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Purpose One-stage revision anterior cruciate ligament reconstruction (ACLR) with the anatomic rectangular tunnel (RT) technique using bone–patellar tendon–bone (BTB) grafts results in anatomically precise tunnel placement and secure graft fixation. This study evaluated knee joint laxity and clinical outcomes in terms of femoral tunnel overlap. It was hypothesised that there would be no significant differences in knee joint laxity or clinical outcomes regardless of femoral tunnel overlap. Methods Between 2012 and 2021, a single surgeon conducted 196 one-stage revision ACLRs with the RT technique using BTB grafts. Patients were divided based on the presence of femoral tunnel overlap. Knee joint laxity was evaluated using the Lachman test, pivot shift test, and side-to-side difference measured with a KT-1000 arthrometer. Clinical outcomes were assessed using the Lysholm score, Knee Injury and Osteoarthritis Outcome Score (KOOS), and International Knee Documentation Committee (IKDC) Knee Examination Form 2000. Knee joint laxity and clinical outcomes were compared between groups after a median follow-up of 2.5 years (range 2.0–8.0). Results The study included 30 and 73 patients in the overlap and non-overlap groups, respectively. No significant differences were observed in the results of the Lachman test, pivot shift test, or KT-1000 arthrometer as well as in the Lysholm, KOOS, or IKDC scores between the two groups. Based on the IKDC scores, all patients were graded as normal or nearly normal. Conclusion One-stage revision ACLR with the RT technique using BTB grafts improved knee joint laxity and had favourable clinical outcomes regardless of femoral tunnel overlap. To achieve optimal results in one-stage revision ACLR, it is crucial to create a tunnel within the anatomical attachment area and ensure proper graft fixation and tensioning. Level of evidence III.

Background: Evaluation of medial meniscal extrusion (MME) under physiological loads is crucial because of the influence of MME on meniscal function. Reducing the MME is essential for meniscal function. Few studies have compared the extent of MME in cases of complete radial tears of the posterior segment of the medial meniscus (MM) treated using basic meniscal repair techniques: the inside-out and all-inside techniques. Purpose: To compare the extent of MME after the treatment of complete radial tears of the posterior segment using inside-out and all-inside meniscal repair techniques in a cadaveric model. Study Design: Controlled laboratory study. Methods: Six fresh-frozen human cadaveric knees were subjected to a compression load of 250 N using a 6 degrees of freedom robotic system under ultrasound evaluation. The MME was evaluated at 30° and 90° knee flexion in 4 meniscal conditions: (1) intact; (2) complete radial tear in the posterior segment of the MM; (3) inside-out repair technique; and (4) all-inside repair technique using 1 horizontal suture. Conditions 3 and 4 were performed on the same knee in a randomized order. Measurements were obtained at the center of the superficial medial collateral ligament (MCL) (central image) and 1 cm posterior to the superficial MCL (posterior image). Statistical analysis was conducted using a 2-factor repeated-measures analysis of variance with Bonferroni post-hoc correction, with significance level set at P < .05. Results: The amount of MME under compression load after inside-out repair was significantly lower than that after all-inside repair (mean ± SD values for the central image: 30°, 1.93 ± 0.26 mm vs 2.45 ± 0.34 mm; 90°, 2.02 ± 0.29 mm vs 2.53 ± 0.42 mm; for the posterior image: 30°, 1.98 ± 0.30 mm vs 2.43 ± 0.35 mm; 90°, 2.45 ± 0.26 mm vs 3 ± 0.42 mm; P < .001 for all comparisons). Conclusion: Although the inside-out repair technique reduced the amount of MME to a greater extent than the all-inside repair technique using a single horizontal stitch for MM posterior segment tears, neither technique was able to reduce MME to the same level as that of the intact state; furthermore, the change in MME was relatively small. Clinical Relevance: The findings indicate that the inside-out repair technique should be used to repair complete radial tears in the posterior segment of the MM.

Mesenchymal stem cells (MSCs) derived from induced pluripotent stem cells (iPSCs) are a promising cell source for the repair of skeletal disorders. Recently, neural crest cells (NCCs) were reported to be effective for inducing mesenchymal progenitors, which have potential to differentiate into osteochondral lineages. Our aim was to investigate the feasibility of MSC-like cells originated from iPSCs via NCCs for osteochondral repair. Initially, MSC-like cells derived from iPSC-NCCs (iNCCs) were generated and characterized in vitro. These iNCC-derived MSC-like cells (iNCMSCs) exhibited a homogenous population and potential for osteochondral differentiation. No upregulation of pluripotent markers was detected during culture. Second, we implanted iNCMSC-derived tissue-engineered constructs into rat osteochondral defects without any preinduction for specific differentiation lineages. The implanted cells remained alive at the implanted site, whereas they failed to repair the defects, with only scarce development of osteochondral tissue in vivo. With regard to tumorigenesis, the implanted cells gradually disappeared and no malignant cells were detected throughout the 2-month follow-up. While this study did not show that iNCMSCs have efficacy for repair of osteochondral defects when implanted under undifferentiated conditions, iNCMSCs exhibited good chondrogenic potential in vitro under appropriate conditions. With further optimization, iNCMSCs may be a new source for tissue engineering of cartilage.

ObjectiveLower extremity sports injuries frequently occur during an individual’s growth period. The object of the current study was to analyse the risk factors for lower extremity sports injuries for youth athletes. The secondary objective was to clarify the factors related to new injuries after a lower extremity injury.MethodsWe extracted information on youth athletes (aged 10–15 years) with sports-related disorders. Background data and injury situations were collected via a specific application. During the follow-up period, new injuries were also recorded. The athletes were divided into two groups according to injury location (lower extremity or other). We performed a multiple logistic regression analysis to clarify the association between injury location and background data.Results1575 complaints of lower extremity disorders and 328 complaints in other body parts were registered. According to the multiple regression analysis, practice time per week was significantly shorter for the lower extremity group than the other locations group (OR 0.98; 95% CI 0.963 to 0.999). Athletes whose future goal was at the recreational level had a significantly low incidence of new injuries after experiencing lower extremity disorders.ConclusionThe practice environments and psychological factors should receive more attention to prevent lower extremity injuries.

Mesenchymal stem cell- (MSC-) based therapy is a promising treatment for cartilage. However, repair tissue in general fails to regenerate an original hyaline-like tissue. In this study, we focused on increasing the expression levels for insulin-like growth factor-1 (IGF-1) to improve repair tissue quality. The IGF-1 gene was introduced into human synovial MSCs with a lentiviral vector and examined the levels of gene expression and morphological status of MSCs under chondrogenic differentiation condition using pellet cultures. The size of the pellets derived from IGF-1-MSCs were significantly larger than those of the control group. The abundance of glycosaminoglycan (GAG) was also significantly higher in the IGF-1-MSC group. The histology of the IGF-1-induced pellets demonstrated similarities to hyaline cartilage without exhibiting features of a hypertrophic chondrocyte phenotype. Expression levels for the Col2A1 gene and protein were significantly higher in the IGF-1 pellets than in the control pellets, but expression levels for Col10, MMP-13, ALP, and Osterix were not higher. Thus, IGF-1 gene transfer to human synovial MSCs led to an improved chondrogenic differentiation capacity without the detectable induction of a hypertrophic or osteogenic phenotype.

Introduction The clinical benefits of high tibial osteotomy (HTO) in patients with mild varus deformity with degenerative medial meniscal tear (DMMT) remain unclear. This study aimed to compare clinical outcomes among middle-aged patients with mild varus deformity who underwent arthroscopic meniscal repair and HTO for DMMT. Materials and methods In this retrospective study, patients who underwent isolated arthroscopic meniscal repair via the inside-out technique and those who underwent medial opening-wedge HTO were assigned to group M and H, respectively. The inclusion criteria were: an age of 40–65 years; percentage of mechanical axis of 30–50% measured using full-length weight-bearing anteroposterior radiographs; Kellgren–Lawrence grade ≤ 2; minimum postoperative two-year follow-up; and HTO correction angle < 10°. Clinical outcomes were assessed using the Knee Injury and Osteoarthritis Outcome Score (KOOS) and minimal clinically important difference achievement rate for the KOOS subscales preoperatively and at the final follow-up. Results Group M and H included 21 and 41 patients, respectively. The median ages were 53 and 58 years in groups M and H, respectively. In group H, 24 cases underwent meniscal repair. No significant differences in all KOOS subscales were found preoperatively. However, the median KOOS symptoms subscale in group H (89.3) was significantly better than that in group M (80.4) at the final follow-up ( p  = 0.04). Conclusion The main finding of the study indicated that KOOS symptoms after HTO were superior to those after isolated arthroscopic meniscal repair for DMMT. HTO might be a potentially useful treatment for DMMT in middle-aged patients with mild varus deformity, even with a small correction angle. Level of evidence Retrospective comparative study, Level III.

Introduction This study evaluated the correlation between postoperative knee joint line obliquity after medial open-wedge high tibial osteotomy and patient-reported outcome measures excluding excessively overcorrected knees. This study further identified preoperative radiological factors related to the increased postoperative knee joint line obliquity. Materials and methods We retrospectively evaluated patients who underwent medial open-wedge high tibial osteotomy between March 2013 and March 2021. Postoperative excessively overcorrected knees with hip-knee-ankle angle > 7° were excluded. We investigated radiological parameters and patient-reported outcome measures preoperatively and at the last follow-up. The following radiologic parameters were measured: hip-knee-ankle angle, weight-bearing line ratio, mechanical medial proximal tibial angle, mechanical lateral distal femoral angle, lateral distal tibial angle, joint line convergent angle, knee joint line obliquity, ankle joint line obliquity, hip abduction angle, tibial posterior slope, Carton-Deschamps index, and patella tilting angle. Clinical outcomes were evaluated using Japanese knee outcome measures. This assessment criterion is based on the Western Ontario McMaster Universities Arthritis Index and MOS Short Form 36. Multiple regression analysis was performed to evaluate the association between postoperative knee joint line obliquity and patient-reported outcome measures or preoperative radiological factors ( P  < .05). Results A total of 52 knees were included. The mean age at the time of the surgery was 61.6 ± 9.0 years and the mean follow-up period was 30.6 ± 10.1 months. Increased postoperative knee joint line obliquity was associated with lower Japanese knee outcome measures. The preoperative hip-knee-ankle angle was significantly associated with postoperative knee joint line obliquity. Conclusions Increased knee joint line obliquity after medial open-wedge high tibial osteotomy is associated with inferior clinical outcomes. Care should be given to the center of the rotational angulation in around-knee osteotomy to avoid postoperative increased knee joint line obliquity. Level of evidence Retrospective comparative study, Level III.

Background Many countries are faced with aging populations. However, few studies have directly compared the clinical outcomes of medial opening-wedge high tibial osteotomy (OWHTO) and mobile-bearing unicompartmental knee arthroplasty (MB-UKA) in early elderly patients. Thus, we aimed to investigate the clinical outcomes after OWHTO and MB-UKA in early elderly patients with similar demographics and osteoarthritis (OA) severity.MethodsThree hundred and fifteen OWHTO and 142 MB-UKA were performed for medial compartment OA by a single surgeon between August 2009 and April 2020. Among them, patients aged 65–74 years with more than two years of follow-up were enrolled. The patient-reported outcome measures (PROMs), including visual analog scale (VAS) score and Japanese Knee Osteoarthritis Measure (JKOM) score, were compared between both procedures preoperatively and at the last follow-up. The PROMs were compared between the groups by Kellgren–Lawrence (K–L) OA grades.ResultsSeventy-three OWHTO and 37 MB-UKA patients were enrolled. No significant differences were found in the distribution of age, gender, follow-up period, body mass index, and Tegner activity scale between the two procedures. The postoperative PROMs in patients with K–L grade 4 were better after MB-UKA than OWHTO at the mean follow-up of 5 years. No significant difference was found in PROMs in patients with K–L grades 2 and 3.ConclusionThePROMs after MB-UKA were superior to that after OWHTO in early elderly patients with severe OA. In particular, pain relief was better after MB-UKA than OWHTO with severe OA. Meanwhile, no significant difference in PROMs was found with moderate OA patients.Level of evidenceLevel IVprospective cohort study.

Comprehensive genomic profiling enables genomic biomarker detection in advanced solid tumors. Here, to evaluate the utility of circulating tumor DNA (ctDNA) genotyping, we compare trial enrollment using ctDNA sequencing in 1,687 patients with advanced gastrointestinal (GI) cancer in SCRUM-Japan GOZILA (no. UMIN000016343), an observational ctDNA-based screening study, to enrollment using tumor tissue sequencing in the same centers and network (GI-SCREEN, 5,621 patients). ctDNA genotyping significantly shortened the screening duration (11 versus 33 days, P  < 0.0001) and improved the trial enrollment rate (9.5 versus 4.1%, P  < 0.0001) without compromising treatment efficacy compared to tissue genotyping. We also describe the clonal architecture of ctDNA profiles in ~2,000 patients with advanced GI cancer, which reinforces the relevance of many targetable oncogenic drivers and highlights multiple new drivers as candidates for clinical development. ctDNA genotyping has the potential to accelerate innovation in precision medicine and its delivery to individual patients. An observational study on a large cohort of patients with gastrointestinal cancer demonstrates the utility of ctDNA analysis for accelerating the enrollment of patients in clinical trials with no accompanying deterioration in treatment efficacy.

Cancer cells in the tumour microenvironment use various mechanisms to evade the immune system, particularly T cell attack 1 . For example, metabolic reprogramming in the tumour microenvironment and mitochondrial dysfunction in tumour-infiltrating lymphocytes (TILs) impair antitumour immune responses 2 , 3 – 4 . However, detailed mechanisms of such processes remain unclear. Here we analyse clinical specimens and identify mitochondrial DNA (mtDNA) mutations in TILs that are shared with cancer cells. Moreover, mitochondria with mtDNA mutations from cancer cells are able to transfer to TILs. Typically, mitochondria in TILs readily undergo mitophagy through reactive oxygen species. However, mitochondria transferred from cancer cells do not undergo mitophagy, which we find is due to mitophagy-inhibitory molecules. These molecules attach to mitochondria and together are transferred to TILs, which results in homoplasmic replacement. T cells that acquire mtDNA mutations from cancer cells exhibit metabolic abnormalities and senescence, with defects in effector functions and memory formation. This in turn leads to impaired antitumour immunity both in vitro and in vivo. Accordingly, the presence of an mtDNA mutation in tumour tissue is a poor prognostic factor for immune checkpoint inhibitors in patients with melanoma or non-small-cell lung cancer. These findings reveal a previously unknown mechanism of cancer immune evasion through mitochondrial transfer and can contribute to the development of future cancer immunotherapies. Mitochondria with mutations in their DNA from cancer cells can be transferred to T cells in the tumour microenvironment, which leads to T cell dysfunction and impaired antitumour immunity.