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Study design General population utility valuation study. Objective The aim of this study was to develop a technique for calculating utilities from the Spine Oncology Study Group Outcomes Questionnaire v2.0 (SOSGOQ2.0). Summary of background data The ability to calculate quality-adjusted life-years (QALYs) for metastatic spine disease would enhance treatment decision-making and facilitate economic analysis. QALYs are calculated using utilities. Methods Using a hybrid concept-retention and factorial analysis shortening approach, we first shortened the SOSGOQ2.0 to eight items (SOSGOQ-8D). This was done to lessen the cognitive burden of the utility valuation exercise. A general population sample of 2730 adults was then asked to evaluate 12 choice sets based on SOSGOQ-8D health states in a Discrete Choice Experiment. A utility scoring rubric was then developed using a mixed multinomial-logit regression model. Results We were able to reduce the SOSGOQ2.0 to an SOSGOQ-8D with a mean error of 0.003 and mean absolute error of 3.078 compared to the full questionnaire. The regression model demonstrated good predictive performance and was used to develop a utility scoring rubric. Regression results revealed that participants did not regard all SOSGOQ-8D items as equally important. Conclusion We provide a simple technique for converting the SOSGOQ2.0 to utilities. The ability to evaluate QALYs in metastatic spine disease will facilitate economic analysis and patient counseling. We also quantify the importance of individual SOSGOQ-8D items. Clinicians should heed these findings and offer treatments that maximize function in the most important items.Level of Evidence: 3.

Currently there is no prospective pain and health related quality of life (HRQOL) data of patients with potentially unstable spinal metastases who were treated with surgery ± radiation or radiation alone.An international prospective cohort multicenter study of patients with potentially unstable spinal metastases, defined by a SINS score 7 to 12, treated with surgery ± radiation or radiotherapy alone was conducted. HRQOL was evaluated with the numeric rating scale (NRS) pain score, the SOSGOQ2.0, the SF-36, and the EQ-5D at baseline and 6, 12, 26, and 52 weeks after treatment.A total of 136 patients were treated with surgery ± radiotherapy and 84 with radiotherapy alone. At baseline, surgically treated patients were more likely to have mechanical pain, a lytic lesion, a greater median Spinal Instability Neoplastic score, vertebral compression fracture, lower performance status, HRQOL, and pain scores. From baseline to 12 weeks post-treatment, surgically treated patients experienced a 3.0-point decrease in NRS pain score (95% CI -4.1 to -1.9, p.001), and a 12.7-point increase in SOSGOQ2.0 score (95% CI 6.3-19.1, p.001). Patients treated with radiotherapy alone experienced a 1.4-point decrease in the NRS pain score (95% CI -2.9 to 0.0, p=.046) and a 6.2-point increase in SOSGOQ2.0 score (95% CI -2.0 to 14.5, p=.331). Beyond 12 weeks, significant improvements in pain and HRQOL metrics were maintained up to 52-weeks follow-up in the surgical cohort, as compared with no significant changes in the radiotherapy alone cohort.Patients treated with surgery demonstrated clinically and statistically significant improvements in pain and HRQOL up to 1-year postsurgery. Treatment with radiotherapy alone resulted in improved pain scores, but these were not sustained beyond 3 months and HRQOL outcomes demonstrated nonsignificant changes over time. Within the SINS potentially unstable group, distinct clinical profiles were observed in patients treated with surgery or radiotherapy alone.

Study Design: International multicenter prospective observational cohort study on patients undergoing radiation +/− surgical intervention for the treatment of symptomatic spinal metastases. Objectives: To investigate the association between the total Spinal Instability Neoplastic Score (SINS), individual SINS components and PROs. Methods: Data regarding patient demographics, diagnostics, treatment, and PROs (SF-36, SOSGOQ, EQ-5D) was collected at baseline, 6 weeks, and 12 weeks post-treatment. The SINS was assessed using routine diagnostic imaging. The association between SINS, PRO at baseline and change in PROs was examined with the Spearmans rank test. Results: A total of 307 patients, including 174 patients who underwent surgery+/− radiotherapy and 133 patients who underwent radiotherapy were eligible for analyses. In the surgery+/− radiotherapy group, 18 (10.3%) patients with SINS score between 0-6, 118 (67.8%) with a SINS between 7-12 and 38 (21.8%) with a SINS between 13-18, as compared to 55 (41.4%) SINS 0-6, 71(53.4%) SINS 7-12 and 7 (5.2%) SINS 13-18 in the radiotherapy alone group. At baseline, the total SINS and the presence of mechanical pain was significantly associated with the SOSGOQ pain domain (r = −0.519, P < 0.001) and the NRS pain score (r = 0.445, P < 0.001) for all patients. The presence of mechanical pain demonstrated to be moderately associated with a positive change in PROs at 12 weeks post-treatment. Conclusion: Spinal instability, as defined by the SINS, was significantly correlated with PROs at baseline and change in PROs post-treatment. Mechanical pain, as a single SINS component, showed the highest correlations with PROs.

Background Patient satisfaction is infrequently investigated despite its importance in assessing efficacy and patient comprehension. The purpose of this study was to investigate patient satisfaction with treatment outcomes after surgery and/or radiotherapy for spinal metastases and to evaluate how health‐related quality of life (HRQOL) is related to patient satisfaction. Methods Patients with spinal metastases treated with surgery and/or radiotherapy were enrolled in a prospective, international, observational study. Demographic, histologic, treatment, and HRQOL data were collected. HRQOL was evaluated with the Numeric Rating Scale pain score, the 3‐level version of the EuroQol 5‐Dimension (EQ‐5D‐3L) instrument, and the Spine Oncology Study Group Outcomes Questionnaire (SOSGOQ2.0). Patient satisfaction was derived from the SOSGOQ2.0 at 6, 12, and 26 weeks after treatment. Patients were classified as satisfied, neutral, or dissatisfied. Results Twelve weeks after treatment, 183 of the surgically treated patients (84%) were satisfied, and only 11 (5%) were dissatisfied; in contrast, 101 of the patients treated with radiotherapy alone (77%) were satisfied, and only 7 (5%) were dissatisfied. Significant improvements in pain, physical function, mental health, social function, leg function, and EQ‐5D were associated with satisfaction after surgery. Satisfaction after radiotherapy was associated with significant improvements in pain, mental health, and overall SOSGOQ2.0 scores. Dissatisfaction after treatment was associated with lower baseline values for leg strength and lower social functioning scores for surgically treated patients and with lower social functioning scores and being single for patients treated with radiotherapy. Conclusions High levels of satisfaction with treatment outcomes are observed after surgery and/or radiotherapy for spinal metastases. Posttreatment satisfaction is associated with significant improvements in pain and different dimensions of HRQOL., High levels of satisfaction with treatment outcomes are observed after surgery and/or radiotherapy for spinal metastases. Posttreatment satisfaction is associated with significant improvements in pain and different dimensions of health‐related quality of life.

Study Design: A narrative review of the literature. Objective: This article reviews the general principles of treatment and investigation for primary bone tumors of the spine. Furthermore, it explores the emerging alternatives. Methods: A review was performed using Medline, Embase, and Cochrane databases. Results: Primary bone tumors of the spine are rare entities that general spine surgeons may encounter only a few times in their career. The treatment algorithm of these complex tumors is filled with nuances and is evolving constantly. For these reasons, patients should be referred to experienced tertiary or quaternary centers who can offer a comprehensive multidisciplinary approach. For most malignant spinal bone tumors, surgery remains the cornerstone of treatment. Respecting oncologic principles has been associated with improved survival and decreased local recurrence in multiple settings. However, even in experienced centers, these surgeries carry a significant risk of adverse events and possible long-term neurologic impairment. The associated morbidity of these procedures and the challenges of local recurrence have encouraged professionals caring for these patients to explore alternatives or adjuncts to surgical treatment. Conclusions: Over the past few years, several advances have occurred in medical oncology, radiation oncology and interventional radiology, changing the treatment paradigm for some tumors. Other advances still need to be refined before being applied in a clinical setting.

Study Design: Literature review. Objective: To provide an overview of the recent advances in spinal oncology, emphasizing the key role of the surgeon in the treatment of patients with spinal metastatic tumors. Methods: Literature review. Results: Therapeutic advances led to longer survival times among cancer patients, placing significant emphasis on durable local control, optimization of quality of life, and daily function for patients with spinal metastatic tumors. Recent integration of modern diagnostic tools, precision oncologic treatment, and widespread use of new technologies has transformed the treatment of spinal metastases. Currently, multidisciplinary spinal oncology teams include spinal surgeons, radiation and medical oncologists, pain and rehabilitation specialists, and interventional radiologists. Consistent use of common language facilitates communication, definition of treatment indications and outcomes, alongside comparative clinical research. The main parameters used to characterize patients with spinal metastases include functional status and health-related quality of life, the spinal instability neoplastic score, the epidural spinal cord compression scale, tumor histology, and genomic profile. Conclusions: Stereotactic body radiotherapy revolutionized spinal oncology through delivery of durable local tumor control regardless of tumor histology. Currently, the major surgical indications include mechanical instability and high-grade spinal cord compression, when applicable, with surgery providing notable improvement in the quality of life and functional status for appropriately selected patients. Surgical trends include less invasive surgery with emphasis on durable local control and spinal stabilization.

Background Spinal chordomas, a subtype of primary spinal column malignancies (PSCM), are rare tumors with poor prognosis, and we have limited understanding of the molecular drivers of neoplasia. Methods Study design was a retrospective review of prospectively collected data with cross-sectional survival. Archived paraffin embedded pathologic specimens were collected for 133 patients from 6 centers within Europe and North America between 1987 and 2012. Tumor DNA was extracted and the human telomerase reverse transcriptase (hTERT) promoter was sequenced. The hTERT mutational status was correlated with overall survival (OS) and time to first local recurrence. Results Ninety-two chordomas, 26 chondrosarcomas, 7 osteosarcomas, 3 Ewing’s sarcomas, and 5 other malignant spinal tumors were analyzed. Median OS following surgery was 5.8 years (95% CI: 4.6 to 6.9) and median time to first local recurrence was 3.9 years (95% CI: 2.5 to 6.7). Eight chordomas, 2 chondrosarcomas, 1 Ewing’s sarcoma, and 1 other malignant spinal tumor harbored either a C228T or C250T mutation in the hTERT promoter. In the overall cohort, all patients with hTERT mutation were alive at 10 years postoperative with a median OS of 5.1 years (95% CI: 4.5 to 6.6) (P = 0.03). hTERT promoter mutation was observed in 8.7% of spinal chordomas, and 100% of chordoma patients harboring the mutation were alive at 10 years postoperative compared with 67% patients without the mutation (P = 0.05). Conclusions We report for the first time that hTERT promoter mutations C228T and C250T are present in approximately 8.7% of spinal chordomas. The presence of hTERT mutations conferred a survival benefit and could potentially be a valuable positive prognostic molecular marker in spinal chordomas.

Given the moderate efficacy of the currently available antidepressants (ADs) in the treatment of major depressive disorder (MDD), the identification of agents that are both able to enhance the effectiveness of ADs and have a good safety profile is a reasonable task for current psychopharmacology. In addition to the well-known drugs (second-generation antipsychotics, levothyroxine, dopaminergic agents, etc.) for augmentation, investigations suggest that several nutraceuticals and over-the-counter (OTC) drugs may be effective and safe as adjunct therapeutic agents to conventional ADs. To identify such active ingredients we first performed a systematic literature search using PubMed and then conducted both backward and forward citation searches. For the PubMed search, we used the following combinations of keywords: 1) "adjunctive" + "therapy" + "antidepressant"; 2) "add-on" + "therapy" + "antidepressant"; 3) "supplementation" + "therapy" + "antidepressant". As a result of those efforts, we found more than 20 agents (e.g. S-Adenosyl-L-Methionine; folate; ω-3 fatty acids; curcumin; N-acetylcysteine; saffron; 5-hydroxytryptophan; NSAIDs) that are supposedly effective in the augmentation of standard AD treatment. We discussed the possible mechanisms of the antidepressant actions of those agents, as well as the preclinical and clinical evidence for their efficacy as stand-alone and adjunct treatments for MDD.

Study Design: Ambispective cohort study design. Objectives: Cervical spine metastases have distinct clinical considerations. The aim of this study was to determine the impact of surgical intervention (± radiotherapy) or radiotherapy alone on health-related quality of life (HRQOL) outcomes in patients treated for cervical metastatic spine tumours. Methods: Patients treated with surgery and/or radiotherapy for cervical spine metastases were identified from the Epidemiology, Process, and Outcomes of Spine Oncology (EPOSO) international multicentre prospective observational study. Demographic, diagnostic, treatment, and HRQOL (numerical rating scale [NRS] pain, EQ-5D (3L), SF-36v2, and SOSGOQ) measures were prospectively collected at baseline, 6 weeks, 3 months, and 6 months postintervention. Results: Fifty-five patients treated for cervical metastases were identified: 38 underwent surgery ± radiation and 17 received radiation alone. Surgically treated patients had higher mean spinal instability neoplastic scores compared with the radiation-alone group (13.0 vs 8.0, P < .001) and higher NRS pain scores and lower HRQOL scores compared to the radiation alone group ( P < .05). From baseline to 6 months posttreatment, surgically treated patients demonstrated statistically significant improvements in NRS pain, EQ-5D (5L), and SOSGOQ2.0 scores compared with nonsignificant improvements in the radiotherapy alone group. Conclusions: Surgically treated cervical metastases patients presented with higher levels of instability, worse baseline pain and HRQOL scores compared with patients who underwent radiotherapy alone. Significant improvements in pain and HRQOL were noted for those patients who received surgical intervention. Limited or no improvements were found in those treated with radiotherapy alone.

Although there is accumulating evidence on the potential influencing factors of medication adherence, the knowledge about patients' attitudes and beliefs toward treatment is only partly utilized in adherence-improving strategies. Several internal and external factors determining adherence have been described regarding many chronic somatic diseases but in recent research, insight on psychiatric patients has been exclusively lacking. As a result, there is a scarcity of effective adherence-improving interventions. Identification of any specific differences or similarities between the attitudes toward treatment of psychiatric and non-psychiatric patients would help to support adherent behavior.We recruited 189 participants from four departments of general psychiatry (GEN PSYCH, n = 106), addictology (ADDICT, n = 42) and somatic diseases (NON PSYCH, n = 41). The Patient's Health Belief Questionnaire on Psychiatric Treatment (PHBQPT) was performed to assess the patients' attitude toward drug treatment, perceived health locus of control, and psychological reactance.The most robust difference of the PHBQT scores occurred between the GEN PSYCH and ADDICT subgroups. ADDICT patients scored significantly higher on the internal and external health locus of control and on the Psychological Reactance subscale as well. While GEN PSYCH subjects provided higher scores on the Positive Aspect of Medication compared to ADDICT persons. Interestingly, the only difference between the GEN PSYCH and NON-PSYCH groups was the more pronounced mistrust in physicians in the case of psychiatric patients.Our data suggest that mistrust toward medication does not differ in psychiatric and non-psychiatric samples, while the acceptance of the doctor's competency may be stronger in the non-psychiatric sample. The analysis of these factors provides information which could help us better understand this important issue and to develop more efficient interventions for improving adherence.

OBJECTIVE Oncological resection of primary spine tumors is associated with lower recurrence rates. However, even in the most experienced hands, the execution of a meticulously drafted plan sometimes fails. The objectives of this study were to determine how successful surgical teams are at achieving planned surgical margins and how successful surgeons are in intraoperatively assessing tumor margins. The secondary objective was to identify factors associated with successful execution of planned resection. METHODS The Primary Tumor Research and Outcomes Network (PTRON) is a multicenter international prospective registry for the management of primary tumors of the spine. Using this registry, the authors compared 1) the planned surgical margin and 2) the intraoperative assessment of the margin by the surgeon with the postoperative assessment of the margin by the pathologist. Univariate analysis was used to assess whether factors such as histology, size, location, previous radiotherapy, and revision surgery were associated with successful execution of the planned margins. RESULTS Three hundred patients were included. The surgical plan was successfully achieved in 224 (74.7%) patients. The surgeon correctly assessed the intraoperative margins, as reported in the final assessment by the pathologist, in 239 (79.7%) patients. On univariate analysis, no factor had a statistically significant influence on successful achievement of planned margins. CONCLUSIONS In high-volume cancer centers around the world, planned surgical margins can be achieved in approximately 75% of cases. The morbidity of the proposed intervention must be balanced with the expected success rate in order to optimize patient management and surgical decision-making.

The assessment of risk of vertebral fracture in patients with lytic metastases is challenging, due to the complexity in modelling the mechanical properties of this heterogeneous material. Currently clinical assessment of patients at high risk of fracture is based on the Spinal Instability Neoplastic Score (SINS), which however in many cases does not provide clear guidelines. The goal of this study was to develop a computational approach to provide a comparative biomechanical assessment of vertebrae with lytic lesions with respect to the adjacent controls and highlight the critical vertebrae. The computed tomography images of the thoracolumbar spine of eight patients suffering of vertebral lytic metastases with SINS between 7 and 12 (indeterminate unstable) were analysed. For each patient one or two vertebrae with lytic lesions were modelled and the closest vertebrae without lesions were considered as control. Metastatic vertebrae (N = 12) and controls (N = 18) were converted to subject-specific, heterogeneous, isotropic, nonlinear finite element models for simulating uniaxial compression. Densitometric and mechanical properties were computed for each vertebra. In average, similar mechanical properties were found for vertebrae with lytic lesions and controls (e.g. ultimate force equal to 6.2 ± 2.7 kN for vertebrae with lytic lesions and to 6.2 ± 3.0 kN for control vertebrae). Only in three patients the vertebrae with lytic lesions were found to be mechanically weaker (−19% to −75% difference for ultimate stress) than the controls. In conclusion, in this study we presented an approach to estimate the mechanical competence of vertebrae with lytic metastases. It remains to be investigated in a clinical study if this method, together with the SINS, can better classify patients with vertebrae with lytic lesions at high risk of fracture.

The STarT Back Tool was developed to identify the specific modifiable prognostic factors for non-specific low back pain and to classify the patients into risk groups; low, medium and high risk of chronicity. Applied therapeutic approaches often involve group physical therapy. The aim of this study was the cross-cultural adaptation and validation of the Hungarian version of the STarT Back Tool and to investigate the predictive ability for global treatment outcome. A prospective cohort study (N = 133) was carried out involving non-specific low back pain patients. Internal consistency, construct validity, reliability and prognostic discriminative ability have been investigated. After 3 months of treatment global outcome was evaluated. A 2-factor structure was found, with moderate internal consistency (Cronbach α = 0.89 for the total and psychosocial subscale 0.62). Between the Hungarian STarT Back Tool, the Oswestry Disability Index, leg pain, low back pain, Tampa Scale for Kinesiophobia, Fear Avoidance Beliefs Questionnaire and the physical subscale of the quality of life questionnaire, significant good to excellent- correlation was found (r > 0.41). The test-retest analysis showed excellent reliability (Intraclass Correlation Coefficient = 0.93) with standard error measurement being 0.49 (minimal detectable change = 1.37). The Area Under the Curve for baseline STarT Back Tool scores was 0.7 and 0.8 for global treatment outcome and distress, respectively. The Area Under the Curve for global treatment outcome versus STarT risk groups proved to be 0.76 representing adequate discriminative ability. The successful cross-cultural adaptation was followed by the validity analysis and as a result the Hungarian version of the STarT Back Tool proved to be a reliable and valid tool in the identification of risk groups of chronicity for patients with low back pain. Patients allocated to the high-risk group were more likely experiencing poor outcome at 3 months follow up, thus it can be used to predict outcome if treated with group physical therapy.Implication for rehabilitationLow back pain is a multifactorial disease where physical and psychosocial risk factors play a role in the development and prognosis of the disease.The STarT-H can be considered as a reliable, valid measurement tool in the identification of risk groups of chronicity for patients with low back pain.Clinical relevance of the STarT-H is that it can be used to stratify patients into risk groups of chronicity in different Hungarian speaking healthcare settings.According to our findings the STarT-H can also be applied to predict global treatment outcome in low back pain patients if treated with group physical therapy. Low back pain is a multifactorial disease where physical and psychosocial risk factors play a role in the development and prognosis of the disease. The STarT-H can be considered as a reliable, valid measurement tool in the identification of risk groups of chronicity for patients with low back pain. Clinical relevance of the STarT-H is that it can be used to stratify patients into risk groups of chronicity in different Hungarian speaking healthcare settings. According to our findings the STarT-H can also be applied to predict global treatment outcome in low back pain patients if treated with group physical therapy.

Background: Surgical site infection (SSI) is a serious complication after routine lumbar spinal operations, and its effect on global treatment outcome (GTO) is less reported. The aim of the current...

BACKGROUND CONTEXT Oncologic resection of primary spine tumors is associated with lower recurrence rates. However, even in the most experienced hands, executing a meticulously drafted plan sometimes fails. PURPOSE The goal of this study was to utilize prospective multicenter data to determine how successful experienced surgical teams are at achieving planned surgical margins and how successful surgeons are in assessing tumor margins intraoperatively. The secondary objective was to identify factors that are associated with successful execution of the planned margins. STUDY DESIGN/SETTING This study was part of a multicenter international prospective registry for the management and outcomes of primary tumors of the spine called Primary Tumor Research and Outcomes Network (PTRON, ClinicalTrials.gov: NCT02790983). PTRON was designed and led by the AO Spine Knowledge Forum Tumor and has established an international network of 16 spine oncology centers from North America, Europe, and Asia that are dedicated to prospective research of patients diagnosed with a primary tumor of the spine. OUTCOME MEASURES Using this registry, we compared (1) planned surgical margin and (2) intraoperative assessment of the margin by the surgeon to the postoperative assessment of the margin by the pathologist. Planned and intraoperative margin assessments by the surgeon were assessed and recorded in the PTRON database in five categories: (1) intralesional; (2) intralesional with planned focal transgression; (3) marginal; (4) wide with marginal at dura, and (5) wide. The pathologist's assessment was documented in four categories for overall margin, at soft tissue, at bone, and at dura: (1) intralesional; (2) intralesional with planned focal transgression; (3) marginal; and (4) wide. The primary endpoints of this analysis were to compare (1) the planned surgical margin and (2) intraoperative assessment of the margin by the surgeon to the postoperative assessment of the margin by the pathologist. For the first endpoint, success was defined as achievement of planned surgical margins or better as confirmed by pathologist assessment. For the second endpoint, success was defined by appropriate intraoperative assessment of the margin by the surgeon when compared to histologic assessment. METHODS Univariate analyses were used to assess factors associated with successful execution of the planned resection. RESULTS A total of 300 patients from 16 centers located in North America, Europe and Asia were included for analysis. Median age was 46.0 years (IQR 27.0 – 61.5). The majority of patients were male (63.0%). Successful achievement of planned margins was attained in 224 patients (74.7%). Overall, marginal or wide margins were attained in 261 patients (87.0%). Surgeon's perception of the margins achieved intraoperatively was correctly determined in 239 patients (79.7%) compared to pathologist assessment. Margins identified as marginal or wide were adequately evaluated intraoperatively as such in 261 patients (87.0%). On univariate analysis, no factors had a statistically significant association with the achievement of successful margins. Conclusions In high volume cancer centers around the world, planned surgical margins can be achieved in approximately 75% of cases. The morbidity of the proposed intervention must be balanced with expected success rates in order to optimize patient management and surgical decision-making. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

Current musculoskeletal modeling does not take the functionally initial standing posture of the lumbar spine system into consideration. This may lead to inaccurate simulation outcomes for clinical decision support. This present study aimed to develop a fusion process from multimodal medical images for developing, simulating, and assessing patient specific musculoskeletal model of the lumbar spine system in functional posture. Computed tomography (CT) and X-rays were acquired on a patient. A 3D/2D matching procedure was developed using feature-based approach to transform CT-based 3D geometries into standing posture. Then, a musculoskeletal model was developed including 7 segments, 18-DOF (degrees of freedom) and 126 muscle fascicles. Model evaluation was performed using X-ray data and curvature metric. Muscle force deviations were quantified for the comparison between image-based model and generic-scaled model as well as for the sensitivity of psoas major attachment point definition. Curvatures of the simulation outcomes fall within the range of X-ray data for extension posture. Difference was noted for flexed posture. The use of generic model leads to a deviation of 66% of the muscle forces according to the image-based model. A maximal relative deviation of 4% of the estimated psoas major fascicle force was found for the analysis of the sensitivity of muscle attachment point. This study proposed a useful data fusion process from multimodal medical images to create patient specific lumbar spine model in correct initial posture leading to perform accurate dynamic simulations. Moreover, this study suggested that image-based model needs to be developed for clinical decision making related to spinal disorders.

BACKGROUND Despite our inability to accurately predict survival in many cancer patients, a life expectancy of at least 3 mo is historically necessary to be considered for surgical treatment of spinal metastases. OBJECTIVE To compare health-related quality of life (HRQOL) in patients surviving 3 mo to assess the validity of this inclusion criteria. METHODS Patients who underwent surgery for spinal metastases between August 2013 and May 2017 were retrospectively identified from an international cohort study. HRQOL was evaluated using generic and disease-specific outcome tools at baseline and at 6 and 12 wk postsurgery. The primary outcome was the HRQOL at 6 wk post-treatment measured by the Spine Oncology Study Group Outcomes Questionnaire (SOSGOQ). RESULTS A total of 253 patients were included: 40 patients died within the first 3 mo after surgery and 213 patients survived more than 3 mo. Patients surviving

Background A critical knowledge gap exists regarding the impact of neurologic deficits on surgical outcomes and health-related quality of life (HRQOL) for patients surgically treated for metastatic epidural spinal cord compression (MESCC). Methods This prospective, multicenter and international study analyzed the impact of the neurologic status on functional status, HRQOL, and postoperative survival. The collected data included the patient demographics, overall survival, American Spinal Injury Association (ASIA) impairment scale, Spinal Instability Neoplastic Score, treatment details and complications and HRQOL measures, including version 2 of the 36-Item Short Form Health Survey (SF-36v2) and version 2.0 of the Spine Oncology Study Group Outcomes Questionnaire (SOSGOQ2.0). Results A total of 239 patients surgically treated for spinal metastases were included. Six weeks after treatment, 99 of the 108 patients with a preoperative ASIA grade of E remained stable, 8 deteriorated to ASIA D, and 1 deteriorated to ASIA A. Of 55 patients with ASIA D, 27 improved to ASIA E, 27 remained stable and 1 deteriorated to ASIA C. Of 11 patients with ASIA A to C, 2 improved to ASIA E, 4 improved to ASIA D, and 5 remained stable. At the 6- and 12-week follow-up, better ASIA scores were associated with better scores on multiple SF-36v2 and SOSGOQ items. Postoperatively, patients with ASIA grades of A to D were more likely to have urinary tract infections and wound complications. Patients with a baseline ASIA grade of E or D survived significantly longer. Conclusions Patients with neurologic deficits due to MESCC have worse HRQOL and decreased overall survival. Nevertheless, surgery can result in stabilization or improvement of neurologic function which may translate into better HRQOL. Postoperative care and follow-up are challenging for patients with neurologic deficits because they experience more complications.

Background Accumulating data suggest that CB2 receptor plays a crucial role in development of anxiety via regulatory function of stress response and neuroimmune crosstalk. Although animal experiments confirm this relationship, relevant human genetic studies on CB2 receptor gene (CNR2) in association with affective phenotype are absent. Methods CNR2 R63Q and FAAH C385A functional polymorphisms were genotyped of 921 volunteers from the general population. Phenotypic variables were measured by the Zung Self-related Depression Scale (ZSDS), The State-Trait Anxiety Inventory (Trait subscale, STAI-T) and the depressive and anxious subscales of the Brief Symptom Inventory (BSI-DEP and BSI-ANX). Early life trauma was assesssed by the Childhood Trauma Questionnaire (CHQ). Using general linear models we tested possible associations between phenotypic variance and genotype distribution. Results There was a significant main effect of RR genotype of R63Q on ZSDS score (p = 0.007) and a remarkble interacting effect of CHQ and R63Q on scores of ZSDS, STAI-T and BSI-ANX scales (p = 0.009; p = 0.003; p = 0.001; respectively). R allele of R63Q and A allele of FAAH C385A were associated with significantly higher ZSDS, STAI-T and BSI-ANX scores compared to non-risk allele carriers (p = 0.009; p = 0.007; p = 0.007, respectively). The highest phenotypic scores were observed in GxGxE model (pZSDS = 0.04; pBSI-DEP = 0.006; pSTAI-T = 0.001; pBSI-ANX = 3.8 × 10−5). Conclusions In this first human genetic study on CNR2 and childhood trauma we revealed that dysfunctional CB2 receptor and FAAH can contribute to greater sensitivity for childhood trauma possibly via weaker inhibiton of inflammatory and overactivated HPA axis.

Background Context Surgical site infection (SSI) is one of the most serious complications of spine surgery. Its predisposing factors, especially in routine surgeries, are less reported. However, a number of patient- and procedure-related risk factors could be avoided or at least determined preoperatively. Moreover, the patient-specific risk for SSI could be estimated before the elective surgery. Purpose The aim of the present study was to analyze the preoperatively determinable risk factors for SSI in patients who require elective routine surgery related to lumbar disc degeneration and to build a multivariable model for the individual risk prediction. Study Design Analysis of prospectively collected standardized clinical data and the validation of the results on an independent prospective cohort were performed. Patient Sample One thousand thirty (N=1,030) patients were included in the study. All subjects underwent primary lumbar single- or two-level decompression, microdiscectomy, or instrumented fusion. Outcome Measures Occurrence of an SSI defined according to the current Centers for Disease Control and Prevention guidelines that required surgical or nonsurgical therapy. Methods The effect of preoperative patient characteristics, comorbidities, disease history, and invasiveness of the elective surgery on the risk of SSI was determined in uni- and multivariate logistic regression models in the test cohort (N=723). The performance of the final multivariable regression model was assessed by measuring its discriminative ability (c-index) in receiver operating characteristic analysis. Performance of the multivariable risk estimation model was tested on the validation (N=307) cohort. Results The prevalence of SSI was 3.5% and 3.9% in the test and in the validation cohorts, respectively. The final multivariable regression model predictive (p=.003) for SSI contained the patient's age, body mass index (BMI), and the presence of 5 comorbidities, such as diabetes, ischemic heart disease, arrhythmia, chronic liver disease, and autoimmune disease as risk factors. The c-index of the model was 0.71, showing good discriminative ability, and it was confirmed by the data of the independent validation cohort (c=0.72). Conclusions Predisposing factors for SSI were older age, higher BMI, and the presence of certain comorbidities in the present study. The cumulative number of risk factors significantly associated with the increasing risk for an SSI (p

Study design Systematic literature review. Objective To investigate if evidence-based principles of oncologic resection for primary spinal tumors are correlated with an acceptable morbidity and mortality profile and satisfactory health-related quality of life (HRQOL) measures. Summary of background data Respecting oncologic principles for primary spinal tumor surgery is correlated with lower recurrence rates. These interventions are, however, often highly morbid. Methods A systematic literature review was performed to address the objectives by searching MEDLINE and EBMR databases. Articles that met our inclusion criteria were reviewed. GRADE guidelines were used for recommendation formulation. Results A total of 25 articles addressing the morbidity and mortality profile of primary spinal tumor surgery were identified. For sacral tumors, complication rates of up to 100% have been reported and complication-related death ranged from 0% to 27%. Mobile spine tumor complication rates varied from 13% to 73.7% and complication-related death ranged from 0% to 7.7%. Seven articles examining HRQOL for this patient population were identified. The limited literature showed comparable patient HRQOL profiles to those with benign conditions such as degenerative disc disease. Conclusion Respecting oncologic principles for primary spinal tumors are correlated with high adverse event rates. We recommend that primary spinal tumor surgeries be performed in experienced centers with multidisciplinary support teams and that prospective adverse event collection be promoted (strong recommendation/very low certainty of the evidence). Oncologic resection of primary tumors of the spine is associated with HRQOL that more closely approximates normative values with increasing duration of follow-up, but decreases with disease recurrence. We recommend primary spinal tumor surgery be performed with a curative intent whenever possible, even at the expense of greater initial morbidity to optimize long-term HRQOL (strong recommendation/very low certainty of the evidence). Level of evidence N/A.

Study design Systematic literature review and expert survey OBJECTIVE.: The aim of this study was to determine factors associated with neurologic improvement in patients with neurologic deficits secondary to metastatic epidural spinal cord compression (MESCC). Clear understanding of these factors will guide surgical decision-making by helping to elucidate which patients are more likely to benefit from surgery and how surgeons can increase the probability of neurologic and functional restoration. Summary of background data Surgical spinal cord decompression has been shown to improve neurologic function in patients with symptomatic MESCC. However, prognostication of neurologic improvement after surgery remains challenging, owing to sparse data and complexity of these patients. Methods PubMed and Embase databases were searched for relevant publications. PRISMA Statement guided publication selection and data reporting. GRADE guidelines were used for evidence quality evaluation and recommendation formulation. Results Low-quality evidence supports the use of the duration and severity of neurologic deficit as predictors of neurological recovery in patients with MESCC. Low-quality evidence supports the use of thoracic level of compression and previous irradiation as adverse predictors of neurological recovery. Nearly all of the AOSpine Knowledge Forum Tumor members who responded to the survey agreed that ambulation with assistance represented a successful surgical result and that duration of ambulation loss and the severity of weakness should be considered when trying to predict whether surgery would result in restoration of ambulation. Conclusions Review of literature and expert opinion support the importance of duration of ambulation loss and the severity of neurologic deficit (muscle strength, bladder function) in prediction of neurologic recovery among patients with symptomatic MESCC. Efforts to reduce the duration of ambulation loss and to prevent progression of neurologic deficits should be made to improve the probability of neurologic recovery. Level of evidence 2.

Purpose: The primary goal of this article is to achieve an automatic and objective method to compute the Pfirrmann’s degeneration grade of intervertebral discs (IVD) from MRI. This grading system is used in the diagnosis and management of patients with low back pain (LBP). In addition, biomechanical models, which are employed to assess the treatment on patients with LBP, require this grading value to compute proper material properties.\ud \ud \ud \ud Materials and methods: T2-weighted MR images of 48 patients were employed in this work. The 240 lumbar IVDs were divided into a training set (140) and a testing set (100). Three experts manually classified the whole set of IVDs using the Pfirrmann’s grading system and the ground truth was selected as the most voted value among them. The developed method employs active contour models to delineate the boundaries of the IVD. Subsequently, the classification is achieved using a trained Neural Network (NN) with eight designed features that contain shape and intensity information of the IVDs.\ud \ud \ud \ud Results: The classification method was evaluated using the testing set, resulting in a mean specificity (95.5 %) and sensitivity (87.3 %) comparable to those of every expert with respect to the ground truth.\ud \ud \ud \ud Conclusions: Our results show that the automatic method and humans perform equally well in terms of the classification accuracy. However, human annotations have inherent inter- and intra-observer variabilities, which lead to inconsistent assessments. In contrast, the proposed automatic method is objective, being only dependent on the input MRI.

Percutaneous cement discoplasty (PCD) is a minimally invasive surgical procedure, that can provide a segmental stabilizing and indirect decompression effect in case of severely degenerated discs characterized by vacuum phenomenon. The objective of this study was to evaluate the effects of PCD on spinopelvic radiological parameters and their associations with the clinical outcome. Retrospective analysis of prospectively collected dataset of 28 patients (112 lumbar segments) who underwent single- or multilevel PCD was performed. Spinopelvic, intrasegmental and intersegmental parameters were measured on lumbar X-rays pre-, postoperatively and 6 months after the surgery. Correlations between radiological parameters and clinical outcome data were determined. Sacral slope significantly increased (p

OBJECTIVEThe purpose of this study was to investigate the spectrum of current treatment protocols for managing newly diagnosed chordoma of the mobile spine and sacrum.METHODSA survey on the treatment of spinal chordoma was distributed electronically to members of the AOSpine Knowledge Forum Tumor, including neurosurgeons, orthopedic surgeons, and radiation oncologists from North America, South America, Europe, Asia, and Australia. Survey participants were pre-identified clinicians from centers with expertise in the treatment of spinal tumors. The suvey responses were analyzed using descriptive statistics.RESULTSThirty-nine of 43 (91%) participants completed the survey. Most (80%) indicated that they favor en bloc resection without preoperative neoadjuvant radiation therapy (RT) when en bloc resection is feasible with acceptable morbidity. The main area of disagreement was with the role of postoperative RT, where 41% preferred giving RT only if positive margins were achieved and 38% preferred giving RT irrespective of margin status. When en bloc resection would result in significant morbidity, 33% preferred planned intralesional resection followed by RT, and 33% preferred giving neoadjuvant RT prior to surgery. In total, 8 treatment protocols were identified: 3 in which en bloc resection is feasible with acceptable morbidity and 5 in which en bloc resection would result in significant morbidity.CONCLUSIONSThe results confirm that there is treatment variability across centers worldwide for managing newly diagnosed chordoma of the mobile spine and sacrum. This information will be used to design an international prospective cohort study to determine the most appropriate treatment strategy for patients with spinal chordoma.

Die operative Behandlung ei­ner symptomatischen degenerativen lumbalen Bandscheibenerkrankung bei alteren Pati­enten ist limitiert, da haufig schwere Komorbiditaten bestehen (z. B. kardiopulmonale Erkrankungen, Hypertonie, Diabetes). In dieser Population sind minimal-invasive Verfahren besser geeignet, da hierdurch die operative Morbiditat und das Komplikationsrisiko gesenkt werden. Die Technik der perkutanen Zement-Diskoplastie („percutaneous cement discoplasty“, PCD) wurde von den Autoren eingefuhrt, um dynamische (und angulare) Instabilitaten des symptomatischen Lendenwirbelsegments zu behandeln, indem Knochenzement (Polymethylmethacrylat, PMMA) uber eine posterolateral positionierte Jamshidi-Nadel in die Bandscheibenzwischenraume mit Vakuumphanomen injiziert wird. Ziel dieses Beitrags ist es, Indikation, Methode und klinische Ergebnisse der PCD zu beschreiben. Wahrend eines 6-Jahres-Zeitraums wurden 81 Patienten in einem tertiaren Behandlungszentrum mittels PCD behandelt. In die aktuelle Studie wurde die erste Gruppe mit 47 konsekutiven Patienten aufgenommen, die unter Verwendung der vi­suellen Analogskala (VAS) und des Oswestry-Disability-Index (ODI) einen pra- und postoperativen Fragebogen bezuglich Bein- und Ruckenschmerzen ausgefullt hatten. Insgesamt wurden 130 Bandscheiben bei diesen 47 Patienten mittels PCD behandelt. Die Mehrzahl der Patienten (69 bzw. 66 %) berichtete postoperativ uber eine Reduzierung ihrer Schmerzen im Bereich der lumbalen Wirbelsaule und in den Beinen (p

The Core Outcome Measure Index (COMI) is a short, multidimensional outcome instrument developed for the evaluation of patients with spinal conditions. The aim of this study was to produce a cross-culturally adapted and validated Hungarian version of the COMI Back questionnaire.A cross-cultural adaptation of the COMI into Hungarian was carried out using established guidelines. Low back pain patients completed a booklet of questionnaires containing the Hungarian versions of COMI, Oswestry Disability Index (ODI) and WHO Quality of Life-BREF assessment (WHOQOL-BREF). The validation of the COMI included assessment of its construct validity, reliability, and responsiveness.145 patients participated in the assessment of reliability and 159 surgically treated patients were included in the responsiveness study. Excellent correlation was found between COMI and ODI scores (rho = 0.83, p0.01). The COMI showed a very good correlation with the physical subscale of WHOQOL-BREF (rho = -0.75, p0.01) and pain (rho = 0.68, p0.01). Test-retest analysis showed that Hungarian COMI is a reliable measurement tool (ICC = 0.92) with an acceptable standard error of measurement (SEM = 0.59) and minimum detectable change (MDC = 1.63). Internal responsiveness analysis indicated a large effect size (1.16) for the change in COMI score after lumbar surgery. The area under the ROC curve (AUC) for the COMI score compared with the global outcome of the surgery was 0.87.The translation and cross-cultural adaptation of the COMI into the Hungarian language was successful, resulting in a reliable and valid measurement tool with good clinimetric properties.

Spinal fusion is a standard surgical treatment for patients suffering from low back pain attributed to disc degeneration. However, results are somewhat variable and unpredictable. With fusion the kinematic behaviour of the spine is altered. Fusion and/or stabilizing implants carrying considerable load and prevent rotation of the fused segments. Associated with these changes, a risk for accelerated disc degeneration at the adjacent levels to fusion has been demonstrated. However, there is yet no method to predict the effect of fusion surgery on the adjacent tissue levels, i.e. bone and disc. The aim of this study was to develop a coupled and patient-specific mechanoregulated model to predict disc generation and changes in bone density after spinal fusion and to validate the results relative to patient follow-up data. To do so, a multiscale disc mechanoregulation adaptation framework was developed and coupled with a previously developed bone remodelling algorithm. This made it possible to determine extra cellular matrix changes in the intervertebral disc and bone density changes simultaneously based on changes in loading due to fusion surgery. It was shown that for 10 cases the predicted change in bone density and degeneration grade conforms reasonable well to clinical follow-up data. This approach helps us to understand the effect of surgical intervention on the adjacent tissue remodelling. Thereby, providing the first insight for a spine surgeon as to which patient could potentially be treated successfully by spinal fusion and in which patient has a high risk for adjacent tissue changes. The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7-ICT-2009-6) under grant agreement n° 269909

Oncological management of skeletal metastases has changed dramatically in the last few decades. A significant number of patients survive for many years with their metastases. Surgeons are more active and the technical repertoire is broader, from plates to intramedullary devices to (tumour) endoprostheses. The philosophy of treatment should be different in the case of a trauma-related fracture and a pathological fracture. A proper algorithm for establishing a diagnosis and evaluation of prognostic factors helps in planning the surgical intervention. The aim of palliative surgery is usually to eliminate pain and to allow the patient to regain his/her mobility as well as to improve the quality of life through minimally invasive techniques using life-long durable devices. In a selected group of patients with an oncologically controlled primary tumour site and a solitary bone metastasis with positive prognostic factors, which meet the criteria for radical excision (approximately 10% to 15% of the cases), a promising three to five years of survival may be achieved, especially in cases of metastases from breast and kidney cancer. Spinal metastases require meticulous evaluation because decisions on treatment mostly depend on the tumour type, segmental stability, the patient’s symptoms and general state of health. Advanced radiotherapy combined with minimally invasive surgical techniques (minimally invasive stabilisation and separation surgery) provides durable local control with a low complication rate in a number of patients.Cite this article: EFORT Open Rev 2017;2:372-381.

Lumbar spinal stenosis (LSS) is a disabling condition associated with narrowing of the spinal canal or vertebral foramina. Paraspinal muscle atrophy and fatty infiltration have been reported in patients with chronic LBP and disc herniation. However, very few imaging studies have examined paraspinal muscle morphology and composition in patients with LSS. The purpose of this study was to investigate the association of paraspinal muscle size, composition and asymmetry with functional status in patients with LSS. Thirty-six patients diagnosed with LSS at L4–L5 with neurogenic claudication were included. Paraspinal muscle measurements were obtained from axial T2-weighted MR images, bilaterally, at the level of the superior and inferior vertebral endplates of L5. Muscle measurements of interest included: total cross-sectional area (CSA), functional CSA (FCSA), the ratio of FCSA to CSA (FCSA/CSA) as an indicator of muscle composition, and relative % asymmetry in muscle CSA. The association between muscle parameters and other patient characteristics with function as indicated from Oswestry Disability Index (ODI) scores and pain interference status was investigated. Greater multifidus muscle fatty infiltration (e.g., lower FCSA/CSA) and lower psoas relative CSA were associated with lower function (higher ODI and pain interference scores) in univariable and multivariable analyses. There was no association between the different muscle parameters and stenosis severity or back or leg pain duration or severity. Our findings suggest an association of multifidus muscle fatty infiltration and psoas muscle size with functional status in patients diagnosed with LSS. Future prospective studies are needed to evaluate whether such muscle parameters are associated with prognosis and functional recovery following surgical treatment.

Background context Although the surgical and oncological therapies of primary spinal tumors (PSTs) have changed significantly over the last few decades, the prognosis of this rare disease is still poor. The decision-making process in the multidisciplinary management is handicapped by the lack of large-scale population-based prognostic studies. Purpose The objective of the present study was to investigate preoperative factors associated with PST mortality and to develop a predictive scoring system of poor survival. Study design This is a large-scale ambispective cohort study. Patient sample The study included 323 consecutive patients with PSTs, treated surgically over an 18-year period at a tertiary care spine referral center for a population of 10 million. Outcome measure Survival was the outcome measure. Methods Patients were randomly divided into a training cohort (n=273) and a validation cohort (n=50). In the training cohort, 12 preoperative factors were investigated using Cox proportional hazard models. Based on the mortality-related variables, a simple scoring system of mortality was created, and three groups of patients were identified. Kaplan-Meier and log-rank analyses were used to compare the survival in the three groups. The model performance was assessed by measuring the discriminative ability (c-index) of the model and by applying a pseudo-R 2 goodness-of-fit test (Nagelkerke R 2 , R N 2 ). Internal validation was performed using bootstrapping in the training cohort and assessing the discrimination and explained variation of the model in the validation cohort. Results Patient age, spinal region, tumor grade, spinal pain, motor deficit, and myelopathy/cauda equina syndrome were significantly associated with poor survival in the multivariate analysis (p R N 2 = 0.799 ). Based on these variables, we developed the Primary Spinal Tumor Mortality Score (PSTMS), where an eight-point scale was divided into three categories (low, medium, and high mortality). The three PSTMS categories were significantly associated with the overall survival (p R N 2 = 0.811 , c=0.82). The model performance remained similarly high in the validation cohort ( R N 2 = 0.831 , c=0.81). Conclusions The present study identifies six predictive variables for mortality in PSTs. Using these six variables, an easy-to-use scoring system was developed that can be applied to the estimation of postoperative survival in all types of PST patients.

SummaryBackgroundContaminated textiles in hospitals contribute to endogenous, indirect-contact, and aerosol transmission of nosocomial related pathogens. Copper oxide impregnated linens have wide-spectrum antimicrobial, antifungal, and antiviral properties. Our aim was to determine if replacing non-biocidal linens with biocidal copper oxide impregnated linens would reduce the rates of healthcare-associated infections (HAI) in a long-term care ward.MethodsWe compared the rates of HAI in two analogous patient cohorts in a head injury care ward over two 6-month parallel periods before (period A) and after (period B) replacing all the regular non-biocidal linens and personnel uniforms with copper oxide impregnated biocidal products.ResultsDuring period B, in comparison to period A, there was a 24% reduction in the HAI per 1000 hospitalization-days (p38.5°C) per 1000 hospitalization-days (p

ObjectiveOsteoporosis (OP) is a multifactorial disease with high heritability but its exact genetic background is still poorly understood. We examined the effect of 24 single nucleotide polymorphisms (SNPs) located in five genes – alkaline phosphatase, matrix metalloproteinase-2, tissue inhibitor of metalloproteases-2 (TIMP2), fibroblast growth factor receptor-1 (FGFR1), and fatty acid-binding protein-3 (FABP3) – previously not associated with OP.DesignWe performed a genotype–phenotype association study at a university hospital.MethodsA total of 360 Hungarian postmenopausal women were involved in the study. Bone mineral density (BMD) was determined at spine, hip, and distal radius. Genomic DNA was extracted from venous blood samples and a high-throughput genotyping method based on single-based primer extension was applied for allelic discrimination. Robust statistical tools were utilized for multiplex data analysis.ResultsSNP rs6996321 in FGFR1 was significantly related to spine BMD (P=0.002) and rs10914367 in FABP3 was associated with hip BMD (P=0.028). Non-vertebral fracture risk was significantly increased in carriers of ‘A’ allele of rs9900972 in TIMP2 (odds ratio=2.06, P=0.0187). We could also identify validated gene–gene interactions significantly affecting BMD and fracture risk.ConclusionsWe identified two previously unreported SNPs in FGFR1 and FABP3 associated with BMD and a third SNP in TIMP2 related to risk for non-vertebral osteoporotic fractures. This is the first report about the association between these allelic variants and the phenotypes of postmenopausal OP. Further studies need to clarify the role of these genes and their polymorphisms in the process of bone loss.

It has been shown previously that a history of low back pain often begins in childhood or adulthood. Indeed, the prevalence of severe back symptoms among schoolchildren is not insignificant. Possibilities for the primary prevention of intervertebral disc degeneration-related conditions are poorly reported in the literature despite the assumed socio-economical impact of the prevention of these conditions. In this review, the authors have collated published data on the prevalence and risk factors of childhood low back pain as well as the structure and results of published primary prevention programs. The prevalence of self-reported low back pain is 7–65 % among children and it increases with age. Several lifestyle factors have been reported as significant risk factors for back pain, many of which are related to the schools. Current educational primary prevention programs in schools show no clear or long-term stable effect. Considering the growing evidence about the importance of normal and bad posture, an exercise-based posture correction program is suggested as a school-based primary prevention of disc degeneration-related symptoms. Further, prospective randomized studies with more than 20 years follow-up, however, are strongly required to confirm it.

Copper has very potent antibacterial, antifungal, antiviral and acaricidal properties. Recently the use of copper alloys in hospital wards has been shown to reduce bioburden and nosocomial infection rates. We hypothesized that the use of copper oxide in textiles and other products that are in close contact with the patients may significantly reduce bioburden in clinical settings and consequently reduce the risk of nosocomial infections. In order to test this hypothesis we intend to conduct a trial in which we will examine if the nosocomial infection rates in a chronic care ward will be reduced when all the textile products will include copper oxide. The risk of adverse reactions due to dermal contact with copper are considered extremely low and medical devices containing copper, such as intrauterine devices and dental amalgams, are safely used for decades. Textile products containing copper oxide are being sold worldwide for several years and not even one adverse reaction was noted. However, in spite of all the above, and in preparation to the clinical trial we intend to conduct in a chronic care ward (long-term care facility), we conducted this preliminary study in which we examined the safety of using copper oxide impregnated diapers in 16 chronic care patients that used the diapers for 6 consecutive months. Importantly, not even one adverse reaction was recorded during the whole trial, indicating the high safety of the diapers. Therefore, this study allows us to examine the efficacy of textiles containing copper oxide in reducing nosocomial infections in larger populations, including in frail chronic care patients.

PURPOSE: Patient-reported outcome measurements (PROMs) are widely used in spine care. The development of reliable and valid National versions of spine-related disability questionnaires is strongly recommended from both the clinical and scientific points-of-view. The aims of this study were to adapt and validate the Oswestry Disability Index (ODI) and the Quebec back pain disability scale (QDS) for use with the Hungarian language. METHODS: After translating and culturally adapting the ODI and QDS, 133 patients with lumbar degenerative spinal disorder filled in the questionnaire booklet twice within 2 weeks. Subjects completed the Hungarian versions of the two PROMs as well as the WHOQoL-BREF validated as a general life quality questionnaire and Visual Analogue Scale of pain. Internal consistency, reliability and construct validity of the questionnaires were determined, as were the standard error of measurement (SEM) and minimal detectable change (MDC) scores. RESULTS: The Hungarian ODI consisted of one factor that showed good internal consistency (Cronbach-α 0.890). The QDS showed a four-factor structure with Cronbach-α values between 0.788 and 0.917. No significant floor or ceiling effects were observed. The test-retest analysis showed excellent reliability of the Hungarian ODI and QDS. The intraclass correlation coefficients (ICC) were 0.927 and 0.923, respectively. SEM values of 4.8 and 5.2 resulted in a MDC of 13 and 14 points in the Hungarian ODI and QDS, respectively. The correlation coefficient (r) between pain and ODI was 0.680 (p < 0.001) and the correlation between the ODI and the physical subscale of WHOQoL was also very good (r = -0.705, p < 0.001). The QDS total score and its four subscales correlated significantly with pain and with the physical subscale of WHOQoL (r > 0.4, p < 0.001). The level of disability measured by the Hungarian ODI and QDS was significantly higher in the surgical subgroup than in non-surgically treated patients (p < 0.001). CONCLUSIONS: Translation and cultural adaptation of the ODI and QDS were successful. Hungarian versions of the ODI and QDS proved to be reliable, valid PROMs confirming that they can be used in future clinical and scientific work with Hungarian-speaking spine patients.

Background Recent investigations have revealed multiple actions of vascular endothelial growth factor (VEGF) in the nervous system. The role of VEGF in the molecular background of mood disorders has also been proposed. In this study we were interested in investigating a possible association between VEGF levels and treatment response in patients with a current episode of major depression (MDE). Methods 34 patients with MDE were enrolled in our study. Depressive symptoms were monitored by the Montgomery–Asberg Depression Rating Scale at baseline (V 1 ) and after a 4-week treatment period (V 2 ). Patients with less than a 50% improvement in MADRS total scores during this period were regarded as non-responders. Results Plasma VEGF levels did not change during the treatment period in either the total sample or in the responder and non-responder subsamples. There was a strong trend for higher baseline VEGF levels in the non-responder group than in the responder group ( p =0.055) and this difference—as a weak trend—was still detectable at the end of the treatment period ( p =0.097). Regression analysis revealed that the baseline VEGF level was a significant predictor for the endpoint MADRS score ( p =0.02). Limitations Sample size was relatively small; sample consists of both patients with MDD and bipolar disorder. Conclusions Our preliminary results raise the possibility that baseline levels of peripheral VEGF may predict treatment response in patients with mood disorders. Considering the limitations of our study, further investigations should resolve whether VEGF is a useful biomarker for treatment response in depression in clinical practice.

Although cannabis use disorder is strongly related to schizophrenia and treatment of patients with double diagnosis provides serious problem, specific pharmacological, molecular and therapeutical data on this subgroup are poorly available. In this paper we pre- sent a critical review on psychopharmacological boundaries of schizophrenia with concurrent cannabis use. The relevant data available in the literature suggest that a weaker compliance, poorer therapy response and higher sensitivity for extrapyramidal side effects are key fea- tures of schizophrenia and comorbid cannabis use disorder and represent a clinical challenge. Because of paucity of available research in the field there is not enough evidence to clearly depict the exact psychopharmacological profile of cannabis related schizophrenia. Further investigations are needed to assess phenotypic characteristics of this entity and to tailor effective treatment options accordingly.

Scheipl S, Froehlich E V, Leithner A, Beham A, Quehenberger F, Mokry M, Stammberger H, Varga P P, Lazary A, Windhager R, Gattenloehner S & Liegl B (2012) Histopathology 60, 999–1003 Does insulin-like growth factor 1 receptor (IGF-1R) targeting provide new treatment options for chordomas? A retrospective clinical and immunohistochemical study Aims: The overall prognosis of chordoma is poor, and current treatment options are limited. The insulin-like growth factor 1 receptor (IGF-1R) pathway is important for cell signalling, and attractive for selective inhibition. We investigated the expression of IGF-1R and its ligands, IGF-1 and IGF-2, in a series of 50 chordomas, in order to assess whether IGF-1R-signalling could be a potential target for specific inhibition in chordomas. Methods and results: Fifty chordomas (34 primary tumours, 16 recurrences) from 44 patients were evaluated immunohistochemically for the expression of IGF-1R, IGF-1 and IGF-2. Thirty-eight chordomas (76%) expressed IGF-1R, 46 (92%) expressed IGF-1 and 25 (50%) expressed IGF-2. Semi-quantitative analyses revealed a moderate to strong staining intensity in ≥50% of tumour cells for IGF-1R, IGF-1 and IGF-2 in 18 (36%), 32 (64%) and eight (16%) chordomas, respectively. Tumour volume correlated significantly with IGF-1R-staining intensity in primary chordomas (P = 0.042). Conclusions: IGF-1R and IGF-1 are expressed in the majority of chordomas. IGF-1 expression is much stronger than IGF-2 expression. Patients whose chordomas show a moderate to strong staining intensity in ≥50% of tumour cells for IGF-1R (36%) might benefit most from IGF-1R targeting, particularly if they suffer from large and surgically non-resectable chordomas.

Oral Diseases (2012) 18, 580–585 Objectives: Osteonecrosis of the jaw (ONJ) is a major complication associated with long-term use of bisphosphonates (BP). We aimed to investigate the effect of CYP2C8 rs1934951 SNP and its relationship to a number of clinical and biochemical factors in 46 Hungarian subjects with bisphosphonate-induced ONJ. Methods: Blood samples were collected from each subject and genomic DNA was extracted. SNP analysis of CYP2C8 gene was carried out by predesigned TaqMan primer/probe sets. The genetic data together with clinical and biochemical variables were evaluated by chi-square test, logistic regression, and principal component analysis (PCA). Results: The risk of mandibular localization of ONJ was 19.2-fold higher in subjects with AG genotype than in normal GG genotype. PCA revealed strong positive correlations between maxillar localization of ONJ and a group of variables including intravenous BP application and serum lipid markers. Mandibular localization of ONJ was correlated positively with serum calcium, 25-hydroxy-vitamin D and PTH levels, oral BP application, and the length of BP therapy. The degree of the disease and the number of recurrences were correlated with the application of hormone-deprivation therapy for breast cancer patients. Conclusion: The statistical approach applying PCA to our data may contribute to the better understanding of factors playing role in the development of bisphosphonate-induced ONJ.

Background Epidemiological studies strongly suggest a bidirectional positive relationship between mood and cardiovascular disorders (CVD). Reduced numbers of circulating endothelial progenitor cells (cEPCs) are associated with elevated risks of CVD. Previously we demonstrated that patients with a current episode of major depression (MDE) have a decreased number of cEPCs. The role of vascular endothelial growth factor (VEGF) and tumor necrosis factor (TNF) has been demonstrated in the etiopathogenesis of depression. In addition these cytokines are also involved in regulation of the vascular system. This suggests that VEGF and/or TNF may also mediate the elevated risk of CVD associated with mood disorders. Methods In the current investigation, which has a self-controlled study design, we examined changes in VEGF and TNF levels and – for the first time – changes in cEPC number during recovery from MDE. Results Twenty-four patients with MDE were enrolled. The severity of their depressive symptoms improved significantly during the one-month treatment period (~ 50% decrease in MADRS score; P ≤ 0.001). We did not find significant differences between baseline and end-point levels of VEGF, TNF and the number of cEPCs. Conclusion Our negative result for alteration in the number of cEPCs in the course of recovery from MDE raises several questions. Before discarding the number of cEPCs as a possible marker of depression – and/or elevated CV risk associated with it – our results would require confirmation in larger samples. Our results for TNF and VEGF do not contradict the findings of prior studies, since these were controversial.

Background Although incidence of schizophrenia is higher among cannabis users and marijuana is the most common abused drug by adolescents, etiological linkage between schizophrenia and cannabis use is still not clarified. Clinical experiences suggest that regular cannabis user can show similar psychotic episode to schizophrenic disorders but it is still unclear if chronic cannabis use with schizophreniform disorder is a distinct entity requiring special therapy or it can be treated as classical schizophrenia. There are no data available on the comparison of pharmacotherapy between schizophreniform patients with and without cannabis use. Methods Clinical data of 85 patients with schizophrenia spectrum disorder were analyzed retrospectively. Cannabis use was not reported by 43 persons (Cnbs0 subgroup) and 42 patients used regularly cannabis during at least 1 year (Cnbs1 subgroup). Comparison of anamnesis, family history, social-demographic condition, positive and negative symptoms, acute and long-term therapies recorded by clinical interviews was performed with chi square tests, logistic binary regression and t-tests using SPSS 13.0 for Windows software. Results Men were over-represented in cannabis dependent group while mean age was lower among them compared to Cnbs0 subgroup. Prevalence of suicidal attempt was increased in men without cannabis use (OR = 5.25, p = 0.016). Patients without cannabis use spent more time in hospital (p = 0.026) and smoking was more frequent among them (OR = 1.36, p = 0.047). The chance to get olanzapine for acute therapy and aripiprazol for long term therapy was more than two fold in Cnbs1 subgroup (OR = 2.66, OR = 3.67, respectively). However, aripiprazol was used for acute therapy with significantly lower risk in Cnbs1 subgroup (OR = 0.47, p = 0.023). Olanzapine was administered for long term therapy in a higher dose to Cnbs0 patients (p = 0.040). Also higher dose of risperidon LAI was used in women without cannabis dependency compared to women of Cnbs1 subgroup (p = 0.020). Positive and negative symptoms and family history did not differ significantly between the two subgroups. Conclusion Although symptom profile was similar, hospitalization time, suicidal anamnesis, smoking habit and also dosage, intensity and lasting of therapy were different between the two subgroups. Further prospective studies are required for the investigation of the clinical and molecular background of this discrepancy in order to determine a relevant protocol of prevention and treatment of the chronic cannabis use related psychotic disorder.

Previous studies suggest that women with premenstrual syndrome (PMS) differ from those without PMS in personality dimensions, but it is not clear what role personality plays in the background of premenstrual symptomatology. Our purpose was to examine personality dimensions measured by the Tridimensional Character Inventory (TCI) in psychiatrically healthy women not suffering from premenstrual dysphoric disorder (PMDD) in relation to the severity of distressing and impairing mental and physical symptoms experienced in the late luteal phase of the menstrual cycle. Forty healthy women completed the prospective record of the Impact and Severity of Menstrual Symptoms (PRISM) calendar every evening through three consecutive menstrual cycles and were assigned into LPS (luteal phase symptom) vs. non-LPS groups. Our grouping did not reflect categorization according to the presence of PMS, since we investigated healthy women. Personality characteristics were evaluated using the TCI. LPS subjects scored significantly higher in subscales associated with novelty seeking (NS), self-directedness (S), cooperation (C) and self-transcendence (ST), and lower in the harm avoidance (HA) scale. Elevated scores of women with higher symptom severity in the late luteal phase in NS, S, ST and C scales and lower HA scores are in contrast with previous results on personality traits associated with PMS. However, we investigated psychiatrically healthy women. Therefore, our results suggest that this personality profile is a protective factor against developing serious psychiatric symptoms when experiencing a distressing and more marked symptomatology associated with the late luteal phase of the reproductive cycle.

ObjectiveReceptor activator of nuclear factor-κB ligand/osteoprotegerin (RANKL/OPG) signaling system plays a crucial role in the regulation of bone resorption. Polymorphic variations in the genes may have an influence on gene expression and bone metabolism. In the present study, we aimed to investigate the influence of RANKL/OPG allelic variations on the in vivo human gene expression of five genes, bone mineral density (BMD), and fracture incidence in Hungarian postmenopausal women.MethodsThree hundred and sixty postmenopausal women (61.6±7.9 years) were genotyped. All together, five single nucleotide polymorphisms (SNPs) in the two genes have been investigated. In addition, bone samples from 17 examined subjects were acquired for gene expression studies. Bone densities and fracture data have also been collected.ResultsAll two SNPs in OPG gene and three SNPs in RANKL gene showed correlation with BMD. Haplotype analysis of these genes gave similar results. The ‘CCT’ haplotype of RANKL promoter region, which was associated with decreased BMD, exhibited a significantly upregulated expression of RANKL mRNA, while the other haplotypes of RANKL or OPG 15 genes did not. No correlation between genetic variations and fracture data was found.ConclusionWe have demonstrated associations between RANKL and OPG haplotypes and BMD as well as between RANKL haplotypes and in vivo RANKL expression in a Hungarian postmenopausal population. Moreover, we have found a new RANKL haplotype associating with reduced BMD and increased in vivo RANKL expression in human bone tissue.

Tobacco smoking is an extremely addictive and harmful form of nicotine (NIC) consumption, but unfortunately also the most prevalent. Although disproportionately high frequencies of smoking and its health consequences among psychiatric patients are widely known, the neurobiological background of this epidemiological association is still obscure. The diverse neuroactive effects of NIC and some other major tobacco smoke constituents in the central nervous system may underlie this association. This present paper summarizes the pharmacology of NIC and its receptors (nAChR) based on a systematic review of the literature. The role of the brain's reward system(s) in NIC addiction and the results of functional and structural neuroimaging studies on smoking-related states and behaviors (i.e. dependence, craving, withdrawal) are also discussed. In addition, the epidemiological, neurobiological, and genetic aspects of smoking in several specific neuropsychiatric disorders are reviewed and the clinical relevance of smoking in these disease states addressed.

Objective The cyclic nature of female reproductive function is a natural part of life accompanied by changes in several physical and psychological phenomena. The aim of our study was to investigate the fluctuation of psychological symptoms throughout the female reproductive cycle in healthy, non-PMDD (premenstrual dysphoric disorder) women. Method 63 psychiatrically healthy, non-PMDD women with normal regular menstrual cycles and not using hormonal contraceptive methods participated in the study. Participants completed the PRISM (Prospective Record of the Impact and Severity of Menstrual Symptoms) calendar every night for three cycles and in addition they completed several other psychometric measures (Symptom Distress Checklist-SCL-51, State Trait Anxiety Inventory-STAI, Zung Self-rating Depression Scale-ZSDS, Eating Attitude Test-EAT, Mind and Body Cathexis Scale) at three predefined days of the first cycle. Based on an at least 66% increase in physical symptoms from the late follicular to the late luteal phase on the PRISM, subjects were assigned to luteal phase physical symptoms (LPPS) and no luteal phase physical symptoms (nonLPPS) groups. The association of psychometric scores with timing within the cycle and with physical symptoms was analysed. Results Significant changes in psychometric scores over time were observed for STAI state anxiety, SCL anxiety, SCL somatization, SCL depression, SCL obsessive-compulsive, SCL interpersonal sensitivity, SCL total, and ZSDS. A significant time × LPPS grouping interaction emerged in case of the SCL somatization subscale and the ZSDS. LPPS grouping was associated with only the interpersonal sensitivity subscale of the SCL51. Conclusion Our results indicate that there is a significant increase in psychological symptoms related to neuroticism and depression from the late follicular to the late luteal phase in a healthy, non-PMDD female population. Although our results may not have direct clinical significance, since the statistically significant increases in psychometric scores are still small, it is an important finding that there is a consistent pattern observable in the fluctuation of psychological symptoms accompanying the female reproductive cycle.

Research concerning the genetic background of traits, temperaments and psychiatric disorders has been rapidly expanding. One of the most frequently studied genetic polymorphisms in the background of psychological and psychiatric phenomena is the 5-HTTLPR polymorphism of the serotonin transporter gene which has earlier been found to be associated with neuroticism and neuroticism-related traits and disorders. However, both the neuroticism trait and psychiatric disorders are complex and composed of several subfacets. The aim of our study was to investigate the association of the 5-HTTLPR polymorphism with several smaller, distinct and better characterisable phenomena related to the neuroticism trait. 169 healthy females participated in the study. All participants completed the Buss–Durkee Hostility Inventory (BDHI), the State-Trait Anxiety Inventory (STAI), The Zung Self-rating Depression Scale (ZSDS), the Beck Hopelessness Scale, the SCL-51, the Temperament and Character Inventory (TCI) and the Temperament Evaluation of Memphis, Pisa, Paris and San Diego (TEMPS-A) questionnaire. All subjects were genotyped for the 5-HTTLPR using PCR. Data were analysed with ANOVA and MANCOVA with age as a covariate. We found that the presence of the s allele was significantly associated with anxiety, depression, hopelessness, guilt, hostility, aggression, presence of neurotic symptoms, self-directedness and affective temperaments carrying a depressive component even when controlling for age. Our study is the first that confirms that traits and characteristics related to neuroticism, such as increased anxiety, depression, hopelessness, somatization, feeling of guilt, hostility, aggression, lack of self-directedness and affective temperament are consistently and independently associated with the 5-HTTLPR polymorphism of the serotonin transporter gene. Our study therefore suggests that neuroticism can be considered a unified construct not only from a phenotypical but also from a genetic point of view and 5HTTLPR can be considered one component of its polygenic background. Our results thus yield further insight into the role of the 5-HTTLPR in the background of neuroticism and neuroticism-related psychiatric disorders.