Oddmund Johansen

Autologous Chondrocyte Implantation Compared with Microfracture in the Knee: A Randomized Trial

BACKGROUND New methods have been used, with promising results, to treat full-thickness cartilage defects. The objective of the present study was to compare autologous chondrocyte implantation with microfracture in a randomized trial. We are not aware of any previous randomized studies comparing these methods. METHODS Eighty patients without general osteoarthritis who had a single symptomatic cartilage defect on the femoral condyle in a stable knee were treated with autologous chondrocyte implantation or microfracture (forty in each group). We used the International Cartilage Repair Society, Lysholm, Short Form-36 (SF-36), and Tegner forms to collect data. An independent observer performed a follow-up examination at twelve and twenty-four months. Two years postoperatively, arthroscopy with biopsy for histological evaluation was carried out. The histological evaluation was done by a pathologist and a clinical scientist, both of whom were blinded to each patients treatment. RESULTS In general, there were small differences between the two treatment groups. At two years, both groups had significant clinical improvement. According to the SF-36 physical component score at two years postoperatively, the improvement in the microfracture group was significantly better than that in the autologous chondrocyte implantation group (p = 0.004). Younger and more active patients did better in both groups. There were two failures in the autologous chondrocyte implantation group and one in the microfracture group. No serious complications were reported. Biopsy specimens were obtained from 84% of the patients, and histological evaluation of repair tissues showed no significant differences between the two groups. We did not find any association between the histological quality of the tissue and the clinical outcome according to the scores on the Lysholm or SF-36 form or the visual analog scale. CONCLUSIONS Both methods had acceptable short-term clinical results. There was no significant difference in macroscopic or histological results between the two treatment groups and no association between the histological findings and the clinical outcome at the two-year time-point. LEVEL OF EVIDENCE Therapeutic study, Level I-1a (randomized controlled trial [significant difference]). See Instructions to Authors for a complete description of levels of evidence.

A randomized trial comparing autologous chondrocyte implantation with microfracture. Findings at five years.

BACKGROUND The optimal treatment for cartilage lesions has not yet been established. The objective of this randomized trial was to compare autologous chondrocyte implantation with microfracture. This paper represents an update, with presentation of the clinical results at five years. METHODS Eighty patients who had a single chronic symptomatic cartilage defect on the femoral condyle in a stable knee without general osteoarthritis were included in the study. Forty patients were treated with autologous chondrocyte implantation, and forty were treated with microfracture. We used the International Cartilage Repair Society, Lysholm, Short Form-36, and Tegner forms to collect clinical data, and radiographs were evaluated with use of the Kellgren and Lawrence grading system. RESULTS At two and five years, both groups had significant clinical improvement compared with the preoperative status. At the five-year follow-up interval, there were nine failures (23%) in both groups compared with two failures of the autologous chondrocyte implantation and one failure of the microfracture treatment at two years. Younger patients did better in both groups. We did not find a correlation between histological quality and clinical outcome. However, none of the patients with the best-quality cartilage (predominantly hyaline) at the two-year mark had a later failure. One-third of the patients in both groups had radiographic evidence of early osteoarthritis at five years. CONCLUSIONS Both methods provided satisfactory results in 77% of the patients at five years. There was no significant difference in the clinical and radiographic results between the two treatment groups and no correlation between the histological findings and the clinical outcome. One-third of the patients had early radiographic signs of osteoarthritis five years after the surgery. Further long-term follow-up is needed to determine if one method is better than the other and to study the progression of osteoarthritis.

The internal obturator muscle may cause sciatic pain.

&NA; Six patients suspected to have piriformis syndrome were operated in the hip region in an attempt to relieve pressure on the sciatic nerve. The piriformis muscle and tendon as well as their relationship to the sciatic nerve were found to be normal. However, the internal obturator muscle was found to be very tense, slightly hyperaemic and pressing the sciatic nerve. During Lasegues testing on the operating table the internal obturator and not the piriformis muscle impinged on the nerve at an early stage in the hip flexion movement. A sectioning of the tendon to the internal obturator muscle near its insertion at the trochanter was performed. Median pain score was found to be reduced from the preoperative value (8.5) to that at 6 weeks (3.5) (P<0.05) and 3 (3.5) (P<0.05) and 6 months (5.5) (N.S.) postoperatively. No significant reduction of pain was found in a control group of six patients followed during the same period. Three patients who needed opioids preoperatively managed without such drugs 6 months after the operation. Two patients in the operated group were at work 50 and 100% after having been out of work for 3 and 10 years, respectively.

A Randomized Multicenter Trial Comparing Autologous Chondrocyte Implantation with Microfracture: Long-term Follow-up at 14 to 15 Years.

BACKGROUND The management of cartilage and osteochondral lesions in the knee remains problematic and controversial. Our group reported the 2-year and 5-year results of a randomized controlled trial comparing autologous chondrocyte implantation (ACI) and microfracture in patients with focal femoral cartilage injuries. The objective of the present study was to report the long-term results. METHODS Eighty patients with a single symptomatic chronic cartilage defect on the femoral condyle without general osteoarthritis were included in the study at the time of the index operation (January 1999 to February 2000). We used the International Cartilage Repair Society (ICRS), Lysholm, Short Form-36 (SF-36), and Tegner forms to collect data at the time of inclusion and at follow-up evaluations. Standing weight-bearing radiographs were evaluated for evidence of osteoarthritis according to the method described by Kellgren and Lawrence. For the long-term follow-up in 2014, we used the Synaflexer frame to standardize the radiographs. The operation was considered to have failed if a reoperation was performed because of symptoms from a lack of healing of the treated defect. RESULTS At the long-term follow-up evaluation, no significant differences between the treatment groups were detected with respect to the results on the clinical scoring systems. At the 15-year evaluation, there were 17 failures in the ACI group compared with 13 in the microfracture group. We observed that more total knee replacements were needed in the ACI group than in the microfracture group (6 compared with 3). The surviving patients in both groups, i.e., those who had not had a failure, had significant improvement in the clinical scores compared with baseline. Fifty-seven percent of the surviving patients in the ACI group and 48% of such patients in the microfracture group had radiographic evidence of early osteoarthritis (a Kellgren and Lawrence grade of ≥2); the difference was not significant. CONCLUSIONS The survivors in both groups improved their clinical scores in the short, medium, and long-term evaluations, and no significant difference between the groups was found at the long-term follow-up. The risk of treatment failure and the frequency of radiographic osteoarthritis are problematic. Our findings raise serious concerns regarding the efficacy of these procedures in delaying osteoarthritis and preventing further surgery. Continued basic and clinical research is needed in this field. LEVEL OF EVIDENCE Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Radiofrequency Microtenotomy : A Promising Method for Treatment of Recalcitrant Lateral Epicondylitis

Background Recalcitrant lateral epicondylitis (elbow tendinosis) is a common cause of elbow pain. There are many forms of treatment, none being superior. Hypothesis The main hypothesis tested in this study is that radiofrequency microtenotomy offers better results than the extensor tendon release and repair operation for elbow tendinosis, especially earlier recovery. Study Design Randomized controlled trial; Level of evidence, 1. Methods Twenty-four patients were randomized into 2 treatment groups, extensor tendon release and repair, and microtenotomy. Dynamic infrared thermography (DIRT) was employed as an objective method to verify the diagnosis as well as to document the outcome 3 months after the surgical procedure. Results Visual analog scale pain scores in the microtenotomy but not in the release group decreased significantly after 3 weeks. There was no statistically significant difference in pain scores between the 2 groups at 3, 6, and 12 weeks, and at 10 to 18 months. At 12 weeks, grip strength had improved significantly in the microtenotomy but not in the release group. The functional score was significantly increased in both groups. The DIRT group showed significant differences in epicondyle skin temperature between diseased and normal elbows both pre- and postoperatively. Abnormal DIRT images correlated well with elevated pain scores. Conclusions Radiofrequency microtenotomy provides a promising alternative to the release operation for elbow tendinosis. Dynamic infrared thermography provides a reliable, noninvasive, objective method for the diagnosis of elbow tendinosis, as well as for evaluation of the outcome following treatment.

The influence of oxygen tension on the structure and function of isolated liver sinusoidal endothelial cells

BackgroundLiver sinusoidal endothelial cells (LSECs) are specialized scavenger cells, with crucial roles in maintaining hepatic and systemic homeostasis. Under normal physiological conditions, the oxygen tension encountered in the hepatic sinusoids is in general considerably lower than the oxygen tension in the air; therefore, cultivation of freshly isolated LSECs under more physiologic conditions with regard to oxygen would expect to improve cell survival, structure and function. In this study LSECs were isolated from rats and cultured under either 5% (normoxic) or 20% (hyperoxic) oxygen tensions, and several morpho-functional features were compared.ResultsCultivation of LSECs under normoxia, as opposed to hyperoxia improved the survival of LSECs and scavenger receptor-mediated endocytic activity, reduced the production of the pro-inflammatory mediator, interleukin-6 and increased the production of the anti-inflammatory cytokine, interleukin-10. On the other hand, fenestration, a characteristic feature of LSECs disappeared gradually at the same rate regardless of the oxygen tension. Expression of the cell-adhesion molecule, ICAM-1 at the cell surface was slightly more elevated in cells maintained at hyperoxia. Under normoxia, endogenous generation of hydrogen peroxide was drastically reduced whereas the production of nitric oxide was unaltered. Culture decline in high oxygen-treated cultures was abrogated by administration of catalase, indicating that the toxic effects observed in high oxygen environments is largely caused by endogenous production of hydrogen peroxide.ConclusionViability, structure and many of the essential functional characteristics of isolated LSECs are clearly better preserved when the cultures are maintained under more physiologic oxygen levels. Endogenous production of hydrogen peroxide is to a large extent responsible for the toxic effects observed in high oxygen environments.

Differences in the secretome of cartilage explants and cultured chondrocytes unveiled by SILAC technology

The main goal of our study was to analyze and compare the profiles of secreted proteins from adult human articular chondrocytes in monolayers, and cartilage explants in culture, using a de novo protein labeling approach. Stable isotope labeling of proteins in culture was used to differentiate between chondrocyte‐derived proteins and other preexisting matrix‐derived components, or proteins coming from serum or synovial fluids. Proteins in culture supernatants were resolved by one‐dimensional SDS‐PAGE electrophoresis, and analyzed in tandem with LC/MS‐MS (liquid chromatography/double mass spectrometry). Results from stable isotope labeling with amino acids in cell culture (SILAC) were validated by specific immunoblotting of four relevant proteins identified in the secretion media. After 8–10 days of culture, over 90% of proteins secreted during monolayer growth contained 13C6‐Arg and 13C6‐Lys. Nonlabeled proteins corresponded mostly to plasma‐associated proteins, indicating background contamination of medium with serum remnants. The majority of the secreted proteins in 2D cultures were extracellular matrix components and matrix regulators, along with some inflammatory agents and metabolic enzymes. In explants, only 25%–30% of proteins were labeled with heavy amino acids, corresponding to matrix regulators and carrier molecules. Nonlabeled proteins corresponded primarily to structural matrix components. In qualitative terms, all labeled proteins coming from cartilage explants were also found in chondrocytes supernatants. In summary, our results show differences in the labeling pattern of proteins found in supernatants from explants and monolayers. Most proteins found in the media of explants were subproducts of matrix turnover rather than newly synthesized. To our knowledge, this study is the first one so far applying SILAC technology in the context of cartilage and chondrocytes physiology.

Redifferentiation of in vitro expanded adult articular chondrocytes by combining the hanging-drop cultivation method with hypoxic environment.

The main purpose of this work has been to establish a new culturing technique to improve the chondrogenic commitment of isolated adult human chondrocytes, with the aim of being used during cell-based therapies or tissue engineering strategies. By using a rather novel technique to generate scaffold-free three-dimensional (3D) structures from in vitro expanded chondrocytes, we have explored the effects of different culture environments on cartilage formation. Three-dimensional chondrospheroids were developed by applying the hanging-drop technique. Cartilage tissue formation was attempted after combining critical factors such as serum-containing or serum-free media and atmospheric (20%) or low (2.5%) oxygen tensions. The quality of the formed microtissues was analyzed by histology, immunohistochemistry, electron microscopy, and real-time PCR, and directly compared with native adult cartilage. Our results revealed highly organized, 3D tissue-like structures developed by the hanging-drop method. All culture conditions allowed formation of 3D spheroids; however, cartilage generated under low oxygen tension had a bigger size, enhanced matrix deposition, and higher quality of cartilage formation. Real-time PCR demonstrated enhanced expression of cartilage-specific genes such us collagen type II and aggrecan in 3D cultures when compared to monolayers. Cartilage-specific matrix proteins and genes expressed in hanging-drop-developed spheroids were comparable to the expression obtained by applying the pellet culture system. In summary, our results indicate that a combination of 3D cultures of chondrocytes in hanging drops and a low oxygen environment represent an easy and convenient way to generate cartilage-like microstructures. We also show that a new specially tailored serum-free medium is suitable for in vitro cartilage tissue formation. This new methodology opens up the possibility of using autogenously produced solid 3D structures with redifferentiated chondrocytes as an attractive alternative to the currently used autologous chondrocyte transplantation for cartilage repair.

Could tendinosis be involved in osteoarthritis

Ten patients, age 60 (48–75 years), with osteoarthritis (OA) of the hip and 10 patients, age 82.5 (60–90 years), with fracture of the collum femoris (FCF; minimum Garden stage III) underwent an open biopsy procedure from the internal obturator tendon in conjunction with a total hip replacement. The histological evaluation revealed that all tendon samples in the OA group revealed scar tissue; the corresponding was found in 50% of patients in the FCF group (P=0.02). There were also more GAGs (P=0.023) and calcium deposits (P=0.001) in the samples from the OA group. The ultrastructural evaluation revealed fewer small and medium‐sized fibrils (P=0.001) and more non‐collagenous extracellular matrix (ECM) (P=0.003) in the OA group. Taken together, the samples from the internal obturator tendon in the OA group revealed a more degenerative appearance with more scar tissue, change in fibril diameter distribution and more non‐collagenous ECM. Our findings suggest that OA and periarticular tendinopathy are closely linked. Further research is needed to determine whether musculotendinous changes in the deep rotators are sequelae of joint pathology, or a contributing factor in the development of degenerative joint change.

Retro-trochanteric sciatica-like pain: current concept

The aim of this manuscript is to review the current knowledge in terms of retro-trochanteric pain syndrome, make recommendations for diagnosis and differential diagnosis and offer suggestions for treatment options. The terminology in the literature is confusing and these symptoms can be referred to as ‘greater trochanteric pain syndrome’, ‘trochanteric bursitis’ and ‘trochanteritis’, among other denominations. The authors focus on a special type of sciatica, i.e. retro-trochanteric pain radiating down to the lower extremity. The impact of different radiographic assessments is discussed. The authors recommend excluding pathology in the spine and pelvic area before following their suggested treatment algorithm for sciatica-like retro-trochanteric pain. Level of evidence II.