The tourniquet's effects on skeletal muscle during total knee arthroplasty.

This study investigates the impact of perioperative tourniquet on skeletal muscle cells during total knee arthroplasty (TKA) and its effects on the gene expression of apoptotic, inflammatory, and angiogenic pathways. The randomized controlled trial included 44 patients undergoing TKA. The patients were randomized to undergo surgery with (n = 23) or without (n = 21) tourniquet. The tourniquet was inflated before skin incision and deflated before wound closure in the tourniquet group. Biopsies from the lateral vastus muscle were obtained from both groups before wound closure and 8 weeks after surgery. The messenger ribonucleic acid (mRNA) expression and protein levels of angiopoietin-like 4 (ANGPTL4), Hypoxia-inducible Factor 1α, and Vascular Endothelial Growth Factor Alpha (VEGF-A) in the biopsies were examined by reverse transcription-quantitative polymerase chain reaction and tissue microarray, respectively. Differences in mean values (ΔCt for mRNA expression and staining positivity for protein expression) were compared with t-tests. The apoptotic marker BID and the angiogenic marker VEGF-A were significantly lower in the tourniquet group compared to the control group (p = 0.03, p = 0.047). However, there was a significant upregulation of VEGF-A 8 weeks after surgery in the tourniquet group compared to perioperative biopsies (p = 0.002), indicating persistent changes. A significant upregulation in protein expression of the angiogenic marker ANGPTL4 was found perioperatively in the tourniquet group (p = 0.02). Our results demonstrate that the angiogenic gene expression is significantly altered by the tourniquet, the effects of which might contribute to postoperative interstitial edema, increased pain, and decreased muscle strength. These effects could lead to delayed rehabilitation and ultimately reduced patient satisfaction after TKA.

The incidence of late-detected developmental dysplasia of the hip and its functional outcomes: a 17-year cohort study using selective ultrasound screening.

BACKGROUND AND PURPOSE: We aimed to establish the incidence of late-detected developmental dysplasia of the hip (DDH) with a selective ultrasound (US) examination over 17 years using the femoral head coverage (FHC) as a US measurement. The secondary aim was to establish the everyday function using patient-reported outcome measures (PROMs). PATIENTS AND METHODS: The incidence of late-detected DDH was based on 60,844 children. Patients diagnosed for the first time after 3 months and before the age of 8 years were included. In the second part of the study, consent to participate was mandatory. PROMIS-25 Pediatric, PROMIS-25 Parent, and EQ-5D-5L were used according to the patient's age to assess everyday function. RESULTS: The incidence of late-detected DDH was 0.48/1,000. The median age at diagnosis was 8 months (range 4-41 months), with a tendency to require repeated treatment with open surgery if DDH was diagnosed later. Most children reported no or minor health problems with a mean of 18 years' follow-up. CONCLUSION: We found that selective US examination of the hips by measuring the FHC is a reliable method to examine newborns for DDH resulting in a low incidence of late-detected DDH amounting to 0.48/1,000 newborn children.

Children treated for developmental dysplasia of the hip at birth and with normal acetabular index at 1 year: How many had residual dysplasia at 5 years?

Purpose: The purpose of the study was to assess the effect of further follow-up for children treated for developmental dysplasia of the hip, with normal clinical and radiological findings at 1-year time point. The effect was quantified by the number of hips with a pathologic deterioration up to 5 years. Methods: Among 47,289 children born in Sør-Trøndelag county in Norway between 2003 and 2015, 265 children had developmental dysplasia of the hip. Of these, 164 children (239 hips) treated for developmental dysplasia of the hip with normal clinical findings and normal acetabular index at the 1-year time point were included in the study. The number of hips with pathologic acetabular index at the 5-year time point were reported. The diagnostic uncertainty related to radiological measurements was quantified together with the effect of introducing a second radiographic measurement, the center edge angle. Results: A total of 239 treated hips were normal at the 1-year time point. At 5-year time point, 10 (4.2%) hips had a pathologic acetabular index measurement and none classified to have developmental dysplasia of the hip caused by measurement inaccuracy. Eight (3.3%) hips had pathologic center edge angle measurement. Four hips had both pathologic acetabular index and center edge angle measurements, with three later treated with surgery. The intra- and interobserver repeatability coefficients were within 3.1°-6.6°. Conclusion: The repeatability coefficient of the acetabular index measurements was high and no hips could be classified to have developmental dysplasia of the hip at the 5-year time point when taking this repeatability into account. Hips classified as pathologic combining acetabular index and center edge angle measurements were likely to be treated with surgery for residual dysplasia. We recommend further follow-up for these children. Level of evidence: level II.

Is the French Paradox cementing philosophy superior to the standard cementing? A randomized controlled radiostereometric trial and comparative analysis.

AIMS: Highly polished stems with force-closed design have shown satisfactory clinical results despite being related to relatively high early migration. It has been suggested that the minimal thickness of cement mantles surrounding the femoral stem should be 2 mm to 4 mm to avoid aseptic loosening. The line-to-line cementing technique of the femoral stem, designed to achieve stem press-fit, challenges this opinion. We compared the migration of a highly polished stem with force-closed design by standard and line-to-line cementing to investigate whether differences in early migration of the stems occur in a clinical study. METHODS: In this single-blind, randomized controlled, clinical radiostereometric analysis (RSA) study, the migration pattern of the cemented Corail hip stem was compared between line-to-line and standard cementing in 48 arthroplasties. The primary outcome measure was femoral stem migration in terms of rotation and translation around and along with the X-, Y-, and Z- axes measured using model-based RSA at three, 12, and 24 months. A linear mixed-effects model was used for statistical analysis. RESULTS: Results from mixed model analyses revealed a lower mean retroversion for line-to-line (0.72° (95% confidence interval (CI) 0.38° to 1.07°; p < 0.001), but no significant differences in subsidence between the techniques (-0.15 mm (95% CI -0.53 to 0.227; p = 0.429) at 24 months. Radiolucent lines measuring < 2 mm wide were found in three and five arthroplasties cemented by the standard and line-to-line method, respectively. CONCLUSION: The cemented Corail stem with a force-closed design seems to settle earlier and better with the line-to-line cementing method, although for subsidence the difference was not significant. However, the lower rate of migration into retroversion may reduce the wear and cement deformation, contributing to good long-term fixation and implant survival. Cite this article: Bone Joint J 2022;104-B(1):19-26.

Early migration of a medially stabilized total knee arthroplasty : a radiostereometric analysis study up to two years.

AIMS: Medial pivot (MP) total knee arthroplasties (TKAs) were designed to mimic native knee kinematics with their deep medial congruent fitting of the tibia to the femur almost like a ball-on-socket, and a flat lateral part. GMK Sphere is a novel MP implant. Our primary aim was to study the migration pattern of the tibial tray of this TKA. METHODS: A total of 31 patients were recruited to this single-group radiostereometric analysis (RSA) study and received a medial pivot GMK Sphere TKA. The distributions of male patients versus female patients and right versus left knees were 21:10 and 17:14, respectively. Mean BMI was 29 kg/m2 (95% confidence interval (CI) 27 to 30) and mean age at surgery was 63 years (95% CI 61 to 66). Maximum total point motions (MTPMs), medial, proximal, and anterior translations and transversal, internal, and varus rotations were calculated at three, 12, and 24 months. Patient-reported outcome measure data were also retrieved. RESULTS: MTPMs at three, 12, and 24 months were 1.0 mm (95% CI 0.8 to 1.2), 1.3 mm (95% CI 0.9 to 1.7), and 1.4 mm (0.8 to 2.0), respectively. The Forgotten Joint Score was 79 (95% CI 39 to 95) and Knee Injury and Osteoarthritis Outcome Score obtained at two years was 94 (95% CI 81 to 100), 86 (95% CI 75 to 93), 94 (95% CI 88 to 100), 69 (95% CI 48 to 88), and 81 (95% CI59 to 100) for Pain, Symptoms, Activities of Daily Living, Sport & Recreation, and Quality of Life, respectively. CONCLUSION: In conclusion, we found that the mean increase in MTPM was lower than 0.2 mm between 12 and 24 months and thus apparently stable. Yet the GMK Sphere had higher migration at one and two years than anticipated. Based on current RSA data, we therefore cannot conclude on the long-term performance of the implant, pending further assessment. Cite this article: Bone Jt Open 2021;2(9):737-744.

Does the line-to-line cementing technique of the femoral stem create an adequate cement mantle?

BACKGROUND: The line-to-line cementing technique is proposed to create a press-fit in the femoral canal, which is contrary to modern cementing techniques. The term 'French paradox' has been used to describe the acceptable results associated with this technique. It has been suggested that the quality of the mantle may not be satisfactory, predisposing to early failure and aseptic loosening. METHODS: The line-to-line cementing technique, where the femoral stem was oversized by 1 size compared to the broach, was compared to the standard cementing technique using corresponding sized broaches and stems, in 6 pairs of human cadaver femora with taper-slip design C-stems. Cement pressure was measured, and cement mantle thickness was analysed. A mixed effects model with random intercepts was used to examine the relationship between thickness of mantle and cementing technique and between pressure and cementing technique. RESULTS: Line-to-line cementing results in significantly higher pressurisation for longer periods of time leading to better interdigitation but a thinner mantle in some areas. CONCLUSIONS: The results of this study describe the in-vitro advantages and disadvantages of the line-to-line cementing technique.

Compensation claims after knee cartilage surgery is rare. A registry-based study from Scandinavia from 2010 to 2015.

BACKGROUND: Focal cartilage defects (FCDs) in the knee joint has a high prevalence. A broad range of treatment options exists for symptomatic patients. Knowledge of patient compensation claims following surgical treatment of FCDs is missing. The purpose of this study is to evaluate compensation claims filed to the Scandinavian registries for patient compensation following treatment of FCDs in the knee joint from 2010 to 2015 and identify possible areas of improvement. METHODS: A cross-sectional study design was used to obtain all complaints following surgical treatment of FCDs from the Scandinavian registries from 2010 to 2015. Data such as age, gender, type of treatment, type of complaint, reason of verdict and amount of compensation were collected and systematically analyzed. RESULTS: 103 patients filed a compensation claim. 43 had received debridement (41.7%), 54 microfracture (MF) (52.4%), 3 mosaicplasty (2.9%) and 3 autologous chondrocyte implantation (ACI) (2.9%). Of the 103 claims, 36 were granted (35%). 21 following debridement (58.3%), 13 after MF (36.1%), 1 following mosaicplasty (2.8%) and 1 after ACI (2.8%). The most common reason for complaint was infection (22.1%), of which 89% were granted. The average compensation was €24.457 (range €209 - €458.943). CONCLUSION: Compensation claims following surgical treatment of knee cartilage injuries in Scandinavia are rare. Establishing nationwide cartilage registries can add further knowledge on this troublesome disease.

Decreased Survival of Medial Pivot Designs Compared with Cruciate-retaining Designs in TKA Without Patellar Resurfacing.

BACKGROUND: The medial pivot TKA design was introduced in the 1990s. These are fixed-bearing, medial-conforming implants with virtually no translation in the medial part of the knee, in contrast to the flat lateral part of the insert allowing for translation similar to the native knee during flexion and extension. Most primary TKAs performed in Norway and Australia are cruciate-retaining. All of the medial pivot implants in our study are cruciate-sacrificing but without a post-cam mechanism. The medial pivot implant design was developed to more closely mimic native knee motion, in the hope of improving function, and not primarily as a more constrained knee for difficult cases. In the past 10 to 12 years, a second-generation medial-pivot design has emerged, but there are no larger registry studies on the survival of these implants. Both cruciate-retaining and medial pivot designs are reported in the Australian and Norwegian registries, allowing for large-scale, comparative survivorship studies. QUESTIONS/PURPOSES: (1) Is there any difference in survival between the medial pivot design and the three most commonly used cruciate-retaining TKA designs? (2) Is there any difference in survival among the different medial pivot implant designs? (3) What are the main indications for revision of medial pivot TKAs? METHODS: Registry data from the Australian Orthopaedic Association National Joint Replacement Registry and Norwegian Arthroplasty Register from 2005 until the end of 2017 were used to compare the five different brands of medial pivot TKA designs (total primary TKAs assessed: 6310). In Australia, the study group of medial pivot implants represented 9% (6012 of 72,477) of the total number of cemented/hybrid TKAs without patellar resurfacing; 345 had cementless femoral components. In Norway, the study group represented 1% (298 of 47,820) of the total number of TKAs with cemented tibias without patellar resurfacing; all had cemented femoral components. The control group consisted of the three most commonly used cruciate-retaining TKA designs (n = 70,870; Australia n = 54,554; Norway n = 16,316). All TKAs used a fixed-bearing, cemented tibial component and did not involve patella resurfacing. Kaplan-Meier survival analysis was assessed to estimate survivorship. We compared the groups by calculating the hazard ratios (HR) using Cox regression adjusted for age, gender and preoperative diagnosis with 95% CI. To answer our third question, we calculated the percentage of each revision indication from the total number of revisions in each group, and used a Cox regression analysis to compare revision causes and HRs. Analyses were performed separately by each registry. Accounting for competing risks (Fine and Gray) did not alter our findings []. RESULTS: After controlling for potential confounding variables such as gender, age and preoperative diagnosis, we found an increased revision risk for the medial pivot compared with cruciate-retaining TKA designs in Australia (HR 1.4 [95% CI 1.2 to 1.7]; p < 0.001), but not in Norway (HR 1.5 [95% CI 0.9 to 2.4]; p = 0.1). Two brands of the medial pivot design reported to the AOANJRR showed an increased risk of revision compared with cruciate-retaining designs: the Advance® II MP (HR 1.7 [95% CI 1.2 to 2.6]; p = 0.004) and the GMK® Sphere (HR 2.0 [95% CI 1.5 to 2.6]; p < 0.001), whereas the MRK (HR 0.7 [95% CI 0.4 to 1.5]; p = 0.4), the Evolution® MP (HR 1.4 [95% CI 1.0 to 1.9]; p = 0.06) and the SAIPH® (HR 0.9 [95% CI 0.5 to 1.5]; p = 0.7) showed no difference. The most common reasons for revision of medial pivot implants in Australia were infection (27%), pain alone (19%), patellar erosion (13%), loosening/lysis (12%); in Norway the primary indications were loosening/lysis (28%), instability (28%), malalignment (11%) and pain alone (11%). CONCLUSIONS: The medial pivot TKA design as a group had a higher revision rate than cruciate-retaining fixed-bearing controls in TKA performed without patellar component resurfacing. By brand, the Advance II MP and the GMK Sphere had inferior survivorship, whereas the MRK, the SAIPH and the Evolution MP had no differences in survivorship compared with cruciate-retaining controls. In Australia, TKAs with the medial pivot design without patella resurfacing had a higher rate of revisions for instability, malalignment, and patella erosion. In Norway, there was an increased risk of revision for lysis and loosening compared with the cruciate-retaining design. Several of these implants had short follow-up in this study. Further registry studies with longer follow up are therefore necessary. LEVEL OF EVIDENCE: Level III, therapeutic study.

Evaluating plasma extracellular vesicle microRNAs as possible biomarkers for osteoarthritis.

Objective: MicroRNAs (miRNAs) are being launched as biomarkers for various diseases, but a robust biomarker for articular cartilage pathology has yet to be discovered. Here we evaluate plasma extracellular vesicle (EV) miRNAs as possible biomarkers for osteoarthritis (OA). Method: We compared miRNA levels found in plasma EVs from patients with OA with controls without OA using next generation sequencing (NGS) technique. The patient and control pairs were matched for age, gender and body mass index. Results: 23 pairs of patients and controls were included. Patients with OA differed significantly from controls in both clinical and radiological assessment of OA. We identified 177 canonical miRNAs in plasma EVs, but found no difference in miRNA levels between the two groups. Interestingly, the concentration of each miRNA in plasma EVs showed minimal difference between the participants, suggesting that the release of miRNAs in EVs from cells within the various organs is a tightly controlled process. Conclusion: This is the first study using NGS in search of a miRNA biomarker in plasma EVs in OA. The levels of each plasma EVs miRNA were surprisingly similar for all participants. No plasma EVs miRNA can be used as a biomarker for OA.

Microfracture is more cost-effective than autologous chondrocyte implantation: a review of level 1 and level 2 studies with 5 year follow-up.

PURPOSE: Focal cartilage defects in the knee may have devastating effect on the knee joint, where two of the main surgical treatment options are microfracture and autologous chondrocyte implantation. Comparative studies have failed to establish which method yields the best clinical results. A cost-effectiveness analysis of microfracture and autologous chondrocyte implantation would contribute to the clinical decision process. METHODS: A PubMed search identifying level I and level II studies with 5 year follow-up was performed. With the data from these studies, decision trees with associated service provision and costs connected to the two different techniques were designed. In addition to hospital costs, we included costs connected to physiotherapy following surgery. To paint a broader cost picture, we also included indirect costs to the society due to productivity loss caused by work absence. RESULTS: Four high-quality studies, with a follow-up of 5 years, met the inclusion criteria. A total of 319 patients were included, 170 undergoing microfracture and 149 autologous chondrocyte implantation. The re-operation rate was 23 (13.5%) following microfracture, and 18 (12.1%) for autologous chondrocyte implantation. Both groups achieved substantially better clinical scores at 5 years compared to baseline. Microfracture was more cost-effective when comparing all clinical scores. CONCLUSION: Microfracture is associated with both lower costs and lower cost per point increase in patient reported outcome measures. There is a need of well-designed, high-quality randomized controlled trials before reliable conclusions regarding cost-effectiveness in the long run is possible. LEVEL OF EVIDENCE: III.

Rotator cuff tear degeneration and cell apoptosis in smokers versus nonsmokers.

PURPOSE: The purpose of this study was to assess the effect of smoking on supraspinatus tendon degeneration, including cellular alterations, proliferation, and apoptosis of tendon cells. METHODS: Supraspinatus tendon samples of 10 smokers and 15 nonsmokers with full-thickness tears were compared, focusing on the severity of tendon histopathology including apoptosis (programmed cell death), cellularity, and proliferation. Immunohistochemistry was used to assess the density of apoptotic cells and proliferation. The extent of tendon degeneration was classified according to a revised version of the Bonar tendon histopathology score. RESULTS: The smokers were younger (P = .01). The symptom duration among smokers was longer (P < .05). The supraspinatus tendons from the smokers presented significantly more advanced degenerative changes (Bonar score, 13.5 [interquartile range, 1.4] v 9 [interquartile range, 3]; P < .001). The smokers' tendons showed increased density of apoptotic cells (0.108 [SE, 0.038] v 0.0107 [SE, 0.007]; P = .024) accompanied by reduced tenocyte density (P = .019) and upregulation of proliferative activity (P < .0001). CONCLUSIONS: Smoking is associated with worsened supraspinatus tendon histopathology and increased apoptosis. CLINICAL RELEVANCE: Pronounced degenerative changes, reduced tendon cellularity, and increased apoptosis may indicate reduced tendon healing capacity in smokers.

Greater glycosaminoglycan content in human patellar tendon biopsies is associated with more pain and a lower VISA score.

BACKGROUND: People with patellar tendinopathy experience chronic pain and activity limitation, but a pertinent biochemical marker correlated with these clinical features has not been identified. The Victoria Institute of Sport Assessment (VISA) questionnaire is a condition-specific patient-rated outcome measure. Since the quantity of glycosaminoglycans (GAGs) increases with advancing tendon pathology, we hypothesised that there would be a correlation between the quantity of GAGs in the patellar tendon and the VISA score. METHODS: Tissue biopsies from athletes with chronic patellar tendinopathy (confirmed by clinical examination and MRI) were recruited (n=7), as well as controls with no history of knee pain (n=4). The quantity of sulphated GAGs in the human patellar tendons was determined with a dimethyl methylene blue (DMMB) assay; this method was first validated with rat tendon tissue. The extent and distribution of GAG species and proteoglycans (decorin, versican and aggrecan) in the human tendon biopsies were examined using immunohistochemistry. RESULTS: Greater sulphated GAG content of the patellar tendon was correlated with the greater tendon dysfunction (R(2)=0.798). The quantity of aggrecan in the tendon, a chondroitin sulphate-rich proteoglycan, also increased with advancing tendon pathology. CONCLUSIONS: Increased GAGs in the pathological human patellar tendon are related to a worse clinical status. These findings indicate that the VISA score reflects the extent of tendon tissue pathology.

Lower muscle regenerative potential in full-thickness supraspinatus tears compared to partial-thickness tears.

BACKGROUND AND PURPOSE: Rotator cuff tears are associated with secondary rotator cuff muscle pathology, which is definitive for the prognosis of rotator cuff repair. There is little information regarding the early histological and immunohistochemical nature of these muscle changes in humans. We analyzed muscle biopsies from patients with supraspinatus tendon tears. METHODS: Supraspinatus muscle biopsies were obtained from 24 patients undergoing arthroscopic repair of partial- or full-thickness supraspinatus tendon tears. Tissue was formalin-fixed and processed for histology (for assessment of fatty infiltration and other degenerative changes) or immunohistochemistry (to identify satellite cells (CD56+), proliferating cells (Ki67+), and myofibers containing predominantly type 1 or 2 myosin heavy chain (MHC)). Myofiber diameters and the relative content of MHC1 and MHC2 were determined morphometrically. RESULTS: Degenerative changes were present in both patient groups (partial and full-thickness tears). Patients with full-thickness tears had a reduced density of satellite cells, fewer proliferating cells, atrophy of MHC1+ and MHC2+ myofibers, and reduced MHC1 content. INTERPRETATION: Full-thickness tears show significantly reduced muscle proliferative capacity, myofiber atrophy, and loss of MHC1 content compared to partial-thickness supraspinatus tendon tears.

Increased levels of apoptosis and p53 in partial-thickness supraspinatus tendon tears.

PURPOSE: The role of apoptosis in the progression of rotator cuff tendinopathy remains poorly understood. In particular, the extent of apoptosis in the partially torn supraspinatus tendon has not been well examined. METHODS: Biopsies were obtained from nine partially torn supraspinatus tendons, from the matched intact subscapularis tendons, and from 10 reference subscapularis tendons. Immunohistochemistry was used to assess the density of apoptotic cells (activated caspase-3; Asp175), proliferation (Ki67), and p53 (M7001), a key protein involved in regulating cell death. The Bonar scale was used to evaluate tendon degeneration. RESULTS: The density of apoptotic tendon cells and the density of cells expressing p53 were significantly increased in both the partially torn supraspinatus tendons and in the matched subscapularis tendons, compared with uninjured reference tendons. The Bonar score revealed significant tendon degeneration in the partially torn supraspinatus tendons compared with both matched and reference subscapularis tendons. Tendon cell proliferation was significantly increased in the partially torn supraspinatus tendons compared with reference subscapularis tendons. CONCLUSIONS: Partial-thickness tears of the supraspinatus tendon demonstrated an increased density of apoptotic, p53+ tendon cells. The fact that apoptosis was accompanied by increased tendon cell proliferation suggests that apoptosis may be related to an ongoing injury-repair process. Increased tenocyte apoptosis may be a relatively early feature in rotator cuff tendinopathy and could represent a possible target for therapeutic intervention.

Glutamate receptors in tendinopathic patients.

Tendinopathy, pain, and degeneration, may be related to the up-regulation of substance P (SP) and its activation of glutamate receptors. We hypothesized that the pathogenesis of tendinopathy involves N-methyl-D-aspartate receptor type 1 (NMDAR1) activation (phosphorylated NMDAR1; phospho-NMDAR1) co-existing with SP. Moreover, we examined the presence of metabotropic receptors that increase (mGluR1 and mGluR5) or decrease (mGluR6 and mGluR7) NMDAR1 excitability. Biopsies from patients with patellar tendinopathy (n = 10) and from controls (n = 8) were immunohistochemically analyzed according to the occurrence and tissue distribution of NMDAR1, phosho-NMDAR1, mGluR (1, 5-7), and SP. The biopsies were immunohistochemically single- and double-stained and semi-quantitatively assessed. Tendinopathic biopsies exhibited increased occurrence of NMDAR1, phospho-NMDAR1, SP, and mGluR5, while mGluR6-7 were not increased and mGluR1 was not found. The occurrence of NMDAR1 and SP correlated in tendinopathy (r(2) = 0.54, p = 0.03), but not in the controls (r(2) = 0.11, p = 0.4). Co-localization of SP and phospho-NMDAR1 within the tendon proper was only found in tendinopathy, localized on hypertrophic tenocytes, blood vessels, and penetrating free-nerve fibres. Up-regulation and activation of the glutamate receptor, phospho-NMDAR1, suggests a role in the pathophysiology of tendinopathy. Increased NMDAR1 excitability may be related to increased SP and mGluR5. The unique co-existence of SP and phospho-NMDAR1 in tendinopathy presumably reflects a tissue proliferative and nociceptive role.

Tenocyte apoptosis in the torn rotator cuff: a primary or secondary pathological event?

Little information exists on the contribution of apoptosis to pathological tendon changes in rotator cuff tendinopathy. The purpose of this study was to quantitate the rate of tenocyte apoptosis in torn supraspinatus tendons and in the matched intact subscapularis and to examine the potential relation between apoptotic index (AI) and tendon pathology. In addition, the authors examined tenocyte density, proliferation rate and p53 gene expression patterns to gain further insight into relevant pathological mechanisms in the torn suprapinatus. 15 torn supraspinatus tendons with matched intact subscapularis tendon samples and 10 reference subscapularis samples were collected. Immunohistochemistry was used to define the AI (F7-26), proliferation rate (Ki67) and presence of p53 (M7001). Tendon degeneration was evaluated according to the Bonar scale. Expression of p53 and relevant genes (n=84) was examined on a subset of samples using microfluidic arrays. The AI was significantly increased in torn supraspinatus tendon and matched subscapularis tendon (R² =0.5742; p=0.0005). Cell density and proliferation rate were also elevated in torn supraspinatus compared with reference subscapularis tendons (p<0.05). A significant increase in p53 occurred specifically in torn supraspinatus tendon (p<0.05), and several genes encoding p53-inhibiting proteins were downregulated in association, including HDAC1 (p<0.05), MDM4 (p<0.001) and PPM1D (p<0.05). Our results suggest that tenocyte apoptosis results from more than one mechanism in the injured rotator cuff, including both intrinsic factors related specifically to the torn supraspinatus tendon, as well as a more generalised effect on the adjacent subscapularis tendon.

VEGF expression in patellar tendinopathy: a preliminary study.

Vascular function and angiogenesis are regulated by vascular endothelial growth factor-A (VEGF). The purpose of this preliminary study was to address the following questions: Is VEGF expression in the patellar tendon more prevalent in patients with patellar tendinopathy than in individuals with normal, pain-free patellar tendons? Which cell populations express VEGF in normal and tendinopathic tendon? Is there a difference in symptom duration between VEGF+ and VEGF- tendons? We collected patellar tendon tissue from 22 patients undergoing open débridement of the patellar tendon and from 10 patients undergoing intramedullary nailing of the tibia. VEGF expression was assessed immunohistochemically. Relevant inflammatory and repair cell types were immunolabeled. VEGF expression was absent from control tendons, but was present in a subset of patients with histopathological evidence of angiofibroblastic tendinosis. VEGF was expressed in the intimal layer of tendon vessels, but was absent in other cell types. Patients demonstrating VEGF expression in the patellar tendon had a shorter symptom duration (12 +/- 7.8 months) than patients with no detectable VEGF (32.8 +/- 23.5 months). VEGF may contribute to the vascular hyperplasia that is a cardinal feature of symptomatic tendinosis, particularly in cases with more recent onset.

Excessive apoptosis in patellar tendinopathy in athletes.

BACKGROUND: The pathogenesis of tendon overuse injuries is poorly understood. The histopathology underlying tendinopathy at various anatomical locations is similar and may reflect a common pathologic process. HYPOTHESIS: Apoptosis contributes to the pathophysiology in patellar tendinopathy. STUDY DESIGN: Case control study; Level of evidence, 3. METHODS: We compared biopsy specimens from the patellar tendon in patients with patellar tendinopathy diagnosed clinically and with typical magnetic resonance image findings with biopsy specimens from a control group without any previous or current knee complaints to suggest patellar tendinopathy. The presence of apoptosis was examined with immunohistochemical methods using a polyclonal antibody recognizing active caspase-3, confirmed by labeling DNA strand breaks (F7-26 antibody) and nuclear morphology (fragmentation and condensation). RESULTS: The number of apoptotic cells per unit area (4.5 mm(2)) was 0.91 +/- 0.81 (SD) in tendinopathic samples and 0.21 +/- 0.21 in controls (P = .026). Although the tendinopathic samples displayed increased cellularity (average 162.5 nuclei/mm(2) vs 98.9 nuclei/mm(2)), the apoptotic index was higher (0.42% vs 0.17%, P = .014). CONCLUSION: Increased apoptotic cell death is a feature of patellar tendinosis. The role of apoptosis within the broader framework and time course of tendon overuse injury remains to be established.

Pronociceptive and antinociceptive neuromediators in patellar tendinopathy.

BACKGROUND: The occurrence of nerve ingrowth and its relation to chronic tendon pain (tendinopathy) are still largely unknown. In healthy tendons, the innervation is confined to the paratenon, whereas the tendon proper is devoid of nerve fibers. In this study on the pathogenesis of tendinopathy, the authors examined sensory and sympathetic nerve fiber occurrence in the patellar tendon. HYPOTHESIS: Nerve ingrowth and altered expression of sensory and sympathetic neuromediators play a major role in the pathophysiology of pain in patellar tendinopathy. STUDY DESIGN: Case control study; Level of evidence, 3. METHODS: Biopsies from the patellar tendon in patients with patellar tendinopathy (n = 10) were compared with biopsies from a control group (n = 10) without any previous or current knee symptoms compatible with patellar tendinopathy. The biopsies were stained immunohistochemically for sensory and autonomic nerve markers. The biopsies from the 2 groups were compared using subjective and semiquantitative methods. RESULTS: Chronic painful patellar tendons exhibited increased occurrence of sprouting nonvascular sensory, substance P-positive nerve fibers and a decreased occurrence of vascular sympathetic nerve fibers, positive to tyroxin hydroxylase, a marker for noradrenaline. CONCLUSION: The altered sensory-sympathetic innervation suggests a role in the pathophysiology of tendinopathy. Ingrowth of sprouting substance P fibers presumably reflects a nociceptive and maybe a proliferative role, possibly as reactions to repeated microtraumata, whereas the decreased occurrence of tyroxin hydroxylase may represent a reduced antinociceptive role. These findings could be used to develop targeted pharmacotherapy for the specific treatment of tendinopathy.

Prevalence of jumper's knee among elite athletes from different sports: a cross-sectional study.

BACKGROUND: The prevalence of jumper's knee across different sports has not been examined, and it is not known if there is a gender difference. Data from surgical case series indicate that there may be a high prevalence in sports with high speed and power demands. HYPOTHESIS: The aim of this study was to estimate the prevalence of jumper's knee in different sports among female and male athletes and to correlate the prevalence to the loading characteristics of the extensor mechanism in these sports. STUDY DESIGN: Cross-sectional study; Level of evidence, 4. METHODS: The authors examined approximately 50 Norwegian male and female athletes at the national elite level from each of the following 9 sports: athletics (male athletes: high jump, 100- and 200-m sprint), basketball (male athletes), ice hockey (male athletes), volleyball (male athletes), orienteering (male athletes), road cycling (male athletes), soccer (male and female athletes), team handball (male and female athletes), and wrestling (male athletes). The examination included an interview on individual characteristics (weight, age, height, and training background), a clinical examination, and self-recorded Victorian Institute of Sport Assessment score from 0 (worst) to 100 (best). RESULTS: The overall prevalence of current jumper's knee was 14.2% (87 of 613 athletes), with a significant difference between sports with different performance characteristics (range, 0%-45%). In addition, 51 athletes (8%) reported previous symptoms. The prevalence of current symptoms was highest in volleyball (44.6%+/-6.6%) and basketball (31.9%+/-6.8%), whereas there were no cases in cycling or orienteering. The prevalence of current jumper's knee was lower among women (5.6%+/-2.2%) compared with men (13.5%+/-3.0%; chi2 test, P=.042). The duration of symptoms among athletes with current jumper's knee (n=87) was 32+/-25 (standard deviation) months, with a Victorian Institute of Sport Assessment score of 64+/-19. CONCLUSION: The prevalence of jumper's knee is high in sports characterized by high demands on speed and power for the leg extensors. The symptoms are often serious, resulting in long-standing impairment of athletic performance.