Performance Measures and Plasma Biomarker Levels in Patients with Multiple Sclerosis after 14 Days of Fampridine Treatment: An Explorative Study.

Peripheral cytokine levels may serve as biomarkers for treatment response and disease monitoring in patients with multiple sclerosis (pwMS). The objectives were to assess changes in plasma biomarkers in PwMS after 14 days of fampridine treatment and to explore correlations between changes in performance measures and plasma biomarkers. We included 27 PwMS, 14 women and 13 men, aged 52.0 ± 11.6 years, with a disease duration of 17 ± 8.5 years, and an Expanded Disability Status Scale of 6 [IQR 5.0/6.5]. Gait and hand function were assessed using performance tests completed prior to fampridine and after 14 days of treatment. Venous blood was obtained, and chemiluminescence analysis conducted to assess plasma cytokines and neurodegenerative markers. All performance measures demonstrated improvements. Biomarkers showed decreased tumor necrosis factor (TNF) receptor-2 levels. Associations were found between change scores in (i) Six Spot Step Test and Interleukin (IL)-2, IL-8, and IL-17 levels; (ii) timed 25-foot walk and interferon-γ, IL-2, IL-8, TNF-α, and neurofilament light levels, and (iii) 12-Item Multiple Sclerosis Walking Scale and IL-17 levels. The associations may reflect increased MS-related inflammatory activity rather than a fampridine-induced response or that a higher level of inflammation induces a better response to fampridine.

Criterion validity of muscle strain analyses of skeletal muscle function in patients with multiple sclerosis.

BACKGROUND: Despite the wide range of existing performance measures to evaluate functional status of patients with multiple sclerosis, the heterogeneous nature of the disease hinders clinical characterization and monitoring of disease severity. Speckle tracking ultrasonography is a non-invasive technique to assess isolated muscle function by evaluating the contractile properties of muscle tissue, i.e. muscle strain. The aim of this study was to investigate whether muscle strain measured by speckle tracking ultrasonography could be a useful quantitative measure of muscle function in patients with multiple sclerosis. The criterion validity of muscle strain was compared to that of validated performance measures of upper and lower extremity function. METHODS: This cross-sectional study used baseline data from an explorative observational cohort study (the MUST study). Participants recruited from a hospital outpatient MS clinic underwent speckle tracking ultrasonography of the biceps brachii, supraspinatus, and soleus muscles of the dominant side according to pre-defined submaximal isometric contractions. Participants also completed the Timed 25-Foot Walk Test, the Six Spot Step Test, the 2-minute walking test, the Nine-Hole Peg Test, the 12-item Multiple Sclerosis Walking Scale, and the Oxford Shoulder Score. Gaussian distribution was investigated by visual inspection of normal probability plots and the Shapiro-Wilk test. The Timed 25-Foot Walk Test and Nine-Hole Peg Test were selected as gold standards for function of the lower and upper extremities, respectively. Criterion validity was assessed using Spearman's rank-order correlation coefficient ρ (rho), comparing the muscle strain and performance measures against predefined gold standards. Differences in criterion validity were estimated using squared correlations on the Fischer's Z-scale, with non-parametric bootstrapping to obtain bias-corrected, accelerated bootstrap confidence intervals (95% BCa). RESULTS: Criterion validity showed good to excellent correlations between the gold standard for lower extremity function and the 2-minute walking test and Six Spot Step Test, and a fair correlation to the 12-item Multiple Sclerosis Walking Scale. No significant correlation was found between the gold standard for upper extremity function and the performance measure. There were no significant correlations between the gold standards and muscle strain. CONCLUSION: The absence of criterion validity for muscle strain alongside fair to strong criterion validity for the performance measures indicates that speckle tracking ultrasonography assessment of muscle strain is either invalid or evaluates other constructs of multiple sclerosis. Muscle strain assessed by speckle tracking ultrasonography cannot be recommended for the evaluation of treatment effects or disease progression in multiple sclerosis.

Gait quality and function after fampridine treatment in patients with multiple sclerosis - A prospective cohort study.

BACKGROUND: Fampridine has shown to improve walking speed, motor control, and balance in patients with multiple sclerosis. However, potential fampridine-induced changes in gait quality and underlying mechanisms, evaluated by three-dimensional gait analysis, are poorly examined. The aim was to examine if two weeks of fampridine treatment would improve gait quality (using Gait Profile Score and Gait Variable Scores from three-dimensional gait analysis) and gait function (using performance-based tests, spatiotemporal parameters, and self-perceived gait function). METHODS: 14 participants with multiple sclerosis were included (9 women and 5 men, age 53.6 ± 12.8 years, disease duration 21 ± 9.1 years) in this cohort study. Tests were completed prior to fampridine and after 14 (± 1) days of treatment. Three-dimensional gait analyses were completed, and kinematic measures were calculated for overall gait quality using Gait Profile Score, and for joint-specific variables, Gait Variable Scores. Gait function was assessed using spatiotemporal parameters, performance-based tests, and a patient-reported outcome measure. Student's paired t-test/Wilcoxon signed rank test were used to compare baseline and follow-up variables. Sample size calculation for Gait Profile Score required at least 9 participants. FINDINGS: No fampridine-induced improvements in gait quality were demonstrated. For gait function, improvements were found in performance-based tests (Timed 25-Foot Walk: -11.5%; Six Spot Step Test: -13.9%; 2-Minute Walk Test: 18.2%) and self-perceived gait function (12-itemMS Walking Scale: -35.2%). INTERPRETATION: Although two weeks of fampridine treatment in patients with multiple sclerosis improved gait function, there was no change in overall kinematic quality of gait. TRIAL REGISTRATION: This work was collected as a part of a registered clinical trial (MUST): ClinicalTrials.govNCT03847545.

Evaluation of functional outcome measures after fampridine treatment in patients with multiple sclerosis - An interventional follow-up study.

OBJECTIVE: The purpose of this interventional study on participants with multiple sclerosis (MS) with walking disability was to evaluate changes in functional hand and walking measurements after fampridine treatment, after stratifying by the Expanded Disability Status Scale (EDSS). We furthermore wanted to investigate different functional measurements to evaluate their ability to detect responders to fampridine with a clinically relevant improvement. METHODS: Patients were recruited from the MS Clinic at Odense University Hospital and were classified into two disability groups based on their EDSS score (moderate EDSS (EDSSMod) 4.5-5.5 [n = 19] and severe EDSS (EDSSSev) 6.0-7.0 [n = 14]). At baseline (visit 1) they completed the Timed 25-Foot Walk (T25FW), 2-Minute Walk Test (2MWT), Nine Hold Peg Test (9HPT), 12-item Multiple Sclerosis Walking Scale (MSWS-12), and the Six Spot Step Test (SSST). Participants were given 10 mg twice daily fampridine for 14 days before retested (visit 2). For each measurement, cut-off values were used to define responders with a clinically relevant improvement to treatment. The measurements were evaluated separately and in combination. RESULTS: Of the 33 participants, 25 (75.8%) were identified as having a clinically relevant improvement (CRI). For all patients combined (EDSSAll), all five measurements showed significant functional improvement after treatment. For the individual measurements, the highest participant response rates after 14 days of fampridine treatment were seen on the MSWS-12 (57.6%) and 2MWT (42.4%). The 2MWT also showed the largest performance improvement (18.5%) from visit 1 to visit 2. For patients with severe disability (EDSSSev), no significant improvement was seen after fampridine treatment on the T25FW, and most of the responders to T25FW had moderate disability (EDSSMod, 71.5%). Conversely for the SSST, most responders were EDSSSev (83.3%). No participants had a clinically relevant improvement on the 9HPT. The combination of T25FW, SSST, and MSWS-12 was less sensitive in distinguishing responders from non-responders, whereas the combination of 2MWT and MSWS-12 identified the same responders and could better distinguish fampridine responders from non-responders. CONCLUSION: EDSS level did not influence the effect of fampridine treatment on functional hand and walking measures and the responsiveness of the measurements differed only a little between moderate and severe EDSS levels. The combination of self-reported walking capacity (MSWS-12) and walking endurance (2MWT) was better than T25FW, SSST, and MSWS-12 at detecting clinically meaningful improvement after fampridine treatment, which could prove useful in the clinical monitoring of walking disabilities in MS during fampridine treatment.

Early-stage inflammation changes in supraspinatus muscle after rotator cuff tear.

BACKGROUND: Rotator cuff (RC) tendon tear leads to impaired shoulder function and pain. The supraspinatus (SS) tendon is most often affected, but the biological response of the SS muscle to SS tendon tear is largely unknown. This study aimed to investigate time-dependent muscle inflammation, degeneration, fatty infiltration, and regeneration in experimental SS tear conditions. METHODS: Forty-five C57BL/6 mice were subjected to SS tendon tear and allowed to recover for 1, 3, 5, 7, 14, or 28 days. The extent of muscle damage was examined using histologic, flow cytometric, proteomic, and chemiluminescence analyses. RESULTS: We found that muscle inflammation peaked around day 5 with increased monocyte infiltration and increased cytokine levels in the ipsilateral compared to the contralateral SS muscle. Bioinformatics analysis of proteomics on mice that survived 5 days after RC tendon tear revealed upregulated proteins involved in "neutrophil activation involved in immune response" and "extracellular matrix organization," whereas "skeletal muscle tissue development and contraction" and "respiratory electron transport chain" were among the most downregulated. Histologic analysis of collagen showed increased collagen accumulation and fatty infiltration of the ipsilateral SS over time. Finally, we observed time- and lesion-dependent changes in satellite cell and fibro-adipogenic progenitor populations. CONCLUSION: Altogether, we demonstrate that the SS muscle shows severe signs of acute inflammation, early degeneration, and fatty infiltration, as well as reduced regenerative potential following SS tendon tear.

Association of acute inflammatory cytokines, fracture malreduction, and functional outcome 12 months after intra-articular ankle fracture-a prospective cohort study of 46 patients with ankle fractures.

BACKGROUND: Several malreduction criteria have been proposed for ankle surgery, but the criteria of most importance for functional outcome remain undetermined. Furthermore, the acute inflammatory response in the ankle joint after fracture is hypothesized to result in osteoarthritis development, but no study has investigated the correlation between the levels of these inflammatory cytokines and post-surgical functional outcomes. We aimed to identify malreduction criteria and inflammatory cytokines associated with functional outcome after ankle surgery. METHODS: During surgery, synovial fluid from the fractured and healthy contralateral ankles of 46 patients was collected for chemiluminescence analysis of 22 inflammatory cytokines and metabolic proteins. The quality of fracture reduction was based on 9 criteria on plain X-rays and 5 criteria on weight-bearing computed tomography (WBCT) scans. After 3 and 12 months, we recorded scores on American Orthopedic Foot and Ankle Society (AOFAS) scale, the Danish version of Foot Function Index (FFI-DK), EQ-5D-5L index score, the Kellgren-Lawrence score, and joint space narrowing. RESULTS: Tibiofibular (TF) overlap (p = 0.02) and dime sign (p = 0.008) correlated with FFI-DK. Tibiotalar tilt correlated positively with joint space narrowing at 3 months (p = 0.01) and 12 months (p = 0.03). TF widening correlated with FFI-DK (p = 0.04), AOFAS (p = 0.02), and EQ-5D-5L (p = 0.02). No consistent correlations between synovial cytokine levels and functional outcomes were found at 12 months. CONCLUSIONS: Malreduction of TF overlap, TF widening, and tibiotalar tilt were the most important criteria for functional outcome after ankle surgery. Increased inflammatory cytokine levels after fracture did not affect functional outcome at 12 months. TRIAL REGISTRATION: This cohort study is registered the 10th of December 2018 at ClinicalTrials.gov ( NCT03769909 ), was approved by the local committee on health ethics (The Regional Committees on Health Research Ethics for Southern Denmark: J.No. S-20170139), and was reported to the National Danish Data Protection Agency (17/28505).

Elevation of Inflammatory Cytokines and Proteins after Intra-Articular Ankle Fracture: A Cross-Sectional Study of 47 Ankle Fracture Patients.

INTRODUCTION: Intra-articular fractures are the leading etiology for posttraumatic osteoarthritis (PTOA) in the ankle. Elevation of proinflammatory cytokines following intra-articular fracture may lead to synovial catabolism and cartilage degradation. We aimed to compare cytokine levels in injured and healthy ankle joints, examine the longer-term cytokine levels in fractured ankles, and investigate the association between cytokine levels in fractured ankles and plasma. MATERIALS AND METHODS: In this cross-sectional study, synovial fluid (SF) and plasma of forty-seven patients with acute intra-articular ankle fractures and eight patients undergoing implant removal were collected prior to surgery. We determined concentrations of sixteen inflammatory cytokines, two cartilage degradation proteins, and four metabolic proteins and compared the levels in acutely injured ankles with those of the healthy contralateral side or during metal removal. Cytokine levels in injured ankles were also compared to serum cytokine levels. Nonparametric Wilcoxon rank-sum and Spearman tests were used for statistical analysis, and a p value below 0.05 was considered significant. RESULTS: Compared to the healthy ankles, the synovial fluid in ankles with acute intra-articular fracture had elevated levels of several proinflammatory cytokines and proteases (IL-1ß, IL-2, IL-6, IL-8, IL-12p70, TNF, IFNγ, MMP-1, MMP-3, and MMP-9) and anti-inflammatory cytokines (IL-1RA, IL-4, IL-10, and IL-13). The levels of cartilage degradation products (ACG, CTX-2) and metabolic mediators (TGF-ß1 and TGF-ß2) were also significantly higher. Synovial concentrations of ACG, IL-12-p70, IFNγ, IL-4, and bFGF correlated with serum levels. While most of the examined synovial cytokines were unchanged after implant removal, IL-4 and IL-6 levels were upregulated. CONCLUSIONS: We show that an acute ankle fracture is followed by an inflammatory reaction and cartilage degeneration. These data contribute to the current understanding of the protein regulation behind the development of PTOA and is a further step towards supplementing the current surgical treatment. This cross-sectional study was "retrospectively registered" on the 31th October 2017 at ClinicalTrials.gov (NCT03769909). The registration was carried out after inclusion of the first patient and prior to finalization of patient recruitment and statistical analyses: https://clinicaltrials.gov/ct2/show/NCT03769909?term=NCT03769909&draw=2&rank=1.

The inflammatory response of the supraspinatus muscle in rotator cuff tear conditions.

BACKGROUND: Rotator cuff (RC) disorders involve a spectrum of shoulder conditions from early tendinopathy to full-thickness tears leading to impaired shoulder function and pain. The pathology of RC disorder is, nonetheless, still largely unknown. Our hypothesis is that a supraspinatus (SS) tendon tear leads to sustained inflammatory changes of the SS muscle along with fatty infiltration and muscle degeneration, which are threshold markers for poor RC muscle function. The aim of this study was to determine the extent of this muscle inflammation in conjunction with lipid accumulation and fibrosis in RC tear conditions. METHODS: We used proteomics, histology, electrochemiluminescence immunoassay, and quantitative polymerase chain reaction analyses to evaluate inflammatory and degenerative markers and fatty infiltration in biopsies from 22 patients undergoing surgery with repair of a full-thickness SS tendon tear. RESULTS: Bioinformatic analysis showed that proteins involved in innate immunity, extracellular matrix organization, and lipid metabolism were among the most upregulated, whereas mitochondrial electronic transport chain along with muscle fiber function was among the most downregulated. Histologic analysis confirmed changes in muscle fiber organization and the presence of inflammation and fatty infiltration. Inflammation appeared to be driven by a high number of infiltrating macrophages, accompanied by elevated matrix metalloprotease levels and changes in transforming growth factor-ß and cytokine levels in the SS compared with the deltoid muscle. CONCLUSIONS: We demonstrated massive SS muscle inflammation after the tendon tear combined with fatty infiltration and degeneration. The regulation of tissue repair is thus extremely complex, and it may have opposite effects at different time points of healing. Inhibition or stimulation of muscle inflammation may be a potential target to enhance the outcome of the repaired torn RC.

[Christmas article: Get to know yourself and your colleague].

INTRODUCTION: The field of medical studies is rich in stereotypical conceptions of the practitioners of the various medical specialisations. METHOD: By means of a Kahoot of 25 questions about practitioners of nine different medical specialisations, we were trying to see, if a group of people from the medical field (n = 20) and a control group of librarians (n = 22) would answer the questions correctly. The questions were jokes about various medical specialisations, and people were supposed to guess, which kind of medical doctor they described. RESULTS: Those with a background in medical studies were faster and more precise than the librarians. Some of the stereotypes described by the jokes, were known to both groups, others were not. The most familiar stereotypes were those describing anaesthesiologists as sleepy and psychiatrists as crazy. It appeared, that many of the medical speciality stereotypes took their point of departure in the idea, that doctors resemble their patients. CONCLUSION: The survey has limited data, and therefore the conclusion is not very wide-reaching. Some stereotypes were familiar to both groups, others were not. The data indicate that in some cases, contradictory stereotypes exist about individual specialisations.

Supraspinatus and deltoid muscle fiber composition in rotator cuff tear conditions.

BACKGROUND: Rotator cuff (RC) tears are associated with RC muscle atrophy and changes in composition that are crucial to the prognosis of RC repair. The aim of this study was to characterize muscle fiber composition in the supraspinatus (SS) muscle under tear conditions. METHODS: Muscle biopsies were obtained from 21 patients undergoing surgery for an RC tendon tear. Biopsies were obtained from the musculotendinous junction of the SS muscle, and control biopsies were harvested from the deltoid muscle (DT). Biopsies were immunohistochemically processed for detection of type 1 (slow type) and type 2 (fast type) fibers and analyzed using unbiased, stereological principles. We counted the total numbers of type 1 and 2 muscle fibers/mm2, and fiber diameter was used to estimate muscle fiber atrophy and hypertrophy. RESULTS: We found significantly more type 2 cells/mm2 in the SS compared with the DT (P < .01). In addition, we found a significantly higher fraction of type 1 fibers than type 2 fibers in the DT (P < .01), whereas both fiber types were equally present in the SS. The diameters of SS cells were generally smaller than those of DT cells. Atrophy of especially SS type 2 fibers was also demonstrated. Fiber atrophy was more pronounced in men than women. CONCLUSION: The changes in the composition of SS muscle cell types suggest a shift from type 1 to type 2 muscle fibers and atrophy of both type 1 and 2 fibers. This composition indicates loss of endurance and rapid fatigue of the SS muscle under RC tear conditions.

Acute Neurofilament Light Chain Plasma Levels Correlate With Stroke Severity and Clinical Outcome in Ischemic Stroke Patients.

Background: Ischemic stroke causes increased blood-brain barrier permeability and release of markers of axonal damage and inflammation. To investigate diagnostic and prognostic roles of neurofilament light chain (NF-L), we assessed levels of NF-L, S100B, interleukin-6 (IL-6), E-selectin, vascular endothelial growth factor-A (VEGF-A), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) in patients with acute ischemic stroke or transient ischemic attack (TIA) and healthy controls. Methods: We studied neurofilament (NF) expression in 2 cases of human postmortem ischemic stroke, representing infarcts aged 3- to >7-days. In a prospective study, we measured plasma NF-L and inflammatory markers <8 h of symptom onset and at 72 h in acute ischemic stroke (n = 31), TIA (n = 9), and healthy controls (n = 29). We assessed whether NF-L, S100B, and IL-6 were associated with clinical severity on admission (Scandinavian Stroke Scale, SSS), diagnosis of ischemic stroke vs. TIA, and functional outcome at 3 months (modified Rankin Scale, mRS). Results: NF expression increased in ischemic neurons and in the infarcted brain parenchyma after stroke. Plasma NF-L levels were higher in stroke patients than in TIA patients and healthy controls, but IL-6 levels were similar. Higher acute NF-L levels were associated with lower SSS scores at admission and higher mRS scores at 3 months. No correlation was observed between NF-L and S100B, NF-L and IL-6, nor between S100B or IL-6 and SSS or mRS. Compared to controls, stroke patients had significantly higher VEGF-A and VCAM-1 at <8 h that remained elevated at 72 h, with significantly higher VEGF-A at <8 h; ICAM-1 was significantly increased at <8 h, while S100B and E-selectin were unchanged. Conclusions: Plasma NF-L levels, but not IL-6 and S100B, were significant predictors of clinical severity on admission and functional outcome at 3 months. Plasma NF-L is a promising biomarker of functional outcome after ischemic stroke.

Neuromuscular Exercises Improve Shoulder Function More Than Standard Care Exercises in Patients With a Traumatic Anterior Shoulder Dislocation: A Randomized Controlled Trial.

BACKGROUND: There is an important gap in knowledge about the effectiveness of nonoperative treatment (exercise) for patients with traumatic primary and recurrent anterior shoulder dislocations (ASDs). PURPOSE/HYPOTHESIS: The purpose of this study was to assess the efficacy and safety of physical therapist-supervised, shoulder instability neuromuscular exercise (SINEX) versus self-managed, home-based, standard care shoulder exercise (HOMEX) in patients with traumatic ASDs. The hypothesis was that SINEX would have a larger effect and fewer adverse events compared with HOMEX. STUDY DESIGN: Randomized controlled trial; Level of evidence, 2. METHODS: A total of 56 participants with radiographically verified, trauma-initiated primary or recurrent ASDs and self-reported decreased shoulder function were randomized to 12 weeks of either SINEX or HOMEX. The SINEX program consisted of 7 exercises, individually progressing from basic (2 × 20 repetitions each day) to elite (2 × 10 repetitions, 3 times weekly). The HOMEX program included 5 shoulder exercises performed 3 times weekly (2 × 10 repetitions). The primary outcome was the Western Ontario Shoulder Instability Index (WOSI) score, ranging from 0 (best possible) to 2100. The between-group minimal clinically important difference at 12 weeks was 250 points. Secondary outcomes included WOSI subdomain scores, patient-reported ratings of kinesiophobia and pain, objective shoulder function, patient satisfaction, and number of adverse events. RESULTS: The between-group mean difference in the WOSI total score at 12 weeks significantly favored SINEX over HOMEX (-228.1 [95% CI, -430.5 to -25.6]). SINEX was furthermore superior to HOMEX in most of the secondary outcomes (3/4 subdomains of the WOSI and pain level during the past 7 days as well as clinical signs of anterior shoulder instability). Also, although not statistically significant, less than half the proportion of the SINEX patients compared with the HOMEX patients (3/27 [11%] vs 6/24 [25%], respectively; P = .204) underwent or were referred for shoulder stabilizing surgery. Satisfaction with both exercise programs was high, and no serious adverse events were reported. CONCLUSION: Neuromuscular shoulder exercise (SINEX) was superior to standard care exercise (HOMEX) in patients with traumatic ASDs. Further long-term follow-ups on treatment effects are needed. REGISTRATION: NCT02371928 (ClinicalTrials.gov identifier).

TNF deficiency causes alterations in the spatial organization of neurogenic zones and alters the number of microglia and neurons in the cerebral cortex.

BACKGROUND: Although tumor necrosis factor (TNF) inhibitors are used to treat chronic inflammatory diseases, there is little information about how long-term inhibition of TNF affects the homeostatic functions that TNF maintains in the intact CNS. MATERIALS AND METHODS: To assess whether developmental TNF deficiency causes alterations in the naïve CNS, we estimated the number of proliferating cells, microglia, and neurons in the developing neocortex of E13.5, P7 and adult TNF knock out (TNF-/-) mice and wildtype (WT) littermates. We also measured changes in gene and protein expression and monoamine levels in adult WT and TNF-/- mice. To evaluate long-term effects of TNF inhibitors, we treated healthy adult C57BL/6 mice with either saline, the selective soluble TNF inhibitor XPro1595, or the nonselective TNF inhibitor etanercept. We estimated changes in cell number and protein expression after two months of treatment. We assessed the effects of TNF deficiency on cognition by testing adult WT and TNF-/- mice and mice treated with saline, XPro1595, or etanercept with specific behavioral tasks. RESULTS: TNF deficiency decreased the number of proliferating cells and microglia and increased the number of neurons. At the same time, TNF deficiency decreased the expression of WNT signaling-related proteins, specifically Collagen Triple Helix Repeat Containing 1 (CTHRC1) and Frizzled receptor 6 (FZD6). In contrast to XPro1595, long-term inhibition of TNF with etanercept in adult C57BL/6 mice decreased the number of BrdU+ cells in the granule cell layer of the dentate gyrus. Etanercept, but not XPro1595, also impaired spatial learning and memory in the Barnes maze memory test. CONCLUSION: TNF deficiency impacts the organization of neurogenic zones and alters the cell composition in brain. Long-term inhibition of TNF with the nonselective TNF inhibitor etanercept, but not the soluble TNF inhibitor XPro1595, decreases neurogenesis in the adult mouse hippocampus and impairs learning and memory after two months of treatment.

Musculoskeletal application and validation of speckle-tracking ultrasonography.

BACKGROUND: Diseased, injured, or dysfunctional skeletal muscles may demonstrate abnormal function and contractility. Currently, only few in vivo imaging techniques are able to characterize the contractile properties of muscle tissue. This study aimed to test the hypothesis that muscle strain can be tracked in two upper extremity skeletal muscles by speckle-tracking ultrasonography (STU) and correlates with isometric muscle contractions. METHODS: A convenience sample of 10 healthy, adult volunteers with normal shoulder function were tested. The 5 women and 5 men had a mean age of 45 years (range: 39-59 years) and BMI < 30. STU was applied to the supraspinatus (SS) and biceps brachii (BB) muscles using a M11 L-MHz linear transducer (frequency 8-15 MHz) hooked to a Vivid E 9TM ultrasound machine. Strain validation was performed by correlating peak strain against standardized sub-maximal, isometric load conditions of the two muscles (20-80% of maximal voluntary contraction) using a custom-built muscle dynamometer based on strain-gauge technique. Data were analyzed offline using the EchoPac speckle-tracking software and were blinded to the examiner. RESULTS: Intramuscular strain measured by STU in the SS and BB muscles showed moderate to strong correlations with external muscle load (SS: r = - 0.76, p < 0.0001 and BB: r = - 0.60, p < 0.0001). We found strain to vary from approximately 10-20% during increasing submaximal, isometric conditions. CONCLUSIONS: We demonstrate that STU can be applied on healthy skeletal musculature (SS and BB muscles). The observed correlations between strain and isometric contractions suggest a valid technique. However, the concept of measuring muscle strain non-invasively needs further investigation for validity, accuracy, responsiveness, and reliability before its therapeutic and research potential can be realized.

Patients with non-operated traumatic primary or recurrent anterior shoulder dislocation have equally poor self-reported and measured shoulder function: a cross-sectional study.

BACKGROUND: Patients with non-operated traumatic primary anterior shoulder dislocation (PASD) are assumed to have less shoulder impairment than patients with recurrent anterior shoulder dislocations (RASD). This may impact treatment decision strategy. The aim was to study whether patients with non-operated traumatic PASD have less shoulder impairment than those with RASD. METHODS: In a cross-sectional study baseline data from patients with PASD and RASD in a randomised controlled trial of non-operative shoulder exercise treatment were used. Shoulder function was self-reported (Western Ontario Shoulder Instability (WOSI), Tampa Scale of Kinesiophobia (TSK), General Health (EQ-5D-VAS), Numeric Pain Rating Scale (NPRS)), and measured (Constant-Murley shoulder Score (CMS total), CMS - Range of Motion (CMS-ROM, CMS - strength, proprioception, clinical tests). RESULTS: In total, 56 patients (34 (28 men) with PASD and 22 (21 men) with RASD) (mean age 26 years) participated. WOSI total was 1064 and 1048, and TSK above 37 (indicating high re-injury fear) was present in 33 (97%) and 21 (96%) of the groups with PASD and RASD, with no group difference. CMS total (66.4 and 70.4), CMS-ROM (28.7 and 31.5), CMS-strength (injured shoulder: 7.6 kg and 9.1 kg), proprioception and clinical tests were the same. Furthermore, 26 (76%) with PASD and 13 (59%) with RASD reported not to have received non-operative shoulder treatment. CONCLUSIONS: Non-operated patients with PASD and self-reported shoulder trouble three-six weeks after initial injury do not have less shoulder impairment (self-reportedly or objectively measured) than non-operated patients RASD and self-reported shoulder trouble three-six weeks after their latest shoulder dislocation event.

How to deal with a glenoid fracture.

The glenoid fossa is involved in approximately 10% of all scapular fractures.Glenoid fossa incongruity is surprisingly well tolerated.Surgery is recommended when 20% or more of the anterior glenoid fossa is involved.Glenoid rim fractures often lead to chronic shoulder instability.Unstable glenoid neck fractures need surgical treatment and stable fractures can be treated conservatively.CT examination with 3D reformations of the glenoid fossa has improved insight into fracture morphology and fracture patterns and is very helpful for clinical decision makers. Cite this article: EFORT Open Rev 2017;2. DOI: 10.1302/2058-5241.2.160082. Originally published online at www.efortopenreviews.org.

A neuromuscular exercise programme versus standard care for patients with traumatic anterior shoulder instability: study protocol for a randomised controlled trial (the SINEX study).

BACKGROUND: Anterior shoulder dislocation is a common injury and may have considerable impact on shoulder-related quality of life (QoL). If not warranted for initial stabilising surgery, patients are mostly left with little to no post-traumatic rehabilitation. This may be due to lack of evidence-based exercise programmes. In similar, high-impact injuries (e.g. anterior cruciate ligament tears in the knee) neuromuscular exercise has shown large success in improving physical function and QoL. Thus, the objective of this trial is to compare a nonoperative neuromuscular exercise shoulder programme with standard care in patients with traumatic anterior shoulder dislocations (TASD). METHODS/DESIGN: Randomised, assessor-blinded, controlled, multicentre trial. Eighty patients with a TASD will be recruited from three orthopaedic departments in Denmark. Patients with primary or recurrent anterior shoulder dislocations due to at least one traumatic event will be randomised to 12 weeks of either a standardised, individualised or physiotherapist-supervised neuromuscular shoulder exercise programme or standard care (self-managed shoulder exercise programme). Patients will be stratified according to injury status (primary or recurrent). Primary outcome will be change from baseline to 12 weeks in the patient-reported QoL outcome questionnaire, the Western Ontario Shoulder Instability Index (WOSI). DISCUSSION: This trial will be the first study to compare the efficacy and safety of two different nonoperative exercise treatment strategies for patients with TASD. Moreover, this is also the first study to investigate nonoperative treatment effects in patients with recurrent shoulder dislocations. Lastly, this study will add knowledge to the shared decision-making process of treatment strategies for clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02371928 . Registered on 9 February 2015 at the National Institutes of Health Clinical Trials Protocol Registration System.

The Use of Physiotherapy among Patients with Subacromial Impingement Syndrome: Impact of Sex, Socio-Demographic and Clinical Factors.

BACKGROUND: Physiotherapy with exercises is generally recommended in the treatment of patients with subacromial impingement syndrome (SIS). OBJECTIVE: We aimed to investigate the use of physiotherapy in patients with SIS in Danish hospital settings as part of initial non-surgical treatment and after SIS-related surgery and to evaluate to which extent sex, socio-demographic and clinical factors predict the use of physiotherapy. METHODS: Using national health registers, we identified 57,311 patients who had a first hospital contact with a diagnosis of ICD-10, groups M75.1-75.9, 1 July 2007 to 30 June 2011. Records of physiotherapy were extracted within 52 weeks after first contact (or until surgery), and for surgically treated patients within 26 weeks after surgery. Predictors of the use of physiotherapy after first contact and after surgery were analysed as time-to-event. RESULTS: Within 52 weeks after first contact, 43% of the patients had physiotherapy and 30% underwent surgery. Within 26 weeks after surgery, 80% had a record of physiotherapy. After first contact and after surgery, exercise was part of physiotherapy in 65% and 84% of the patients, respectively. A public hospital contact, physiotherapy before hospital contact, administrative region, female sex, a diagnosis of other or unspecified disorders (M75.8-M75.9), and surgical procedure predicted higher use of physiotherapy. Low education level predicted slightly lower use of physiotherapy after first contact, but not after surgery. CONCLUSION: In patients with SIS in Danish hospital settings, physiotherapy was more often used after surgery than as part of initial non-surgical treatment. The use of physiotherapy was less common among men than women, whereas unequal use of physiotherapy in relation to education level was not noticeable. The use of physiotherapy with exercises in initial non-surgical treatment was relatively limited.

Effectiveness of Standardized Physical Therapy Exercises for Patients With Difficulty Returning to Usual Activities After Decompression Surgery for Subacromial Impingement Syndrome: Randomized Controlled Trial.

BACKGROUND: Little is known about the effectiveness of exercise programs after decompression surgery for subacromial impingement syndrome. For patients with difficulty returning to usual activities, special efforts may be needed to improve shoulder function. OBJECTIVE: The purpose of this study was to evaluate the effectiveness at 3 and 12 months of a standardized physical therapy exercise intervention compared with usual care in patients with difficulty returning to usual activities after subacromial decompression surgery. DESIGN: A multicenter randomized controlled trial was conducted. SETTING: The study was conducted in 6 public departments of orthopedic surgery, 2 departments of occupational medicine, and 2 physical therapy training centers in Central Denmark Region. PATIENTS: One hundred twenty-six patients reporting difficulty returning to usual activities at the postoperative clinical follow-up 8 to 12 weeks after subacromial decompression surgery participated. INTERVENTION: A standardized exercise program consisting of physical therapist-supervised individual training sessions and home training was used. OUTCOME MEASURES: The primary outcome measure was the Oxford Shoulder Score. Secondary outcome measures were the Constant Score and the Fear-Avoidance Beliefs Questionnaire. RESULTS: At 3 and 12 months, follow-up data were obtained for 92% and 83% of the patients, respectively. Intention-to-treat analyses suggested a between-group difference on the Oxford Shoulder Score favoring the exercise group at 3 months, with an adjusted mean difference of 2.0 (95% confidence interval=-0.5, 4.6), and at 12 months, with an adjusted mean difference of 5.8 (95% confidence interval=2.8, 8.9). Significantly larger improvements for the exercise group were observed for most secondary and supplementary outcome measures. LIMITATIONS: The nature of the exercise intervention did not allow blinding of patients and care providers. CONCLUSION: The standardized physical therapy exercise intervention resulted in statistically significant and clinically relevant improvement in shoulder pain and function at 12 months compared with usual care.

Responsiveness and Minimal Clinically Important Change: A Comparison Between 2 Shoulder Outcome Measures.

Study Design A prospective cohort study nested in a randomized controlled trial. Objectives To determine and compare responsiveness and minimal clinically important change of the modified Constant score (CS) and the Oxford Shoulder Score (OSS). Background The OSS and the CS are commonly used to assess shoulder outcomes. However, few studies have evaluated the measurement properties of the OSS and CS in terms of responsiveness and minimal clinically important change. Methods The study included 126 patients who reported having difficulty returning to usual activities 8 to 12 weeks after arthroscopic decompression surgery for subacromial impingement syndrome. The assessment at baseline and at 3 months included the OSS, the CS, and the European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) index. Responsiveness was assessed as follows: by correlation analysis between the change scores of the OSS, CS, and EQ-5D-3L index, and the Patient Global Impression of Change (PGIC) scale; by receiver-operating-characteristic (ROC) curve analysis using the PGIC scale as an external anchor; and by effect-size statistics. Results At 3 months, a follow-up assessment of 112 patients (89%) was conducted. The change scores of the CS and the OSS were more strongly correlated with the external anchor (PGIC scale) than the change score of the EQ-5D-3L index. The areas under the ROC curves exceeded 0.80 for both shoulder scores, with no significant differences between them, and comparable effect-size estimates were observed for the CS and the OSS. Minimal clinically important change ROC values were 6 points for the OSS and 11 points for the CS, with upper 95% cutoff limits of 12 and 22 points, respectively. Conclusion The CS and the OSS were both suitable for assessing improvement after decompression surgery.