Deterioration After Surgery for Degenerative Cervical Myelopathy: An Observational Study From the Canadian Spine Outcomes and Research Network.

STUDY DESIGN: A Prospective cohort study. OBJECTIVE: To investigate the incidence, etiology, and outcomes of patients who experience neurological deterioration after surgery for Degenerative Cervical Myelopathy (DCM). SUMMARY OF BACKGROUND DATA: Postoperative neurological deterioration is one of the most undesirable complications that can occur after surgery for DCM. METHODS: We analyzed data from the Canadian Spine Outcomes and Research Network DCM prospective cohort study. We defined postoperative neurological deterioration as any decrease in modified Japanese Orthopaedic Association (mJOA) score by at least one point from baseline to three months after surgery. Adverse events were collected using the Spinal Adverse Events Severity protocol. Secondary outcomes included patient-reported pain, disability, and health-related quality of life. RESULTS: Among a study cohort of 428 patients, 50 (12%) deteriorated by at least one mJOA point after surgery for DCM (21 by one point, 15 by two points, and 14 by three points or more). Significant risk factors included older age, female sex, and milder disease. Among those who deteriorated, 13 experienced contributing intraoperative or postoperative adverse events, six had alternative non-DCM diagnoses, and 31 did not have an identifiable reason for deterioration. Patients who deteriorated had significantly lower mJOA scores at one year after surgery [13.5 (SD 2.7) vs. 15.2 (SD 2.2), P <0.01 and those with larger deteriorations were less likely to recover their mJOA to at least their preoperative baseline, but most secondary measures of pain, disability, and health-related quality of life were unaffected. CONCLUSIONS: The incidence of deterioration of mJOA scores after surgery for DCM was approximately one in 10, but some deteriorations were unrelated to actual spinal cord impairment and most secondary outcomes were unaffected. These findings can inform patient and surgeon expectations during shared decision-making, and they demonstrate that the interpretation of mJOA scores without clinical context can sometimes be misleading.

Preoperative Factors Predict Postoperative Trajectories of Pain and Disability Following Surgery for Degenerative Lumbar Spinal Stenosis.

STUDY DESIGN: Longitudinal analysis of prospectively collected data. OBJECTIVE: Investigate potential predictors of poor outcome following surgery for degenerative lumbar spinal stenosis (LSS). SUMMARY OF BACKGROUND DATA: LSS is the most common reason for an older person to undergo spinal surgery, yet little information is available to inform patient selection. METHODS: We recruited LSS surgical candidates from 13 orthopedic and neurological surgery centers. Potential outcome predictors included demographic, health, clinical, and surgery-related variables. Outcome measures were leg and back numeric pain rating scales and Oswestry disability index scores obtained before surgery and after 3, 12, and 24 postoperative months. We classified surgical outcomes based on trajectories of leg pain and a composite measure of overall outcome (leg pain, back pain, and disability). RESULTS: Data from 529 patients (mean [SD] age = 66.5 [9.1] yrs; 46% female) were included. In total, 36.1% and 27.6% of patients were classified as experiencing a poor leg pain outcome and overall outcome, respectively. For both outcomes, patients receiving compensation or with depression/depression risk were more likely, and patients participating in regular exercise were less likely to have poor outcomes. Lower health-related quality of life, previous spine surgery, and preoperative anticonvulsant medication use were associated with poor leg pain outcome. Patients with ASA scores more than two, greater preoperative disability, and longer pain duration or surgical waits were more likely to have a poor overall outcome. Patients who received preoperative chiropractic or physiotherapy treatment were less likely to report a poor overall outcome. Multivariable models demonstrated poor-to acceptable (leg pain) and excellent (overall outcome) discrimination. CONCLUSION: Approximately one in three patients with LSS experience a poor clinical outcome consistent with surgical non-response. Demographic, health, and clinical factors were more predictive of clinical outcome than surgery-related factors. These predictors may assist surgeons with patient selection and inform shared decision-making for patients with symptomatic LSS. LEVEL OF EVIDENCE: 2.

Mindfulness-based cognitive therapy improves emotional reactivity to social stress: results from a randomized controlled trial.

The high likelihood of recurrence in depression is linked to a progressive increase in emotional reactivity to stress (stress sensitization). Mindfulness-based therapies teach mindfulness skills designed to decrease emotional reactivity in the face of negative affect-producing stressors. The primary aim of the current study was to assess whether Mindfulness-Based Cognitive Therapy (MBCT) is efficacious in reducing emotional reactivity to social evaluative threat in a clinical sample with recurrent depression. A secondary aim was to assess whether improvement in emotional reactivity mediates improvements in depressive symptoms. Fifty-two individuals with partially remitted depression were randomized into an 8-week MBCT course or a waitlist control condition. All participants underwent the Trier Social Stress Test (TSST) before and after the 8-week trial period. Emotional reactivity to stress was assessed with the Spielberger State Anxiety Inventory at several time points before, during, and after the stressor. MBCT was associated with decreased emotional reactivity to social stress, specifically during the recovery (post-stressor) phase of the TSST. Waitlist controls showed an increase in anticipatory (pre-stressor) anxiety that was absent in the MBCT group. Improvements in emotional reactivity partially mediated improvements in depressive symptoms. Limitations include small sample size, lack of objective or treatment adherence measures, and non-generalizability to more severely depressed populations. Given that emotional reactivity to stress is an important psychopathological process underlying the chronic and recurrent nature of depression, these findings suggest that mindfulness skills are important in adaptive emotion regulation when coping with stress.

High throughput crystallography of TB drug targets.

Tuberculosis (TB) infects one-third of the world population. Despite 50 years of available drug treatments, TB continues to increase at a significant rate. The failure to control TB stems in part from the expense of delivering treatment to infected individuals and from complex treatment regimens. Incomplete treatment has fueled the emergence of multi-drug resistant (MDR) strains of Mycobacterium tuberculosis (Mtb). Reducing non-compliance by reducing the duration of chemotherapy will have a great impact on TB control. The development of new drugs that either kill persisting organisms, inhibit bacilli from entering the persistent phase, or convert the persistent bacilli into actively growing cells susceptible to our current drugs will have a positive effect. We are taking a multidisciplinary approach that will identify and characterize new drug targets that are essential for persistent Mtb. Targets are exposed to a battery of analyses including microarray experiments, bioinformatics, and genetic techniques to prioritize potential drug targets from Mtb for structural analysis. Our core structural genomics pipeline works with the individual laboratories to produce diffraction quality crystals of targeted proteins, and structural analysis will be completed by the individual laboratories. We also have capabilities for functional analysis and the virtual ligand screening to identify novel inhibitors for target validation. Our overarching goals are to increase the knowledge of Mtb pathogenesis using the TB research community to drive structural genomics, particularly related to persistence, develop a central repository for TB research reagents, and discover chemical inhibitors of drug targets for future development of lead compounds.

Pain and function after intradiscal electrothermal treatment (IDET) for symptomatic lumbar disc degeneration.

The goal of this study was to evaluate the short-term effects of intradiscal electrothermal treatment (IDET) for chronic discogenic low back pain. Twenty consecutive patients with symptomatic degenerative discs were treated with IDET and evaluated preoperatively, and 3 and 6 months postoperatively. Pain was measured with a 100-mm visual analog scale (VAS) and function was evaluated with the Oswestry score and SF-36 questionnaire. The VAS scores improved by 14 mm on average (P=0.046), but the individual scores show great variation. The Oswestry scores did not improve significantly. The SF-36 showed improvement, but only for the subscales vitality (P=0.023) and bodily pain (P=0.047). Based on these results, we conclude that IDET is not effective in reducing pain and improving functional performance in a sample of 20 patients treated for chronic discogenic low back pain after 6 months follow-up.

Comparison of the construction of unmarked deletion mutations in Mycobacterium smegmatis, Mycobacterium bovis bacillus Calmette-Guérin, and Mycobacterium tuberculosis H37Rv by allelic exchange.

Until recently, genetic analysis of Mycobacterium tuberculosis, the causative agent of tuberculosis, was hindered by a lack of methods for gene disruptions and allelic exchange. Several groups have described different methods for disrupting genes marked with antibiotic resistance determinants in the slow-growing organisms Mycobacterium bovis bacillus Calmette-Guérin (BCG) and M. tuberculosis. In this study, we described the first report of using a mycobacterial suicidal plasmid bearing the counterselectable marker sacB for the allelic exchange of unmarked deletion mutations in the chromosomes of two substrains of M. bovis BCG and M. tuberculosis H37Rv. In addition, our comparison of the recombination frequencies in these two slow-growing species and that of the fast-growing organism Mycobacterium smegmatis suggests that the homologous recombination machinery of the three species is equally efficient. The mutants constructed here have deletions in the lysA gene, encoding meso-diaminopimelate decarboxylase, an enzyme catalyzing the last step in lysine biosynthesis. We observed striking differences in the lysine auxotrophic phenotypes of these three species of mycobacteria. The M. smegmatis mutant can grow on lysine-supplemented defined medium or complex rich medium, while the BCG mutants grow only on lysine-supplemented defined medium and are unable to form colonies on complex rich medium. The M. tuberculosis lysine auxotroph requires 25-fold more lysine on defined medium than do the other mutants and is dependent upon the detergent Tween 80. The mutants described in this work are potential vaccine candidates and can also be used for studies of cell wall biosynthesis and amino acid metabolism.

[Mandibular distraction using a dynamic osteosynthesis system: MD-DOS. Concepts and surgical technic]. / Un système de distraction mandibulaire par ostéosynthèse dynamique: DM-SOD. Concept et technique chirurgicale.

MD-DOS (mandibular distraction with a dynamic osteosynthesis system) is an intra-oral mandibular distractor that can be placed via the oral route, enabling application under local anesthesia. The aim of the article is to describe the technical-surgical aspects of the treatment concept, based on an initial experience of 35 cases. The device is characterised by a single horizontal posterior fixation screw-implant, a vertical hinge that copes with the lateral force vector in the condyles, a telescopic distraction module, and an anterior fixation unit that is fixed with monocortical screws. The main indication was mandibular lengthening in Angle Class II, deep bite cases. The third molars could be removed in the same session. Of importance was the horizontal placement of the posterior fixation unit (PFU), together with the distraction module, in order not to interfere with lateral jaw movements and with the lower sulcus. Equally important was the use of at least one 7.5 mm long osteosynthesis screw together with at least three 5.5 mm screws. Near complete mobilisation of the segments, firmly blocking the posterior fixation unit with the vertical hinge in a perpendicular position, and placing MD-DOS as close as possible to the dental arch, were also important parameters for success.

Biosynthesis of diaminopimelate, the precursor of lysine and a component of peptidoglycan, is an essential function of Mycobacterium smegmatis.

Diaminopimelate (DAP) is a unique metabolite used for both the biosynthesis of lysine in bacteria and the construction of the peptidoglycan of many species of bacteria, including mycobacteria. DAP is synthesized by bacteria as part of the aspartate amino acid family, which includes methionine, threonine, isoleucine, and lysine. Aspartokinase, the first enzyme in this pathway, is encoded by the ask gene in mycobacteria. Previous attempts to disrupt this gene in Mycobacterium smegmatis were unsuccessful, even when the cells were supplied with all the members of the aspartate family, suggesting that unlike other bacteria, mycobacteria may have an absolute requirement for this pathway even when growing in rich medium containing DAP. The purpose of this study was to determine if the ask gene and the aspartate pathway are essential to M. smegmatis. This study describes a test for gene essentiality in mycobacteria, utilizing a counterselectable marker (streptomycin resistance) in conjunction with a specially constructed merodiploid strain. We have used this system to show that the ask gene could not be disrupted in wild-type M. smegmatis, using selective rich medium supplemented with DAP unless there was an extra copy of ask provided elsewhere in the chromosome. Disruption of ask was also possible in a lysine auxotroph incapable of converting DAP to lysine. The ask mutant, mc21278 (ask1::aph), exhibits multiple auxotrophy (Met-, Thr-, DAP-, and Lys-) and is complemented by the ask gene. This is the first description of DAP auxotrophy in mycobacteria. The ask mutant lyses when deprived of DAP in culture, a characteristic which can be exploited for the reproducible preparation of protoplasts and mycobacterial extracts. The evidence presented here indicates that the aspartate pathway is essential to M. smegmatis and that DAP is the essential product of this pathway.