Sonographic pathoanatomy of greater trochanteric pain syndrome.

AIMS: To identify and highlight pertinent US features that could serve as imaging biomarkers to describe different patient phenotypes, within Great Trochanteric Pain Syndrome (GTPS) clinical diagnosis. MATERIALS AND METHODS: Using ultrasound we evaluated eighty-eight clinically diagnosed patients with GTPS, for tendon matrix changes and calcium deposits in the gluteus medius (superoposterior and lateral aspects) and in the gluteus minimus. Peritrochanteric examination included fascia lata, trochanteric bursa, cortical irregularities and the presence of enthesophytes. The association of pathological changes with pain and functionality was evaluated using multivariate regression models. RESULTS: Out of the 88 patients, 86 examinations (97.7%) detected gluteus medius tendinopathy, and 54 patients (61.4%) had gluteus minimus tendinopathy in addition. Calcium deposits were present in 97.7% of patients, associated with tenderness (p = 0.009), and most often located in the gluteus medius rather than in the gluteus minimus (p = 0.014); calcifications were associated with tendon thickness (p = 0.042), hypoechogenicity (p = 0.005) and the presence of partial tears (p = 0.030). Bursa swelling occurred in 36 patients (40.9%); multivariate regression models predicted less pain in patients with bursa distension (p = 0.008) and dysfunction in patients with gluteal muscle atrophy (p = 0.001) and loss of fibrillar pattern in the gluteus medius (p = 0.002). CONCLUSION: GTPS involves both degenerative calcifying gluteal tendinopathy and alterations in the peritrochanteric space associated with physical function and pain. The severity of GTPS can be assessed using ultrasound imaging biomarkers.

Biological Targets of Multimolecular Therapies in Middle-Age Osteoarthritis.

Knee osteoarthritis (OA) is a common condition, prevalent in middle-agedness, associated with chronic pain and impaired quality of life. Two interrelated biological processes fuel early OA progression: inflammation and structural tissues catabolism. Procatabolic and proinflammatory mediators are interconnected and form part of a self-perpetuating loop. They leverage OA research complexity because of the impossibility to discern certain spatiotemporal tissues' changes from others. Both are shared targets of versatile regenerative multimolecular therapies. In particular, platelet-rich plasma can interfere with inflammation and inflammatory pain. The therapeutic approach is to alter the vicious inflammatory loop by modifying the molecular composition of the synovial fluid, thereby paracrine cellular cross talk. Intra-articular injections of platelet-rich plasma can provide key factors balancing proinflammatory and anti-inflammatory factors, targeting macrophage dysfunction and modulating immune mechanisms within the knee.

Unraveling the Signaling Secretome of Platelet-Rich Plasma: Towards a Better Understanding of Its Therapeutic Potential in Knee Osteoarthritis.

Platelets and their secretory products play an important role in determining the balance between tissue repair and tissue damage. To obtain novel insights into the molecular composition of platelet-rich plasma (PRP) and contextualize them in knee osteoarthritis (OA), two different plasma formulations, namely PRP and platelet-poor plasma (PPP), were prepared from six healthy donors following a biobank-automated protocol. Inter-donor differences were analyzed, and pools were created before performing multiplexing protein arrays. In addition, PRP and PPP were prepared from six patients following our in-house protocols. Supernatants from PRP and PPP were harvested one hour after calcium chloride activation. Multiplexing protein arrays were performed in parallel for all plasma formulations. Results were normalized to fold change in relation to PPP and examined using Ingenuity Pathway Analysis Software. Bioinformatic predictions showed that PRPs constitute a signaling system with interrelated networks of inflammatory and angiogenic proteins, including but not limited to interleukin-6 and -8 (IL-6, IL-8), insulin like growth factor 1 (IGF-1), transforming growth factor beta, (TGF-b), and vascular endothelial growth factor (VEGF) signaling, underlying biological actions. Predictions of canonical systems activated with PRP molecules include various inflammatory pathways, including high-mobility group box protein (HMGB1) and interleukin 17 (IL-17) signaling, neuroinflammation, and nuclear factor-kappa b (NF-κB) pathways. Eventually, according to these predictions and OA evolving knowledge, selected PRP formulations should be tailored to modulate different inflammatory phenotypes, i.e., meta-inflammation, inflame-aging or posttraumatic inflammatory osteoarthritis. However, further research to discriminate the peculiarities of autologous versus allogeneic formulations and their effects on the various OA inflammatory phenotypes is needed to foster PRPs.

Moving toward targeting the right phenotype with the right platelet-rich plasma (PRP) formulation for knee osteoarthritis.

Intra-articular injections of platelet-rich plasma (PRP) and other novel blood-derived products developed specifically for osteoarthritis (OA) can provide pain relief and potential benefits in disease progression. Meta-analyses show the clinical superiority of PRP compared with other intra-articular injections, but results are modest and the effect sizes are small. PRP injections in knee OA are performed indiscriminately, but the clinical response varies enormously between patients because of an array of mixed OA phenotypes. Subgroup analyses are scarce; some studies stratify patients according to radiographic severity and found better results in early OA, without consensus for more advanced stages of the condition. Parallel identification of soluble and imaging biomarkers is essential to personalise and leverage PRP therapies. The inflammatory phenotype is most interesting from the PRP perspective because PRPs modulate inflammation by releasing a large pool of chemokines and cytokines, which interact with synovial fibroblasts and macrophages; in addition, they can modulate the innate immune response. No soluble biomarkers have been discovered that have implications for OA research and PRP interventions. Clinical examination of patients based on their inflammatory phenotype and imaging identification of pain sources and structural alterations could help discern who will respond to PRP. Synovial inflammation and bone marrow lesions are sources of pain, and intra-articular injections of PRP combined with subchondral bone injection can enhance clinical outcomes. Further refining ultrasound phenotypes may aid in personalising PRP therapies. Intra-articular delivery combined with injections in altered ligamentous structures, medial and coronal ligaments or premeniscal pes anserinus showed positive clinical outcomes. Although the evidence supporting these approaches are weak, they merit further consideration to refine PRP protocols and target the right OA phenotypes.

Platelet-rich plasma versus lidocaine as tenotomy adjuvants in people with elbow epicondylopathy: a randomized controlled trial.

OBJECTIVES: To determine the efficacy of platelet-rich plasma (PRP) compared to lidocaine as a tenotomy adjuvant for people with elbow tendinopathy. METHODS: Our study was a parallel-group, double-blind, randomized trial involving 71 patients with recalcitrant elbow tendinopathy who received two sessions of ultrasound-guided tenotomy with either PRP or lidocaine in a tertiary public hospital. The primary end point was the percentage of patients with an improvement exceeding 25% reduction in disability (Spanish version of the Disabilities of the Arm, Shoulder and Hand questionnaires-DASH-E) at 6 and 12 months; the secondary outcome was the percentage of patients exceeding 25% reduction in pain (VAS-P). RESULTS: There was no evidence of significant differences in the proportion of patients who experienced clinically relevant improvements. After 6 months, 18 patients (78.59%) in the lidocaine group and 19 patients (73.08%) in the PRP group showed improved function above 25% (unadjusted odds ratio, 0.90; 95% confidence interval [CI], 0.90 (0.17 to 4.60)); 21 patients (72.21%) in the lidocaine group versus 22 patients (84.62%) in the PRP group achieved more than 25% pain reduction (unadjusted odds ratio, 0.48; 95% CI, 0.10 to 2.37). After 12 months, 17 patients (70.83%) in the lidocaine group versus 19 patients (76%) in the PRP group had improved function (unadjusted odds ratio, 0.71; 95% CI, 0.13 to 3.84), and 19 patients (76%) in the lidocaine group versus 20 patients (90.91%) in the PRP group had improved pain above 25% (unadjusted odds ratio, 0.35; 95% CI, 0.06 to 2.51). Hypercholesterolemia and baseline vascularization influenced outcomes. There were no differences between groups in the adjusted odds ratios. CONCLUSION: PRP results in similar improvements to those obtained with lidocaine. Selecting patients according to their pretreatment status can improve treatment efficacy. TRIAL REGISTRATION: NCT01945528 , EudraCT 2013-000478-32. Registered 18 August 2013, enrolment of the first participant 10 March 2014.

Needle tenotomy with PRP versus lidocaine in epicondylopathy: clinical and ultrasonographic outcomes over twenty months.

OBJECTIVE: To investigate whether pathological changes in elbow epicondylopathy, as assessed by conventional ultrasonography and clinical outcomes, could be modified following tenotomy with platelet-rich plasma (PRP) versus tenotomy with lidocaine. METHODS: This prospective sub-study was part of a patient- and assessor-blinded, superiority-type, randomized, lidocaine-controlled trial that was performed in a tertiary hospital to assess the effectiveness of PRP versus lidocaine as tenotomy adjuvants in patients with epicondylopathy. Patients were followed after two sessions of tenotomy with either PRP or lidocaine adjuvants (4 ml) within a 2-week interval. Tendon thickness, echotexture, and neovascularization were assessed as secondary outcome measurements at baseline and at 3, 6, 12, and 20 months after treatment, and correlations with clinical outcomes were examined. RESULTS: Twenty months after treatment, tenotomy induced changes in tendon structure, thickness (± = 0.0006), vascularity (p < 0.0001), and echotexture (p < 0.0001). In Disabilities of the Arm, Shoulder and Hand (DASH-E) and pain (VAS-P) scores, 80.85% and 90.91% of patients showed a meaningful clinical improvement, respectively, without differences between PRP and lidocaine. There were significant differences in between-group changes in vascularity over time, p = 0.037 and p = 0.049 in the unadjusted and adjusted models, respectively. There was no relationship between pain or function and sonographic entities at the various time points. CONCLUSIONS: Two successive needle tenotomies induced structural changes in recalcitrant epicondylopathy, with PRP displaying more vascularization and increased thickness over time compared to lidocaine. PRP compared with lidocaine did not result in improved function or decreased pain over 20 months.

Predictors of Outcome Following Tenotomy in Patients with Recalcitrant Epicondylopathy.

BACKGROUND: Elbow tendinopathies are associated with tenderness, pain, and functional disability with ensuing socioeconomic costs. There is lack of consensus regarding the best treatment for patients recalcitrant to first-line conservative treatments. Percutaneous needle tenotomy is considered a regenerative approach that injures the tendon to elicit a healing response. OBJECTIVE: To investigate whether demographic characteristics, clinical factors, baseline sonographic entities, or their interactions are related to the likelihood of responding positively to needle tenotomy over a 1-year follow-up period. DESIGN: Prospective case series. SETTING: Tertiary institutional hospital. PARTICIPANTS: Patients with elbow tendinopathy for whom conservative treatments had failed and who had persistent symptoms lasting for at least 3 months. METHODS: Patients underwent needle tenotomy with or without PRP followed by a lighter needle tenotomy within a 2-week interval as part of treatment. MAIN OUTCOME MEASUREMENTS: Disabilities of the Arm, Shoulder and Hand (DASH) and Visual Analogue Scale for pain (VAS-P) scores were assessed before intervention (baseline) and at 6 weeks and 3, 6, and 12 months after intervention. A generalized linear mixed effects model was created to examine whether injectate type, clinical, demographic, or pretreatment sonographic entities or their interactions influenced clinical outcomes. RESULTS: The authors analyzed 74 elbows (71 patients). At baseline, analyzed patients (mean age: 49.48 years; 51.35% women) scored 43.30 and 5.83 on the DASH and VAS-P, respectively. Pretreatment tendon vascularization was a predictor of pain (P = .011) and DASH score changes (P = .019). The linear mixed effect model revealed that male gender and hypercholesterolemia were associated with enhanced functional recovery, (P = .020 and P < .001, respectively). Moreover, the interactions between pretreatment vascular status (P = .039), echotexture (P = .037) and enthesophytes (P = .028) influenced the temporal pattern of functional recovery after needle tenotomy. CONCLUSIONS: Baseline patient characteristics, such as gender and hypercholesterolemia, along with ultrasound features may be predictive of outcomes following needle tenotomy for elbow tendinopathy. LEVEL OF EVIDENCE: IV (NCT01945528).

Percutaneous needling of Morton's complex: a technical note.

BACKGROUND: the Morton's complex, i.e. fibrotic mass enfolding the medial plantar nerve, the bursa and the interdigital transverse ligament in the web space, is a common cause of pain and functional disability. Conservative and operative treatments are investigated but currently the best approach to treat the Morton's complex is unknown. METHODS: we describe a non-invasive, straight forward intervention consisting on multiple percutaneous punctures, shearing the fibrotic tissue in lateromedial and anteroposterior directions. The goal is to break up fibrosis occupying the intermetatarsal space thus releasing the affected nerve from the adjacent structures, there by stimulating tissue remodelling. RESULTS: slow tissue remodelling occurs following sequential fibrosis cleavage through multiple needling. Needling of the intermetatarsal fibrosis is performed every eight weeks until pain resolution. Echographic changes are associated to pain reduction as measured by Visual Analogue Score (VAS). CONCLUSION: we present an original idea that may improve Morton's management. Upcoming prospective clinical studies have to demonstrate the symptomatic benefits and the usefulness of this novel echographic intervention.

Platelet-rich plasma (PRP) in chronic epicondylitis: study protocol for a randomized controlled trial.

BACKGROUND: Tendinopathy is a difficult problem to manage and can result in significant patient morbidity. Currently, the clinical use of platelet-rich plasma (PRP) in painful tendons is widespread but its efficacy remains controversial. METHODS/DESIGN: This study is a single-center, randomized double-blind controlled trial. Eighty patients will be allocated to have ultrasound (US)-guided needling combined with a leukocyte-depleted (that is, pure) PRP or lidocaine each alternate week for a total of two interventions. Outcome data will be collected before intervention, and at 6 weeks, 3, 6, and 12 months after intervention. MAIN OUTCOME MEASURE: Changes in pain and activity levels, as assessed by Disabilities of the Arm, Shoulder and Hand (DASH-E, Spanish version) score, at 6 months. We will compare the percentage of patients in each group that achieve a successful treatment defined as a reduction of at least 25% in the DASH-E score. Secondary outcome measures include changes in DASH-E at 3 and 12 months, changes in pain as assessed by the visual analogue scale (VAS) at the 6-week, 3-, 6-, and 12-month follow-up, changes in sonographic features and neovascularity, and percentage of patients in each group with adverse reactions at 3, 6, and 12 months. DISCUSSION: The results of this study will provide insights into the effect of pure PRP in tendon and may contribute to identifying the best protocol for PRP application in tendinopathies. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01945528.