Favourable long-term functional and radiographical outcome after osteoautograft transplantation surgery of the knee: a minimum 10-year follow-up.

PURPOSE: The aim of this study was to assess the progression of radiological cartilage changes and to document the functional, long-term results during a follow-up of 10 years after osteoautograft transplantation (OAT) knee surgery. METHODS: The study was a retrospective analysis of all patients who underwent OAT at Turku University Hospital from 1999 to 2007. Pre- and postoperative cartilage changes were estimated based on standardised radiographs. The extent of osteoarthritis (OA) was graded according to the Kellgren-Lawrence scale. Clinical outcomes were evaluated with the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire. RESULTS: A total of 60 patients (64 knees) with a median age of 30 years (range 14-62) were included. The median follow-up was 140 months (range 47-205). Of the 64 knees examined, 14 (22%) had a traumatic chondral lesion and 50 (78%) had osteochondritis dissecans (OCD). Preoperatively, 71% of the patients had Kellgren-Lawrence grades of 0-1; during the follow-up period, 50% of the patients showed radiographical progression of OA. OA progressed most significantly in patients with normal preoperative Kellgren-Lawrence grades (p = 0.0003). Patients with no progression in joint space narrowing had statistically significantly better overall KOOS (p = 0.02) than patients whose Kellgren-Lawrence grades worsened. Patients with defect sizes > 3.0 cm2 scored statistically significantly better in all subscales than patients with smaller defect sizes (p = 0.02). Patients with OCD had statistically significantly better KOOS than patients with chondral defects (p = 0.008). CONCLUSIONS: OAT surgery for treating patients with cartilage defects of the knee had good clinical results after a mean follow-up of 11 years. Radiological analyses revealed a progression of cartilage degeneration in 50% of the operated knees. Patients with no progression of the degenerative changes scored statistically significantly better on the KOOS self-assessment test. These results indicate that OAT surgery appears to be a reasonable therapeutic option to restore knee function in patients with cartilage lesions. LEVEL OF EVIDENCE: IV.

Signature of circulating small non-coding RNAs during early fracture healing in mice.

Fracture healing is a complex process with multiple overlapping metabolic and differentiation phases. Small non-coding RNAs are involved in the regulation of fracture healing and their presence in circulation is under current interest due to their obvious value as potential biomarkers. Circulating microRNAs (miRNAs) have been characterized to some extent but the current knowledge on tRNA-derived small RNA fragments (tsRNAs) is relatively scarce, especially in circulation. In this study, the spectrum of circulating miRNAs and tsRNAs was analysed by next generation sequencing to show their differential expression during fracture healing in vivo. Analysed tsRNA fragments included stress-induced translation interfering tRNA fragments (tiRNAs or tRNA halves) and internal tRNA fragments (i-tRF), within the size range of 28-36 bp. To unveil the expression of these non-coding RNAs, genome-wide analysis was performed on two months old C57BL/6 mice on days 1, 5, 7, 10, and 14 (D1, D5, D7, D10, and D14) after a closed tibial fracture. Valine isoacceptor tRNA-derived Val-AAC 5'end and Val-CAC 5'end fragments were the major types of 5'end tiRNAs in circulation, comprising about 65 % of the total counts. Their expression was not affected by fracture. After a fracture, the levels of two 5'end tiRNAs Lys-TTT 5' and Lys-CTT 5' were decreased and His-GTG 5' was increased through D1-D14. The level of miR-451a was decreased on the first post-fracture day (D1), whereas miR-328-3p, miR-133a-3p, miR-375-3p, miR-423-5p, and miR-150-5p were increased post-fracture. These data provide evidence on how fracture healing could provoke systemic metabolic effects and further pinpoint the potential of small non-coding RNAs as biomarkers for tissue regeneration.

Multiple targets identified with genome wide profiling of small RNA and mRNA expression are linked to fracture healing in mice.

Long-bone fracture is a common injury and its healing process at the fracture site involves several overlapping phases, including inflammation, migration of mesenchymal progenitors into the fracture site, endochondral ossification, angiogenesis and finally bone remodelling. Increasing evidence shows that small noncoding RNAs are important regulators of chondrogenesis, osteogenesis and fracture healing. MicroRNAs are small single-stranded, non-coding RNA-molecules intervening in most physiological and biological processes, including fracture healing. Angiogenin-cleaved 5' tRNA halves, also called as tiRNAs (stress-induced RNAs) have been shown to repress protein translation. In order to gain further understanding on the role of small noncoding RNAs in fracture healing, genome wide expression profiles of tiRNAs, miRNAs and mRNAs were followed up to 14 days after fracture in callus tissue of an in vivo mouse model with closed tibial fracture and, compared to intact bone and articular cartilage at 2 months of age. Total tiRNA expression level in cartilage was only approximately one third of that observed in control D0 bone. In callus tissue, 11 mature 5'end tiRNAs out of 191 tiRNAs were highly expressed, and seven of them were differentially expressed during fracture healing. When comparing the control tissues, 25 miRNAs characteristic to bone and 29 miRNAs characteristic to cartilage tissue homeostasis were identified. Further, a total of 54 out of 806 miRNAs and 5420 out of 18,700 mRNAs were differentially expressed (DE) in callus tissue during fracture healing and, in comparison to control bone. They were associated to gene ontology processes related to mesenchymal tissue development and differentiation. A total of 581 miRNA-mRNA interactions were identified for these 54 DE miRNAs by literature searches in PubMed, thereby linking by Spearman correlation analysis 14 downregulated and 28 upregulated miRNAs to 164 negatively correlating and 168 positively correlating miRNA-mRNA pairs with chondrogenic and osteogenic phases of fracture healing. These data indicated that tiRNAs and miRNAs were differentially expressed in fracture callus tissue, suggesting them important physiological functions during fracture healing. Hence, the data provided by this study may contribute to future clinical applications, such as potential use as biomarkers or as tools in the development of novel therapeutic approaches for fracture healing.

Preference for information and behavioral control among adult ambulatory surgical patients.

This empirical study aimed to describe the ambulatory surgical patients' information and control preferences with reference to received knowledge. The results indicate that patients' information preferences and behavioral preferences are not very high, and they seem to receive most knowledge in the biophysiological domain. The most important finding is that patients with higher preferences seem to receive less knowledge than those with lower preferences. The results suggest the need to further study nurses in the ambulatory surgery setting and the extent to which the information expectations of patients are met.

Repair of full-thickness rotator cuff tears is recommended regardless of tear size and age: a retrospective study of 218 patients.

Conservative therapy has been recommended for the treatment of a chronic cuff lesion with relatively good results. However, recent reports about operative treatment of cuff lesions have yielded more favorable results. Although the current literature seems to favor early treatment, there is an ongoing debate about the timing of the operation. During a 16-year period, 415 chronic full-thickness rotator cuff tears were operated on at our institution. The indication for operative treatment was persistent, severe or moderate pain at rest and impairment of shoulder function after initial conservative treatment. At follow-up, the symptoms were assessed by an interview, and all patients were clinically examined. Pain, function, range of active forward flexion, active abduction, strength (manual muscle testing), and patient satisfaction were recorded, and the results were evaluated by the University of California, Los Angeles shoulder rating scale. On the basis of our results, we recommend operative treatment of the rotator cuff for all cases in which the tear is full thickness, regardless of tear size, if patients have any symptoms, especially pain.

Soluble activin type IIB receptor improves fracture healing in a closed tibial fracture mouse model.

Fractures still present a significant burden to patients due to pain and periods of unproductivity. Numerous growth factors have been identified to regulate bone remodeling. However, to date, only the bone morphogenetic proteins (BMPs) are used to enhance fracture healing in clinical settings. Activins are pleiotropic growth factors belonging to the TGF-ß superfamily. We and others have recently shown that treatment with recombinant fusion proteins of activin receptors greatly increases bone mass in different animal models by trapping activins and other ligands thus inhibiting their signaling pathways. However, their effects on fracture healing are less known. Twelve-week old male C57Bl mice were subjected to a standardized, closed tibial fracture model. Animals were divided into control and treatment groups and were administered either PBS control or a soluble activin type IIB receptor (ActRIIB-Fc) intraperitoneally once a week for a duration of two or four weeks. There were no significant differences between the groups at two weeks but we observed a significant increase in callus mineralization in ActRIIB-Fc-treated animals by microcomputed tomography imaging at four weeks. Bone volume per tissue volume was 60%, trabecular number 55% and bone mineral density 60% higher in the 4-week calluses of the ActRIIB-Fc-treated mice (p<0.05 in all). Biomechanical strength of 4-week calluses was also significantly improved by ActRIIB-Fc treatment as stiffness increased by 64% and maximum force by 45% (p<0.05) compared to the PBS-injected controls. These results demonstrate that ActRIIB-Fc treatment significantly improves healing of closed long bone fractures. Our findings support the previous reports of activin receptors increasing bone mass but also demonstrate a novel approach for using ActRIIB-Fc to enhance fracture healing.

NF1 gene expression in mouse fracture healing and in experimental rat pseudarthrosis.

Neurofibromatosis type 1 (NF1) is an inherited disease with an incidence of about 1:3000 worldwide. Approximately half of all patients with NF1 present osseous manifestations, which can vary from mild to severely debilitating changes such as congenital pseudarthrosis. In the present study, fracture healing of mouse tibia was followed and specimens were collected 5, 9, 14, and 22 days postoperatively. Experimental pseudarthrosis of rat was followed up to 15 weeks postoperatively. In situ hybridization and immunohistochemistry were used to demonstrate expression of NF1 tumor suppressor and phosphorylated p44/42 mitogen-activated protein kinase (MAPK), an indicator of the Ras-MAPK pathway. The results showed that ossified callus was formed in mouse fracture 22 days after the operation. The final outcome of rat pseudarthrosis was detected 9 weeks after the operation, presenting abundant cartilaginous callus at the pseudarthrosis. NF1 gene expression was noted in the maturing and in the hypertrophic cartilages during normal mouse fracture healing, and in rat pseudarthrosis. Phosphorylated p44/42 MAPK was detected in a subpopulation of the hypertrophic chondrocytes in both models. Furthermore, positive labeling for NF1 mRNA and protein was detected in endothelium in both the pseudarthrosis and in the fracture. In conclusion, NF1 gene expression and function are needed for normal fracture healing, possibly restraining excessive Ras-MAPK pathway activation.

How to structure an empowering patient education program for internet.

There is a lot of health related information in the Internet. However a little is known about the quality of that. The purpose of this study is to analyze the structure and the applicability of the empowering internet based ambulatory surgery patients' education program. The education material was created and tested for this study. The structure is evaluated with structure analysis and applicability with AWStats-counter program and a survey. The evaluation of the program's structure and applicability, gives feedback about the usability of the program and helps to create criteria for a useable structure of the patients' education program.

Osteochondritis dissecans of the humeral capitellum in identical twins.

Osteochondritis dissecans (OCD) of the humeral capitellum is a disorder affecting mainly boys between the ages of 12 and 15 years. The exact etiology of OCD is not clear, but it is believed that repetitive trauma is the primary cause. Genetic factors are thought to play a secondary role in the pathogenesis. We present 17-year-old identical twins with similar MRI and arthroscopic findings, suggesting that genetic components are involved in the etiology of OCD of the humeral capitellum.

Ambulatory orthopaedic surgery patients' knowledge expectations and perceptions of received knowledge.

AIM: This paper is a report of a study to compare orthopaedic ambulatory surgery patients' knowledge expectations before admission and their perceptions of received knowledge 2 weeks after discharge. BACKGROUND: Advances in technology and population ageing are driving up the number of ambulatory orthopaedic surgical procedures. Shorter hospital stays present a major challenge for patient education. METHODS: A descriptive comparative cross-sectional study (pre- and post-test) design was adopted. The data were collected from 120 consecutive patients in 2004, using the Hospital Patient's Knowledge Expectations Scale and Hospital Patient's Received Knowledge Scale. All patients participated in a preoperative education session given by a nurse. RESULTS: Patients expected more knowledge than they actually perceived that they received on all dimensions except the bio-physiological. They perceived that they received least knowledge about experiential, ethical, social and financial dimensions of knowledge. Knowledge expectations correlated with age and professional education. Perceptions of received knowledge correlated with earlier ambulatory surgery, and both expected knowledge and perceptions of received knowledge were related to the level of basic education. CONCLUSION: Patients' knowledge expectations are greater than the knowledge they perceived that they receive, and they cannot become empowered if they lack important knowledge. Further research is needed to learn about meeting patients' knowledge expectations.

Results of early operative treatment of rotator cuff tears with acute symptoms.

The distinction among an acute tear, acute symptoms of a chronic tear, or the acute extension of an existing chronic tear is very difficult, if not impossible, to make. In general, operative treatment of lesions with a sudden onset has yielded favorable results in many studies. However, the timing of the operation for tears with an acute onset of symptoms is still a very controversial issue, as are the treatment options for chronic tears with acute symptoms. This study analyzes the follow-up results of early operative treatment of rotator cuff tears with an acute onset of symptoms, regardless of tear type. Twenty-nine patients with a sudden onset of symptoms and significant impairment of shoulder function had a full-thickness rotator cuff tear. The patients were operated on within 3 weeks from the beginning of the symptoms. Twenty-six patients underwent follow-up. The results were evaluated by use of the UCLA shoulder rating scale. At follow-up, 22 patients (85%) had no pain and 21 (81%) had returned to normal activities and had normal shoulder function. Active forward flexion averaged 51 degrees preoperatively and 167 degrees at follow-up. After repair of the tear, shoulder strength was normal in 22 of 26 shoulders (85%); 3 patients had fair strength, all after repair of a massive tear. Of the patients, 25 (96%) were satisfied with the result. The overall result was excellent in 20 patients (77%), good in 4 (15%), fair in 1 (4%), and poor in 1 (4%). Early operative treatment appears to be better for rotator cuff tears with a sudden onset of symptoms and poor function to achieve maximal return of shoulder function. With time, the tear may enlarge, and the cuff may lose its elasticity, thus making the late surgical repair more difficult or even impossible.

Diminished callus size and cartilage synthesis in alpha 1 beta 1 integrin-deficient mice during bone fracture healing.

Integrins mediate cell adhesion to extracellular matrix components. Integrin alpha 1 beta 1 is a collagen receptor expressed on many mesenchymal cells, but mice deficient in alpha 1 integrin (alpha1-KO) have no gross structural defects. Here, the regeneration of a fractured long bone was studied in alpha1-KO mice. These mice developed significantly less callus tissue than the wild-type (WT) mice, and safranin staining revealed a defect in cartilage formation. The mRNA levels of nine extracellular matrix genes in calluses were evaluated by Northern blotting. During the first 9 days the mRNA levels of cartilage-related genes, including type II collagen, type IX collagen, and type X collagen, were lower in alpha1-KO mice than in WT mice, consistent with the reduced synthesis of cartilaginous matrix appreciated in tissue sections. Histological observations also suggested a diminished number of chondrocytes in the alpha 1-KO callus. Proliferating cell nuclear antigen staining revealed a reduction of mesenchymal progenitors at the callus site. Although, the number of mesenchymal stem cells (MSCs) obtained from WT and alpha 1-KO whole marrow was equal, in cell culture the proliferation rate of the MSCs of alpha 1-KO mice was slower, recapitulating the in vivo observation of reduced callus cell proliferation. The results demonstrate the importance of proper collagen-integrin interaction in fracture healing and suggest that alpha1 integrin plays an essential role in the regulation of MSC proliferation and cartilage production.