Early shoulder-girdle MRI findings in severe COVID-19-related intensive care unit-acquired weakness: a prospective cohort study.

OBJECTIVE: To describe clinical and early shoulder-girdle MR imaging findings in severe COVID-19-related intensive care unit-acquired weakness (ICU-AW) after ICU discharge. METHODS: A single-center prospective cohort study of all consecutive patients with COVID-19-related ICU-AW from November 2020 to June 2021. All patients underwent similar clinical evaluations and shoulder-girdle MRI within the first month and then 3 months (± 1 month) after ICU discharge. RESULTS: We included 25 patients (14 males; mean [SD] age 62.4 [12.5]). Within the first month after ICU discharge, all patients showed severe proximal predominant bilateral muscular weakness (mean Medical Research Council total score = 46.5/60 [10.1]) associated with bilateral, peripheral muscular edema-like MRI signals of the shoulder girdle in 23/25 (92%) patients. At 3 months, 21/25 (84%) patients showed complete or quasi-complete resolution of proximal muscular weakness (mean Medical Research Council total score > 48/60) and 23/25 (92%) complete resolution of MRI signals of the shoulder girdle, but 12/20 (60%) patients experienced shoulder pain and/or shoulder dysfunction. CONCLUSIONS: Early shoulder-girdle MRI findings in COVID-19-related ICU-AW included muscular edema-like peripheral signal intensities, without fatty muscle involution or muscle necrosis, with favorable evolution at 3 months. Precocious MRI can help clinicians distinguish critical illness myopathy from alternative, more severe diagnoses and can be useful in the care of patients discharged from intensive care with ICU-AW. KEY POINTS: • We describe the clinical and shoulder-girdle MRI findings of COVID-19-related severe intensive care unit-acquired weakness. • This information can be used by clinicians to achieve a nearly specific diagnosis, distinguish alternative diagnoses, assess functional prognosis, and select the more appropriate health care rehabilitation and shoulder impairment treatment.

Scoliosis.

Scoliosis is a three-dimensional spinal deformity that can occur at any age. It may be idiopathic or secondary in children, idiopathic and degenerative in adults. Management of patients with scoliosis is multidisciplinary, involving rheumatologists, radiologists, orthopaedic surgeons, and prosthetists. Imaging plays a central role in diagnosis, including the search for secondary causes, follow-up, and preoperative work-up if surgery is required. Evaluating scoliosis involves obtaining frontal and lateral full-spine radiographs in the standing position, with analysis of coronal and sagittal alignment. For adolescent idiopathic scoliosis, imaging follow-up is often required, accomplished using low-dose stereoradiography such as EOS imaging. For adult degenerative scoliosis, the crucial characteristic is rotatory subluxation, also well detected on radiographs. Magnetic resonance imaging is usually more informative than computed tomography for visualizing associated canal and foraminal stenoses. Radiologists must also have a thorough understanding of postoperative features and complications of scoliosis surgery because aspects can be misleading.

Barriers and facilitators to bracing in adults with painful degenerative scoliosis: a single-centred mixed-method feasibility study.

BACKGROUND: Conservative treatments including bracing and exercise therapy are prescribed on the first-line in adults with degenerative scoliosis. However, adherence to conservative treatments is low. We aimed to assess barriers and facilitators to bracing in adults with painful degenerative scoliosis. METHODS: We conducted a single-centred mixed-method pilot and feasibility study. All patients scheduled for a multidisciplinary custom-made bracing consultation, from July 2019 to January 2020, in a French tertiary care centre, were screened. Patients were eligible if they had painful adult degenerative scoliosis and a prescription for a rigid custom-made lumbar-sacral orthosis. The primary outcome was barriers and facilitators to bracing assessed by a qualitative approach using semi-structured interviews. Secondary outcomes were back pain, spine-specific activity limitations, symptoms of depression and satisfaction with bracing post-intervention assessed by a quantitative approach. RESULTS: Overall, 56 patients were screened and 14 (25%) were included. Mean age was 68.2 (12.3) years. Mean follow-up was 9.8 (2.0) months. Barriers to bracing were increased limitations in some activities, discomfort in hot weather and burden of aesthetic appearance. Facilitators to bracing were reduced pain, improved activities of daily living, suitable weight and improved spinal alignment. Participants self-implemented solutions to enhance adherence. The mean reduction from baseline in pain intensity was 1.7 (2.3) of 10 points, and 6 of 13 patients (46%) had pain intensity < 4 of 10 points. CONCLUSION: Bracing is a feasible intervention for people with painful adult degenerative scoliosis. Patients self-implemented their own solutions to enhance adherence.

Degenerative Lumbar Spine Disease: Imaging and Biomechanics.

Chronic low back pain (CLBP) is one of the most common diagnoses encountered when considering years lived with disability. The degenerative changes of the lumbar spine include a wide spectrum of morphological modifications visible on imaging, some of them often asymptomatic or not consistent with symptoms. Phenotyping by considering both clinical and imaging biomarkers can improve the management of CLBP. Depending on the clinical presentation, imaging helps determine the most likely anatomical nociceptive source, thereby enhancing the therapeutic approach by targeting a specific lesion. Three pathologic conditions with an approach based on our experience can be described: (1) pure painful syndromes related to single nociceptive sources (e.g., disk pain, active disk pain, and facet joint osteoarthritis pain), (2) multifactorial painful syndromes, representing a combination of several nociceptive sources (such as lumbar spinal stenosis pain, foraminal stenosis pain, and instability pain), and (3) nonspecific CLBP, often explained by postural (muscular) syndromes.

Can T2-weighted Dixon fat-only images replace T1-weighted images in degenerative disc disease with Modic changes on lumbar spine MRI?

OBJECTIVES: To evaluate the diagnostic performance and interobserver agreement of a magnetic resonance imaging (MRI) protocol that only includes sagittal T2-weighted Dixon fat and water images as an alternative to a standard protocol that includes both sagittal T1-weighted sequence and T2-weighted Dixon water images as reference standard in lumbar degenerative disc disease with Modic changes. METHODS: From February 2017 to March 2019, 114 patients who underwent lumbar spine MRI for low back pain were included in this retrospective study. All MRI showed Modic changes at least at one vertebral level. Two radiologists read the standard protocol and 1 month later the alternative protocol. All MRI were assessed for Modic changes (types, location, extension) as well as structural changes (endplate defects, facet arthropathy, spinal stenosis, foraminal stenosis, Schmorl nodes, spondylolisthesis, disc bulges, and degeneration). Interobserver agreement was assessed, as well as diagnostic performance using the standard protocol as reference standard. RESULTS: Interobserver agreement was moderate to excellent (kappa ranging from 0.51 to 0.92). Diagnostic performance of the alternative protocol was good for detection of any Modic change (sensitivity = 100.00% [95% CI, 99.03-100.00]; specificity = 98.89% [95% CI, 98.02-99.44]), as well as for detection of each Modic subtype and structural variables (sensitivity respectively 100% and ranging from 88.43 to 99.75% ; specificity ranging respectively from 97.62 to 100% and 99.58 to 99.91% ). CONCLUSIONS: Combined with T2-weighted Dixon water images, T2-weighted Dixon fat images provide good diagnostic performance compared to T1-weighted images in lumbar degenerative disc disease with Modic changes, and could therefore allow for a shortened protocol. KEY POINTS: • Combined with T2-weighted Dixon water images, T2-weighted Dixon fat images (in comparison to T1-weighted sequence) can provide good diagnostic performance in lumbar degenerative disc disease with Modic changes. • Interobserver agreement of the alternative protocol including sagittal T2-weighted Dixon fat and water images was substantial to excellent for every studied variable except for facet arthropathy. • A shortened MRI protocol including T2-weighted Dixon sequence without T1-weighted sequence could be proposed in this clinical setting.

Conservative treatment for chronic coccydynia: a 36-month prospective observational study of 115 patients.

PURPOSE: To describe long-term outcomes of conservative treatment for chronic coccydynia. METHODS: We conducted a 36-month prospective observational study. Adults with chronic coccydynia (> 2 months) were included. The first-line treatment was coccygeal corticosteroid injection. The second-line treatment was either manual therapy or coccygectomy. The primary endpoint was the mean variation from baseline of coccydynia intensity at 6 and 36 months, using a numeric rating scale (0, no pain; 10, maximal pain). Evolution was considered unfavorable when coccydynia intensity was > 3 of 10 points at 36 months or coccygectomy had been performed. We carried out bivariate and multivariate analyses to identify variables associated with an unfavorable evolution. RESULTS: We included 115 participants. Mean (SD) age was 43.5 (12.3) years, duration of coccydynia 18.4 (21.6) months and coccydynia intensity 6.5 (2.0) of 10 points. Mean variations for coccydynia intensity were - 1.5 (3.0) at 6 months and - 2.8 (3.2) at 36 months. At 36 months, 59/115 (51%) participants had an unfavorable evolution. In bivariate analysis, posterior coccyx dislocations were numerically more frequent in participants with an unfavorable evolution compared to others (29/59 (48%) versus 17/56 (30%), p = 0.057). In multivariate analysis, longer duration of coccydynia was associated with an unfavorable evolution (OR = 1.04, 95% CI from 1.01 to 1.07, p = 0.023). CONCLUSION: In adults with chronic coccydynia receiving conservative treatment, symptoms decrease overtime, but significantly persist at 36 months in more than half of them. For patients with posterior coccyx dislocation, coccygectomy may be considered rapidly.

Construction of an ICF core set and ICF-based questionnaire assessing activities and participation in patients with systemic sclerosis.

OBJECTIVES: To develop an International Classification of Functioning, Disability and Health (ICF) core set for SSc and to conceive a patient-centred ICF-based questionnaire assessing activities and participation in patients with SSc. METHODS: The construction of the ICF core set followed two steps. In the first step, meaningful concepts related to SSc were collected using data source triangulation from patients (n = 18), experts (n = 10) and literature (n = 174 articles). In the second step, concepts were linked to the best-matching ICF categories by one reviewer according to prespecified linking rules. Finally, patient-reported activities and participation categories of the ICF core set were translated into understandable questions. RESULTS: After linking concepts to ICF categories, 150 ICF categories were collected from focus groups, 22 from experts and 82 from literature. After fusion of the sources and removal of duplicates, the ICF core set included 164 categories: one at the first level, 157 at the second level and six at the third level, with 50 categories on body functions, 15 on body structures, 52 on activities and participation, and 47 on environmental factors. Patient-reported ICF categories on activities and participation were translated into a patient-centred ICF-based 65-item questionnaire. CONCLUSION: The present study proposes an ICF core set that offers a conceptual framework for SSc patients' care and health policy. Using a patient-centred approach, a patient-centred ICF-based questionnaire, the Cochin Scleroderma ICF-65 questionnaire, assessing activities and participation in patients with SSc, was conceived. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT01848418.

Diagnosis and management of lumbar spinal stenosis in primary care in France: a survey of general practitioners.

BACKGROUND: Lumbar spinal stenosis (LSS) is a common spinal condition and the most frequent indication for spinal surgery in elderly people. General practitioners (GPs) are on the 1st line for its diagnosis and treatment. We aimed to assess how GPs diagnose and treat people with LSS in France. METHODS: We conducted a cross-sectional survey in a primary care setting. French GPs were selected by a random draw from the French Medical Board. The questionnaire was designed by 3 physicians specialized in physical and rehabilitation medicine and a resident in general practice. A provisional questionnaire was tested in a pilot survey of 11 French GPs. Participants' feedbacks served to build the final questionnaire. This latter was submitted by e-mail or mail to 330 GPs. GPs were surveyed about the 3 main domains relevant to the management of people with LSS in primary care: 1/ diagnosis, 2/ pharmacological treatments and 3/ non-pharmacological treatments, using self-administered open- and closed-ended questions and visual analog scales. RESULTS: Overall, 90/330 (27.3%) GPs completed the survey. 51/89 (57.3%) GPs were confident with managing people with LSS. Low back pain 51/87 (58.6%), neurogenic claudication 38/87 (43.7%) and paresthesia in the lower limbs 31/87 (35.6%) were the 3 most frequently cited clinical signs leading to the diagnosis of LSS. Improvement with lumbar flexion was mentioned by 9/87 (10.3%) GPs. 85/86 (98.8%) would consider prescribing lumbar imaging, 60/84 (71.4%) corticoid spinal injections and 42/79 (53.2%) would never prescribe lumbar flexion-based endurance training. All GPs would refer people with LSS to another specialist. CONCLUSIONS: French GPs lack confidence with diagnosing LSS and prescribing pharmacological and non-pharmacological treatments for people with LSS.

Unilateral winged scapula: Clinical and electrodiagnostic experience with 128 cases, with special attention to long thoracic nerve palsy.

INTRODUCTION: In this study we report a large series of patients with unilateral winged scapula (WS), with special attention to long thoracic nerve (LTN) palsy. METHODS: Clinical and electrodiagnostic data were collected from 128 patients over a 25-year period. RESULTS: Causes of unilateral WS were LTN palsy (n = 70), spinal accessory nerve (SAN) palsy (n = 39), both LTN and SAN palsy (n = 5), facioscapulohumeral dystrophy (FSH) (n = 5), orthopedic causes (n = 11), voluntary WS (n = 6), and no definite cause (n = 2). LTN palsy was related to neuralgic amyotrophy (NA) in 61 patients and involved the right side in 62 patients. DISCUSSION: Clinical data allow for identifying 2 main clinical patterns for LTN and SAN palsy. Electrodiagnostic examination should consider bilateral nerve conduction studies of the LTN and SAN, and needle electromyography of their target muscles. LTN palsy is the most frequent cause of unilateral WS and is usually related to NA. Voluntary WS and FSH must be considered in young patients. Muscle Nerve 57: 913-920, 2018.

Intradiscal Glucocorticoid Injection for Patients With Chronic Low Back Pain Associated With Active Discopathy: A Randomized Trial.

BACKGROUND: Active discopathy is associated with a specific phenotype of chronic low back pain (LBP). Local inflammation has a role in active discopathy-associated symptoms. OBJECTIVE: To assess the efficacy of a single glucocorticoid intradiscal injection (GC IDI) in patients with chronic LBP with active discopathy. DESIGN: Prospective, parallel-group, double-blind, randomized, controlled study. (ClinicalTrials.gov: NCT00804531). SETTING: 3 tertiary care centers in France. PATIENTS: 135 patients with chronic LBP with active discopathy on magnetic resonance imaging (MRI). INTERVENTION: A single GC IDI (25 mg prednisolone acetate) during discography (n = 67) or discography alone (n = 68). MEASUREMENTS: The primary outcome was the percentage of patients with LBP intensity less than 40 on an 11-point numerical rating scale (0 [no pain] to 100 [maximum pain] in 10-point increments) in the previous 48 hours at 1 month after the intervention. The main secondary outcomes were LBP intensity and persistent active discopathy on MRI at 12 months and spine-specific limitations in activities, health-related quality of life, anxiety and depression, employment status, and use of analgesics and nonsteroidal anti-inflammatory drugs at 1 and 12 months. RESULTS: All randomly assigned patients were included in the primary efficacy analysis. At 1 month after the intervention, the percentage of responders (LBP intensity <40) was higher in the GC IDI group (36 of 65 [55.4%]) than the control group (21 of 63 [33.3%]) (absolute risk difference, 22.1 percentage points [95% CI, 5.5 to 38.7 percentage points]; P = 0.009). The groups did not differ in LBP intensity at 12 months and in most secondary outcomes at 1 and 12 months. LIMITATION: Tertiary care setting. CONCLUSION: In chronic LBP associated with active discopathy, a single GC IDI reduces LBP at 1 month but not at 12 months. PRIMARY FUNDING SOURCE: French Ministry of Health.

Intervertebral disc and vertebral endplate subchondral changes associated with Modic 1 changes of the lumbar spine: a cross-sectional study.

BACKGROUND: Modic 1 changes are usually associated with degenerative disc disease (DDD). We aimed to compare Modic 1 changes with advanced degenerative disc disease (>50%-intervertebral space narrowing [IVSN]) to Modic 1 changes with less advanced lumbar degenerative disc disease (≤50%-IVSN). METHODS: We conducted a cross-sectional study. The computerized MRI database from a French tertiary care hospital was searched. Patients were included if they were ≥ 18 years old and had a lumbar MRI between January 1, 2006 and January 31, 2008, that showed a Modic 1 signal at a single level. The strength of the magnet was 1.5 T. MRI were reviewed by 2 assessors. Age and gender were recorded. MRI changes involving the intervertebral disc and the vertebral endplate subchondral bone were assessed for Modic 1 signal, intervertebral space narrowing, asymmetrical degenerative disc disease, spondylolisthesis, anterior and posterior intervertebral disc herniation, and anterior and lateral osteophytes. These outcomes were compared between >50%-IVSN Modic 1 and ≤50%-IVSN Modic 1 groups. For bivariate analysis, comparisons involved nonparametric Kruskal-Wallis test for quantitative variables and nonparametric Fisher's exact test for qualitative variables. Multivariate analysis was conducted to determine factors independently associated with <50%-IVSN Modic 1 changes by backward stepwise regression. Informed consent and formal approval from Institutional Review Board is not required for this type of study. This statement was confirmed by our Institutional Review Board. RESULTS: MRI for 101 individuals were eligible. Patients' mean (SD) age was 56.6(13.4) years, and 41/101(40.6%) were men. Modic 1 were most frequently observed at L4/L5 and L5/S1 (37[36.6%] cases each). As compared with >50%-IVSN Modic 1 patients, ≤50%-IVSN Modic 1 patients were younger (mean[SD] age 51.5[14.1] vs 58.8[12.6] years, p = 0.019), Modic 1 were more frequent at L5/S1 level (19[61.3%] vs 18[25.7%], p = 0.001), and anterior and lateral osteophytes were less frequent (13[41.9%] vs 55[78.6%], p < 0.001, and 11[35.5%] vs 48[68.6%], p = 0.002, respectively). CONCLUSIONS: ≤50%-IVSN Modic 1 are rather found in young men at L5/S1 level and are associated with less frequent osteophytes than >50%-IVSN Modic, while >50%-IVSN Modic 1 are rather found in older women at L4/L5 level.

Control of retinoid levels by CYP26B1 is important for lymphatic vascular development in the mouse embryo.

During embryogenesis, lymphatic endothelial progenitor cells first arise from a subset of blood vascular endothelial cells in the dorsolateral aspects of the cardinal veins. The molecular cues responsible for defining the regionalisation of such a discrete pool of progenitors remain uncharacterised. Here we identify a novel function for CYP26B1, an enzyme known to play a role in tissue morphogenesis by fine-tuning retinoic acid (RA) concentration, in regulating lymphangiogenesis. Cyp26b1-null mice, in which RA levels are elevated, exhibited an increased number of lymphatic endothelial progenitor cells in the cardinal veins, together with hyperplastic, blood filled lymph sacs and hyperplastic dermal lymphatic vessels. Conversely, mice over-expressing Cyp26b1 had hypoplastic lymph sacs and lymphatic vessels. Our data suggest that RA clearance by CYP26B1 in the vicinity of lymphatic endothelial progenitor cells is important for determining the position and size of the progenitor pool specified. Our studies identify a genetic pathway that underpins the architecture of the developing lymphatics and define CYP26B1 as a novel modulator of lymphatic vascular patterning.

From Modic 1 vertebral-endplate subchondral bone signal changes detected by MRI to the concept of 'active discopathy'.

Late-1980s MRI-detected vertebral-endplate subchondral bone signal changes associated with degenerative disc disease as well as recent studies suggest that in some patients, non-specific chronic low back pain (NS cLBP) can be defined by specific clinical, radiological and biological features, for a concept of active discopathy. This concept allows for associating a particular NS cLBP phenotype to a specific anatomical lesion, namely those with Modic 1 signal changes seen on MRI. Local inflammation is thought to play a pivotal role in these changes. Other etiopathogenic processes may include local infection and mechanical or biochemical stress combined with predisposing genetic factors; treatment strategies remain debated. Modic 1 changes detected by MRI can be considered a first biomarker in NS cLBP. Such changes are of high clinical relevance because they are associated with a specific clinical phenotype and can be targeted by specific treatments.

High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis.

BACKGROUND: Exercise or physical activity is recommended for improving pain and functional status in people with knee or hip osteoarthritis. These are complex interventions whose effectiveness depends on one or more components that are often poorly identified. It has been suggested that health benefits may be greater with high-intensity rather than low-intensity exercise or physical activity. OBJECTIVES: To determine the benefits and harms of high- versus low-intensity physical activity or exercise programs in people with hip or knee osteoarthritis. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; issue 06, 2014), MEDLINE (194 8 to June 2014) , EMBASE (198 0 to June 2014), CINAHL (1982 to June 2014), PEDro (1929 to June 2014), SCOPUS (to June 2014) and the World Health Organization (WHO) International Clinical Registry Platform (to June 2014) for articles, without a language restriction. We also handsearched relevant conference proceedings, trials, and reference lists and contacted researchers and experts in the field to identify additional studies. SELECTION CRITERIA: We included randomized controlled trials of people with knee or hip osteoarthritis that compared high- versus low-intensity physical activity or exercise programs between the experimental and control group.High-intensity physical activity or exercise programs training had to refer to an increase in the overall amount of training time (frequency, duration, number of sessions) or the amount of work (strength, number of repetitions) or effort/energy expenditure (exertion, heart rate, effort). DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study eligibility and extracted data on trial details. We contacted authors for additional information if necessary. We assessed the quality of the body of evidence for these outcomes using the GRADE approach. MAIN RESULTS: We included reports for six studies of 656 participants that compared high- and low-intensity exercise programs; five studies exclusively recruited people with symptomatic knee osteoarthritis (620 participants), and one study exclusively recruited people with hip or knee osteoarthritis (36 participants). The majority of the participants were females (70%). No studies evaluated physical activity programs. We found the overall quality of evidence to be low to very low due to concerns about study limitations and imprecision (small number of studies, large confidence intervals) for the major outcomes using the GRADE approach. Most of the studies had an unclear or high risk of bias for several domains, and we judged five of the six studies to be at high risk for performance, detection, and attrition bias.Low-quality evidence indicated reduced pain on a 20-point Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain scale (mean difference (MD) -0.84, 95% confidence interval (CI) -1.63 to -0.04; 4% absolute reduction, 95% CI -8% to 0%; number needed to treat for an additional beneficial outcome (NNTB) 11, 95% CI 14 to 22) and improved physical function on the 68-point WOMAC disability subscale (MD -2.65, 95% CI -5.29 to -0.01; 4% absolute reduction; NNTB 10, 95% CI 8 to 13) immediately at the end of the exercise programs (from 8 to 24 weeks). However, these results are unlikely to be of clinical importance. These small improvements did not continue at longer-term follow-up (up to 40 weeks after the end of the intervention). We are uncertain of the effect on quality of life, as only one study reported this outcome (0 to 200 scale; MD 4.3, 95% CI -6.5 to 15.2; 2% absolute reduction; very low level of evidence).Our subgroup analyses provided uncertain evidence as to whether increased exercise time (duration, number of sessions) and level of resistance (strength or effort) have an impact on the exercise program effects.Three studies reported withdrawals due to adverse events. The number of dropouts was small. Only one study systematically monitored adverse effects, but four studies reported some adverse effects related to knee pain associated with an exercise program. We are uncertain as to whether high intensity increases the number of adverse effects (Peto odds ratio 1.72, 95% CI 0.51 to 5.81; - 2% absolute risk reduction; very low level of evidence). None of the included studies reported serious adverse events. AUTHORS' CONCLUSIONS: We found very low-quality to low-quality evidence for no important clinical benefit of high-intensity compared to low-intensity exercise programs in improving pain and physical function in the short term. There was insufficient evidence to determine the effect of different types of intensity of exercise programs.We are uncertain as to whether higher-intensity exercise programs may induce more harmful effects than those of lower intensity; this must be evaluated by further studies. Withdrawals due to adverse events were poorly monitored and not reported systematically in each group. We downgraded the evidence to low or very low because of the risk of bias, inconsistency, and imprecision.The small number of studies comparing high- and low-intensity exercise programs in osteoarthritis underscores the need for more studies investigating the dose-response relationship in exercise programs. In particular, further studies are needed to establish the minimal intensity of exercise programs needed for clinical effect and the highest intensity patients can tolerate. Larger studies should comply with the Consolidated Standards of Reporting Trials (CONSORT) checklist and systematically report harms data to evaluate the potential impact of highest intensities of exercise programs in people with joint damage.

The status of strontium in biological apatites: an XANES/EXAFS investigation.

Osteoporosis represents a major public health problem through its association with fragility fractures. The public health burden of osteoporotic fractures will rise in future generations, due in part to an increase in life expectancy. Strontium-based drugs have been shown to increase bone mass in postmenopausal osteoporosis patients and to reduce fracture risk but the molecular mechanisms of the action of these Sr-based drugs are not totally elucidated. The local environment of Sr(2+) cations in biological apatites present in pathological and physiological calcifications in patients without such Sr-based drugs has been assessed. In this investigation, X-ray absorption spectra have been collected for 17 pathological and physiological calcifications. These experimental data have been combined with a set of numerical simulations using the ab initio FEFF9 X-ray spectroscopy program which takes into account possible distortion and Ca/Sr substitution in the environment of the Sr(2+) cations. For selected samples, Fourier transforms of the EXAFS modulations have been performed. The complete set of experimental data collected on 17 samples indicates that there is no relationship between the nature of the calcification (physiological and pathological) and the adsorption mode of Sr(2+) cations (simple adsorption or insertion). Such structural considerations have medical implications. Pathological and physiological calcifications correspond to two very different preparation procedures but are associated with the same localization of Sr(2+) versus apatite crystals. Based on this study, it seems that for supplementation of Sr at low concentration, Sr(2+) cations will be localized into the apatite network.

Genicular artery embolization for knee osteoarthritis: Results of the LipioJoint-1 trial.

PURPOSE: The purpose of this study was to evaluate the safety and efficacy of transient genicular artery embolization (GAE) using an ethiodized oil-based emulsion for the treatment of knee osteoarthritis (KOA). MATERIALS AND METHODS: This prospective, single-arm, open-label, multicenter, first-in-human cohort trial was registered on ClinicalTrials.gov (NCT04733092). The main inclusion criterion was diagnosis of KOA according to a visual analogue scale (VAS) pain score ≥ 40 mm (score range: 0-100 mm), despite conservative treatment for at least three months. Treatment efficacy was assessed using changes in VAS pain score, Mean Western Ontario & McMaster Universities osteoarthritis (WOMAC) function score (normalized to 100; score ranging from 0 to100) and outcome measures in rheumatoid arthritis clinical trials (OMERACT)-Osteoarthritis Research Society (OARSI) set of responder criteria. RESULTS: Twenty-two consecutive participants (13 women; mean age, 66 ± 9 [standard deviation (SD)]) were included and underwent GAE. Emulsion consisted in a mixture of ioversol and ethiodized oil (ratio 1:3, respectively) prepared extemporaneously. The rate of serious adverse events attributed to GAE within one month was 5% (1/22), corresponding to reversible worsening of renal function. Immediate technical success rate was 100%. Mean VAS pain score dropped from 74.4 ± 16.5 (SD) mm at baseline to 37.2 ± 26.7 (SD) mm at three months (P < 0.001). Mean WOMAC function score (normalized to 100: score ranging from 0 to 100) decreased from 57.3 ± 17.1 (SD) at baseline to 33.5 ± 25.9 (SD) at three months (P < 0.001). At three months, 16 out of 22 participants (73%) were considered responders according to the OMERACT-OARSI set of responder criteria, including high improvement in either pain or WOMAC function, or improvement in both pain and WOMAC function. CONCLUSION: GAE using an ethiodized oil-based emulsion is safe and improves pain and function in participants with KOA for at least three months.

Arthro-distension with early and intensive mobilization for shoulder adhesive capsulitis: A randomized controlled trial.

BACKGROUND: There are several therapeutic options for the management of shoulder adhesive capsulitis (AC). The superiority of arthro-distension over intra-articular steroid injection (ISI) for AC remains controversial. OBJECTIVES: To evaluate the efficacy of a single arthro-distension procedure combined with early and intensive mobilization (ADM) and physiotherapy, versus ISI and physiotherapy, in people with AC lasting ≥3 months. METHODS: This was a prospective, 2 parallel-group, 2-center, observer-blind randomized controlled trial conducted in tertiary care settings. Adults with AC were randomly assigned to the treatment or control group. Efficacy was assessed using the self-administered Shoulder Pain and Disability Index (SPADI). Total, pain and disability SPADI scores 15 days, 6 weeks, and 3, 6 and 12 months after the procedure (total SPADI at 15 days: primary outcome; other outcomes were secondary) were compared between groups using analysis of covariance (ANCOVA). A post hoc analysis stratified on the initial range of passive glenohumeral abduction, which had not been pre-specified, was conducted. RESULTS: There were 33 participants in each group. Both groups improved over time. Mean (SD) total SPADI score at 15 days was 33.8 (19.6) in the treatment group and 32.8 (17.5) in the control group, p = 0.393. There were no significant differences for any variables in the overall sample. The post hoc analysis found ADM to be associated with a significant decrease in total SPADI score at 15 days compared with ISI (p = 0.049) in individuals with initial passive glenohumeral abduction >45°. CONCLUSIONS: The effects of ADM on pain and function were not statistically different from those of ISI. However, ADM may be useful in individuals with initial passive glenohumeral abduction >45°. DATABASE REGISTRATION: NCT00724113.

Adrenomedullin(22-52) combats inflammation and prevents systemic bone loss in murine collagen-induced arthritis.

OBJECTIVE: Adrenomedullin(22-52) is a truncated peptide derived from adrenomedullin, a growth factor with antiapoptotic and immunoregulatory properties. It can act as an agonist or an antagonist depending on cell type. Its in vivo effects are unknown, but adrenomedullin(22-52) could possess immunomodulatory properties. This study was undertaken to evaluate the effect of adrenomedullin(22-52) in a mouse model of arthritis. METHODS: DBA/1 mice with collagen-induced arthritis (CIA) were treated with 1.2 µg/gm adrenomedullin(22-52) , adrenomedullin, or saline at arthritis onset. Bone mineral density was measured at the beginning of the experiment and when mice were killed. Mouse joints were processed for histologic analysis and protein studies, and spleens were examined for Treg cell expression. Cytokine expression was studied in mouse joint tissue and serum. RESULTS: In mice with CIA, adrenomedullin and adrenomedullin(22-52) reduced clinical and histologic arthritis scores and shifted the pattern of articular and systemic cytokine expression from Th1 to Th2, as compared to untreated mice with CIA (controls). Tumor necrosis factor α, interleukin-6 (IL-6), and IL-17A levels were significantly decreased in the joints of mice with CIA treated with adrenomedullin or adrenomedullin(22-52) as compared to controls, whereas IL-4 and IL-10 levels were increased. Adrenomedullin(22-52) was more effective than adrenomedullin in modulating cytokine content and enhanced Treg cell function without changing Treg cell expression compared to controls. Adrenomedullin receptor binding and transcriptional adrenomedullin receptor expression were markedly increased in joints from controls, whereas adrenomedullin receptor binding was considerably decreased in treated animals. Mice with CIA treated with adrenomedullin or adrenomedullin(22-52) had considerably fewer apoptotic chondrocytes and diminished cartilage degradation. Adrenomedullin(22-52) completely prevented systemic bone loss by preserving osteoblastic activity, but without changes in osteoclastic activity. CONCLUSION: Our findings indicate that adrenomedullin(22-52) , which has no vasoactive or tumor-inducing effects, is a potent antiinflammatory and bone-protective agent in this arthritis model.