does not improve functional performance and clinical outcomes following ACL reconstruction in an all-male population.

Although double-bundle anterior cruciate ligament (ACL) reconstruction has theoretical benefits such as more accurate reproduction of ACL anatomy, it is technically more demanding surgery. This report describes the case of a one stage revision single-bundle ACL reconstruction after primary double-bundle ACL reconstruction. A professional dancer had an ACL previously reconstructed with a double-bundle technique, but the femoral tunnels were malpositioned resulting in residual laxity and rotational instability. The previous femoral tunnel positions were vertical and widened. The previous vertical tunnels were filled with impacted bone graft and a revision single-bundle ACL reconstruction was performed via the new femoral tunnel with a 2 O'clock position between the previous two tunnels. After 10 months of postoperative rehabilitation, the patient returned to professional dancing with sound bony union and without any residual instability., Competing Interests: There are no conflicts of interest.

Purpose: To investigate pain and tenderness, stress testing, clinical outcome scores, complications, and operation time at 24 months and magnetic resonance imaging (MRI) analysis at 12 months after the release of the distal attachment of the superficial medial collateral ligament (sMCL) during medial meniscus posterior root tear (MMPRT) fixation., Methods: Patients who received MMPRT fixation with a follow-up of at least 2 years were included. During fixation, the release of the distal attachment of the sMCL on the proximal tibia was performed to improve visualization and provide sufficient working space. Pain and tenderness at the released area, manual valgus stress tests of 30° and 0° flexion (grade 0/1/2/3), and subjective instability during weight bearing were evaluated serially at postoperative 3, 6, 12, and 24+ months. The contour of detachment area was assessed using MRI 12 months postoperatively. As a subgroup analysis, tourniquet time (minutes) and final clinical scores were compared between release and nonrelease groups., Results: The numbers of participants in the release and nonrelease groups were 118 and 20 patients, and their mean follow-up durations were 42.4 ± 19.3 (24-95) and 37.2 ± 7.8 (30-55) months, respectively. In the release group, percentages of patients with pain and tenderness at 3 months were 15% and 18%, respectively; however, no patients had symptoms at 12 months. In valgus stress tests (30°, 0°), 12% and 2% of patients showed grade 1 laxity at 3 months, and 7% had grade 1 laxity in only 30° flexion at the final follow-up. However, no patients had subjective valgus laxity. An intact contour was confirmed in all cases among 94 patients checked by performing follow-up MRI. Tourniquet time was significantly shorter in the release group (42.4 ± 19.3) than in the nonrelease group (58.5 ± 9.5; P < .001). Between release and nonrelease groups, Lysholm (84.4 ± 12.1, 88.1 ± 12.8; P = .117) and International Knee Documentation Committee scores (73.6 ± 11.2, 77.5 ± 11.9; P = .112) did not differ., Conclusions: The release of the distal attachment of the sMCL during fixation of MMPRT did not result in pain and tenderness, residual instability, and complication. An intact contour of the sMCL was confirmed in all cases with MRI. This procedure reduced operation time and showed similar clinical results when compared between the release and nonrelease groups. However, this study had low power to detect the difference for clinical scores between the 2 groups., Level of Evidence: Level IV, therapeutic case series., (Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

We investigated whether betulin affects the gene expression, secretion and proteolytic activity of matrix metalloproteinase-3 (MMP-3) in primary cultured rabbit articular chondrocytes, as well as in vivo production of MMP-3 in the rat knee joint to evaluate the potential chondroprotective effect of betulin. Rabbit articular chondrocytes were cultured and reverse transcription-polymerase chain reaction (RT-PCR) was used to measure interleukin-1β (IL-1β)-induced gene expression of MMP-3, MMP-1, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4), ADAMTS-5 and type II collagen. Effect of betulin on IL-1β-induced secretion and proteolytic activity of MMP-3 was investigated using western blot analysis and casein zymography, respectively. Effect of betulin on MMP-3 protein production was also examined in vivo . The results were as follows: (1) betulin inhibited the gene expression of MMP-3, MMP-1, MMP-13, ADAMTS-4, and ADAMTS-5, but increased the gene expression of type II collagen; (2) betulin inhibited the secretion and proteolytic activity of MMP-3; (3) betulin suppressed the production of MMP-3 protein in vivo . These results suggest that betulin can regulate the gene expression, secretion, and proteolytic activity of MMP-3, by directly acting on articular chondrocytes., Competing Interests: The authors have no conflicts of interest to declare.

Background: Medial meniscus posterior root tears (MMPRTs) lead to extrusion of the meniscus during weightbearing as well as loss of the ability of the meniscus to generate hoop stress. This loss of load-sharing ability leads to progressive arthritic changes. However, there have been no studies that correlate the correction of meniscus extrusion with clinical outcomes., Hypothesis: Decreased meniscus extrusion is associated with better clinical and radiographic outcomes compared with increased meniscus extrusion after MMPRT pullout fixation., Study Design: Case-control study; Level of evidence, 3., Methods: A total of 39 patients who underwent MMPRT pullout fixation and had been observed for more than 5 years were recruited for this study. The mean follow-up period was 69.8 months. Participants were categorized into 2 groups according to the direction of meniscus extrusion: group A (increased extrusion; 23 patients) and group B (decreased extrusion; 16 patients). Meniscus extrusion was assessed in the coronal plane on magnetic resonance imaging preoperatively and at 1 year postoperatively. The postoperative clinical outcomes (Lysholm and International Knee Documentation Committee [IKDC] scores) and radiographic results (Kellgren-Lawrence [K-L] grade and medial joint space) were compared between groups., Results: Meniscus extrusion in group A increased significantly from a mean (±SD) of 3.5 ± 0.9 mm preoperatively to 5.1 ± 1.4 mm at 1 year postoperatively ( P < .001), whereas in group B, it decreased significantly from 4.1 ± 1.3 mm preoperatively to 3.5 ± 1.4 mm at 1 year postoperatively ( P < .001). The K-L arthritis grade (0/1/2/3/4) significantly progressed in group A (from 2/12/9/0/0 preoperatively to 0/1/14/8/0 postoperatively, respectively; P = .009) but not in group B (from 1/11/4/0/0 preoperatively to 0/6/8/2/0 postoperatively, respectively; P = .274). The mean final Lysholm and IKDC scores in group B (88.1 ± 12.1 and 79.0 ± 11.4, respectively) were significantly better than those in group A (81.0 ± 9.0 and 71.1 ± 7.8, respectively) ( P < .05). There was less medial joint space narrowing at final follow-up in group B (0.6 ± 0.8 mm) than in group A (1.1 ± 0.6 mm) ( P = .015). Progression of the K-L arthritis grade was seen in 50% (8/16) of the patients in group B compared with 87% (20/23) of the patients in group A ( P = .027)., Conclusion: The current study demonstrates that in patients with MMPRTs, pullout fixation leads to favorable midterm outcomes, regardless of meniscus extrusion at 1-year follow-up. However, patients with decreased meniscus extrusion at postoperative 1 year have more favorable clinical scores and radiographic findings at midterm follow-up than those with increased extrusion at 1 year. This study indicates that one of the main goals of the repair of MMPRTs is to reduce meniscus extrusion as much as possible.

Purpose: To identify predictors of unfavorable clinical and radiologic outcomes a minimum of 5 years after pullout fixation for medial meniscus posterior root tears (MMPRTs)., Methods: In total, 40 patients who were followed for >5 years after pullout fixation in MMPRT were recruited. The mean follow-up duration was 71.1 months. Clinical outcomes, including Lysholm score and International Knee Documentation Committee (IKDC) score, and radiographic results, including Kellgren-Lawrence (K-L; 0/1/2/3/4) grade and medial joint space width, were evaluated preoperatively and at final follow-up. Preoperative prognostic factors, including age, sex, body mass index, degree of varus alignment, K-L grade, medial joint space width, meniscal extrusion, and cartilage status, by the modified Outerbridge classification (grades 1 or 2 v 3 or 4), for relatively unfavorable (fair or poor grade) Lysholm or IKDC score, and progression of K-L grade were investigated by multivariate logistic regression analysis., Results: The mean Lysholm score (52.1 ± 8.8 to 83.8 ± 11.9) and IKDC score (40.1 ± 7.6 to 73.3 ± 10.9) were improved significantly (P < .001), although the loss of medial joint space width (4.8 ± 1.1 to 3.9 ± 1.1 mm) and K-L grade (6/25/9/0/0 to 0/11/20/9/0) progressed significantly (P < .001). Unfavorable prognostic factors of the Lysholm score were grade ≥3 chondral lesions (odds ratio [OR] = 5.993; P = .028) and varus mechanical alignment (OR = 1.644; P = .017), for IKDC score were grade ≥3 chondral lesions (OR = 11.146; P = .038) and older age (OR = 1.200; P = .017). Preoperative chondral lesion grade ≥3 increased the risk of K-L grade progression (OR = 11.000; P = .031)., Conclusions: Clinically, modified Outerbridge classification grade ≥3 chondral lesions, varus alignment, and older age were found to predict a poor prognosis after MMPRT fixation. In terms of radiographic K-L grade progression, grade ≥3 chondral lesions were identified as a poor prognostic factor., Level of Evidence: Level IV, case series., (Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Purpose: Although interest in medial meniscus posterior root tear (MMPRT) repair has increased, few case series have been reported. This meta-analysis aimed to examine the clinical and radiological effects of MMPRT repair by pooling pre- and post-operative data from case-series reports., Methods: A literature search was performed using MEDLINE/PubMed, the Cochrane Central Register of Controlled Trials, and EMBASE databases. Pre- and post-operative data were pooled to investigate the effects of MMPRT repair, including the Lysholm score improvement, meniscal extrusion (mm) reduction, progression of the Kellgren-Lawrence (K-L) grade, and cartilage status according to the Outerbridge classification. Treatment effects included paired standardized mean differences (difference in the pre- and post-operative mean outcomes divided by the standard deviation) for the Lysholm score and meniscal extrusion, as well as the pooled event rates of progression of K-L grade and cartilage status., Results: As treatment effects, the Lysholm score increased by as much as 3.675 (P < 0.001), whereas meniscus extrusion was not reduced (n.s.). The overall pooled event rates of progression of K-L grade and cartilage status were 10.6 and 17.3 % (P < 0.001), respectively., Conclusions: According to the current literature, MMPRT repair resulted in significant improvements in the post-operative clinical subjective scores compared with the preoperative status. However, meniscus extrusion was not reduced. Considering the occurrence of progression of K-L grade and cartilage status, it did not prevent the progression of arthrosis completely. Based on these results, repair results in favourable outcomes for MMPRT., Level of Evidence: Meta-analysis, Level IV.

Idiopathic pulmonary fibrosis is a disease characterized by progressive, unrelenting lung scarring, with death from respiratory failure within 2-4 years unless lung transplantation is performed. New effective therapies are clearly needed. Fibroblast activation protein (FAP) is a cell surface-associated serine protease up-regulated in the lungs of patients with idiopathic pulmonary fibrosis as well as in wound healing and cancer. We postulate that FAP is not only a marker of disease but influences the development of pulmonary fibrosis after lung injury. In two different models of pulmonary fibrosis, intratracheal bleomycin instillation and thoracic irradiation, we find increased mortality and increased lung fibrosis in FAP-deficient mice compared with wild-type mice. Lung extracellular matrix analysis reveals accumulation of intermediate-sized collagen fragments in FAP-deficient mouse lungs, consistent within vitrostudies showing that FAP mediates ordered proteolytic processing of matrix metalloproteinase (MMP)-derived collagen cleavage products. FAP-mediated collagen processing leads to increased collagen internalization without altering expression of the endocytic collagen receptor, Endo180. Pharmacologic FAP inhibition decreases collagen internalization as expected. Conversely, restoration of FAP expression in the lungs of FAP-deficient mice decreases lung hydroxyproline content after intratracheal bleomycin to levels comparable with that of wild-type controls. Our findings indicate that FAP participates directly, in concert with MMPs, in collagen catabolism and clearance and is an important factor in resolving scar after injury and restoring lung homeostasis. Our study identifies FAP as a novel endogenous regulator of fibrosis and is the first to show FAP's protective effects in the lung., (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.)

Total knee arthroplasty (TKA) is one of the most successful and effective surgical options to reduce pain and restore function for patients with severe osteoarthritis. The purpose of this article was to review and summarize the recent literatures regarding patient satisfaction after TKA and to analyze the various factors associated with patient dissatisfaction after TKA. Patient satisfaction is one of the many patient-reported outcome measures (PROMs). Patient satisfaction can be evaluated from two categories, determinants of satisfaction and components of satisfaction. The former have been described as all of the patient-related factors including age, gender, personality, patient expectations, medical and psychiatric comorbidity, patient's diagnosis leading to TKA and severity of arthropathy. The latter are all of the processes and technical aspects of TKA, ranging from the anesthetic and surgical factors, type of implants and postoperative rehabilitations. The surgeon- and patient-reported outcomes have been shown to be disparate occasionally. Among various factors that contribute to patient satisfaction, some factors can be managed by the surgeon, which should be improved through continuous research. Furthermore, extensive discussion and explanation before surgery will reduce patient dissatisfaction after TKA.

A complete radial tear of the meniscus posterior root, which can effectively cause a state of total meniscectomy via loss of hoop tension, requires that the torn root be repaired. Several methods have been used to repair medial meniscus posterior root tears, most of which are based on a simple stitch technique that is known to have stitch-holding strength. We applied a modified version of the Mason-Allen stitch technique, which is recognized as a method for rotator cuff repair surgery because its locking effect overcomes the potential weakness of simple stitches. This article introduces the medial meniscus posterior root tears repair procedure based on a modified Mason-Allen stitch technique in which 2 strands (i.e., 1 simple horizontal and 1 simple vertical stitch) are used.

Background: After an anterior cruciate ligament (ACL) injury, the uninjured contralateral lower limb may become weakened because of neuromuscular changes, proprioceptive deficits, and disuse of the limb; this weakness predisposes the limb to ACL injury. However, no results have been reported regarding weakness in the contralateral limb after ACL injury., Hypothesis: Muscle strength and functional status of the contralateral lower limb are reduced after unilateral ACL injury., Study Design: Cohort study; Level of evidence, 3., Methods: The ACL group consisted of 75 patients who underwent primary unilateral ACL reconstruction and were followed at 3, 6, 12, and 24 months postoperatively. A group of 75 healthy individuals (controls) were matched one-to-one with the ACL group for age, sex, body mass index, and initial Tegner activity level. The side that was evaluated in each control subject corresponded to the injured limb in the matched ACL subject. Isokinetic muscle strength, including extension peak torque per body weight (EPT) and flexion peak torque per body weight (FPT), was evaluated at angular velocities of 60 and 180 deg/s. Patients were also evaluated by single-legged hop test., Results: Compared with the EPT at 60 deg/s in the control group (290.9 ± 40.1 N · m/kg), the value in the ACL group 24-month follow-up (276.6 ± 42.8 N · m/kg) as well as other follow-up times was significantly lower (P < .05), whereas the EPT at 180 deg/s and the FPT at 60 and 180 deg/s in the ACL group were significantly lower than the control group at 3-month follow-up but were restored to normal levels at final follow-up. Results from the single-legged hop test demonstrated that the ACL group performed at a significantly lower level than the control group at 24-month follow-up (158.4 ± 25.3 vs 176.3 ± 24.7 cm; P < .05) as well as other follow-up times. However, both measurements improved significantly as the follow-up time progressed., Conclusion: After ACL injury, isokinetic extensor muscle strength and functional status of the contralateral limb were reduced, even at 24 months after ACL reconstruction. However, both measurements improved significantly as the follow-up time progressed. In contrast, flexion muscle strength was restored to normal levels. Therefore, care should be taken to restore muscle strength and functional status in not only the ACL-reconstructed knee but also the uninjured limb., (© 2015 The Author(s).)

Purpose: To examine the incidence and diagnostic rate of traumatic medial meniscus posterior root tear associated with severe medial instability and to evaluate the effectiveness of pullout repair., Methods: From 2007 to 2011, 51 patients who underwent operation due to multiple ligament injuries including medial collateral ligament rupture were reviewed retrospectively. The International Knee Documentation Committee (IKDC) subjective and Lysholm score were evaluated pre- and postoperatively. Postoperative magnetic resonance imaging (MRI) was performed, and if indicated, a second-look arthroscopic examination was conducted., Results: Fourteen out of 51 patients were associated with severe medial instability. Seven patients were diagnosed with traumatic medial meniscus posterior root tear and underwent arthroscopic pullout repair. Five of them were missed at initial diagnosis using MRI. In seven patients, the mean Lysholm and IKDC subjective scores improved from 74.6 ± 10.3 and 47.6 ± 7.3 to 93.0 ± 3.7 and 91.6 ± 2.6, respectively. All showed complete healing of meniscus root on follow-up MRI and second-look arthroscopy., Conclusion: Medial meniscus posterior root tear may occur in severe medial instability from trauma. It is a common mistake that surgeons may not notice on the diagnosis of those injuries using MRI. Therefore, a high index of suspicion is required for the diagnosis of medial meniscus posterior root tear in this type of injuries. The traumatic medial meniscus posterior root tear could be healed successfully using arthroscopic pullout repair technique., Clinical Relevance: The possibility of the medial meniscus posterior root tear should be considered in severe medial instability and arthroscopic pullout repair can be an effective option for treatment., Level of Evidence: Case series with no comparison group, Level IV.

Purpose: To compare the clinical and radiologic results of partial meniscectomy with those of refixation in patients with medial meniscus posterior root tears (MMPRTs) at a minimum 5-year follow-up., Methods: Between 2005 and 2009, patients with MMPRTs who had been followed up for at least 5 years after a partial meniscectomy (group M, n = 20) or pullout repair (group R, n = 37) were recruited. The mean follow-up duration was 67.5 months in group M and 72.0 months in group R. Clinical assessments, including the Lysholm score and International Knee Documentation Committee (IKDC) Subjective Knee Form score, and radiographic assessments, including the Kellgren-Lawrence (K-L) grade and medial joint space width, were evaluated preoperatively and at final follow-up. We compared the preoperative results with the final results in each group, and we compared the final results of groups M and R. Five-year survival rates were also evaluated., Results: The mean Lysholm score (P = .039) and IKDC score (P = .037) improved significantly. However, the width of the medial joint space (P < .001) and K-L grade (P < .001) worsened significantly in both groups. When we compared the final results, group R had significantly better Lysholm scores (P = .002) and IKDC scores (P < .001) than group M. Group R showed less K-L grade progression (P = .005) and less medial joint space narrowing (P < .001) than group M. The rate of conversion to total knee arthroplasty was 35% in group M, whereas there was no conversion to total knee arthroplasty in group R. The 5-year survival rates in groups M and R were 75% and 100%, respectively (P < .001)., Conclusions: For MMPRTs, refixation was more effective than partial meniscectomy in terms of the clinical and radiologic outcomes and survival for at least 5 years' follow-up. Refixation slowed the progression of arthritic changes compared with partial meniscectomy, although it did not prevent the progression of arthrosis completely., Level of Evidence: Level III, retrospective comparative study., (Copyright © 2015 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study is to evaluate the risk of sequential bilateral total knee arthroplasty (TKA) under 1 anesthesia in patients 75 years or older., Materials and Methods: Patients aged 75 years or older who underwent sequential bilateral TKA (bilateral group, n=159) and unilateral TKA (unilateral group, n=159) between 2002 and 2012 were selected. All patients were evaluated for underlying medical diseases, such as cardiac, pulmonary, and renal problems, and high-risk patients were recommended to postpone the surgery. We compared the underlying diseases, major postoperative complications, and the length of hospital stay between bilateral and unilateral groups., Results: The prevalence of underlying diseases of the bilateral group was 74.8% and major complications occurred in 6 patients (3.8%). The prevalence of underlying diseases of the unilateral group was 52.4% and complications were observed in 4 patients (2.4%). Although the complication rate of the bilateral group was slightly higher than that of the unilateral group, the difference was not statistically meaningful (p=0.204). The length of hospital stay was 21.9 days for the bilateral group and 24.9 days for the unilateral group., Conclusions: There was no significant difference in postoperative complications between groups. The result shows that bilateral TKA can be relatively safe compared with unilateral TKA in patients 75 years or older. However, careful selection of low-risk patients is advised.

Background: To compare the ceiling effect of the Lysholm and IKDC subjective scores for assessing functional outcome after ACL reconstruction and evaluated the correlation with the one-leg hop test., Methods: A total of 134 patients who underwent ACL reconstruction between 2007 and 2011 were enrolled in this study. All patients fulfilled the postoperative 6- and 12-month evaluations. The ceiling effect of the Lysholm and IKDC subjective scores was assessed, and the correlations between two scales and one-leg hop test were analysed., Results: For the entire sample, the ceiling effect for the Lysholm score was 14.9% and 30.6% at 6 and 12 months postoperatively. The values for the IKDC subjective score were 5.2% and 17.2%, respectively. In all subjects, the correlation coefficients [95% confidence intervals] between the IKDC subjective score and one-leg hop test at 6 and 12months (r=0.492, [0.34 to 0.62]; r=0.296, [0.12 to 0.46]) were higher than those for the Lysholm score (r=0.355, [0.18 to 0.51]; r=0.241, [0.06 to 0.41]), respectively.(p<0.05)., Conclusion: With regard to evaluating ACL reconstruction outcomes in patients, no significant difference between the IKDC subjective and the Lysholm scores exists in terms of the amount of ceiling effect and the correlation with the LSI. However, the concern that the ceiling effect of the Lysholm score was greater than the IKDC subjective score, should be addressed in assessing the patient's functional status postoperatively., Level of Evidence: III, retrospective comparative study., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Although ACL reconstruction is prevalent, the most effective method for ACL reconstruction still remains controversial. The purpose of this study was to evaluate the effect of the preserved remnant in ACL reconstruction on graft morphology at second-look arthroscopy and clinical outcomes., Methods: 66 consecutive patients who underwent a second-look arthroscopy after a remnant-preserving ACL reconstruction were enrolled. The patients were divided into two groups according to whether the remnant ACL fibers could be preserved by over 50% (Group I) or not (Group II). The Lysholm score, IKDC subjective score, Tegner activity score, pivot-shift test, and KT-2000 arthrometric findings were evaluated preoperatively and just prior to the second-look arthroscopy to assess clinical outcomes. At second-look arthroscopy, graft morphology was evaluated using hypertrophy rate and synovialization., Results: At second-look arthroscopy, the hypertrophy rate of Group I (42.1%) was higher than Group II (25.1%), which was statistically significant (p=0.002). In graft synovialization, there was a statistically significant difference between the two groups (p<0.001). The IKDC subjective score improved from 42.9, 43.1 to 77.8, 75.0 for Group I and Group II, respectively (p=0.025). For the Lysholm score, Group I and Group II improved from 55.4 and 55.7 to 87.8 and 84.9 (p=0.031). There was also a significant difference between the pivot shift tests between the groups (p=0.039). Other clinical tests showed no statistically significant differences., Conclusion: Preserving the remnant ACL tissue during ACL reconstruction could have a positive effect on graft hypertrophy, synovialization and clinical outcomes., Level of Evidence: III, retrospective comparative study., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Revision anterior cruciate ligament reconstruction can be performed in a 1- or 2-stage procedure. Restoration of bone stock using bone grafting is often required for good results. The authors performed 1-stage revision surgery with a more lateral and oblique femoral tunnel and an impacted bone graft to avoid the bone defect caused by the previous screw removal from a malpositioned tunnel. No evidence existed of revision surgery failure or viral transmission in any of 17 cases at 2-year follow-up. The authors' technique is also useful for a slightly misplaced femoral tunnel., (Copyright 2013, SLACK Incorporated.)

Purpose: To report on the results of 12 complete radial tears of the meniscus treated using arthroscopic inside-out repair with fibrin clots, the results showed good meniscal healing and excellent clinical outcomes., Methods: From 2007 to 2009, 12 patients with complete radial tears of the meniscus were treated by arthroscopic inside-out repair with fibrin clots. In all patients, the International Knee Documentation Committee (IKDC) subjective knee form and Lysholm score were determined pre- and post-operatively. We performed magnetic resonance imaging (MRI) and if indicated, we performed a second-look arthroscopic examination., Results: At a mean of 30 ± 4 postoperative months, the Lysholm score and IKDC subjective knee score had improved from 65 ± 6 and 57 ± 7 to 94 ± 3 and 92 ± 3, respectively. Eleven of 12 cases showed complete healing on follow-up MRI. Six of 7 patients undergoing a second-look arthroscopic examination had healed completely., Conclusion: This study shows successful meniscal repairs using fibrin clots in complete radial tears. This surgical procedure appears to be a good treatment method for complete radial tear of the meniscus., Level of Evidence: Case series, level IV.

Purpose: The purposes of this study were to evaluate the effect on tibiofemoral contact mechanics of repair of the posterior root of the medial meniscus and the effect of meniscal allograft transplantation (MAT) with medial collateral ligament (MCL) release at different flexion angles., Methods: Ten fresh-frozen human cadaveric knees (five pairs) were used. A digital pressure sensor was inserted by capsulotomy, and experiments were performed serially under the following six conditions, that is, with an intact medial meniscus (normal controls), with a root tear, after root repair, after total meniscectomy, after MAT, and after MAT plus MCL release. During each experiment, knees were positioned at 0°, 30°, 60°, and 90° of flexion, and peak pressure (kPa) and contact area (cm2) were measured., Results: At 0° of flexion, contact pressure did not differ among the six experimental settings. However, at 30° and 60° of flexion, contact pressure differed significantly between root tear and root repair specimens (p = 0.04 and 0.03, respectively), and between total meniscectomy and MAT specimens (p = 0.02 and 0.03, respectively). On the other hand, mean contact pressures were different between normal (476.7 ± 473.1 and 573.3 ± 479.1 kPa) and root repair (575.7 ± 357.8 and 598.6 ± 415.8), and between normal and MAT (635.7 ± 437.4 and 674.3 ± 533.2). At 0°, 30°, 60°, and 90° of flexion, contact areas differed significantly between normal and total meniscectomy specimens (p = 0.02, 0.01, 0.02, and 0.02, respectively), and between MAT and total meniscectomy specimens (p = 0.03, 0.02, 0.02, and 0.03, respectively). Contact areas differed significantly between root tear and root repair specimens at 60° of flexion (p = 0.04), and between normal control and root repair specimens at 60° and 90° of flexion (p = 0.03 and 0.04, respectively). The effects of MAT plus MCL release on contact mechanics were not different from the effects of MAT alone (n.s.)., Conclusions: Both meniscal root repair and transplantation of meniscus improved contact mechanics, but it did not appear that repair of the meniscal root or transplantation of meniscus restores the biomechanical function back to normal level. The MAT plus MCL release was similar to those after MAT alone. Therefore, it is better to preserve meniscus and MCL release could be done during the MAT.

B7-H4 (VTCN1, B7x, B7s) is a ligand for inhibitory coreceptors on T cells implicated in antigenic tolerization. B7-H4 is expressed by tumor cells and tumor-associated macrophages (TAM), but its potential contributions to tumoral immune escape and therapeutic targeting have been less studied. To interrogate B7-H4 expression on tumor cells, we analyzed fresh primary ovarian cancer cells collected from patient ascites and solid tumors, and established cell lines before and after in vivo passaging. B7-H4 expression was detected on the surface of all fresh primary human tumors and tumor xenotransplants, but not on most established cell lines, and B7-H4 was lost rapidly by tumor xenograft cells after short-term in vitro culture. These results indicated an in vivo requirement for B7-H4 induction and defined conditions for targeting studies. To generate anti-B7-H4-targeting reagents, we isolated antibodies by differential cell screening of a yeast-display single-chain fragments variable (scFv) library derived from patients with ovarian cancer. We identified anti-B7-H4 scFv that reversed in vitro inhibition of CD3-stimulated T cells by B7-H4 protein. Notably, these reagents rescued tumor antigen-specific T-cell activation, which was otherwise inhibited by coculture with antigen-loaded B7-H4+ APCs, B7-H4+ tumor cells, or B7-H4- tumor cells mixed with B7-H4+ TAMs; peritoneal administration of anti-B7-H4 scFv delayed the growth of established tumors. Together, our findings showed that cell surface expression of B7-H4 occurs only in tumors in vivo and that antibody binding of B7-H4 could restore antitumor T-cell responses. We suggest that blocking of B7-H4/B7-H4 ligand interactions may represent a feasible therapeutic strategy for ovarian cancer., (©2013 AACR.)

Purpose: The purposes of this study were (1) to predict the tibial insertion of the posterior cruciate ligament (PCL) and posterior cortex that aligned with the tibial tunnel (PCTT) by use of 2-dimensional plain radiographs by evaluating the relation between plain radiograph and computed tomography (CT) images and (2) to determine the safe angle of the tibial guide for preventing breakage of the posterior cortex., Methods: In 10 fresh cadaveric tibias, the soft tissues were dissected and the tibial footprint of the PCL was identified. The insertion of the PCL, the longest distance from the PCTT to the posterior cortex that aligned with the tibial plateau (PCTP), and the possible maximum angle of the tibial guide to the most posteriorly positioned cortical line were measured from simple anteroposterior (AP) and lateral radiographs, as well as CT., Results: The mean tibial insertion of the PCL from the joint line was located between 5.9 ± 1.1 and 17.4 ± 2.4 mm on the simple AP radiographs and between 2.2 ± 1.2 and 12.3 ± 1.5 mm on the simple lateral radiographs (P = .005). The PCL insertion was from the posterior 48% of the area of the posterior intercondylar fossa to the posterior cortex. The longest distance from the PCTT to the PCTP was 10.8 ± 2.2 mm. The maximum angle of the tibial guide to the PCTT possible on CT and the PCTP on lateral radiographs was 52° ± 5° and 62° ± 4.5°, respectively (P = .005)., Conclusions: The mean tibial insertion of the PCL from the joint line was located higher on the lateral radiographs than on the AP radiographs, and the PCL insertion was in the posterior 48% of the area of the PCL fovea to the posterior cortex. The maximum possible angle of the tibial guide to the PCTT based on CT was 52°. Therefore the angle of the tibial guide pin must be limited for tibial footprint reconstruction to prevent posterior wall breakage., Clinical Relevance: Increasing the tibial guide angle may have some advantages, but there is a limit because of posterior wall breakage., (Copyright © 2011 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Background: Meniscus allograft transplantation (MAT) is useful for meniscus-deficient knees. Although meniscal extrusion is common after MAT, there is no consensus regarding the criteria for normal meniscal extrusion or the relationship between clinical and radiologic results., Hypothesis: Meniscal extrusion after MAT results in poor clinical, radiologic, and arthroscopic outcomes., Study Design: Case series; Level of evidence, 4., Methods: Thirty-six of 60 patients undergoing MAT from September 2002 to June 2007 who were available for follow-up evaluation for more than 2 years were evaluated. The study population (31 men, 5 women) consisted of 15 and 21 cases of medial and lateral meniscus transplant, respectively. Knee status was evaluated by Lysholm score, plain radiography, and magnetic resonance imaging preoperatively and postoperatively. Second-look examinations were performed in 18 cases., Results: Mean follow-up was 31.4 months (range, 24-36). Lysholm knee score increased significantly (mean, 88.2; range, 70-100) on final visit versus the preoperative value (mean, 61.2; range, 26-83; P < .001). Joint-space narrowing was 0.08 mm (range, -2.58 to 1.92) in extension AP and -0.09 mm (range, -2.3 to 1.8) in Rosenberg view. Kellgren-Lawrence arthrosis grade did not change in 28 knees (77.8%) and progressed by 1 grade in 8 knees. Meniscal extrusion extent was 3.87 ± 1.94 mm and relative percentage extrusion was 42.1% ± 17.7%. Seven cases (19.4%) showed minor extrusion (<3 mm), 27 (75%) showed major extrusion (>3 mm), and 2 (5.6%) showed no extrusion. Further degeneration was absent in 28 knees (77.8%) on magnetic resonance imaging. In second-look arthroscopic examinations at an average of 26.3 months, 11 of 18 (63.6%) cases showed no progression of cartilage degeneration. There was no significant correlation between meniscal extrusion and other parameters., Conclusion: This study indicated that MAT can improve the clinical status of the meniscectomized knee. Although meniscal extrusion occurred after surgery in most cases, there was no significant correlation with various clinical, radiologic, or arthroscopic outcomes. Further studies are required to evaluate long-term effects of meniscal extrusion.

Matrix metalloproteinases are maintained in an inactive state by a bond between the thiol of a conserved cysteine in the prodomain and a zinc atom in the catalytic domain. Once this bond is disrupted, MMPs become active proteinases and can act on a variety of extracellular protein substrates. In vivo, matrilysin (MMP7) activates pro-alpha-defensins (procryptdins), but in vitro, processing of these peptides is slow, with about 50% conversion in 8-12 h. Similarly, autolytic activation of promatrilysin in vitro can take up to 12-24 h for 50% conversion. These inefficient reactions suggest that natural cofactors enhance the activation and activity of matrilysin. We determined that highly sulfated glycosaminoglycans (GAG), such as heparin, chondroitin-4,6-sulfate (CS-E), and dermatan sulfate, markedly enhanced (>50-fold) the intermolecular autolytic activation of promatrilysin and the activity of fully active matrilysin to cleave specific physiologic substrates. In contrast, heparan sulfate and less sulfated forms of chondroitin sulfate did not augment matrilysin activation or activity. Chondroitin-2,6-sulfate (CS-D) also did not enhance matrilysin activity, suggesting that the presentation of sulfates is more important than the overall degree of sulfation. Surface plasmon resonance demonstrated that promatrilysin bound heparin (K(D), 400 nm) and CS-E (K(D), 630 nm). Active matrilysin bound heparin (K(D), 150 nm) but less so to CS-E (K(D), 60 microm). Neither form bound heparan sulfate. These observations demonstrate that sulfated GAGs regulate matrilysin activation and its activity against specific substrates.

As their name implies, MMPs were first described as proteases that degrade extracellular matrix proteins, such as collagens, elastin, proteoglycans, and laminins. However, studies of MMP function in vivo have revealed that these proteinases act on a variety of extracellular protein substrates, often to activate latent forms of effector proteins, such as antimicrobial peptides and cytokines, or to alter protein function, such as shedding of cell-surface proteins. Because their substrates are diverse, MMPs are involved in variety of homeostatic functions, such as bone remodeling, wound healing, and several aspects of immunity. However, MMPs are also involved in a number of pathological processes, such as tumor progression, fibrosis, chronic inflammation, tissue destruction, and more. A key step in regulating MMP proteolysis is the conversion of the zymogen into an active proteinase. Several proMMPs are activated in the secretion pathway by furin proprotein convertases, but for most the activation mechanisms are largely not known. In this review, we discuss both authentic and potential mechanisms of proMMP activation.

To quantitatively elucidate attributes of myocyte-matrix adhesion, muscle cells were controllably peeled from narrow strips of collagen-coated glass. Initial growth of primary quail myoblasts on collagen strips was followed by cell alignment, elongation and end-on fusion between neighbors. This geometric influence on differentiation minimized lateral cell contact and cell branching, enabling detailed study of myocyte-matrix adhesion. A micropipette was used to pull back one end of a quasi-cylindrical cell while observing in detail the non-equilibrium detachment process. Peeling velocities fluctuated as focal roughness, microm in scale, was encountered along the detachment front. Nonetheless, mean peeling velocity ( microm/second) generally increased with detachment force (nN), consistent with forced disruption of adhesion bonds. Immunofluorescence of beta1-integrins correlated with the focal roughness and appeared to be clustered in axially extended focal contacts. In addition, the peeling forces and rates were found to be moderately well described by a dynamical peeling model for receptor-based adhesion (Dembo, M., Torney, D. C., Saxman, K. and Hammer, D. (1988). Proc. R. Soc. Lond. B 234, 55-83). Estimates were thereby obtained for the spontaneous, molecular off-rate (kooff, (less than or equal to)10/seconds) and the receptor complex stiffness (kappa, approx. 10(-5)-10(-6) N/m) of adherent myocytes. Interestingly, the local stiffness is within the range of flexible proteins of the spectrin superfamily. The overall approach lends itself to elucidating the developing function of other structural and adhesive components of cells, particularly skeletal muscle cells with specialized components, such as the spectrin-homolog dystrophin and its membrane-linked receptor dystroglycan.