Differential MMP 1 and MMP 13 expression in proliferation and ligamentization phases of graft remodeling in anterior cruciate ligament reconstruction.

Purpose: Graft remodeling in anterior cruciate ligament reconstruction (ACLR) demonstrates three distinct phases: necrosis, proliferation and ligamentization. Biological enhancement involves modulating these processes, but the cellular activities related to extracellular matrix remodeling have not been investigated. We hypothesized that changes in matrix metalloproteinases (MMPs) 1 and 13 expression are involved in the transition of proliferation phase to ligamentization phase of graft remodeling.Materials and methods: Thirty-three rats underwent ACLR. Tendon grafts were harvested at week 1 (necrosis), 2 (proliferation), or 12 (ligamentization) post-operation for histological examination (n = 3), or for isolation of graft-derived cells (n = 8) for flow cytometry, proliferation assay, cell invasion assay, measurement of gene expression related to matrix remodeling (Col1A1, Col3A1, MMP1, tissue inhibitor of marix metalloproteinase 1 (TIMP1), and MMP13) and total MMP activities.Results: Increased cellularity in tendon graft was contributed by active cell proliferation and migration at week 2 post-operation, while decreased cellularity were paralleled by increased apoptosis at week 12. All genes measured (Col1A1, Col3A1, MMP1, TIMP1, and MMP13) increased significantly in week 2 cells compared to week 1 cells. MMP1 expression subsided at week 12, while MMP13 expression kept increasing till 12 weeks post-operation. Total MMP activities was 3-fold higher in cultured graft-derived cells from week 2 as compared to cells from week 12. Two distinct processes of graft remodeling were identified, characterized by increased MMP1 expression with cell proliferation and increased MMP13 expression with cell apoptosis.Conclusions: Unfavorable matrix remodeling during the proliferation phase is found with increased MMP1, while remodeling leading to ligamentization is associated with increased MMP13 expression.

A systematic review of inflammatory cells and markers in human tendinopathy.

BACKGROUND: This article systematically reviews the current evidence regarding inflammation in Tendinopathy with the aim to increase understanding of a potential common pathophysiology. METHODS: Following the PRISMA statements, the terms: (tendinopathy OR (tendons AND rupture)) AND (inflammation OR (inflammation AND cells) OR immune system OR inflammation mediators OR bacteria) were used. One thousand four hundred thirty-one articles were identified which was screened down to 53. RESULTS: 39/53 studies mentioned inflammatory cells but had contradicting conclusions. Macrophages were the most common cell type and inflammatory markers were detectable in all the articles which measure them. CONCLUSIONS: The included studies show different conclusions, but this heterogeneity is not unexpected since the clinical criteria of 'tendinopathy' encompass a huge clinical spectrum. Different 'tendinopathy' conditions may have different pathophysiology, and even the same clinical condition may be at different disease stages during sampling, which can alter the histological and biochemical picture. Control specimen sampling was suboptimal since the healthy areas of the pathological-tendon may actually be sub-clinically diseased, as could the contralateral tendon in the same subject. Detection of inflammatory cells is most sensitive using immunohistochemistry targeting the cluster of differentiation markers, especially when compared to the conventional haematoxylin and eosin staining methods. The identified inflammatory cell types favour a chronic inflammatory process; which suggests a persistent stimulus. This means NSAID and glucocorticoids may be useful since they suppress inflammation, but it is noted that they may hinder tendon healing and cause long term problems. This systematic review demonstrates a diversity of data and conclusions in regard to inflammation as part of the pathogenesis of Tendinopathy, ranging from ongoing or chronic inflammation to non-inflammatory degeneration and chronic infection. Whilst various inflammatory markers are present in two thirds of the reviewed articles, the heterogenicity of data and lack of comparable studies means we cannot conclude a common pathophysiology from this systematic review.

Acute and Long-Term Effects of Mechanotherapy on the Outcome After an Achilles Repair: A Prospective Cohort Study With Historical Controls.

OBJECTIVES: To evaluate the effects of vibration on Achilles' tendon microcirculation and characteristics following surgical repair of Achilles' tendon rupture. DESIGN: Cohort study with historical controls. SETTING: A university institute. PARTICIPANTS: Participants (N=32), including 19 (16 men, 3 women; median [range] age: 43.0 [25.0-57.0] years) and 13 (10 men, 3 women; 44.00 [29.0-60.0] years) in the vibration (application to the ball of the foot, 30Hz, 2mm amplitude, 4kg pressure, and self-administration) and control groups, respectively, who underwent unilateral Achilles' tendon repairs were recruited. INTERVENTION: A 4-week vibration intervention in the vibration group. MAIN OUTCOME MEASUREMENTS: The tendon microcirculation was measured after the first session of vibration. The participants were evaluated repeatedly with bilateral follow-up measurements of tendon stiffness, 3 functional outcome tests, and a questionnaire survey. RESULTS: Acute effects of the vibration were observed immediately after the 5-minute vibration (P≤.001). Lower total hemoglobin and oxygen saturation were respectively observed (P=.043) in the repaired legs 3 and 6 months postsurgery in the vibration group as compared with the control group. The vibration group also showed greater tendon stiffness, heel raising height and hopping distance 3 or 6 months postoperation in both the repaired and noninjured legs (all P<.05). The microcirculatory characteristics 2 months postoperation were correlated with the outcomes at 6 months postoperation. CONCLUSIONS: Differences in microcirculatory characteristics and better rehabilitation outcomes were observed in the legs with an Achilles repair that underwent the early vibration intervention.

Neuromechanical characteristics in the knees of patients who had primary conservative treatment for a torn cruciate ligament and reconstruction afterward.

BACKGROUND/PURPOSE: To compare the neuromechanical characteristics and subjective outcomes for knees of patients with a cruciate ligament tear and reconstruction with those for knees of controls at three time intervals, and to determine correlations between the characteristics and subjective outcomes. METHODS: Ten participants with a cruciate ligament tear and at least a 12-week conservative treatment prior to ligament reconstruction were prospectively measured prior to and 3 months and 6 months after surgery. Ten healthy individuals were recruited as controls. Questionnaire surveys regarding the injured knee were conducted, as were bilateral measurements of root mean square electromyography (EMG), the rate of EMG rise, the median frequency in the vastus medialis of the quadriceps muscles and antagonist coactivation from the semitendinosus muscle, and force capacities, including peak torque, rate of force development, and total works of the knee extension. Correlations between the EMG variables (of the vastus medialis and semitendinosus) and the force capacities, and between the EMG variables and the knee injury and osteoarthritis outcome scores (KOOS), and between force capacities and the KOOS were assessed in the participants with a ligament reconstruction. RESULTS: Pre- and postoperative results of EMG variable and force capacities were lower in both knees of the experimental group participants than in the control group participants (all p < 0.05). Correlations between EMG and force capacities, and between these parameters and the KOOS were found. CONCLUSION: There were bilateral neuromechanical defects in the knees of the participants who had undergone conservative treatment as well as reconstruction after a cruciate ligament tear.

Expression of Wnt pathway mediators in metaplasic tissue in animal model and clinical samples of tendinopathy.

OBJECTIVE: Tissue metaplasia is observed in both ossified failed healing animal model and clinical samples of tendinopathy. The Wnt signalling pathway plays a vital role in pathological calcification. We hypothesized that the Wnt signalling pathway might contribute to tissue metaplasia and failed healing in tendinopathy. This study aimed to examine the spatial-temporal expression of Wnt pathway mediators in an ossified failed tendon healing animal model and clinical samples of tendinopathy. The effect of Wnt3a on the osteogenic differentiation of tendon-derived stem cells (TDSCs) was also examined. METHODS: Ossified failed tendon healing was induced by the injection of collagenase into the patellar tendon of rats. At various times the tendons were harvested for immunohistochemical staining of Wnt3a, ß-catenin, Lrp5 and Tcf1. Patellar tendon samples were obtained from 13 patients with patellar tendinopathy (11 unossified and 2 ossified) and 10 controls. Immunohistochemical staining of Wnt3a, ß-catenin, Lrp5 and Tcf1 was similarly performed. Rat patellar TDSCs were treated with Wnt3a. The osteogenic differentiation of TDSCs was examined by ALP activity, alizarin red S staining and mRNA expression of osteogenic markers. RESULTS: There was increased expression of Wnt3a, ß-catenin, Lrp5 and Tcf1 in the healing fibroblast-like cells, chondrocyte-like cells and ossified deposits in the animal model and in some clinical samples of tendinopathy. Wnt3a increased ALP activity, calcium nodule formation and expression of osteogenic markers in TDSCs. CONCLUSION: Activation of the Wnt signalling pathway and its effect on TDSCs might contribute to tissue metaplasia and failed healing in some cases of tendinopathy.

Effect of graft tensioning on mechanical restoration in a rat model of anterior cruciate ligament reconstruction using free tendon graft.

PURPOSE: Initial graft tensioning is important in anterior cruciate ligament reconstruction (ACLR), but its effect on graft healing is still not clear. Since all previous animal studies on graft tensioning used bone-patellar tendon-bone, this study aimed to investigate the effect of initial graft tensioning on ACLR using tendon graft. METHODS: Fifty-five Sprague-Dawley rats underwent ACLR using flexor digitorum longus tendon graft. A constant force of 2 or 4 N was applied during graft fixation. At 0, 2, and 6 weeks, knee samples were harvested (n = 6) for static knee laxity test and graft pull-out test. Histological examination was performed at 2 and 6 weeks post-injury (n = 4). RESULTS: At time zero, knee laxity was restored by ACLR with 2 or 4 N tensioning as compared to ACL-deficient group (p < 0.001), and the 4 N group exhibited a better restoration as compared to 2 N group (p = 0.031). At week 2 post-operation, the 4 N group still exhibited a better restoration in knee laxity (p = 0.001) and knee stiffness (p = 0.002) than the 2 N group; the graft pull-out force (p = 0.032) and stiffness (p = 0.010) were also higher. At week 6 post-operation, there was no significant difference between the 2 and 4 N group in knee laxity and graft pull-out strength. Histological examination showed that the beneficial effect of higher initial graft tension may be contributed by maintenance of graft integrity at mid-substance and reduction in adverse peri-graft bone changes in the femoral tunnel region. CONCLUSIONS: A higher initial graft tension favours the restoration of knee laxity and promotes graft healing in ACLR using free tendon graft in the rat model.

Expression of chondro-osteogenic BMPs in clinical samples of patellar tendinopathy.

PURPOSE: The pathogenesis of patellar tendinopathy remains unclear. Expression of BMP-2/-4/-7 was reported in an ossified failed tendon healing animal model of patellar tendinopathy. This study aimed to investigate the expression of these chondro-osteogenic BMPs in clinical samples of patellar tendinopathy. METHODS: Patellar tendon samples were collected from 16 consecutive patients with patellar tendinopathy and 16 consecutive controls undergoing anterior cruciate ligament reconstruction with bone-patellar tendon-bone autograft in the authors' hospital after getting their consent. The expression of BMP-2/-4/-7 was examined in all samples using immunohistochemistry. Ossification observed in two tendinopathy samples was characterized by histology, alizarin red S staining, alcian blue staining, TRAP staining and immunohistochemical staining of Sox9, osteopontin (OPN) and osteocalcin (OCN). RESULTS: Regions of hypo- and hyper-cellularity and vascularity, with loss of crimp structure of collagen matrix, were observed in patellar tendinopathy samples. Round cells and in some cases, cells with typical chondrocyte phenotype were observed. For the ossified tendinopathy samples with positive alizarin red S staining, OPN-positive and Sox9-positive chondrocyte-like cells in alcian blue-stained extracellular matrix, OCN-positive osteoblast-like cells and TRAP-positive multi-nucleated cells were observed around the ossified deposits. No expression of BMP-2/-4/-7 was observed in healthy patellar tendons. However, the expression of BMP-2/-4/-7 was observed in all patellar tendinopathy samples with or without ossification. CONCLUSIONS: Clinical samples of patellar tendinopathy showed ectopic expression of BMP-2/-4/-7. This was not evident in control samples from healthy patellar tendons. LEVEL OF EVIDENCE: Prognostic studies, Level III.

Microcirculatory Responses to Muscle and Tendon Exercises in Individuals With and Without Type 2 Diabetes Mellitus and the Association Between Microcirculatory and Exercise Performance.

Background: This study aimed to measure and compare (1) the microcirculation and microcirculatory responses of the muscles and tendons at rest and during isometric muscle contractions in participants with and without diabetes mellitus (DM) and (2) to determine correlations between microcirculation and muscle strength. Methods: Sixty-three participants with type 2 DM and 42 physically matched controls were recruited. Baseline measurements of the microcirculation of the rectus femoris (RF) and medial gastrocnemius (MG) muscles and patellar (PT) and Achilles tendons (AT), as well as their microcirculatory changes during maximal isometric exercises, were performed and recorded by using near-infrared spectroscopy and a red laser. Data on various laboratory tests (including glycated hemoglobin, triglyceride, high-density cholesterol), the monofilament test, and the ankle-brachial index were also obtained. Results: The baseline measurements indicated that, compared with the controls, the diabetic participants had lower oxygen saturation (SpO2) in their RF and MG muscles (both P < 0.001), and the total hemoglobin in the diabetic PT and AT was higher (P = 0.001 and P = 0.01). The minimal SpO2 levels in the aforementioned muscles during isometric contractions were lower in the diabetes group than in the control group (P ≤ 0.001). Furthermore, there were correlations between the microcirculatory change of the RF muscle and the knee extension force. Conclusions: This study demonstrated the effects of diabetes on the microcirculation of skeletal muscles and tendons during baseline measurements and responses to maximal isometric exercises. The results support the need for preventive strategies for diabetic muscles to prevent adverse complications when performing resistance training.

Muscular Morphomechanical Characteristics After an Achilles Repair.

BACKGROUND: The purpose of the study was to compare the morphomechanical and functional characteristics during maximal isometric, concentric, and eccentric contractions in the legs of patients that underwent unilateral Achilles tendon repair with those in their noninjured control legs. METHODS: Twenty participants (median age = 38.2 years; range, 21.1-57.3 years) who underwent Achilles repair between 3 and 12 months ago were recruited with the following measures: (1) mechanical stiffness of the aponeurosis and (2) electromyography and medial gastrocnemius fascicle angle and length, standing muscle and tendon length, and height of heel rise with isometric contraction. RESULTS: Compared to the noninjured legs, the repaired legs showed less resting fascicle length, standing muscle length, isometric plantarflexion torque, and heel raise distance ( Ps ranged between .044 and <.001). During the concentric and eccentric phases of the raising and lowering test, the repaired legs demonstrated less fascicle length ( P ≤ .028) but greater tendinous tissue length ( Ps ranged between .084 and <.001) and fascicle angle ( Ps ranged between .247 and .008) and fewer change magnitudes of the fascicle length and tendinous tissue length ( P ≤ .003). The change magnitudes of the morphological characteristics showed correlations with the torque or distance. CONCLUSION: Selecting the appropriate surgical repair and rehabilitation for Achilles tendon ruptures is recommended for restoring the length and mechanical strength of the muscle-tendon unit of plantar-flexion muscles. LEVEL OF EVIDENCE: Level III, comparative study.

Hydrogen peroxide induced tendinopathic changes in a rat model of patellar tendon injury.

Tendinopathy includes cases with chronic tendon pain and spontaneous tendon ruptures, which is putatively resulted from failed tendon healing. Overuse is a major risk factor of tendinopathy, which can impose mechanical and oxidative stress to tendons. Previous studies investigated the influences of mechanical stress, but the direct impact of oxidative stress on tendon healing remains unclear. We hypothesized that imposed oxidative stress can impair tendon healing and lead to tendinopathic changes. Thirty-nine rats were operated for patellar tendon window injury. From weeks 3-5 post-operation, the rats received three weekly subcutaneous injections of saline, 50 or 500 µM H2 O2 (n = 13) over patellar tendon. Gait analysis for pain assessment and 3D ultrasound imaging for detection of tendinopathic changes were performed at pre-injury and 6-week post-operation. At week 6, knee specimens were harvested for histology or tensile mechanical test. Elastic modulus of the healing patellar tendons was significantly lower in 50 µM but not 500 µM H2 O2 group, while ultimate mechanical stress was not significantly different across groups. Similarly, only the 50 µM H2 O2 group exhibited pain-associated gait asymmetry. Significant tendon swelling with increased tendon volume was observed in the 50 µM H2 O2 group. There were hypoechogenic changes in the tendon wound, but there was no significant difference in percentage vascularity. H2 O2 impaired tendon healing and elicited tendinopathic changes, with respect to pain and structural abnormalities. Oxidative stress plays a role in the failed tendon healing of tendinopathies, and H2 O2 -induced failed tendon healing may serve as a good animal model to study tendinopathy. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:3268-3274, 2018.

Anterior internal impingement of the shoulder in rugby players and other overhead athletes.

BACKGROUND/OBJECTIVE: Impingement syndromes are a common cause of shoulder pain in overhead athletes. Anterior internal impingement is a recently suggested mechanism for activity-related pain of the shoulder. Impingement syndromes were initially described to occur due to repetitive or excessive contact between the rotator cuff and other structures in the shoulder. METHODS: This is a retrospective, clinical case study reporting 54 consecutive cases of anterior internal impingement in overhead athletes, of which 28 (51.2%) cases were of rugby players. All had undergone physiotherapy without relief of the symptoms. Of 54, there were 45 male and 9 female patients with an average age of 27 years (range, 17-51). The mean duration from injury to surgery was 40.7 weeks (range, 5-364). Of the 54 patients, 29 (53.7%) were full-time professional and 25 (46.3%) were semiprofessional or recreational athletes. The players associated the onset of pain occurred following an injury in 29/54 cases (53.4%), whereas in the remaining 25 cases (46.2%), a gradual onset of symptoms was described. All 54 patients could demonstrate a "functional impingement sign" in positioning their arm and provoke pain. RESULT: On examination, the examiner could reproduce the same pain in 38/54 (70.3%) patients only. Of the 54 patients, "SLAP tests" including O'Brien's test, Palm up test, and compression rotation test were positive in shoulders of 39 (72.2 %) patients, Jobe's test in 27 (50%), Gerber's lift off test in 6 (11%), and Hawkin's test in 6 (11%) patients. During arthroscopic assessment, impinging flap tears were found in 44 (81.4%) patients from the SLAP, whereas undersurface rotator cuff flap tears were found in 24 (44.4%), flap tears from the anterior or inferior labrum were found in 16 (29.6%), and distal subscapularis flap tears were found in 10 (18.5%) patients. Only in 12/54 patients (22.2%) was an isolated pathology found, in all cases SLAP tears. Treatment included vaporisation and excision of the impinging flaps. In 15/54 (27.7%) patients, repair of an unstable SLAP tear was undertaken using absorbable suture anchors and fibre wires. All athletes returned to their previous activity level within 17.2 weeks (range, 6-36) from surgery and were discharged when they claimed that they were symptom free. CONCLUSION: This series of anterior internal impingement, which we believe is the largest in the literature to date, demonstrates the value of an to assess and successfully treat overhead athletes with anterior impingement syndrome.

Morphomechanical alterations in the medial gastrocnemius muscle in patients with a repaired Achilles tendon: Associations with outcome measures.

BACKGROUND: Functional deficits are found in ankles that have sustained an Achilles rupture. This study sought to evaluate and compare the morphomechanical characteristics of the medial gastrocnemius muscle in the legs of participants within six months of a unilateral Achilles repair to determine any correlations between those characteristics and objective outcomes and self-reported functional levels. METHODS: Fifteen participants were assessed via measurements of muscle morphologies (fascicle length, pennation angle, and muscle thickness) in a resting state, the mechanical properties of the proximal aponeurosis of the medial gastrocnemius muscle, the pennation angle during ramping maximal voluntary isometric contractions (MVIC), the heel raise test, and the Taiwan Chinese version of the Lower Extremity Functional Scale (LEFS-TC) questionnaire. Findings Compared with the non-injured legs, the repaired legs showed a lower muscle fascicle length (mean 4.4 vs. 5.0cm) and thickness (1.7 vs. 1.9cm), lower stiffness of the GM tendon and aponeurosis (174.1 vs. 375.6N/mm), and a greater GM pennation angle (31.2 vs. 28.9°) during 90% MVIC (all p≤0.05). Correlations were found between the morphomechanical results and maximal heel raise heights or the LEFS-TC score, and between the symmetry ratios of the fascicle lengths and the LEFS-TC score. Interpretation There are decreases in fascicle length, muscle thickness and mechanical properties in the medial gastrocnemius muscles of the participants within the first six months after an Achilles repair. These morphomechanical alterations demonstrate associations with functional levels in the lower extremities and indicated the need for early mobilization of the calf muscles after the repair.

Presence of Bacteria in Spontaneous Achilles Tendon Ruptures.

BACKGROUND: The structural pathology of Achilles tendon (AT) ruptures resembles tendinopathy, but the causes remain unknown. Recently, a number of diseases were found to be attributed to bacterial infections, resulting in low-grade inflammation and progressive matrix disturbance. The authors speculate that spontaneous AT ruptures may also be influenced by the presence of bacteria. HYPOTHESIS: Bacteria are present in ruptured ATs but not in healthy tendons. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Patients with spontaneous AT ruptures and patients undergoing anterior cruciate ligament (ACL) reconstruction were recruited for this study. During AT surgical repair, excised tendinopathic tissue was collected, and healthy tendon samples were obtained as controls from hamstring tendon grafts used in ACL reconstruction. Half of every sample was reserved for DNA extraction and the other half for histology. Polymerase chain reaction (PCR) was conducted using 16S rRNA gene universal primers, and the PCR products were sequenced for the identification of bacterial species. A histological examination was performed to compare tendinopathic changes in the case and control samples. RESULTS: Five of 20 AT rupture samples were positive for the presence of bacterial DNA, while none of the 23 hamstring tendon samples were positive. Sterile operating and experimental conditions and tests on samples, controlling for harvesting and processing procedures, ruled out the chance of postoperative bacterial contamination. The species identified predominantly belonged to the Staphylococcus genus. AT rupture samples exhibited histopathological features characteristic of tendinopathy, and most healthy hamstring tendon samples displayed normal tendon features. There were no apparent differences in histopathology between the bacterial DNA-positive and bacterial DNA-negative AT rupture samples. CONCLUSION: The authors have demonstrated the presence of bacterial DNA in ruptured AT samples. It may suggest the potential involvement of bacteria in spontaneous AT ruptures.

Glucocorticoids inhibit tenocyte proliferation and Tendon progenitor cell recruitment.

Corticosteroid injection is commonly used to treat tendon injuries but is often associated with tendon rupture and impaired tendon healing. The effects of dexamethasone on tenocytes have been studied in vitro but only using high concentrations of dexamethasone in monolayer cultures of tenocytes over short periods of time. We have therefore investigated the effects of physiological and pharmacological concentrations of dexamethasone on monolayer cultures of tenocytes over extended time periods. We have also used fibroblastic-colony forming unit cultures to examine the effects of dexamethasone on a progenitor cell population located in tendons. Culturing tenocytes in the presence of dexamethasone for a period of 24 days resulted in a concentration-related decrease in cell number and collagen synthesis as compared to control cultures. This effect was time dependent with cell number in both dexamethasone-treated and control cultures leveling off after 14 days with the control cultures reaching higher cell densities. In contrast in control cultures, collagen accumulation continued to increase until week 4, whereas in the presence of dexamethasone, this tended to level off after 14 days. To study the role of progenitor cell recruitment, the effects of dexamethasone were investigated using the fibroblastic-colony forming unit assay. Treatment with dexamethasone at concentrations of 0.1 nM to 10 microM leads to a progressive reduction in mean colony size as compared to control cultures. Colony number remained constant at concentrations below 10 nM but fell progressively at concentrations above this. In conclusion, dexamethasone reduces both cell number and collagen synthesis in tenocyte cultures in a concentration-dependent manner by both direct effects on tenocyte proliferation and collagen accumulation, and also by modulating the recruitment of tendon progenitor cells.

Critical review on the socio-economic impact of tendinopathy.

There are currently no studies that determine the total burden that tendinopathy places on patients and society. A systematic search was conducted to understand the impact of tendinopathy. It demonstrated that the current prevalence is underestimated, particularly in active populations, such as athletes and workers. Search results demonstrate that due to the high prevalence, impact on patients' daily lives and the economic impact due to work-loss, treatments are significantly higher than currently observed. A well-accepted definition by medical professionals and the public will improve documentation and increase awareness, in order to better tackle the disease burden.

Medial collateral ligament bursitis in a 12-year-old girl.

A 12-year-old female athlete, training for an international career in pentathlon, was referred to our clinic because of 2 years of recurrent localized swelling and activity-related pain in the medial aspect of her right knee, since falling from a horse and hitting her knees on the ground. She had been examined by a number of doctors over this period and treated with physiotherapy without a proper diagnosis and with no improvement. She could run only very limited distances before excruciating pain and swelling, and she had to abandon participation in competitions. During rest, the swelling decreased but never disappeared entirely. Clinical examination revealed minor effusion and localized tenderness on palpation around the medial joint line. Magnetic resonance imaging showed fluid between the medial capsule and medial collateral ligament, but could not identify any connection to the joint. Arthroscopy revealed a cleavage in the posterior medial joint capsule, superior and close to the medial meniscus, that was connected to the medial collateral ligament bursa. The cleavage was simply expanded, which emptied the bursa, followed by compression bandage and ice for 2 weeks. An immediate positive effect was observed and she could run pain free without swelling within 3 weeks of surgery. Six months after surgery, there has been no recurrence. To our knowledge, this is the first time this injury has been described in a child.

Tripeptide-copper complex GHK-Cu (II) transiently improved healing outcome in a rat model of ACL reconstruction.

After anterior cruciate ligament reconstruction (ACLR), the biological healing of the graft is a rate-limiting step which can contribute to graft failure. The tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu(II) (GHK-Cu) is a well-known activator of tissue remodeling. We investigated whether GHK-Cu can improve graft healing following ACLR. Seventy-two rats underwent unilateral ACLR were randomized to saline, 0.3 or 3 mg/ml GHK-Cu groups (n = 24). Post-operational intra-articular injections were given from week 2, once a week, for 4 weeks. Gait analysis was performed pre-injury and at harvesting time. At 6 or 12 weeks post-operation, knee specimens were harvested for knee laxity test, graft pull-out test, and histology. At 6 weeks post-ACLR, GHK-Cu groups resulted in a smaller side-to-side difference in knee laxity as compared to the saline group (p = 0.009), but there was no significant difference at 12 weeks post-operation. The graft complex in the 0.3 mg/ml GHK-Cu group had higher stiffness than saline group at 6 weeks post-operation (p = 0.026), but there was no significant difference in ultimate load, gait parameters, and histological scores among treatment groups. All grafts failed mid-substance during pull-out test. Intra-articular supplementation with a bioactive small molecule GHK-Cu improved graft healing following ACLR in rat, but the beneficial effects could not last as treatment discontinued.

Acute achilles tendon ruptures: incidence of injury and surgery in Sweden between 2001 and 2012.

BACKGROUND: Population-based incidence rates and trends of acute Achilles tendon ruptures are not known. It is also not known whether recent high-quality randomized controlled trials not favoring surgery have had an effect on treatment protocols. PURPOSE: To assess the incidence of acute Achilles tendon ruptures in Sweden and to examine the trends in surgical treatment. STUDY DESIGN: Descriptive epidemiology study. METHODS: We conducted a nationwide registry-based study including all adult (≥18 years of age) inpatient and outpatient hospital visits because of an acute Achilles tendon rupture in Sweden between 2001 and 2012. RESULTS: We identified a total of 27,702 patients (21,979 men, 79%) with acute Achilles tendon ruptures between 2001 and 2012. In 2001, the sex-specific incidence of acute Achilles tendon ruptures was 47.0 (per 100,000 person-years) in men and 12.0 in women. In 2012, the corresponding values were 55.2 in men and 14.7 in women, with an increase of 17% in men and 22% in women. The proportion of surgically treated patients declined from 43% in 2001 to 28% in 2012 in men and from 34% in 2001 to 22% in 2012 in women. CONCLUSION: The incidence of acute Achilles tendon ruptures in Sweden is increasing. The most probable reason for this increase is the rise in the number of older adults participating in high-demand sports. The proportion of surgically treated patients is decreasing most likely because of recent high-quality randomized controlled trials and their meta-analyses supporting similar results between surgical and nonsurgical approaches.

Systematic Review of Biological Modulation of Healing in Anterior Cruciate Ligament Reconstruction.

BACKGROUND: Whether biological modulation is effective to promote healing in anterior cruciate ligament (ACL) reconstruction remains unclear. PURPOSE: To perform a systematic review of both clinical and experimental evidence of preclinical animal studies on biological modulation to promote healing in ACL reconstruction. STUDY DESIGN: Systematic review; Level of evidence, 2. METHODS: A systematic search was performed using the PubMed, Ovid, and Scopus search engines. Inclusion criteria were clinical and animal studies involving subjects with ACL injury with the use of biological modulation to promote healing outcomes. Methodological quality of clinical studies was evaluated using the Critical Appraisal Skill Programme (CASP) appraisal tool, and animal studies were evaluated by a scoring system based on a published checklist of good animal studies. RESULTS: Ten clinical studies and 50 animal studies were included. Twenty-five included studies were regarded as good quality, with a methodological score ≥5. These studies suggested that transforming growth factor-beta (TGF-ß), mesenchymal stem cells, osteogenic factors, and modalities that reduce local inflammation may be beneficial to promote graft healing in ACL reconstruction. CONCLUSION: This systematic review suggests that biological modulation is able to promote healing on top of surgical treatment for ACL injuries. This treatment strategy chiefly works through promotion of healing at the tunnel-graft interface, but the integrity of the intra-articular midsubstance of the graft would be another target for biological modulation.

Incidence of knee dislocation and concomitant vascular injury requiring surgery: a nationwide study.

BACKGROUND: Acute knee (tibiofemoral joint) dislocation is a serious knee injury, although population-based numbers and incidence rates of knee dislocation with or without concomitant vascular injury are unknown. METHODS: The study covered the whole adult population of 4 million persons (aged ≥ 18 years) in Finland during the 11-year period from January 1, 1998, to December 31, 2011. Data on hospitalization caused by acute knee dislocations and concomitant vascular injuries requiring operative treatment were obtained from the nationwide National Hospital Discharge Registry. RESULTS: During the 14-year study period, a total of 837 patients with knee dislocation diagnosis were hospitalized in Finland. The highest incidence rates in men were in persons aged 18 years to 29 years (incidence, 29 per 1 million person-years in 2011), and the incidence decreased by age, while in women, this incidence was rather similar in all age groups. The most common injury mechanism of knee dislocation was low-energy fall at the same level (46%). The median length of hospital stay was 2 days (range, 1-109 days). In 107 cases (13%), knee dislocation required immediate open (69 cases) or closed (38 cases) reduction in the operating room. Popliteal artery injury requiring acute surgical intervention was found in 13 patients (1.6%), and amputation at the level above the tibiofemoral joint was performed for one patient (0.1%). CONCLUSION: This is the first study describing the population-based incidence of acute knee dislocation. Men aged 18 years to 29 years had the highest incidence rates. Half of the injuries were low-energy trauma. Popliteal artery injury requiring surgical intervention was a rare concomitant injury, but when present, the injury required immediate surgical repair to avoid dramatic consequences. LEVEL OF EVIDENCE: Nationwide epidemiologic study, level I.