Elevated fluid and glycosaminoglycan content in the Achilles tendon contribute to higher intratendinous pressures:Implications for Achilles tendinopathy

Background:Tendinopathy alters the compositional properties of the Achilles tendon by increasing fluid and glycosaminoglycan content.It has been speculated that these changes may affect intratendinous pressure,but the extent of this relationship remains unclear.Therefore,we aimed to investigate the impact of elevated fluid and glycosaminoglycan content on Achilles tendon intratendinous pressure and to determine whether hyaluronidase(HYAL) therapy can intervene in this potential relationship.Methods:Twenty paired fresh-frozen cadaveric Achilles tendons were mounted in a tensile-testing machine and loaded up to 5% strain.Intratendinous resting(at 0% strain) and dynamic pressure(at 5% strain) were assessed using the microcapillary infusion technique.First,intratendinous pressure was measured under native conditions before and after infusion of 2 mL physiological saline.Next,80 mg of glycosaminoglycans were administered bilaterally to the paired tendons.The right tendons were additionally treated with 1500 units of HYAL.Finally,both groups were retested,and the glycosaminoglycan content was analyzed.Results:It was found that both elevated fluid and glycosaminoglycan content resulted in higher intratendinous resting and dynamic pressures(p <0.001).HYAL treatment induced a 2.3-fold reduction in glycosaminoglycan content(p=0.002) and restored intratendinous pressures.Conclusion:The results of this study demonstrated that elevated fluid and glycosaminoglycan content in Achilles tendinopathy contribute to increased intratendinous re sting and dynamic pressures,which can be explained by the associated increased volume and reduced permeability of the tendon matrix,respectively.HYAL degrades glycosaminoglycans sufficiently to lower intratendinous pressures and may,therefore,serve as a promising treatment.

Endoscopic debridement for non-insertional Achilles tendinopathy with and without platelet-rich plasma

Background:When non-operative management fails to improve symptoms in patients with non-insertional Achilles tendinopathy,surgery may be required.Various open and endoscopic techniques have been proposed,and platelet-rich plasma(PRP)injections have been proposed as an adjunct to aid tendon healing.Methods:Thirty-six patients with mid-portion Achilles tendinopathy were randomized to undergo endoscopic debridement alone(n=19)or in combination with intraoperative PRP application(n=17).Clinical outcome measures included the Visual Analogue Scale for pain,function,and satisfaction and the Victorian Institute of Sports Assessment-Achilles(VISA-A)questionnaire.Patients were followed-up at 6 weeks,3months,6 months,and 12 months after surgery.An MRI examination at 3 and 12 months was used to assess signal alterations within the tendon.Results:Both groups showed significant clinical improvement(p<0.05)after surgery,with no difference between the 2 groups.Tendon diameter increased at 3 months and decreased at 12 months.The tendinopathy area increased at 3 months and decreased at 12 months below baseline level in both groups.There was no significant difference between the groups regarding the MRI parameters.Nodular thickening and MRIdetected signal alteration persisted after surgery,with no association between imaging and clinical outcome.Five minor complications were reported:2 in the PRP group and 3 in the control group.Conclusion:Endoscopic debridement of the Achilles tendon improved clinical outcomes in patients with mid-portion tendinopathy.The addition of PRP did not improve outcomes compared to debridement alone.MRI parameters showed no association with clinical outcomes.

Role of platelet-rich plasma in the treatment of rotator cuff tendinopathy

Shoulder pain is a common musculoskeletal complaint,and rotator cuff(RC)pathologies are one of the main causes.The RC undergoes various tendinopathic and avascular changes during the aging process.Other degenerative changes affecting its healing potential make it an appealing target for biological agents.Platelet-rich plasma(PRP)has demonstrated the potential to deliver a high concentration of several growth factors and anti-inflammatory mediators,and its clinical use is mainly supported by experiments that demonstrated its positive effect on muscle,ligaments,and tendinous cells.This review aimed to specify the role of PRP and its future applications in RC tendinopathies based on the current clinical evidence.Due to the different characteristics and conflicting outcomes,clinicians should use PRP with moderate expectations until more consistent evidence is available.However,it is reasonable to consider PRP in patients with contraindications to corticosteroid injections or those with risk factors for inadequate healing.Its autologous origin makes it a safe treatment,and its characteristics make it a promising option for treating RC tendinopathy,but the efficacy has yet to be established.

Minimally invasive surgeries for insertional Achilles tendinopathy:A commentary review

Studies of minimally invasive surgery for insertional Achilles tendinopathy are limited.To establish this surgery,the following techniques must be minimally invasive:Exostosis resection at the Achilles tendon insertion,debridement of degenerated Achilles tendon,reattachment using anchors or augmentation using flexor hallucis longus(FHL)tendon transfer,and excision of the posterosuperior calcaneal prominence.Studies on these four perspectives were reviewed to establish minimally invasive surgery for insertional Achilles tendinopathy.Techniques for exostosis resection were demonstrated in one case study,where blunt dissection around the exostosis was performed,and the exostosis was resected using an abrasion burr under fluoroscopic guidance.Techniques for debridement of degenerated Achilles tendon were demonstrated in the same case study,where the space left after resection of the exostosis was used as an endoscopic working space,and the degenerated Achilles tendon and intra-tendinous calcification were debrided endoscopically.Achilles tendon reattachment techniques using suture anchors have been demonstrated in several studies.However,there are no studies on FHL tendon transfer techniques for Achilles tendon reattachment.In contrast,endoscopic posterosuperior calcaneal prominence resection is already established.Additionally,studies on ultrasound-guided surgeries and percutaneous dorsal wedge calcaneal osteotomy as minimally invasive surgery were reviewed.

Therapeutic Effects of Acupuncture on Tendinopathy: Systematic Review and Meta-Analysis

Objective:To compare the effects of acupuncture and other treatments on tendinopathy through Meta-analysis.Methods:Computerized databases,including PubMed,EBSCO,EMBASE,WanFang database,Web of Science,OVID and Cochrane Library were searched for trials concerning acupuncture for tendinopathy from establishing time to October 2021.Randomized controlled trials,quasi-randomized controlled trials,and non-randomized controlled trials related to acupuncture for tendinopathy were involved.Ultimately,we used Review Manager 5.3 to perform a Meta-analysis of included studies.Results:Meta-analysis of ten studies showed that the reductions in visual analog scale were significantly different between two groups whether in short-time follow-up(MD=–0.61,95%CI[–1.07 to–0.15],P=0.009)or in long-time follow-up(MD=–1.92,95%CI[–2.08 to–1.77],P<0.00001).The cure rates were significantly different(OR=8.97,95%CI[1.57–51.09],P=0.01),as well as the adverse events(OR=0.91,95%CI[0.30–2.74],P=0.87).Conclusion:Acupuncture provides superior pain relief,improvement in function,and safety than other control conditions/active non-acupuncture interventions in tendinopathy patients.

Ultrasonographic evaluation of the effect of extracorporeal shock wave therapy on calcific tendinopathy of the rectus femoris tendon:A case report

BACKGROUND Calcific tendinopathy denotes calcific deposits in a specific tendon.It is also known as calcifying tendinitis,calcifying periarticulitis,or periarticular apatite deposition disease.Recently,extracorporeal shock wave therapy(ESWT)has been reported to be effective in relieving and treating pain in calcific tendinopathy.CASE SUMMARY A 36-year-old female patient suffered from left hip joint pain for six months.The pain was increased during abduction of the hip,waking,and jumping.B-mode ultrasonography was performed by a physiatrist with an L12-5 linear transducer.A single session of ESWT was given in the marking area under ultrasound guidance at 4 Hz,2500 shots with intensity of stimulation using energy of 0.1 mJ/mm2.The hip pain of the patient slowly decreased within 4 wk after starting the ESWT.After six weeks of ESWT,her hip pain was completely resolved.However,the size of calcification showed almost no reduction in simple radiography at the final follow-up.CONCLUSION Ultrasonography is a very good modality not only for diagnosing calcified tendinitis by classical appearance,but also for evaluating the effect of ESWT during the follow-up period.

Understanding cellular and molecular mechanisms of pathogenesis of diabetic tendinopathy

There is accumulating evidence of an increased incidence of tendon disorders in people with diabetes mellitus.Diabetic tendinopathy is an important cause of chronic pain,restricted activity,and even tendon rupture in individuals.Tenocytes and tendon stem/progenitor cells(TSPCs)are the dominant cellular components associated with tendon homeostasis,maintenance,remodeling,and repair.Some previous studies have shown alterations in tenocytes and TSPCs in high glucose or diabetic conditions that might cause structural and functional variations in diabetic tendons and even accelerate the development and progression of diabetic tendinopathy.In this review,the biomechanical properties and histopathological changes in diabetic tendons are described.Then,the cellular and molecular alterations in both tenocytes and TSPCs are summarized,and the underlying mechanisms involved are also analyzed.A better understanding of the underlying cellular and molecular pathogenesis of diabetic tendinopathy would provide new insight for the exploration and development of effective therapeutics.

Analysing the outcome of surgery for chronic Achilles tendinopathy over the last 50 years

AIM: To determine an association between when the study was performed, the robustness of the study and the outcomes for insertional and non-insertional Achilles tendinopathy surgery. METHODS: We performed a systematic review in accordance with the PRISMA guidelines to assess the methodology of studies investigating the outcome of surgery in chronic Achilles tendinopathy over the last 50 years to identify any trends that would account for the variable results. The Coleman Methodology Scores were correlated with the reported percentage success rates and with the publication year to determine any trends using Pearson's correlation. RESULTS: We identified 62 studies published between 1964 and 2014 reporting on a total of 2923 surgically treated Achilles tendinopathies. The average followup time was 40 mo(range 5-204 mo), and the mean reported success rate was 83.5%(range 36%-100%). The Coleman Methodology Scores were highly reproducible(r = 0.99, P < 0.01), with a mean of 40.1(SD 18.9, range 2-79). We found a negative correlation between reported success rate and overall methodology scores(r =-0.40, P < 0.001), and a positive correlation between year of publication and overall methodology scores(r = 0.46, P < 0.001). CONCLUSION: We conclude that although the success rate of surgery for chronic Acilles tendinopathy described in the literature has fallen over the last 50 years, this is probably due to a more rigorous methodology of the studies.

Exercise for tendinopathy

Tendinopathies are one of the most common sports/musculoskeletal injury in modern western societies.Many physiotherapy approaches have been recommended in the literature for the management of tendinopathy.The most effective treatment in the management of tendinopathy is the eccentric training.Load,speed and frequency of contractions are the three principles of eccentric exercises,discussed in this report.However,eccentric training is not effective for all patients withtendinopathy and the effectiveness of this approach when applied as monotherapy is lower than it is applied as part of the rehabilitation process.For this reason,clinicians combine eccentric training with other physiotherapy techniques such as stretching,isometric and lumbar stability exercises,electrotherapy,manual therapy,soft tissue manipulation techniques,taping and acupuncture in the management of tendinopathies.Further research is needed to find out which treatment strategy combined with eccentric training will provide the best results in the rehabilitation of tendinopathy.

Lateral elbow tendinopathy: Evidence of physiotherapy management

Lateral elbow tendinopathy(LET) is a common musculoskeletal/sports injury. A plethora of physiotherapy techniques has been proposed in the management of LET. The exercise programme is the most common treatment in the management of LET. The optimal protocol of exercise programme is still unknown. The effectiveness of the exercise programme is low when it is applied as monotherapy. Therefore, exercise programme is combined with other physiotherapy modalities such as soft tissue techniques, external support, acupuncture, manual therapy and electrotherapy, in the treatment of LET. Future research is needed to determine which treatment strategy combined with exercise programme will provide the best results in LET rehabilitation.

Advanced glycation end productions and tendon stem/progenitor cells in pathogenesis of diabetic tendinopathy

Tendinopathy is a challenging complication observed in patients with diabetes mellitus.Tendinopathy usually leads to chronic pain,limited joint motion,and even ruptured tendons.Imaging and histological analyses have revealed pathological changes in various tendons of patients with diabetes,including disorganized arrangement of collagen fibers,microtears,calcium nodules,and advanced glycation end product(AGE)deposition.Tendon-derived stem/progenitor cells(TSPCs)were found to maintain hemostasis and to participate in the reversal of tendinopathy.We also discovered the aberrant osteochondrogenesis of TSPCs in vitro.However,the relationship between AGEs and TSPCs in diabetic tendinopathy and the underlying mechanism remain unclear.In this review,we summarize the current findings in this field and hypothesize that AGEs could alter the properties of tendons in patients with diabetes by regulating the proliferation and differentiation of TSPCs in vivo.

Can extracorporeal shock-wave therapy be used for the management of lateral elbow tendinopathy?

Lateral elbow tendinopathy(LET) is one of the two most common tendinopathies of the upper limb. The most effective treatment in the management of LET is the exercise program. Clinicians combine exercise program with other physiotherapy, electrotherapeutic and no, techniques. Extracorporeal shock wave therapy(ESWT) is one of the most common recommended electrotherapeutic modalities for the management of LET. Further research is needed to find out the optimal treatment protocol of ESWT in the management of

Patellar Tendinopathy: A Physiotherapist’s Perspective

The pathology of patellar tendinopathy and the mechanisms of pain are poorly understood. The most popular treatment modality is the Eccentric overload Exercise. However, there is insufficient evidence to recommend a specific protocol and yet it is the most commonly used treatment modality. The aim of this case study is to present the possible mechanisms of pain and a treatment approach on a patient who was diagnosed as having patellar tendinopathy. It is suggested that hyper extension of the knee might be the source of patellar tendon pain in this patient. Following a course of pulsed short wave diathermy the patient was symptom free and remained so at 6 month review. Further studies to evaluate effectiveness of pulsed short wave diathermy is suggested.

Achilles Tendoscopy for Non-Insertional Tendinopathy

Achilles tendinopathy is a very common pathology, especially in the athletic population. Its etiology is multifactorial and the underlying pathophysiology is still not fully understood. For non-insertional tendinopathy is increasingly recognized the influence of paratendinopathy in the genesis of patients symptoms, so various surgical treatments have been accordingly developed;they are indicated when conservative treatment fails. The Achilles tendoscopy is one of these techniques, it has the advantages of minimally invasive surgery, resulting in a low complication rate and good functional results. In relation to this procedure we review the surgical technique, which is exemplified by the case of a high performance athlete treated satisfactorily.

Chronic Achilles Tendinopathy in Runners: Relationship between Pain and Tendon Vascularity and Efficacy and Safety of the Radial Extracorporeal Shock Wave Therapy

Few studies report the possible correlation pain-paratendon microvascularity during the painful phase of the chronic Achilles tendinopathy and the efficacy of the radial shock wave therapy re-spect to other therapies. The aim of the present longitudinal, controlled study is to demonstrate the variation of the tendon micro vascularization in athletes affected by Achilles tendinopathy and the efficacy and safety of the radial extracorporeal shock wave therapy. Twelve elite runners with Achilles tendinopathy were compared with 12 healthy amateurs, both treated by radial extracorporeal shock wave therapy in 3 sessions (1/every 3 days). VAS scale was used for pain evaluation at one and six months after treatment and a Color and Power Doppler echography was performed to observe the paratendon microvascularity before the beginning of the treatment and at one and six months after. One month after the beginning of the treatment, it was observed a decrease of the hypervascularity in all 12 subjects with tendinopathy and no variation in the control group participants. Clinically, 80% of patients referred pain relief and they were able to return to sports activity. The decrease of the paratendon microvascularity confirms the correlation between the disappearance of the pain and the normalization of the vascularity in the athletes. Moreover, radial extracorporeal shock wave therapy consented a quickly pain relief and returned to the sport. These results confirmed the efficacy and safety of this physical therapy that it could be considered a good therapeutic choice in the treatment of the chronic Achilles tendinopathy.

Ultrasound and Color Doppler-Guided Surgery for Insertional Achilles Tendinopathy-Results of a Pilot Study

Background: Treatment of insertional achilles tendinopathy is known to be difficult. Eccentric calf muscle exercises and extracorporeal shockwave therapy have been proposed as the primary treatments for this condition, but surgery is indicated after failed conservative management. There is no consensus about the most efficient surgical treatment. Objectives: To evaluate a new ultrasound and color Doppler-guided surgical treatment for insertional achilles tendinopathy. Patients and methods: 24 consecutive patients (13 men and 11 women, mean age 47 years) with a long duration of insertional achilles tendon pain (median 18 months) were included in the study. The surgical procedure consisted of extirpation of the subcutaneous and retrocalcaneal bursa, scraping of the ventral distal achilles tendon and removal of prominent bone at the upper calcaneal tuberosity (Haglund’s deformity). In 13 patients, the plantaris tendon was also cut and excised. VAS for pain during activity, satisfaction with the treatment result and the SF-36 score to measure quality of life were used for evaluation. Results: The mean VAS had decreased from 72 before surgery to 19 after surgery (p 0.001), and 20/24 (83%) patients were satisfied with the result and had returned to full tendon loading activity at the one-year follow-up. The SF-36 score had improved significantly. Conclusion: Ultrasound and color Doppler-guided surgical treatment seems to be a good method for treatment of chronic painful insertional achilles tendinopathy. Longer follow-up studies on larger materials are needed.

Ultrafine Structure of Calcific Deposits Developed in Calcific Tendinopathy

The ultrafine structure of tendons deposits formed in three patients, males aged 52 and 61 years and a female aged 71 years were evaluated by atomic force microscopy. Three distinctly different structures of deposit surface were identified: (i) compact, smooth and uneven surface composed of closely packed nanoparticles of diameter 30 nm;(ii) surfaces consisting of plate-like crystalline particles about 30 nm thick that formed larger entities divided by deep depressions;(iii) rough surface formed by individual or closely attached elongated needle-like particles with elliptical cross-section of diameter about 30 nm. These surface structures were developed by different formation mechanisms: (i) Aggregation of Posner’s clusters into nanoparticles formed on biological calcific able surfaces and in the bulk of body fluid surrounding the deposits that subsequently settled onto the deposit surface;(ii) Regular crystal growth on surface nuclei generated at low supersaturation of body fluid with respect to the phosphatic phase and/or in a narrow cavity containing a very limited volume of liquid;(iii) Solution mediated re-crystallization of the upper layers of a deposit or unstable crystalline growth governed by volume diffusion of building units to the particle tip. Small rods, 40 nm wide and from 100 to 300 nm long, with no apparent order were detected only on the surface of deposit formed in the female patient. These rods could be debris of collagen fibres that disintegrated into individual building units (macromolecules) with some showing breakdown into smaller fragments.

Major physical but also psychological effects after pain relief from surgical scraping in patients with Achilles tendinopathy—A 1-year follow-up study

Treatment with Ultrasound (US) and Color Doppler (CD)-guided surgical scraping has shown good short-term clinical results in patients with chronic painful midportion Achilles tendinopathy. The objective was to prospectively follow the patients 1-year after surgery. Material: Sixty- four tendons in 47 patients (28 men and 19 women, mean age 52 (+/-12 years) on different activity levels) were in local anaestesia operated with US+CD-guided surgical scraping. In 43/64 tendons, there was also removal of the plantaris tendon. Methods: Questionnaires evaluating activity level, VAS for pain during activity, satisfaction with treatment result, and the SF-36 score (quality of life), were used before and 1-year after surgery. Results: At follow-up, the mean VAS for pain during activity had decreased from 62 (+/-20) before surgery to 15 (+/-15) after surgery (p < 0.001). All patients were satisfied with the result and had returned to full tendon loading activity. There were no complications. Both the physical and psychological parameters in the SF-36 score had improved significantly. Conclusions: For patients with chronic painful midportion Achilles tendinopathy, US+CD-guided surgical scraping, often combined with plantaris tendon removal, seems to be an efficient treatment method to recover physically and psychologically.

Ultrasmall copper-based clusterzymes ameliorate Achilles tendinopathy by inhibiting acute oxidative stress

Tendinopathy is a prevalent musculoskeletal disorder,accounting for over 30%of musculoskeletal lesions.However,current therapeutic strategies for tendinopathy are limited and often yield unsatisfactory clinical outcomes.Therefore,there is a critical need to explore novel therapeutic approaches with minimal side effects for tendinopathy and its early lesions.In this study,we successfully designed and synthesized a copper(I)-based nanocluster,named Cu_(11),which possesses remarkable enzyme-like and ROS-scavenging activities.This unique combination of properties qualifies Cu_(11)as an attractive anti-inflammatory and anti-ROS agent.The Cu_(11)clusterzymes specifically target mitochondria,effectively scavenging excessive reactive oxygen species(ROS)and reducing oxidative stress.Furthermore,Cu_(11)clusterzymes inhibit the activation of key signaling pathways involved in inflammation,namely tumor necrosis factor(TNF),mitogen-activated protein kinase(MAPK),and nuclear factor(NF)-κB,leading to a decrease in the release of proinflammatory cytokines.Excitingly,our in vivo experiments using a collagenase-induced acute Achilles tendinopathy model demonstrated that Cu_(11)clusterzymes effectively alleviate inflammation and oxidative stress,without causing systemic toxicity.This study highlights the potential of copper-based clusterzymes as therapeutic agents for the treatment of Achilles tendinopathy and other inflammatory diseases.The unique enzyme-like and ROS-scavenging activities of Cu_(11)make it a promising candidate for further development and clinical translation.

Antioxidant and anti-inflammatory injectable hydrogel microspheres for in situ treatment of tendinopathy

Tendinopathy is a common disorder that causes local dysfunction and reduces quality of life.Recent research has indicated that alterations in the inflammatory microenvironment play a vital role in the pathogenesis of tendinopathy.Herein,injectable methacrylate gelatin(GelMA)microspheres(GM)were fabricated and loaded with heparin-dopamine conjugate(HDC)and hepatocyte growth factor(HGF).GM@HDC@HGF were designed to balance the inflammatory microenvironment by inhibiting oxidative stress and inflammation,thereby regulating extracellular matrix(ECM)metabolism and halting tendon degeneration.Combining growth factors with heparin was expected to improve the encaption,the catechol groups on dopamine have adhesion and antioxidant properties,allowing potential attachment at the injured site,and better function synergized with HGF.GM@HDC@HGF injected in situ in rat Achilles tendinopathy(AT)models significantly downregulated oxidative stress and inflammation,and ameliorated ECM degradation.In conclusion,the multifunctional platform developed presents a promising alternative for the treatment of tendinopathy.