Søren Ohrt-Nissen

How does extracerebral trauma affect the clinical value of S100B measurements

Background Protein S100B has proven to be a useful biomarker for cerebral damage. The predictive ability of S100B may, however, be affected by extracerebral injuries. The aim of this study was to investigate serum levels of S100B in patients with either isolated head injury (IHI), multi trauma with head injury (MTHI), or no head injury (NHI). The primary aim was to assess if a significant difference in serum levels of S100B could be found between IHI and MTHI patients. Methods Patients (233) were primarily admitted to the trauma centre. Serum samples were drawn on admission and 6 h after trauma and then stored at −80°C until analysed. Variables included Abbreviated Injury Scale (AIS) for head trauma, Injury Severity Score (ISS) and 30-day survival. Results Two patients could not be classified. IHI occurred in 28, MTHI in 102 and NHI was found in 101. The median S100B concentrations on arrival were 0.47, 1.68 and 0.49 μg/l, respectively (p<0.0001). The corresponding values at 6 h were 0.14, 0.31 and 0.15 μg/l, respectively (p<0.0001). S100B was significantly higher in patients with MTHI than in patients with IHI at both time points (p values 0.0005 and 0.01). There was no significant difference in S100B between patients having IHI and patients with NHI (p=0.81 and p=0.67). Conclusions High serum levels of S100B were found early after trauma. The highest concentrations of S100B were found in patients with multi trauma. This suggests that S100B serum concentrations are significantly affected by extracerebral injuries.

Characterization of miRNA Expression in Human Degenerative Lumbar Disks

Background data: microRNAs (miRNAs) are short ∼22 nucleotide RNA sequences that regulate messengerRNA translation. miRNAs have shown to play a role in synthesis of inflammatory mediators. Since inflammation play a role in intervertebral disk (IVD) degeneration, the objective was to isolate miRNA from human lumbar intervertebral disks and subsequently characterize the difference in miRNA expression between the annulus fibrosus (AF) and nucleus pulposus (NP). Methods: Fourteen patients undergoing anterior interbody fusion for degenerative disk disease of the lumbar spine were included. During surgery biopsies from the intervertebral disks were obtained and immediately placed in RNAlater. The RNAlater was decanted and the samples frozen at –80˚C until RNA extraction. This was performed using the Trizol method. Global miRNA expression analysis was performed using the Affymetrix GeneChip® miRNA array. Results: We developed a method allowing the extraction of miRNA from human intervertebral disks usually yielding 1–4 µg of total RNA pr. 100 mg of disk. Twenty-seven miRNAs had a higher expression in the AF and 10 had the highest expression in the NP. Among the top 15 signaling pathways most likely to be controlled by these miRNAs were the transforming growth factor β (TGFβ), platelet-derived growth factor (PDGF), insulin-like growth factor (IGF) epidermal growth factor (EGF), and actin cytoskeletal pathway. Conclusion: We have demonstrated the presence of miRNA in the human IVD. The miRNA expression differs from muscle tissue and there are differences between the miRNA expressed in the NP and AF. The miRNAs identified control signaling pathways important for maintenance of the IVD. Future studies may determine the importance of miRNA in the development of IVD disease.

Characterization and Predictive Value of Segmental Curve Flexibility in Adolescent Idiopathic Scoliosis Patients

Study Design. A prospective radiographic analysis of adolescent idiopathic scoliosis (AIS) patients managed with alternate-level pedicle screw fixation was performed. Objective. The objective of this study was to characterize segmental curve flexibility and to determine its predictive value in curve correction in AIS patients. Summary of Background Data. Little is known regarding the distinct segmental curve characteristics and their ability to predict curve correction in patients with AIS. Methods. The segmental Cobb angle was measured on posteroanterior standing radiographs and on fulcrum bending radiographs. Radiographs were analyzed preoperatively and at 2 years postoperatively and the curve was divided into upper, mid, and lower segments based on predefined criteria. The segmental flexibility and the segmental fulcrum bending correction index (FBCI) were calculated. Results. Eighty patients were included with mean age of 15 years. Preoperative mean segmental Cobb angles were 18, 31, and 17 degrees in the upper, mid, and lower segments, respectively. Segmental bending Cobb angles were 6, 13, and 4 degrees, respectively, corresponding to segmental flexibilities of 50%, 47%, and 83% in the upper, mid, and lower segments, respectively (P < 0.001). At 2-year follow up, the mean segmental FBCI were 155%, 131%, and 100% in the upper, mid, and lower segments, respectively (P < 0.001), which suggested that the lower segment of the curve was more flexible than the other segments and that higher correction was noted in the upper segments. A significant, positive correlation was noted between the segmental bending Cobb angle and the segmental FBCI (P < 0.05), whereby the strength of the correlation varied based on the curve segment. Conclusion. This is the first study to demonstrate the segmental variations in curve flexibility using the fulcrum bending radiograph in AIS patients. Curve flexibility is not uniform throughout the curve and different segments exhibit greater flexibility/correctibility than others. Segmental flexibility should be considered in assessing AIS patients and in the clinical decision-making strategy to optimize curve correction outcomes. Level of Evidence: 03

Curve Magnitude in Patients Referred for Evaluation of Adolescent Idiopathic Scoliosis: Five Years' Experience From a System Without School Screening

STUDY DESIGN Retrospective cross-sectional study. OBJECTIVES To analyze the referral pattern of patients with adolescent idiopathic scoliosis (AIS) in a tertiary hospital in a nationalized health care system without school screening and to compare curve magnitude on referral with results reported in the literature. In Denmark, school screening for AIS has not been in effect for more than two decades, and there is limited knowledge of curve magnitude and pattern of referral to specialized treatment in our country. Other studies, however, have assessed the effectiveness of school scoliosis screening. Our tertiary institution receives referrals for evaluation of AIS from general practitioners (GPs) and other hospitals or private specialists. METHOD A review was conducted on all patients diagnosed with AIS between 2010 and 2015. Data collection included age, gender, menarchal status, recommended treatment, and major curve Cobb angle for all patients aged 10-19 years referred for evaluation of AIS. Major curve magnitude was categorized as 10-19, 20-39, or ≥40 degrees, and the distribution of categories was compared to a screened population reported in the litterature. RESULTS A total of 166 of 460 newly referred AIS patients were referred from GP. Mean age was 15 years (standard deviation = 2) and median Cobb angle was 35 degrees. Overall, 33% were initially recommended treatment with a brace. This group had a median curve size of 41 degrees, and 28% presented more than 1 year past menarche. We found a significantly larger curve magnitude at the time of referral in our GP cohort compared to a screened population (p <.001), and 22% versus 8% had a Cobb angle >40 degrees (p <.001). CONCLUSION The present study confirms that in a health care system without school screening, patients with AIS referred for evaluation by GPs have larger curve sizes compared to systems with school screening. LEVEL OF EVIDENCE III.STUDY DESIGN Retrospective cross-sectional study. OBJECTIVES To analyze the referral pattern of patients with adolescent idiopathic scoliosis (AIS) in a tertiary hospital in a nationalized health care system without school screening and to compare curve magnitude on referral with results reported in the literature. SUMMARY OF BACKGROUND DATA In Denmark, school screening for AIS has not been in effect for more than two decades, and there is limited knowledge of curve magnitude and pattern of referral to specialized treatment in our country. Other studies, however, have assessed the effectiveness of school scoliosis screening. Our tertiary institution receives referrals for evaluation of AIS from general practitioners (GPs) and other hospitals or private specialists. METHOD A review was conducted on all patients diagnosed with AIS between 2010 and 2015. Data collection included age, gender, menarchal status, recommended treatment, and major curve Cobb angle for all patients aged 10-19 years referred for evaluation of AIS. Major curve magnitude was categorized as 10-19, 20-39, or ≥40 degrees, and the distribution of categories was compared to a screened population reported in the litterature. RESULTS A total of 166 of 460 newly referred AIS patients were referred from GP. Mean age was 15 years (standard deviation = 2) and median Cobb angle was 35 degrees. Overall, 33% were initially recommended treatment with a brace. This group had a median curve size of 41 degrees, and 28% presented more than 1 year past menarche. We found a significantly larger curve magnitude at the time of referral in our GP cohort compared to a screened population (p < .001), and 22% versus 8% had a Cobb angle >40 degrees (p < .001). CONCLUSION The present study confirms that in a health care system without school screening, patients with AIS referred for evaluation by GPs have larger curve sizes compared to systems with school screening. LEVEL OF EVIDENCE III.

Supine Lateral Bending Radiographs Predict the Initial In-brace Correction of the Providence Brace in Patients With Adolescent Idiopathic Scoliosis.

Study Design. Retrospective, cross-sectional. Objective. To determine the initial curve correction of the providence brace (PB) and to determine to what extend the in-brace Cobb angle corresponds to the curve seen on supine lateral bending radiographs (SLBR). Summary of Background Data. SLBR are used to assess curve flexibility in patients undergoing surgical treatment for adolescent idiopathic scoliosis (AIS). A low rate of in-brace correction (IBC) has been associated with a higher risk of curve progression, but to what extent SLBR can be used to predict IBC before initiating bracing treatment is unknown. Methods. All patients with AIS treated with the PB from January 1, 2006 to December 31, 2013 with a major curve of 25 to 45 degrees° were included. Cobb angle on SLBR before treatment and on initial standing, in-brace radiograph (IBR) were measured twice for each patient by one observer 30 days apart. Using a repeated measure mixed effect model, mean difference and 95% limits of agreement (LOA) between Cobb angles on each type of radiograph were estimated. Correction index (CI) was calculated as: curve flexibility (%)/curve correction (%). Results. A total of 127 patients were included. Mean long-standing Cobb angle was 35° (SD: 6°), which was reduced to mean 13° (SD: 8) on IBR (P < 0.05). No difference in curve correction between curve types was found when adjusting for flexibility using correction index (P = 0.77). Overall mean difference between SLBR and IBR was 0.2° (LOA ± 10°). Mean difference for thoracic curves was 0.2° (LOA ± 8°), for thoracolumbar/lumbar curves 0.9° (LOA ± 10°) and for double major curves 0.4° (LOA ± 16). Conclusion. SLBR provide a close estimation to the expected in-brace correction with a mean difference of less than one degree. SLRB could potentially serve as prognostic parameter for curve progression before initiating brace treatment. Level of Evidence: 3

Flexibility Predicts Curve Progression in Providence Nighttime Bracing of Patients With Adolescent Idiopathic Scoliosis.

Study Design. Retrospective cohort study. Objective. To determine treatment outcome with providence brace (PB) and to assess the ability of pretreatment supine lateral bending radiographs (SLBR) in predicting curve progression. Summary of Background Data. Results from treatment with the PB for adolescent idiopathic ccoliosis (AIS) have been inconsistent and further research is needed. The association between flexibility, as determined by pretreatment SLBR, and curve progression has not previously been examined. Methods. All patients treated with the PB from 2006 to 2011 who met Scoliosis Research Society (SRS) bracing criteria were included. Flexibility of the curve was determined based on SLBR and radiographic variables were registered at beginning of treatment and at skeletal maturity (SM) or before surgery. An increase in standing Cobb angle by more than 5 degrees was considered progression. Follow-up SRS-22 scores were compared with a control group with minor AIS. Analysis included multiple linear and logistic regression. Results. A total of 63 patients were included. Mean age was 13.3 years (SD: 1.5) and mean standing Cobb angle was 34° (SD: 5°). Radiographic progression was observed in 43% of patients at SM and surgical rate was 27% and 37% at SM and 2-year follow up, respectively. SRS-22 total scores were similar but the mental health score was significantly better in the control group (P = 0.042). Multiple linear regression analysis showed that decreased flexibility adjusted for age, Cobb angle, and menarchal status was significantly associated with curve progression (P < 0.001). Multiple logistic regression analysis showed that a one percent increase in flexibility was associated with a decrease in risk of curve progression ≥6° (odds ratio = 0.95; 95% confidence interval 0.90–0.98; P = 0.013). Conclusion. Progression was seen in 43% of AIS patients treated with the PB. Increase in flexibility was independently associated with a decreased risk of progression. Level of Evidence: 3

Radiographic and Functional Outcome in Adolescent Idiopathic Scoliosis Operated With Hook/Hybrid Versus All-Pedicle Screw Instrumentation—A Retrospective Study in 149 Patients

STUDY DESIGN Retrospective cohort study. OBJECTIVE To compare radiographic outcome and health-related quality of life in patients with adolescent idiopathic scoliosis (AIS) treated with hook/hybrid (H/H) or all-pedicle screw (PS) instrumentation. PS instrumentation has largely replaced H/H in the surgical treatment of AIS but whether a normalized sagittal profile can be obtained with the PS construct is still debated. Additionally, comparative studies assessing HRQL and surgical complications are needed. METHODS Two consecutive series of surgically treated AIS patients were included. Surgical treatment consisted of H/H or low-profile all-PS instrumentation. Radiographic and clinical follow-up, including SRS-22r questionnaires, was performed a minimum of two years postoperatively. RESULTS There were 85 and 64 patients in the H/H and PS group, respectively. The groups did not differ on baseline parameters apart from a lower flexibility in the H/H group (34% ± 14% vs. 39% ± 14% in the PS group, p =.026). Mean curve correction at final follow-up was 31% ± 13% versus 49% ± 12% in the H/H and PS group, respectively (p <.001), and mean loss of correction was 7° versus 4° (p <.001). The Cincinnati correction index was significantly higher in the PS group at final follow-up (p <.001). Postoperative thoracic kyphosis was significantly higher in the H/H group (27° ± 11° vs. 22° ± 11° in the PS group) with a mean change in kyphosis of 3° ± 9° versus -3° ± 12° in the H/H and PS group, respectively. SRS-22 scores did not differ between the two groups (p >.090), and the reoperation rate at final follow-up was 9% in the H/H group and 6% in the PS group (p =.556). CONCLUSIONS In a large consecutive cohort of AIS patients followed for a minimum of two years, we found a significantly better curve correction and less loss of correction with PS instrumentation compared to H/H. There was no significant difference in SRS-22r scores at final follow-up. LEVEL OF EVIDENCE Level III.STUDY DESIGN Retrospective cohort study. OBJECTIVE To compare radiographic outcome and health-related quality of life in patients with adolescent idiopathic scoliosis (AIS) treated with hook/hybrid (H/H) or all-pedicle screw (PS) instrumentation. SUMMARY OF BACKGROUND DATA PS instrumentation has largely replaced H/H in the surgical treatment of AIS but whether a normalized sagittal profile can be obtained with the PS construct is still debated. Additionally, comparative studies assessing HRQL and surgical complications are needed. METHODS Two consecutive series of surgically treated AIS patients were included. Surgical treatment consisted of H/H or low-profile all-PS instrumentation. Radiographic and clinical follow-up, including SRS-22r questionnaires, was performed a minimum of two years postoperatively. RESULTS There were 85 and 64 patients in the H/H and PS group, respectively. The groups did not differ on baseline parameters apart from a lower flexibility in the H/H group (34% ± 14% vs. 39% ± 14% in the PS group, p = .026). Mean curve correction at final follow-up was 31% ± 13% versus 49% ± 12% in the H/H and PS group, respectively (p < .001), and mean loss of correction was 7° versus 4° (p < .001). The Cincinnati correction index was significantly higher in the PS group at final follow-up (p < .001). Postoperative thoracic kyphosis was significantly higher in the H/H group (27° ± 11° vs. 22° ± 11° in the PS group) with a mean change in kyphosis of 3° ± 9° versus -3° ± 12° in the H/H and PS group, respectively. SRS-22 scores did not differ between the two groups (p > .090), and the reoperation rate at final follow-up was 9% in the H/H group and 6% in the PS group (p = .556). CONCLUSIONS In a large consecutive cohort of AIS patients followed for a minimum of two years, we found a significantly better curve correction and less loss of correction with PS instrumentation compared to H/H. There was no significant difference in SRS-22r scores at final follow-up. LEVEL OF EVIDENCE Level III.

Sagittal Alignment After Surgical Treatment of Adolescent Idiopathic Scoliosis—Application of the Roussouly Classification

STUDY DESIGN Retrospective cohort study. OBJECTIVES To investigate spinopelvic alignment and spine shape in patients surgically treated for adolescent idiopathic scoliosis (AIS) and to assess the distribution and clinical applicability of the Roussouly classification. How spinopelvic alignment is affected in AIS patients is not well established. Roussouly et al. proposed a classification based on the sagittal spinal profile and spinopelvic alignment that may have clinical utility in these patients. METHODS A consecutive cohort of 134 surgically treated AIS patients were included. Whole-spine standing lateral radiographs were analyzed preoperatively, one-week postoperatively and at two-year follow-up. Patients were categorized using the modified Roussouly classification and analyzed for sagittal alignment. RESULTS Postoperatively, global thoracic kyphosis (TK) decreased by 2.6° and lumbar lordosis (LL) decreased by 6.2°(p ≤ .012) while Pelvic tilt (PT) increased 1.4° (p = .024). At two-year follow-up, TK and LL had returned to preoperative values (p ≥ .346) while PT had decreased from preoperative 9.7 ± 7.6° to 7.0 ± 7.5° (p > .001). Proximal junctional angle increased from 8.4 ± 5.0° preoperatively to 12.8 ± 8.9 (p < .001). Preoperatively, Roussouly curve types were distributed equally apart from a lower rate of type 1 (12%). At final follow-up, 30% were categorised as type 3 with pelvic anteversion which is considerably higher than the normal adolescent population. Only three patients were type 1 at the final follow-up. Overall, we found a high rate of proximal junctional kyphosis (16%), PI-LL mismatch (60%) and pelvic anteversion (38%). In preoperative type 1 patients, the rate was 50%, 82% and 64%, respectively. CONCLUSION We found that immediate postoperative changes in lordosis and kyphosis were reversed at final follow-up and found evidence of proximal junctional kyphosation and pelvic anteversion as the main compensatory mechanisms. Poor sagittal alignment was frequent in type 1 curves, and surgical treatment may need to be individualized according to the sagittal profile. LEVEL OF EVIDENCE III.

Neural Axis Abnormalities in Patients With Adolescent Idiopathic Scoliosis: Is Routine Magnetic Resonance Imaging Indicated Irrespective of Curve Severity?

Objective Magnetic resonance imaging (MRI)-verified neural axis abnormalities (NAAs) have been described in adolescent idiopathic scoliosis (AIS), and several risk factors have been associated with the presence of NAAs in AIS patients. However, the clinical significance of these findings is unclear. The purpose of the present study was to determine the prevalence of NAAs in a large consecutive cohort of AIS patients and to evaluate the clinical significance of previously proposed risk factors. Methods We prospectively included AIS patients referred to a tertiary facility for evaluation. Full-spine MRI scans were performed on all included patients irrespective of curve magnitude or proposed treatment modality. MRI scans were prospectively analyzed by a neuroradiologist and the pathologic findings were confirmed by a second independent radiologist. Results NAA was observed in 34 of the 381 patients (8.9%): 32 patients had a syrinx, 1 patient had an arachnoid cyst, and 1 patient had a Chiari malformation. Four patients were referred for a neurosurgical evaluation but none received any neurosurgical treatment. No statistically significant difference was observed between the NAA and non-NAA groups in terms of sex, major curve size, thoracic kyphosis, left thoracic curve, curve convexity, curve progression, or level of pain (p>0.05). Conclusion In this prospective study examining the risk factors for NAA in AIS patients, we found that previously proposed risk factors could not predict the MRI outcomes. The finding of an NAA had no clinical implications and we do not support MRI scans as a routine diagnostic modality in all AIS patients.

Use of a distraction-to-stall lengthening procedure in magnetically controlled growing rods: A single-center cohort study

Purpose: The objective of this study was to assess the outcome of patients treated with magnetically controlled growing rods (MCGRs) using a standardized distraction procedure with intended distraction-to-stall and to compare the outcomes between idiopathic and nonidiopathic patients. Methods: This was a retrospective single-center cohort study. Conversion cases were excluded. Distractions were performed with 2- to 3-month intervals with the intention of distraction-to-stall on both rods. Distraction length was measured on X-rays every 6 months. Spinal height was assessed using T1-T12 and T1-S1 annual increase. Results: 19 patients (eight idiopathic and 11 nonidiopathic) were included. Mean age at surgery was 9.7 ± 1.9 years, and median follow-up was 1.9 years (interquartile range (IQR): 1.3–2.2). Major curve improved from median 76° (IQR: 64–83) preoperatively to 42° (IQR: 32–51) postoperatively (p < 0.001) corresponding to a curve correction of 43% (IQR: 33–51). Correction was maintained at 1- and 2-year follow-up. Median annual T1-T12 and T1-S1 height increase were 10 mm (IQR: 6–16) and 11 mm (IQR: 7–33), respectively. A total of 159 distraction procedures were performed; 83.5% of these were distracted-to-stall, and 16.5% were stopped due to discomfort. Median rod distraction per procedure was 2.0 mm (IQR: 1.6–2.7) for the concave side and 1.7 mm (IQR: 1.4–2.5) for the convex side. Five patients had implant-related complications. Patients with nonidiopathic etiology were significantly younger and had lower flexibility compared with idiopathic patients (p ≤ 0.040). However, we found no statistically significant difference in curve correction, spinal height increase, distraction length, or complications between the two groups (p ≥ 0.109). Conclusion: MCGR effectively corrected the deformity and increased spinal height using a distraction procedure with intended distraction-to-stall. Five of 19 patients had implant-related complications, and we found no difference in the outcomes between idiopathic and nonidiopathic patients.