Allogeneic Umbilical Cord Blood-Derived Mesenchymal Stem Cell Implantation Versus Microfracture for Large, Full-Thickness Cartilage Defects in Older Patients: A Multicenter Randomized Clinical Trial and Extended 5-Year Clinical Follow-up

Background: There is currently no optimal method for cartilage restoration in large, full-thickness cartilage defects in older patients. Purpose: To determine whether implantation of a composite of allogeneic umbilical cord blood-derived mesenchymal stem cells and 4% hyaluronate (UCB-MSC-HA) will result in reliable cartilage restoration in patients with large, full-thickness cartilage defects and whether any clinical improvements can be maintained up to 5 years postoperatively. Study design: Randomized controlled trial; Level of evidence, 1. Methods: A randomized controlled phase 3 clinical trial was conducted for 48 weeks, and the participants then underwent extended 5-year observational follow-up. Enrolled were patients with large, full-thickness cartilage defects (International Cartilage Repair Society [ICRS] grade 4) in a single compartment of the knee joint, as confirmed by arthroscopy. The defect was treated either with UCB-MSC-HA implantation through mini-arthrotomy or with microfracture. The primary outcome was proportion of participants who improved by ≥1 grade on the ICRS Macroscopic Cartilage Repair Assessment (blinded evaluation) at 48-week arthroscopy. Secondary outcomes included histologic assessment; changes in pain visual analog scale (VAS) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and International Knee Documentation Committee (IKDC) score from baseline; and adverse events. Results: Among 114 randomized participants (mean age, 55.9 years; 67% female; body mass index, 26.2 kg/m2), 89 completed the phase 3 clinical trial and 73 were enrolled in the 5-year follow-up study. The mean defect size was 4.9 cm2 in the UCB-MSC-HA group and 4.0 cm2 in the microfracture group (P = .051). At 48 weeks, improvement by ≥1 ICRS grade was seen in 97.7% of the UCB-MSC-HA group versus 71.7% of the microfracture group (P = .001); the overall histologic assessment score was also superior in the UCB-MSC-HA group (P = .036). Improvement in VAS pain, WOMAC, and IKDC scores were not significantly different between the groups at 48 weeks, however the clinical results were significantly better in the UCB-MSC-HA group at 3- to 5-year follow-up (P < .05). There were no differences between the groups in adverse events. Conclusion: In older patients with symptomatic, large, full-thickness cartilage defects with or without osteoarthritis, UCB-MSC-HA implantation resulted in improved cartilage grade at second-look arthroscopy and provided more improvement in pain and function up to 5 years compared with microfracture. Registration: NCT01041001, NCT01626677 (ClinicalTrials.gov identifier).ope

Efficacy and safety of single injection of cross-linked sodium hyaluronate vs. three injections of high molecular weight sodium hyaluronate for osteoarthritis of the knee: a double-blind, randomized, multi-center, non-inferiority study

BACKGROUND: This randomized, double-blind, multi-center, non-inferiority trial was conducted to assess the efficacy and safety of a cross-linked hyaluronate (XLHA, single injection form) compared with a linear high molecular hyaluronate (HMWHA, thrice injection form) in patients with symptomatic knee osteoarthritis. METHODS: Two hundred eighty seven patients with osteoarthritis (Kellgren-Lawrence grade I to III) were randomized to each group. Three weekly injections were given in both groups but two times of saline injections preceded XLHA injection to maintain double-blindness. Primary endpoint was the change of weight-bearing pain (WBP) at 12 weeks after the last injection. Secondary endpoints included Western Ontario and McMaster Universities Osteoarthritis index; patient's and investigator's global assessment; pain at rest, at night, or in motion; OMERACT-OARSI responder rate; proportion of patients achieving at least 20 mm or 40% decrease in WBP; and rate of rescue medicine use and its total consumption. RESULTS: Mean changes of WBP at 12 weeks after the last injection were -33.3 mm with XLHA and -29.2 mm with HMWHA, proving non-inferiority of XLHA to HMWHA as the lower bound of 95% CI (-1.9 mm, 10.1 mm) was well above the predefined margin (-10 mm). There were no significant between-group differences in all secondary endpoints. Injection site pain was the most common adverse event and no remarkable safety issue was identified. CONCLUSIONS: This study demonstrated that a single injection of XLHA was non-inferior to three weekly injections of HMWHA in terms of WBP reduction, and supports XLHA as an effective and safe treatment for knee osteoarthritis.ope

Do Rotation and Measurement Methods Affect Reliability of Anterior Cruciate Ligament Tunnel Position on 3D Reconstructed Computed Tomography?

Background: The literature has seldom investigated the anterior cruciate ligament (ACL) tunnel position while considering the effect of rotation of 3-dimensional computed tomography (3D-CT) images during measurements. Hypothesis: We hypothesized that (1) measurement of the ACL tunnel position in the femur and tibia through use of 3D-CT is considerably influenced by rotation of the 3D model and (2) there exists a reliable measurement method for ACL tunnel position least affected by rotation. Study Design: Controlled laboratory study. Methods: The 3D-CT images of 30 randomly selected patients who underwent single-bundle ACL reconstruction were retrospectively reviewed. For femoral tunnel assessments, rectangular reference frames were used that involved the highest point of the intercondylar notch and outer margins of the lateral femoral condyle (method 1), the highest point of the intercondylar notch and outer margins of the lateral wall of the intercondylar notch (method 2), and the lowest point of the intercondylar notch and outer margins of the lateral femoral condyle (method 3). For tibial tunnel assessments, rectangular reference frames with the cortical outline at the articular surface of the tibia (method A) and the cortical outline of the proximal tibia (method B) were used. For both femoral and tibial assessments, the tunnel positions at 5°, 10°, and 15° of rotation of the 3D model were compared with that at a neutral position. Results: The values measured by methods 1 and 3 showed significant differences at greater than 5° of rotation compared with the value at the neutral position, whereas method 2 showed relatively consistent results. However, the values measured with both methods A and B showed significant differences at greater than 5° of rotation compared with the value at the neutral position. Conclusion: The tunnel position on 3D-CT images was significantly influenced by rotation during measurements. For femoral tunnel position, measurement with a reference frame using the lateral wall of the intercondylar notch (method 2) was the least affected by rotation, with relatively consistent results. Clinical Relevance: This study demonstrates that measurement using the lateral wall of the intercondylar notch might be a consistent and reliable method for evaluating the ACL femoral tunnel position considering the effect of 3D-CT image rotation during measurements. However, both methods to measure tibial tunnel position described in this study were similarly affected by rotation.ope

Incidence and risk factors analysis for mortality after total knee arthroplasty based on a large national database in Korea

This study aimed to analyze the rates and risk factors of postoperative mortality among 560,954 patients who underwent total knee arthroplasty (TKA) in Korea. The National Health Insurance Service-Health Screening database was used to analyze 560,954 patients who underwent TKA between 2005 and 2018. In-hospital, ninety-day, and one-year postoperative mortality, and their association with patient's demographic factors and various comorbidities (ie., cerebrovascular disease, congestive heart failure, and myocardial infarction) were assessed. In-hospital, ninety-day and one-year mortality rates after TKA were similar from 2005 to 2018. The risk of in-hospital mortality increased with comorbidities like cerebrovascular disease (hazard ratio [HR] = 1.401; 95% confidence interval [CI] = 1.064-1.844), congestive heart failure (HR = 2.004; 95% CI = 1.394 to 2.881), myocardial infarction (HR = 2.111; 95% CI = 1.115 to 3.998), and renal disease (HR = 2.641; 95% CI = 1.348-5.173). These co-morbidities were also independent predictors of ninety-day and one-year mortality. Male sex and old age were independent predictors for ninety-day and one-year mortality. And malignancy was risk factor for one-year mortality. The common preoperative risk factors for mortality in all periods were male sex, old age, cerebrovascular disease, congestive heart failure, myocardial infarction, and renal disease. Malignancy was identified as risk factor for one-year mortality. Patients with these comorbidities should be provided better perioperative care.ope

Risk factors of postoperative complications following total knee arthroplasty in Korea: A nationwide retrospective cohort study

Background: The number of patients undergoing total knee arthroplasty (TKA) is gradually increasing and there is also increase in postoperative complications. The patient's demographic, socio-economic factors, hospital and clinical factors are all factors that can influence postoperative complications. The purpose of this study was to determine the risk factors associated with complications following TKA in a large national cohort. Methods: Among patients diagnosed with primary knee arthrosis, a total of 560,954 patients older than 50 years who underwent TKA from January 1, 2005 to December 31, 2018 were included in the study. The risk of postoperative complications (surgical site infection, sepsis, cardiovascular complications, respiratory complications, pulmonary embolism, stroke, acute renal failure, periprosthetic joint infection, and periprosthetic fracture) were assessed with eight independent variables: gender, age, place of residence, household income, hospital bed size, procedure type (unilateral or bilateral, primary or revision TKA), length of stay (LOS), use of transfusion. Multivariable Cox Proportional Hazard model analysis was used. The significant predictors for complications (P < .05) were as follows. Results: Surgical site infection: male, procedure type (bilateral, revision), LOS (≥35 days), transfusion. Sepsis: male, household income, procedure type (bilateral, revision), LOS (≥35 days), transfusion. Cardiovascular complications: male, age, household income, procedure type (bilateral, revision), LOS (≥35 days), transfusion. Respiratory complications: male, household income, procedure type (bilateral, revision), LOS (≥35 days), transfusion. Pulmonary embolism: male, household income, procedure type (bilateral, revision), LOS (≥35 days), transfusion. Stroke: male, age, procedure type (bilateral, revision), LOS (≥35 days), transfusion. Acute renal failure: male, household income, procedure type (bilateral, revision), LOS (≥35 days), transfusion. Periprosthetic joint infection: male, household income, procedure type (bilateral, revision), LOS (≥35 days), transfusion. Periprosthetic fracture: male, procedure type (bilateral, revision), LOS (≥35 days), transfusion. Conclusion: In summary, male, procedure type (bilateral, revision), LOS (≥35 days), and use of transfusion were shown to be risk factors of postoperative complications following TKA.ope

A Comparison of Accuracy between MRI and Arthroscopic Finding in the Diagnosis of Acute ACL Tear

Purpose: The purpose of this study is to evaluate the accuracy of magnetic resonance imaging (MRI) in the diagnosis of acute anterior cruciate ligament (ACL) injury and its tear pattern in comparison with arthroscopic finding. Materials and Methods: Sixty consecutive patients with acute ACL injury were taken NRI followed by arthroscopic examination between January 2002 and June 2004. MRI findings were reviewed according to the presence of ACL discontinuity, diffuse swelling or thickening, focal edema, collapse on distal end, and any combined tear. The pathologic findings were then confirmed arthroscopically. The diagnostic accuracy of MRI on ACL tear pattern was analyzed by obtaining its positive predictive value. Results: All fifty two cases with presence of discontinuity on MRI showed ACL rupture arthroscopically. The location of ACL tear, diffuse swelling and focal edema on MRI also corresponded with arthroscopic findings respectively. However, the diagnostic accuracy of MRI was relatively lower in the presence of other ACL patterns such as collapses and combined tear. Conclusion: Preoperative MRI findings seem to be in accordance with arthroscopic findings and is significantly accurate in detection of location and diffuse swelling and focal edema of ACL tear.ope

Assessment of the Influence of Acetic Acid Residue on Type I Collagen during Isolation and Characterization

Various methods for isolation of type I collagen using acids, bases, enzymes, and their combinations have been applied. However, a lack of standardization exists among type I collagens isolated by various approaches. Consequently, in this study, we assessed the influence of acetic acid residue on type I collagen isolated by pepsin-acetic acid treatment, the fabrication of collagen-based porous scaffolds, and the seeded cells on collagen scaffolds. Unlike the isolated collagen dialyzed by deionized water (DDW), collagen dialyzed by 0.5 M acetic acid (DAC) exhibited structural and thermal denaturation. Both DDW- and DAC-based porous scaffolds at all collagen concentrations (0.5, 1 and 2% w/v) showed the high degree of porosity (>98%), and their pore morphologies were comparable at the same concentrations. However, the DDW- and DAC-based collagen scaffolds displayed significant differences in their physical properties (weight, thickness, and volume) and swelling behaviors. In particular, the weight losses induced by mechanical stimulation reflected the high degradation of DAC-collagen scaffolds. In cell culture experiments using adipose-derived stem cells (ADSCs), the characteristics of mesenchymal stem cell (MSC) did not change in both DDW- and DAC-collagen scaffolds for 10 days, although cells proliferated less in the DAC-collagen scaffolds. Our results suggest that the elimination of acetic acid residue from isolated collagen is recommended to produce collagen scaffolds that provide a stable environment for cells and cell therapy-related applications.ope

The effect of medial open wedge high tibial osteotomy on the patellofemoral joint: comparative analysis according to the preexisting cartilage status

BACKGROUND: Although it has been known that medial open wedge high tibial osteotomy (MOWHTO) would adversely affect the patellofemoral joint, no previous study examined the surgical outcome of MOWHTO according to the preexisting cartilage status of the patellofemoral joint. The aim of this study was to investigate the effect of MOWHTO on the patellofemoral joint with regard to objective and subjective aspects according to the preexisting cartilage status. METHODS: Ninety-two patients who underwent MOWHTO and a following second-look arthroscopic assessment were included in this study. The patients were divided into two groups according to the preexisting cartilage status of the patellofemoral joint: group 1 (International Cartilage Repair Society [ICRS] grade 2 or 3) and group 2 (ICRS grade 0 or 1). Comparative analysis was performed regarding clinical scores, radiographic parameters, and arthroscopic measurements between the two groups. RESULTS: Clinical outcomes showed overall improvement from baseline to the time of second-look operation, with no significant difference between the two groups at each time point. There were no significant differences in radiographic parameters between the two groups. Radiographic grade of patellofemoral osteoarthritis in both groups showed a tendency to progress, without statistical significance. In arthroscopic assessment, the size of the cartilage lesion on the patellofemoral joint increased with time in both groups (P = 0.003), but the degree of change over time between the two groups was not statistically significant. Consistently, there was no significant difference in the frequency of progression of cartilage lesion grade in the patellofemoral joint between the two groups. CONCLUSIONS: MOWHTO would contribute to osteoarthritis progression of the patellofemoral joint regardless of the preexisting cartilage status, without an association with clinical outcomes in short-term follow-up.ope

A Randomized, Multicenter, Phase III Trial to Evaluate the Efficacy and Safety of Polmacoxib Compared with Celecoxib and Placebo for Patients with Osteoarthritis

Background: The aim of this study was to evaluate the safety and analgesic efficacy of polmacoxib 2 mg versus placebo in a superiority comparison or versus celecoxib 200 mg in a noninferiority comparison in patients with osteoarthritis (OA). Methods: This study was a 6-week, phase III, randomized, double-blind, and parallel-group trial followed by an 18-week, single arm, open-label extension. Of the 441 patients with knee or hip OA screened, 362 were randomized; 324 completed 6 weeks of treatment and 220 completed the extension. Patients were randomized to receive oral polmacoxib 2 mg (n = 146), celecoxib 200 mg (n = 145), or placebo (n = 71) once daily for 6 weeks. During the extension, all participants received open-label polmacoxib 2 mg. The primary endpoint was the change in Western Ontario and McMaster Universities (WOMAC)-pain subscale score from baseline to week 6. Secondary endpoints included WOMAC-OA Index, OA subscales (pain, stiffness, and physical function) and Physician's and Subject's Global Assessments at weeks 3 and 6. Other outcome measures included adverse events (AEs), laboratory tests, vital signs, electrocardiograms, and physical examinations. Results: After 6 weeks, the polmacoxib-placebo treatment difference was -2.5 (95% confidence interval [CI], -4.4 to -0.6; p = 0.011) and the polmacoxib-celecoxib treatment difference was 0.6 (CI, -0.9 to 2.2; p = 0.425). According to Physician's Global Assessments, more subjects were "much improved" at week 3 with polmacoxib than with celecoxib or placebo. Gastrointestinal and general disorder AEs occurred with a greater frequency with polmacoxib or celecoxib than with placebo. Conclusions: Polmacoxib 2 mg was relatively well tolerated and demonstrated efficacy superior to placebo and noninferior to celecoxib after 6 weeks of treatment in patients with OA. The results obtained during the 18-week trial extension with polmacoxib 2 mg were consistent with those observed during the 6-week treatment period, indicating that polmacoxib can be considered safe for long-term use based on this relatively small scale of study in a Korean population. More importantly, the results of this study showed that polmacoxib has the potential to be used as a pain relief drug with reduced gastrointestinal side effects compared to traditional nonsteroidal anti-inflammatory drugs for OA.ope

Treatment of Multiple Ligaments Injuries

Multiple ligament injury, which means disruption of at least 3 of the 4 major ligaments, generally occurs due to high energy trauma. Knee dislocation usually leads to the multiple ligament injury, and the terms 'knee dislocation' and 'multiple ligament injury' are used interchangeably. In some cases, a dislocated knee may have been spontaneously reduced immediately after the trauma. This is the reason why we should consider the possibility of knee dislocation and carry out a thorough vascular and neurologic evaluation when a patient with multiple ligament injury presents to an emergency department. Multiple ligament injury, when not properly treated, may lead to instability of the knee joint, resulting in posttraumatic arthritis. Though treatment and rehabilitation of multiple ligament injury is difficult, we should pursue full recovery of the knee joint through precise examination and proper treatment. There is controversy about conservative vs. surgical treatment, early vs. delayed surgeory, and repair vs. reconstruction, but surgical treatment and early reconstruction are now preferredope