Epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China:a hospital-based retrospective study

Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even death.China has the largest population of patients with traumatic spinal cord injury.Previous studies of traumatic spinal cord injury in China have mostly been regional in scope;national-level studies have been rare.To the best of our knowledge,no national-level study of treatment status and economic burden has been performed.This retrospective study aimed to examine the epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China at the national level.We included 13,465 traumatic spinal cord injury patients who were injured between January 2013 and December 2018 and treated in 30 hospitals in 11 provinces/municipalities representing all geographical divisions of China.Patient epidemiological and clinical features,treatment status,and total and daily costs were recorded.Trends in the percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department and cost of care were assessed by annual percentage change using the Joinpoint Regression Program.The percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department did not significantly change overall(annual percentage change,-0.5%and 2.1%,respectively).A total of 10,053(74.7%)patients underwent surgery.Only 2.8%of patients who underwent surgery did so within 24 hours of injury.A total of 2005(14.9%)patients were treated with high-dose(≥500 mg)methylprednisolone sodium succinate/methylprednisolone(MPSS/MP);615(4.6%)received it within 8 hours.The total cost for acute traumatic spinal cord injury decreased over the study period(-4.7%),while daily cost did not significantly change(1.0%increase).Our findings indicate that public health initiatives should aim at improving hospitals’ability to complete early surgery within 24 hours,which is associated with improved sensorimotor recovery,increasing the awareness rate of clinical guidelines related to high-dose MPSS/MP to reduce the use of the treatment with insufficient evidence.

Modulation of autophagy for neuroprotection and functional recovery in traumatic spinal cord injury

Spinal cord injury(SCI) is a serious central nervous system trauma that leads to loss of motor and sensory functions in the SCI patients. One of the cell death mechanisms is autophagy, which is ‘self-eating' of the damaged and misfolded proteins and nucleic acids, damaged mitochondria, and other impaired organelles for recycling of cellular building blocks. Autophagy is different from all other cell death mechanisms in one important aspect that it gives the cells an opportunity to survive or demise depending on the circumstances. Autophagy is a therapeutic target for alleviation of pathogenesis in traumatic SCI. However, functions of autophagy in traumatic SCI remain controversial. Spatial and temporal patterns of activation of autophagy after traumatic SCI have been reported to be contradictory. Formation of autophagosomes following therapeutic activation or inhibition of autophagy flux is ambiguous in traumatic SCI studies. Both beneficial and harmful outcomes due to enhancement autophagy have been reported in traumatic SCI studies in preclinical models. Only further studies will make it clear whether therapeutic activation or inhibition of autophagy is beneficial in overall outcomes in preclinical models of traumatic SCI. Therapeutic enhancement of autophagy flux may digest the damaged components of the central nervous system cells for recycling and thereby facilitating functional recovery. Many studies demonstrated activation of autophagy flux and inhibition of apoptosis for neuroprotective effects in traumatic SCI. Therapeutic induction of autophagy in traumatic SCI promotes axonal regeneration, supporting another beneficial role of autophagy in traumatic SCI. In contrast, some other studies demonstrated that disruption of autophagy flux in traumatic SCI strongly correlated with neuronal death at remote location and impaired functional recovery. This article describes our current understanding of roles of autophagy in acute and chronic traumatic SCI, crosstalk between autophagy and apoptosis, therapeutic activation or inhibition of autophagy for promoting functional recovery, and future of autophagy in traumatic SCI.

Reducing intrathecal pressure after traumatic spinal cord injury: a potential clinical target to promote tissue survival

Spinal cord injury （SCI） is an unexpected event that is both devastating and debilitating, resulting in not just motor and sensory loss, but also autonomic dysfunction of the bladder, bowel and sexual organs. Currently, there are no treatments available to improve outcome follow- ing SCI, leaving individuals with permanent and lifelong physical disability. Worldwide it is estimated that more than 500,000 people sustain a SCI each year, with average lifetime cost of paraplegia and quadriplegia estimated at $5 million and $9.5 million respectively. We therefore urgently need effective therapies to improve quality of life following SCI, and this requires a greater understanding of how cell and axonal injury develops after the traumatic event.

Altered leukocyte gene expression after traumatic spinal cord injury:clinical implications

In addition to changes in motor and sensory function, individuals with spinal cord injury （SCI） experience immunological changes. These changes are clinically significant, as infections are the leading cause of death for this population. Along with increased infections, inflammation is commonly observed in persons with SCI, where it may promote many common medical consequences. These include elevated risk of cardio- vascular disease, impaired wound healing, diabetes and neuropathic pain. It has also been proposed that chronic inflammation dampens neurological recovery. In order to identify therapeutic strategies to im- prove immune function, we need a greater understanding of the molecular changes that occur in immune cells after SCI. The purpose of this mini-review is to discuss two recent studies that used functional genom- ics to investigate gene expression in circulating leukocytes isolated from persons with SCI. In the future, the molecular pathways that are altered after SCI may be targeted to improve immunological function, as well as overall health and functional recovery, after SCI.

Urinary bladder cancer as a late sequela of traumatic spinal cord injury

Background:Traumatic spinal cord injury(SCI)is also a combat-related injury that is increasing in modern warfare.The aim of this work is to inform medical experts regarding the different course of bladder cancer in able-bodied patients compared with SCI patients based on the latest medical scientific knowledge,and to present decision-making aids for the assessment of bladder cancer as a late sequela of traumatic SCI.Methods:A study conducted between January 1998 and December 2019 in the BG Trauma Hospital Hamburg formed the basis for the decision-making aids.Urinary bladder cancer was diagnosed in 40 out of 7396 treated outpatient and inpatient SCI patients.General patient information,latency period,age at initial diagnosis,type of bladder management and survival of SCI patients with bladder cancer were collected and analysed.T category,grading and tumor entity in these patients were compared with those in the general population.Relevant bladder cancer risk factors in SCI patients were analysed.Furthermore,relevant published literature was taken into consideration.Results:Initial diagnosis of urinary bladder cancer in SCI patients occurs at a mean age of 56.4 years(SD±10.7 years),i.e.,approximately 20 years earlier as compared with the general population.These bladder cancers are significantly more frequently muscle invasive(i.e.,T category≥T2)and present a higher grade at initial diagnosis.Furthermore,SCI patients show a significantly higher proportion of the more aggressive squamous cell carcinoma than that of the general population in areas not endemic for the tropical disease schistosomiasis.Consequently,the survival time is extremely unfavourable.A very important finding,for practical reasons is that,in the Hamburg study as well as in the literature,urinary bladder cancer is more frequently observed after 10 years or more of SCI.Based on these findings,a matrix was compiled where the various influencing factors,either for or against the recognition of an association between SCI and urinary bladder cancer,were weighted according to their relevance.Conclusions:The results showed that urinary bladder cancer in SCI patients differs considerably from that in ablebodied patients.The presented algorithm is an important aid in everyday clinical practice for assessing the correlation between SCI and bladder cancer.

An Analysis of Pain Following Traumatic Spinal Cord Injury among Adults in Zimbabwe

The purpose of the study was to analyse on pain following traumatic spinal cord injury, its prevalence, the types of pain present, the common treatments used and their perceived effectiveness in the management of these reported pain types. A cross sectional study was carried out at St Giles Rehabilitation Centre and from members of the Spinal Injuries Association of Zimbabwe (SIAZ). A researcher-administered questionnaire was used to collect data from 24 participants with traumatic spinal cord injury. The questionnaire elicited information on demographic data, pain characteristics and the perceived effectiveness of the common treatments used. Among the 24 participants in the study, 17 were males (70.8%) and 7 were females (29.2%). Pain prevalence was 79.2% among the study participants and approximately a fifth (21.03%) of all participants rated their pain as severe. Eight (33.3%) of the participants had neuropathic pain while 11 (45.8%) had both nociceptive and neuropathic pain types. However, no association was found between sex, age, time post injury when tested against the presence of pain (p > 0.05). Weather changes aggravated almost every type of pain reported. Both pharmacological and non-pharmacological methods were used to manage the pain but their perceived effectiveness was rated as low. The majority of the traumatic spinal cord injured people experienced some pain and this pain was severe in a fifth of all participants. Pain significantly affected their quality of life. Physiotherapists and other medical professionals need to be aware of this and should employ pain reducing modalities and empathy when dealing with these patients.

An injectable,self-healing,electroconductive extracellular matrix-based hydrogel for enhancing tissue repair after traumatic spinal cord injury

Injectable biomaterial-based treatment is a promising strategy to enhance tissue repair after traumatic spinal cord injury(SCI)by bridging cavity spaces.However,there are limited reports of injectable,electroconductive hydrogels with self-healing properties being employed for the treatment of traumatic SCI.Hence,a natural extracellular matrix(ECM)biopolymer(chondroitin sulphate and gelatin)-based hydrogel containing polypyrrole,which imparted electroconductive properties,is developed for traumatic SCI repair.The resulting hydrogels showed mechanical(~928 Pa)and conductive properties(4.49 mS/cm)similar to natural spinal cord tissues.Moreover,the hydrogels exhibited shear-thinning and self-healing abilities,which allows it to be effectively injected into the injury site and to fill the lesion cavity to accelerate the tissue repair of traumatic SCI.In vitro,electroconductive ECM hydrogels promoted neuronal differentiation,enhanced axon outgrowth,and inhibited astrocyte differentiation.The electroconductive ECM hydrogel activated endogenous neural stem cell neurogenesis in vivo(n=6),and induced myelinated axon regeneration into the lesion site via activation of the PI3K/AKT and MEK/ERK pathways,thereby achieving significant locomotor function restoration in rats with spinal cord injury(p<0.001,compared to SCI group).Overall,the injectable self-healing electroconductive ECM-based hydrogels developed in this study are ideal biomaterials for treatment of traumatic SCI.

Management of acute spinal cord injury:A summary of the evidence pertaining to the acute management,operative and non-operative management

Acute traumatic spinal cord injury is often a lifechanging and devastating event with considerable mortality and morbidity.Over half a million people suffer from traumatic spinal cord injury annually with the majority resulting from road traffic accidents or falls.The Individual,societal and economic costs are enormous.Initial recognition and treatment of acute traumatic spinal cord injury are crucial to limit secondary injury to the spinal cord and to provide patients with the best chance of some functional recovery.This article is an overview of the management of the acute traumatic spinal cord injury patient presenting to the emergency department.We review the initial assessment,criteria for imaging and clearing the spine,and evaluate the literature to determine the optimum timing of surgery and the role of non-surgical treatment in patients presenting with acute spinal cord injury.

Economic impact of traumatic spinal cord injuries in the United States

Individuals having sustained traumatic spinal cord injury(TSCI)in the United States are living longer as compared to historical trends,thanks to an ever-evolving understanding of the nature of this injury.Despite this,multiple barriers to care for TSCI patients remain including variations in government-issued veteran insurance,privatized insurance,and among uninsured individuals.The United States alone experiences 12,000 new TSCI cases every year,many of these are found to occur in a growing proportion of elderly individuals.It is crucial to understand both the short-term direct costs as wells as the long-term rehabilitation costs required by these TSCI patients.The lifetime financial burden for those having sustained a TSCI can be immense for patients,insurance companies,and hospital systems alike.Among those with TSCI,re-hospitalization rates are high,leading to increased healthcare resource utilization within this specific patient population.Costs can quickly balloon into hundreds of thousands of dollars and cause a profound financial burden for these patients.This review article seeks to communicate an understanding of the current financial landscape surrounding TSCI patients.The authors will also examine the costs of acute emergency room surgical care such as American spinal injury association grade,hospital length of stay,as well as the timing delay between injury and surgical decompression.Long-term costs associated with TSCI such as rehabilitation,care of secondary comorbidities,and post-injury employment prospects will be examined as well.These costs will be framed from the patient's perspective as well as from both the hospital and insurance company's perspectives.It is hoped a complete understanding as to what makes TSCI such a medically and financially burdensome injury will allow for improved healthcare resource utilization in this population.

The therapeutic potential of targeting exchange protein directly activated by cyclic adenosine 3',5'-monophosphate(Epac)for central nervous system trauma

Millions of people worldwide are affected by traumatic spinal cord injury,which usually results in permanent sensorimotor disability.Damage to the spinal cord leads to a series of detrimental events including ischaemia,haemorrhage and neuroinflammation,which over time result in further neural tissue loss.Eventually,at chronic stages of traumatic spinal cord injury,the formation of a glial scar,cystic cavitation and the presence of numerous inhibitory molecules act as physical and chemical barriers to axonal regrowth.This is further hindered by a lack of intrinsic regrowth ability of adult neurons in the central nervous system.The intracellular signalling molecule,cyclic adenosine 3′,5′-monophosphate(cAMP),is known to play many important roles in the central nervous system,and elevating its levels as shown to improve axonal regeneration outcomes following traumatic spinal cord injury in animal models.However,therapies directly targeting cAMP have not found their way into the clinic,as cAMP is ubiquitously present in all cell types and its manipulation may have additional deleterious effects.A downstream effector of cAMP,exchange protein directly activated by cAMP 2(Epac2),is mainly expressed in the adult central nervous system,and its activation has been shown to mediate the positive effects of cAMP on axonal guidance and regeneration.Recently,using ex vivo modelling of traumatic spinal cord injury,Epac2 activation was found to profoundly modulate the post-lesion environment,such as decreasing the activation of astrocytes and microglia.Pilot data with Epac2 activation also suggested functional improvement assessed by in vivo models of traumatic spinal cord injury.Therefore,targeting Epac2 in traumatic spinal cord injury could represent a novel strategy in traumatic spinal cord injury repair,and future work is needed to fully establish its therapeutic potential.