Influence of cytokine inhibitors on concentration and activity of MMP-1 and MMP-3 in disc herniation

INTRODUCTION: Spontaneous resorption of disc herniation (DH) after sciatica is well documented. The matrix metalloproteinases (MMP)-1 and MMP-3 are enzymes potentially involved in this process. Glucocorticoid injections are commonly used for treatment, and other anti-inflammatory molecules like tumor necrosis factor (TNF) inhibitors are under clinical investigation. However, little is known about the effect of these molecules on DH resorption. METHODS: DH tissue was harvested from patients undergoing surgery for sciatica. Samples were thoroughly washed. Diced explants were cultured ex-vivo in 1) 0.5 ml Dulbecco's modified Eagle's medium (DMEM) 10% fetal calf serum (FCS), (controls), 2) recombinant interleukin 1 receptor antagonist (IL-1Ra), (100 ng/ml), 3) dexamethasone (10E-5 M), or 4) TNF inhibitor monoclonal antibody (10 microg/ml). Supernatants were harvested at 48 hours and frozen. Immunocapture activity assays determined total MMP activity, active MMP levels and pro-MMP levels. RESULTS: Fourteen DH tissue samples were analysed. Levels of all forms of MMP-3 were higher than the respective levels of MMP-1(P < 0.01). In particular, the median (interquartile range [IQR]) total MMP-3 level was 0.97 (0.47 - 2.19) ng/mg of tissue compared to 0.024 (0.01 - 0.07) ng/mg of total MMP-1 level (P < 0.01). Incubation with IL-1Ra, dexamethasone, or TNF inhibitors significantly decreased levels of all forms of MMP-3 (P < 0.05). Dexamethasone significantly decreased the ratio of active MMP-3 to total MMP-3 activity. A significant inhibitory effect of dexamethasone was observed only on active MMP-1, while IL-1 and TNF inhibitor had no significant effect on any form. CONCLUSIONS: MMP-3 appears to play a greater role than MMP-1 in DH resorption. Dexamethasone, IL-1-Ra and TNF inhibitor decreased active MMP-3, indicating that the clinical use of these drugs may affect the resorption of DH under certain conditions

Reliability and validity of the cross-culturally adapted French version of the Core Outcome Measures Index (COMI) in patients with low back pain

Purpose: To conduct a cross-cultural adaptation of the Core Outcome Measures Index (COMI) into French according to established guidelines. Methods: Seventy outpatients with chronic low back pain were recruited from six spine centres in Switzerland and France. They completed the newly translated COMI, and the Roland Morris disability (RMQ), Dallas Pain (DPQ), adjectival pain rating scale, WHO Quality of Life, and EuroQoL-5D questionnaires. After ~14days RMQ and COMI were completed again to assess reproducibility; a transition question (7-point Likert scale; "very much worse” through "no change” to "very much better”) indicated any change in status since the first questionnaire. Results: COMI whole scores displayed no floor effects and just 1.5% ceiling effects. The scores for the individual COMI items correlated with their corresponding full-length reference questionnaire with varying strengths of correlation (0.33-0.84, P<0.05). COMI whole scores showed a very good correlation with the "multidimensional” DPQ global score (Rho=0.71). 55 patients (79%) returned a second questionnaire with no/minimal change in their back status. The reproducibility of individual COMI 5-point items was good, with test-retest differences within one grade ranging from 89% for ‘social/work disability' to 98% for ‘symptom-specific well-being'. The intraclass correlation coefficient for the COMI whole score was 0.85 (95% CI 0.76-0.91). Conclusions: In conclusion, the French version of this short, multidimensional questionnaire showed good psychometric properties, comparable to those reported for German and Spanish versions. The French COMI represents a valuable tool for future multicentre clinical studies and surgical registries (e.g. SSE Spine Tango) in French-speaking countrie

Validity of the French version of the Core Outcome Measures Index for low back pain patients: a prospective cohort study

Purpose: Among the many questionnaires available to evaluate low back pain (LBP) patients, the Core Outcome Measures Index (COMI) has the unique advantage to investigate five dimensions using seven short questions. The aim of this study was to explore additional properties of the questionnaire in a French-speaking non-surgical population. Methods: This study was conducted on 168 patients suffering from subacute or chronic LBP and followed up for 6months in three French-speaking countries. In addition to basic psychometric properties (e.g., construct validity, floor and ceiling effect, reproducibility), internal validity was analyzed by a factor analysis using Cronbach's alpha. Responsiveness and sensitivity to change were assessed through minimal detectable change (MDC), effect size, and Minimal Clinically Important Improvement (MCII). We used an anchor-based method with receiver operating characteristic (ROC) curve analysis to assess MCII and the Patient Acceptable Symptom State. Results: Construct validity, reliability (Cronbach's alpha=0.87), reproducibility and the absence of floor and ceiling effects were confirmed. Factor analysis indicated a one-dimensional construct that validates the use of a sum score. The MDC (2.1) was inferior to the MCII (2.3). The limit below which the patient claims to be in a fair condition (Patient Acceptable Symptom State) was set at 3. Conclusions: The COMI is a self-report questionnaire with the capacity to easily and quickly explore several dimensions in patients with LBP that can be then summarized in a meaningful sum score. Additional knowledge provided by our study should encourage the widespread use of the COMI among the spine community

What low back pain is and why we need to pay attention

Low back pain is a very common symptom. It occurs in high-income, middle-income, and low-income countries and all age groups from children to the elderly population. Globally, years lived with disability caused by low back pain increased by 54% between 1990 and 2015, mainly because of population increase and ageing, with the biggest increase seen in low-income and middle-income countries. Low back pain is now the leading cause of disability worldwide. For nearly all people with low back pain, it is not possible to identify a specific nociceptive cause. Only a small proportion of people have a well understood pathological cause—eg, a vertebral fracture, malignancy, or infection. People with physically demanding jobs, physical and mental comorbidities, smokers, and obese individuals are at greatest risk of reporting low back pain. Disabling low back pain is over-represented among people with low socioeconomic status. Most people with new episodes of low back pain recover quickly; however, recurrence is common and in a small proportion of people, low back pain becomes persistent and disabling. Initial high pain intensity, psychological distress, and accompanying pain at multiple body sites increases the risk of persistent disabling low back pain. Increasing evidence shows that central pain-modulating mechanisms and pain cognitions have important roles in the development of persistent disabling low back pain. Cost, health-care use, and disability from low back pain vary substantially between countries and are influenced by local culture and social systems, as well as by beliefs about cause and effect. Disability and costs attributed to low back pain are projected to increase in coming decades, in particular in low-income and middle-income countries, where health and other systems are often fragile and not equipped to cope with this growing burden. Intensified research efforts and global initiatives are clearly needed to address the burden of low back pain as a public health problem

The pandemic toll and post-acute sequelae of SARS-CoV-2 in healthcare workers at a Swiss University Hospital.

Healthcare workers have potentially been among the most exposed to SARS-CoV-2 infection as well as the deleterious toll of the pandemic. This study has the objective to differentiate the pandemic toll from post-acute sequelae of SARS-CoV-2 infection in healthcare workers compared to the general population. The study was conducted between April and July 2021 at the Geneva University Hospitals, Switzerland. Eligible participants were all tested staff, and outpatient individuals tested for SARS-CoV-2 at the same hospital. The primary outcome was the prevalence of symptoms in healthcare workers compared to the general population, with measures of COVID-related symptoms and functional impairment, using prevalence estimates and multivariable logistic regression models. Healthcare workers (n=3,083) suffered mostly from fatigue (25.5%), headache (10.0%), difficulty concentrating (7.9%), exhaustion/burnout (7.1%), insomnia (6.2%), myalgia (6.7%) and arthralgia (6.3%). Regardless of SARS-CoV-2 infection, all symptoms were significantly higher in healthcare workers than the general population (n=3,556). SARS-CoV-2 infection in healthcare workers was associated with loss or change in smell, loss or change in taste, palpitations, dyspnea, difficulty concentrating, fatigue, and headache. Functional impairment was more significant in healthcare workers compared to the general population (aOR 2.28; 1.76-2.96), with a positive association with SARS-CoV-2 infection (aOR 3.81; 2.59-5.60). Symptoms and functional impairment in healthcare workers were increased compared to the general population, and potentially related to the pandemic toll as well as post-acute sequelae of SARS-CoV-2 infection. These findings are of concern, considering the essential role of healthcare workers in caring for all patients including and beyond COVID-19

Development and validation of a questionnaire assessing volitional competencies to enhance the performance of physical activities in chronic low back pain patients

BACKGROUND: Motivation has long been emphasized as the most important determinant of action. However, there is a substantial gap between people's goals and their attainment. Patients may be motivated and yet unable to take action if their volitional competencies are insufficient. One of the important tasks of volition is goal-maintenance. Research has stressed the importance of a volitional tool, the implementation intentions. Implementation intentions indicate where, when, and how the action leading to the goal will be performed. Forming implementation intentions favours the execution of goal-directed efforts, and reinforces the relationship between intentions and behaviours. Results from various studies clearly suggest that volitional competencies and implementation intentions could play a role in low back pain (LBP) patients. However, there is at present no questionnaire allowing assessing the capacity of implementation intentions of physical activities in LBP patients. METHODS/DESIGN: This study will develop such a questionnaire, using a 3-step approach. A first qualitative step to build categories and generate items; 30 patients suffering chronic LBP will be invited to participate in semi-structured interviews; verbatim and derived items will then be submitted to a panel of experts, using a Delphi method; a second quantitative step to examine the properties of items, and determine the factorial structure of the questionnaire; 100 patients suffering chronic LBP will be recruited to respond to this phase; and third, preliminary psychometric analyses (item-scale correlations, construct validity, reliability); 180 chronic LBP patients will be recruited for this phase of the study. The relationships between implementation intentions and variables affecting physical activity on chronic LBP patients, i.e. pain, physical capacities, fear-avoidance beliefs, kinesiophobia, work status, and level of physical activity will be considered. DISCUSSION: Developing a questionnaire to assess implementation intentions would allow investigating the role of these intentions in the transition from acute to chronic LBP. The results of this study should contribute to the understanding of the psychological processes at stake in the development of chronic LBP, and in particular to the identification of factors eventually favouring patients' participation in and adherence to active physical treatments

TNF-alpha in the Pathophysiology of Sciatica. Breakthrough or Dead End

Over the past 20 years, the hypothesis that inflammation was an important component of the pathophysiology of sciatica has slowly emerged. Numerous studies in a variety of animal models have been published to sustain this hypothesis, but it is only recently that we were able to produce the first evidence that tumor necrosis factor (TNF)-α could be an important mediator in human sciatica. We were able to demonstrate that there was a higher concentration of TNF-α in the vicinity of the inflamed nerve root in sciatica cases than in controls with other types of back pain. On the other hand, the results from a randomized, double-blind, placebo-controlled trial confirmed the initial impression from a pilot study of the efficacy of TNF-α inhibitors in the treatment of acute severe sciatica. However, the effect was more limited than expected and, both at the bench and at the bedside, clues are accumulating to suggest that other alternatives to systemically delivered TNF-α inhibitors should now be explored

Lombalgie du sujet âgé: le cas méconnu de la scoliose adulte

Degenerative scoliosis is often unappreciated in all-day clinical practice, however more and more frequent in the elderly population and deserves particular attention. This article aims to provide practitioners with practical guidelines to track these patients, organise radiological assessment in accordance with clinical situations, and implement an adequate therapeutic strategy

STarT back screening tool (SBT)

Le STarT Back Screening Tool (SBT) est un questionnaire de triage qui vise à identi fier des facteurs de risque de chronicité chez des patients atteints de lombalgie a fin de proposer un traitement adapté au niveau de risque. Ce questionnaire, simple et rapide à remplir, a été élaboré sur la base des principaux facteurs pronostiques modi fiables identifiés dans la littérature [1]. Il strati fie les patients en trois groupes : (1) risque faible ; (2) risque moyen ; (3) risque élevé. Pour les patients qui présentent un risque faible, une seule séance (par un médecin ou un physiothérapeute) est proposée pour rassurer et donner les conseils de base tels que « l’activité progressive est le meilleur traitement ». Les patients qui présentent un risque moyen – prédominance de facteurs de risques physiques – ont des séances de physiothérapie centrée sur le mouvement. Les patients qui présentent un risque élevé ont une prépondérance de facteurs de risques psychosociaux. Ces patients devraient rapidement être dirigés vers des thérapeutes capables de combiner une approche physique et psychologique, sur les principes des thérapies cognitivo-comportementale