Haris S. Vasiliadis

Autologous Chondrocyte Implantation: A Long-term Follow-up

Background: The medium-term results of autologous chondrocyte implantation (ACI) have shown good to excellent outcomes for the majority of patients. However, no long-term results 10 to 20 years after the surgery have been reported. Hypothesis: Autologous chondrocyte implantation provides a durable solution to the treatment of full-thickness cartilage lesions of the knee, maintaining good clinical results even 10 to 20 years after implantation. Study Design: Case series; Level of evidence, 4. Methods: In this uncontrolled study, questionnaires with the Lysholm, Tegner-Wallgren, Brittberg-Peterson, modified Cincinnati (Noyes), and Knee Injury and Osteoarthritis Outcome Score (KOOS) scores were sent to 341 patients. Preoperative Lysholm, Tegner-Wallgren, and Brittberg-Peterson scores were also retrieved when possible from patients’ files. The patients were asked to grade their status during the past 10 years as better, worse, or unchanged. Finally, they were asked if they would do the operation again. Results: There were 224 of 341 patients who replied to our posted questionnaires and were assessed. The mean cartilage lesion size was 5.3 cm2. Ten to 20 years after the implantation (mean, 12.8 years), 74% of the patients reported their status as better or the same as the previous years. There were 92% who were satisfied and would have the ACI again. The Lysholm, Tegner-Wallgren, and Brittberg-Peterson scores were improved compared with the preoperative values. The average Lysholm score improved from 60.3 preoperatively to 69.5 postoperatively, the Tegner from 7.2 to 8.2, and the Brittberg-Peterson from 59.4 to 40.9. At the final measurement, the KOOS score was on average 74.8 for pain, 63 for symptoms, 81 for activities of daily living (ADL), 41.5 for sports, and 49.3 for quality of life (QOL). The average Noyes score was 5.4. Patients with bipolar lesions had a worse final outcome than patients with multiple unipolar lesions. The presence of meniscal injuries before ACI or history of bone marrow procedures before the implantation did not appear to affect the final outcomes. The age at the time of the operation or the size of lesion did not seem to correlate with the final outcome. Conclusion: Autologous chondrocyte implantation has emerged as an effective and durable solution for the treatment of large full-thickness cartilage and osteochondral lesions of the knee joint. Our study suggests that the clinical and functional outcomes remain high even 10 to 20 years after the implantation.

Evaluation of inconsistency in networks of interventions

BACKGROUND The assumption of consistency, defined as agreement between direct and indirect sources of evidence, underlies the increasingly popular method of network meta-analysis. No evidence exists so far regarding the extent of inconsistency in full networks of interventions or the factors that control its statistical detection. METHODS In this paper we assess the prevalence of inconsistency from data of 40 published networks of interventions involving 303 loops of evidence. Inconsistency is evaluated in each loop by contrasting direct and indirect estimates and by employing an omnibus test of consistency for the entire network. We explore whether different effect measures for dichotomous outcomes are associated with differences in inconsistency, and evaluate whether different ways to estimate heterogeneity affect the magnitude and detection of inconsistency. RESULTS Inconsistency was detected in from 2% to 9% of the tested loops, depending on the effect measure and heterogeneity estimation method. Loops that included comparisons informed by a single study were more likely to show inconsistency. About one-eighth of the networks were found to be inconsistent. The proportions of inconsistent loops do not materially change when different effect measures are used. Important heterogeneity or the overestimation of heterogeneity was associated with a small decrease in the prevalence of statistical inconsistency. CONCLUSIONS The study suggests that changing the effect measure might improve statistical consistency, and that an analysis of sensitivity to the assumptions and an estimator of heterogeneity might be needed before reaching a conclusion about the absence of statistical inconsistency, particularly in networks with few studies.

Autologous chondrocyte implantation in cartilage lesions of the knee: long-term evaluation with magnetic resonance imaging and delayed gadolinium-enhanced magnetic resonance imaging technique.

Background Various treatment options are available for articular cartilage lesions, but controversy exists regarding the quality of the repair tissue and the durability of the results posttreatment. Noninvasive techniques are needed for the assessment of the repair tissue. Hypothesis Magnetic resonance imaging (MRI) with delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) can give valuable information regarding the quality and quantity of the repaired cartilage lesion. Study Design Cohort study; Level of evidence, 3. Methods Thirty-six knees in 31 patients were assessed 9 to 18 years after treatment with autologous chondrocyte implantation (ACI). All patients had isolated lesions. The knees were clinically evaluated with the Knee injury and Osteoarthritis Outcome Score and the dGEMRIC technique. The T1 value was measured for 2 regions of interest (ROIs), 1 in the repair tissue area (ROI 1) and 1 in the surrounding cartilage (ROI 2), giving information of the content of proteoglycans. Results The average T1 value in ROI 1 was 467.5 milliseconds and in ROI 2, 495.3 milliseconds, which yielded no significant difference, thus suggesting comparable levels of proteoglycans in the repair tissue and surrounding cartilage. Intralesional osteophytes were in 64% of the lesions, mainly in younger patients with osteochondritis dissecans lesions or a history of subchondral bone surgeries. Medium or large bone marrow edema was found in 14% of the knees and subchondral cysts, in 39%. There was no correlation between the KOOS and any MRI findings. Conclusion Magnetic resonance imaging with dGEMRIC gives valuable information for the macroscopic appearance and micro-molecular quality of the repair tissue after ACI. Nine to 18 years posttreatment, the quality of the repair tissue is similar to the surrounding normal cartilage, although intralesional osteophytes, subchondral cysts, and bone marrow edema were common. The defect area is restored in most patients. However, there was no correlation between the dGEMRIC values and the KOOS outcomes.

Characteristics of networks of interventions: a description of a database of 186 published networks.

Systematic reviews that employ network meta-analysis are undertaken and published with increasing frequency while related statistical methodology is evolving. Future statistical developments and evaluation of the existing methodologies could be motivated by the characteristics of the networks of interventions published so far in order to tackle real rather than theoretical problems. Based on the recently formed network meta-analysis literature we aim to provide an insight into the characteristics of networks in healthcare research. We searched PubMed until end of 2012 for meta-analyses that used any form of indirect comparison. We collected data from networks that compared at least four treatments regarding their structural characteristics as well as characteristics of their analysis. We then conducted a descriptive analysis of the various network characteristics. We included 186 networks of which 35 (19%) were star-shaped (treatments were compared to a common comparator but not between themselves). The median number of studies per network was 21 and the median number of treatments compared was 6. The majority (85%) of the non-star shaped networks included at least one multi-arm study. Synthesis of data was primarily done via network meta-analysis fitted within a Bayesian framework (113 (61%) networks). We were unable to identify the exact method used to perform indirect comparison in a sizeable number of networks (18 (9%)). In 32% of the networks the investigators employed appropriate statistical methods to evaluate the consistency assumption; this percentage is larger among recently published articles. Our descriptive analysis provides useful information about the characteristics of networks of interventions published the last 16 years and the methods for their analysis. Although the validity of network meta-analysis results highly depends on some basic assumptions, most authors did not report and evaluate them adequately. Reviewers and editors need to be aware of these assumptions and insist on their reporting and accuracy.

Anterior cruciate ligament reconstruction results in alterations in gait variability

INTRODUCTION The temporal structure of gait variability has shown that healthy human gait exhibits long-range correlations and deterministic properties which allow the neuromuscular system to be flexible and adaptable to stresses. Pathology results in deterioration of these properties. We examined structure of gait variability after ACL reconstruction with either BPTB or quadrupled ST/G tendon autografts. METHODS Six patients with BPTB reconstruction, six with ST/G reconstruction and six healthy controls walked on a treadmill at their self-selected pace. Two minutes of continuous kinematic data were recorded with a 6-camera optoelectronic system. The nonlinear measure of the largest Lyapunov Exponent (LyE) was estimated from the knee flexion-extension time series from 100 continuous walking strides to assess the structure of gait variability. RESULTS The reconstructed limbs in both reconstructed groups exhibited significantly larger LyE values than the control limbs (p<0.05), even though clinical outcomes indicated complete restoration. No significant differences were found between the two autografts. In addition, the intact contralateral leg produced significant higher LyE values as compared with the ACL-reconstructed leg in both groups. No interaction was found. DISCUSSION The larger LyE values indicate that the reconstructed knees of both reconstructed groups exhibit more divergence in the movement trajectories during gait. The larger Lye values found in the intact leg in both reconstructed groups could be interpreted as a compensatory mechanism. However, the increased divergence found in both limbs may present an alternative explanation for the impaired neuromuscular performance and increased susceptibility to future pathology, which is supported by the increased amount of osteoarthritis found in ACL-reconstructed patients.

The Effect of Anterior Cruciate Ligament Reconstruction on Stride-to-Stride Variability

PURPOSE The purpose of our study was to investigate the functional outcome after anterior cruciate ligament (ACL) reconstruction using bone-patellar tendon-bone (BPTB) and quadrupled semitendinosus and gracilis tendon (ST/G) autografts by evaluating stride-to-stride variability. METHODS Six patients with BPTB and 6 patients with STG ACL reconstruction, 2 years postoperatively, and 6 healthy control subjects walked on a treadmill at a self-selected pace while 2 minutes of continuous kinematic data were recorded with a 6-camera optoelectronic system. Stride-to-stride variability was calculated from the knee flexion/extension data using the nonlinear measure of approximate entropy, which estimates the regularity of movement patterns over time. RESULTS ACL reconstruction affects stride-to-stride variability. Both the BPTB and the ST/G groups had significantly larger approximate entropy values than the healthy controls. No differences were found between the BPTB and the ST/G approximate entropy values. CONCLUSIONS After ACL reconstruction using either BPTB or quadrupled ST/G, there is increased gait variability as compared to healthy individuals. This could be caused by the altered neuromuscular activity found in ACL-reconstructed limbs. LEVEL OF EVIDENCE Level III, case control study.

Endoscopic Versus Open Carpal Tunnel Release

PURPOSE This study compared endoscopic carpal tunnel release with the conventional open technique with respect to short- and long-term improvements in functional and clinical outcomes. METHODS We assessed 72 outpatients diagnosed with carpal tunnel syndrome. Of these patients, 37 underwent the endoscopic method according to Chow and 35 were assigned to the open method. Improvement in symptoms, severity, and functionality were evaluated at 2 days, 1 week, 2 weeks, and 1 year postoperatively. Changes in clinical outcomes were evaluated at 1 year postoperatively. Complications were also assessed. RESULTS Both groups showed similar improvement in all but 1 outcome 1 year after the release; increase in grip strength was significantly higher in the endoscopic group. However, the endoscopic method showed a greater improvement in symptoms and functional status compared with the open method at 2 days, 1 week, and 2 weeks postoperatively. Separate analysis of the questions referring to pain showed that the delay in improvement in the open group was because of the persistence of pain for a longer period. Paresthesias and numbness decrease immediately after the operation with comparable rates for both groups. CONCLUSIONS Endoscopic carpal tunnel release provides a faster recovery to operated patients for the first 2 weeks, with faster relief of pain and faster improvement in functional abilities. Paresthesia and numbness subside in an identical manner with the 2 techniques. At 1 year postoperatively, both open and endoscopic techniques seem to be equivalently efficient.

Effects of study precision and risk of bias in networks of interventions: a network meta-epidemiological study

BACKGROUND Empirical research has illustrated an association between study size and relative treatment effects, but conclusions have been inconsistent about the association of study size with the risk of bias items. Small studies give generally imprecisely estimated treatment effects, and study variance can serve as a surrogate for study size. METHODS We conducted a network meta-epidemiological study analyzing 32 networks including 613 randomized controlled trials, and used Bayesian network meta-analysis and meta-regression models to evaluate the impact of trial characteristics and study variance on the results of network meta-analysis. We examined changes in relative effects and between-studies variation in network meta-regression models as a function of the variance of the observed effect size and indicators for the adequacy of each risk of bias item. Adjustment was performed both within and across networks, allowing for between-networks variability. RESULTS Imprecise studies with large variances tended to exaggerate the effects of the active or new intervention in the majority of networks, with a ratio of odds ratios of 1.83 (95% CI: 1.09,3.32). Inappropriate or unclear conduct of random sequence generation and allocation concealment, as well as lack of blinding of patients and outcome assessors, did not materially impact on the summary results. Imprecise studies also appeared to be more prone to inadequate conduct. CONCLUSIONS Compared to more precise studies, studies with large variance may give substantially different answers that alter the results of network meta-analyses for dichotomous outcomes.

Comparison of early mobilization protocols in radial head fractures.

Objectives: We compared 2 different protocols of early mobilization with a protocol of delayed mobilization in patients with simple radial head fractures (B2.1 type of Orthopaedic Trauma Association Classification). An attempt to correlate certain characteristics of the radial head fractures with outcome was made. Design: Prospective randomized comparative study. Setting: Level 1 trauma center. Patients/Participants: One hundred eighty consecutive patients were randomly allocated into 3 different protocols. Intervention: In the first group, immediate mobilization of the elbow joint was applied. In the second, a sling was used for 2 days and then active mobilization was introduced. The third protocol represented the control group where immobilization in a cast for 7 days before the mobilization was applied. Main Outcome Measurements: Broberg and Morrey score, The American Shoulder and Elbow Surgeons-Elbow score, visual analogue scale, and grip and pinch strength were evaluated. Results: The 2 protocols introducing early mobilization resulted in better outcome compared with immobilization. The first protocol resulted in worse pain in the first 3 days. Range of motion, strength, and functional outcome was better in patients allocated to the second protocol. These differences were more evident in displaced fractures. A fragment displacement of more than 4 mm and an angulation of more than 30 degrees proved to impair outcome. Conclusions: Early mobilization of simple radial head fractures seemed to be a safe and an effective treatment option. It seems that a delay of 48 hours before early mobilization could be advantageous. Individualization of treatment in accordance to the characteristics of fracture could be a decisive factor for outcome. Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

HLA associations with multiple sclerosis in Greece

BACKGROUND Multiple sclerosis (MS) is a demyelinating inflammatory disease of the central nervous system originated by a complex interplay of environmental and genetic factors. The association of MS with the human leukocyte antigen (HLA) class II alleles was investigated in MS patients in northwest Greece, in the geographical region of Epirus. OBJECTIVE Our aim was to estimate the prevalence of the HLA-DRB1*1501, HLA-DQB1*0602 and HLA-DQA1*0102 alleles, consisting the most common susceptibility haplotype in North European and North American Caucasians. METHODS We studied 126 MS patients and 93 age and sex matched healthy controls. HLA typing was performed by a polymerase chain reaction (PCR) amplification with sequence-specific primers (PCR-SSP) method. RESULTS We found that HLA-DRB1*1501, HLA-DQB1*0602 and HLA-DQA1*0102 alleles were significantly more frequent among patients (34% versus 11%, p=0.00015; 69% versus 51%, p=0.01; 76% versus 55%, p=0.002, respectively). HLA-DRB1*1501, HLA-DQB1*0602, HLA-DQA1*0102 haplotype was significantly more common among patients (p=0.00067). HLA-DRB1*1501 and HLA-DQB1*0602 alleles were more frequently detected in patients with initial symptoms from the brainstem or the cerebellum (p=0.024). No significant correlation was observed among these alleles with sex, disease clinical course, or age at onset. CONCLUSION This is the first study to investigate genetic susceptibility to MS in Greece. Our results are in line with previous reports in North European and North American patients.