Intraoperative clonidine in endometriosis and spine surgery: A protocol for two randomised, blinded, placebo-controlled trials.

BACKGROUND: A high proportion of patients who undergo surgery continue to suffer from moderate to severe pain in the early postoperative period despite advances in pain management strategies. Previous studies suggest that clonidine, an alpha2 adrenergic agonist, administered during the perioperative period could reduce acute postoperative pain intensity and opioid consumption. However, these studies have several limitations related to study design and sample size and hence, further studies are needed. AIM: To investigate the effect of a single intravenous (IV) dose of intraoperative clonidine on postoperative opioid consumption, pain intensity, nausea, vomiting and sedation after endometriosis and spine surgery. METHODS: Two separate randomised, blinded, placebo-controlled trials are planned. Patients scheduled for endometriosis (CLONIPAIN) will be randomised to receive either 150 µg intraoperative IV clonidine or placebo (isotonic saline). Patients undergoing spine surgery (CLONISPINE) will receive 3 µg/kg intraoperative IV clonidine or placebo. We aim to include 120 patients in each trial to achieve power of 90% at an alpha level of 0.05. OUTCOMES: The primary outcome is opioid consumption within the first three postoperative hours. Secondary outcomes include pain intensity at rest and during coughing, nausea, vomiting and sedation within the first two postoperative hours and opioid consumption within the first six postoperative hours. Time to discharge from the PACU will be registered. CONCLUSION: This study is expected to provide valuable information on the efficacy of intraoperative clonidine in acute postoperative pain management in patients undergoing endometriosis and spine surgery.

Traumatic spinal cord injury and its correlation to risk of autoimmune/-inflammatory disease.

STUDY DESIGN: Nationwide epidemiological open cohort study. OBJECTIVES: To evaluate whether individuals with traumatic spinal cord injury (TSCI) are more prone to develop autoimmune diseases compared to a general non-TSCI population. SETTING: Danish public national registries. METHODS: An open nationwide cohort, including individuals born in Denmark from or alive during 1945-2018 was collected and the study period was 1980-2018. Poissons Log-linear regression estimated the incidence rate ratio (IRR) for developing eight groups of autoimmune diseases. A dose-response relationship based on the cervical/thoracic level of injury was assessed by stratification. RESULTS: The cohort included 3,272 individuals with TSCI and 4.8 million background individuals, accounting for 50,865 and 140 million person-years respectively. The TSCI population had an overall IRR of 1.81 (95% CI, 1.59 to 2.05) of getting any autoimmune disease. Subgroup analysis found positive associations for; a) Other neurologic IRR 5.19 (95% CI, 2.79 to 9.65), b) multiple sclerosis IRR 3.70 (95% CI, 2.54 to 5.40), c) Dermatologic IRR 2.57 (95% CI, 1.86 to 3.55), d) Type 1 diabetes mellitus IRR 2.01 (95% CI, 1.54 to 2.61), e) Systemic 1.92 (95% CI, 1.44 to 2.55), and f) Gastroenterologic IRR 1.42 (95% CI, 1.05 to 1.92). Cervical levels of TSCI showed an IRR of 1.70 (95% CI, 1.43 to 2.02), while thoracic levels had an IRR 1.98 (95% CI, 1.63 to 2.39). CONCLUSIONS: TSCI may be an individual risk factor of developing an autoimmune disease. There does not appear to exist a dose-response relationship from the level of injury. SPONSORSHIP: None.

An individualised tapering protocol reduces opioid use 1 year after spine surgery: A randomised controlled trial of patients with preoperative opioid use.

BACKGROUND: Persistent opioid use following surgery is common especially in patients with preoperative opioid use. This study aims to determine the long-term effect of an individualised opioid tapering plan versus standard of care in patients with a preoperative opioid use undergoing spine surgery at Aarhus University Hospital, Denmark. METHODS: This is the 1-year follow-up of a prospective, single-centre, randomised trial of 110 patients who underwent elective spine surgery for degenerative disease. The intervention was an individualised tapering plan at discharge and telephone counselling 1 week after discharge, compared to standard of care. Postoperative outcomes after 1 year include opioid use, reasons for opioid use and pain intensity. RESULTS: The overall response rate to the 1-year follow-up questionnaire was 94% (intervention group 52/55 patients and control group 51/55 patients). Forty-two patients (proportion = 0.81, 95% CI 0.67-0.89) in the intervention group compared to 31 (0.61, 95% CI 0.47-0.73; p = .026) patients in the control group succeeded in tapering to zero 1 year after discharge (p = .026). One patient (0.02, 95% CI 0.01-0.13) in the intervention group compared to seven patients (0.14, 95% CI 0.07-0.26) in the control group were unable to taper to their preoperative dose 1 year after discharge (p = .025). Back/neck and radicular pain intensity was similar between study groups. CONCLUSION: These results suggest that an individualised tapering plan at discharge combined with telephone counselling 1 week after discharge can reduce opioid use 1 year after spine surgery.

Glial fibrillary acidic protein is a robust biomarker in cerebrospinal fluid and peripheral blood after traumatic spinal cord injury: a prospective pilot study.

PURPOSE: Biochemical biomarkers to determine the injury severity and the potential for functional recovery of traumatic spinal cord injury (TSCI) are highly warranted; however, it remains to be clarified whether cerebrospinal fluid (CSF) or peripheral blood (PB) is the ideal sample media. This study aims to measure and compare biomarker concentrations in CSF and PB and to explore associations between biomarker concentrations and injury severity, i.e., American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade, and biomarker concentrations and clinical outcome, i.e., AIS grade improvement and Spinal Cord Independent Measure version III (SCIM-III) score. METHODS: From 2018 to 2020, we conducted a single-center prospective pilot study of TSCI patients (n=15) and healthy controls (n=15). Sample collection and clinical outcome assessment were performed at median 13 h [IQR: 19], 9 days [IQR: 2], and 148 days [IQR: 49] after TSCI. Concentrations of neuron-specific enolase (NSE); glial fibrillary acid protein (GFAP); neurofilament light chain (NfL); interferon-γ (IFN-γ); interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, and IL-13; and tumor necrosis factor α (TNF-α) were measured and associated to clinical outcomes. RESULTS: The biomarker concentrations were higher in CSF than PB. CSF concentrations of GFAP, NSE, IFN-y, TNF-a, IL-2, IL-12p70, IL-4, IL-10, and IL-13 and PB concentrations of GFAP and IFN-y were significantly associated with AIS grade, but not with AIS grade improvement or SCIM-III score. CONCLUSIONS: Our results support GFAP as a potential diagnostic biomarker that may be measured in CSF as well as PB.

Incidence and risk factors for incidental durotomy in spine surgery for lumbar stenosis and herniated disc.

PURPOSE: Incidental durotomy (ID) is one of the most common complications in degenerative surgery. Due to the negative consequences of ID, knowledge about incidence and risk factors is warranted. METHODS: A total of 1,139 surgical procedures for lumbar spinal stenosis (LS) and lumbar herniated disc (LDH) were included from the spine surgery database: DaneSpine. Uni- and multivariate analyses were performed for the assessment of possible risk factors. RESULTS: ID occurred in 10.4% of the surgical procedures. A multivariate regression analysis revealed an increased relative risk of ID by 2% per year of age, 58% by revision surgery, and 55% by decompression on multiple levels. CONCLUSION: In our single-centre cohort study, one in ten patients experiences an ID. Increasing age, revision surgery and decompression of multiple levels are risk factors of ID in degenerative surgery of the lumbar spine.

Diffusional kurtosis imaging as a possible prognostic marker of cervical incomplete spinal cord injury outcome: a prospective pilot study.

BACKGROUND: Spinal cord injury (SCI) is associated with substantial chronic morbidity and mortality. Routine imaging techniques such as T1- and T2-weighted magnetic resonance imaging (MRI) are not effective in predicting neurological deficiency grade or outcome. Diffusional kurtosis imaging (DKI) is an MR imaging technique that provides microstructural information about biological tissue. There are no longitudinal prospective studies assessing DKI metrics in acute traumatic SCI. Therefore, the purpose of this study was to establish a DKI protocol for acute SCI and correlate the DKI metrics to the functional neurological outcome of the patients. METHODS: Eight consecutive SCI patients referred to our institution with cervical SCI were included in the study. An acute diagnostic MRI scan was supplemented with a novel fast, mean kurtosis DKI protocol, which describes the average deviation from Gaussian diffusional along nine different directions. Mean kurtosis values were measured at the injury site and normalized to the mean kurtosis values of a non-injured site. At discharge form specialized rehabilitation, patients were evaluated using the Spinal Cord Independence Measure-III (SCIM-III). The DKI metrics and SCIM-III were analysed using Spearman's rank correlation. RESULTS: This pilot study found a significant correlation between decreasing mean kurtosis values at the injury site of the spinal cord and higher grade of disability measured by the SCIM-III (p = 0.002). CONCLUSION: This pilot study found that DKI may be a valuable tool as a prognostic marker in the acute phase of SCI.

The inflammatory response and blood-spinal cord barrier integrity in traumatic spinal cord injury: a prospective pilot study.

PURPOSE: Triggering of inflammatory responses and disruption of blood-spinal cord barrier (BSCB) integrity are considered pivotal events in the pathophysiology of traumatic spinal cord injury (TSCI). Yet, these events are poorly understood and described in humans. This study aims to describe inflammatory responses and BSCB integrity in human TSCI. METHODS: Fifteen TSCI patients and fifteen non-TSCI patients were prospectively recruited from Aarhus University Hospital, Denmark. Peripheral blood (PB) and cerebrospinal fluid (CSF) were collected at median day 0 [IQR: 1], median day 9 [IQR: 2], and median day 148 [IQR: 49] after injury. PB and CSF were analyzed for immune cells by flow cytometry, cytokines by multiplex immunoassay, and BSCB integrity by IgG Index. RESULTS: Eleven TSCI patients completed follow-up. Results showed alterations in innate and adaptive immune cell counts over time. TSCI patients had significantly increased cytokine concentrations in CSF at the first and second follow-up, while only concentrations of interleukin (IL)-4, IL-8, and tumor necrosis factor-α remained significantly increased at the third follow-up. In PB, TSCI patients had significantly increased IL-6, IL-8, and IL-10 concentrations and significantly decreased interferon-γ concentrations at the first follow-up. Results further showed increased IgG Index indicative of BSCB disruption in seven TSCI patients at the first follow-up, five TSCI patients at the second follow-up, and two patients at the third follow-up. CONCLUSIONS: Our results suggest that TSCI mainly triggers innate inflammatory responses that resolves over time, although with some degree of non-resolving inflammation, particularly in CSF. Our results cannot confirm BSCB disruption in all TSCI patients.

A review of spinal cord perfusion pressure guided interventions in traumatic spinal cord injury.

PURPOSE: To evaluate the causality between interventions on spinal cord perfusion pressure and neurological outcome in traumatic spinal cord injury. METHODS: A systematic review was conducted in concordance with PRISMA guidelines. The literature was found in the EMBASE, PUBMED, SCOPUS, and WEB OF SCIENCE. Eligible studies included those that reported measurements and interventions on the spinal cord perfusion pressure in either animals or patients suffering from spinal cord injury. Only studies that reported a clinical or relevant clinical outcome measure (i.e., neurophysiology) were included. RESULTS: The search yielded 795 unique records, and six studies were included after careful review. These studies suggested a positive correlation between spinal cord perfusion pressure and neurological outcome, but conclusions on causality could not be made. CONCLUSION: In spite of growing indications that neurological outcomes are related to the spinal cord perfusion pressure in traumatic spinal cord injuries, a solid conclusion cannot be made due to the limited literature available. Additional well-designed studies are needed to address this issue.

Early clinical predictors of functional recovery following traumatic spinal cord injury: a population-based study of 143 patients.

BACKGROUND: Traumatic spinal cord injuries (TSCI) are associated with uncertainty regarding the prognosis of functional recovery. The aim of the present study was to evaluate the potential of early clinical variables to predict the degree of functional independence assessed by Spinal Cord Independence Measure III (SCIM-III) up to 1 year after injury. METHODS: Prospectively collected data from 143 SCI patients treated in Western Denmark during 2012-2019 were retrospectively analysed. Data analysis involved univariate methods and multivariable linear regression modelling total SCIM-III scores against age, gender, body mass index (BMI), comorbidity, American Spinal Injury Association (ASIA) Impairment Scale (AIS) grades A-B and C-D, ASIA Motor Score (AMS), timing of surgical treatment and occurrence of medical complications. Statistical significance was set at p < .05. RESULTS: Univariate analyses indicated that variables significantly associated with decreased functional independence included increased age (p = .023), increased BMI (p = .012), pre-existing comorbidity (p = .001), AIS grades A-B (p < .001), decreased AMS (p < .001) and occurrence of medical complications (p < .001). However, in the multivariable regression model were pre-existing comorbidity (p = .010), AIS grades A-B (p < .001), low AMS (p < .001) and late surgical treatment (p = .018) significant predictors of decreased functional independence 1 year after injury. CONCLUSION: TSCI patients with greatest potential for functional recovery up to 1 year after injury seem to be patients that immediately after trauma present with few or no comorbidities, who sustain motor-incomplete injuries and undergo early decompressive surgery.

Comparison of outcomes and complications between one- and two-level anterior cervical discectomy and fusion: a population-based study of 410 patients.

OBJECTIVE: The objective of this study was to compare outcomes and patient satisfaction, and secondly to compare complication rates between one- and two-level anterior cervical discectomy and fusion (ACDF) for cervical radiculopathy. METHODS: Data from patients receiving one- or two-level ACDF for cervical radiculopathy at two institutions were prospectively collected and retrospectively analysed. Patients were separated into one-level ACDF and two-level ACDF. Comparison analyses of patient-reported outcome measures (PROMs) comprising Visual Analogue Scale for neck pain (VAS-NP) and arm pain (VAS-AP), Neck Disability Index (NDI), and EQ-5D 3-level version (EQ-5D-3L) were performed between baseline and 1-year follow-up and between groups as well as achievement of minimal clinically important differences (MCID) in PROMs and satisfaction. Additionally, complications were compared between groups. RESULTS: A total of 410 patients (270 one-level and 140 two-level) were included. PROMs improved significantly from baseline to 1-year follow-up (p < 0.001) in both groups. When comparing PROMs between one- and two-level ACDF, a trend towards greater improvement was observed in patients undergoing one-level ACDF, notably in EQ-5D-3L (p = 0.073). Significantly more patients in the one-level group achieved MCID in VAS-NP compared to patients in the two-level group (56% vs 44%, p = 0.025). Two hundred and ninety-six (67%) patients reported to be satisfied, but the one-level group trended to be more satisfied (70% vs. 62%). One-level ACDF further demonstrated a trend of more favourable complication profiles; however, complication rates were low in both groups. The risk of intraoperative complications was 2.4%, postoperative complications in-hospital were 1.2%, and patient-reported postoperative events post-discharge 42%. CONCLUSIONS: One- and two-level ACDF are effective procedures for degenerative cervical nerve root compression. Yet, significantly more patients in the one-level group achieved MCID in neck pain compared to patients in the two-level group.

Outcome and negative events in thoracic disc herniation surgery: a Danish registry study.

BACKGROUND: Thoracic disc herniation (TDH) is a surgically demanding entity. Various surgical approaches have been developed and advanced in an attempt to achieve sufficient outcomes and reduce consecutive complication rates. Still, controversy exists regarding selecting the best surgical approach. This retrospective study aims to support decision-making regarding surgical approach. METHODS: We performed a retrospective analysis of 71 patients who underwent thoracic discectomy at Aarhus University Hospital, Denmark, between 1996 and 2015. Patients were divided into two groups depending on whether a lateral approach or a posterior approach was used. Data on demographics, symptomatology, peri- and post-operative events, length of hospitalization and discharge disposition were assembled from medical records. RESULTS: Lateral and posterior approach had an approximately equal peri-operative event rate (39% versus 36%), whereas the lateral approach was associated with a higher post-operative event rate in-hospital and post-discharge than the posterior approach (50% versus 18%; 45% versus 40%). The overall probability of improvement in clinical outcome regardless approach at follow-up was 77% in the short-term and 80% in the long-term. Odds of clinical improvement at any time point was 29% higher with the lateral approach than with the posterior approach (OR = 1.29, 95% CI: 0.52-3.21, p = .76). Adjusting for time, the odds of clinical improvement at short-term follow-up was twice as high for the lateral than for the posterior approach (OR = 2.16, 95% CI: 0.16-30.11); however, the trend seems to fade away over time (OR = 1.10, 95% CI: 0.07-17.55). CONCLUSIONS: The probability of improving after TDH surgery is good. However, a clear conclusion regarding the best surgical approach cannot be established; thus, surgeons should consider pros and cons of each approach when allocating a patient to surgery.

Cranial nerve palsies due to incidental durotomy in lumbar Spine surgery: a case report.

We present a 65-year old man who underwent a partial laminectomy at L4. During surgery an incidental durotomy (ID) appeared. Postoperatively he developed cranial nerve palsies. Subsequent to surgical closure of the ID, symptoms completely resolved within three months.

Early decompressive surgery in patients with traumatic spinal cord injury improves neurological outcome.

BACKGROUND: The role and timing of a decompressive surgical intervention in patients with traumatic spinal cord injury (SCI) remain controversial. Given the impact of SCI on the individual and society, decompressive surgery to reduce the extent of tissue destruction and improving neurological outcome after initial spinal cord trauma are needed. OBJECTIVE: To evaluate any possible correlation between the time of a decompressive procedure after traumatic SCI and end-neurologic outcome for traumatic SCI patients. METHODS: A retrospective cohort study on patients with traumatic SCI in Western Denmark from 2010 to 2017. Data on date and time of injury and time of surgery and data on neurologic status at admission and one-year post-trauma were found in the Electronic Patients Journal (EPJ) and in paper journals. Patients were divided into 4 groups (< 6 h, < 12 h, < 24 h, and > 24 h) based on the time between injury and surgery. Further, patients were separated into two groups depending on whether they did or did not achieve neurological improvement one-year post-trauma. We used Fisher's exact test to compare the abovementioned groups to examine an eventual correlation between time from injury to operation and change in neurological outcome one-year post-trauma. RESULTS: Patients undergoing surgery < 24 h after trauma obtained a significantly better neurological outcome as compared with patients who underwent surgery > 24 h after trauma (p < 0.001). This result did not change for subgroups of incomplete SCI patients (p = 0.002). However, complete SCI patients operated < 24 h as compared with > 24 h did not obtain better outcome (p = 0.14). We did not find a statistically significant correlation when time from trauma to surgery was reduced further to < 6 or < 12 h post-trauma. Furthermore, stratification on patients undergoing surgery before and after 24 h was made regarding gender, completeness, and years of age. The groups did not differ concerning gender and SCI completeness, but significant difference in age was found (44 and 58 years of age, respectively, p < 0.001). The chance of improved outcome was significantly higher for patients < 50 years of age (42% versus 24%, p = 0.05). Patients under the age of 50 seemed to benefit from early intervention (50% improvement versus 23%); however, difference was not statistically significant (p = 0.08). In patients aged above 50, the trend was similar, but significant correlation was found (40% versus 16%, p = 0.05). CONCLUSION: The present study reports a beneficial effect of early decompression surgery, especially for incomplete SCI patients; however, surgical decision-making is complex, and all cases of acute spinal cord injury should be cautiously interpreted and handled on an individual basis.

Penetrating cervical traumatic spinal cord injury due to lawn mowing: an unusual case report.

We present a case of a 55-year-old farmer who suddenly experienced an electric sensation in the left half of his body during lawn mowing. Neurological examination discovered neurological deficits corresponding to an incomplete spinal cord injury. Magnetic resonance imaging displayed an artifact in the cervical region. Following, a computer tomography imaging showed a metal object, located intramedullary, in the cervical spinal cord. The conclusion was a traumatic lesion from the metal object obtained during lawn mowing. The object was evacuated surgically. Three years postoperatively, the patient was improved. Caution in diagnostics following usage of heavy machinery is advised.

Effect of spinal anterior root stimulation and sacral deafferentation on bladder and sexual dysfunction in spinal cord injury.

BACKGROUND: Spinal cord injury (SCI) is a highly devastating injury with a variety of complications; among them are neurogenic bladder, bowel, and sexual dysfunction. We aimed to evaluate the effect of sacral anterior root stimulation with sacral deafferentation (SARS-SDAF) on neurogenic bladder and sexual dysfunction in a large well-defined spinal cord injury cohort. METHODS: In the manner of cross-sectional study, subjects undergone SARS-SDAF between September 1986 and July 2011 answered a questionnaire concerning conditions before and after surgery in the department of Neuro-Urology, Bad Wildungen, Germany. RESULTS: In total 287 of 587 subjects were analyzed. Median age was 49 years (range 19-80), median time from SCI to surgery was 10 years (range 0-49), and from surgery to follow-up 13 years (range 1-25). Of the analyzed subjects, 100% of both gender used SARS for bladder emptying. On the visual analogue scale (VAS) ranging from 0 to 10 (best), satisfaction with SARS-SDAF was 10 concerning bladder emptying, however 5 and 8 regarding sexual performance, for female and male users, respectively. Baseline and follow-up comparison showed a decline in self-intermittent catheterization (p < 0.0001), partial catheterization by attendant (p = 0.0125), complete catheterization and suprapubic catheterization (p < 0.0001), transurethral catheterization (p < 0.0011), and fewer cases of involuntary urine leakage (p < 0.0001). CONCLUSIONS: The SARS-SDAF is a beneficial multi-potential treatment method with simultaneous positive effect on multi-organ dysfunction among SCI subjects.

The artificial somato-autonomic reflex arch does not improve lower urinary tract function in patients with spinal cord lesions.

PURPOSE: The artificial somato-autonomic reflex arch (Xiao procedure) was proposed as treatment for neurogenic bladder dysfunction. We investigated the effects of the procedure on lower urinary tract function. MATERIALS AND METHODS: Seven and 3 patients with a median age of 46 years (range 19 to 64) had AIS A and B spinal cord injury, respectively. In these patients an anastomosis was created between the ventral (motor) part of L5 and the ventral part of the S2 root. Urodynamics were performed and a standard questionnaire was completed at baseline and 18 months postoperatively. RESULTS: Artificial reflex arch stimulation did not initiate voiding or increase bladder pressure. Maximum bladder capacity did not change significantly from baseline to followup (median 427.5 ml, range 168 to 581 vs 498.5, range 271 to 580, p = 0.09). Likewise, bladder compliance did not significantly differ at baseline and followup (median 16.9 ml/cm H2O, range 15.0 to 65.0 vs 25.1, range 17.5 to 50.0, p = 0.95). No difference was found in awareness of bladder emptying, incontinence episodes, bladder emptying method or medication use for neurogenic bladder dysfunction. The only statistically significant change was a decreased incidence of leakage at followup on urodynamics (p = 0.03). Postoperatively decreased genital sensation and erectile dysfunction developed in 1 patient and another experienced a minor cerebrovascular accident with no long-term complications. CONCLUSIONS: In contrast to earlier findings, creation of an artificial somato-autonomic reflex arch in patients with spinal cord injury had no clinically relevant effect on lower urinary tract function.

Peripheral nervous system involvement in chronic spinal cord injury.

INTRODUCTION: Upper motor neuron disorders are believed to leave the peripheral nervous system (PNS) intact. In this study we examined whether there is evidence of PNS involvement in spinal cord injury (SCI). METHODS: Twelve subjects with chronic low cervical or thoracic SCI were included prospectively. Needle electromyography was done in 10 different muscles in each subject bilaterally. Nerve conduction studies (NCS) were conducted in the fibular, tibial, and femoral motor and fibular and sural sensory nerves. RESULTS: Half the subjects had widespread abnormal spontaneous activity (SA), and the amount of SA correlated inversely with reflex activity and nerve length. Fibular nerve entrapment across the knee was seen in 6 subjects, and sciatic nerve entrapment was seen in 1. Apart from entrapment neuropathies, NCS changes were found predominantly in motor nerves. CONCLUSION: The presence of widespread electrophysiologic changes outside entrapment sites indicates that SCI has a significant impact on the entire PNS, affecting the motor part predominantly.

Cryoneurolysis versus radiofrequency ablation outcome on pain experience in chronic low back pain (COPE): a single-blinded randomised controlled trial.

OBJECTIVE: A comparison of cryoneurolysis or radio frequency (RF) with placebo in patients with facetogenic chronic low back pain (LBP) for patient global impression of change (PGIC), pain intensity, function and quality of life, with 1-year follow-up. DESIGN: Single-centre, single-blinded placebo-controlled randomised controlled trial. SETTING: Single-centre study. PARTICIPANTS: Inclusion from March 2020 to September 2022: consenting adults over 18 years of age, LBP>3 months, average Numeric Rating Scale LBP≥4 average last 14 days and a positive response to a diagnostic medial branch block (>50% pain reduction after 60 min). INTERVENTIONS: 120 patients were block randomised 1:1:1 to cryoneurolysis, RF or placebo of the medial branch nerves. Physical therapy was added after 4 weeks for all groups. MAIN OUTCOME MEASURES: Primary outcome was PGIC 4 weeks after the intervention. Secondary outcomes included pain intensity (Numeric Rating Scale, NRS), quality of life (Short Form 36, EQ-5D-5L), disability (Oswestry Disability Index), depression (Major Depression Inventory) and catastrophising (Pain Catastrophising Scale). Outcomes were measured at 4 weeks, 3, 6 and 12 months. RESULTS: There was no statistically significant difference in PGIC at 4 weeks between cryoneurolysis and placebo (risk ratio (RR) 2; 95% CI 0.75 to 5.33, p=0.17) and RF and placebo (RR 1.6; 95% CI 0.57 to 4.49, p=0.37), except PGIC for cryoneurolysis at 6-month follow-up (RR 5.1; 95% CI 1.20 to 22.03, p=0.03). No statistically significant differences were found in secondary follow-up endpoints. CONCLUSIONS: Denervation of the medial branch nerve by either cryoneurolysis or RF compared with placebo did not demonstrate significant improvement in PGIC, pain intensity, function and quality of life in patients with facetogenic chronic LBP at short-term or long-term follow-up. TRIAL REGISTRATION NUMBER: NCT04786145.

A 72-h sedated porcine model of traumatic spinal cord injury.

Introduction: There is an increasing focus on the prevention of secondary injuries following traumatic spinal cord injury (TSCI), especially through improvement of spinal cord perfusion and immunological modulation. Such therapeutic strategies require translational and controlled animal models of disease progression of the acute phases of human TSCI. Research question: Is it possible to establish a 72-h sedated porcine model of incomplete thoracic TSCI, enabling controlled use of continuous, invasive, and non-invasive modalities during the entire sub-acute phase of TSCI? Material and methods: A sham-controlled trial was conducted to establish the model, and 10 animals were assigned to either sham or TSCI. All animals underwent a laminectomy, and animals in the TSCI group were subjected to a weight-drop injury. Animals were then kept sedated for 72 h. The amount of injury was assessed by ex-vivo measures MRI-based fiber tractography, histology and immunohistochemistry. Results: In all animals, we were successful in maintaining sedation for 72 h without comprising vital physiological parameters. The MRI-based fiber tractography showed that all TSCI animals revealed a break in the integrity of spinal neurons, whereas histology demonstrated no transversal sections of the spine with complete injury. Notably, some animals displayed signs of secondary ischemic tissue in the cranial and caudal sections. Discussion and conclusions: This study succeeded in producing a porcine model of incomplete TSCI, which was physiologically stable up to 72 h. We believe that this TSCI model will constitute a potential translational model to study the pathophysiology secondary to TSCI in humans.