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Academic procrastination is one of the major factors that can be a serious obstacle for students to achieve academic progress and success. This research aimed to investigate and predict academic procrastination based on academic self-efficacy and emotional regulation difficulties of students of one of the medical sciences universities in southern Iran in 2024. This descriptive-analytical cross-sectional study was conducted on 290 students of different fields in the south of Iran between January and April 2024. Data was collected using standard questionnaires of academic procrastination, academic self-efficacy, and difficulty in emotional regulation. Descriptive statistics, t-test, ANOVA, Pearson's correlation coefficient, and multiple linear regression were employed to examine the data using SPSS 23 software. A significant level of 0.05 was considered. The average score of academic procrastination, academic self-efficacy, and difficulty in emotional regulation of the studied students was 66.21 ± 4.06 (out of 108), 59.58 ± 5.84 (out of 120), and 121.42 ± 6.88 (out of 180), respectively, which indicates a moderate level of academic self-efficacy and academic procrastination and a high level of difficulty in emotional regulation. A statistically significant correlation was observed between students' academic procrastination and academic self-efficacy (r = -0.648, p < 0.001) and the difficulty in emotional regulation (r = 0.701, p < 0.001). Based on the results of multiple linear regression, components of academic self-efficacy, including effort, talent, and context, as well as components of difficulty in emotion regulation, including difficulty in performing purposeful behavior, lack of emotional awareness, limited access to emotional regulation strategies, non-acceptance of emotional responses, difficulty in impulse control, and lack of emotional clarity, were identified as predictors of academic procrastination (p < 0.05). Considering the students' academic procrastination and the effect of academic self-efficacy and difficulty in emotional regulation on it, it is suggested that university administrators provide the field of improvement and promotion of students' academic self-efficacy and emotional regulation through holding related courses and workshops so that in this way procrastination can be reduced., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: This study is approved by Jiroft University of Medical Sciences Ethics Committee with the ID number of IR.JMU.REC.1402.002. All the methods were carried out in accordance with relevant guidelines and regulations. Meanwhile, informed consent was obtained from all subjects and/or their legal guardian(s)., (© 2025. The Author(s).)

Background: Critical thinking, moral courage, and moral sensitivity are among the topics that are widely considered today in response to turbulent and complex environments in organizations. The purpose of this study was to investigate the state of critical thinking and its effect on moral courage and moral sensitivity in nurses working in hospitals under Jiroft University of Medical Sciences in southern Iran in 2024., Methods: This descriptive-analytical cross-sectional study was conducted on 385 nurses. The data collection tools were standard questionnaires of critical thinking, moral courage and moral sensitivity. Data were analyzed using t-test, ANOVA, Pearson's correlation coefficient and multiple linear regression using SPSS23 software., Results: The average scores of critical thinking, moral courage, and moral sensitivity of the studied nurses were 188.16 ± 8.22 out of 450, 62.32 ± 7.45 out of 105, and 71.55 ± 6.39 out of 100, respectively, indicating the weak level of critical thinking and the average level of moral courage and moral sensitivity of nurses. Between moral courage (p < 0.001, r = 0.574) and moral sensitivity (p < 0.001, r = 0.611) with critical thinking, a statistically significant correlation was observed in the direct direction. Based on the results of multiple linear regression, the components of critical thinking, which include truth-seeking, inquisitiveness, analyticity, systematicity, self-confidence, cognitive maturity, and open-mindedness, respectively, were identified as predictors of moral sensitivity and moral courage (P < 0.001)., Conclusion: The critical thinking of the examined nurses was estimated at a weak level, and moral courage and moral sensitivity were estimated at a moderate level. Based on the results, there is a possibility that by improving critical thinking, the state of moral courage and moral sensitivity of nurses will improve. Therefore, it is suggested that the hospital managers provide an opportunity to improve the critical thinking status of nurses by holding related courses and workshops, so that by this means, we can witness the growth and improvement of their courage and moral sensitivity., Competing Interests: Declarations Ethics approval and consent to participate This study is approved by Jiroft University of Medical Sciences Ethics Committee with the ID number of IR.JMU.REC.1402.032. All the methods were carried out in accordance with relevant guidelines and regulations. Meanwhile, the informed consent was obtained from all the study participants. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Study Design: Retrospective cohort study of prospectively accrued data., Objective: To evaluate a large, prospective, multicentre dataset of surgically treated degenerative cervical myelopathy (DCM) cases on the contemporary risk of C5 palsy with surgical approach., Summary of Background Data: The influence of surgical technique on postoperative C5 palsy after decompression for DCM is intensely debated. Comprehensive, covariate-adjusted analyses are needed using contemporary data., Methods: Patients with moderate to severe DCM were prospectively enrolled in the multicenter, randomized, Phase III CSM-Protect clinical trial and underwent either anterior or posterior decompression between Jan 31, 2012 and May 16, 2017. The primary outcome was the incidence of postoperative C5 palsy, defined as the onset of muscle weakness by at least one grade in manual muscle test at the C5 myotome with slight or absent sensory disruption after cervical surgery. Two comparative cohorts were made based on the anterior or posterior surgical approach. Multivariate hierarchical mixed-effects logistic regression was used to estimate odds ratios (OR) with 95% confidence intervals (CI) for C5 palsy., Results: A total of 283 patients were included, and 53.4% underwent posterior decompression. The total incidence of postoperative C5 palsy was 7.4% and was significantly higher in patients who underwent posterior decompression compared with anterior decompression (11.26% vs. 3.03%, P =0.008). After multivariable regression, the posterior approach was independently associated with greater than four times the likelihood of postoperative C5 palsy ( P =0.017). Rates of C5 palsy recovery were comparable between the two surgical approaches., Conclusion: The odds of postoperative C5 palsy are significantly higher after posterior decompression compared to anterior decompression for DCM. This may influence surgical decision-making when there is equipoise in deciding between anterior and posterior treatment options for DCM., Level of Evidence: Therapeutic Level-II., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To investigate the factors for pulmonary embolism (PE) development and the necessity of inferior vena cava (IVC) filter placement. Specifically, propose a scoring system to identify patient populations who benefit from IVC filter placement., Methods: A single-institution retrospective cohort study was performed between 2010 and 2022. Inclusion criteria were open posterior thoracolumbar fusion, ≥7 segments, and adult patients ≥18 years old. Patients undergoing any surgical approach other than posterior were excluded. Risk factors such as smoking status, illicit drug use/type, body mass index, gender, age, anticoagulation history, and status on the presence of PE were reviewed., Results: A total of 365 patients were identified; 170 patients (46.6%) were male, and 195 (53.4%) were female. Twenty-four patients (6.6%) had IVC filters placed before the surgery. The overall rate of PE was 8 (2.2%), all in patients without IVC filter. Analysis showed that gender, age, and body mass index did not affect the incidence of PE. Smoking status, history of illicit drug use (cocaine/cannabis), and history of deep vein thrombosis/PE significantly increased the incidence of PE. Based on multivariate logistic regression, we developed a scoring system composed of the significant risk factors outlined earlier to determine the risk of developing PE. Our scoring system stratified risk to low risk (0-3 points), medium risk (4-6 points), and high risk (7 or 8 points)., Conclusions: The risk of PE is relatively low after long-segment posterior thoracolumbar fusion. Smoking (former and current), history of cocaine/cannabis use, and history of venous thromboembolism are risk factors in such patients. We recommend prophylactic IVC filter use only in high-risk subgroups and under discretion between physician and patient in medium-risk subgroups., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: The modified Japanese Orthopaedic Association (mJOA) scale is the most common scale used to represent outcomes of degenerative cervical myelopathy (DCM); however, it lacks consideration for neck pain scores and neglects the multidimensional aspect of recovery after surgery., Objective: To use a global statistical approach that incorporates assessments of multiple outcomes to reassess the efficacy of riluzole in patients undergoing spinal surgery for DCM., Design, Setting, and Participants: This was a secondary analysis of prespecified secondary end points within the Efficacy of Riluzole in Surgical Treatment for Cervical Spondylotic Myelopathy (CSM-PROTECT) trial, a multicenter, double-blind, phase 3 randomized clinical trial conducted from January 2012 to May 2017. Adult surgical patients with DCM with moderate to severe myelopathy (mJOA scale score of 8-14) were randomized to receive either riluzole or placebo. The present study was conducted from July to December 2023., Intervention: Riluzole (50 mg twice daily) or placebo for a total of 6 weeks, including 2 weeks prior to surgery and 4 weeks following surgery., Main Outcomes and Measures: The primary outcome measure was a difference in clinical improvement from baseline to 1-year follow-up, assessed using a global statistical test (GST). The 36-Item Short Form Health Survey Physical Component Score (SF-36 PCS), arm and neck pain numeric rating scale (NRS) scores, American Spinal Injury Association (ASIA) motor score, and Nurick grade were combined into a single summary statistic known as the global treatment effect (GTE)., Results: Overall, 290 patients (riluzole group, 141; placebo group, 149; mean [SD] age, 59 [10.1] years; 161 [56%] male) were included. Riluzole showed a significantly higher probability of global improvement compared with placebo at 1-year follow-up (GTE, 0.08; 95% CI, 0.00-0.16; P = .02). A similar favorable global response was seen at 35 days and 6 months (GTE for both, 0.07; 95% CI, -0.01 to 0.15; P = .04), although the results were not statistically significant. Riluzole-treated patients had at least a 54% likelihood of achieving better outcomes at 1 year compared with the placebo group. The ASIA motor score and neck and arm pain NRS combination at 1 year provided the best-fit parsimonious model for detecting a benefit of riluzole (GTE, 0.11; 95% CI, 0.02-0.16; P = .007)., Conclusions and Relevance: In this secondary analysis of the CSM-PROTECT trial using a global outcome technique, riluzole was associated with improved clinical outcomes in patients with DCM. The GST offered probability-based results capable of representing diverse outcome scales and should be considered in future studies assessing spine surgery outcomes.

More than half of all spinal cord injuries (SCIs) occur at the cervical level and often lead to life-threatening breathing motor dysfunction. The C2 hemisection (C2Hx) and high cervical contusion mouse and rat models of SCI are widely utilized both to understand the pathological effects of SCI and to develop potential therapies. Despite rigorous research effort, pre-clinical therapeutics studied in those animal models of SCI sometimes fail when evaluated in the clinical setting. Differences between standard-of-care treatment for acute SCI administered to clinical populations and experimental animal models of SCI could influence the heterogeneity of outcome between pre-clinical and clinical studies. In this review, we have summarized both the standard clinical interventions used to treat patients with cervical SCI and the various veterinary aftercare protocols used to care for rats and mice after experimentally induced C2Hx and high cervical contusion models of SCI. Through this analysis, we have identified areas of marked dissimilarity between clinical and veterinary protocols and suggest the modification of pre-clinical animal care particularly with respect to analgesia, anticoagulative measures, and stress ulcer prophylaxis. In our discussion, we intend to inspire consideration of potential changes to aftercare for animal subjects of experimental SCI that may help to bridge the translational "Valley of Death" and ultimately contribute more effectively to finding treatments capable of restoring independent breathing function to persons with cervical SCI.

Our understanding of Central Cord Syndrome (CCS), a form of incomplete spinal cord injury characterized by disproportionate upper extremity weakness, is evolving. Recent advances challenge the traditional somatotopic model of corticospinal tract organization within the spinal cord, suggesting that CCS is likely a diffuse injury rather than focal lesion. Diagnostic criteria for CCS lack consensus, and varied definitions impact patient identification and treatment. Evidence has mounted for early surgery for CCS, although significant variability persists in surgical timing preferences among practitioners. A demographic shift toward an aging population has increased the overlap between CCS and Degenerative Cervical Myelopathy (DCM). Understanding this intersection is crucial for comprehensive patient care. Assessment tools, including quantitative measures and objective evaluations, aid in distinguishing CCS from DCM. The treatment landscape for CCS in the context of pre-existing DCM is complex, requiring careful consideration of pre-existing neurologic injury, patient factors, and injury factors. This review synthesizes emerging evidence, outlines current guidelines in diagnosis and management, and emphasizes the need for ongoing research to refine our understanding and treatment strategies for this evolving patient population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Shakil, Santaguida, Wilson, Farhadi, Levi and Wilcox.)

Objective: There is ongoing debate on the relative benefits and drawbacks of polyetheretherketone (PEEK) versus titanium (Ti) in generating a bone-to-implant surface microenvironment conducive to osseointegration. Micro- and nanoscale internal and topographic cage modifications have recently been posited to facilitate osseointegration and fusion, but human in vivo confirmation remains lacking. The authors of this study sought to directly compare early radiological outcomes in adults undergoing 1- and 2-level transforaminal lumbar interbody fusion (TLIF) procedures using either PEEK or nano-etched Ti interbody cages with an incorporated microlattice structure., Methods: Patients were enrolled in a single academic center using a single-blind randomized controlled superiority design. Screening was undertaken from a pool of consecutive patients eligible for TLIF to undergo placement in a 1:1 ratio of either lordotic PEEK or activated Ti cages at each level of 1- or 2-level procedures. An a priori power analysis was performed and a preplanned interim analysis was undertaken once 50 of 70 patients were enrolled. Patient study data were collected perioperatively and uploaded to a Research Electronic Data Capture (REDCap) registry. Interbody fusion was assessed based on 6-month postoperative lumbar dual-energy CT (DECT) studies using the method of Brantigan and Steffee, as modified to describe the Fraser definition of locked pseudarthrosis (Brantigan-Steffee-Fraser [BSF] scale)., Results: In the final cohort of 50 patients, 40 interbody levels implanted with PEEK cages were compared with 34 interbody levels with activated Ti cages. The trial was stopped early given the results of an interim analysis with respect to the primary outcome. Surgical parameters including number of levels treated, average cage height, and position were not different between groups. For the PEEK and activated Ti groups, 20.6% versus 84.0% demonstrated BSF grade 3 fusion on 6-month postoperative DECT imaging (p < 0.001). Subsidence at 6 months on DECT was identified in 12 (41.4%) of PEEK levels versus 5 (20.8%) of activated Ti levels (p < 0.001). BSF-3 grading was predictive of segmental stability and numeric rating scale (NRS) leg pain improvement at 1 year postoperatively. Oswestry Disability Index and NRS back and leg pain scores all improved similarly in both cohorts at 1 year postoperatively., Conclusions: Activated Ti interbody cages mediate early fusion at significantly higher rates with lower rates of subsidence as compared with PEEK cages. These findings support the idea that interbody cage microscale properties, including surface topography, may play a primary role in facilitating osseointegration and fusion.

Nodular fasciitis (NF) is a benign proliferation of fibroblasts and myofibroblasts occurring most commonly in the upper extremities that can mimic a variety of mesenchymal tumors including sarcoma. Although reported in almost all anatomic locations, only 7 cases of intraneural nodular fasciitis have been reported in English literature. The CTNNB1::USP6 gene fusion has not been previously reported in intraneural nodular fasciitis, although it has been reported in three entities including aneurysmal bone cyst, nodular fasciitis, and intravascular fasciitis. We report a case of a 29-year-old female with a 6-month history of left leg weakness, myalgia, and paresthesia of the left foot prompting a clinical diagnosis of a peripheral nerve sheath tumor. Surgical resection was performed, and histologic sections revealed a circumscribed lesion composed of banal spindle cells with variable interstitial collagen and occasional mitotic figures. By immunohistochemistry, the lesional cells were positive for smooth muscle actin, smooth muscle heavy chain myosin, p16, and H-caldesmon and negative for desmin, S-100, SOX10, HMB45, CD34, and beta-catenin. Fluorescence in Situ Hybridization for USP6 gene rearrangement was positive and consistent with the diagnosis of nodular fasciitis. Next-generation sequencing uncovered the presence of a CTNNB1::USP6 gene fusion involving CTNNB1 gene in exon 1 at the genomic position chr3:41241161 and the USP6 gene in exon 1 at the genomic position chr17:5033231. This gene fusion was confirmed by Sanger sequencing. Herein, we report a case that underscores the rare incidence of intraneural nodular fasciitis and highlights the pitfalls associated with the clinical differential diagnoses of intraneural tumors.

Objective: Degenerative cervical myelopathy (DCM) is routinely treated with surgical decompression, but disparate postoperative outcomes are frequently observed, ranging from complete neurological recovery to persistent decline. Although numerous clinical and radiological factors have been independently associated with failure to improve, the relative impact of these proposed risk factors remains obscure. In this study, the authors assess the combined role of clinical and radiographic parameters in contributing to failure to attain neurological improvement after surgery., Methods: A consecutive series of patients who underwent surgery for DCM between July 2013 and August 2018 at a single institution was identified from a prospectively maintained database. Retrospective chart review was undertaken to record perioperative clinical and radiographic parameters. Failure to improve on the last follow-up evaluation after surgery, defined as a change in modified Japanese Orthopaedic Association (mJOA) score less than 2, was the primary outcome in univariate and multivariate analyses., Results: The authors included 183 patients in the final cohort. In total, 109 (59.6%) patients improved (i.e., responders with ΔmJOA score ≥ 2) after surgery and 74 (40.4%) were nonresponders with ΔmJOA score < 2. Baseline demographic variables and comorbidity rates were similar, whereas baseline Nurick score was the only clinical variable that differed between responders and nonresponders (2.7 vs 3.0, p = 0.02). In contrast, several preoperative radiographic variables differed between the groups, including presence and degree of cervical kyphosis, number of levels with bidirectional cord compression, presence and number of levels with T2-weighted signal change, intramedullary lesion (IML) length, Torg ratio, and both narrowest spinal canal and cord diameter. On multivariate analysis, preoperative degree of kyphosis at C2-7 (OR 1.19, p = 0.004), number of levels with bidirectional compression (OR 1.83, p = 0.003), and IML length (OR 1.14, p < 0.001) demonstrated the highest predictive power for nonresponse (area under the receiver operating characteristic curve 0.818). A risk factor point system that predicted failure of improvement was derived by incorporating these 3 variables., Conclusions: When a large spectrum of both clinical and radiographic variables is considered, the degree of cervical kyphosis, number of levels with bidirectional compression, and IML length are the most predictive of nonresponse after surgery for DCM. Assessment of these radiographic factors can help guide surgical decision-making and more appropriately stratify patients in clinical trials.

Background: Proximal junctional fractures (PJFr) can be a catastrophic complication associated with adult spinal deformity surgery. Osteoporosis can be a major risk factor for the cause of PJFr. Recent studies suggest using surrogate computed tomography (CT) scans in place of spinal dual-energy x-ray absorptiometry (DEXA) scores for bone mineral density (BMD). Investigate the feasibility of using preoperative CT based bone mineral density at upper instrumented vertebrae (UIV) and one level proximally (UIV+1) and distally (UIV-1) to predict the possibility of PJFr risk., Methods: Retrospective two-academic center case-controlled study, reviewed consecutive adult spinal deformity surgeries; included constructs encompassing at least five fusion levels and fusions to pelvis. Examined demographic, surgical, and radiographic data preoperatively, postoperatively, and final follow-up. Formed groups based on type of proximal junctional deformity (PJD): Control (no PJD), proximal junctional kyphosis (PJK) and PJFr. Preoperative CT BMD values measured in Hounsfield units (HU) for sagittal and axial planes at UIV, UIV+1, and UIV-1 and compared between groups., Results: N=92 patients. Preoperative CT scan BMD values were significantly lower in PJFr vs. control at: UIV+1 in sagittal (p=0.007), axial (p=0.02) planes; UIV sagittal (p=0.04) and axial (p=0.03) planes; and UIV-1 sagittal (p=0.05) plane. Similarly, lower CT scan BMD values noted in PJFr vs. PJK at: UIV+1 in sagittal (p=0.04) and axial (p=0.03) planes. Trend seen with lower CT scan BMD values at UIV+1 level in PJFr vs. PJK in sagittal (p=0.12) and axial (p=0.10) planes. Preoperative global sagittal imbalance measurements significantly lower in control, but comparable between PJK and PJFr., Conclusions: Higher preoperative global sagittal imbalance with lower preoperative CT BMD values at UIV and UIV+1 vertebral body may increase the risk of proximal junctional fractures after adult spine deformity surgery. Proximal junctional hooks may supplement the pathogenesis. Readers should note the small sample size. Level of Evidence: 3., Competing Interests: This study was performed with the approval of SUNY Upstate Medical University IRB and The Ohio State University Wexner Medical Center IRB and in accordance with the boards’ regulations. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Background Context: Postoperative ileus is a major barrier to gastrointestinal recovery following surgery. Opioid analgesics likely play an important causative role, particularly in spinal or orthopedic surgeries not involving bowel manipulation. Methylnaltrexone, a peripherally-acting µ-opioid receptor antagonist, is a potential prophylactic treatment., Purpose: To assess the influence of perioperative subcutaneous methylnaltrexone administration on gastrointestinal recovery following short-segment lumbar arthrodesis surgeries., Design: This is a randomized, double-blind, controlled trial., Patient Sample: Eligible patients undergoing posterior short-segment lumbar arthrodesis surgeries at a single institution between February 2019 and April 2021 were enrolled in this study., Outcome Measures: The primary outcome measure was time-to-first bowel movement. Secondary outcome measures included time-to-discharge/discharge eligibility. Exploratory outcome measures included daily postoperative opioid consumption and pain scores., Methods: In this study, eligible patients were enrolled to receive either methylnaltrexone or placebo perioperatively. Time-to-bowel movement, time-to-discharge/discharge eligibility, intra and postoperative analgesic administration, and pain scores were recorded and compared., Results: Eighty two patients in total were enrolled; 41 to the methylnaltrexone and 41 to the placebo group. Both groups were similar in their baseline characteristics. There was no difference in median (range) time-to-bowel movement between the 2 groups [61.8 hours (35.7-93.6) versus 50.7 hours (17.8-110.8), p = .391]. There was also no difference in time-to-discharge/discharge eligibility [105.0 hours (81.0 - 201.3) versus 90.7 (77.5 - 184.5), p=.784]. Finally, there were no differences in either postoperative opioid consumption or numeric rating scores for back, leg, or abdominal pain on postoperative days 0 to 4 (p>.05)., Conclusions: Methylnaltrexone did not accelerate gastrointestinal recovery and did not affect opioid consumption or pain scores following short-segment spinal surgery as compared to placebo. Additional studies will be needed to identify effective opioid receptor antagonist dosing regimens for patients undergoing either short- or long-segment spinal arthrodesis procedures., Competing Interests: Declarations of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Steerable "banana" cages have been posited to increase segmental lordosis in short-segment transforaminal lumbar interbody fusions (TLIF). The same is not necessarily true for straight "bullet" cages. Although increased lordosis is generally thought to be advantageous, a potential complication is decreased foraminal height. Here we evaluate for any association between cage type and change in foraminal height and clinical outcomes following short-segment TLIFs., Methods: We retrospectively reviewed consecutive 1- and 2-level TLIFs with bilateral facetectomies with minimum 1-year clinical and radiographic follow-up. Two cohorts were based on cage morphology: steerable "banana" cage or straight "bullet" cage. Patient reported outcome measures (PROMs), radiographic measurements, and revision rates were compared., Results: A total of 46 patients with 53 straight and 95 patients with 131 steerable cage levels were included. Steerable cages showed increased segmental lordosis (9.1° vs. 13.5°, P < 0.001) and decreased foraminal height (20.3 vs. 18.5 mm, P < 0.001) after surgery. Straight cages demonstrated similar segmental lordosis (8.7° vs 8.1°, P = 0.30) and foraminal height (19.4 vs 20.0 mm, P < 0.065). Both cohorts showed improved PROMs at last follow-up (P ≤ 0.005). Subanalysis comparing patients who had increased or decreased foraminal height revealed similarly improved PROMs between cohorts. Revision rates at 1 year were similar between cohorts (4.3% for straight and 3.2% for steerable group, P = 0.72)., Conclusions: Although the increased segmental lordosis afforded by placement of steerable cages may decrease foraminal height after short segment TLIF, clinical outcomes are not negatively affected by this association., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Postoperative ileus (POI) is a common complication with no proven prophylactic measures in place. While perioperative opioid use has been implicated in POI development, current treatments fail to target this disease mechanism. Methylnaltrexone (MNTX) has been used to prevent the effects of opioids on the bowel and could reduce the incidence of POI when administered preoperatively., Methods: In this phase IIb randomized controlled trial, we assessed the effect of perioperative MNTX on time-to-first-bowel movement following spinal arthrodesis surgeries., Results: 82 patients were randomly selected in a 1:1 ratio to be included in either the treatment or placebo groups. Comparison of relevant factors of included patients to patients who refused to participate (n = 21) and to a prior retrospective series (n = 241) revealed no differences in age, male sex, liver disease, and number of surgical levels. Overall treatment fidelity (98% adherence) and retention (100% at one-month follow-up) were high. The predicted POI incidence (9.3-11.1%) was also equivalent to a prior retrospective series. However, the overall observed POI incidence (3.7%) was lower than expected, which could reflect a superimposed 'trial effect' related to standardized care in a research setting., Conclusions: Since exposure to significant opioid doses represents a barrier to enhanced recovery after surgery, the results of this innovative trial may provide further guidance for the peri-operative use of opioid-receptor blockers. Here, we show that MNTX can be effectively administered in the peri-operative period with appropriate follow-up achieved in a representative population of patients undergoing spinal surgery., Trial Registration Numbers: Clinicaltrials.gov - NCT03852524 and Institutional Review Board - 2018H0260., (Copyright © 2021 Elsevier Inc. All rights reserved.)

While spinal interbody cage options have proliferated in the past decade, relatively little work has been done to explore the comparative potential of biomaterial technologies in promoting stable fusion. Innovations such as micro-etching and nano-architectural designs have shown purported benefits in in vitro studies, but lack clinical data describing their optimal implementation. Here, we critically assess the pre-clinical data supportive of various commercially available interbody cage biomaterial, topographical, and structural designs. We describe in detail the osteointegrative and osteoconductive benefits conferred by these modifications with a focus on polyetheretherketone (PEEK) and titanium (Ti) interbody implants. Further, we describe the rationale and design for two randomized controlled trials, which aim to address the paucity of clinical data available by comparing interbody fusion outcomes between either PEEK or activated Ti lumbar interbody cages. Utilizing dual-energy computed tomography (DECT), these studies will evaluate the relative implant-bone integration and fusion rates achieved by either micro-etched Ti or standard PEEK interbody devices. Taken together, greater understanding of the relative osseointegration profile at the implant-bone interface of cages with distinct topographies will be crucial in guiding the rational design of further studies and innovations., (© 2021. The Author(s).)

Objective: The aim of this study was to determine whether cage morphology influences clinical and radiographic outcomes following short-segment transforaminal lumbar interbody fusion (TLIF) procedures., Methods: The authors retrospectively reviewed one- and two-level TLIFs at a single tertiary care center between August 2012 and November 2019 with a minimum 1-year radiographic and clinical follow-up. Two cohorts were compared based on interbody cage morphology: steerable "banana" cage or straight "bullet" cage. Patient-reported outcome measures (PROMs), radiographs, and complications were analyzed., Results: A total of 135 patients with 177 interbody levels were identified; 45 patients had 52 straight cages and 90 patients had 125 steerable cages. Segmental lordosis increased with steerable cages, while it decreased with straight cages (+3.8 ± 4.6 vs -1.9 ± 4.3, p < 0.001). Conversely, the mean segmental lordosis of adjacent lumbar levels decreased in the former group, while it increased in the latter group (-0.52 ± 1.9 vs +0.52 ± 2.1, p = 0.004). This reciprocal relationship results in global sagittal parameters, including pelvic incidence minus lumbar lordosis and lumbar distribution index, which did not change after surgery with either cage morphology. Multivariate analysis confirmed that steerable cage morphology, anterior cage positioning, and less preoperative index-level segmental lordosis were associated with greater improvement in index-level segmental lordosis. PROMs were improved after surgery with both cage types, and the degree of improvement did not differ between cohorts (p > 0.05). Perioperative and radiographic complications were similar between cohorts (p > 0.05). Overall reoperation rates, as well as reoperation rates for adjacent-segment disease within 2 years of surgery, were not significantly different between cohorts., Conclusions: Steerable cages are more likely to lie within the anterior disc space, thus increasing index-level segmental lordosis, which is accompanied by a reciprocal change in segmental alignment at the adjacent lumbar levels. The converse relationship occurs for straight cages, with a kyphotic change at the index levels and reciprocal lordosis occurring at adjacent levels.

Objective: Despite the increasing incidence of spinal epidural abscess (SEA), the baseline parameters potentially predictive of treatment failure remain poorly characterized. In this study, the authors identify the relevant baseline parameters that predict multimodal treatment failure in patients with either intravenous drug use (IVDU)-associated SEA or non-IVDU-associated SEA., Methods: The authors reviewed the electronic medical records of a large institutional series of consecutive patients with diagnosed SEA between January 2011 and December 2017 to characterize epidemiological trends as well as the complement of baseline measures that are predictive of failure after multimodal treatment in patients with and without concomitant IVDU. The independent impact of clinical and imaging factors in detecting treatment failure was assessed by performing stepwise binary logistic regression analysis., Results: A total of 324 consecutive patients with diagnosed SEA were identified. Overall, 226 patients (69.8%) had SEA related to other causes and 98 (30.2%) had a history of recent IVDU. While non-IVDU SEA admission rates remained constant, year-over-year admissions of patients with IVDU SEA nearly tripled. At baseline, patients with IVDU SEA were distinct in many respects including younger age, greater unemployment and disability, less frequent diabetes mellitus (DM), and more frequent methicillin-resistant Staphylococcus aureus infection. However, differences in length of stay, loss to follow-up, and treatment failure did not reach statistical significance between the groups. The authors constructed independent multivariate logistic regression models for treatment failure based on identified parameters in the two cohorts. For the non-IVDU cohort, the authors identified four variables as independent factors: DM, hepatitis B/C, osteomyelitis, and compression deformity severity. In contrast, for patients with IVDU, the authors identified three variables: albumin, endocarditis, and endplate destruction. Receiver operating characteristic and area under the curve (AUC) analyses were undertaken for the multivariate models predicting the likelihood of treatment failure in the two cohorts (AUC = 0.88 and 0.89, respectively), demonstrating that the derived models could adequately predict the risk of multimodal treatment failure. Treatment failure risk factor point scales were derived for the identified variables separately for both cohorts., Conclusions: Patients with IVDU SEA represent a unique population with a distinct set of baseline parameters that predict treatment failure. Identification of relevant prognosticating factors will allow for the design of tailored treatment and follow-up regimens.

Background: Degenerative cervical myelopathy represents the most common form of non-traumatic spinal cord injury. This trial investigated whether riluzole enhances outcomes in patients undergoing decompression surgery for degenerative cervical myelopathy., Methods: This multicentre, double-blind, placebo-controlled, randomised, phase 3 trial was done at 16 university-affiliated centres in Canada and the USA. Patients with moderate-to-severe degenerative cervical myelopathy aged 18-80 years, who had a modified Japanese Orthopaedic Association (mJOA) score of 8-14, were eligible. Patients were randomly assigned (1:1) to receive either oral riluzole (50 mg twice a day for 14 days before surgery and then for 28 days after surgery) or placebo. Randomisation was done using permuted blocks stratified by study site. Patients, physicians, and outcome assessors remained masked to treatment group allocation. The primary endpoint was change in mJOA score from baseline to 6 months in the intention-to-treat (ITT) population, defined as all individuals who underwent randomisation and surgical decompression. Adverse events were analysed in the modified intention-to-treat (mITT) population, defined as all patients who underwent randomisation, including those who did not ultimately undergo surgical decompression. This study is registered with ClinicalTrials.gov, NCT01257828., Findings: From Jan 31, 2012, to May 16, 2017, 408 patients were screened. Of those screened, 300 were eligible (mITT population); 290 patients underwent decompression surgery (ITT population) and received either riluzole (n=141) or placebo (n=149). There was no difference between the riluzole and placebo groups in the primary endpoint of change in mJOA score at 6-month follow-up: 2·45 points (95% CI 2·08 to 2·82 points) versus 2·83 points (2·47 to 3·19), difference -0·38 points (-0·90 to 0·13; p=0·14). The most common adverse events were neck or arm or shoulder pain, arm paraesthesia, dysphagia, and worsening of myelopathy. There were 43 serious adverse events in 33 (22%) of 147 patients in the riluzole group and 34 serious adverse events in 29 (19%) of 153 patients in the placebo group. The most frequent severe adverse events were osteoarthrosis of non-spinal joints, worsening of myelopathy, and wound complications., Interpretation: In this trial, adjuvant treatment for 6 weeks perioperatively with riluzole did not improve functional recovery beyond decompressive surgery in patients with moderate-to-severe degenerative cervical myelopathy. Whether riluzole has other benefits in this patient population merits further study., Funding: AOSpine North America., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: Lumbar radicular Syndrome (LRS) is a common spinal pathology and is attributed to complex interplay of mechanical, inflammatory and immunological processes. Epidural injection of steroids has a significant therapeutic role in mitigating the inflammatory component of LRS. Trans-foraminal approach under image guidance enables a targeted drug delivery. The current narrative review discusses the various aspects related to lumbar trans-foraminal epidural injection of steroid (LTFIS)., Methods: An elaborate search on PubMed, Google and Medline databases was made using keywords "lumbar selective nerve root block", "lumbar trans-foraminal epidural steroid injection", "selective nerve root block in lumbar disc prolapse", "trans-foraminal epidural steroid injection in lumbar prolapse", "selective nerve root block in lumbar radiculopathy", and "trans-foraminal epidural steroid injection in lumbar radiculopathy" The articles were selected based on specific inclusion criteria., Results: Our search identified 539 articles. All articles discussing alternate procedures, LTFIS in other pathologies, diagnostic roles of LTFIS, not pertaining to concerned questions, in non-English language and duplicate articles were excluded. Review articles, randomised controlled trials or level 1 studies were given preference. Overall, 108 articles were included. Being a focussed narrative review, further screening [Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) or Methodological Index for non-randomized studies (MINORS) criteria] was not performed to select articles. Based on the evidence, LTFIS is an effective and useful treatment modality. It is offered to patients with lumbar disc herniation (LDH) presenting with persistent, unilateral, radiculopathy after a course of conservative measures for around 6 weeks' duration. It has been reported to yield better results than caudal or inter-laminar epidural injections. The anti-inflammatory and nociceptive signal stabilization actions of steroids, as well as mechanical effects of washout of inflammatory mediators and neural lysis contribute to its efficacy. The three different approaches include sub-pedicular, retro-neural and retro-discal. The procedure is performed under image guidance using a water-soluble contrast under fluoroscopy. The four described radiculogram patterns include "arm", "arrow", "linear" and "splash". Computerised tomography, ultrasonography and magnetic resonance imaging are other modalities, which may be helpful in performing LTFIS. The use of particulate versus non-particulate steroids is controversial., Conclusion: The overall success rate of SNRB is reported to be 76-88%. The majority of benefits are observed during immediate and early post-injection period. Clinical factors including duration and severity of symptoms, and radiological factors like presence of osteophytes, location, size and type of disc prolapse influence outcomes. The radiculogram "splash" pattern is associated with poor outcomes., (© 2020 Delhi Orthopedic Association. All rights reserved.)

Introduction: Acute traumatic spinal cord injury (tSCI) is a devastating neurological disorder with no pharmacological neuroprotective strategy proven effective to date. Progressive haemorrhagic necrosis (PHN) represents an increasingly well-characterised mechanism of secondary injury after tSCI that negatively impacts neurological outcomes following acute tSCI. Preclinical studies evaluating the use of the Food and Drug Administration-approved sulfonylurea receptor 1-transient receptor potential melastatin 4 channel blocker glyburide in rodent models have shown reduced secondary microhaemorrhage formation and the absence of capillary fragmentation, the pathological hallmark of PHN., Methods and Analysis: In this initial phase multicentre open-label pilot study, we propose to enrol 10 patients with acute cervical tSCI to primarily assess the feasibility, and safety of receiving oral glyburide within 8 hours of injury. Secondary objectives include pharmacokinetics and preliminary evaluations on neurological recovery as well as blood and MRI-based injury biomarkers. Analysis will be performed using the descriptive and non-parametric statistics., Ethics and Dissemination: Glyburide has been shown as an effective neuroprotective agent in preclinical tSCI models and in the treatment of ischaemic stroke with the additional risk of a hypoglycaemic response. Given the ongoing secondary injury and the traumatic hyperglycaemic stress response seen in patients with tSCI, glyburide; thus, offers an appealing neuroprotective strategy to supplement standard of care treatment. The study protocol was approved by the Ohio State University Biomedical Institutional Review Board. The protocol was amended in February 2017 with changes related to study feasibility and patient recruitment. Specifically, the route of administration was changed to the oral form to allow for streamlined and rapid drug administration, and the injury-to-drug time window was extended to 8 hours in an effort to further enhance enrolment. Participants or legally authorised representatives are informed about the trial and its anticipated risks orally and in written form using an approved informed consent form prior to inclusion. The findings of this study will be disseminated to the participants and to academic peers through scientific conferences and peer-reviewed journal publications., Trial Registration Numbers: NCT02524379 and 2014H0335., Competing Interests: Competing interests: JMS reports personal fees from Remedy Pharmaceuticals, personal fees from Biogen, outside the submitted work. In addition, JMS has a US patent (#7,872,048), ‘Methods for treating spinal cord injury with a compound that inhibits a NC(Ca-ATP) channel' with royalties paid to University of Maryland., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Postoperative ileus (POI) is associated with abdominal pain, nausea, vomiting, and delayed mobilization that in turn lead to diminished patient satisfaction, increased hospital length of stay (LOS), and increased healthcare costs. In this study, the authors developed a risk assessment scale to predict the likelihood of developing POI following spinal surgery., Methods: The authors undertook a retrospective review of a prospectively maintained registry of consecutive patients who underwent arthrodesis/fusion surgeries between May 2013 and December 2017. They extracted clinical information, including cumulative intraoperative and postoperative opioid doses using standardized converted morphine milligram equivalent (MME) values. Univariate and multivariate analyses were performed and several categorical and continuous variables were evaluated in a binary logistic regression model built with backward elimination to assess for independent predictors. A points-based prediction model was developed and validated to determine the risk of POI., Results: A total of 334 patients who underwent spinal fusion surgeries were included. Fifty-six patients (16.8%) developed POI, more frequently in those who underwent long-segment surgeries compared to short-segment surgeries (33.3% vs 10.4%; p < 0.001). POI was associated with an increased LOS when compared with patients who did not develop POI (8.0 ± 4.5 days vs 4.4 ± 2.4 days; p < 0.01). The incidences of liver disease (16% vs 3.7%; p = 0.01) and substance abuse history (12.0% vs 3.2%; p = 0.04) were higher in POI patients than non-POI patients undergoing short-segment surgeries. While the incidences of preoperative opioid intake (p = 0.23) and cumulative 24-hour (87.7 MME vs 73.2 MME; p = 0.08) and 72-hour (225.6 MME vs 221.4 MME; p = 0.87) postoperative opioid administration were not different, remifentanil (3059.3 µg vs 1821.5 µg; p < 0.01) and overall intraoperative opioid (326.7 MME vs 201.7 MME; p < 0.01) dosing were increased in the POI group. The authors derived a multivariate model based on the 5 most significant factors predictive of POI (number of surgical levels, intraoperative MME, liver disease, age, and history of substance abuse) and calculated relative POI risks using a derived 32-point system., Conclusions: Intraoperative opioid administration, incorporated in a comprehensive risk assessment scale, represents an early and potentially modifiable predictor of POI. These data indicate that potential preventive strategies, implemented as part of enhanced recovery after surgery protocols, could be instituted in the preoperative phase of care to reduce POI incidence.

Sublaminar implants that encircle cortical bone are well-established adjuncts to pedicle screw-rod constructs in pediatric deformity surgery. Sublaminar bands (SLBs) in particular carry the advantage of relatively greater bone contact surface area as compared to wires and pullout loads that are independent of bone mineral density, in contrast to pedicle screws. Whereas the relevant technical considerations have been reported for pediatric deformity correction, an understanding of the relative procedural specifics of these techniques is missing for adult spinal deformity (ASD), despite several case series that have used distinct posterior tethering techniques for proximal junctional kyphosis prevention. In this paper, the authors summarize the relevant literature and describe a novel technique wherein bilateral tensioned SLBs are introduced at the nonfused proximal junctional level of long-segment ASD constructs.

OBJECTIVEProximal junctional kyphosis (PJK) and failure (PJF) are potentially catastrophic complications that result from abrupt changes in stress across rigid instrumented and mobile non-fused segments of the spine (transition zone) after adult spinal deformity surgery. Recently, data have indicated that extension (widening) of the transitional zone via use of proximal junctional (PJ) semi-rigid fixation can mitigate this complication. To assess the biomechanical effectiveness of 3 semi-rigid fixation constructs (compared to pedicle screw fixation alone), the authors performed cadaveric studies that measured the extent of PJ motion and intradiscal pressure changes (ΔIDP).METHODSTo measure flexibility and ΔIDP at the PJ segments, moments in flexion, extension, lateral bending (LB), and torsion were conducted in 13 fresh-frozen human cadaveric specimens. Five testing cycles were conducted, including intact (INT), T10-L2 pedicle screw-rod fixation alone (PSF), supplemental hybrid T9 Mersilene tape insertion (MT), hybrid T9 sublaminar band insertion (SLB1), and hybrid T8/T9 sublaminar band insertion (SLB2).RESULTSCompared to PSF, SLB1 significantly reduced flexibility at the level rostral to the upper-instrumented vertebral level (UIV+1) under moments in 3 directions (flexion, LB, and torsion, p ≤ 0.01). SLB2 significantly reduced motion in all directions at UIV+1 (flexion, extension, LB, torsion, p < 0.05) and at UIV+2 (LB, torsion, p ≤ 0.03). MT only reduced flexibility in extension at UIV+1 (p = 0.02). All 3 constructs revealed significant reductions in ΔIDP at UIV+1 in flexion (MT, SLB1, SLB2, p ≤ 0.02) and torsion (MT, SLB1, SLB2, p ≤ 0.05), while SLB1 and SLB2 significantly reduced ΔIDP in extension (SLB1, SLB2, p ≤ 0.02) and SLB2 reduced ΔIDP in LB (p = 0.05). At UIV+2, SLB2 similarly significantly reduced ΔIDP in extension, LB, and torsion (p ≤ 0.05).CONCLUSIONSCompared to MT, the SLB1 and SLB2 constructs significantly reduced flexibility and ΔIDP in various directions through the application of robust anteroposterior force vectors at UIV+1 and UIV+2. These findings indicate that semi-rigid sublaminar banding can most effectively expand the transition zone and mitigate stresses at the PJ levels of long-segment thoracolumbar constructs.

Objective: Segmental instability traditionally is investigated with flexion and extension (F/E) radiographs. We sought to determine whether motion between upright and supine (U/S) views can serve as an alternative sensitive diagnostic tool that predicts similar outcomes., Methods: Ambispective collection of data was performed for 222 consecutive patients who underwent transforaminal lumbar interbody fusion. Patients were divided into either group 1 (≥3 mm spondylolisthesis difference between F/E radiographs) or group 2 (≥3 mm spondylolisthesis difference between U/S imaging and otherwise not meeting group 1 criteria)., Results: In total, 77 patients met all inclusion/exclusion criteria. Patients in group 1 (n = 26) and group 2 (n = 51) did not differ with respect to key demographic criteria. Average clinical follow-up for groups 1 and 2 were 31.8 and 35.6 months (P = 0.43). Average spondylolisthesis was 8.1 mm and 8.0 mm for groups 1 and 2 (P = 0.93). The incidence of facet joint hyperintensity on T2-weighted magnetic resonance imaging and average maximal facet joint widening (P > 0.2) did not differ between groups. Average F/E slip change was 5.0 mm for group 1 and average U/S slip change was 5.2 mm for group 2. For both groups, Numeric Rating Scale Back Pain and Numeric Rating Scale Leg Pain, Oswestry Disability Index v2.1a, and Short-Form 36 RAND (P < 0.02) improved significantly after surgery. Furthermore, ΔNumeric Rating Scale Back Pain, ΔNumeric Rating Scale Leg Pain, ΔOswestry Disability Index v2.1a, and ΔShort-Form 36 RAND (P > 0.2) were not significantly different between groups., Conclusions: No differences in outcomes were noted between patients based on either imaging criteria. These data suggest that static U/S imaging may identify a distinct group of patients who may benefit from transforaminal lumbar interbody fusion surgery., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Variable and unpredictable spontaneous recovery can occur after acute cervical traumatic spinal cord injury (tSCI). Despite the critical clinical and interventional trial planning implications of this tSCI feature, baseline measures to predict neurologic recovery accurately are not well defined. In this study, we used data derived from 99 consecutive patients (78 male, 21 female) with acute cervical tSCIs to assess the sensitivity and specificity of various clinical and radiological factors in predicting recovery at one year after injury. Categorical magnetic resonance imaging parameters included maximum canal compromise (MCC), maximum spinal cord compression (MSCC), longitudinal length of intramedullary lesion (IML), Brain and Spinal Injury Center (BASIC) score, and a novel derived Combined Axial and Sagittal Score (CASS). Logistic regression analysis of the area under the receiver operating characteristic curve (AUC) was applied to assess the differential predictive value of individual imaging markers. Admission American Spinal Injury Association Impairment Scale (AIS) grade, presence of a spinal fracture, and central cord syndrome were predictive of AIS conversion at one year. Both BASIC and IML were stronger predictors of AIS conversion compared with MCC and MSCC (p = 0.0002 and p = 0.04). The BASIC score demonstrated the highest overall predictive value for AIS conversion at one year (AUC 0.94). We conclude that admission intrinsic cord signal findings are robust predictive surrogate markers of neurologic recovery after cervical tSCI. Direct comparison of imaging parameters in this cohort of patients indicates that the BASIC score is the single best acute predictor of the likelihood of AIS conversion.

Split cord malformation (SCM) is a rare form of spinal dysraphism wherein the spinal cord is divided longitudinally into two distinct hemicords. Surgery is usually performed in children while management in adults, who rarely manifest symptoms, remains controversial. Both expectant management and prophylactic surgery have been variously advocated. The present article describes our experience in two adult patients with predominant pain-related complaints who underwent surgical excision of type 1 SCM lesions. A comprehensive review of the literature on SCM in adults is also provided. While pain, disability, and quality of life scores improved in these two patients, further larger studies will be required to define the role of surgery in adults with type 1 SCM and a pain-dominant presentation., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

OBJECTIVE Proximal junctional kyphosis (PJK) can progress to proximal junctional failure (PJF), a widely recognized early and serious complication of multisegment spinal instrumentation for the treatment of adult spinal deformity (ASD). Sublaminar band placement has been suggested as a possible technique to prevent PJK and PJF but carries the theoretical possibility of a paradoxical increase in these complications as a result of the required muscle dissection and posterior ligamentous disruption. In this study, the authors prospectively assess the safety as well as the early clinical and radiological outcomes of sublaminar band insertion at the upper instrumented vertebra (UIV) plus 1 level (UIV+1). METHODS Between August 2015 and February 2017, 40 consecutive patients underwent either upper (T2-4) or lower (T8-10) thoracic sublaminar band placement at the UIV+1 during long-segment thoracolumbar arthrodesis surgery. Outcome measures were prospectively collected and uploaded to a web-based REDCap database specifically designed to include demographic, clinical, and radiological data. All patients underwent clinical assessment, as well as radiological assessment with anteroposterior and lateral 36-inch whole-spine standing radiographs both pre- and postoperatively. RESULTS Forty patients (24 women and 16 men) were included in this study. Median age at surgery was 64.0 years with an IQR of 57.7-70.0 years. Median follow-up was 12 months (IQR 6-15 months). Three procedure-related complications were noted, including 2 intraoperative cerebrospinal spinal fluid leaks and 1 transient neurological deficit. Median visual analog scale (VAS) scores for back pain significantly improved after surgery (preoperatively: 8.0, IQR 6.0-10.0; 1-year follow-up: 2.0, IQR 0.0-6.0; p = 0.001). Median Oswestry Disability Index (version 2.1a) scores also significantly improved after surgery (preoperatively: 56.0, IQR 45.0-64.0; 1-year follow-up: 46.0, IQR 22.2-54.0; p < 0.001). Sagittal vertical axis (preoperatively: 9.0 cm, IQR 5.3-11.6 cm; final follow-up: 4.7 cm, IQR 2.0-6.6 cm; p < 0.001), pelvic incidence-lumbar lordosis mismatch (24.7°, IQR 11.2°-31.2°; 7.7°, IQR -1.2° to 19.5°; p < 0.001), and pelvic tilt (28.7°, IQR 20.4°-32.6°; 17.1°, IQR 10.8°-25.2°; p < 0.001) were all improved at the final follow-up. While proximal junctional (PJ) Cobb angles increased overall at the final follow-up (preoperatively: 4.2°, IQR 1.9°-7.4°; final follow-up: 8.0°, IQR 5.8°-10.3°; p = 0.002), the significant increase was primarily noted starting at the immediate postoperative time point (7.2°, IQR 4.4°-11.8°; p = 0.001) and not beyond. Three patients (7.5%) developed radiological PJK (mean ΔPJ Cobb 15.5°), while there were no instances of PJF in this cohort. CONCLUSIONS Sublaminar band placement at the UIV+1 during long-segment thoracolumbar instrumented arthrodesis is relatively safe and is not associated with an increased rate of PJK. Moreover, no subjects developed PJF. Prospective large-scale and long-term analysis is needed to define the potential benefit of sublaminar bands in reducing the incidence of PJK and PJF following surgery for ASD. Clinical trial registration no.: NCT02411799 (clinicaltrials.gov).

Loss of bladder control is a challenging outcome facing patients with spinal cord injury (SCI). We report that systemic blocking of pro-nerve growth factor (proNGF) signaling through p75 with a CNS-penetrating small-molecule p75 inhibitor resulted in significant improvement in bladder function after SCI in rodents. The usual hyperreflexia was attenuated with normal bladder pressure, and automatic micturition was acquired weeks earlier than in the controls. The improvement was associated with increased excitatory input to the spinal cord, in particular onto the tyrosine hydroxylase-positive fibers in the dorsal commissure. The drug also had an effect on the bladder itself, as the urothelial hyperplasia and detrusor hypertrophy that accompany SCI were largely prevented. Urothelial cell loss that precedes hyperplasia was dependent on p75 in response to urinary proNGF that is detected after SCI in rodents and humans. Surprisingly, death of urothelial cells and the ensuing hyperplastic response were beneficial to functional recovery. Deleting p75 from the urothelium prevented urothelial death, but resulted in reduction in overall voiding efficiency after SCI. These results unveil a dual role of proNGF/p75 signaling in bladder function under pathological conditions with a CNS effect overriding the peripheral one.

Cognitive deficits after traumatic brain injury (TBI) are debilitating and contribute to the morbidity and loss of productivity of over 10 million people worldwide. Cell transplantation has been linked to enhanced cognitive function after experimental traumatic brain injury, yet the mechanism of recovery is poorly understood. Since the hippocampus is a critical structure for learning and memory, supports adult neurogenesis, and is particularly vulnerable after TBI, we hypothesized that stem cell transplantation after TBI enhances cognitive recovery by modulation of endogenous hippocampal neurogenesis. We performed lateral fluid percussion injury (LFPI) in adult mice and transplanted embryonic stem cell-derived neural progenitor cells (NPC). Our data confirm an injury-induced cognitive deficit in novel object recognition, a hippocampal-dependent learning task, which is reversed one week after NPC transplantation. While LFPI alone promotes hippocampal neurogenesis, as revealed by doublecortin immunolabeling of immature neurons, subsequent NPC transplantation prevents increased neurogenesis and is not associated with morphological maturation of endogenous injury-induced immature neurons. Thus, NPC transplantation enhances cognitive recovery early after LFPI without a concomitant increase in neuron numbers or maturation.

Background: Intradural spinal arachnoid cysts (ISACs) with associated neurologic deficits are encountered infrequently. Various management strategies have been proposed with minimal data on comparative outcomes., Objective: We describe the clinical and radiologic presentation as well as the outcomes of 14 surgically managed patients who presented with an ISAC and associated myelopathy., Methods: We retrospectively reviewed the clinical course of consecutive patients presenting with neurologic deficits associated with idiopathic ISACs at our institution. The diagnoses were based on preoperative magnetic resonance imaging studies followed by intraoperative and histopathological confirmation., Results: A total of 14 consecutive patients with ISACs (1 cervicothoracic, 12 thoracic, and 1 thoracolumbar) and associated myelopathy were identified. Syringomyelia was noted in 8 patients. All ISACs were treated with cyst fenestration and partial wall resection through a posterior approach. Preoperative neurologic symptoms were noted to be stable or improved in all patients starting at 6-week postoperative follow-up. The median (interquartile range) preoperative mJOA score was 13 (12.0-14.8), whereas the postoperative median score at a mean follow-up of 22 months (range 6-50 months) was 16 (14.0-17.0), which represents a median improvement (ΔmJOA) of 2.0 (1.3-3.0) (P < 0.001). Comparison of ΔmJOA scores between cases without and with associated syrinxes did not reveal a significant difference (P = 0.23). Postoperative magnetic resonance imaging scans revealed spinal cord re-expansion at the level of the ISAC in all cases and either complete or partial syrinx resolution in 7 of 8 cases., Conclusions: Early treatment with fenestration and partial wall resection allows for cord decompression, syrinx resolution, and gradual resolution of myelopathic symptoms in most cases., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Aim: Bacteria are ubiquitous in the environment. In keeping with the continued expansion of urbanization and the growing population, an increasing number of people use automated banking, i.e. automated teller machines (ATMs). The aim of this study was to investigate the bacterial contamination and its antibiotic sensitivity on computer keyboards located at ATMs in Hamadan province, Iran. Method: Out of 360 ATMs at four locations in Hamadan, 96 were randomly selected for this study. The antibiotic susceptibility pattern of all isolates was determined by the agar disk diffusion method using gentamicin (10 µg), vancomycin (30 µg), trimethoprim/sulfamethoxazole (25 µg), amikacin (30 µg), tobramycin (10 µg), cephalotin (30 µg), norfloxacin (5 µg), and ceftizoxim (30 µg) disks. Results: Melli and Saderat Banks had the most frequently contaminated ATMS, with 18 (27.7%) and 12 (18.5%), respectively. The most frequently isolated bacteria were Staphylococcus epidermidis in 12 (18.5%) ATMs, Pseudomonas aeruginosa in 12 (18.5%), Bacillus subtilis in 11 (16.9%), Escherichia coli in 6 (9.2%), Klebsiella spp. in 8 (12.3%), Enterobacter spp. in 2 (3.1%), Bacillus cereus in 6 (9.2%), Staphylococcus aureus in 3 (4.6%), and Micrococcaceae spp. in 5 (7.69%) cases. All isolated bacteria were susceptible to gentamicin, cephalotin, tobramycin, amikacin, norfloxacin, and vancomycin. The S. aureus resistance rate to trimethoprim/sulfamethoxazole was 50%. Conclusion: All tested ATM keyboards were contaminated with at least one species of bacteria. Based on these findings, it is recommendable to disinfect the hands after entering one's own apartment, work area or a hospital, in order to hinder the spread of critical pathogens in the personal environment or in the hospital.

Objective: This study aims to visualize the subjective symptoms before and after the treatment of whiplash injury using infrared (IR) thermography., Methods: IR thermography was performed for 42 patients who were diagnosed with whiplash injury. There were 19 male and 23 female patients. The mean age was 43.12 years. Thermal differences (ΔT) in the neck and shoulder and changes in the thermal differences (ΔdT) before and after treatment were analyzed. Pain after injury was evaluated using visual analogue scale (VAS) before and after treatment (ΔVAS). The correlations between ΔdT and ΔVAS results before and after the treatment were examined. We used Digital Infrared Thermal Imaging equipment of Dorex company for IR thermography., Results: The skin temperature of the neck and shoulder immediately after injury showed 1-2℃ hyperthermia than normal. After two weeks, the skin temperature was normal range. ΔT after immediately injuy was higher than normal value, but it was gradually near the normal value after two weeks. ΔdT before and after treatment were statistically significant (p<0.05). VAS of the neck and shoulder significantly reduced after 2 week (p=0.001). Also, there was significant correlation between ΔdT and reduced ΔVAS (the neck; r=0.412, p<0.007) (the shoulder; r=0.648, p<0.000)., Conclusion: The skin temperature of sites with whiplash injury is immediately hyperthermia and gradually decreased after two weeks, finally it got close to normal temperature. These were highly correlated with reduced VAS. IR thermography can be a reliable tool to visualize the symptoms of whiplash injury and the effectiveness of treatment in clinical settings.

Background Context: Myxomas are benign tumors of mesenchymal cell origin that usually present as solitary lesions. They are infrequently associated with fibrous dysplasia, as in McCune-Albright or Mazabraud syndrome. Myxomas can develop in a variety of locations, although the most frequent sites are the thigh, buttocks, shoulder, and upper arm. Intramuscular myxomas (IMs) refer to lesions that occur within muscle compartments. They have been infrequently reported in the neck musculature., Purpose: To date, only five cases have been reported within the posterior neck muscles without associated intraspinal extension. To our knowledge, this is the first case of an IM presenting with extension into the spinal canal., Study Design: We report a case of posterior cervical IM with intraspinal extension presenting in a 63-year-old woman as a palpable mass., Methods: Complete intralesional resection of the tumor was achieved by standard midline posterior approach. Meticulous resection of the entire capsule was achieved and all margins were confirmed to be free of neoplasm., Results: A diagnosis of myxoma was provided on pathologic evaluation. Follow-up at 1.5 years confirmed maintained complete resolution of the preoperative symptoms, with no evidence of local recurrence on imaging., Conclusions: Intramuscular myxomas should be included in the differential diagnosis of cervical paraspinal tumors. Furthermore, we suggest that masses involving the axial muscles should be closely monitored and the patient counseled regarding potential neurologic sequelae., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Nerve conduits have emerged as alternatives to autologous nerve grafts, but their use in large-diameter nerve deficits remains untested. We report four patients who underwent repair of large-diameter nerves using absorbable nerve conduits and discuss the failed clinical outcomes. The reported cases demonstrate the importance of evaluating the length, diameter, and function of nerves undergoing conduit repair. In large-diameter nerves, the use of conduits should be carefully considered.

Myelin basic protein (MBP) gene expression is conferred in oligodendrocytes and Schwann cells by different upstream enhancers. In Schwann cells, expression is controlled by a 422 bp enhancer lying -9 kb from the gene. We show here that it contains 22 mammalian conserved motifs > or =6 bp. To investigate their functional significance, different combinations of wild-type or mutated motifs were introduced into reporter constructs that were inserted in single copy at a common hypoxanthine phosphoribosyltransferase docking site in embryonic stem cells. Lines of transgenic mice were derived, and the subsequent qualitative and quantitative expression phenotypes were compared at different stages of maturation. In the enhancer core, seven contiguous motifs cooperate to confer Schwann cell specificity while different combinations of flanking motifs engage, at different stages of Schwann cell maturation, to modulate expression level. Mutation of a Krox-20 binding site reduces the level of reporter expression, whereas mutation of a potential Sox element silences reporter expression. This potential Sox motif was also found conserved in other Schwann cell enhancers, suggesting that it contributes widely to regulatory function. These results demonstrate a close relationship between phylogenetic footprints and regulatory function and suggest a general model of enhancer organization. Finally, this investigation demonstrates that in vivo functional analysis, supported by controlled transgenesis, can be a robust complement to molecular and bioinformatics approaches to regulatory mechanisms.

Myelin basic protein (MBP) is required for normal myelin compaction and is implicated in both experimental and human demyelinating diseases. In this study, as an initial step in defining the regulatory network controlling MBP transcription, we located and characterized the function of evolutionarily conserved regulatory sequences. Long-range human-mouse sequence comparison revealed over 1 kb of conserved noncoding MBP 5' flanking sequence distributed into four widely spaced modules ranging from 0.1 to 0.4 kb. We demonstrate first that a controlled strategy of transgenesis provides an effective means to assign and compare qualitative and quantitative in vivo regulatory programs. Using this strategy, single-copy reporter constructs, designed to evaluate the regulatory significance of modular and intermodular sequences, were introduced by homologous recombination into the mouse hprt (hypoxanthine-guanine phosphoribosyltransferase) locus. The proximal modules M1 and M2 confer comparatively low-level oligodendrocyte expression primarily limited to early postnatal development, whereas the upstream M3 confers high-level oligodendrocyte expression extending throughout maturity. Furthermore, constructs devoid of M3 fail to target expression to newly myelinating oligodendrocytes in the mature CNS. Mutation of putative Nkx6.2/Gtx sites within M3, although not eliminating oligodendrocyte targeting, significantly decreases transgene expression levels. High-level and continuous expression is conferred to myelinating or remyelinating Schwann cells by M4. In addition, when isolated from surrounding MBP sequences, M3 confers transient expression to Schwann cells elaborating myelin. These observations define the in vivo regulatory roles played by conserved noncoding MBP sequences and lead to a combinatorial model in which different regulatory modules are engaged during primary myelination, myelin maintenance, and remyelination.

In peripheral nerves, large caliber axons are ensheathed by myelin-elaborating Schwann cells. Multiple lines of evidence demonstrate that expression of the genes encoding myelin structural proteins occurs in Schwann cells in response to axonal instructions. To gain further insight into the mechanisms controlling myelin gene expression, we used reporter constructs in transgenic mice to search for the DNA elements that regulate the myelin basic protein (MBP) gene. Through this in vivo investigation, we provide evidence for the participation of multiple, widely distributed, positive and negative elements in the overall control of MBP expression. Notably, all constructs bearing a 0.6 kb far-upstream sequence, designated Schwann cell enhancer 1 (SCE1), expressed at high levels in myelin-forming Schwann cells. In addition, robust targeting activity conferred by SCE1 was shown to be independent of other MBP 5' flanking sequence. These observations suggest that SCE1 will make available a powerful tool to drive transgene expression in myelinating Schwann cells and that a focused analysis of the SCE1 sequence will lead to the identification of transcription factor binding sites that positively regulate MBP expression.

We examined the biosynthesis and post-translational processing of the brain-derived neurotrophic factor precursor (pro-BDNF) in cells infected with a pro-BDNF-encoding vaccinia virus. Metabolic labeling, immunoprecipitation, and SDS-polyacrylamide gel electrophoresis reveal that pro-BDNF is generated as a 32-kDa precursor that is N-glycosylated and glycosulfated on a site, within the pro-domain. Some pro-BDNF is released extracellularly and is biologically active as demonstrated by its ability to mediate TrkB phosphorylation. The precursor undergoes N-terminal cleavage within the trans-Golgi network and/or immature secretory vesicles to generate mature BDNF (14 kDa). Small amounts of a 28-kDa protein that is immunoprecipitated with BDNF antibodies is also evident. This protein is generated in the endoplasmic reticulum through N-terminal cleavage of pro-BDNF at the Arg-Gly-Leu-Thr(57)- downward arrow-Ser-Leu site. Cleavage is abolished when Arg(54) is changed to Ala (R54A) by in vitro mutagenesis. Blocking generation of 28-kDa BDNF has no effect on the level of mature BDNF and blocking generation of mature BDNF with alpha(1)-PDX, an inhibitor of furin-like enzymes, does not lead to accumulation of the 28-kDa form. These data suggest that 28-kDa pro-BDNF is not an obligatory intermediate in the formation of the 14-kDa form in the constitutive secretory pathway.

Hippocampal neurons release nerve growth factor (NGF) through the constitutive secretory pathway, thus allowing the protein to be continuously available for promoting nerve cell survival. In contrast, hippocampal neurons use the regulated secretory pathway to process brain-derived neurotrophic factor (BDNF), which alters synaptic activity when released acutely from dense-core vesicles. Thus, understanding how neurons sort and deliver neurotrophins may provide clues to their functions in brain. In this study, we monitored the processing and delivery of neurotrophin-3 (NT-3). Pulse-chase studies, immunocytochemistry, and secretagogue-induced release experiments were performed on cultured hippocampal neurons and AtT-20 cells infected with vaccinia viruses encoding the NT-3 precursor (pro-NT-3). Results show that most newly synthesized NT-3 is released through the constitutive secretory pathway as a result of furin-mediated endoproteolytic cleavage of pro-NT-3 in the trans-Golgi network. Pro-NT-3 can also be diverted into the regulated secretory pathway when cells are treated with alpha1-PDX, a selective inhibitor of furin-like enzymes, or when pro-NT-3 expression is increased by transient transfection methods. In cells coinfected with viruses coding for pro-NT-3 and pro-BDNF, NT-3 is sorted into the regulated pathway, stored in secretory granules, and released in response to extracellular cues together with BDNF, apparently as a result of heterodimerization, as suggested by coimmunoprecipitation data. Taken together, these data show that sorting of the NT-3 precursor can occur in both the constitutive and regulated secretory pathways, which is consistent with NT-3 having both survival-promoting and synapse-altering functions.

Nerve growth factor (NGF) is released through the constitutive secretory pathway from cells in peripheral tissues and nerves where it can act as a target-derived survival factor. In contrast, brain-derived neurotrophic factor (BDNF) appears to be processed in the regulated secretory pathway of brain neurons and secreted in an activity-dependent manner to play a role in synaptic plasticity. To determine whether sorting differences are intrinsic to the neurotrophins or reflect differences between cell types, we compared NGF and BDNF processing in cultured hippocampal neurons using a Vaccinia virus expression system. Three independent criteria (retention or release from cells after pulse-chase labeling, depolarization-dependent release, and immunocytochemical localization) suggest that the bulk of newly synthesized NGF is sorted into the constitutive pathway, whereas BDNF is primarily sorted into the regulated secretory pathway. Similar results occurred with AtT 20 cells, including those transfected with cDNAs encoding neurotrophin precursor-green fluorescent protein fusions. The NGF precursor, but not the BDNF precursor, is efficiently cleaved by the endoprotease furin in the trans-Golgi network (TGN). Blocking furin activity in AtT 20 cells with alpha1-PDX as well as increasing the expression of NGF precursor partially directed NGF into the regulated secretory pathway. Therefore, neurotrophins can be sorted into either the constitutive or regulated secretory pathways, and sorting may be regulated by the efficiency of furin cleavage in the TGN. This mechanism may explain how neuron-generated neurotrophins can act both as survival factors and as neuropeptides.