Search

BACKGROUND: In patients with aneurysmal subarachnoid haemorrhage, short-term antifibrinolytic therapy with tranexamic acid has been shown to reduce the risk of rebleeding. However, whether this treatment improves clinical outcome is unclear. We investigated whether ultra-early, short-term treatment with tranexamic acid improves clinical outcome at 6 months.METHODS: In this multicentre prospective, randomised, controlled, open-label trial with masked outcome assessment, adult patients with spontaneous CT-proven subarachnoid haemorrhage in eight treatment centres and 16 referring hospitals in the Netherlands were randomly assigned to treatment with tranexamic acid in addition to care as usual (tranexamic acid group) or care as usual only (control group). Tranexamic acid was started immediately after diagnosis in the presenting hospital (1 g bolus, followed by continuous infusion of 1 g every 8 h, terminated immediately before aneurysm treatment, or 24 h after start of the medication, whichever came first). The primary endpoint was clinical outcome at 6 months, assessed by the modified Rankin Scale, dichotomised into a good (0-3) or poor (4-6) clinical outcome. Both primary and safety analyses were according to intention to treat. This trial is registered at ClinicalTrials.gov, NCT02684812.FINDINGS: Between July 24, 2013, and July 29, 2019, we enrolled 955 patients; 480 patients were randomly assigned to tranexamic acid and 475 patients to the control group. In the intention-to-treat analysis, good clinical outcome was observed in 287 (60%) of 475 patients in the tranexamic acid group, and 300 (64%) of 470 patients in the control group (treatment centre adjusted odds ratio 0·86, 95% CI 0·66-1·12). Rebleeding after randomisation and before aneurysm treatment occurred in 49 (10%) patients in the tranexamic acid and in 66 (14%) patients in the control group (odds ratio 0·71, 95% CI 0·48-1·04). Other serious adverse events were comparable between groups.INTERPRETATION: In patients with CT-proven subarachnoid haemorrhage, presumably caused by a ruptured aneurysm, ultra-early, short-term tranexamic acid treatment did not improve clinical outcome at 6 months, as measured by the modified Rankin Scale.FUNDING: Fonds NutsOhra.

Background and ObjectivesThe ULTRA trial showed that ultra-early and short-term tranexamic acid treatment after subarachnoid hemorrhage did not improve clinical outcome at 6 months. An expected proportion of the included patients experienced nonaneurysmal subarachnoid hemorrhage. In this post hoc study, we will investigate whether ultra-early and short-term tranexamic acid treatment in patients with aneurysmal subarachnoid hemorrhage improves clinical outcome at 6 months.MethodsThe ULTRA trial is a multicenter, prospective, randomized, controlled, open-label trial with blinded outcome assessment, conducted between July 24, 2013, and January 20, 2020. After confirmation of subarachnoid hemorrhage on noncontrast CT, patients were allocated to either ultra-early and short-term tranexamic acid treatment with usual care or usual care only. In this post hoc analysis, we included all ULTRA participants with a confirmed aneurysm on CT angiography and/or digital subtraction angiography. The primary endpoint was clinical outcome at 6 months, assessed by the modified Rankin scale (mRS), dichotomized into good (0–3) and poor (4–6) outcomes.ResultsOf the 813 ULTRA trial patients who experienced an aneurysmal subarachnoid hemorrhage, 409 (50%) were assigned to the tranexamic acid group and 404 (50%) to the control group. In the intention-to-treat analysis, 233 of 405 (58%) patients in the tranexamic acid group and 238 of 399 (60%) patients in the control group had a good clinical outcome (adjusted odds ratio [aOR] 0.92; 95% CI 0.69–1.24). None of the secondary outcomes showed significant differences between the treatment groups: excellent clinical outcome (mRS 0–2) (aOR 0.76; 95% CI 0.57–1.03), all-cause mortality at 30 days (aOR 0.91; 95% CI 0.65–1.28), and all-cause mortality at 6 months (aOR 1.10; 95% CI 0.80–1.52).DiscussionUltra-early and short-term tranexamic acid treatment did not improve clinical outcomes at 6 months in patients with aneurysmal subarachnoid hemorrhage and therefore cannot be recommended.Trial Registration InformationClinicalTrials.gov(NCT02684812; submission date February 18, 2016, first patient enrollment on July 24, 2013).Classification of EvidenceThis study provides Class II evidence that tranexamic acid does not improve outcomes in patients presenting with aneurysmal subarachnoid hemorrhage.

Background: Awareness of treatment group assignment in a clinical trial may influence patient behavior and bias outcome reporting. The objective of this study was to compare 2-year clinical outcomes in blinded vs unblinded patients who were treated with lumbar discectomy and a bone-anchored annular closure device (ACD) for prevention of lumbar disc reherniation. Methods: This was a secondary analysis of a randomized trial comparing lumbar discectomy with (n=272) vs without (n=278) implantation of a bone-anchored ACD. Among patients who received ACD implantation, 35 (13%) were blinded and 237 (87%) were unblinded to treatment allocation. In patients treated with ACD, propensity score-matching (1:1) was performed to account for imbalances in patient characteristics between blinded and unblinded groups. Key clinical outcomes were back pain severity (0–100 scale), leg pain severity (0–100 scale), Oswestry Disability Index (ODI, 0–100 scale), symptomatic reherniation, reoperation at the treated lumbar level, and device-or procedure-related serious adverse events (AEs). Outcomes were reported through 2 years of follow-up, which coincided with the time at which blinded patients were unblinded. Results: There were no statistically significant differences in 2-year outcomes between propensity score-matched blinded (n=35) and unblinded (n=35) patients treated with the ACD. In blinded vs unblinded ACD patients compared to baseline, back pain severity decreased by 40 vs 37 points (P=0.61), leg pain severity decreased by 75 points in each group (P>0.99), and ODI decreased by 47 vs 43 points (P=0.19). The risks of symptomatic reherniation (5.7% vs 9.1%; P=0.59), reoperation (8.6% vs 12.2%, P=0.62), and device-or procedure-related serious AEs (5.7% vs 8.9%, P=0.63) were comparably low in blinded and unblinded patients. Conclusion: In patients treated with lumbar discectomy and a bone-anchored ACD, there were no clinically important or statistically significant differences in back pain, leg pain, ODI, symptomatic reherniation, reoperation, or serious AEs over 2 years of follow-up when comparing patients who were blinded vs unblinded to their treatment assignment. The main limitations of this study were the post hoc nature of the analysis and the potential for bias due to surgeon awareness of treatment assignment.

IntroductionRobotic guidance (RG) and computer-assisted navigation (NV) have seen increased adoption in instrumented spine surgery over the last decade. Although there exists some evidence that these techniques increase radiological pedicle screw accuracy compared with conventional freehand (FH) surgery, this may not directly translate to any tangible clinical benefits, especially considering the relatively high inherent costs. As a non-randomised, expertise-based study, the European Robotic Spinal Instrumentation Study aims to create prospective multicentre evidence on the potential comparative clinical benefits of RG, NV and FH in a real-world setting.Methods and analysisPatients are allocated in a non-randomised, non-blinded fashion to the RG, NV or FH arms. Adult patients that are to undergo thoracolumbar pedicle screw instrumentation for degenerative pathologies, infections, vertebral tumours or fractures are considered for inclusion. Deformity correction and surgery at more than five levels represent exclusion criteria. Follow-up takes place at 6 weeks, as well as 12 and 24 months. The primary endpoint is defined as the time to revision surgery for a malpositioned or loosened pedicle screw within the first postoperative year. Secondary endpoints include patient-reported back and leg pain, as well as Oswestry Disability Index and EuroQOL 5-dimension questionnaires. Use of analgesic medication and work status are recorded. The primary analysis, conducted on the 12-month data, is carried out according to the intention-to-treat principle. The primary endpoint is analysed using crude and adjusted Cox proportional hazards models. Patient-reported outcomes are analysed using baseline-adjusted linear mixed models. The study is monitored according to a prespecified monitoring plan.Ethics and disseminationThe study protocol is approved by the appropriate national and local authorities. Written informed consent is obtained from all participants. The final results will be published in an international peer-reviewed journal.Trial registration numberClinical Trials.gov registryNCT03398915; Pre-results, recruiting stage.

Objective To determine whether presence of a bone-anchored annular closure device (ACD) impacts reoperation strategies and subsequent outcomes. Methods Patients with large annular defects after single-level limited lumbar discectomy were randomly allocated to receive an ACD or discectomy alone (controls) and were followed for at least 3 years. Results Among 550 patients, reoperation risk was lower with ACD (11.0% vs. 19.3%). The types of reoperations and operative time were similar in each group, and the ACD did not interfere with surgical planning or operative technique. Fusion success was 87% with ACD versus 85% for controls. Perioperative complications occurred in 22% and 19% of reoperations, respectively. Leg pain and back function were improved with ACD versus controls after fusion procedures, and no group differences were observed after non-fusion reoperations. Conclusions In patients undergoing post-discectomy reoperation, patients with an ACD were treated with similar operative techniques, were not exposed to additional surgical risks, and reported comparable clinical outcomes versus those without an ACD.

Anterior cervical spine surgery is associated with postoperative dysphagia, sore throat and dysphonia. It is unclear, whether this is caused by increased endotracheal tube (ETT) cuff pressure after retractor placement. This study aims to assess the effect of ETT cuff pressure adjustment on postoperative dysphagia, sore throat and dysphonia. In this, single-centre, observer and patient-blinded randomized controlled trial patients treated with anterior cervical spine surgery were randomized to adjustment of the ETT cuff pressure to 20 mmHg after placement of the retractor versus no adjustment. Primary outcome was the incidence and severity of postoperative dysphagia. Secondary outcomes were sore throat and dysphonia. Outcomes were evaluated on day one and 2 months after the operation. Of 177 enrolled patients, 162 patients (92.5%) could be evaluated. The incidence of dysphagia was 75.9% on day one and 34.6% 2 months after surgery. Dysphagia in the intervention and control group was present in 77.8% versus 74.1% of patients on day one (odds ratio (OR) 1.2, 95% confidence interval (CI) (0.6–2.5)) and 28.4% versus 40.7% of patients after 2 months (OR 0.6, 95% CI 0.3–1.1), respectively. Severity of dysphagia, sore throat and dysphonia was similar in both groups. Anterior cervical spine surgery is accompanied by a high incidence of postoperative dysphagia, lasting until at least 2 months after surgery in over a third of our patients. Adjusting ETT cuff pressure to 20 mmHg after retractor placement, as compared to controls, did not lower the risk for both short- and long-term dysphagia. Netherlands National Trial Registry Number: NTR 3542. These slides can be retrieved under electronic supplementary material.

Anterior cervical discectomy with fusion is a common procedure for treating radicular arm pain. Polyetheretherketone (PEEK) plastic is a frequently used material in cages for interbody fusion. Silicon nitride is a new alternative with desirable bone compatibility and imaging characteristics. The aim of the present study is to compare silicon nitride implants with PEEK cages filled with autograft harvested from osteophytes. The study is a prospective, randomized, blinded study of 100 patients with 2 years follow-up. The primary outcome measure was improvement in the Neck Disability Index. Other outcome measures included SF-36, VAS arm pain, VAS neck pain, assessment of recovery, operative characteristics, complications, fusion and subsidence based on dynamic X-ray and CT scan. There was no significant difference in NDI scores between the groups at 24 months follow-up. At 3 and 12 months the NDI scores were in favor of PEEK although the differences were not clinically relevant. On most follow-up moments there was no difference in VAS neck and VAS arm between both groups, and there was no statistically significant difference in patients’ perceived recovery during follow-up. Fusion rate and subsidence were similar for the two study arms and about 90% of the implants were fused at 24 months. Patients treated with silicon nitride and PEEK reported similar recovery rates during follow-up. There was no significant difference in clinical outcome at 24 months. Fusion rates improved over time and are comparable between both groups.

Object: Neuroforaminal stenosis has been documented frequently in patients with degenerative lumbar scoliosis. Pedicle screw fixation with posterior lumbar interbody fusion is usually performed although a debate has been started on the need for unilateral or bilateral screws, or interbody fusion only. Trabecular Metal is a porous tantalum biomaterial with good osteoconductive properties, which may be suitable for unilateral interbody fusion aiming at enlargement of neuroforamen. Methods: From July 2011 until January 2013, 20 consecutive patients with degenerative scoliosis-related foraminal stenosis were treated with unilateral stand-alone Trabecular Metal cages (Zimmer TM 500) without additional pedicle screw fixation. All patients presented with leg pain, with or without low back pain. Patients underwent CT and MRI to confirm neuroforaminal stenosis on the concave side of the degenerative scoliosis. All patients were followed-up and examined at 2 months after surgery (follow-up moment 1). Long-term follow-up (moment 2; mean 36 months) was available of 17 patients; 2 patients died of unrelated disease and 1 patient was lost to follow-up. On both follow-up moments, neutral and dynamic flexion-extension images were documented. Based on these images, the position of the cage was determined and the Cobb’s angle of the segmental scoliosis (angle between the cranial endplate of the upper vertebral body and the caudal endplate of the lower vertebral body) was measured. The clinical outcome was measured by the patients’ global perceived recovery according to the 7-point Likert scale; “complete recovery” and “almost complete recovery” were determined as good results. Results: Most of the patients were operated on L3L4 and L4L5 (70%). The mean duration of surgery was 56 ± 15 minutes. Surgical complications occurred in 5 patients, namely cerebrospinal fluid leakage (4 patients) and nerve root injury (1 patient) with sensory deficit. Good outcome (Likert 1 or 2) was reported by 14 patients (70%) on the shortterm follow-up (moment 1), and by 9 patients (53%) on the long-term follow-up (moment 2). Whenever Likert 1-3 was dichotomized, 95% of the patients on the short-term and 83% of the patients on the long-term reported at least some benefit from the operation. The mean Cobb’s angle improved significantly from 13.4 ± 5.1o pre-operatively, to 6.1 ± 3.5o at moment 1, and 7.1 ± 3.6o at moment 2 (P < 0.001). On follow-up moment 1 and 2, radiographic examination showed subsidence in 3 and 9 patients, respectively. Pseudarthrosis around the stand-alone cage was only seen at follow-up moment 2 in 3 patients. Conclusions: Instrumented fusion with bilateral pedicle screw fixation and interbody fusion may not always be necessary in patients with scoliosis-related foraminal stenosis. Unilateral stand-alone TM cages could be an alternative strategy in a subgroup of patients leading to correction of Cobb’s angle and improvement of symptoms in most cases. However, the long-term result is moderately satisfying and could be explained by the development of cage subsidence over time.

OBJECTIVE The performance of surgery for spinal metastases is rapidly increasing. Different surgical procedures, ranging from stabilization alone to stabilization combined with corpectomy, are thereby performed for various indications. Little is known about the impact of these different procedures on patient quality of life (QOL), but this factor is crucial when discussing the various therapeutic options with patients and their families. Thus, the authors of this study investigated the effect of various surgical procedures for spinal metastases on patient QOL. METHODS The authors prospectively followed a cohort of 113 patients with spinal metastases who were referred to their clinic for surgical evaluation between July 2012 and July 2014. Quality of life was assessed using the EQ-5D at intake and at 3, 6, 9, and 12 months after treatment. RESULTS Nineteen patients were treated conservatively, 41 underwent decompressive surgery with or without stabilization, 47 underwent a piecemeal corpectomy procedure with stabilization and expandable cage reconstruction, and 6 had a stabilization procedure without decompression. Among all surgical patients, the mean EQ-5D score was significantly increased from 0.44 pretreatment to 0.59 at 3 months after treatment (p < 0.001). Mean EQ-5D scores at 1 year after surgery further increased to 0.84 following decompression with stabilization, 0.74 after corpectomy with stabilization, and 0.94 after stabilization without decompression. Frankel scores also improved after surgery. There were no significant differences in improvements in EQ-5D scores and Frankel grades among the different surgical procedures. In addition, mortality and complication rates were similar. CONCLUSIONS Quality of life can improve significantly after various extensive and less extensive surgical procedures in patients with spinal metastases. The relatively invasive corpectomy procedure, as compared with alternative less invasive techniques, does not negatively affect outcome.

Juvenile chronic arthritis (JCA) is a systemic disease of childhood affecting particularly joints. JCA is a heterogeneous group of inflammatory joint disorders with onset before the age of 16 years and is comprised of 7 subtype groups. The pathogenesis of JCA seen in the cervical spine is synovial inflammation, hyperaemia, and pannus formation at the occipitoatlantoaxial joints resulting in characteristic craniovertebral junction findings. Treatment of craniovertebral junction instability as a result of JCA is a challenge. The best treatment strategy may be difficult because of various radiological and clinical severities. A review of the literature and management considerations is presented.No randomised controlled trial or systematic review on this subject has been published. Only experts' opinions, case reports, and case series have been described. Thirty-four studies have been reviewed in this study. Involvement of the cervical spine in patients with JCA can lead to pain and functional disability. The subtypes that usually affect the cervical spine are the polyarticular type and systemic onset type and rarely the pauciarticular type. The most common cervical spine changes related to JCA are as follows: (1) apophyseal joint ankylosis at C2-C3, (2) atlantoaxial subluxation, (3) atlantoaxial impaction, (4) atlantoaxial rotatory fixation, and (5) growth disturbances of the cervical spine. The incidence of severe subluxations has decreased in the last decade as result of antirheumatoid drugs and biologicals. However, neurological compromise still occurs in JCA patients necessitating surgical treatment.Whenever the cervical spine is involved in rheumatoid arthritis patients without neurological deficits, conservative treatment is legitimate. Once patients develop neurological signs and symptoms, surgical treatment should be considered with particular focus to age, severity of the disease, and general health condition. Skilled anaesthesia is crucial and the surgical procedure should only be carried out in centres with experience in craniovertebral junction abnormalities.

Introduction Juvenile chronic arthritis (JCA) is a systemic disease of childhood affecting particularly joints. JCA is a heterogeneous group of inflammatory joint disorders with onset before the age of 16 years and is comprised of 7 subtype groups. The pathogenesis of JCA seen in the cervical spine is synovial inflammation, hyperaemia, and pannus formation at the occipitoatlantoaxial joints resulting in characteristic craniovertebral junction findings. Treatment of craniovertebral junction instability as a result of JCA is a challenge. The best treatment strategy may be difficult because of various radiological and clinical severities. A review of the literature and management considerations is presented.

In anterior cervical spine surgery a retractor is obligatory to approach the spine. Previous studies showed an increase of endotracheal tube cuff pressure after placement of a retractor. It is known that high endotracheal tube cuff pressure increases the incidence of postoperative dysphagia, hoarseness, and sore throat. However, until now no evidence supports the fact whether adjusting the endotracheal tube cuff pressure during anterior cervical spine surgery will prevent this comorbidity. We present the design of a randomized controlled trial to determine whether adjusting endotracheal tube cuff pressure after placement of a retractor during anterior cervical spine surgery will prevent postoperative dysphagia. 177 patients (aged 18–90 years) scheduled for anterior cervical spine surgery on 1 or more levels will be included. After intubation, endotracheal tube cuff pressure is manually inflated to 20 mm Hg in all patients. Patients will be randomized into two groups. In the control group endotracheal tube cuff pressure is not adjusted after retractor placement. In the intervention group endotracheal tube cuff pressure after retractor placement is maintained at 20 mm Hg and air is withdrawn when cuff pressure exceeds 20 mm Hg. Endotracheal tube cuff pressure is measured after intubation, before and after placement and removal of the retractor. Again air is inflated if cuff pressure sets below 20 mmHg after removal of the retractor. The primary outcome measure is postoperative dysphagia. Other outcome measures are postoperative hoarseness, postoperative sore throat, degree of dysphagia, length of hospital stay, and pneumonia. The study is a single centre double blind randomized trial in which patients and research nurses will be kept blinded for the allocated treatment during the follow-up period of 2 months. Postoperative dysphagia occurs frequently after anterior cervical spine surgery. This may be related to high endotracheal tube cuff pressure. Whether adaptation and maintaining the pressure after placement of the retractor will decrease the incidence of dysphagia, has to be determined by this trial. Netherlands Trial Register (NTR) 3542: http://www.trialregister.nl .

Background: Same-level reherniation and progressive degeneration with disc height loss are main causes of poor outcome after discectomy and may necessitate reoperation. A novel prosthesis for anular closure was developed to address these causes.Methods: The design of a multicenter, prospective, randomized, post-market superiority trial comparing limited lumbar discectomy augmented with this device (intervention group) with limited lumbar discectomy alone (control group) is presented.Results: Patients with single-level (L1-S1) posterior or posterolateral disc herniation and radiologic confirmation of neural compression for whom at least six weeks of conservative treatment has failed are eligible. Patients must have posterior disc height ≥5 mm at index level and baseline Oswestry and VAS leg pain scores of ≥40/100. Intraoperatively, subjects meeting anular defect size criteria post-discectomy (4-6 mm tall and 6-10 mm wide) will be randomized to study groups in a 1:1 ratio using centralized, web-based software. A Bayesian statistical approach will be used to enroll 400 to 800 subjects who will be followed for at least 24 months. Two co-primary endpoints will be assessed at 24 months: 1) a composite of leg pain, clinical function, disc height maintenance, and absence of reherniation, reoperation, and device failure; and 2) absence of reherniation based upon independent radiologic analysis. Conclusions: This type of analysis is becoming increasingly important as governments and health insurers continue to be pressured to spend limited healthcare funding wisely.