SARS-CoV-2 Viral Replication Persists in the Human Lung for Several Weeks after Symptom Onset.

Rationale: In the upper respiratory tract, replicating (culturable) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is recoverable for ∼4-8 days after symptom onset, but there is a paucity of data about the frequency and duration of replicating virus in the lower respiratory tract (i.e., the human lung).Objectives: We undertook lung tissue sampling (needle biopsy) shortly after death in 42 mechanically ventilated decedents during the Beta and Delta waves. An independent group of 18 ambulatory patients served as a control group.Methods: Lung biopsy cores from decedents underwent viral culture, histopathological analysis, electron microscopy, transcriptomic profiling, and immunohistochemistry.Measurements and Main Results: Thirty-eight percent (16 of 42) of mechanically ventilated decedents had culturable virus in the lung for a median of 15 days (persisting for up to 4 wk) after symptom onset. Lung viral culture positivity was not associated with comorbidities or steroid use. Delta but not Beta variant lung culture positivity was associated with accelerated death and secondary bacterial infection (P < 0.05). Nasopharyngeal culture was negative in 23.1% (6 of 26) of decedents despite lung culture positivity. This hitherto undescribed biophenotype of lung-specific persisting viral replication was associated with an enhanced transcriptomic pulmonary proinflammatory response but with concurrent viral culture positivity.Conclusions: Concurrent rather than sequential active viral replication continues to drive a heightened proinflammatory response in the human lung beyond the second week of illness and was associated with variant-specific increased mortality and morbidity. These findings have potential implications for the design of interventional strategies and clinical management of patients with severe coronavirus disease (COVID-19).

Consensus methods in patellofemoral pain: how rigorous are they? A scoping review.

OBJECTIVE: Clinicians treating patients with patellofemoral pain (PFP) rely on consensus statements to make the best practice recommendations in the absence of definitive evidence on how to manage PFP. However, the methods used to generate and assess agreement for these recommendations have not been examined. Our objective was to map the methods used to generate consensus-based recommendations for PFP and apply four novel questions to assess the rigour of consensus development. DESIGN: Scoping review. DATA SOURCES: We searched Medline, SPORTDiscus, CINAHL and Embase from inception to May 2022 to identify consensus-derived statements or practice guidelines on PFP. The Joanna Briggs Institute Manual for Evidence Synthesis was followed to map the existing evidence. We measured the consensus methods based on four sets of questions addressing the panel composition, application of the consensus method chosen, agreement process and the use of evidence mapping. ELIGIBILITY CRITERIA: All consensus statements or clinical guidelines on PFP were considered. RESULTS: Twenty-two PFP consensus statements were identified. Panel composition: 3 of the 22 (14%) consensus groups reported the panellists' experience, 2 (9%) defined a desired level of expertise, 10 (45%) reported panellist sex and only 2 (9%) included a patient. Consensus method: 7 of 22 (32%) reported using an established method of consensus measurement/development. Agreement process: 10 of 22 (45%) reported their consensus threshold and 2 (9%) acknowledged dissenting opinions among the panel. Evidence mapping: 6 of 22 (27%) reported using systematic methods to identify relevant evidence gaps. CONCLUSIONS: PFP consensus panels have lacked diversity and excluded key partners including patients. Consensus statements on PFP frequently fail to use recognised consensus methods, rarely describe how 'agreement' was defined or measured and often neglect to use systematic methods to identify evidence gaps.

Cerebral revascularization surgery reduces cerebrovascular events in children with sickle cell disease and moyamoya syndrome: Results of the stroke in sickle cell revascularization surgery retrospective study.

BACKGROUND: Recent studies suggest that cerebral revascularization surgery may be a safe and effective therapy to reduce stroke risk in patients with sickle cell disease and moyamoya syndrome (SCD-MMS). METHODS: We performed a multicenter, retrospective study of children with SCD-MMS treated with conservative management alone (conservative group)-chronic blood transfusion and/or hydroxyurea-versus conservative management plus surgical revascularization (surgery group). We monitored cerebrovascular event (CVE) rates-a composite of strokes and transient ischemic attacks. Multivariable logistic regression was used to compare CVE occurrence and multivariable Poisson regression was used to compare incidence rates between groups. Covariates in multivariable models included age at treatment start, age at moyamoya diagnosis, antiplatelet use, CVE history, and the risk period length. RESULTS: We identified 141 patients with SCD-MMS, 78 (55.3%) in the surgery group and 63 (44.7%) in the conservative group. Compared with the conservative group, preoperatively the surgery group had a younger age at moyamoya diagnosis, worse baseline modified Rankin scale scores, and increased prevalence of CVEs. Despite more severe pretreatment disease, the surgery group had reduced odds of new CVEs after surgery (odds ratio = 0.27, 95% confidence interval [CI] = 0.08-0.94, p = .040). Furthermore, comparing surgery group patients during presurgical versus postsurgical periods, CVEs odds were significantly reduced after surgery (odds ratio = 0.22, 95% CI = 0.08-0.58, p = .002). CONCLUSIONS: When added to conservative management, cerebral revascularization surgery appears to reduce the risk of CVEs in patients with SCD-MMS. A prospective study will be needed to validate these findings.

Exposure to oxLDL impairs TGF-ß activity in human tendon cells.

BACKGROUND: Previous studies have shown that patients with hypercholesterolemia experience elevated levels of oxidized LDL (oxLDL), a molecule which triggers inflammation and collagenase activity. In this study we discovered novel mechanistic effects of oxLDL on tendon cells and the mediators regulating matrix remodeling by analyzing the expression and activity of related proteins and enzymes. These effects may contribute to tendon damage in patients with high cholesterol. METHODS: Isolated human tendon cells (male and female donors age 28 ± 1.4 age 37 ± 5.7, respectively) were incubated in the presence or absence of oxLDL. The influence of oxLDL on the expression level of key mRNA and proteins was examined using real time quantitative PCR, ELISA and Western blots. The activities of enzymes relevant to collagen synthesis and breakdown (lysyl oxidase and matrix metalloproteinases) were quantified using fluorometry. Finally, the isolated human tendon cells in a 3D construct were exposed to combinations of oxLDL and TGF-ß to examine their interacting effects on collagen matrix remodeling. RESULTS: The one-way ANOVA of gene expression indicates that key mRNAs including TGFB, COL1A1, DCN, and LOX were significantly reduced in human tendon cells by oxLDL while MMPs were increased. The oxLDL reduced the activity of LOX at 50 µg/ml, whereas conversely MMP activities were induced at 25 µg/ml (P ≤ 0.01). COL1A1 synthesis and TGF-ß secretion were also inhibited (P ≤ 0.05). Adding recombinant TGF-ß reversed the effects of oxLDL on the expression of collagens and LOX. OxLDL also impaired collagen matrix remodeling (P ≤ 0.01), and adding TGF-ß restored the native phenotype. CONCLUSION: Exposure to oxLDL in patients with hypercholesterolemia may adversely affect the mechanical and structural properties of tendon tissue through a direct action of oxLDL on tendon cells, including impairment of TGF-ß expression. This impairment leads to disturbed matrix remodeling and synthesis, thereby potentially leading to increased risk of acute or chronic tendon injury. Our discovery may provide an opportunity for developing effective treatments for tendon injury in hypercholesterolemia patients by targeting the TGF-ß pathway.

Combined hormonal contraceptive use is not protective against musculoskeletal conditions or injuries: a systematic review with data from 5 million females.

OBJECTIVE: Assess the association between combined hormonal contraceptives (CHC) use and musculoskeletal tissue pathophysiology, injuries or conditions. DESIGN: Systematic review with semiquantitative analyses and certainty of evidence assessment, guided by the Grading of Recommendations Assessment, Development and Evaluation approach. DATA SOURCES: MEDLINE, EMBASE, CENTRAL, SPORTDiscus, CINAHL searched from inception to April 2022. ELIGIBILITY: Intervention and cohort studies that assessed the association between new or ongoing use of CHC and an outcome of musculoskeletal tissue pathophysiology, injury or condition in postpubertal premenopausal females. RESULTS: Across 50 included studies, we assessed the effect of CHC use on 30 unique musculoskeletal outcomes (75% bone related). Serious risk of bias was judged present in 82% of studies, with 52% adequately adjusting for confounding. Meta-analyses were not possible due to poor outcome reporting, and heterogeneity in estimate statistics and comparison conditions. Based on semiquantitative synthesis, there is low certainty evidence that CHC use was associated with elevated future fracture risk (risk ratio 1.02-1.20) and total knee arthroplasty (risk ratio 1.00-1.36). There is very low certainty evidence of unclear relationships between CHC use and a wide range of bone turnover and bone health outcomes. Evidence about the effect of CHC use on musculoskeletal tissues beyond bone, and the influence of CHC use in adolescence versus adulthood, is limited. CONCLUSION: Given a paucity of high certainty evidence that CHC use is protective against musculoskeletal pathophysiology, injury or conditions, it is premature and inappropriate to advocate, or prescribe CHC for these purposes. PROSPERO REGISTRATION NUMBER: This review was registered on PROSPERO CRD42021224582 on 8 January 2021.

Validation of a bluetooth-enabled load cell for objective and accessible assessment of lower extremity strength.

High magnitude loading from performing resistance-based exercise has been found to improve tendon strength and reduce symptoms of Achilles tendinopathy (AT) but is difficult to quantify without specialist equipment. Here, we assess the validity and reliability of a novel AT rehabilitation tool (the "PhysViz" system) compared to a "gold-standard" dynamometer for assessing plantarflexion maximal voluntary isometric contractions (MVIC). 41 participants aged 18-60 completed the study. A within-subject test-retest study design was used to examine and compare the validity and reliability of the two systems during plantarflexion MVICs. Test - retest reliability of the two methods were determined by calculating intra-class correlation coefficients (ICCs) and 95% confidence intervals. Method agreement was assessed with Bland - Altman Limits of Agreement (LoA) analysis. The PhysViz demonstrated excellent test-retest reliability; ICC, SEM and MDC were numerically comparable to the dynamometer (ICC 0.93 vs. 0.92; SEM 2.01 vs. 2.95 kg and MDC 5.58 vs. 8.18 kg, respectively), indicating that the novel system is valid and reliable for measuring plantarflexor MVICs. Future studies should address its utility in monitoring AT rehabilitative loading remotely over time.

The effect of rigid tape on wrist postures during tree planting.

Taping has been suggested to reduce the incidence of tendinopathy in tree planters. However, the ability of taping to reduce wrist postures during planting has not yet been formally evaluated. The primary aim was to test the effect of rigid taping on wrist postures during tree planting tasks. Eleven tree planters planted up to 50 trees in three conditions: no-tape (NT), tape-on-the-dorsum-of-the-hand (T1) and tape-on-the-thumb (T2) in a randomised cross-over, within-participant, repeat-measures design. Electrogoniometers (EG) recorded continuous wrist postures. Digital video recordings were used to segment EG traces of each planting cycle (one planted tree) into 4 kinematically distinct Phases. The tree and shovel wrist were analysed separately. Tree-wrist peak ulnar deviation and frequency of shovel-wrist awkward frontal plane postures were significantly reduced in the T2 condition. Taping may be effective at reducing non-neutral postures and should be researched further to determine its effectiveness in reducing tree planting injuries.Practitioner summary: The effect of rigid taping on wrist postures during tree planting has not yet been formally evaluated. A randomised cross-over, within-participant, repeat measures design was used to evaluate the effect of rigid taping on wrist postures during planting. Thumb rigid taping appeared to reduce wrist range of motion during planting. KEY POINTSTaping of the thumb reduced peak ulnar deviation of the tree wrist and frequency of awkward frontal plane postures of the shovel wrist.While taping of the dorsum of the hand appeared to be more restrictive, it did not significantly reduce wrist movement; this is likely because only its effect on sagittal plane posture was assessed which had a higher variance.Upon application, tape appeared to restrict voluntary movement patterns, decreased voluntary grip force exertion and physically restrain wrist movement.Overall, rigid tape was found to be an acceptable intervention for the tree planting occupation, with financial costs and perceived effort identified as the primary barriers to acceptability.

Best-response dynamics, playing sequences, and convergence to equilibrium in random games.

We analyze the performance of the best-response dynamic across all normal-form games using a random games approach. The playing sequence-the order in which players update their actions-is essentially irrelevant in determining whether the dynamic converges to a Nash equilibrium in certain classes of games (e.g. in potential games) but, when evaluated across all possible games, convergence to equilibrium depends on the playing sequence in an extreme way. Our main asymptotic result shows that the best-response dynamic converges to a pure Nash equilibrium in a vanishingly small fraction of all (large) games when players take turns according to a fixed cyclic order. By contrast, when the playing sequence is random, the dynamic converges to a pure Nash equilibrium if one exists in almost all (large) games.

Can Achilles tendon xanthoma be distinguished from Achilles tendinopathy using Dixon method MRI? A cross-sectional exploratory study.

BACKGROUND: Familial hypercholesterolemia is a genetic condition characterized by life-long elevations of plasma low-density lipoprotein cholesterol. In addition to life-threatening cardiovascular complications, intratendinous cholesterol deposits (xanthomas) can lead to pain and tendon thickening, particularly in the Achilles. Clinical detection of xanthomas currently relies upon visual assessment and palpation, or ultrasound-based measures of tendon thickening or echotexture. Misdiagnosis of xanthoma can delay the commencement of potentially life-saving lipid-lowering therapy. Our primary purpose was to determine whether analysis of separated fat and water magnetic resonance images may be able to differentiate between xanthomatic and nonxanthomatic Achilles tendons through quantification of intratendinous fat content. The main hypothesis was that Achilles tendon xanthomas will demonstrate greater lipid content than Achilles tendinopathy or healthy control tendons. METHODS: Bilateral MRI scans of Achilles tendons from 30 participants (n = 10 Achilles tendon xanthoma, n = 10 Achilles overuse tendinopathy, n = 10 healthy controls) were analyzed for total lipid content using the Dixon method of fat and water signal separation. Secondary outcome measures included tendon water content, as well as ultrasound characterization of tendon tissue organization and thickness. RESULTS: Fat content was greater in Achilles tendon xanthomas compared to the tendinopathy (p < 0.0001) and control groups (p < 0.0001). Water content was also greater in Achilles tendon xanthomas compared to the tendinopathy (p < 0.0001) and control groups (p = 0.0002). Ultrasound tissue characterization revealed worse tissue organization in Achilles tendon xanthoma tendons compared to Achilles tendinopathy (p < 0.05) but demonstrated largely overlapping distributions. Achilles tendon xanthoma tendons were, on average, significantly thicker than the tendons of the other two groups (p < 0.01 and p < 0.001, respectively). CONCLUSION: MRI-derived measures of Achilles tendon fat content may be able to distinguish xanthomas from control and tendinopathic tissue. Dixon method MRI warrants further evaluation in an adequately powered study to develop and test clinically relevant diagnostic thresholds.

The Validity and Reliability of Two Commercially Available Load Sensors for Clinical Strength Assessment.

OBJECTIVE: Handheld dynamometers are common tools for assessing/monitoring muscular strength and endurance. Health/fitness Bluetooth load sensors may provide a cost-effective alternative; however, research is needed to evaluate the validity and reliability of such devices. This study assessed the validity and reliability of two commercially available Bluetooth load sensors (Activ5 by Activbody and Progressor by Tindeq). METHODS: Four tests were conducted on each device: stepped loading, stress relaxation, simulated exercise, and hysteresis. Each test type was repeated three times using the Instron ElectroPuls mechanical testing device (a gold-standard system). Test-retest reliability was assessed through intraclass correlations. Agreement with the gold standard was assessed with Pearson's correlation, interclass correlation, and Lin's concordance correlation. RESULTS: The Activ5 and Progressor had excellent test-retest reliability across all four tests (ICC(3,1) ≥ 0.999, all p ≤ 0.001). Agreement with the gold standard was excellent for both the Activ5 (ρ ≥ 0.998, ICC(3,1) ≥ 0.971, ρc ≥ 0.971, all p's ≤ 0.001) and Progressor (ρ ≥ 0.999, ICC(3,1) ≥ 0.999, ρc ≥ 0.999, all p's ≤ 0.001). Measurement error increased for both devices as applied load increased. CONCLUSION: Excellent test-retest reliability was found, suggesting that both devices can be used in a clinical setting to measure patient progress over time; however, the Activ5 consistently had poorer agreement with the gold standard (particularly at higher loads).

ICON PART-T 2019-International Scientific Tendinopathy Symposium Consensus: recommended standards for reporting participant characteristics in tendinopathy research (PART-T).

We aimed to establish consensus for reporting recommendations relating to participant characteristics in tendon research. A scoping literature review of tendinopathy studies (Achilles, patellar, hamstring, gluteal and elbow) was followed by an online survey and face-to-face consensus meeting with expert healthcare professionals (HCPs) at the International Scientific Tendon Symposium, Groningen 2018. We reviewed 263 papers to form statements for consensus and invited 30 HCPs from different disciplines and geographical locations; 28 completed the survey and 15 attended the meeting. There was consensus that the following data should be reported for cases and controls: sex, age, standing height, body mass, history of tendinopathy, whether imaging was used to confirm pathology, loading tests, pain location, symptom duration and severity, level of disability, comorbidities, physical activity level, recruitment source and strategies, and medication use history. Standardised reporting of participant characteristics aims to benefit patients and clinicians by guiding researchers in the conduct of their studies. We provide free resources to facilitate researchers adopting our recommendations.

ICON 2019-International Scientific Tendinopathy Symposium Consensus: There are nine core health-related domains for tendinopathy (CORE DOMAINS): Delphi study of healthcare professionals and patients.

BACKGROUND: The absence of any agreed-upon tendon health-related domains hampers advances in clinical tendinopathy research. This void means that researchers report a very wide range of outcome measures inconsistently. As a result, substantial synthesis/meta-analysis of tendon research findings is almost futile despite researchers publishing busily. We aimed to determine options for, and then define, core health-related domains for tendinopathy. METHODS: We conducted a Delphi study of healthcare professionals (HCP) and patients in a three-stage process. In stage 1, we extracted candidate domains from clinical trial reports and developed an online survey. Survey items took the form: 'The 'candidate domain' is important enough to be included as a core health-related domain of tendinopathy'; response options were: agree, disagree, or unsure. In stage 2, we administered the online survey and reported the findings. Stage 3 consisted of discussions of the findings of the survey at the ICON (International Scientific Tendinopathy Symposium Consensus) meeting. We set 70% participant agreement as the level required for a domain to be considered 'core'; similarly, 70% agreement was required for a domain to be relegated to 'not core' (see Results next). RESULTS: Twenty-eight HCP (92% of whom had >10 years of tendinopathy experience, 71% consulted >10 cases per month) and 32 patients completed the online survey. Fifteen HCP and two patients attended the consensus meeting. Of an original set of 24 candidate domains, the ICON group deemed nine domains to be core. These were: (1) patient rating of condition, (2) participation in life activities (day to day, work, sport), (3) pain on activity/loading, (4) function, (5) psychological factors, (6) physical function capacity, (7) disability, (8) quality of life and (9) pain over a specified time. Two of these (2, 6) were an amalgamation of five candidate domains. We agreed that seven other candidate domains were not core domains: range of motion, pain on clinician applied test, clinical examination, palpation, drop out, sensory modality pain and pain without other specification. We were undecided on the other five candidate domains of physical activity, structure, medication use, adverse effects and economic impact. CONCLUSION: Nine core domains for tendon research should guide reporting of outcomes in clinical trials. Further research should determine the best outcome measures for each specific tendinopathy (ie, core outcome sets).

Angiopoietin-like 4 promotes angiogenesis in the tendon and is increased in cyclically loaded tendon fibroblasts.

KEY POINTS: Angiopoietin-like 4 (ANGPTL4) modulates tendon neovascularization. Cyclic loading stimulates the activity of transforming growth factor-ß and hypoxia-inducible factor 1α and thereby increases the expression and release of ANGPTL4 from human tendon cells. Targeting ANGPTL4 and its regulatory pathways is a potential avenue for regulating tendon vascularization to improve tendon healing or adaptation. ABSTRACT: The mechanisms that regulate angiogenic activity in injured or mechanically loaded tendons are poorly understood. The present study examined the potential role of angiopoietin-like 4 (ANGPTL4) in the angiogenic response of tendons subjected to repetitive mechanical loading or injury. Cyclic stretching of human tendon fibroblasts stimulated the expression and release of ANGPTL4 protein via transforming growth factor-ß (TGF-ß) and hypoxia-inducible factor 1α (HIF-1α) signalling, and the released ANGPTL4 was pro-angiogenic. Angiogenic activity was increased following ANGPTL4 injection into mouse patellar tendons, whereas the patellar tendons of ANGPTL4 knockout mice displayed reduced angiogenesis following injury. In human rotator cuff tendons, the expression of ANGPTL4 was correlated with the density of tendon endothelial cells. To our knowledge, this is the first study characterizing a role of ANGPTL4 in the tendon. ANGPTL4 may assist in the regulation of vascularity in the injured or mechanically loaded tendon. TGF-ß and HIF-1α comprise two signalling pathways that modulate the expression of ANGPTL4 by mechanically stimulated tendon fibroblasts and, in the future, these could be manipulated to influence tendon healing or adaptation.

Do Dietary Factors Influence Tendon Metabolism?

There is very little direct research to conclusively prove the relevance of diet in primary tendinopathies, however it seems prudent to ask whether our current knowledge about the impact of nutrition on collagen metabolism could be useful in assessing, preventing, or treating tendinopathy. The objective of this chapter is to discuss the potential impact (negative or positive) that nutrition may have on the metabolism of tendons by summarizing the related research. The chapter briefly discusses the roles that specific vitamins, amino acids, lipids, and antioxidants have in various processes of the body that may be directly or indirectly related to tenocyte metabolism.

Can Shockwave Therapy Improve Tendon Metabolism?

Shockwave treatments are commonly used in the management of tendon injuries and there is increasing evidence for its clinical effectiveness. There is a paucity of fundamental (in vivo) studies investigating the biological action of shockwave therapy. Destruction of calcifications, pain relief and mechanotransduction-initiated tissue regeneration and remodeling of the tendon are considered to be the most important working mechanisms. The heterogeneity of systems (focussed shockwave therapy vs. radial pressurewave therapy), treatment protocols and study populations, and the fact that there seem to be responders and non-responders, continue to make it difficult to give firm recommendations with regard to the most optimal shockwave therapy approach. Specific knowledge with regard to the effects of shockwave therapy in patients with metabolic tendon disorders is not available. Further fundamental and clinical research is required to determine the value of shockwave therapy in the management of tendinopathy.

Rehabilitation of Tendon Problems in Patients with Diabetes Mellitus.

Exercise is crucial in the management of diabetes mellitus and its associated complications. However, individuals with diabetes have a heightened risk of musculoskeletal problems, including tendon pathologies. Diabetes has a significant impact on the function of tendons due to the accumulation of advanced glycation end-products in the load-bearing collagen. In addition, tendon vascularity and healing may be reduced due to diabetes-induced changes in the peripheral vascular system, and impaired synthesis of collagen and glycosaminoglycan. The current chapter presents an evidence-based discussion of considerations for the rehabilitation of tendon problems in people with diabetes. The following conditions are discussed in detail - calcific tendinopathy, tenosynovitis, tendon rupture, and non-calcifying tendinopathy. Common diabetes-related findings are presented, along with their potential impact on tendinopathy management and suggested modifications to standard tendinopathy treatment protocols. A holistic approach should be used to optimize musculotendinous function, including a comprehensive exercise prescription addressing strength, flexibility, and aerobic fitness.

Dexamethasone decreases substance P expression in human tendon cells: an in vitro study.

OBJECTIVE: Glucocorticoid injections are used by rheumatologists to treat chronic tendinopathy. Surprisingly, the mechanisms by which corticosteroids induce pain relief in this condition have not been investigated. Previous studies have shown local substance P (SP) levels to be correlated with tendon pain and tissue pathology. The objective of this study was to determine whether SP production in human tenocytes is modulated by exposure to dexamethasone. METHODS: Human tendon fibroblasts were cultured in the presence or absence of dexamethasone (1-400 nM), an inhibitor of the glucocorticoid receptor, RU486, recombinant TGF-ß (2.5 or 5.0 ng/ml) or an inhibitor of the TGF-ß receptor (A83.01), recombinant human IL-1ß and IL-6. Expression levels of the genes encoding for SP (TAC1) and its preferred receptor (NK1R), IL-1α, IL-1ß and IL-6 were determined with quantitative PCR and protein levels of SP were examined by EIA and western blot. RESULTS: Exposure of human tendon cells to dexamethasone resulted in a time-dependent reduction of mRNA for SP in both hamstrings and Achilles tenocytes, whereas NK1R was unaffected. The reduction of SP mRNA was dependent on signalling through the glucocorticoid receptor. SP protein was substantially decreased by dexamethasone. Dexamethasone also prevented induction of SP by IL-1ß and by cyclic mechanical loading. CONCLUSION: This study demonstrates that dexamethasone treatment of human tendon fibroblasts reduces the expression of SP through a glucocorticoid receptor-dependent pathway. Drugs interfering with SP signalling could be a future target in the treatment of tendinopathy.