Clinical and radiological outcome 1-year after cervical total disc replacement using the Signus ROTAIO - Prosthesis.

INTRODUCTION The instantaneous center of rotation (iCOR) of a motion segment has been shown to correlate with its total range of motion (ROM). Importantly, a correlation of the correct placement of cervical total disc replacement (cTDR) to preserve a physiological iCOR has been previously identified. However, changes of these parameters and the corresponding clinical relevance have hardly been analyzed. This study assesses the radiological and clinical correlation of iCOR and ROM following cTDR. MATERIALS/METHODS A retrospective multi-center observational study was conducted and radiological as well as clinical parameters were evaluated preoperatively and 1 year after cTDR with an unconstrained device. Radiographic parameters including flexion/extension X-rays (flex/ex), ROM, iCOR and the implant position in anterior-posterior direction (IP ap), as well as corresponding clinical parameters [(Neck Disability Index (NDI) and the visual analogue scale (VAS)] were assessed. RESULTS 57 index segments of 53 patients treated with cTDR were analyzed. Pre- and post-operative ROM showed no significant changes (8.0° vs. 10.9°; p > 0.05). Significant correlations between iCOR and IP (Pearson's R: 0.6; p < 0.01) as well as between ROM and IP ap (Pearson's R: - 0.3; p = 0.04) were identified. NDI and VAS improved significantly (p < 0.01). A significant correlation between NDI and IP ap after 12 months (Pearson's R: - 0.39; p < 0.01) was found. CONCLUSION Implantation of the tested prosthesis maintains the ROM and results in a physiological iCOR. The exact position of the device correlates with the clinical outcome and emphasize the importance of implant design and precise implant positioning

Elevated Autoantibodies in Subacute Human Spinal Cord Injury Are Naturally Occurring Antibodies

Spinal cord injury (SCI) results in long-term neurological and systemic consequences, including antibody-mediated autoimmunity, which has been related to impaired functional recovery. Here we show that autoantibodies that increase at the subacute phase of human SCI, 1 month after lesion, are already present in healthy subjects and directed against non-native proteins rarely present in the normal spinal cord. The increase of these autoantibodies is a fast phenomenon–their levels are already elevated before 5 days after lesion–characteristic of secondary immune responses, further supporting their origin as natural antibodies. By proteomics studies we have identified that the increased autoantibodies are directed against 16 different nervous system and systemic self-antigens related to changes known to occur after SCI, including alterations in neural cell cytoskeleton, metabolism and bone remodeling. Overall, in the context of previous studies, our results offer an explanation to why autoimmunity develops after SCI and identify novel targets involved in SCI pathology that warrant further investigation

Duroplasty for injured cervical spinal cord with uncontrolled swelling: protocol of the DISCUS randomized controlled trial

Background Cervical traumatic spinal cord injury is a devastating condition. Current management (bony decompression) may be inadequate as after acute severe TSCI, the swollen spinal cord may become compressed against the surrounding tough membrane, the dura. DISCUS will test the hypothesis that, after acute, severe traumatic cervical spinal cord injury, the addition of dural decompression to bony decompression improves muscle strength in the limbs at 6 months, compared with bony decompression alone. Methods This is a prospective, phase III, multicenter, randomized controlled superiority trial. We aim to recruit 222 adults with acute, severe, traumatic cervical spinal cord injury with an American Spinal Injury Association Impairment Scale grade A, B, or C who will be randomized 1:1 to undergo bony decompression alone or bony decompression with duroplasty. Patients and outcome assessors are blinded to study arm. The primary outcome is change in the motor score at 6 months vs. admission; secondary outcomes assess function (grasp, walking, urinary + anal sphincters), quality of life, complications, need for further surgery, and mortality, at 6 months and 12 months from randomization. A subgroup of at least 50 patients (25/arm) also has observational monitoring from the injury site using a pressure probe (intraspinal pressure, spinal cord perfusion pressure) and/or microdialysis catheter (cord metabolism: tissue glucose, lactate, pyruvate, lactate to pyruvate ratio, glutamate, glycerol; cord inflammation: tissue chemokines/cytokines). Patients are recruited from the UK and internationally, with UK recruitment supported by an integrated QuinteT recruitment intervention to optimize recruitment and informed consent processes. Estimated study duration is 72 months (6 months set-up, 48 months recruitment, 12 months to complete follow-up, 6 months data analysis and reporting results). Discussion We anticipate that the addition of duroplasty to standard of care will improve muscle strength; this has benefits for patients and carers, as well as substantial gains for health services and society including economic implications. If the addition of duroplasty to standard treatment is beneficial, it is anticipated that duroplasty will become standard of care. Trial registration IRAS: 292031 (England, Wales, Northern Ireland) - Registration date: 24 May 2021, 296518 (Scotland), ISRCTN: 25573423 (Registration date: 2 June 2021); ClinicalTrials.gov number : NCT04936620 (Registration date: 21 June 2021); NIHR CRN 48627 (Registration date: 24 May 2021)

Structural and functional rejuvenation of the aged brain by an approved anti-asthmatic drug

As human life expectancy has improved rapidly in industrialized societies, age-related cognitive impairment presents an increasing challenge. Targeting histopathological processes that correlate with age-related cognitive declines, such as neuroinflammation, low levels of neurogenesis, disrupted blood-brain barrier and altered neuronal activity, might lead to structural and functional rejuvenation of the aged brain. Here we show that a 6-week treatment of young (4 months) and old (20 months) rats with montelukast, a marketed anti-asthmatic drug antagonizing leukotriene receptors, reduces neuroinflammation, elevates hippocampal neurogenesis and improves learning and memory in old animals. By using gene knockdown and knockout approaches, we demonstrate that the effect is mediated through inhibition of the GPR17 receptor. This work illustrates that inhibition of leukotriene receptor signalling might represent a safe and druggable target to restore cognitive functions in old individuals and paves the way for future clinical translation of leukotriene receptor inhibition for the treatment of dementias

Zur Kenntnis der D-Fructofuranose

Methyliert man eine Gleichgewichts-Lösung von D-Fructose in Dimethylformamid ([α]d22 = −22°C gegenüber [α]d21 = −92°C in Wasser) mit CH3J und Ag2O, so erhält man als Hauptprodukt ein 1.3.4.6-Tetramethyl-methyl-D-fructofuranosid, das von verd. Schwefelsäure etwas schneller als Octamethylsaccharose gespalten wird. Die aus diesem Tetramethyläther-glykosid durch Säurehydrolyse erhaltene 1.3.4.6-Tetramethyl-D-fructofuranose ist mit dem Spaltstück des permethylierten Rohrzuckers identisch. Sie gibt wie dieses Spaltstück kristallisiertes Methyl-3.4.6-O-trimethyl-fructofuronamid vom Schmp. 100–101°C (Mischprobe). Die Aktivierungsenergie für den Übergang der D-Fructopyranose in die D-Fructofuranose in Dimethylformamid beträgt ca. 21 kcal; im Gleichgewicht liegen ca. 80% der Fructose als Furanose vor. — Für eine Reihe von weiteren reduzierenden Zuckern werden kinetische Messungen über die Geschwindigkeit der Mutarotation in Dimethylformamid mitgeteilt. Ähnlich wie bei Fructose wird auch bei Arabinose und Galaktose die Lage des Mutarotations-Gleichgewichts durch Dimethylformamid stark verschoben