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| 2. |
- Dietrich, Franciele, et al.
(författare)
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Dexamethasone Enhances Achilles Tendon Healing in an Animal Injury Model, and the Effects Are Dependent on Dose, Administration Time, and Mechanical Loading Stimulation
- 2022
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Ingår i: American Journal of Sports Medicine. - : Sage Publications Inc. - 0363-5465 .- 1552-3365. ; 50:5, s. 1306-1316
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Tidskriftsartikel (refereegranskat)abstract
- Background: Corticosteroid treatments such as dexamethasone are commonly used to treat tendinopathy but with mixed outcomes. Although this treatment can cause tendon rupture, it can also stimulate the tendon to heal. However, the mechanisms behind corticosteroid treatment during tendon healing are yet to be understood. Purpose: To comprehend when and how dexamethasone treatment can ameliorate injured tendons by using a rat model of Achilles tendon healing. Study Design: Controlled laboratory study. Methods: An overall 320 rats were used for a sequence of 6 experiments. We investigated whether the drug effect was time-, dose-, and load-dependent. Additionally, morphological data and drug administration routes were examined. Healing tendons were tested mechanically or used for histological examination 12 days after transection. Blood was collected for flow cytometry analysis in 1 experiment. Results: We found that the circadian rhythm and drug injection timing influenced the treatment outcome. Dexamethasone treatment at the right time point (days 7-11) and dose (0.1 mg/kg) significantly improved the material properties of the healing tendon, while the adverse effects were reduced. Local dexamethasone treatment did not lead to increased peak stress, but it triggered systemic granulocytosis and lymphopenia. Mechanical loading (full or moderate) is essential for the positive effects of dexamethasone, as complete unloading leads to the absence of improvements. Conclusion: We conclude that dexamethasone treatment to improve Achilles tendon healing is dose- and time-dependent, and positive effects are perceived even in a partly unloaded condition.
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| 3. |
- Dietrich-Zagonel, Franciele, et al.
(författare)
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Stimulation of Tendon Healing With Delayed Dexamethasone Treatment Is Modified by the Microbiome
- 2018
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Ingår i: American Journal of Sports Medicine. - : Sage Publications. - 0363-5465 .- 1552-3365. ; 46:13, s. 3281-3287
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Tidskriftsartikel (refereegranskat)abstract
- Background:The immune system reflects the microbiome (microbiota). Modulation of the immune system during early tendon remodeling by dexamethasone treatment can improve rat Achilles tendon healing. The authors tested whether changes in the microbiota could influence the effect of dexamethasone treatment.Hypothesis:A change in microbiome would influence the response to dexamethasone on regenerate remodeling, specifically tendon material properties (peak stress).Study Design:Controlled laboratory study.Methods:Specific opportunist and pathogen-free female rats were housed separately (n = 41) or together with specific pathogen-free rats carrying opportunistic microbes such as Staphylococcus aureus (n = 41). After 6 weeks, all co-housed rats appeared healthy but now carried S aureus. Changes in the gut bacterial flora were tested by API and RapID biochemical tests. All rats (clean and contaminated) underwent Achilles tendon transection under aseptic conditions. Flow cytometry was performed 8 days postoperatively on tendon tissue. Sixty rats received subcutaneous dexamethasone or saline injections on days 5 through 9 after transection. The tendons were tested mechanically on day 12. The predetermined primary outcome was the interaction between contamination and dexamethasone regarding peak stress, tested by 2-way analysis of variance.Results:Dexamethasone increased peak stress in all groups but more in contaminated rats (105%) than in clean rats (53%) (interaction, P = .018). A similar interaction was found for an estimate of elastic modulus (P = .021). Furthermore, dexamethasone treatment reduced transverse area but had small effects on peak force and stiffness. In rats treated with saline only, contamination reduced peak stress by 16% (P = .04) and elastic modulus by 35% (P = .004). Contamination led to changes in the gut bacterial flora and higher levels of T cells (CD3+CD4+) in the healing tendon (P < .05).Conclusion:Changes in the microbiome influence tendon healing and enhance the positive effects of dexamethasone treatment during the early remodeling phase of tendon healing.Clinical Relevance:The positive effect of dexamethasone on early tendon remodeling in rats is strikingly strong. If similar effects could be shown in humans, immune modulation by a few days of systemic corticosteroids, or more specific compounds, could open new approaches to rehabilitation after tendon injury.
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| 4. |
- Forslund, Carina, et al.
(författare)
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Improved healing of transected rabbit Achilles tendon after a single injection of cartilage-derived morphogenetic protein-2
- 2003
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Ingår i: American Journal of Sports Medicine. - 0363-5465 .- 1552-3365. ; 31:4, s. 555-559
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Tidskriftsartikel (refereegranskat)abstract
- Background: Achilles tendon ruptures in humans might be treated more efficiently with the help of a growth factor. Cartilage-derived morphogenetic protein-2 has been shown to induce formation of tendon-like tissue. Hypothesis: Cartilage-derived morphogenetic protein-2 has a positive effect on mechanical parameters for tendon healing in a rabbit model with Achilles tendon transection. Study Design: Controlled laboratory study. Methods: The right Achilles tendon of 40 rabbits was transected without tendon suture. Cartilage-derived morphogenetic protein-2 (10 ╡g) or vehicle control (acetate buffer) was injected locally 2 hours postoperatively. All tendons were tested biomechanically at 8 and 14 days, and treated tendons were histologically and radiographically evaluated at 56 days. Results: At 14 days, both failure load and stiffness of treated tendons were increased by 35%. The treated tendons had significantly larger callus size at 8 and 14 days. Histologic and radiographic examination showed no signs of ossification in the treated tendons after 56 days. Conclusions: A single injection of cartilage-derived morphogenetic protein-2 led to a stronger and stiffer tendon callus than that in the controls without inducing bone formation. Clinical Relevance: Similar results from a larger animal model would suggest a possible future use of cartilage-derived morphogenetic protein-2 in the treatment of human Achilles tendon ruptures. ⌐ 2003 American Orthopaedic Society for Sports Medicine.
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| 5. |
- Rendek, Zlatica, et al.
(författare)
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Early Tensile Loading in Nonsurgically Treated Achilles Tendon Ruptures Leads to a Larger Tendon Callus and a Lower Elastic Modulus : A Randomized Controlled Trial
- 2022
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Ingår i: American Journal of Sports Medicine. - : Sage Publications Inc. - 0363-5465 .- 1552-3365. ; 50:12, s. 3286-3298
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Tidskriftsartikel (refereegranskat)abstract
- Background: Early tensile loading improves material properties of healing Achilles tendon ruptures in animal models and in surgically treated human ruptures. However, the effect of such rehabilitation in patients who are nonsurgically treated remains unknown. Hypothesis: In nonsurgically treated Achilles tendon ruptures, early tensile loading would lead to higher elastic modulus 19 weeks after the injury compared with controls. Study Design: Randomized controlled trial; Level of evidence, 2. Methods: Between October 2015 and November 2018, a total of 40 nonsurgically treated patients with acute Achilles tendon rupture were randomized to an early tensile loading (loaded group) or control group. Tantalum bead markers were inserted percutaneously into the tendon stumps 2 weeks after the injury to allow high-precision measurements of callus deformation under mechanical testing. The loaded group used a training pedal twice daily to produce a gradual increase in tensile load during the following 5 weeks. Both groups were allowed full weightbearing in an ankle orthosis and unloaded range of motion exercises. Patients were followed clinically and via roentgen stereophotogrammetric analysis and computed tomography at 7, 19, and 52 weeks after the injury. Results: The mean +/- standard deviation elastic modulus at 19 weeks was 95.6 +/- 38.2 MPa in the loaded group and 108 +/- 45.2 MPa in controls (P = .37). The elastic modulus increased in both groups, although it was lower in the loaded group at all time points. Tendon cross-sectional area increased from 7 weeks to 19 weeks, from 231 +/- 99.5 to 388 +/- 142 mm(2) in the loaded group and from 188 +/- 65.4 to 335 +/- 87.2 mm(2) in controls (P < .001 for the effect of time). Cross-sectional area for the loaded group versus controls at 52 weeks was 302 +/- 62.4 mm(2) versus 252 +/- 49.2 mm(2), respectively (P = .03). Gap elongation was 7.35 +/- 13.9 mm in the loaded group versus 2.86 +/- 5.52 mm in controls (P = .27). Conclusion: Early tensile loading in nonsurgically treated Achilles tendon ruptures did not lead to higher elastic modulus in the healing tendon but altered the structural properties of the tendon via an increased tendon thickness. Registration: NCT0280575 (ClinicalTrials.gov identifier).
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| 6. |
- Schepull, Thorsten, et al.
(författare)
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Autologous Platelets Have No Effect on the Healing of Human Achilles Tendon Ruptures A Randomized Single-Blind Study
- 2011
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Ingår i: AMERICAN JOURNAL OF SPORTS MEDICINE. - : American Journal of Sports Medicine. - 0363-5465 .- 1552-3365. ; 39:1, s. 38-47
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Tidskriftsartikel (refereegranskat)abstract
- Background: Animal studies have shown that local application of platelet-rich plasma (PRP) stimulates tendon repair. Preliminary results from a retrospective case series have shown faster return to sports. Hypothesis: Autologous PRP stimulates healing of acute Achilles tendon ruptures. Study Design: Randomized controlled trial; Level of evidence, 2. Methods: Thirty patients were recruited consecutively. During surgery, tantalum beads were implanted in the Achilles tendon proximal and distal to the rupture. Before skin suture, randomization was performed, and 16 patients were injected with 10 mL PRP (10 times higher platelet concentration than peripheral blood) whereas 14 were not. With 3-dimensional radiographs (roentgen stereophotogrammetric analysis; RSA), the distance between the beads was measured at 7, 19, and 52 weeks while the patient resisted different dorsal flexion moments over the ankle joint, thereby estimating tendon strain per load. An estimate of elasticity modulus was calculated using callus dimensions from computed tomography. At 1 year, functional outcome was evaluated, including the heel raise index and Achilles Tendon Total Rupture Score. The primary effect variables were elasticity modulus at 7 weeks and heel raise index at 1 year. Results: The mechanical variables showed a large degree of variation between patients that could not be explained by measuring error. No significant group differences in elasticity modulus could be shown. There was no significant difference in heel raise index. The Achilles Tendon Total Rupture Score was lower in the PRP group, suggesting a detrimental effect. There was a correlation between the elasticity modulus at 7 and 19 weeks and the heel raise index at 52 weeks. Conclusion: The results suggest that PRP is not useful for treatment of Achilles tendon ruptures. The variation in elasticity modulus provides biologically relevant information, although it is unclear how early biomechanics is connected to late clinical results.
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| 7. |
- Schepull, Thorsten, et al.
(författare)
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Early Controlled Tension Improves the Material Properties of Healing Human Achilles Tendons After Ruptures : A Randomized Trial
- 2013
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Ingår i: American Journal of Sports Medicine. - : SAGE Publications. - 0363-5465 .- 1552-3365. ; 41:11, s. 2550-2557
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Tidskriftsartikel (refereegranskat)abstract
- Background: Weightbearing in a fixed brace after acute Achilles tendon ruptures does not necessarily lead to mechanical tension in the tendon. Early motion has a positive effect on the clinical outcome, but it is not clear if this is because of effects on tendon strength or unspecific effects. The aim of this study was to examine if tensional loading leads to an improvement in the mechanical properties of the healing Achilles tendon. Hypothesis: The elastic modulus of the tendon callus is increased by early tensional loading. Study Design: Randomized controlled trial; Level of evidence, 2. Methods: Thirty-five patients with an acute Achilles tendon rupture were recruited consecutively. They underwent surgery with a single suture and received metal markers in the distal and proximal parts of the tendon. After surgery, the patients were randomized to either cast immobilization for 7 weeks or tensional loading. The latter group wore a cast for 2 weeks and then a removable foam walker boot for 5 weeks. They were instructed to remove the boot twice daily and push a special training pedal to produce a predetermined, gradually increasing tensional load on the healing tendon. At 7, 19, and 52 weeks postoperatively, the patients were investigated with roentgen stereophotogrammetric analysis under different loading conditions and computed tomography. The collected data allowed calculation of the modulus of elasticity. At 52 weeks, the clinical outcome was also examined using the Achilles tendon Total Rupture Score (ATRS) and the heel-raise index. Results: The elastic modulus at 19 and 52 weeks was higher in the tensional loading group. There was no significant difference in the ATRS or heel-raise index at 52 weeks. As in previous studies, there was a significant correlation between the modulus at 7 weeks and the heel-raise index at 52 weeks. There were no signs of tendon elongation. Conclusion: Early tensional loading improves the mechanical properties of the healing Achilles tendon.
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| 8. |
- Virchenko, Olena, 1975-, et al.
(författare)
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Parecoxib impairs early tendon repair but improves later remodeling
- 2004
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Ingår i: American Journal of Sports Medicine. - : SAGE Publications. - 0363-5465 .- 1552-3365. ; 32:7, s. 1743-1747
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cyclooxygenase-2 inhibitors inhibit bone repair. Hypothesis: Cyclooxygenase inhibitors might also have a negative effect on early tendon repair, although a positive effect on late tendon repair previously has been shown. Study Design: Controlled laboratory study. Methods: Achilles tendon transection was performed on 80 rats. Sixty rats were given daily intramuscular injections of either parecoxib (6.4 mg/kg body weight) or saline for the first 5 days after surgery and sacrificed either at 8 or 14 days. The remaining 20 rats were given intramuscular parecoxib or saline injections from day 6 until sacrifice at 14 days. Results: At 8 days, early parecoxib treatment caused a 27% decrease in force at failure (P = .007), a 25% decrease in maximum stress (P = .01), and a 31 % decrease in energy uptake (P = .05). Stiffness and transverse area were not significantly affected. At 14 days, early parecoxib treatment caused a decrease in stiffness (P = .004). In contrast to early treatment, late parecoxib treatment caused a 16% decrease in cross-sectional area (P = .03) and a 29% increase in maximum stress (P = .04). Conclusions: During early tendon repair, a cyclooxygenase-2 inhibitor had a detrimental effect. During remodelling, however, inflammation appears to have a negative influence, and cyclooxygenase-2 inhibitors might be of value. Clinical Relevance: The results suggest that cyclooxygenase-2 inhibitors should be used with care in the early period after tendon injury.
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