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  1. Saw KY, Anz AW, Ng RC, Jee CS, Low SF, Dorvault C, et al.
    Arthroscopy, 2021 08;37(8):2502-2517.
    PMID: 34265388 DOI: 10.1016/j.arthro.2021.01.067
    PURPOSE: The purpose of this study was to evaluate the safety and efficacy of intra-articular injections of autologous peripheral blood stem cells (PBSCs) plus hyaluronic acid (HA) after arthroscopic subchondral drilling into massive chondral defects of the knee joint and to determine whether PBSC therapy can improve functional outcome and reduce pain of the knee joint better than HA plus physiotherapy.

    METHODS: This is a dual-center randomized controlled trial (RCT). Sixty-nine patients aged 18 to 55 years with International Cartilage Repair Society grade 3 and 4 chondral lesions (size ≥3 cm2) of the knee joint were randomized equally into (1) a control group receiving intra-articular injections of HA plus physiotherapy and (2) an intervention group receiving arthroscopic subchondral drilling into chondral defects and postoperative intra-articular injections of PBSCs plus HA. The coprimary efficacy endpoints were subjective International Knee Documentation Committee (IKDC) and Knee Injury and Osteoarthritis Outcome Score (KOOS)-pain subdomain measured at month 24. The secondary efficacy endpoints included all other KOOS subdomains, Numeric Rating Scale (NRS), and Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) scores.

    RESULTS: At 24 months, the mean IKDC scores for the control and intervention groups were 48.1 and 65.6, respectively (P < .0001). The mean for KOOS-pain subdomain scores were 59.0 (control) and 86.0 (intervention) with P < .0001. All other KOOS subdomain, NRS, and MOCART scores were statistically significant (P < .0001) at month 24. Moreover, for the intervention group, 70.8% of patients had IKDC and KOOS-pain subdomain scores exceeding the minimal clinically important difference values, indicating clinical significance. There were no notable adverse events that were unexpected and related to the study drug or procedures.

    CONCLUSIONS: Arthroscopic marrow stimulation with subchondral drilling into massive chondral defects of the knee joint followed by postoperative intra-articular injections of autologous PBSCs plus HA is safe and showed a significant improvement of clinical and radiologic scores compared with HA plus physiotherapy.

    LEVEL OF EVIDENCE: Level I, RCT.

  2. Saw KY, Hussin P, Loke SC, Azam M, Chen HC, Tay YG, et al.
    Arthroscopy, 2009 Dec;25(12):1391-400.
    PMID: 19962065 DOI: 10.1016/j.arthro.2009.07.011
    PURPOSE: The purpose of the study was to determine whether postoperative intra-articular injections of autologous marrow aspirate (MA) and hyaluronic acid (HA) after subchondral drilling resulted in better cartilage repair as assessed histologically by Gill scoring.
    METHODS: In a goat model we created a 4-mm full-thickness articular cartilage defect in the stifle joint (equivalent to 1.6 cm in the human knee) and conducted subchondral drilling. The animals were divided into 3 groups: group A (control), no injections; group B (HA), weekly injection of 1 mL of sodium hyaluronate for 3 weeks; and group C (HA + MA), similar to group B but with 2 mL of autologous MA in addition to HA. MA was obtained by bone marrow aspiration, centrifuged, and divided into aliquots for cryopreservation. Fifteen animals were equally divided between the groups and sacrificed 24 weeks after surgery, when the joint was harvested, examined macroscopically and histologically.
    RESULTS: Of the 15 animals, 2 from group A had died of non-surgery-related complications and 1 from group C was excluded because of a joint infection. In group A the repair constituted mainly scar tissue, whereas in group B there was less scar tissue, with small amounts of proteoglycan and type II collagen at the osteochondral junction. In contrast, repair cartilage from group C animals showed almost complete coverage of the defect with evidence of hyaline cartilage regeneration. Histology assessed by Gill scoring was significantly better in group C with 1-way analysis of variance yielding an F statistic of 10.611 with a P value of .004, which was highly significant.
    CONCLUSIONS: Postoperative intra-articular injections of autologous MA in combination with HA after subchondral drilling resulted in better cartilage repair as assessed histologically by Gill scoring in a goat model.
    CLINICAL RELEVANCE: After arthroscopic subchondral drilling, this novel technique may result in better articular cartilage regeneration.
  3. Saw KY, Anz A, Merican S, Tay YG, Ragavanaidu K, Jee CS, et al.
    Arthroscopy, 2011 Apr;27(4):493-506.
    PMID: 21334844 DOI: 10.1016/j.arthro.2010.11.054
    PURPOSE: The purpose of this study was to evaluate the quality of articular cartilage regeneration after arthroscopic subchondral drilling followed by postoperative intraarticular injections of autologous peripheral blood progenitor cells (PBPCs) in combination with hyaluronic acid (HA).
    METHODS: Five patients underwent second-look arthroscopy with chondral core biopsy. These 5 patients are part of a larger pilot study in which 180 patients with International Cartilage Repair Society grade III and IV lesions of the knee joint underwent arthroscopic subchondral drilling followed by postoperative intra-articular injections. Continuous passive motion was used on the operated knee 2 hours per day for 4 weeks. Partial weight bearing was observed for the first 6 to 8 weeks. Autologous PBPCs were harvested 1 week after surgery. One week after surgery, 8 mL of the harvested PBPCs in combination with 2 mL of HA was injected intra-articularly into the operated knee. The remaining PBPCs were divided into vials and cryopreserved. A total of 5 weekly intra-articular injections were given.
    RESULTS: Second-look arthroscopy confirmed articular cartilage regeneration, and histologic sections showed features of hyaline cartilage. Apart from the minimal discomfort of PBPC harvesting and localized pain associated with the intra-articular injections, there were no other notable adverse reactions.
    CONCLUSIONS: Articular hyaline cartilage regeneration is possible with arthroscopic subchondral drilling followed by postoperative intraarticular injections of autologous PBPCs in combination with HA.
    LEVEL OF EVIDENCE: Level IV, therapeutic case series.
  4. Saw KY, Anz A, Jee CSY, Merican S, Ching-Soong Ng R, Roohi SA, et al.
    Arthroscopy, 2013 Apr;29(4):684-94.
    PMID: 23380230 DOI: 10.1016/j.arthro.2012.12.008
    PURPOSE: The purpose of this study was to compare histologic and magnetic resonance imaging (MRI) evaluation of articular cartilage regeneration in patients with chondral lesions treated by arthroscopic subchondral drilling followed by postoperative intra-articular injections of hyaluronic acid (HA) with and without peripheral blood stem cells (PBSC).
    METHODS: Fifty patients aged 18 to 50 years with International Cartilage Repair Society (ICRS) grade 3 and 4 lesions of the knee joint underwent arthroscopic subchondral drilling; 25 patients each were randomized to the control (HA) and the intervention (PBSC + HA) groups. Both groups received 5 weekly injections commencing 1 week after surgery. Three additional injections of either HA or PBSC + HA were given at weekly intervals 6 months after surgery. Subjective IKDC scores and MRI scans were obtained preoperatively and postoperatively at serial visits. We performed second-look arthroscopy and biopsy at 18 months on 16 patients in each group. We graded biopsy specimens using 14 components of the International Cartilage Repair Society Visual Assessment Scale II (ICRS II) and a total score was obtained. MRI scans at 18 months were assessed with a morphologic scoring system.
    RESULTS: The total ICRS II histologic scores for the control group averaged 957 and they averaged 1,066 for the intervention group (P = .022). On evaluation of the MRI morphologic scores, the control group averaged 8.5 and the intervention group averaged 9.9 (P = .013). The mean 24-month IKDC scores for the control and intervention groups were 71.1 and 74.8, respectively (P = .844). One patient was lost to follow-up. There were no notable adverse events.
    CONCLUSIONS: After arthroscopic subchondral drilling into grade 3 and 4 chondral lesions, postoperative intra-articular injections of autologous PBSC in combination with HA resulted in an improvement of the quality of articular cartilage repair over the same treatment without PBSC, as shown by histologic and MRI evaluation.
    LEVEL OF EVIDENCE: Level II, randomized controlled trial (RCT).
  5. Kondo E, Merican AM, Yasuda K, Amis AA
    Arthroscopy, 2014 Mar;30(3):335-43.
    PMID: 24581258 DOI: 10.1016/j.arthro.2013.12.003
    The purpose of this study was to clarify the changes in the kinematics of the knee that result from isolated deficiency of the anteromedial (AM) or posterolateral (PL) bundle.
  6. Lee YS, Lee OS, Lee SH, Hui TS
    Arthroscopy, 2018 02;34(2):592-602.
    PMID: 28974333 DOI: 10.1016/j.arthro.2017.07.023
    PURPOSE: The purpose of this systematic review and meta-analysis was to evaluate the effect of the timing of anterior cruciate ligament (ACL) reconstruction on clinical and stability outcomes by analyzing high-quality studies that assessed timing as a primary objective.

    METHODS: The MEDLINE, EMBASE, and Cochrane database were systematically searched. The inclusion criteria were as follows: (1) English articles, (2) noncomparative study or relevant study reporting clinical and/or stability results, and (3) timing of the ACL reconstruction as a primary objective. Study type, level of evidence, randomization method, exclusion criteria, number of cases, age, sex, timing of ACL reconstruction, follow-up, clinical outcomes, stability outcomes, and other relevant findings were recorded. Statistical analysis of the Lysholm scores and KT-1000 arthrometer measurements after early and delayed ACL reconstruction was performed using R version 3.3.1.

    RESULTS: Seven articles were included in the final analysis. There were 6 randomized controlled trials and 1 Level II study. Pooled analysis was performed using only Level I studies. All studies assessed the timing of ACL reconstruction as a primary objective. The definition of early ranged broadly from 9 days to 5 months and delayed ranged from 10 weeks to >24 months, and there was an overlap of the time intervals between some studies. The standard timing of the delayed reconstruction was around 10 weeks from injury in the pooled analysis. After pooling of data, clinical result was not statistically different between groups (I2: 47%, moderate level of heterogeneity). No statistically significant difference was observed in the KT-1000 arthrometer measurements between groups (I2: 76.2%, high level of heterogeneity) either.

    CONCLUSION: This systematic review and meta-analysis performed using currently available high-quality literature provides relatively strong evidence that early ACL reconstruction results in good clinical and stability outcomes. Early ACL reconstruction results in comparable clinical and stability outcomes compared with delayed ACL reconstruction.

    LEVEL OF EVIDENCE: Level II, a systematic review and meta-analysis of Level I and II studies.

  7. Yeo DYT, Suhaimi F, Parker DA
    Arthroscopy, 2019 11;35(11):3146-3164.e2.
    PMID: 31699269 DOI: 10.1016/j.arthro.2019.06.016
    PURPOSE: To identify factors that affect patient-reported outcome measures (PROMs) and failure rates after arthroscopic meniscal repair.

    METHODS: Embase, Embase Classic, and MEDLINE were searched on August 7, 2015, December 23, 2016, and March 11, 2018, for factors associated with PROMs and failure rates after arthroscopic meniscal repair. We excluded studies that (1) were non-English language, (2) did not use human patients, (3) were nonclinical, (4) did not analyze for factors that predicted PROMs or failure rates, and (5) were below Level IV evidence. Studies were graded into higher and lower quality using the Downs and Black scale.

    RESULTS: A total of 34 articles met our criteria, and 32 were graded. We identified 16 articles as higher quality. Among higher-quality studies, factors that significantly predicted reduced failure rates were concurrent anterior cruciate ligament reconstruction (ACLR) (n = 6) and reduced tear complexity (n = 4). Factors that did not significantly impact failure rates were side of repair (n = 8), sex (n = 7), time from injury to surgery (n = 7), age (n = 7), rim width (n = 6), and tear length (n = 5). Factors predicting better PROMs were time from injury to surgery of less than 3 months (n = 1), Outerbridge scores below grade 3 or 4 (n = 2), and reduced varus alignment (n = 2). Factors that did not significantly impact PROMs were equipment used (n = 3) and concurrent ACLR (n = 1).

    CONCLUSIONS: Factors affecting failure rates and PROMs after arthroscopic meniscal repair were identified. However, more and higher-quality studies supported concurrent ACLR and less complex tears as predictors of lower failure rates. PROMs were negatively affected by a longer time from injury to surgery, higher Outerbridge scores, and greater varus alignment before surgery.

    LEVEL OF EVIDENCE: Level IV, systematic review of Level II to IV studies.

  8. Saw KY, Anz A, Jee CS, Ng RC, Mohtarrudin N, Ragavanaidu K
    Arthroscopy, 2015 Oct;31(10):1909-20.
    PMID: 26008951 DOI: 10.1016/j.arthro.2015.03.038
    PURPOSE: To histologically evaluate the quality of articular cartilage regeneration from the medial compartment after arthroscopic subchondral drilling followed by postoperative intra-articular injections of autologous peripheral blood stem cells (PBSCs) and hyaluronic acid with concomitant medial open-wedge high tibial osteotomy (HTO) in patients with varus deformity of the knee joint.
    METHODS: Eight patients with varus deformity of the knee joint underwent arthroscopic subchondral drilling of International Cartilage Repair Society (ICRS) grade 4 bone-on-bone lesions of the medial compartment with concomitant HTO. These patients were part of a larger pilot study in which 18 patients underwent the same procedure. PBSCs were harvested and cryopreserved preoperatively. At 1 week after surgery, 8 mL of PBSCs was mixed with 2 mL of hyaluronic acid and injected intra-articularly into the knee joint; this was repeated once a week for 5 consecutive weeks. Three additional intra-articular injections were administered weekly at intervals of 6, 12, and 18 months postoperatively. Informed consent was obtained at the time of hardware removal for opportunistic second-look arthroscopy and chondral biopsy. Biopsy specimens were stained with H&E, safranin O, and immunohistochemical staining for type I and II collagen. Specimens were graded using the 14 components of the ICRS Visual Assessment Scale II, and a total score was obtained.
    RESULTS: Second-look arthroscopy showed satisfactory healing of the regenerated cartilage. Histologic analysis showed significant amounts of proteoglycan and type II collagen. The total ICRS Visual Assessment Scale II histologic scores comparing the regenerated articular cartilage (mean, 1,274) with normal articular cartilage (mean, 1,340) indicated that the repair cartilage score approached 95% of the normal articular cartilage score. There were no infections, delayed unions, or nonunions.
    CONCLUSIONS: Chondrogenesis with stem cells in combination with medial open-wedge HTO for varus deformity correction of the knee joint regenerates cartilage that closely resembles the native articular cartilage.
    LEVEL OF EVIDENCE: Level IV, therapeutic case series.
  9. Ling JL, Teo SH, Mohamed Al-Fayyadh MZ, Mohamed Ali MR, Ng WM
    Arthroscopy, 2019 02;35(2):596-604.
    PMID: 30611592 DOI: 10.1016/j.arthro.2018.08.038
    PURPOSE: To assess the effectiveness of a low-cost self-made arthroscopic camera (LAC) in basic arthroscopic skills training compared with a commercial arthroscopic camera (CAC).

    METHODS: One hundred fifty-three orthopaedic residents were recruited and randomly assigned to either the LAC or CAC. They were allocated 2 practice sessions, with 20 minutes each, to practice 4 given arthroscopic tasks: task 1, transferring objects; task 2, stacking objects; task 3, probing numbers; and task 4, stretching rubber bands. The time taken for participants to complete the given tasks was recorded in 3 separate tests; before practice, immediately after practice, and after a period of 3 months. A comparison of the time taken between both groups to complete the given tasks in each test was measured as the primary outcome.

    RESULTS: Significant improvements in time completion were seen in the post-practice test for both groups in all given arthroscopic tasks, each with P < .001. However, there was no significant difference between the groups for task 1 (P = .743), task 2 (P = .940), task 3 (P = .932), task 4 (P = .929), and total (P = .944). The outcomes of the tests (before practice, after practice, and at 3 months) according to repeated measures analysis of variance did not differ significantly between the groups in task 1 (P = .475), task 2 (P = .558), task 3 (P = .850), task 4 (P = .965), and total (P = .865).

    CONCLUSIONS: The LAC is equally as effective as the CAC in basic arthroscopic skills training with the advantage of being cost-effective.

    CLINICAL RELEVANCE: In view of the scarcity in commercial arthroscopic devices for trainees, this low-cost device, which trainees can personally own and use, may provide a less expensive and easily available way for trainees to improve their arthroscopic skills. This might also cultivate more interest in arthroscopic surgery among junior surgeons.

  10. Cartwright-Terry M, Yates J, Tan CK, Pengas IP, Banks JV, McNicholas MJ
    Arthroscopy, 2014 Jul;30(7):811-7.
    PMID: 24794571 DOI: 10.1016/j.arthro.2014.02.039
    To present a 5-year comparison of the functional outcomes of combined anterior cruciate ligament (ACL) and posterolateral corner (PLC) reconstruction with those of isolated ACL reconstruction.
  11. Anz AW, Torres J, Plummer HA, Siew-Yoke Jee C, Dekker TJ, Johnson KB, et al.
    Arthroscopy, 2021 11;37(11):3347-3356.
    PMID: 33940122 DOI: 10.1016/j.arthro.2021.04.036
    PURPOSE: The primary objective of this study was to reproduce and validate the harvest, processing and storage of peripheral blood stem cells for a subsequent cartilage repair trial, evaluating safety, reliability, and potential to produce viable, sterile stem cells.

    METHODS: Ten healthy subjects (aged 19-44 years) received 3 consecutive daily doses of filgrastim followed by an apheresis harvest of mononuclear cells on a fourth day. In a clean room, the apheresis product was prepared for cryopreservation and processed into 4 mL aliquots. Sterility and qualification testing were performed pre-processing and post-processing at multiple time points out to 2 years. Eight samples were shipped internationally to validate cell transport potential. One sample from all participants was cultured to test proliferative potential with colony forming unit (CFU) assay. Five samples, from 5 participants were tested for differentiation potential, including chondrogenic, adipogenic, osteogenic, endoderm, and ectoderm assays.

    RESULTS: Fresh aliquots contained an average of 532.9 ± 166. × 106 total viable cells/4 mL vial and 2.1 ± 1.0 × 106 CD34+ cells/4 mL vial. After processing for cryopreservation, the average cell count decreased to 331.3 ± 79. × 106 total viable cells /4 mL vial and 1.5 ± 0.7 × 106 CD34+ cells/4 mL vial CD34+ cells. Preprocessing viability averaged 99% and postprocessing 88%. Viability remained constant after cryopreservation at all subsequent time points. All sterility testing was negative. All samples showed proliferative potential, with average CFU count 301.4 ± 63.9. All samples were pluripotent.

    CONCLUSIONS: Peripheral blood stem cells are pluripotent and can be safely harvested/stored with filgrastim, apheresis, clean-room processing, and cryopreservation. These cells can be stored for 2 years and shipped without loss of viability.

    CLINICAL RELEVANCE: This method represents an accessible stem cell therapy in development to augment cartilage repair.

  12. Lee YS, Teo SH, Ahn JH, Lee OS, Lee SH, Lee JH
    Arthroscopy, 2017 Oct;33(10):1884-1895.
    PMID: 28655477 DOI: 10.1016/j.arthro.2017.04.006
    PURPOSE: To evaluate the surgical treatment of the discoid lateral meniscus (DLM) with long-term follow-up and to search which factors are related to good clinical or radiological outcomes.

    METHODS: Search was performed using a MEDLINE, EMBASE, and Cochrane database, and each of the selected studies was evaluated for methodological quality using a risk of bias (ROB) covering 7 criteria. Clinical and radiological outcomes with more than 5 years of follow-up were evaluated after surgical treatment of DLM. They were analyzed according to the age, follow-up period, kind of surgery, DLM type, and alignment.

    RESULTS: Eleven articles (422 DLM cases) were included in the final analysis. Among 7 criteria, 3 criteria showed little ROB in all studies. However, 4 criteria showed some ROB ("Yes" in 63.6% to 81.8%). The minimal follow-up period was 5.5 years (weighted mean follow-up: 9.1 years). Surgical procedures were performed with open or arthroscopic partial central meniscectomy, subtotal meniscectomy, total meniscectomy, or partial meniscectomy with repair. The majority of the studies showed good clinical results. Mild joint space narrowing was reported in the lateral compartment, but none of the knees demonstrated moderate or advanced degenerative changes. Increased age at surgery, longer follow-up period, and subtotal or total meniscectomy could be related to degenerative change. The majority of the complications was osteochondritis dissecans at the lateral femoral condyle (13 cases) and reoperation was performed by osteochondritis dissecans (4 cases), recurrent swelling (2 cases), residual symptom (1 case), stiffness (1 case), and popliteal stenosis (1 case).

    CONCLUSIONS: Good clinical results were obtained with surgical treatment of symptomatic DLM. The progression of degenerative change was minimal and none of the knees demonstrated moderate or advanced degenerative changes. Increased age at surgery, longer follow-up period, and subtotal or total meniscectomy were possible risk factors for degenerative changes.

    LEVEL OF EVIDENCE: Level IV, systematic review of Level IV studies.

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