Autologous Chondrocyte Implantation as Treatment for Unsalvageable Osteochondritis Dissecans: 10- to 25-Year Follow-up.

BACKGROUND: An unsalvageable osteochondritis dissecans (OCD) fragment has been defined as one that cannot be saved. Unsalvageable OCD lesions have been treated with various techniques, including fragment excision, microfracture, osteochondral autograft transfer, fresh osteochondral allograft transplantation, and autologous chondrocyte implantation (ACI). HYPOTHESIS: Patients who underwent ACI as treatment for unsalvageable OCD more than 10 years ago would maintain satisfactory patient-oriented outcome measures and have a low need for additional open surgery, especially arthroplasty. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: All Swedish and Norwegian patients (59 patients with 67 OCD lesions) who underwent ACI for OCD under the direction of the senior author between 1990 and 2005 were identified through manual chart review. Features of the patient, OCD lesion, and surgery were extracted from the medical record and intraoperative photographs. Patients were sent questionnaires to assess the Knee injury and Osteoarthritis Outcome Score, Tegner-Wallgren activity score, and Lysholm score. In addition, patients were asked whether they had to undergo further surgery, including knee replacement, of the knee that underwent ACI. They were asked whether they would have the surgery again if in the same situation. RESULTS: A total of 55 patients (93%) with 61 OCD lesions (91%) responded. The median follow-up duration was 19 years (range, 10-26 years) and the median age at follow-up was 43 years (range, 28-69 years). Subsequent arthroscopy was performed in the majority of cases, although many of these were scheduled "second looks" as part of a study. With respect to other subsequent surgery, 12 knees (20%) underwent any additional open surgery, but only 2 knees (3%) underwent arthroplasty. Eight knees (13%) underwent revision ACI. Most patients reached their preinjury activity level (62%) and would undergo ACI again if in the same situation (85%). If failure is defined as revision of the graft or conversion to arthroplasty, then survivorship after ACI for OCD in the current study would be 87% at 10 years, 85% at 15 years, and 82% at 20 years. CONCLUSION: ACI for OCD provides a durable treatment option. At a median follow-up of 19 years, there was a very low (~3%) conversion to total knee arthroplasty.

Does Multimodal Rehabilitation for Ankle Instability Improve Patients' Self-assessed Functional Outcomes? A Network Meta-analysis.

BACKGROUND: Although there are many nonsurgical treatment options for the primary management of chronic ankle instability, the most effective nonoperative intervention has not been defined. QUESTIONS/PURPOSES: The purpose of this study was to perform a network meta-analysis to compare the results of different standalone and/or combined nonsurgical interventions on chronic ankle instability as measured by (1) the Cumberland Ankle Instability Tool (CAIT) at 0 to 6 months after treatment and (2) treatment-related complications. METHODS: We searched PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and Scopus in August 2017 for completed studies published between 2005 and 2016. We conducted random-effects pairwise and network meta-analysis considering randomized trials, which compared the effects of various nonoperative therapies for ankle instability. Studies assessing patients with functional ankle instability and/or mechanical ankle instability and/or recurrent ankle sprains were eligible for inclusion. After combining data from self-administered questionnaires, we analyzed patient self-reported outcomes of function at the end of the rehabilitation period and 1 to 6 months after treatment. We thereafter reexpressed standardized mean differences to mean differences with CAIT. For this instrument, scores vary between 0 and 30, and higher scores indicate better ankle stability. We included 21 trials involving 789 chronically unstable ankles. The rehabilitation interventions included, but were not limited to, balance training, strengthening exercises, a combination of the balance and strengthening exercises, manual therapy, and multimodal treatment. The implemented multistation protocols were targeted at four main areas of rehabilitation (ROM, balance, strength, and overall activity). Control was defined as placebo and/or wait and see. Treatment-related complications were defined as any major or minor adverse event observed after rehabilitation as reported by the source studies. Statistically, we did not detect significant inconsistency in the network meta-analysis. We also assessed the quality of the trials using the Cochrane risk of bias tool and judged 12, eight, and one studies to be at a low, unclear, and high risk of bias, respectively. We also considered the quality of evidence to be of moderate strength utilizing the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. We defined the minimum clinically important difference (MCID) in the CAIT to be 3 points. RESULTS: A 4-week supervised rehabilitation program, which included balance training, strengthening, functional tasks, and ROM exercises, was favored over control according to the results of four trials by a clinically important margin (mean difference between multimodal and control groups in the CAIT was -10; 95% confidence interval [CI], -16 to -3; p = 0.001). Among the standalone interventions, only balance training was better than control according to the findings of seven trials (mean difference between balance training and control in the CAIT was -5; 95% CI, -10 to -0.03; p = 0.049); this difference likewise exceeded the MCID and so is believed to be a clinically important difference. Adverse events associated with the enrolled rehabilitation protocols were transient, mild, and uncommon. CONCLUSIONS: Although a supervised impairment-based program after chronic ankle instability was superior to control, we note that followup in the included trials tended to be short and inconsistent, although the effect size exceeded the MCID and so likely would be identified as clinically important by patients. Future randomized trials should determine whether the short-term benefits of these interventions are sustained over time. LEVEL OF EVIDENCE: Level I, therapeutic study.

Glucosamine and chondroitin for the treatment of osteoarthritis.

The prevalence of primary or idiopathic osteoarthritis (OA) of knee and hip joints has substantially increased in general population during the last decades. Analgesics and non-steroidal anti-inflammatory drugs are currently extensively used as non-surgical treatment options. However, they act as symptomatic treatments, not offering a cure of OA and they are accused for an increased risk of adverse events. Glucosamine (GL) and chondroitin (CH) are nutritional supplements that have recently gained widespread use as treatment options for OA. They potentially or theoretically act as chondroprotectors or/and as "disease-modifying OA drugs" offering not only symptomatic relief but also alteration of the natural history of OA. However, although many studies have showed a significant treatment effect, accompanied with remarkable safety, there is still controversy regarding their relative effectiveness compared with placebo or other treatments. The scope of this review is to present and critically evaluate the current evidence-based information regarding the administration of GL and CH for the treatment of knee or hip OA. Our focus is to investigate the clinical efficacy and safety after the use of these supplements. An effect of GL and CH on both clinical and radiological findings has been shown. However, only a few high-quality level I trials exist in the literature, especially on the assessment of radiological progression of OA. The effect sizes are generally small and probably not clinically relevant. Even the validity of these results is limited by the high risk of bias introduced in the studies. Both GL and CH seem to be safe with no serious adverse events reported. There is currently no convincing information for the efficacy of GL and CH on OA.

Injection therapies for plantar fasciopathy ('plantar fasciitis'): a systematic review and network meta-analysis of 22 randomised controlled trials.

OBJECTIVE: To compare the efficacy of different injection therapies for plantar fasciopathy (historically known as 'plantar fasciitis'). DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Electronic databases (MEDLINE, CENTRAL, Web of Science and Scopus) were searched up to 11 July 2015 for completed studies. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We considered randomised trials comparing various injection therapies in adults with plantar fasciopathy. The primary outcome was pain relief. Secondary outcomes included functional disability, composite and health-related outcomes. All outcomes were assessed (1) in the short term (up to 2 months), (2) the intermediate term (2-6 months) and (3) the medium term (more than 6 months to 2 years). Quality assessment was performed using the Cochrane risk of bias tool. RESULTS: We included 22 trials comprising 1216 patients. Dehydrated amniotic membrane injections were significantly superior to corticosteroids in the short term in achieving the primary and composite outcomes (mean difference (MD) in visual analogue scale (VAS) was -7.32, 95% CIs -11.2 to -3.38; and MD in the foot health status questionnaire was 31.2, 95% CIs 13.9 to 48.6, respectively). For pain relief, botulinum toxin-A provided a significant short-term advantage over placebo, which was still present at 6 months (MD in VAS was -2.9, 95% CIs -4.44 to -1.39; and MD -4.34, 95% CIs -7.18 to -1.54, respectively). SUMMARY: Although the dehydrated amniotic membrane provided significant clinical relief at 0-2 months, there were no data about this treatment at 2 months and beyond. Botulinum toxin-A injections significantly reduced pain intensity at 0-6 months. SYSTEMATIC REVIEW REGISTRATION NUMBER: CRD42015017353.

Temporary liver and stomach necrosis after lateral approach for interbody fusion and deformity correction of lumbar spine: report of two cases and review of the literature.

INTRODUCTION: Corrections of spinal deformities have been associated with a potential of postoperative vessel-originating complications. Reports of occlusions of celiac artery seem though to be very rare. CASE REPORTS: We present two cases that developed acute arterial supply impairment and subsequent liver and gastric necrosis due to an occlusion of celiac artery, after a spine deformity correction. In both patients a lateral surgical approach to the superior lumbar spine, lateral placement of cages and then a subsequent posterior fixation were performed. REVIEW: The literature search reveals the report of three similar cases, with potentially different pathogenetic mechanisms and with a different prognosis. This complication is assumed to occur due to a Medial Arcuate Ligament syndrome (MALS) developed postoperatively that leaded to compression of the celiac artery against the Medial Arcuate Ligament. The pathogenesis though remains unclear and two theories are assumed to explain the acute appearance of the syndrome; the alteration of the anatomic relationship between the vessels and the surrounding tissues due to the spine deformity correction and an intraoperative direct or indirect traction injury of the celiac trunk that caused or increased its pressure against the medial arcuate ligament. CONCLUSION: The spine surgeon should be aware of the possibility of postoperative ischemia of the liver and stomach by occlusion of the celiac artery or its supplying branches. Specifically when a large correction of a kyphotic/kyphoscoliotic spine is planed, the surgeon should be alert for an appearance of a MALS.

Endoscopic and Open Release Similarly Safe for the Treatment of Carpal Tunnel Syndrome. A Systematic Review and Meta-Analysis.

BACKGROUND: The Endoscopic Release of Carpal Tunnel Syndrome (ECTR) is a minimal invasive approach for the treatment of Carpal Tunnel Syndrome. There is scepticism regarding the safety of this technique, based on the assumption that this is a rather "blind" procedure and on the high number of severe complications that have been reported in the literature. PURPOSE: To evaluate whether there is evidence supporting a higher risk after ECTR in comparison to the conventional open release. METHODS: We searched MEDLINE (January 1966 to November 2013), EMBASE (January 1980 to November 2013), the Cochrane Neuromuscular Disease Group Specialized Register (November 2013) and CENTRAL (2013, issue 11 in The Cochrane Library). We hand-searched reference lists of included studies. We included all randomized or quasi-randomized controlled trials (e.g. study using alternation, date of birth, or case record number) that compare any ECTR with any OCTR technique. Safety was assessed by the incidence of major, minor and total number of complications, recurrences, and re-operations.The total time needed before return to work or to return to daily activities was also assessed. We synthesized data using a random-effects meta-analysis in STATA. We conducted a sensitivity analysis for rare events using binomial likelihood. We judged the conclusiveness of meta-analysis calculating the conditional power of meta-analysis. CONCLUSIONS: ECTR is associated with less time off work or with daily activities. The assessment of major complications, reoperations and recurrence of symptoms does not favor either of the interventions. There is an uncertain advantage of ECTR with respect to total minor complications (more transient paresthesia but fewer skin-related complications). Future studies are unlikely to alter these findings because of the rarity of the outcome. The effect of a learning curve might be responsible for reduced recurrences and reoperations with ECTR in studies that are more recent, although formal statistical analysis failed to provide evidence for such an association. LEVEL OF EVIDENCE: I.

Endoscopic release for carpal tunnel syndrome.

BACKGROUND: Carpal tunnel syndrome (CTS) is the most common compressive neuropathy of the upper extremity. It is caused by increased pressure on the median nerve between the transverse carpal ligament and the carpal bones. Surgical treatment consists of the release of the nerve by cutting the transverse carpal ligament. This can be done either with an open approach or endoscopically. OBJECTIVES: To assess the effectiveness and safety of the endoscopic techniques of carpal tunnel release compared to any other surgical intervention for the treatment of CTS. More specifically, to evaluate the relative impact of endoscopic techniques in relieving symptoms, producing functional recovery (return to work and return to daily activities) and reducing complication rates. SEARCH METHODS: This review fully incorporates the results of searches conducted up to 5 November 2012, when we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE and EMBASE. There were no language restrictions. We reviewed the reference lists of relevant articles and contacted trial authors. We also searched trial registers for ongoing trials. We performed a preliminary screen of searches to November 2013 to identify any additional recent publications. SELECTION CRITERIA: We included any randomised controlled trials (RCTs) and quasi-RCTs comparing endoscopic carpal tunnel release (ECTR) with any other surgical intervention for the treatment of CTS. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by the Cochrane Collaboration. MAIN RESULTS: Twenty-eight studies (2586 hands) were included. Twenty-three studies compared ECTR to standard open carpal tunnel release (OCTR), five studies compared ECTR with OCTR using a modified incision, and two studies used a three-arm design to compare ECTR, standard OCTR and modified OCTR.At short-term follow-up (three months or less), only one study provided data for overall improvement. We found no differences on the Symptom Severity Scale (SSS) (scale zero to five) (five studies, standardised mean difference (SMD) -0.13, 95% CI -0.47 to 0.21) or on the Functional Status Scale (FSS) (scale zero to five) (five studies, SMD -0.23, 95% CI -0.60 to 0.14) within three months postoperatively between ECTR and OCTR. Pain scores favoured ECTR over conventional OCTR (two studies, SMD -0.41, 95% CI -0.65 to -0.18). No difference was found between ECTR and OCTR (standard and modified) when pain was assessed on non-continuous dichotomous scales (five studies, RR 0.69, 95% CI 0.33 to 1.45). Also, no difference was found in numbness (five studies, RR 1.14; 95% CI 0.76 to 1.71). Grip strength was increased after ECTR when compared with OCTR (six studies, SMD 0.36, 95% CI 0.09 to 0.63). This corresponds to a mean difference (MD) of 4 kg (95% CI 1 to 6.9 kg) when compared with OCTR, which is probably not clinically significant.In the long term (more than three months postoperatively) there was no significant difference in overall improvement between ECTR and OCTR (four studies, RR 1.04, 95% CI 0.95 to 1.14). SSS and FSS were also similar in both treatment groups (two studies, MD 0.02, 95% CI -0.18 to 0.22 for SSS and MD 0.01, 95% CI -0.14 to 0.16 for FSS). ECTR and OCTR did not differ in the long term in pain (six studies, RR 0.88, 95% CI 0.57 to 1.38) or in numbness (four studies, RR 0.64, 95% CI 0.31 to 1.35). Results from grip strength testing favoured ECTR (two studies, SMD 1.13, 95% CI 0.56 to 1.71), corresponding to an MD of 11 kg (95% CI 6.2 to 18.81). Participants treated with ECTR returned to work or daily activities eight days earlier than participants treated with OCTR (four studies, MD -8.10 days, 95% CI -14.28 to -1.92 days).Both treatments were equally safe with only a few reports of major complications (mainly with complex regional pain syndrome) (15 studies, RR 1.00, 95% CI 0.38 to 2.64).ECTR resulted in a significantly lower rate of minor complications (18 studies, RR 0.55, 95% CI 0.38 to 0.81), corresponding to a 45% relative drop in the probability of complications (95% CI 62% to 19%). ECTR more frequently resulted in transient nerve problems (ie, neurapraxia, numbness, and paraesthesiae), while OCTR had more wound problems (ie, infection, hypertrophic scarring, and scar tenderness). ECTR was safer than OCTR when the total number of complications were assessed (20 studies, RR 0.60, 95% CI 0.40 to 90) representing a relative drop in the probability by 40% (95% CI 60% to 10%).Rates of recurrence of symptoms and the need for repeated surgery were comparable between ECTR and OCTR groups.The overall risk of bias in studies that contribute data to these results is rather high; fewer than 25% of the included studies had adequate allocation concealment, generation of allocation sequence or blinding of the outcome assessor.The quality of evidence in this review may be considered as generally low. Five of the studies were presented only as abstracts, with insufficient information to judge their risk of bias. In selection bias, attrition bias or other bias (baseline differences and financial conflict of interest) we could not reach a safe judgement regarding a high or low risk of bias. Blinding of participants is impossible due to the nature of interventions.We identified three further potentially eligible studies upon updating searches just prior to publication. These compared ECTR with OCTR (two studies) or mini-open carpal tunnel release (one study) and will be fully assessed when we update the review. AUTHORS' CONCLUSIONS: In this review, with support from low quality evidence only, OCTR and ECTR for carpal tunnel release are about as effective as each other in relieving symptoms and improving functional status, although there may be a functionally significant benefit of ECTR over OCTR in improvement in grip strength. ECTR appears to be associated with fewer minor complications compared to OCTR, but we found no difference in the rates of major complications. Return to work is faster after endoscopic release, by eight days on average. Conclusions from this review are limited by the high risk of bias, statistical imprecision and inconsistency in the included studies.

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.

Low-grade central osteosarcoma of distal femur, resembling fibrous dysplasia.

We report a case of a 32 year-old male, admitted for a lytic lesion of the distal femur. One month after the first X-ray, clinical and imaging deterioration was evident. Open biopsy revealed fibrous dysplasia. Three months later, the lytic lesion had spread to the whole distal third of the femur reaching the articular cartilage. The malignant clinical and imaging features necessitated excision of the lesion and reconstruction with a custom-made total knee arthroplasty. Intra-operatively, no obvious soft tissue infiltration was evident. Nevertheless, an excision of the distal 15.5 cm of the femur including 3.0 cm of the surrounding muscles was finally performed. The histological examination of the excised specimen revealed central low-grade osteosarcoma. Based on the morphological features of the excised tumor, allied to the clinical findings, the diagnosis of low-grade central osteosarcoma was finally made although characters of a fibrous dysplasia were apparent. Central low-grade osteosarcoma is a rare, well-differentiated sub-type of osteosarcoma, with clinical, imaging, and histological features similar to benign tumours. Thus, initial misdiagnosis is usual with the condition commonly mistaken for fibrous dysplasia. Central low-grade osteosarcoma is usually treated with surgery alone, with rare cases of distal metastases. However, regional recurrence is quite frequent after close margin excision.

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.

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.

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.

The influence of graft choice on isokinetic muscle strength 4-24 months after anterior cruciate ligament reconstruction.

PURPOSE: Regaining adequate strength of the quadriceps and hamstrings after anterior cruciate ligament (ACL) reconstruction is important for maximizing functional performance. However, the outcome of muscle strength after either BPTB or hamstrings autograft is unclear given the plethora of published studies that report post-operative muscle strength. The purpose of this study was to systematically compare the muscle strength of patients who have undergone ACL reconstruction using either Bone Patellar Tendon Bone (BPTB) or Hamstrings (HST) autograft. METHODS: The databases of MEDLINE, Cinahal and EMBASE were systematically searched for articles that report muscle strength outcome following ACL reconstruction. The quality of the studies was evaluated and a meta-analysis of the muscle strength outcomes was conducted on reported data. RESULTS: Fourteen studies were included in this systematic review: eight Randomized Control Studies (RCT) and six non-Randomized Control Studies (non-RCT). A meta-analysis was performed involving eight of the included studies (4 RCTs & 3 non-RCTs). At 60°/s and 180°/s, patients with BPTB graft showed a greater deficit in extensor muscle strength and lower deficit in flexor muscle strength compared with patients with HST. CONCLUSION: This systematic review of Level III evidence showed that isokinetic muscle strength deficits following ACL reconstruction are associated with the location of the donor site. These deficits appear to be unresolved up to 2 years after ACL reconstruction. LEVEL OF EVIDENCE: III.

Malalignment and cartilage lesions in the patellofemoral joint treated with autologous chondrocyte implantation.

PURPOSE: The aim of our current study is to present the 12.6 years' follow-up results in patients with cartilage lesions of the patellofemoral joint, treated with autologous chondrocyte implantation (ACI) with the use of periosteum. METHODS: Ninety-two patients having patella or trochlea lesion participated in this study. Lysholm and Tegner questionnaires were completed 12.6 years (SD 2.3 years) after the surgery. The patients were asked whether they feel better, worse or had not experienced any difference compared to previous years and whether they would undergo the operation again. Complications or subsequent surgeries were also assessed. RESULTS: Median Tegner score was three, improved by one level compared with preoperative values (P = 0.02). Median Lysholm score was 70, improved by nine points (n.s.). Seventy-two percent of the patients were better or unchanged while 93% would undergo the operation again. Patients with no kissing lesions appeared to have a better prognosis. Patients with malalignment or instability that had undergone a realignment procedure had comparable outcomes to the patients that did not need any additional surgery. Realignment procedures increased the incidence of serious complications but they were associated with decreased incidence of periosteal hypertrophy. No association was found between the age of the patients at the time of the ACI or the size per lesion and any of the clinical outcomes. CONCLUSION: ACI provides a satisfactory outcome for the treatment of cartilage lesions of the patellofemoral joint, even for the cases with concomitant patellar instability. It seems that correcting the coexisting background factors with realignment, stabilizing or unloading procedures, along with the treatment of cartilage lesions, is improving the clinical outcomes over time and decreases the incidence of periosteal hypertrophies although increasing the incidence of serious complications. Our study reveals the good results and the high level of patients' activities (as shown by Tegner score), were preserved 12.6 years after the implantation, in both isolated trochlea and patella lesions and also in multiple and in kissing lesions where an intervention could be considered as a salvage procedure.

Autologous chondrocyte implantation for full thickness articular cartilage defects of the knee.

BACKGROUND: Treatments for managing articular cartilage defects of the knee, including drilling and abrasion arthroplasty, are not always effective. When they are, long-term benefits may not be maintained and osteoarthritis may develop. An alternative is autologous chondrocyte implantation (ACI), the surgical implantation of healthy cartilage cells into the damaged areas. OBJECTIVES: To determine the efficacy and safety of ACI in people with full thickness articular cartilage defects of the knee. SEARCH STRATEGY: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (3 December 2008), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2008, Issue 4), MEDLINE (1950 to November Week 3 2008), EMBASE (1980 to Week 48 2008), SPORTDiscus (3 December 2008), the WHO International Clinical Trials Registry Platform (4 December 2008), and Current Controlled Trials (3 December 2008). SELECTION CRITERIA: Randomised and quasi-randomised trials comparing ACI with any other type of treatment (including no treatment or placebo) for symptomatic cartilage defects of the medial or lateral femoral condyle, femoral trochlea or patella. DATA COLLECTION AND ANALYSIS: Review authors selected studies for inclusion independently. We assessed risk of bias based on adequacy of the randomisation and allocation concealment process, potential for selection bias after allocation and level of masking. We did not pool data due to clinical and methodological heterogeneity. MAIN RESULTS: Six heterogeneous trials were identified with 431 participants. Methodological flaws of the included trials included incomplete follow-up and inadequate reporting of outcomes. Three trials compared ACI versus mosaicplasty. One reported statistically significant results in favour of ACI at one year in the numbers of people with 'good' or 'excellent' functional results. Conversely, another trial found significant improvement for the mosaicplasty group when assessed using one functional scoring system at two years, but no statistically significant differences based on two other scoring systems. A third trial found no difference between ACI and mosaicplasty, 10 months on average after the surgery.There was no statistically significant difference in functional outcomes at two years in single trials comparing ACI with microfracture or characterised chondrocyte implantation versus microfracture. The results of the sixth trial comparing matrix-guided ACI versus microfracture were undermined by the severe loss to follow-up. AUTHORS' CONCLUSIONS: There is insufficient evidence to draw conclusions on the use of ACI for treating full thickness articular cartilage defects in the knee. Further good quality randomised controlled trials with long-term functional outcomes are required.

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.

Autologous chondrocyte implantation for the treatment of cartilage lesions of the knee: a systematic review of randomized studies.

Autologous chondrocyte implantation (ACI) techniques are becoming more popular for the treatment of full thickness cartilage lesions of the knee joint. However, there is no systematic information for the efficacy of the new generation ACI techniques compared to other treatment options. A systematic review of the existing evidence from randomized clinical trials of ACI treatment would contribute to understanding the advantages and limitations of this method and would inform the planning of future studies. Using pre-defined criteria, we searched a number of electronic databases to identify all the existing randomized control trials of any type of ACI treatment. Risk of bias was assessed and an analysis of the reported outcomes was performed. Information on the clinical efficacy and safety of ACI compared to other interventions was collected and presented. Nine trials were identified with 626 patients. Patients ranged from 15 to 52 years, and the size of treated lesions was between 1 and 22 cm(2). ACI was associated with improvement in clinical outcomes compared to baseline. However, the body of evidence did not suggest any superiority of ACI over other treatments. Complication rates were comparable between interventions except from an increased rate of graft hypertrophies after ACI with periosteum. ACI is an effective treatment for full thickness chondral defects of the knee, providing an improvement of clinical outcomes. However, there is insufficient data to say whether ACI is superior to other treatment strategies. More high quality studies and harmonization in the reported outcomes are needed before specific suggestions for practice can be made.

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.