Despite advances in treating acute spinal cord injury (SCI), measures to mitigate permanent neurological deficits in affected patients are limited. Augmentation of mean arterial blood pressure (MAP) to promote blood flow and oxygen delivery to the injured cord is one of the only currently available treatment options to potentially improve neurological outcomes after acute spinal cord injury (SCI). However, to optimize such hemodynamic management, clinicians require a method to measure and monitor the physiological effects of these MAP alterations within the injured cord in real-time. To address this unmet clinical need, we developed a series of miniaturized optical sensors and a monitoring system based on multi-wavelength near-infrared spectroscopy (MW-NIRS) technique for direct transdural measurement and continuous monitoring of spinal cord hemodynamics and oxygenation in real-time. We conducted a feasibility study in a porcine model of acute SCI. We also completed two separate animal studies to examine the function of the sensor and validity of collected data in an acute experiment and a seven-day post-injury survival experiment. In our first animal experiment, nine Yorkshire pigs underwent a weight-drop T10 vertebral level contusion-compression injury and received episodes of ventilatory hypoxia and alterations in MAP. Spinal cord hemodynamics and oxygenation were monitored throughout by a transdural NIRS sensor prototype, as well as an invasive intraparenchymal (IP) sensor as a comparison. In a second experiment, we studied six Yucatan miniature pigs that underwent a T10 injury. Spinal cord oxygenation and hemodynamics parameters were continuously monitored by an improved NIRS sensor over a long period. Episodes of MAP alteration and hypoxia were performed acutely after injury and at two- and seven-days post-injury to simulate the types of hemodynamic changes patients experience after an acute SCI. All NIRS data were collected in real-time, recorded and analyzed in comparison with IP measures. Noninvasive NIRS parameters of tissue oxygenation were highly correlated with invasive IP measures of tissue oxygenation in both studies. In particular, during periods of hypoxia and MAP alterations, changes of NIRS-derived spinal cord tissue oxygenation percentage were significant and corresponded well with the changes in spinal cord oxygen partial pressures measured by the IP sensors (p < 0.05). Our studies indicate that a novel optical biosensor developed by our team can monitor real-time changes in spinal cord hemodynamics and oxygenation over the first seven days post-injury and can detect local tissue changes that are reflective of systemic hemodynamic changes. Our implantable spinal cord NIRS sensor is intended to help clinicians by providing real-time information about the effects of hemodynamic management on the injured spinal cord. Hence, our novel NIRS system has the near-term potential to impact clinical care and improve neurologic outcomes in acute SCI. To translate our studies from bench to bedside, we have developed an advanced clinical NIRS sensor that is ready to be implanted in the first cohort of acute SCI patients in 2022

Acute spinal cord injury (SCI) is most often secondary to trauma, and frequently presents with associated injuries. A neurological examination is routinely performed during trauma assessment, including through Advanced Trauma Life Support (ATLS). However, there is no standard neurological assessment tool specifically used for trauma patients to detect and characterize SCI during the initial evaluation. The International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) is the most comprehensive and popular tool for assessing SCI, but it is not adapted to the acute trauma patients such that it is not routinely used in that setting. Therefore, the objective is to develop a new tool that can be used routinely in the initial evaluation of trauma patients to detect and characterize acute SCI, while preserving basic principles of the ISNCSCI. The completion rate of the ISCNSCI during the initial evaluation after an acute traumatic SCI was first estimated. Using a modified Delphi technique, we designed the Montreal Acute Classification of Spinal Cord Injuries (MAC-SCI), a new tool to detect and characterize the completeness (grade) and level of SCI in the polytrauma patient. The ability of the MAC-SCI to detect and characterize SCI was validated in a cohort of 35 individuals who have sustained an acute traumatic SCI. The completeness and neurological level of injury (NLI) were assessed by two independent assessors using the MAC-SCI, and compared to those obtained with the ISNCSCI. Only 33% of patients admitted after an acute traumatic SCI had a complete ISNCSCI performed at initial presentation. The MAC-SCI includes 53 of the 134 original elements of the ISNCSCI which is 60% less. There was a 100% concordance between the severity grade derived from the MAC-SCI and from the ISNCSCI. Concordance of the NLI within two levels of that obtained from the ISNCSCI was observed in 100% of patients with the MAC-SCI and within one level in 91% of patients. The ability of the MAC-SCI to discriminate between cervical (C0 to C7) vs. thoracic (T1 to T9) vs. thoraco-lumbar (T10 to L2) vs. lumbosacral (L3 to S5) injuries was 100% with respect to the ISNCSCI. The rate of completion of the ISNCSCI is low at initial presentation after an acute traumatic SCI. The MAC-SCI is a streamlined tool proposed to detect and characterize acute SCI in polytrauma patients, that is specifically adapted to the acute trauma setting. It is accurate for determining the completeness of the SCI and localize the NLI (cervical vs. thoracic vs. lumbar). It could be implemented in the initial trauma assessment protocol to guide the acute management of SCI patients

Acute spinal cord injury (SCI) is most often secondary to trauma, and frequently presents with associated injuries. A neurological examination is routinely performed during trauma assessment, including through Advanced Trauma Life Support (ATLS). However, there is no standard neurological assessment tool specifically used for trauma patients to detect and characterize SCI during the initial evaluation. The International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) is the most comprehensive and popular tool for assessing SCI, but it is not adapted to the acute trauma patients such that it is not routinely used in that setting. Therefore, the objective is to develop a new tool that can be used routinely in the initial evaluation of trauma patients to detect and characterize acute SCI, while preserving basic principles of the ISNCSCI. The completion rate of the ISCNSCI during the initial evaluation after an acute traumatic SCI was first estimated. Using a modified Delphi technique, we designed the Montreal Acute Classification of Spinal Cord Injuries (MAC-SCI), a new tool to detect and characterize the completeness (grade) and level of SCI in the polytrauma patient. The ability of the MAC-SCI to detect and characterize SCI was validated in a cohort of 35 individuals who have sustained an acute traumatic SCI. The completeness and neurological level of injury (NLI) were assessed by two independent assessors using the MAC-SCI, and compared to those obtained with the ISNCSCI. Only 33% of patients admitted after an acute traumatic SCI had a complete ISNCSCI performed at initial presentation. The MAC-SCI includes 53 of the 134 original elements of the ISNCSCI which is 60% less. There was a 100% concordance between the severity grade derived from the MAC-SCI and from the ISNCSCI. Concordance of the NLI within two levels of that obtained from the ISNCSCI was observed in 100% of patients with the MAC-SCI and within one level in 91% of patients. The ability of the MAC-SCI to discriminate between cervical (C0 to C7) vs. thoracic (T1 to T9) vs. thoraco-lumbar (T10 to L2) vs. lumbosacral (L3 to S5) injuries was 100% with respect to the ISNCSCI. The rate of completion of the ISNCSCI is low at initial presentation after an acute traumatic SCI. The MAC-SCI is a streamlined tool proposed to detect and characterize acute SCI in polytrauma patients, that is specifically adapted to the acute trauma setting. It is accurate for determining the completeness of the SCI and localize the NLI (cervical vs. thoracic vs. lumbar). It could be implemented in the initial trauma assessment protocol to guide the acute management of SCI patients

Acute spinal cord injury (SCI) is most often secondary to trauma, and frequently presents with associated injuries. A neurological examination is routinely performed during trauma assessment, including through Advanced Trauma Life Support (ATLS). However, there is no standard neurological assessment tool specifically used for trauma patients to detect and characterize SCI during the initial evaluation. The International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) is the most comprehensive and popular tool for assessing SCI, but it is not adapted to the acute trauma patients such that it is not routinely used in that setting. Therefore, the objective is to develop a new tool that can be used routinely in the initial evaluation of trauma patients to detect and characterize acute SCI, while preserving basic principles of the ISNCSCI. The completion rate of the ISCNSCI during the initial evaluation after an acute traumatic SCI was first estimated. Using a modified Delphi technique, we designed the Montreal Acute Classification of Spinal Cord Injuries (MAC-SCI), a new tool to detect and characterize the completeness (grade) and level of SCI in the polytrauma patient. The ability of the MAC-SCI to detect and characterize SCI was validated in a cohort of 35 individuals who have sustained an acute traumatic SCI. The completeness and neurological level of injury (NLI) were assessed by two independent assessors using the MAC-SCI, and compared to those obtained with the ISNCSCI. Only 33% of patients admitted after an acute traumatic SCI had a complete ISNCSCI performed at initial presentation. The MAC-SCI includes 53 of the 134 original elements of the ISNCSCI which is 60% less. There was a 100% concordance between the severity grade derived from the MAC-SCI and from the ISNCSCI. Concordance of the NLI within two levels of that obtained from the ISNCSCI was observed in 100% of patients with the MAC-SCI and within one level in 91% of patients. The ability of the MAC-SCI to discriminate between cervical (C0 to C7) vs. thoracic (T1 to T9) vs. thoraco-lumbar (T10 to L2) vs. lumbosacral (L3 to S5) injuries was 100% with respect to the ISNCSCI. The rate of completion of the ISNCSCI is low at initial presentation after an acute traumatic SCI. The MAC-SCI is a streamlined tool proposed to detect and characterize acute SCI in polytrauma patients, that is specifically adapted to the acute trauma setting. It is accurate for determining the completeness of the SCI and localize the NLI (cervical vs. thoracic vs. lumbar). It could be implemented in the initial trauma assessment protocol to guide the acute management of SCI patients

Initial treatment of traumatic spinal cord injury remains as controversial in 2023 as it was in the early 19th century, when Sir Astley Cooper and Sir Charles Bell debated the merits or otherwise of surgery to relieve cord compression. There has been a lack of high-class evidence for early surgery, despite which expeditious intervention has become the surgical norm. This evidence deficit has been progressively addressed in the last decade and more modern statistical methods have been used to clarify some of the issues, which is demonstrated by the results of the SCI-POEM trial. However, there has never been a properly conducted trial of surgery versus active conservative care. As a result, it is still not known whether early surgery or active physiological management of the unstable injured spinal cord offers the better chance for recovery. Surgeons who care for patients with traumatic spinal cord injuries in the acute setting should be aware of the arguments on all sides of the debate, a summary of which this annotation presents. Cite this article: Bone Joint J 2023;105-B(4):347–355

This review provides a concise outline of the advances made in the care of patients and to the quality of life after a traumatic spinal cord injury (SCI) over the last century. Despite these improvements reversal of the neurological injury is not yet possible. Instead, current treatment is limited to providing symptomatic relief, avoiding secondary insults and preventing additional sequelae. However, with an ever-advancing technology and deeper understanding of the damaged spinal cord, this appears increasingly conceivable. A brief synopsis of the most prominent challenges facing both clinicians and research scientists in developing functional treatments for a progressively complex injury are presented. Moreover, the multiple mechanisms by which damage propagates many months after the original injury requires a multifaceted approach to ameliorate the human spinal cord. We discuss potential methods to protect the spinal cord from damage, and to manipulate the inherent inhibition of the spinal cord to regeneration and repair. Although acute and chronic SCI share common final pathways resulting in cell death and neurological deficits, the underlying putative mechanisms of chronic SCI and the treatments are not covered in this review

Primary spinal cord injury is followed by secondary, biochemical, immunological, cellular changes in the injured cord. A review article written by Brian Kwon looking critically at the use of hypothermia for SCI. It shows that it is neuroprotective in some settings (i.e. cardiac arrest). However, there are 25 animal studies with mixed results and only eight human SCI studies. Importantly, they are all case series of local, not systemic hypothermia. And the last one published was in 1984. Rho is a critical molecule in SCI. Rho ultimately inhibits axonal growth cone proliferation. Stopping RHO therefore will promote the growth cone. There are two drugs that ultimately targets rho. These are anti nogo antibodies and cethrin both of which ultimately inhibit rho. President Obama lifted the ban on federal funding of stem cell research. This was a monumental occasion and was right around the time that the FDA approved the first trial of hESC for SCI. The FDA trial of Geron is with Thoracic ASIA A SCI patients with transplantation of ESC directly into the cord at 7 to 14 days after injury. Geron has provided evidence to the FDA that there is no teratoma formation with transplantation of a human ESC to a rat or mouse. However, we do not know what will happen in a human to human transplant. In conclusion, use of steroids in setting of SCI is diminishing. There is no clinical evidence to support use of systemic hypothermia. Current clinical trials of pharmacologic therapy include Minocycline and RILUTEK(r) (riluzole) for neuroprotection, Anti-Nogo Antibodies and Cethrin(r) for axonal growth by ultimately inhibiting Rho. There is only one small study supporting safety, not efficacy of OEC transplantation

Aims. Spinal deformity surgery carries the risk of neurological injury. Neurophysiological monitoring allows early identification of intraoperative cord injury which enables early intervention resulting in a better prognosis. Although multimodal monitoring is the ideal, resource constraints make surgeon-directed intraoperative transcranial motor evoked potential (TcMEP) monitoring a useful compromise. Our experience using surgeon-directed TcMEP is presented in terms of viability, safety, and efficacy. Methods. We carried out a retrospective review of a single surgeon’s prospectively maintained database of cases in which TcMEP monitoring had been used between 2010 and 2017. The upper limbs were used as the control. A true alert was recorded when there was a 50% or more loss of amplitude from the lower limbs with maintained upper limb signals. Patients with true alerts were identified and their case history analyzed. Results. Of the 299 cases reviewed, 279 (93.3%) had acceptable traces throughout and awoke with normal clinical neurological function. No patient with normal traces had a postoperative clinical neurological deficit. True alerts occurred in 20 cases (6.7%). The diagnoses of the alert group included nine cases of adolescent idiopathic scoliosis (AIS) (45%) and six of congenital scoliosis (30%). The incidence of deterioration based on diagnosis was 9/153 (6%) for AIS, 6/30 (20%) for congenital scoliosis, and 2/16 (12.5%) for spinal tuberculosis. Deterioration was much more common in congenital scoliosis than in AIS (p = 0.020). Overall, 65% of alerts occurred during rod instrumentation: 15% occurred during decompression of the internal apex in vertebral column resection surgery. Four alert cases (20%) awoke with clinically detectable neurological compromise. Conclusion. Surgeon-directed TcMEP monitoring has a 100% negative predictive value and allows early identification of physiological cord distress, thereby enabling immediate intervention. In resource constrained environments, surgeon-directed TcMEP is a viable and effective method of intraoperative spinal cord monitoring. Level of evidence: III. Cite this article: Bone Joint J 2021;103-B(3):547–552

Aims. Traumatic central cord syndrome (CCS) typically follows a hyperextension injury and results in motor impairment affecting the upper limbs more than the lower, with occasional sensory impairment and urinary retention. Current evidence on mortality and long-term outcomes is limited. The primary aim of this study was to assess the five-year mortality of CCS, and to determine any difference in mortality between management groups or age. Methods. Patients aged ≥ 18 years with a traumatic CCS between January 2012 and December 2017 in Wales were identified. Patient demographics and data about injury, management, and outcome were collected. Statistical analysis was performed to assess mortality and between-group differences. Results. A total of 65 patients were identified (66.2% male (n = 43), mean age 63.9 years (SD 15.9)). At a minimum of five years’ follow-up, 32.3% of CCS patients (n = 21) had died, of whom six (9.2%) had died within 31 days of their injury. Overall, 69.2% of patients (n = 45) had been managed conservatively. There was no significant difference in age between conservatively and surgically managed patients (p = 0.062). Kaplan-Meier analysis revealed no significant difference in mortality between patients managed conservatively and those managed surgically (p = 0.819). However, there was a significant difference in mortality between the different age groups (< 50 years vs 50 to 70 years vs > 70 years; p = 0.001). At five years’ follow-up, 55.6% of the patient group aged > 70 years at time of injury had died (n = 15). Respiratory failure was the most common cause of death (n = 9; 42.9%). Conclusion. Almost one-third of patients with a traumatic CCS in Wales had died within five years of their injury. The type of management did not significantly affect mortality but their age at the time of injury did. Further work to assess the long-term functional outcomes of surviving patients is needed to generate more reliable prognostic information. Cite this article: Bone Joint J 2023;105-B(8):920–927

Aims. The aim of this study was to determine whether early surgical treatment results in better neurological recovery 12 months after injury than late surgical treatment in patients with acute traumatic spinal cord injury (tSCI). Methods. Patients with tSCI requiring surgical spinal decompression presenting to 17 centres in Europe were recruited. Depending on the timing of decompression, patients were divided into early (≤ 12 hours after injury) and late (> 12 hours and < 14 days after injury) groups. The American Spinal Injury Association neurological (ASIA) examination was performed at baseline (after injury but before decompression) and at 12 months. The primary endpoint was the change in Lower Extremity Motor Score (LEMS) from baseline to 12 months. Results. The final analyses comprised 159 patients in the early and 135 in the late group. Patients in the early group had significantly more severe neurological impairment before surgical treatment. For unadjusted complete-case analysis, mean change in LEMS was 15.6 (95% confidence interval (CI) 12.1 to 19.0) in the early and 11.3 (95% CI 8.3 to 14.3) in the late group, with a mean between-group difference of 4.3 (95% CI -0.3 to 8.8). Using multiply imputed data adjusting for baseline LEMS, baseline ASIA Impairment Scale (AIS), and propensity score, the mean between-group difference in the change in LEMS decreased to 2.2 (95% CI -1.5 to 5.9). Conclusion. Compared to late surgical decompression, early surgical decompression following acute tSCI did not result in statistically significant or clinically meaningful neurological improvements 12 months after injury. These results, however, do not impact the well-established need for acute, non-surgical tSCI management. This is the first study to highlight that a combination of baseline imbalances, ceiling effects, and loss to follow-up rates may yield an overestimate of the effect of early surgical decompression in unadjusted analyses, which underpins the importance of adjusted statistical analyses in acute tSCI research. Cite this article: Bone Joint J 2023;105-B(4):400–411

Abstract. Objective. Spinal cord surgery is a technically challenging endeavour with potentially devastating complications for patients and surgeons. Intra-operative neurophysiological monitoring(IONM), or spinal cord monitoring (SCM), is one method of preventing and identifying damage to the spinal cord. At present, indications for its use are based more on individual surgeon preference and for medico legal purposes. Our study aimed to determine IONM's utility as a clinical tool. Methods. This is a retrospective case series of 169 patients who underwent spinal surgery with IONM at two institutions between 2013 and 2018. Signal changes detected were recorded as well as the surgeon's response to these changes. Patients were followed up to one-year post-surgery using our institution's EVOLVE system. The main outcome measure in this study was new post-operative neurological signs and/or symptoms and what effect, if any, IONM and subsequent surgeon intervention had on these complications. Result. Indications for IONM included cervical stenosis, cervical disc prolapse, unstable fractures and bony metastases. Signal changes were observed in 33% (n=55) of cases. 24 of these patients responded to re-positioning. There were 7 total complications with full resolution by 12 months. False negative rate was 2.4% (n=4). There was one true positive. The largest cohort of patients included those who experienced no signal changes and subsequently no post-operative deficits (n=124). Conclusion. IONM is a non-invasive clinical tool that may be utilised for medicolegal reasons. Its use as a clinical tool is questionable given its relatively high false negative rate and low false positive rate. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Aims. Traumatic central cord syndrome (CCS) typically follows a hyperextension injury and results in a motor impairment affecting the upper limbs more than the lower limbs, with occasional sensory impairment and urinary retention seen. Current evidence on mortality and long-term outcomes is limited. The primary aim of this study is to assess the five-year mortality of CCS, and to determine any difference in mortality between management groups or age. Patients and Methods. Patients ≥18 years with traumatic CCS between January 2012 and December 2017 in Wales were identified. Patient demographics and injury, management and outcome data was collected. Statistical analysis was performed to assess mortality and between group differences. Results. 65 patients were identified (66.2% male, mean age 63.9 years). At five-years follow-up, 32.3% (n=21) of CCS patients were dead. 6 (9.2%) patients had died within 31 days of their injury. 69.2% (n=45) of patients were managed conservatively and there was no significant difference (p=0.062) in age between conservatively and surgically managed patients. Kaplan-Meier analysis revealed no significant difference in mortality between patients managed conservatively compared to those managed surgically (log rank test, p=0.819). However, there was a significant difference (p=0.001) in mortality between the different age groups (<50 years vs 50–70 years vs >70 years). At five-years follow up, 55.6% of the patient group aged >70 years at time of injury were dead. Respiratory failure was the most common cause of death (n=9, 42.9%). Conclusion. Almost one third of patients with traumatic CCS in Wales were dead at five years following their injury. Management type did not significantly affect mortality, however age at time of injury did. Further work assessing the long-term functional outcomes of surviving patients is needed, to allow more reliable prognostic information and functional recovery predictions to be given

Metastatic epidural compression of the spinal cord is a significant source of morbidity in patients with systemic cancer. With improved oncological treatment, survival in these patients is improving and metastatic cord compression is encountered increasingly often. The treatment is mostly palliative. Surgical management involves early circumferential decompression of the cord with concomitant stabilisation of the spine. Patients with radiosensitive tumours without cord compression benefit from radiotherapy. Spinal stereotactic radiosurgery and minimally invasive techniques, such as vertebroplasty and kyphoplasty, with or without radiofrequency ablation, are promising options for treatment and are beginning to be used in selected patients with spinal metastases. In this paper we review the surgical management of patients with metastatic epidural spinal cord compression

Aim. Decubitus ulcers are found in approximately 4.7% of hospitalized patients, with a higher prevalence (up to 30%) among those with spinal cord injuries. These ulcers are often associated with hip septic arthritis and/or osteomyelitis involving the femur. Girdlestone resection arthroplasty is a surgical technique used to remove affected proximal femur and acetabular tissues, resulting in a substantial defect. The vastus lateralis flap has been employed as an effective option for managing this dead space. The aim of this study was to evaluate the long-term outcomes of this procedure in a consecutive series of patients. Method. A retrospective single-center study was conducted from October 2012 to December 2022, involving 7 patients with spinal cord injuries affected by chronic severe septic hip arthritis and/or femoral head septic necrosis as a consequence of decubitus ulcers over trochanter area. All patients underwent treatment using a multidisciplinary approach by the same surgical team (orthopedic and plastic surgeons) along with infectious disease specialists. The treatment consisted of a one-stage procedure combining Girdlestone resection arthroplasty with unilateral vastus lateralis flap reconstruction, alongside targeted antibiotic therapy. Complications and postoperative outcomes were assessed and recorded. The mean follow-up period was 8 years (range 2-12). Results. Of the 7 patients, 5 were male and 2 were female, with a mean age of 50.3 years at the time of surgery. Minor wound dehiscence occurred in 28.6% of the flap sites, and 2 patients required additional revisional procedures—one for hematoma and the other for bleeding. There were no instances of flap failure, and complete wound healing was achieved in an average of 32 days (range 20-41), with the ability to load over the hip area. No cases of infection recurrence or relapse were observed. Conclusions. An aggressive surgical approach is strongly recommended for managing chronic hip septic arthritis or proximal femur osteomyelitis in patients with spinal cord injuries. A single-stage procedure combining Girdlestone resection arthroplasty with immediate vastus lateralis muscle flap reconstruction proves to be an effective strategy for dead space management and localized antibiotic delivery through the vastus muscle, giving reliable soft tissue coverage around the proximal femur to avoid the recurrence of pressure ulcers. The implementation of a standardized multidisciplinary protocol contributes significantly to the success of reconstruction efforts

To analyse the causes and factors associated with mortality in patients admitted to ASCI unit in a low- or middle-income country. The study was performed at a Tertiary Hospital at Groote Schuur Hospital, Cape Town South Africa. Data between 1996 –2022 were retrospectively collected from hospital records of patients admitted to the ASCI Unit. There was approximately 3223 admissions for the study period. 682 patients were confirmed dead 87% were male and 64% were unemployed. The mean age was 46 years (ranging from 14 – 87 years). A 1/3 of injuries were caused by a MVA, a ¼ by a fall (low energy and from a height), and 1/5 by a gunshot wound. Average length of stay was 47 days (SD = 52 days), ranging from as short as 1 day to 512 days for one patient. Majority (65%) were admitted for more than a week but less than 2 months 32% were ventilated, and 17% with a CPAP facemask. 10% of patients had a pre-existing ulcer prior to admission. 65% of patients had surgery via the posterior approach, 33% via the anterior approach. On average patients died within 5 years of being admitted to hospital, ranging from dying in the same year as the injury to 20 years later. 73% of the deaths were classified as natural deaths and 20% as unnatural. There is a high mortality in patients with acute spinal cord injury, causes are multifactorial, and in depth critical analyses is required to improve clinical outcomes and rationalise resource allocation

Macromolecular crowding (MMC) is a biophysical phenomenon that accelerates thermodynamic activities and biological processes by several orders of magnitude. Herein, we ventured to identify the optimal crowder and to assess the influence of MMC in umbilical cord mesenchymal stem cell. 7 types of carrageenan (κ&λ, κ-LV1, κ-LV2, λ-MV, λ-HV, ι-MV, ι-HV) acted as crowder and biophysical properties were assessed respectively. Human umbilical cord mesenchymal stem cells were seeded at 15,000 cells/cm. 2. in 24 well plates and allowed to attach for 24 h. Subsequently, the medium was changed to medium with 7 types of carrageenan (10, 50, 100, 500 μg/ml) and 100 μM L-ascorbic acid phosphate (Sigma Aldrich). Medium without carrageenan was used as control. Cell morphology and SDS-PAGE analysis were conducted after 3, 5 and 7 days. Biophysical assessment showed 7 types of carrageenan have increased particle size with concentration, good polydispersity and negative charges. SDS-PAGE and densitometric analyses revealed significant increase (p < 0.001) in collagen deposition in the presence of 10 μg/ml carrageenan λ and ι at all the time points. SDS-PAGE and densitometric analysis also showed that the highest collagen deposition was observed in culture at 50 μg/ml carrageenan λ. No significant difference was observed in cell morphology between the groups. Collectively, these data primarily illustrate the beneficial effect of carrageenan λ in human umbilical cord mesenchymal stem cell culture

There are many causes of paraspinal muscle weakness which give rise to the dropped-head syndrome. In the upper cervical spine the central portion of the spinal cord innervates the cervical paraspinal muscles. Dropped-head syndrome resulting from injury to the central spinal cord at this level has not previously been described. We report two patients who were treated acutely for this condition. Both presented with weakness in the upper limbs and paraspinal cervical musculature after a fracture of C2. Despite improvement in the strength of the upper limbs, the paraspinal muscle weakness persisted in both patients. One ultimately underwent cervicothoracic fusion to treat her dropped-head syndrome. While the cause of the dropped-head syndrome cannot be definitively ascribed to the injuries to the spinal cord, this pattern is consistent with the known patho-anatomical mechanisms of both injury to the central spinal cord and dropped-head syndrome

Silver nanoparticles (AgNPs) possess anti-inflammatory activities and have been widely deployed for promoting tissue repair. Here we explored the efficacy of AgNPs on functional recovery after spinal cord injury (SCI). Our data indicated that, in a SCI rat model, local AgNPs delivery could significantly recover locomotor function and exert neuroprotection through reducing of pro-inflammatory M1 survival. Furthermore, in comparison with Raw 264.7-derived M0 and M2, a higher level of AgNPs uptake and more pronounced cytotoxicity were detected in M1. RNA-seq analysis revealed the apoptotic genes in M1 were upregulated by AgNPs, whereas in M0 and M2, pro-apoptotic genes were downregulated and PI3k-Akt pathway signaling pathway was upregulated. Moreover, AgNPs treatment preferentially reduced cell viability of human monocyte-derived M1 comparing to M2, supporting its effect on M1 in human. Overall, our findings reveal AgNPs could suppress M1 activity and imply its therapeutic potential in promoting post-SCI motor recovery

For patients who took joint replacement, one of the complications, aseptic joint loosening, could cause a high risk of revision surgery. Studies have shown that MSCs have the ability of homing and differentiating, and also have highly effective immune regulation and anti-inflammatory effects. However, few studies had focused on the stem cells in preventing the occurrence and development of aseptic loosening. In this research, we aimed to clarify whether human umbilical cord mesenchymal stem cells could inhibited the aseptic joint loosening caused by wear particles. A Cranial osteolysis mice model was established on mice to examine the effect of hUC-MSCs on the Titanium particles injection area through micro-CT. The amount of stem cells injected was 2 × 10 5 cells. One week later, the mouse Cranial were obtained for micro-CT scan, and then stained with HE analysis immunohistochemical analysis of TNF-α, CD68, CCL3 and Il-1β. All mice were free of fever and other adverse reactions, and there was no death occurred. Titanium particles caused the osteolysis at the mice cranial, while local injection of hUC-MSCs did inhibit the cranial osteolysis, with a lower BV/TV and a higher porosity. Immunohistochemical results suggested that the expression of TNF-α, CD68, CCL3 and Il-1β in the cranial in Titanium particles mice increased significantly, but was significantly reduced in mice injected with hUC-MSCs. The inhibited CD68 expression indicated that the number of macrophage was lower, which might be a result of the inhibition of CCL3. According to the studies above, HUC-MSCs treatment of mouse cranial osteolysis model can significantly reduce osteolysis, inhibit macrophage recruitment, alleviate inflammatory response, without causing adverse reactions. It may become a promising treatment of aseptic joint loosening

Aim. The aim of the study was to define the peculiarities of bone remodeling and identify specific parameters to development to heterotopic ossification. Materials and methods. Markers of bone formation (Osteocalcin, serum type 1 procollagen (N-terminal) (tP1NP)) and bone resorption (serum collagen type 1 cross-linked C-telopeptide (β-CTx)) were determined by the electrochemiluminiscence immunoassay “ECLIA” for Elecsys user cobas immunoassay analyser. In the study were included 23 patients with spinal cord injury – first group (average age 26.8 ± 3.9, duration of spinal cord injury from 3 to 12 months) and 23 healthy people's appropriate age and gender (average age 30.6 ± 6.0, years). In the first group included 11 patients with spinal cord injury with the presence of heterotopic ossification – subgroup I and 12 patients with spinal cord injury without heterotopic ossification – subgroup II. Results. The results of examination showed that patients of first group had significantly higher bone markers than control group: P1NP (256.7±48.2 ng/ml vs 49.3±5.1 ng/ml, p<0.001), serum β-CTx (1.47±0.23 ng/ml vs 0.45±0.04 ng/ml, p<0.0001), osteocalcin (52.2±9.8 ng/ml vs 24.9±2.08 ng/ml, p<0.001). There were obtained that levels of bone remodeling markers in patients with HO were significantly higher in comparison with patients without HO: P1NP (404.9±84.9 ng/ml vs 133.2±15.7 ng/ml, p<0.001), serum β-CTx (1.75±0.23 ng/ml vs 0.28±0.14 ng/ml, p<0.0001), osteocalcin (87.1±18.9 ng/ml vs 29.4±3.7 ng/ml, p<0.001). Conclusion. The bone formation and bone resorption markers in patient of first group were significantly higher than in healthy individuals of appropriate age. The rate of bone turnover markers in patient with HO was considerably higher than in patient without HO and the process of formation dominated over the resorption in patient with HO