Correction: Cross-cultural translation and psychometric validation of the French version of the Fear-Avoidance Components Scale (FACS).

[This corrects the article DOI: 10.1371/journal.pone.0288899.].

Validity, reliability and responsiveness of a French translation of the Western Ontario Osteoarthritis of the Shoulder index (WOOS).

INTRODUCTION: While several general questionnaires can be used to evaluate shoulder conditions, very few tools specifically evaluate the impact of shoulder osteoarthritis. The WOOS (Western Ontario Osteoarthritis of the Shoulder index) is a patient-reported outcome measure with excellent psychometric properties intended for patients suffering from shoulder osteoarthritis. Unfortunately, there is no validated French version of this questionnaire. OBJECTIVE: Produce a validated French version of the WOOS that is suitable for the Francophone populations of Europe and North America. MATERIAL AND METHODS: A validated protocol was used to create a French version of the WOOS (WOOS-Fr). Included were patients whose first language was French, who could read French and who had shoulder osteoarthritis destined for treatment (surgical treatment = arthroplasty). The WOOS-Fr was compared to the F-QuickDASH-D/S (Disability of the Arm, Shoulder and Hand - French translation) to assess its validity. Reliability and responsiveness were also analyzed. RESULTS: A French version of the WOOS (WOOS-Fr) was accepted by a multinational committee. The WOOS-Fr was validated in 71 French-speaking subjects. A strong positive correlation was found between the WOOS-Fr and the F-QuickDASH-D/S during the initial evaluation. The intra-class correlation (ICC) of the total WOOS-Fr score indicated good reliability between the initial WOOS and the 1-week WOOS (ICC: 0.84; 95% CI: [0.767; 0.896]; p value: <.001) in 57 patients. The responsiveness between the initial WOOS-Fr and at 1 year postoperative was high in the 36 operated patients (standardized mean response of 1.95). DISCUSSION: A French translation of the WOOS questionnaire was created and validated for use in French-speaking populations. This questionnaire will make it easier to evaluate the psychometric results of patients with shoulder osteoarthritis in Francophone countries. LEVEL OF EVIDENCE: III; multicenter cohort study.

Apelin stimulation of the vascular skeletal muscle stem cell niche enhances endogenous repair in dystrophic mice.

Impaired skeletal muscle stem cell (MuSC) function has long been suspected to contribute to the pathogenesis of muscular dystrophy (MD). Here, we showed that defects in the endothelial cell (EC) compartment of the vascular stem cell niche in mouse models of Duchenne MD, laminin α2-related MD, and collagen VI-related myopathy were associated with inefficient mobilization of MuSCs after tissue damage. Using chemoinformatic analysis, we identified the 13-amino acid form of the peptide hormone apelin (AP-13) as a candidate for systemic stimulation of skeletal muscle ECs. Systemic administration of AP-13 using osmotic pumps generated a pro-proliferative EC-rich niche that supported MuSC function through angiocrine factors and markedly improved tissue regeneration and muscle strength in all three dystrophic mouse models. Moreover, EC-specific knockout of the apelin receptor led to regenerative defects that phenocopied key pathological features of MD, including vascular defects, fibrosis, muscle fiber necrosis, impaired MuSC function, and reduced force generation. Together, these studies provide in vivo proof of concept that enhancing endogenous skeletal muscle repair by targeting the vascular niche is a viable therapeutic avenue for MD and characterized AP-13 as a candidate for further study for the systemic treatment of MuSC dysfunction.

Validity, reliability and responsiveness of the French translation of the Patient-Rated Wrist Evaluation Questionnaire (PRWE).

INTRODUCTION: The patient-rated wrist evaluation questionnaire (PRWE) is a specific wrist questionnaire, developed in Canada that has been validated and proved reliable and sensitive. It assesses pain and function. Unfortunately, there was no validated French-language version. It is important that a translation should be methodologically rigorous, as both linguistic and cultural factors come into play. OBJECTIVE: To produce a French-language version of the PRWE, culturally adapted to the French-speaking populations of Europe and North America. MATERIALS AND METHODS: A validated protocol was used to produce a French-language version of the PRWE (PRWE-Fr) that would be culturally acceptable for the French-speaking populations of Europe and North America. Reliability and responsiveness analyses were performed and PRWE-Fr scores were compared to F-QuickDASH-D/S (French translation of short-form Disabilities of the Arm, Shoulder and Hand-Disability/Symptoms) scores to assess validity. RESULTS: A French-language version of the PRWE (PRWE-Fr) was accepted by a multinational committee, then validated in 65 French-speaking subjects, divided into 2 groups for analyses. A strong positive correlation was found between PRWE-Fr and F-QuickDASH-D/S scores. Comparison of results between two PRWE-Fr sessions at a 1-week interval found a very strong correlation (ρ=0.93; r2=0.868; p<0.001). The intraclass correlation coefficient for total PRWE-Fr score demonstrated excellent reliability (ICC: 0.93; 95% CI: [0.859; 0.969]; p<0.001). Responsiveness analysis revealed greater sensitivity to change than for the F-QuickDASH-D/S (standardized response mean [SRM], 1.14 versus 1.04 respectively). DISCUSSION: A French-language version of the PRWE was produced and validated for use in French-speaking populations. It should facilitate evaluation of results in French-speaking settings, collaboration in multinational studies and comparison between studies performed in different countries. LEVEL OF EVIDENCE: II; Multicenter cohort study.

Estimated diameter increase from a 4S to a 6S hamstring graft configuration - A cadaveric study.

PURPOSE: Graft diameter in anterior cruciate ligament reconstructions has been shown to influence the risk of failure. It is therefore important to be able to adjust the graft configuration to modify the diameter. To measure the impact of a 6-strand (6S) hamstring autograft configuration on graft diameter compared to the standard 4-strand (4S) configuration. METHODS: Cadaveric study on 33 knees, using the usual hamstring graft harvesting technique. Semitendinosus and gracilis tendons were harvested and their length, width, and diameter were measured in 4S and 6S configurations separately by three evaluators. RESULTS: 6S configuration leads to a median increase of 1.5 (range: 0.0-2.0) mm in diameter compared to 4S (p < 0.001). A graft diameter of more than 8 mm is attained in less than a third of 4S grafts within this population in comparison to 84% when the 6S configuration is used. DISCUSSION: The 6S hamstring graft configuration increases the graft diameter by a median of 1.5 millimeters compared to the traditional 4S configuration. It can reliably be used to obtain an 8.5 mm graft diameter or more in cases where the semitendinosus measures at least 270.5 mm and the 4S configuration has a diameter of 7.5 mm or 8 mm. This information helps to better delineate the impact of a 6S configuration in a pre-operative or intra-operative setting to optimize the decisional process and surgical flow and to easily adapt the graft diameter. LEVEL OF EVIDENCE: V (cadaveric study).

Cross-cultural translation and psychometric validation of the French version of the Fear-Avoidance Components Scale (FACS).

BACKGROUND: The Fear-Avoidance Components Scale (FACS) is a reliable and valid instrument widely used to assess fear-avoidance beliefs related to pain and disability. However, there is a scarcity of validated translations of the FACS in different cultural and linguistic contexts, including the French population. This study aimed to translate and validate the French version of the FACS (FACS-Fr/CF), examining its psychometric properties among French-speaking individuals. METHODS: A cross-cultural translation process-including forward translation, backward translation, expert committee review, and pre-testing-was conducted to develop the FACS-Fr/CF. The translated version was administered to a sample of French-speaking adults (n = 55) with chronic musculoskeletal pain. Internal consistency (including confirmatory analyses of the 2 factors identified in the Serbian version), test-retest reliability and convergent validity were then assessed. RESULTS: The FACS-Fr/CF demonstrated high global internal consistency (α = 0.94, 95% CI: 0.91-0.96) as well as high internal consistency of the 2 factors identified in the Serbian version (α = 0.90, 95% CI: 0.86-0.94 and α = 0.90, 95% CI: 0.85-0.94, respectively). Test-retest analysis revealed a moderate (close to high) reliability (ICC = 0.89; 95% CI: 0.82-0.94 and r = 0.89; p<0.005). Convergent validity was supported by significant correlations between the FACS-Fr/CF scores and the Tampa Scale for Kinesiophobia (r = 0.82; p < 0.005), the Pain Catastrophizing Scale (r = 0.72; p < 0.005) and the Hospital Anxiety and Depression Scale (r = 0.66; p < 0.005). CONCLUSION: The present study provides evidence for the cross-cultural translation and psychometric validation of the FACS-Fr/CF. The FACS-Fr/CF exhibits a high internal consistency, a moderate (close to high) test-retest reliability, and good construct validity, suggesting its utility in assessing fear-avoidance beliefs in the French-speaking population. This validated tool can enhance the assessment and understanding of fear-avoidance behaviors and facilitate cross-cultural research in pain-related studies.

Relationship between Motor Corticospinal System, Endogenous Pain Modulation Mechanisms and Clinical Symptoms in Patients with Knee Osteoarthritis: New Perspectives on an Old Disease.

Knee osteoarthritis (OA) is a painful condition characterized by joint and bone changes. A growing number of studies suggest that these changes only partially explain the pain experienced by individuals with OA. The purpose of the current study was to evaluate if corticospinal and bulbospinal projection measurements were interrelated in patients with knee OA, and to explore the relationship between these neurophysiological measures and temporal summation (excitatory mechanisms of pain) on one hand, and clinical symptoms on the other. Twenty-eight (28) patients with knee OA were recruited. Corticospinal projections were measured using transcranial magnetic stimulation, while bulbospinal projections were evaluated with a conditioned pain modulation (CPM) protocol using a counter-irritation paradigm. Validated questionnaires were used to document clinical and psychological manifestations. All participants suffered from moderate to severe pain. There was a positive association between corticospinal excitability and the effectiveness of the CPM (rs = 0.67, p = 0.01, n = 13). There was also a positive relationship between pain intensity and corticospinal excitability (rs = 0.45, p = 0.03, n = 23), and between pain intensity and temporal summation (rs = 0.58, p = 0.01, n = 18). The results of this study highlight some of the central nervous system changes that could be involved in knee OA and underline the importance of interindividual variability to better understand and explain the semiology and pathophysiology of knee OA.

The POSI study: gender differences in 94 cases of postoperative shoulder surgery infection: results of a 7-year retrospective multicenter study.

BACKGROUND: Contrary to lower limb infection, POstoperative Shoulder surgery Infection (POSI) often involves Cutibacterium acnes. Our aim was to describe patient characteristics and pathogens retrieved in POSI to guide initial empiric antibiotic selection with suspected infection during revision. We also compared microorganisms in infection following trauma, arthroplasty (AP), and arthroscopy (AS). METHODS: A multicenter retrospective study from 2010 to 2016 reviewed laboratory databases and medical records to identify patients with a previous shoulder surgery and a confirmed shoulder infection. The following procedures were included: AP, AS, fracture fixation (FF), and another open surgery (OS). A confirmed shoulder infection was defined as 2 positive cultures or more of the same microorganism, or clear clinical infection with 1 positive culture or more. RESULTS: Among the 5 hospitals and 28 surgeons involved, 94 POSI cases were identified. Mean age was 59 years at index surgery (range: 22-91) with a majority of men (n = 70, 74%). Among POSI cases, AP was the most common index surgery (n = 41), followed by FF (n = 27), AS (n = 16), and OS (n = 10). The median time between index surgery and the first positive sample was 5 months and the mean was 23 months (minimum 6 days to maximum 27 years), illustrating a positively skewed distribution. Cutibacterium spp were identified in 64 patients (68%), including 59 C acnes patients (63%), which was the most frequent germ in all 4 surgical groups. In 86% of cases, C acnes was identified at the first revision. The other 2 most common germs were Staphylococcus epidermidis and Staphylococcus aureus, with 29% and 17%, respectively. Polymicrobial infection was present in 30% of patients. Gender analysis revealed that C acnes was twice as frequent in men (male = 52 of 70, female = 7 of 24; P < .001). S epidermidis was more prevalent in women (n = 11; 46%) compared with men (n = 16; 21%) (P = .032). C acnes infection was most frequent in arthroscopic surgery (n = 14; 70%, P = .049). S epidermidis was 3 times more prevalent in chronic than in acute cases. CONCLUSION: Empiric antimicrobial therapy following POSI, while waiting for culture results, should cover C acnes, S epidermidis, and S aureus. There is a significant gender difference regarding POSI culture results. C acnes is more frequent in men, but should still be covered in women as it was found in 29% of cases.

Phone Administration of the Western Ontario Shoulder Instability Index Is More Reliable Than Administration via Email.

BACKGROUND: The Western Ontario Shoulder Instability (WOSI) questionnaire is a 21-item questionnaire to evaluate quality of life in patients with shoulder instability. Completing the questionnaire is time-consuming because each item is evaluated on a visual analog scale. Telephone or email versions of the score are appealing alternatives to administering it during the standard in-person patient visit; however, their validity and reliability remain unknown. QUESTIONS/PURPOSES: (1) Does the numerical scale (NS) version of the WOSI correlate with the original WOSI and Quick-DASH? (2) Do telephone and email administration of the NS-WOSI have good reliability and consistency? (3) Compared with the original WOSI form, does the NS form lead to faster completion for patients and quicker data extraction for researchers? METHODS: Between 2014 and 2019, 50 patients with a documented history of shoulder dislocation with persistent symptomatic shoulder instability, whether anterior, posterior, or multidirectional; patients scheduled for surgery; and patients with traumatic or nontraumatic injuries were prospectively recruited from the outpatient clinic of two university hospitals acting as Level 1 trauma centers and sports traumatology tertiary referral centers. The median (IQR) age was 28 years (24 to 36), and 80% (40 of 50) were men. Most (52% [26 of 50]) patients had two to five lifetime shoulder dislocations. Validity of the NS-WOSI was assessed using the Pearson correlation coefficient during an in-person visit; the original WOSI questionnaire (or its previously validated French-language version), NS-WOSI, and Quick-DASH questionnaires were administered in a random order. After a minimum 7-day interval, 78% (39 of 50) of patients completed the phone interview, and 74% (37 of 50) of patients completed the email version of the NS-WOSI score to evaluate NS-WOSI's reliability using the intraclass correlation coefficient (ICC), which was interpreted as poor (< 0.5), moderate (0.50-0.75), strong (0.75-0.90), and very strong (> 0.90). The standard error of measurement (SEM) was used to evaluate variability around the true score, with a low value indicating a high reliability. The 95% minimal detectable change (MDC 95% ) was calculated to evaluate the minimal change in score that was not related to measurement errors. Lastly, the Cronbach alpha was used to assess internal consistency (intercorrelation strength), where a value > 0.70 was considered good. The time needed for the patient to complete the various versions and for researchers to extract data was recorded. RESULTS: The NS-WOSI score was very strongly correlated with the original WOSI score (r = 0.96 [95% confidence interval (CI) 0.93 to 0.98]; p < 0.001). Although telephone-acquired and email-acquired data for the NS-WOSI questionnaires were correlated with the NS-WOSI (telephone r = 0.91 [95% CI 0.83 to 0.95]; p < 0.001; email r = 0.84 [95% CI 0.71 to 0.91]; p < 0.001), the ICC was higher for telephone interviews (0.92 [95% CI 0.86 to 0.96] versus email 0.80 [95% CI 0.64 to 0.89]), indicating that although both had good reliability, the phone interview was more suitable. The phone interview was also preferable to email regarding SEM (3% [52 of 2100 points] versus 6% [132 of 2100 points]) and the MDC 95% (7% [144 of 2100 points] versus 17% [366 of 2100 points]). The 95% CI of the MDC acquired by email was superior to the reported minimum clinically important difference for the original WOSI (7% [152 of 2100 points]), meaning that an error of measurement could wrongly be interpreted as a clinically significant change in score. Internal consistency was deemed good, with a Cronbach alpha of 0.96 (95% CI 0.92 to 98) and 0.89 (95% CI 0.79 to 0.94) for NS-WOSI telephone and email, respectively. The time to complete the NS-WOSI was reduced compared with the original WOSI (221 ± 153 seconds versus 266 ± 146 seconds, mean difference -45 seconds [95% CI -72 to -12]; p = 0.009). Lastly, data extraction was faster (62 ± 15 seconds versus 209 ± 52 seconds, mean difference -147 seconds [95% CI -164 to -130]; p < 0.001) with the NS-WOSI than with the original WOSI. CONCLUSION: The NS-WOSI in person, by telephone, or by email is a valid, reliable, and timesaving alternative to the original WOSI questionnaire. However, the reliability of data acquisition by telephone interviews was superior to that of email. CLINICAL RELEVANCE: Given that there were no important differences in performance for the NS-WOSI, regardless of whether it was administered in person or by phone, we suggest that physicians use both interchangeably based on patient convenience. However, we do not recommend using the email version, especially for research purposes, since it was not as reliable when compared with in-person administration. The responsiveness of the modified NS-WOSI, as well as factors influencing response rates to phone interview, are questions that remain to be explored.

A Partial-Thickness Quadriceps Autograft Reliably Augments the Size of the Hamstring Graft During Anterior Cruciate Ligament Reconstruction.

Purpose: To measure the increase in diameter resulting from the augmentation of a hamstring autograft with a partial width rectus femoris tendon band in anterior cruciate ligament reconstruction. Methods: Thirty-three cadaveric knees were dissected to harvest semitendinosus and gracilis tendons (4S) along with a 6-mm wide tendon band from the rectus femoris. Harvesting was done according to the usual surgical techniques of both harvests. Measures of length and diameter in 4S and 4S augmented with the rectus femoris band (4S +Q) configurations were performed separately by 3 evaluators. Results: The quadriceps augmentation led to an average increase of 1.49 mm (95% confidence interval 1.03-1.95 mm) in diameter of the 4-strand hamstring grafts. The previously demonstrated threshold diameter of 8.5 mm was attained in only 30% of 4S grafts within this population in comparison with 88% when augmented with a quadriceps band. Conclusions: In conclusion, supplementing doubled hamstring graft (4S) with quadricipital tendon in anterior cruciate ligament reconstruction (ACLR) increases the graft diameter by an average of 1.49 mm. It has the physical potential to reliably augment hamstring grafts that measure 7.5 mm in diameter or more in order to obtain an 8.5 mm when necessitated. Clinical Relevance: Increased graft diameter is associated with a decreased risk of graft failure after ACLR. Because of this, it is important to identify methods to increase the size of grafts. This study investigates the use of a partial-width rectus femoris tendon band as an option to reliably augment graft sizes during ACLR.

Anterior Cruciate Ligament Sizing Tools Can Be Interchanged Without Affecting Graft Diameter Measurement.

Purpose: To determine whether different types of measurement tools can be interchanged without significantly affecting the resulting graft diameter. Methods: Hamstrings (gracilis and semitendinosus) and quadriceps tendons in 33 cadaver knees were harvested. Three different anterior cruciate ligament (ACL) graft combinations were created using these tendons, making 99 cadaver grafts samples available to measure. The grafts were randomly passed through sizing tubes and a slotted measurement block to determine their diameter. Interobserver and intraobserver reliabilities of measurements were assessed. Pearson correlation test, as well as Bland Altman graph, were used to evaluate the interchangeability of the tools. Results: In 95% of cases, the diameter difference between the tubes and the block measures was less than the 0.5 mm in increment cutoff. Both the intraobserver and interobserver reliability were excellent. Conclusions: This study showed that the ACL graft diameter measurement does not vary whether a slotted block or sizing tube from the same company is used. Clinical Relevance: ACL graft size has an influence on the surgical technique and clinical outcomes. Therefore it is important to have reliable sizing tools.

Using ultrasound imaging to assess novice physiotherapy students' ability to locate musculoskeletal structures with palpation.

OBJECTIVE: Use ultrasound imaging to assess success rates of novice physiotherapy students attempting to locate two tendons and two joint spaces using palpation. DESIGN: Cross-sectional study. SETTING: Master of physiotherapy program at an academic institution. PARTICIPANTS: Twenty-two end of first-year physiotherapy students. METHODS: Participants were asked to palpate and locate the long head of the biceps (LHBT) and tibialis posterior (PTT) tendons as well as the acromioclavicular joint (ACJ) and medial tibiofemoral joint (TFJ) spaces on two human models. A truncated needle was taped onto the skin, parallel to the palpated structure. Ultrasound imaging was used to assess the position of the needle relative to the structures. MAIN OUTCOME MEASURES: Success or failure was determined based on a judgment call on the needle position relative to the targeted structure on the ultrasound images. Inter-evaluator agreement for judgment criteria was investigated using Cohen's kappa tests and success rates subsequently calculated. RESULTS: Kappa coefficients were 1.00 for all structures collectively, 1.00 for LHBT and PTT tendons, 1.006 for ACJ, and 0.79 for TFJ. Palpation success rates were: 9% for LHBT, 64% for PTT, 23% for ACJ, and 31% for medial TFJ. CONCLUSION: These results highlight the fact that there is room for improvement in anatomy and palpation skill teaching methods and ultrasound imaging is valuable tool to assess this important skill.

Editorial Commentary: Should We Condemn the Shoulder Instability Severity Index Scoring System? Not at All!... Can We Improve Its Radiographic Component? Yes, We Can!

Is patient selection necessary in shoulder instability surgery? Absolutely. The risk-benefit discussion that the surgeon must have with the patient before proposing an arthroscopic Bankart repair remains crucial to provide informed consent. The most important preoperative risk factors are incorporated in the instability severity index (ISI) score to assist surgeons in the decision-making process. This 10-point score is based on factors derived from a preoperative questionnaire, physical examination, and simple plain radiographs. Using this score at the first visit, the surgeon can explain to the patient and family why a Bankart repair may be contraindicated and why other surgical options may be more suitable. A recent study found that the ISI score has no limited predictive value when applied in a preselected population of military patients without severe bone loss or hyperlaxity. This is not surprising because the authors analyzed a preselected patient population with lower risk than the general population. The value of the ISI scoring system relies on the fact that this tool has been developed after evaluation of arthroscopic Bankart repair in an unselected patient population and that there is no need for sophisticated imaging studies to make the decision. This scoring system should not be condemned but complemented with preoperative advanced imaging studies (computed tomography [CT] scanning or magnetic resonance imaging) to assess the severity of the bone lesions more accurately. Today, the choice of the surgical procedure depends not only on the clinical risk factors included in the ISI score (age, type of sports, level of practice, hyperlaxity) but also on the presence, location and size of bony lesions, as identified and measured on advanced CT scanning images.

Transcranial direct current stimulation (a-tCDS) after subacromial injections in patients with subacromial pain syndrome: a randomized controlled pilot study.

BACKGROUND: Subacromial pain syndrome (SAPS) is a common complaint in orthopaedics. Subacromial corticosteroid injections (CSI) can relieve pain in the short term. Anodal transcranial direct current stimulation (a-tDCS) has been used for symptomatic pain relief in a variety of chronic pain conditions. The aim of this pilot study was to assess whether the application a-tDCS could enhance the symptomatic relief provided by CSI in patients affected by SAPS. METHODS: Thirty-eight participants (18 to 65-year-old) suffering from SAPS were recruited to have a CSI and randomly allocated to receive, 1 weeks post CSI, real a-tDCS (r-tDCS), sham tDCS (s-tDCS) or no intervention (Control). Upper limb function was measured 1 week prior to the CSI, at the 2- and 4-week follow-ups using self-administered questionnaires and physical measures. Self-reported pain and activity during each day were logged by the participants using visual analog scales (VAS). Differences between groups were tested using repeated-measures ANOVAs. RESULTS: Pain VAS and the Single Assessment Numeric Evaluation scale (SANE) showed significant improvement from baseline 2 weeks and 4 weeks after CSI in all groups (p < 0.05). There were no significant group X time interaction 2 weeks following tDCS treatment in any of the variables. CONCLUSION: All groups showed significant improvement in pain VAS and SANE scores following the CSI. One session of a-tDCS treatment 2 weeks following CSI did not result in any additive or potentializing effects when compared to a s-tDCS or a control group. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03967574 . Registered 30 May 2019 - Retrospectively registered.

14-3-3η Promotes Invadosome Formation via the FOXO3-Snail Axis in Rheumatoid Arthritis Fibroblast-like Synoviocytes.

Erosive destruction of joint structures is a critical event in the progression of rheumatoid arthritis (RA), in which fibroblast-like synoviocytes (FLS) are the primary effectors. We previously reported that the ability of RA FLS to degrade extracellular matrix (ECM) components depends on the formation of actin-rich membrane protrusions, called invadosomes, through processes that remain elusive. 14-3-3η belongs to a family of scaffolding proteins involved in a wide range of cellular functions, and its expression is closely related to joint damage and disease activity in RA patients. In this study, we sought to assess the role of 14-3-3η in joint damage by examining its contribution to the invadosome formation phenotype of FLS. Using human primary FLS, we show that 14-3-3η expression is closely associated with their ability to form invadosomes. Furthermore, knockdown of 14-3-3η using shRNAs decreases the level of invadosome formation in RA FLS, whereas addition of the recombinant protein to FLS from healthy individuals promotes their formation. Mechanistic studies suggest that 14-3-3η regulates invadosome formation by increasing Snail expression, a mechanism that involves nuclear exclusion of the transcription repressor FOXO3. Our results implicate the 14-3-3η-FOXO3-Snail axis in promoting the aggressive ECM-degrading phenotype of RA FLS, and suggest a role for this scaffolding protein in cartilage degradation.

Deltopectoral vs. deltoid split approach for proximal HUmerus fracture fixation with locking plate: a prospective RAndomized study (HURA).

BACKGROUND: This study aimed to compare the functional and clinical outcomes between the deltoid split (DS) approach and the classic deltopectoral (DP) approach for locking plate fixation of proximal humerus fractures (PHF) in a prospective randomized multicenter study. METHODS: From 2007 to 2015, all patients with a PHF Neer II/III were invited to participate. Exclusion criteria were pre-existing pathology to the limb, patient refusing or too ill to undergo surgery, patient needing another type of treatment (nail, arthroplasty), and axillary nerve impairment. After consent, patients were randomized to one of the 2 treatments using the dark envelope method. Functional outcome was evaluated by validated questionnaires (12-Item Short Form Health Survey: version 2, Quick-DASH) with a minimum follow-up of 12 months. Complications were noted. RESULTS: A total of 85 patients (44 DS, 41 DP) were randomized (mean age of 62). Groups were equivalent in terms of age, gender, body mass index, severity of fracture, and preinjury scores. The mean follow-up was 26 months. All clinical outcome measures were in favor of the deltopectoral approach. Specifically, the Q-DASH and SF-12v2 were better in the DP group (12 vs. 26, P = .003 and 56 vs. 51, P = .049, respectively). There were more complications in DS patients, but they did not reach statistical significance. CONCLUSIONS: The primary hypothesis on the superiority of the deltoid split incision was rebutted. On the basis of our study, the DP approach seems to offer better function compared with the DS approach for fixation of Neer 2 and 3 PHF fractures fixed with a locking plate.

Both Human Hematoma Punctured from Pelvic Fractures and Serum Increase Muscle Resident Stem Cells Response to BMP9: A Multivariate Statistical Approach.

Hematoma and skeletal muscles play a crucial role in bone fracture healing. The muscle resident mesenchymal stromal cells (mrSCs) can promote bone formation by differentiating into osteoblasts upon treatment by bone morphogenetic proteins (BMP), such as BMP9. However, the influence of hematoma fracture extracts (Hema) on human mrSC (hmrSC) response to BMP9 is still unknown. We therefore determined the influence of Hema, human healthy serum (HH), and fetal bovine serum (FBS, control) on BMP9-induced osteoblast commitment of hmrSC by measuring alkaline phosphatase activity. Multiplex assays of 90 cytokines were performed to characterize HH and Hema composition and allow their classification by a multivariate statistical approach depending on their expression levels. We confirmed that BMP9 had a greater effect on osteoblastic differentiation of hmrSCs than BMP2 in presence of FBS. The hmrSCs response to BMP9 was enhanced by both Hema and HH, even though several cytokines were upregulated (IL-6, IL-8, MCP-1, VEGF-A and osteopontin), downregulated (BMP9, PDGF) or similar (TNF-alpha) in Hema compared with HH. Thus, hematoma may potentiate BMP9-induced osteogenic differentiation of hmrSCs during bone fracture healing. The multivariate statistical analyses will help to identify the cytokines involved in such phenomenon leading to normal or pathological bone healing.

Wrist-Based Accelerometers and Visual Analog Scales as Outcome Measures for Shoulder Activity During Daily Living in Patients With Rotator Cuff Tendinopathy: Instrument Validation Study.

BACKGROUND: Shoulder pain secondary to rotator cuff tendinopathy affects a large proportion of patients in orthopedic surgery practices. Corticosteroid injections are a common intervention proposed for these patients. The clinical evaluation of a response to corticosteroid injections is usually based only on the patient's self-evaluation of his function, activity, and pain by multiple questionnaires with varying metrological qualities. Objective measures of upper extremity functions are lacking, but wearable sensors are emerging as potential tools to assess upper extremity function and activity. OBJECTIVE: This study aimed (1) to evaluate and compare test-retest reliability and sensitivity to change of known clinical assessments of shoulder function to wrist-based accelerometer measures and visual analog scales (VAS) of shoulder activity during daily living in patients with rotator cuff tendinopathy convergent validity and (2) to determine the acceptability and compliance of using wrist-based wearable sensors. METHODS: A total of 38 patients affected by rotator cuff tendinopathy wore wrist accelerometers on the affected side for a total of 5 weeks. Western Ontario Rotator Cuff (WORC) index; Short version of the Disability of the Arm, Shoulder, and Hand questionnaire (QuickDASH); and clinical examination (range of motion and strength) were performed the week before the corticosteroid injections, the day of the corticosteroid injections, and 2 and 4 weeks after the corticosteroid injections. Daily Single Assessment Numeric Evaluation (SANE) and VAS were filled by participants to record shoulder pain and activity. Accelerometer data were processed to extract daily upper extremity activity in the form of active time; activity counts; and ratio of low-intensity activities, medium-intensity activities, and high-intensity activities. RESULTS: Daily pain measured using VAS and SANE correlated well with the WORC and QuickDASH questionnaires (r=0.564-0.815) but not with accelerometry measures, amplitude, and strength. Daily activity measured with VAS had good correlation with active time (r=0.484, P=.02). All questionnaires had excellent test-retest reliability at 1 week before corticosteroid injections (intraclass correlation coefficient [ICC]=0.883-0.950). Acceptable reliability was observed with accelerometry (ICC=0.621-0.724), apart from low-intensity activities (ICC=0.104). Sensitivity to change was excellent at 2 and 4 weeks for all questionnaires (standardized response mean=1.039-2.094) except for activity VAS (standardized response mean=0.50). Accelerometry measures had low sensitivity to change at 2 weeks, but excellent sensitivity at 4 weeks (standardized response mean=0.803-1.032). CONCLUSIONS: Daily pain VAS and SANE had good correlation with the validated questionnaires, excellent reliability at 1 week, and excellent sensitivity to change at 2 and 4 weeks. Daily activity VAS and accelerometry-derived active time correlated well together. Activity VAS had excellent reliability, but moderate sensitivity to change. Accelerometry measures had moderate reliability and acceptable sensitivity to change at 4 weeks.

Muscle injury-induced hypoxia alters the proliferation and differentiation potentials of muscle resident stromal cells.

BACKGROUND: Trauma-induced heterotopic ossification (HO) is a complication that develops under three conditions: the presence of an osteogenic progenitor cell, an inducing factor, and a permissive environment. We previously showed that a mouse multipotent Sca1+ CD31- Lin- muscle resident stromal cell (mrSC) population is involved in the development of HO in the presence of inducing factors, members of the bone morphogenetic protein family. Interestingly, BMP9 unlike BMP2 causes HO only if the muscle is damaged by injection of cardiotoxin. Because acute trauma often results in blood vessel breakdown, we hypothesized that a hypoxic state in damaged muscles may foster mrSCs activation and proliferation and trigger differentiation toward an osteogenic lineage, thus promoting the development of HO. METHODS: Three- to - six-month-old male C57Bl/6 mice were used to induce muscle damage by injection of cardiotoxin intramuscularly into the tibialis anterior and gastrocnemius muscles. mrSCs were isolated from damaged (hypoxic state) and contralateral healthy muscles and counted, and their osteoblastic differentiation with or without BMP2 and BMP9 was determined by alkaline phosphatase activity measurement. The proliferation and differentiation of mrSCs isolated from healthy muscles was also studied in normoxic incubator and hypoxic conditions. The effect of hypoxia on BMP synthesis and Smad pathway activation was determined by qPCR and/or Western blot analyses. Differences between normally distributed groups were compared using a Student's paired t test or an unpaired t test. RESULTS: The hypoxic state of a severely damaged muscle increased the proliferation and osteogenic differentiation of mrSCs. mrSCs isolated from damaged muscles also displayed greater sensitivity to osteogenic signals, especially BMP9, than did mrSCs from a healthy muscle. In hypoxic conditions, mrSCs isolated from a control muscle were more proliferative and were more prone to osteogenic differentiation. Interestingly, Smad1/5/8 activation was detected in hypoxic conditions and was still present after 5 days, while Smad1/5/8 phosphorylation could not be detected after 3 h of normoxic incubator condition. BMP9 mRNA transcripts and protein levels were higher in mrSCs cultured in hypoxic conditions. Our results suggest that low-oxygen levels in damaged muscle influence mrSC behavior by facilitating their differentiation into osteoblasts. This effect may be mediated partly through the activation of the Smad pathway and the expression of osteoinductive growth factors such as BMP9 by mrSCs. CONCLUSION: Hypoxia should be considered a key factor in the microenvironment of damaged muscle that triggers HO.

The Addition of Glenohumeral Adductor Coactivation to a Rotator Cuff Exercise Program for Rotator Cuff Tendinopathy: A Single-Blind Randomized Controlled Trial.

BACKGROUND: Treatments for rotator cuff tendinopathy include rotator cuff muscle strengthening to promote better muscle recruitment in order to minimize subacromial narrowing during active movement. Glenohumeral adductor recruitment has also been shown to prevent such narrowing in asymptomatic individuals; therefore, adding glenohumeral adductor coactivation during rotator cuff strengthening could enhance the efficacy of rotator cuff strengthening. However, no study has explored its benefits. OBJECTIVES: To compare the short-term efficacy of adding glenohumeral adductor coactivation to a rotator cuff-strengthening program to improve function, reduce symptoms, and increase acromiohumeral distance in adults with rotator cuff tendinopathy. METHODS: In this single-blind randomized controlled trial, 42 participants with rotator cuff tendinopathy were randomly assigned to 2 groups, one that received strengthening of the scapular and rotator cuff muscles or one that received rotator cuff strengthening plus coactivation with pectoralis major and latissimus dorsi recruitment. The daily programs were performed at home for 6 weeks, with supervised training and follow-up sessions. Functional limitations/symptoms (Disabilities of the Arm, Shoulder and Hand [DASH] questionnaire as the primary outcome, and the Western Ontario Rotator Cuff index), pain (visual analog scale), and acromiohumeral distance were measured at baseline, 3 weeks, and 6 weeks. Data were analyzed using a mixed-model analysis of variance. RESULTS: No significant group-by-time interaction was observed for the Disabilities of the Arm, Shoulder and Hand questionnaire, Western Ontario Rotator Cuff index, visual analog scale, and acromiohumeral distance (P≥.055). Significant time effects were obtained for the Western Ontario Rotator Cuff index and visual analog scale for pain with movement (P<.001). CONCLUSION: The present findings show that adding glenohumeral adductor coactivation to a rotator cuff-strengthening program does not result in improved short-term efficacy in any of the measured outcomes. This study was registered with ClinicalTrials.gov (NCT02837848). LEVEL OF EVIDENCE: Therapy, level 1b. J Orthop Sports Phys Ther 2019;49(3):126-135. Epub 30 Nov 2018. doi:10.2519/jospt.2019.8240.