Sacral dome resection and single-stage posterior reduction in the treatment of high-grade high dysplastic spondylolisthesis in adolescents and young adults

Objective: The description of the operation technique and retrospective review of 15 consecutive patients who were treated by posterior sacral dome resection and single-stage reduction with pedicle screw fixation for high-grade, high-dysplastic spondylolisthesis. Materials and methods: All the patients had high-grade, high-dysplatic spondylolisthesis L5 and were treated by posterior sacral dome resection and posterior single-stage reduction from L4-S1. The average age at the time of surgery was 17.3 (11-28) years. The average follow-up time is 5.5 (2-11.6) years. Clinical and radiologica data were retrospectively reviewed. Results: Spondylolisthesis was reduced from average 99% preoperative to 29% at the last follow-up. L5 incidence improved from 74° to 56°, the lumbosacral angle improved from 15° kyphosis to 6° lordosis, lumbar lordosis decreased from 69° to 53° from preoperative to the last follow-up. While pelvic incidence of 77° remained unchanged, sacral slope decreased from 51° to 46° and pelvic tilt increased from 25° to 30°. Clinical outcome was subjectively rated to be much better than before surgery by 14 out of 15 patients. Four out of 15 patients had temporary sensory impairment of the L5 nerve root which resolved completely within 12 weeks. There were no permanent neurological complications or no pseudarthrosis. Conclusion: The sacral dome resection is a shortening osteotomy of the lumbosacral spine which allows a single-stage reduction of L5 without lengthening of lumbosacral region in high-grade spondylolisthesis, which helps to avoid neurological complications. This is a safe surgical technique resulting in a good multidimensional deformity correction and restoration of spino-pelvic alignment towards normal values with a satisfactory clinical outcom

Analysis of internal construct validity of the SRS-24 questionnaire

Purpose: The SRS-24 questionnaire was originally validated using methods of classical test theory, but internal construct validity has never been shown. Internal construct validity, i.e. unidimensionality and linearity, is a fundamental arithmetic requirement and needs to be shown for a scale for summating any set of Likert-type items. Here, internal construct validity of the SRS-24 questionnaire in adolescent idiopathic scoliosis (AIS) patients is analyzed. Methods: 232 SRS-24 questionnaires distributed to 116 patients with AIS pre-operatively and at postoperative follow-up were analyzed. 103 patients were females; the average age was 16.5±7.1years. The questionnaires were subjected to Rasch analysis using the RUMM2020 software package. Results: All seven domains of the SRS-24 showed misfit to the Rasch model, and three of seven were unidimensional. Unidimensionality and linearity could only be achieved for an aggregate score by separating pre- and postoperative items and omitting items which caused model misfit. Reducing the questionnaire to six pre-operative items (p=0.098; 2.25% t tests) and five postoperative items (p=0.267; 3.70% t tests) yields model fit and unidimensionality for both summated scores. The person-separation indices (PSI) were 0.67 and 0.69, respectively, for the pre- and postoperative patients. Conclusions: The SRS-24 score is a non-linear and multidimensional construct. Adding the items into a single value is therefore not supported and invalid in principle. Making profound changes to the questionnaire yields a score which fulfills the properties of internal construct validity and supports its use a change score for outcome measuremen

Effect of age on fatty infiltration of supraspinatus muscle after experimental tendon release in rats

Rotator cuff tendon tear is a leading cause for atrophy, fibrosis and fatty infiltration of the rotator cuff muscles. The pathophysiology of fatty muscle infiltration is not well understood. An animal model suited to study cellular and molecular mechanisms would therefore be desirable. While a rat model has been established for chronic rotator cuff tendon pathology, sufficient and easily identifiable fatty infiltration of the muscle has not yet been shown in rats. As younger animals regenerate better, we hypothesized that the absence of a sufficient amount of fatty infiltration in previous experiments was due to the selection of young animals and that older animals would exhibit higher amounts of fatty infiltration after tendon tear. FINDINGS: The supraspinatus tendon was released using tenotomy in 3 young (6 weeks old) and in 3 aged (24 months old) Sprague Dawley rats (group I and II). Another 3 aged (24 months old) rats underwent sham surgery and served as a control group (group III). In group I and II retraction of the musculotendinous unit was allowed for 6 weeks. All animals were sacrificed 6 weeks after surgery and the supraspinatus muscles were harvested. Each sample was examined for fatty infiltration of the muscle by histological methods and micro-CT. In histology, fat cells were counted with a 10-fold magnification in 6 fields of view twice. An adjusted measurement setup was developed for the use of micro-CT to quantify the absorption coefficient of the muscle as a reciprocal indicator for fatty infiltration, based on the established procedure for quantification of fatty infiltration on CT in humans.Tenotomy resulted in an insignificant increase of fat cells in histological sections in both, aged and young rats. Micro-CT was able to quantify small differences in the absorption coefficients of muscle samples; the absorption coefficient was 8.1% ± 11.3% lower in retracted muscles (group I and II) compared with the control (group III), indicating a tendency towards a higher amount of intra- and/or extracellular fat. Absorption was 4.28% ± 3.2% higher in aged compared with young muscles; however, this difference could not be confirmed by histology. CONCLUSIONS: Substantial fatty muscle infiltration following chronic retraction after supraspinatus tenotomy could be documented histologically neither in young nor aged rats. Although micro-CT was able to reveal minor differences in absorption between the studied groups, the differences were too small to make the rat supraspinatus model interesting to study fatty infiltration of the chronically retracted muscle

Systematic discovery of genetic modulation by Jumonji histone demethylases in Drosophila

Jumonji (JmjC) domain proteins influence gene expression and chromatin organization by way of histone demethylation, which provides a means to regulate the activity of genes across the genome. JmjC proteins have been associated with many human diseases including various cancers, developmental and neurological disorders, however, the shared biology and possible common contribution to organismal development and tissue homeostasis of all JmjC proteins remains unclear. Here, we systematically tested the function of all 13 Drosophila JmjC genes. Generation of molecularly defined null mutants revealed that loss of 8 out of 13 JmjC genes modify position effect variegation (PEV) phenotypes, consistent with their ascribed role in regulating chromatin organization. However, most JmjC genes do not critically regulate development, as 10 members are viable and fertile with no obvious developmental defects. Rather, we find that different JmjC mutants specifically alter the phenotypic outcomes in various sensitized genetic backgrounds. Our data demonstrate that, rather than controlling essential gene expression programs, Drosophila JmjC proteins generally act to “fine-tune” different biological processes

Evolution of the Cross-Sectional Area of the Osseous Lumbar Spinal Canal across Decades: A CT Study with Reference Ranges in a Swiss Population.

Spinal canal dimensions may vary according to ethnicity as reported values differ among studies in European and Chinese populations. Here, we studied the change in the cross-sectional area (CSA) of the osseous lumbar spinal canal measured in subjects from three ethnic groups born 70 years apart and established reference values for our local population. This retrospective study included a total of 1050 subjects born between 1930 and 1999 stratified by birth decade. All subjects underwent lumbar spine computed tomography (CT) as a standardized imaging procedure following trauma. Three independent observers measured the CSA of the osseous lumbar spinal canal at the L2 and L4 pedicle levels. Lumbar spine CSA was smaller at both L2 and L4 in subjects born in later generations (p < 0.001; p = 0.001). This difference reached significance for patients born three to five decades apart. This was also true within two of the three ethnic subgroups. Patient height was very weakly correlated with the CSA at both L2 and L4 (r = 0.109, p = 0.005; r = 0.116, p = 0.002). The interobserver reliability of the measurements was good. This study confirms the decrease of osseous lumbar spinal canal dimensions across decades in our local population

Pelvic incidence-lumbar lordosis mismatch results in increased segmental joint loads in the unfused and fused lumbar spine

Purpose: Symptomatic adjacent segment disease (ASD) has been reported to occur in up to 27% of lumbar fusion patients. A previous study identified patients at risk according to the difference of pelvic incidence and lordosis. Patients with a difference between pelvic incidence and lumbar lordosis >15° have been found to have a 20 times higher risk for ASD. Therefore, it was the aim of the present study to investigate forces acting on the adjacent segment in relation to pelvic incidence-lumbar lordosis (PILL) mismatch as a measure of spino-pelvic alignment using rigid body modeling to decipher the underlying forces as potential contributors to degeneration of the adjacent segment. Methods: Sagittal configurations of 81 subjects were reconstructed in a musculoskeletal simulation environment. Lumbar spine height was normalized, and body and segmental mass properties were kept constant throughout the population to isolate the effect of sagittal alignment. A uniform forward/backward flexion movement (0°-30°-0°) was simulated for all subjects. Intervertebral joint loads at lumbar level L3-L4 and L4-L5 were determined before and after simulated fusion. Results: In the unfused state, an approximately linear relationship between sagittal alignment and intervertebral loads could be established (shear: 0° flexion r=0.36, p<0.001, 30° flexion r=0.48, p<0.001; compression: 0° flexion r=0.29, p<0.01, 30° flexion r=0.40, p<0.001). Additionally, shear changes during the transition from upright to 30° flexed posture were on average 32% higher at level L3-L4 and 14% higher at level L4-L5 in alignments that were clinically observed to be prone to ASD. Simulated fusion affected shear forces at the level L3-L4 by 15% (L4-L5 fusion) and 23% (L4-S1 fusion) more for alignments at risk for ASD. Conclusion: Higher adjacent segment shear forces in alignments at risk for ASD already prior to fusion provide a mechanistic explanation for the clinically observed correlation between PILL mismatch and rate of adjacent segment degeneration

Findings from a pilot randomized trial of spinal decompression alone or spinal decompression plus instrumented fusion

Aims: Symptomatic spinal stenosis is a very common problem, and decompression surgery has been shown to be superior to nonoperative treatment in selected patient groups. However, performing an instrumented fusion in addition to decompression may avoid revision and improve outcomes. The aim of the SpInOuT feasibility study was to establish whether a definitive randomized controlled trial (RCT) that accounted for the spectrum of pathology contributing to spinal stenosis, including pelvic incidence-lumbar lordosis (PI-LL) mismatch and mobile spondylolisthesis, could be conducted. Methods: As part of the SpInOuT-F study, a pilot randomized trial was carried out across five NHS hospitals. Patients were randomized to either spinal decompression alone or spinal decompression plus instrumented fusion. Patient-reported outcome measures were collected at baseline and three months. The intended sample size was 60 patients. Results: Of the 90 patients screened, 77 passed the initial screening criteria. A total of 27 patients had a PI-LL mismatch and 23 had a dynamic spondylolisthesis. Following secondary inclusion and exclusion criteria, 31 patients were eligible for the study. Six patients were randomized and one underwent surgery during the study period. Given the low number of patients recruited and randomized, it was not possible to assess completion rates, quality of life, imaging, or health economic outcomes as intended. Conclusion: This study provides a unique insight into the prevalence of dynamic spondylolisthesis and PI-LL mismatch in patients with symptomatic spinal stenosis, and demonstrates that there is a need for a definitive RCT which stratifies for these groups in order to inform surgical decision-making. Nonetheless a definitive study would need further refinement in design and implementation in order to be feasible

C2 Odontoid Fracture Associated with C1-C2 Rotatory Dislocation: A Retrospective Analysis of 2 Surgical Techniques.

Odontoid fractures in association with a C1-C2 rotatory luxation reports are seldom found in the literature. The fusion between the lateral mass of C1 and C2 could be of interest to ensure adequate treatment in these particular cases. We report 23 cases where there was coexistence of an odontoid fracture and rotatory subluxation, which were treated surgically using cages between C1 and C2 or just traditional Goel-Harms technique. We evaluated the radiologic fusion rate, reoperation rate, and complications. This was a single-center, retrospective, cohort study of patients with C2 fractures (mixed type and C1-C2 rotatory luxation according to the Fielding classification) who were treated surgically. Radiologic computed tomography scans were used to assess fusion (presence of bridging trabecular bone end plate or pseudoarthrosis) between 6 months and 1.5 years after the surgery. Twenty-three patients were diagnosed with C2 fractures and C1-C2 rotatory luxation that were treated surgically and were suitable for the analysis; 11 patients underwent C1-C2 fusion with intra-articular cages, and 12 underwent a classical Goel-Harms technique. The fusion rate at the C1-C2 joint was higher in the cages group. Only 12 patients exhibited fusion at the level of the odontoid fracture. C2 fractures associated with C1-C2 rotatory dislocation are rare. The fusion rate at the level of the odontoid in these patients appears to be lower than that reported in patients without rotatory dislocation. It may be of special interest to obtain a clear fusion at the C1-C2 joint, where this type of implant seems to offer an advantage

Identification and characterization of a Ross River virus variant that grows persistently in macrophages, shows altered disease kinetics in a mouse model, and exhibits resistance to type I interferon

Alphaviruses, such as chikungunya virus, o'nyong-nyong virus, and Ross River virus (RRV), cause outbreaks of human rheumatic disease worldwide. RRV is a positive-sense single-stranded RNA virus endemic to Australia and Papua New Guinea. In this study, we sought to establish an in vitro model of RRV evolution in response to cellular antiviral defense mechanisms. RRV was able to establish persistent infection in activated macrophages, and a small-plaque variant (RRVPERS) was isolated after several weeks of culture. Nucleotide sequence analysis of RRV PERS found several nucleotide differences in the nonstructural protein (nsP) region of the RRV PERS genome. A point mutation was also detected in the E2 gene. Compared to the parent virus (RRV-T48), RRV PERS showed significantly enhanced resistance to beta interferon (IFN-β)-stimulated antiviral activity. RRV PERS infection of RAW 264.7 macrophages induced lower levels of IFN-β expression and production than infection with RRV-T48. RRV PERS was also able to inhibit type I IFN signaling. Mice infected with RRV PERS exhibited significantly enhanced disease severity and mortality compared to mice infected with RRV-T48. These results provide strong evidence that the cellular antiviral response can direct selective pressure for viral sequence evolution that impacts on virus fitness and sensitivity to alpha/beta IFN (IFN-α/β).Facultad de Ciencias Exacta