Risk Factors for Failure After Osteochondral Allograft Transplantation of the Knee: A Systematic Review and Exploratory Meta-analysis.

BACKGROUND: Graft failure after osteochondral allograft transplantation (OCA) of the knee is a devastating outcome, often necessitating subsequent interventions. A comprehensive understanding of the risk factors for failure after OCA of the knee may provide enhanced prognostic data for the knee surgeon and facilitate more informed shared decision-making discussions before surgery. PURPOSE: To perform a systematic review and meta-analysis of risk factors associated with graft failure after OCA of the knee. STUDY DESIGN: Systematic review and meta-analysis; Level of evidence, 4. METHODS: The PubMed, Ovid/MEDLINE, and Cochrane databases were queried in April 2021. Data pertaining to study characteristics and risk factors associated with failure after OCA were recorded. DerSimonian-Laird binary random-effects models were constructed to quantitatively evaluate the association between risk factors and graft failure by generating effect estimates in the form of odds ratios (ORs) with 95% CIs, while mean differences (MDs) were calculated for continuous data. Qualitative analysis was performed to describe risk factors that were variably reported. RESULTS: A total of 16 studies consisting of 1401 patients were included. The overall pooled prevalence of failure was 18.9% (range, 10%-46%). There were 44 risk factors identified, of which 9 were explored quantitatively. There was strong evidence to support that the presence of bipolar chondral defects (OR, 4.20 [95% CI, 1.17-15.08]; P = .028) and male sex (OR, 2.04 [95% CI, 1.17-3.55]; P = .012) were significant risk factors for failure after OCA. Older age (MD, 5.06 years [95% CI, 1.44-8.70]; P = .006) and greater body mass index (MD, 1.75 kg/m2 [95% CI, 0.48-3.03]; P = .007) at the time of surgery were also significant risk factors for failure after OCA. There was no statistically significant evidence to incontrovertibly support that concomitant procedures, chondral defect size, and defect location were associated with an increased risk of failure after OCA. CONCLUSION: Bipolar chondral defects, male sex, older age, and greater body mass index were significantly associated with an increased failure rate after OCA of the knee. No statistically significant evidence presently exists to support that chondral defect size and location or concomitant procedures are associated with an increased graft failure rate after OCA of the knee. Additional studies are needed to evaluate these associations.

Strategies to prevent suppurative chondritis following auricular burns: a systematic review.

OBJECTIVE: Suppurative chondritis is a potentially devastating complication of burns to the ear. The infection and inflammation can liquify cartilage, leading to significant aesthetic deformities which are difficult to treat. This article reviews published measures for preventing post-burn chondritis. METHOD: A comprehensive search of all available literature up to September 2020 was performed, according to PRISMA guidelines, for studies assessing preventive measures for post-burn chondritis. Randomised controlled trials (RCT), cohort studies, case-control studies, case reports and series were eligible for inclusion. RESULTS: A total of 10 studies, including one RCT and nine retrospective observational analyses, were included, incorporating 1369 patients with burns to the ear. The most common interventions were pressure avoidance (70%), daily cleansing (60%), topical mafenide acetate (60%) and targeted debridement (30%). Packages of measures which included pressure avoidance were the most effective, all of which achieved a chondritis incidence of <6%. CONCLUSION: Low-level but strong published evidence suggests that important treatment principles include prevention by pressure relief, targeted debridement, prophylactic local antibiotics, local antisepsis and the avoidance of desiccation.

The difference in joint instability affects the onset of cartilage degeneration or subchondral bone changes.

OBJECTIVE: It has been debated whether the onset of knee osteoarthritis is initiated in cartilage or subchondral bone. The purpose of this study was to clarify the effects of increasing or decreasing joint instability on cartilage degeneration and subchondral bone changes in knee OA by comparing different models of joint instability. DESIGN: We used the anterior cruciate ligament transection (ACL-T) model and the destabilization of the medial meniscus (DMM) model. In addition, we created a controlled abnormal tibial translation (CATT) model and a controlled abnormal tibial rotation (CATR) model. We performed joint instability analysis, micro-computed tomography analysis, histological and immunohistological analysis in 4 and 6 weeks. RESULTS: The CATT group suppressed joint instability in the ACL-T group (6 weeks; P = 0.032), and the CATR group suppressed joint instability in the DMM group (6 weeks; P = 0.032). Chondrocyte hypertrophy in the ACL-T and DMM groups was increased compared to the Sham group (6 weeks; [ACL-T vs Sham], P = 0.002, 95%CI [5.983-33.025]; [DMM vs Sham], P = 0.022, 95%CI [1.691-28.733]). In the subchondral bone, the BV/TV in the DMM and CATR groups was increased compared to the ACL-T and CATT groups (6 weeks; [DMM vs ACL-T], P = 0.002, 95%CI [7.404-37.582]; [DMM vs CATT], P = 0.014, 95%CI [2.881-33.059]; [CATR vs ACL-T], P = 0.006, 95%CI [4.615-34.793]; [CATR vs CATT], P = 0.048, 95%CI [0.092-30.270]). CONCLUSIONS: This study showed that joint instability promotes chondrocyte hypertrophy, but subchondral bone changes were influenced by differences in ACL and meniscus function.

How Does Chondrolabral Damage and Labral Repair Influence the Mechanics of the Hip in the Setting of Cam Morphology? A Finite-Element Modeling Study.

BACKGROUND: Individuals with cam morphology are prone to chondrolabral injuries that may progress to osteoarthritis. The mechanical factors responsible for the initiation and progression of chondrolabral injuries in these individuals are not well understood. Additionally, although labral repair is commonly performed during surgical correction of cam morphology, the isolated mechanical effect of labral repair on the labrum and surrounding cartilage is unknown. QUESTION/PURPOSES: Using a volunteer-specific finite-element analysis, we asked: (1) How does cam morphology create a deleterious mechanical environment for articular cartilage (as evaluated by shear stress, tensile strain, contact pressure, and fluid pressure) that could increase the risk of cartilage damage compared with a radiographically normal hip? (2) How does chondrolabral damage, specifically delamination, delamination with rupture of the chondrolabral junction, and the presence of a chondral defect, alter the mechanical environment around the damage? (3) How does labral repair affect the mechanical environment in the context of the aforementioned chondrolabral damage scenarios? METHODS: The mechanical conditions of a representative hip with normal bony morphology (characterized by an alpha angle of 37°) and one with cam morphology (characterized by an alpha angle of 78°) were evaluated using finite-element models that included volunteer-specific anatomy and kinematics. The bone, cartilage, and labrum geometry for the hip models were collected from two volunteers matched by age (25 years with cam morphology and 23 years with normal morphology), BMI (both 24 kg/m2), and sex (both male). Volunteer-specific kinematics for gait were used to drive the finite-element models in combination with joint reaction forces. Constitutive material models were assigned to the cartilage and labrum, which simulate a physiologically realistic material response, including the time-dependent response from fluid flow through the cartilage, and spatially varied response from collagen fibril reinforcement. For the cam hip, three models were created to represent chondrolabral damage conditions: (1) "delamination," with the acetabular cartilage separated from the bone in one region; (2) "delamination with chondrolabral junction (CLJ) rupture," which includes separation of the cartilage from the labrum tissue; and (3) a full-thickness chondral defect, referred to throughout as "defect," where the acetabular cartilage has degraded so there is a void. Each of the three conditions was modeled with a labral tear and with the labrum repaired. The size and location of the damage conditions simulated in the cartilage and labrum were attained from reported clinical prevalence of the location of these injuries. For each damage condition, the contact area, contact pressure, tensile strain, shear stress, and fluid pressure were predicted during gait and compared. RESULTS: The cartilage in the hip with cam morphology experienced higher stresses and strains than the normal hip. The peak level of tensile strain (25%) and shear stress (11 MPa) experienced by the cam hip may exceed stable conditions and initiate damage or degradation. The cam hip with simulated damage experienced more evenly distributed contact pressure than the intact cam hip, as well as decreased tensile strain, shear stress, and fluid pressure. The peak levels of tensile strain (15% to 16%) and shear stress (2.5 to 2.7 MPa) for cam hips with simulated damage may be at stable magnitudes. Labral repair only marginally affected the overall stress and strain within the cartilage, but it increased local tensile strain in the cartilage near the chondrolabral junction in the hip with delamination and increased the peak tensile strain and shear stress on the labrum. CONCLUSION: This finite-element modeling pilot study suggests that cam morphology may predispose hip articular cartilage to injury because of high shear stress; however, the presence of simulated damage distributed the loading more evenly and the magnitude of stress and strain decreased throughout the cartilage. The locations of the peak values also shifted posteriorly. Additionally, in hips with cam morphology, isolated labral repair in the hip with a delamination injury increased localized strain in the cartilage near the chondrolabral junction. CLINICAL RELEVANCE: In a hip with cam morphology, labral repair alone may not protect the cartilage from damage because of mechanical overload during the low-flexion, weightbearing positions experienced during gait. The predicted findings of redistribution of stress and strain from damage in the cam hip may, in some cases, relieve disposition to damage progression. Additional studies should include volunteers with varied acetabular morphology, such as borderline dysplasia with cam morphology or pincer deformity, to analyze the effect on the conclusions presented in the current study. Further, future studies should evaluate the combined effects of osteochondroplasty and chondrolabral treatment.

Clinically suspected fibrocartilaginous embolism: a case report and literature review.

Spinal cord infarction (SCI) occurs rarely and is characterized by abrupt onset of neck or back pain and neurologic deterioration. Fibrocartilaginous embolism (FCE) of the spinal cord is a rare but possible cause of acutely progressive spinal cord symptoms. Here, we report the case of an older woman who developed acute paraplegia with SCI on the 10th day after thoracic spine surgery. Although definitive FCE diagnosis can be confirmed only histologically, the characteristic clinical and radiological features were highly suggestive of FCE. Furthermore, 40 clinically suspected cases of FCE are reviewed.

The role of TNFRSF11B in development of osteoarthritic cartilage.

OBJECTIVES: OA is a complex genetic disease with different risk factors contributing to its development. One of the genes, TNFRSF11B, previously identified with gain-of-function mutation in a family with early-onset OA with chondrocalcinosis, is among the highest upregulated genes in lesioned OA cartilage (RAAK-study). Here, we determined the role of TNFRSF11B overexpression in development of OA. METHODS: Human primary articular chondrocytes (9 donors RAAK study) were transduced using lentiviral particles with or without TNFRSF11B. Cells were cultured for 1 week in a 3 D in-vitro chondrogenic model. TNFRSF11B overexpression was confirmed by RT-qPCR, immunohistochemistry and ELISA. Effects of TNFRSF11B overexpression on cartilage matrix deposition, matrix mineralization, and genes highly correlated to TNFRSF11B in RNA-sequencing dataset (r >0.75) were determined by RT-qPCR. Additionally, glycosaminoglycans and collagen deposition were visualized with Alcian blue staining and immunohistochemistry (COL1 and COL2). RESULTS: Overexpression of TNFRSF11B resulted in strong upregulation of MMP13, COL2A1 and COL1A1. Likewise, mineralization and osteoblast characteristic markers RUNX2, ASPN and OGN showed a consistent increase. Among 30 genes highly correlated to TNFRSF11B, expression of only eight changed significantly, with BMP6 showing the highest increase (9-fold) while expression of RANK and RANKL remained unchanged indicating previously unknown downstream pathways of TNFRSF11B in cartilage. CONCLUSION: Results of our 3D in vitro chondrogenesis model indicate that upregulation of TNFRSF11B in lesioned OA cartilage may act as a direct driving factor for chondrocyte to osteoblast transition observed in OA pathophysiology. This transition does not appear to act via the OPG/RANK/RANKL triad common in bone remodeling.

Delayed Gadolinium-Enhanced Magnetic Resonance Imaging of Cartilage Values in Hips With Bone Marrow Lesions.

OBJECTIVE: Bone marrow lesions (BMLs) are associated with painful and progressive osteoarthritis (OA). Quantitative magnetic resonance imaging (MRI) has been used to study early cartilage degeneration in knees with BML, but similar work has not been done in hips. The purpose of this study was to compare mean delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) relaxation values (T1Gd) in hips with BML to hips without BML in a population-based study. Reduced T1Gd suggests depleted glycosaminoglycan. Our hypothesis was that mean T1Gd is lower in hips with BML compared to hips without BML. METHODS: Study participants (n = 128) were recruited from a cross-sectional population-based study of people ages 20-49 years with and without hip pain. dGEMRIC and proton density (PD)-weighted MRI scans of 1 hip from each participant were used for this analysis. BMLs were identified from PD-weighted fat-suppressed images. We applied a sampling-weighted linear regression model to determine the association of the presence of BMLs with mean cartilage T1Gd (significance: P < 0.05). The model was adjusted for age, sex, body mass index (BMI), hip pain, cam/pincer deformity, and physical activity. RESULTS: Thirty-two (25%) of the 128 participants had at least 1 BML. Subjects with at least 1 BML, compared to those without, had similar weighted characteristics of age, BMI, physical activity levels, and frequency of hip pain. Mean T1Gd was 75.25 msec lower (95% confidence interval -149.69, -0.81; P = 0.048) (9%) in the BML compared to the no-BML group. CONCLUSION: Our results suggest that hips with BMLs are associated with hip cartilage degeneration early in the OA disease process.

Regenerative Potential of Platelet Concentrate Lysate in Mechanically Injured Cartilage and Matrix-Associated Chondrocyte Implantation In Vitro.

Adjuvant therapy in autologous chondrocyte implantation (ACI) can control the post-traumatic environment and guide graft maturation to support cartilage repair. To investigate both aspects, we examined potential chondro-regenerative effects of lysed platelet concentrate (PC) and supplementary interleukin 10 (IL-10) on mechanically injured cartilage and on clinically used ACI scaffolds. ACI remnants and human cartilage explants, which were applied to an uniaxial unconfined compression as injury model, were treated with human IL-10 and/or PC from thrombocyte concentrates. We analyzed nuclear blebbing/TUNEL, sGAG content, immunohistochemistry, and the expression of COL1A1, COL2A1, COL10A1, SOX9, and ACAN. Post-injuriously, PC was associated with less cell death, increased COL2A1 expression, and decreased COL10A1 expression and, interestingly, the combination with Il-10 or Il-10 alone had no additional effects, except on COL10A1, which was most effectively decreased by the combination of PC and Il-10. The expression of COL2A1 or SOX9 was statistically not modulated by these substances. In contrast, in chondrocytes in ACI grafts the combination of PC and IL-10 had the most pronounced effects on all parameters except ACAN. Thus, using adjuvants such as PC and IL-10, preferably in combination, is a promising strategy for enhancing repair and graft maturation of autologous transplanted chondrocytes after cartilage injury.

Shenjinhuoxue Mixture Attenuates Inflammation, Pain, and Cartilage Degeneration by Inhibiting TLR-4 and NF-κB Activation in Rats with Osteoarthritis: A Synergistic Combination of Multitarget Active Phytochemicals.

Osteoarthritis (OA), a highly prevalent chronic joint disease, involves a complex network of inflammatory mediators that not only triggers pain and cartilage degeneration but also accelerates disease progression. Traditional Chinese medicinal shenjinhuoxue mixture (SHM) shows anti-inflammatory and analgesic effects against OA with remarkable clinical efficacy. This study explored the mechanism underlying anti-OA properties of SHM and evaluated its efficacy and safety via in vivo experiments. Through network pharmacology and published literature, we identified the key active phytochemicals in SHM, including ß-sitosterol, oleanolic acid, licochalcone A, quercetin, isorhamnetin, kaempferol, morusin, lupeol, and pinocembrin; the pivotal targets of which are TLR-4 and NF-κB, eliciting anti-OA activity. These phytochemicals can enter the active pockets of TLR-4 and NF-κB with docking score ≤ -3.86 kcal/mol, as shown in molecular docking models. By using surface plasmon resonance assay, licochalcone A and oleanolic acid were found to have good TLR-4-binding affinity. In OA rats, oral SHM at mid and high doses (8.72 g/kg and 26.2 g/kg) over 6 weeks significantly alleviated mechanical and thermal hyperalgesia (P < 0.0001). Accordingly, the expression of inflammatory mediators (TLR-4, interleukin (IL-) 1 receptor-associated kinase 1 (IRAK1), NF-κB-p65, tumor necrosis factor (TNF-) α, IL-6, and IL-1ß), receptor activator of the NF-κB ligand (RANKL), and transient receptor potential vanilloid 1 (TRPV1) in the synovial and cartilage tissue of OA rats was significantly decreased (P < 0.05). Moreover, pathological observation illustrated amelioration of cartilage degeneration and joint injury. In chronic toxicity experiment of rats, SHM at 60 mg/kg demonstrated the safety. SHM had an anti-inflammatory effect through a synergistic combination of active phytochemicals to attenuate pain and cartilage degeneration by inhibiting TLR-4 and NF-κB activation. This study provided the experimental foundation for the development of SHM into a more effective dosage form or new drugs for OA treatment.

Postoperative malrotation of humerus shaft fracture causes degeneration of rotator cuff and cartilage.

We hypothesized that postoperative malrotation of humeral shaft fractures can alter the bio-mechanical environment of the shoulder; thus, rotator cuff and cartilage degeneration could be induced. Therefore, we designed an animal experiment to evaluate the impact of malrotation deformities after minimally invasive surgery for humeral fractures on the rotator cuff and cartilage, which has rarely been described in previous studies. Twenty-four New Zealand white rabbits were randomly divided into the sham control group (A), negative control group (B) and malrotated group (C). A sham operation with surgical exposure alone was performed in group A. Humeral shaft osteotomy was performed in Group B and C. In Group B, the fractures were fixed in situ with plate -screw system. While in Group C, iatrogenic rotational deformity was created after the proximal end of the fracture being internally rotated by 20 degrees and then subsequently fixed. The animals with bone healing were sacrificed for pathological and biochemical examination. In group C, the modified Mankin scale for cartilage pathology evaluation and the modified Movin scale for tendon both showed highest score among groups with statistical significance (P < 0.05); Disordered alignment and proportion of collagen I/III of rotator cuff were confirmed with picrosirius red staining; Transmission electron microscopy also showed ultrastructural tendon damage. Immunohistochemistry showed that both MMP-1 and MMP-13 expression were significantly higher in group C than groups A and B(P < 0.05). Minimally invasive techniques for humerus shaft fracture might be cosmetically advantageous, but the consequent postoperative malrotation could increase the risk of rotator cuff and cartilage degeneration. This conclusion is supported here by primary evidence from animal experiments.

Cellular carbon stress is a mediator of obesity-associated osteoarthritis development.

OBJECTIVE: 'Carbon stress' is a newly found mechanism that links obesity and dysregulated metabolism. It is defined as the cellular accumulation of metabolites during obesity post-translationally modifying metabolic proteins and decreasing their enzymatic activity. The objective of this study was to investigate if 'carbon stress' also occurs in cartilage and contributes to obesity associated OA development. METHODS: We histologically evaluated for OA pathology in wild-type (WT) and hyperphagic mice (Pomc-neuron specific enhancer one deficient, PomcΔ1) that were subjected to standard chow (Chow, n = 6 for both genotypes) or high-fat feeding (HFD, n = 7 for both genotypes). Joints were stained and quantified for 'carbon stress' markers, including succinyl-lysine (SCK), malonyl-lysine (MAK), and acetyl-lysine (ACK). Lastly, we used a mouse model with deletion of Sirt5 (n = 7), which is an enzyme that removes SCK and MAK, to test if changing the abundance of 'carbon stress' would affect OA pathogenesis. RESULTS: Both HFD and Pomc deficiency associated obesity induced cartilage degeneration as well as greater abundance of SCK and MAK in the cartilage. PomcΔ1-HFD mice did not have exacerbated OA pathology as compared to PomcΔ1-Chow mice. ACK was mildly increased in the obese groups comparing to WT-Chow. Sirt5-/- mice developed early-OA like phenotype at 40 weeks of age as characterized by cartilage fibrillation and more hypertrophic chondrocytes. Cartilage from Sirt5-/- mice also had increased SCK and MAK, while ACK remained unchanged comparing to WT mice. CONCLUSION: Our data suggests that carbon stress also occurs in cartilage tissue during obesity and can potentially contribute to obesity-associated OA.

Patients With Symptomatic Sequelae of Slipped Capital Femoral Epiphysis Have Advanced Cartilage Wear at the Time of Surgical Intervention.

BACKGROUND: Slipped capital femoral epiphysis (SCFE) is a common hip problem in children. The resulting deformity can cause impingement similar to cam-type idiopathic femoroacetabular impingement (FAI). Although there are similarities between FAI and SCFE, deformity patterns, severity, and time of onset of symptoms varies, which may impact management. The purpose of this study was to describe patterns of articular cartilage damage in patients undergoing surgical hip dislocation for sequelae of SCFE in comparison to patients undergoing arthroscopic surgery for primary FAI. METHODS: Patients were identified who underwent surgical treatment for hip pain due to primary FAI (cam type) or sequelae of SCFE. Clinical data and radiographic measurements were recorded. Cartilage was assessed intraoperatively. Severity was classified using the modified Beck classification, while location was classified into 6 sectors. Statistical analysis was performed to test for differences in demographic and radiographic characteristics between the SCFE and FAI patients. χ2 or Fisher exact tests were used to evaluate trends in patterns of acetabular and femoral cartilage wear between SCFE and FAI groups. RESULTS: The SCFE group had 28 hips compared with 304 in the FAI group. SCFE patients were younger (19 vs. 32, P<0.001), had higher body mass index (30±5.9 vs. 24±4.8, P<0.001), and were more often male (61% vs. 27%, P<0.001). Deformity severity based on α-angle was higher in the SCFE group [AP 74 vs. 55 (P=0.001) and Dunn 72 vs. 58 (P<0.001)]. There were no significant differences with regards to lateral center edge angle, anterior center edge angle, or Tonnis angle. In both groups the most common locations for cartilage lesions in both groups were the anterior peripheral and superolateral peripheral regions with fewer but more widely distributed femoral head lesions. The SCFE group had higher rates of femoral head and superolateral central cartilage lesions compared with the FAI group. There was no statistical difference between high-grade femoral or acetabular cartilage lesions between groups. CONCLUSIONS: Patients with SCFE were younger at the time of surgery and presented with more severe deformity based on radiographic α-angle compared to patients with FAI. Our results suggest higher prevalence of femoral head lesions and more diffuse cartilage injury in patients with SCFE. This study can be used to support early surgical intervention in patients with symptomatic sequelae of SCFE due to risk of premature joint damage. LEVEL OF EVIDENCE: Level III-prognostic study.

Effect of a subset of adipose-derived stem cells isolated with liposome magnetic beads to promote cartilage repair.

This study aimed to investigate the ability of CD146+ subset of ADSCs to repair cartilage defects. In this study, we prepared CD146+ liposome magnetic beads (CD146+ LMB) to isolate CD146+ ADSCs. The cells were induced for chondrogenic differentiation and verified by cartilage-specific mRNA and protein expression. Then a mouse model of cartilage defect was constructed and treated by filling the induced cartilage cells into the damaged joint, to evaluate the function of such cells in the cartilage microenvironment. Our results demonstrated that the CD146+ LMBs we prepared were uniform, small and highly stable, and cell experiments showed that the CD146+ LMB has low cytotoxicity to the ADSCs. ADSCs isolated with CD146+ LMB were all CD146+ , CD105+ , CD166+ and CD73+ . After chondrogenic induction, the cells showed significantly increased expression of cartilage markers Sox9, collagen Ⅱ and aggrecan at protein level and significantly increased Sox9, collagen Ⅱ and aggrecan at mRNA level, and the protein expression and mRNA expression of CD146+ ADSCs group were higher than those of ADSCs group. The CD146+ ADSCs group showed superior tissue repair ability than the ADSCs group and blank control group in the animal experiment, as judged by gross observation, histological observation and histological scoring. The above results proved that CD146+ LMB can successfully isolate the CD146+ ADSCs, and after chondrogenic induction, these cells successfully promoted repair of articular cartilage defects, which may be a new direction of tissue engineering.

Repair of full-thickness articular cartilage defects using IEIK13 self-assembling peptide hydrogel in a non-human primate model.

Articular cartilage is built by chondrocytes which become less active with age. This declining function of the chondrocytes, together with the avascular nature of the cartilage, impedes the spontaneous healing of chondral injuries. These lesions can progress to more serious degenerative articular conditions as in the case of osteoarthritis. As no efficient cure for cartilage lesions exist yet, cartilage tissue engineering has emerged as a promising method aiming at repairing joint defects and restoring articular function. In the present work, we investigated if a new self-assembling peptide (referred as IEIK13), combined with articular chondrocytes treated with a chondrogenic cocktail (BMP-2, insulin and T3, designated BIT) could be efficient to restore full-thickness cartilage defects induced in the femoral condyles of a non-human primate model, the cynomolgus monkey. First, in vitro molecular studies indicated that IEIK13 was efficient to support production of cartilage by monkey articular chondrocytes treated with BIT. In vivo, cartilage implant integration was monitored non-invasively by contrast-enhanced micro-computed tomography, and then by post-mortem histological analysis and immunohistochemical staining of the condyles collected 3 months post-implantation. Our results revealed that the full-thickness cartilage injuries treated with either IEIK13 implants loaded with or devoid of chondrocytes showed similar cartilage-characteristic regeneration. This pilot study demonstrates that IEIK13 can be used as a valuable scaffold to support the in vitro activity of articular chondrocytes and the repair of articular cartilage defects, when implanted alone or with chondrocytes.

Chondrodermatitis nodularis helicis in a teenager caused by frequent headphone use.

Chondrodermatitis nodularis helicis is a benign condition that presents as a painful ear nodule and is commonly seen in older adults. Herein, we highlight a pediatric case of chondrodermatitis nodularis helicis caused by an increasingly common age-related behavior of frequent headphone use.

Factors Related to Meniscal Extrusion and Cartilage Lesions in Medial Meniscus Root Tears.

The purpose of this study was to identify factors affecting medial meniscus extrusion and cartilage degeneration in medial meniscus root tears (MMRT) and to determine the optimal cut-off values for the factors that predict disease severity. We retrospectively evaluated 86 consecutive patients diagnosed with an isolated MMRT by magnetic resonance imaging (MRI) examinations and arthroscopic procedures for 2 years. Patient-specific factors such as age, sex, the time between injury and MRI (mTIME), the time between injury and surgery (sTIME), the time between MRI and surgery (dTIME), Kellgren-Lawrence (KL) grades, and the mechanical tibiofemoral axis angle (mTFA) were documented. Regression analyses and receiver operating characteristic (ROC) curve analyses were performed. The mTIME was only positively correlated with meniscal extrusion (r = 0.425, p < 0.001). The patients who had grades 3 and 4 cartilage lesions had only significantly higher KL grades and longer sTIME than the patients who had lower grades of cartilage lesion (6.5 months [interquartile range (IQ): 3.0-12.0) vs. 2.5 months [IQ: 0.9-3.9]; p < 0.001). The cut-off value of mTIME and sTIME were 2.5 and 6 months. Relapse times greater than 2.5 months and 6 months after a specific event were associated with a 7.8-fold increased risk for meniscus extrusion and an 18.2-fold increased risk for cartilage lesions, respectively. The risk of medial extrusion of the meniscus and the severity of articular cartilage lesions increased with time after an injury. The period of time from 2.5 to 6 months after traumatic event might be a critical window for intervention in the patients with MMRT to perform the repair in the status which the meniscus did not extrude more than 3 mm and the cartilage lesion did not progress more than grade 3. This study is a retrospective and uncontrolled case series and reflects level IV of evidence.

Development of an Ex Vivo Murine Osteochondral Repair Model.

OBJECTIVE: Mouse models are commonly used in research applications due to the relatively low cost, highly characterized strains, as well as the availability of many genetically modified phenotypes. In this study, we characterized an ex vivo murine osteochondral repair model using human infrapatellar fat pad (IPFP) progenitor cells. DESIGN: Femurs from euthanized mice were removed and clamped in a custom multidirectional vise to create cylindrical osteochondral defects 0.5 mm in diameter and 0.5 mm deep in both condyles. The IPFP contains progenitors that are a promising cell source for the repair of osteochondral defects. For proof of concept, human IPFP-derived progenitor cells, from osteoarthritic (OA) patients, cultured as pellets, were implanted into the defects and cultured in serum-free medium with TGFß3 for 3 weeks and then processed for histology and immunostaining. RESULTS: The custom multidirectional vise enabled reproducible creation of osteochondral defects in murine femoral condyles. Implantation of IPFP-derived progenitor cells led to development of cartilaginous tissue with Safranin O staining and deposition of collagen type II in the extracellular matrix. CONCLUSIONS: We showed feasibility in creating ex vivo osteochondral defects and demonstrated the regenerative potential of OA human IPFP-derived progenitors in mouse femurs. The murine model can be used to study the effects of aging and OA on tissue regeneration and to explore molecular mechanisms of cartilage repair using genetically modified mice.

Imaging appearance of post-arthroscopic radiocarpal chondrolysis: comparison with osteoarthritis associated with scapholunate dissociation.

BACKGROUND: Since the diagnosis of post-arthroscopic chondrolysis is very difficult, it can be underdiagnosed and confused with other diseases in clinical practice. PURPOSE: To propose imaging features of post-arthroscopic radiocarpal chondrolysis (PRCC) and to compare these with osteoarthritis associated with scapholunate dissociation which are the most common misdiagnoses of PRCC. MATERIAL AND METHODS: To identify missed diagnoses of PRCC, 994 magnetic resonance imaging scans performed in 910 patients were retrospectively reviewed. After the identification of 73 patients who exhibited significant radiocarpal cartilage loss, 11 were diagnosed with PRCC. Since scapholunate advanced collapse was the most common incorrect diagnosis of PRCC (4/11), the imaging findings were compared among the 11 patients with PRCC and 14 patients with osteoarthritis caused by scapholunate dissociation who were diagnosed in the same period. The following imaging features were evaluated: scapholunate dissociation; the center of disease and grade of radiocarpal joint destruction; characteristics of bone marrow edema; the presence of radial styloid and distal scaphoid osteophytes; and the extent of joint effusion and synovitis. RESULTS: The imaging diagnosis of PRCC was significantly differentiated from osteoarthritis associated with scapholunate dissociation based on occurrence at a younger age, bone marrow edema crossing the joint, center of disease in the proximal radioscaphoid joint, and absence of radial styloid and scaphoid osteophytes (P < 0.05). PRCC occasionally presented with arch-shape bone marrow edema based on the proximal carpal row. CONCLUSION: The diagnosis of PRCC can be aided if its characteristic imaging findings are differentiated from other disease entities in patients with a history of arthroscopy.

Determining a Threshold of Medial Meniscal Extrusion for Prediction of Knee Pain and Cartilage Damage Progression Over 4 Years: Data From the Osteoarthritis Initiative.

BACKGROUND. The extent of medial meniscal extrusion (MME) that is associated with structural and symptomatic progression of knee osteoarthritis has not been defined yet. OBJECTIVE. The purpose of our study was to investigate MRI-based thresholds of MME that are associated with structural progression of knee degenerative disease and symptoms over a period of 4 years. METHODS. We studied 328 knees of 235 participants that were randomly selected from the Osteoarthritis Initiative cohort. MME was quantified on coronal sections of intermediate-weighted MRI sequences obtained at 3 T. Knee pain and cartilage abnormalities were measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scale and the cartilage whole-organ MRI score (WORMS). General estimating equations with logistic regression models were used to correlate baseline MME and changes in pain (WOMAC) and cartilage damage (WORMS). ROC analyses were performed to determine the area under the ROC curve (AUROC). Individual thresholds were determined by maximizing the product of sensitivity and specificity. RESULTS. The AUROC for predicting progression of knee pain, medial compartment cartilage damage, and medial tibial cartilage damage were 0.71, 0.70, and 0.72, respectively, and the individual thresholds for MME were 2.5, 2.7, and 2.8 mm. A single threshold of 2.5 mm was determined by maximizing the mean of the product of sensitivity and specificity of the three outcome variables (knee pain progression, medial compartmental cartilage damage progression, and medial tibial cartilage damage progression). CONCLUSION. MME was associated with knee pain and cartilage damage progression over 4 years. A single threshold of 2.5 mm was found to be the most useful threshold for predicting knee pain, medial compartment cartilage damage progression, and tibial cartilage damage progression over 4 years. CLINICAL IMPACT. This threshold could be used to standardize the diagnostic criterion of extrusion and to better characterize the risk for subsequent structural and symptomatic progression of knee osteoarthritis.