High-Dimensional Analysis Delineates Myeloid and Lymphoid Compartment Remodeling during Successful Immune-Checkpoint Cancer Therapy.

Although current immune-checkpoint therapy (ICT) mainly targets lymphoid cells, it is associated with a broader remodeling of the tumor micro-environment. Here, using complementary forms of high-dimensional profiling, we define differences across all hematopoietic cells from syngeneic mouse tumors during unrestrained tumor growth or effective ICT. Unbiased assessment of gene expression of tumor-infiltrating cells by single-cell RNA sequencing (scRNAseq) and longitudinal assessment of cellular protein expression by mass cytometry (CyTOF) revealed significant remodeling of both the lymphoid and myeloid intratumoral compartments. Surprisingly, we observed multiple subpopulations of monocytes/macrophages, distinguishable by the markers CD206, CX3CR1, CD1d, and iNOS, that change over time during ICT in a manner partially dependent on IFNγ. Our data support the hypothesis that this macrophage polarization/activation results from effects on circulatory monocytes and early macrophages entering tumors, rather than on pre-polarized mature intratumoral macrophages.

A Subset of Type I Conventional Dendritic Cells Controls Cutaneous Bacterial Infections through VEGFα-Mediated Recruitment of Neutrophils.

Skin conventional dendritic cells (cDCs) exist as two distinct subsets, cDC1s and cDC2s, which maintain the balance of immunity to pathogens and tolerance to self and microbiota. Here, we examined the roles of dermal cDC1s and cDC2s during bacterial infection, notably Propionibacterium acnes (P. acnes). cDC1s, but not cDC2s, regulated the magnitude of the immune response to P. acnes in the murine dermis by controlling neutrophil recruitment to the inflamed site and survival and function therein. Single-cell mRNA sequencing revealed that this regulation relied on secretion of the cytokine vascular endothelial growth factor α (VEGF-α) by a minor subset of activated EpCAM+CD59+Ly-6D+ cDC1s. Neutrophil recruitment by dermal cDC1s was also observed during S. aureus, bacillus Calmette-Guérin (BCG), or E. coli infection, as well as in a model of bacterial insult in human skin. Thus, skin cDC1s are essential regulators of the innate response in cutaneous immunity and have roles beyond classical antigen presentation.

Human Innate Lymphoid Cell Subsets Possess Tissue-Type Based Heterogeneity in Phenotype and Frequency.

Animal models have highlighted the importance of innate lymphoid cells (ILCs) in multiple immune responses. However, technical limitations have hampered adequate characterization of ILCs in humans. Here, we used mass cytometry including a broad range of surface markers and transcription factors to accurately identify and profile ILCs across healthy and inflamed tissue types. High dimensional analysis allowed for clear phenotypic delineation of ILC2 and ILC3 subsets. We were not able to detect ILC1 cells in any of the tissues assessed, however, we identified intra-epithelial (ie)ILC1-like cells that represent a broader category of NK cells in mucosal and non-mucosal pathological tissues. In addition, we have revealed the expression of phenotypic molecules that have not been previously described for ILCs. Our analysis shows that human ILCs are highly heterogeneous cell types between individuals and tissues. It also provides a global, comprehensive, and detailed description of ILC heterogeneity in humans across patients and tissues.

Radiotherapy concepts for spinal metastases-results from an online survey among radiation oncologists of the German Society for Radiation Oncology.

PURPOSE: Spinal metastases (SM) are a common radiotherapy (RT) indication. There is limited level I data to drive decision making regarding dose regimen (DR) and target volume definition (TVD). We aim to depict the patterns of care for RT of SM among German Society for Radiation Oncology (DEGRO) members. METHODS: An online survey on conventional RT and Stereotactic Body Radiation Therapy (SBRT) for SM, distributed via e­mail to all DEGRO members, was completed by 80 radiation oncologists between February 24 and April 29, 2022. Participation was voluntary and anonymous. RESULTS: A variety of DR was frequently used for conventional RT (primary: n = 15, adjuvant: n = 14). 30 Gy/10 fractions was reported most frequently. TVD in adjuvant RT was heterogenous, with a trend towards larger volumes. SBRT was offered in 65% (primary) and 21% (adjuvant) of participants' institutions. A variety of DR was reported (primary: n = 40, adjuvant: n = 27), most commonly 27 Gy/3 fractions and 30 Gy/5 fractions. 59% followed International Consensus Guidelines (ICG) for TVD. CONCLUSION: We provide a representative depiction of RT practice for SM among DEGRO members. DR and TVD are heterogeneous. SBRT is not comprehensively practiced, especially in the adjuvant setting. Further research is needed to provide a solid data basis for detailed recommendations.

Quantifying neurodegeneration of the cervical cord and brain in degenerative cervical myelopathy: A multicentre study using quantitative magnetic resonance imaging.

BACKGROUND AND PURPOSE: Simultaneous assessment of neurodegeneration in both the cervical cord and brain across multiple centres can enhance the effectiveness of clinical trials. Thus, this study aims to simultaneously assess microstructural changes in the cervical cord and brain above the stenosis in degenerative cervical myelopathy (DCM) using quantitative magnetic resonance imaging (MRI) in a multicentre study. METHODS: We applied voxelwise analysis with a probabilistic brain/spinal cord template embedded in statistical parametric mappin (SPM-BSC) to process multi parametric mapping (MPM) including effective transverse relaxation rate (R2*), longitudinal relaxation rate (R1), and magnetization transfer (MT), which are indirectly sensitive to iron and myelin content. Regression analysis was conducted to establish associations between neurodegeneration and clinical impairment. Thirty-eight DCM patients (mean age ± SD = 58.45 ± 11.47 years) and 38 healthy controls (mean age ± SD = 41.18 ± 12.75 years) were recruited at University Hospital Balgrist, Switzerland and Toronto Western Hospital, Canada. RESULTS: Remote atrophy was observed in the cervical cord (p = 0.002) and in the left thalamus (0.026) of the DCM group. R1 was decreased in the periaqueductal grey matter (p = 0.014), thalamus (p = 0.001), corpus callosum (p = 0.0001), and cranial corticospinal tract (p = 0.03). R2* was increased in the primary somatosensory cortices (p = 0.008). Sensory impairments were associated with increased iron-sensitive R2* in the thalamus and periaqueductal grey matter in DCM. CONCLUSIONS: Simultaneous assessment of the spinal cord and brain revealed DCM-induced demyelination, iron deposition, and atrophy. The extent of remote neurodegeneration was associated with sensory impairment, highlighting the intricate and expansive nature of microstructural neurodegeneration in DCM, reaching beyond the stenosis level.

The spinal cord injury-induced immune deficiency syndrome: results of the SCIentinel study.

Infections are prevalent after spinal cord injury (SCI), constitute the main cause of death and are a rehabilitation confounder associated with impaired recovery. We hypothesize that SCI causes an acquired lesion-dependent (neurogenic) immune suppression as an underlying mechanism to facilitate infections. The international prospective multicentre cohort study (SCIentinel; protocol registration DRKS00000122; n = 111 patients) was designed to distinguish neurogenic from general trauma-related effects on the immune system. Therefore, SCI patient groups differing by neurological level, i.e. high SCI [thoracic (Th)4 or higher]; low SCI (Th5 or lower) and severity (complete SCI; incomplete SCI), were compared with a reference group of vertebral fracture (VF) patients without SCI. The primary outcome was quantitative monocytic Human Leukocyte Antigen-DR expression (mHLA-DR, synonym MHC II), a validated marker for immune suppression in critically ill patients associated with infection susceptibility. mHLA-DR was assessed from Day 1 to 10 weeks after injury by applying standardized flow cytometry procedures. Secondary outcomes were leucocyte subpopulation counts, serum immunoglobulin levels and clinically defined infections. Linear mixed models with multiple imputation were applied to evaluate group differences of logarithmic-transformed parameters. Mean quantitative mHLA-DR [ln (antibodies/cell)] levels at the primary end point 84 h after injury indicated an immune suppressive state below the normative values of 9.62 in all groups, which further differed in its dimension by neurological level: high SCI [8.95 (98.3% confidence interval, CI: 8.63; 9.26), n = 41], low SCI [9.05 (98.3% CI: 8.73; 9.36), n = 29], and VF without SCI [9.25 (98.3% CI: 8.97; 9.53), n = 41, P = 0.003]. Post hoc analysis accounting for SCI severity revealed the strongest mHLA-DR decrease [8.79 (95% CI: 8.50; 9.08)] in the complete, high SCI group, further demonstrating delayed mHLA-DR recovery [9.08 (95% CI: 8.82; 9.38)] and showing a difference from the VF controls of -0.43 (95% CI: -0.66; -0.20) at 14 days. Complete, high SCI patients also revealed constantly lower serum immunoglobulin G [-0.27 (95% CI: -0.45; -0.10)] and immunoglobulin A [-0.25 (95% CI: -0.49; -0.01)] levels [ln (g/l × 1000)] up to 10 weeks after injury. Low mHLA-DR levels in the range of borderline immunoparalysis (below 9.21) were positively associated with the occurrence and earlier onset of infections, which is consistent with results from studies on stroke or major surgery. Spinal cord injured patients can acquire a secondary, neurogenic immune deficiency syndrome characterized by reduced mHLA-DR expression and relative hypogammaglobulinaemia (combined cellular and humoral immune deficiency). mHLA-DR expression provides a basis to stratify infection-risk in patients with SCI.

Cervical excitatory neurons sustain breathing after spinal cord injury.

Dysfunctional breathing is the main cause of morbidity and mortality after traumatic injury of the cervical spinal cord1,2 and often necessitates assisted ventilation, thus stressing the need to develop strategies to restore breathing. Cervical interneurons that form synapses on phrenic motor neurons, which control the main inspiratory muscle, can modulate phrenic motor output and diaphragmatic function3-5. Here, using a combination of pharmacogenetics and respiratory physiology assays in different models of spinal cord injury, we show that mid-cervical excitatory interneurons are essential for the maintenance of breathing in mice with non-traumatic cervical spinal cord injury, and are also crucial for promoting respiratory recovery after traumatic spinal cord injury. Although these interneurons are not necessary for breathing under normal conditions, their stimulation in non-injured animals enhances inspiratory amplitude. Immediately after spinal cord injury, pharmacogenetic stimulation of cervical excitatory interneurons restores respiratory motor function. Overall, our results demonstrate a strategy to restore breathing after central nervous system trauma by targeting a neuronal subpopulation.

Bystander CD8+ T cells are abundant and phenotypically distinct in human tumour infiltrates.

Various forms of immunotherapy, such as checkpoint blockade immunotherapy, are proving to be effective at restoring T cell-mediated immune responses that can lead to marked and sustained clinical responses, but only in some patients and cancer types1-4. Patients and tumours may respond unpredictably to immunotherapy partly owing to heterogeneity of the immune composition and phenotypic profiles of tumour-infiltrating lymphocytes (TILs) within individual tumours and between patients5,6. Although there is evidence that tumour-mutation-derived neoantigen-specific T cells play a role in tumour control2,4,7-10, in most cases the antigen specificities of phenotypically diverse tumour-infiltrating T cells are largely unknown. Here we show that human lung and colorectal cancer CD8+ TILs can not only be specific for tumour antigens (for example, neoantigens), but also recognize a wide range of epitopes unrelated to cancer (such as those from Epstein-Barr virus, human cytomegalovirus or influenza virus). We found that these bystander CD8+ TILs have diverse phenotypes that overlap with tumour-specific cells, but lack CD39 expression. In colorectal and lung tumours, the absence of CD39 in CD8+ TILs defines populations that lack hallmarks of chronic antigen stimulation at the tumour site, supporting their classification as bystanders. Expression of CD39 varied markedly between patients, with some patients having predominantly CD39- CD8+ TILs. Furthermore, frequencies of CD39 expression among CD8+ TILs correlated with several important clinical parameters, such as the mutation status of lung tumour epidermal growth factor receptors. Our results demonstrate that not all tumour-infiltrating T cells are specific for tumour antigens, and suggest that measuring CD39 expression could be a straightforward way to quantify or isolate bystander T cells.

Risk stratification for early postoperative infection in Pediatric spinal deformity correction: development and validation of the Pediatric scoliosis infection risk score (PSIR score).

BACKGROUND CONTEXT: Postoperative infection after spinal deformity correction in pediatric patients is associated with significant costs. Identifying risk factors associated with postoperative infection would help surgeons identify high-risk patients that may require interventions to minimize infection risk. PURPOSE: To investigate risk factors associated with 30-day postoperative infection in pediatric patients who have received posterior arthrodesis for spinal deformity correction. STUDY DESIGN/SETTING: Retrospective review of prospectively collected data. PATIENT SAMPLE: The National Surgical Quality Improvement Program Pediatric database for years 2016-2021 was used for this study. Patients were included if they received posterior arthrodesis for scoliosis or kyphosis correction (CPT 22,800, 22,802, 22,804). Anterior only approaches were excluded. OUTCOME MEASURES: TThe outcome of interest was 30-day postoperative infection. METHODS: Patient demographics and outcomes were analyzed using descriptive statistics. Multivariable logistic regression analysis using likelihood ratio backward selection method was used to identify significant risk factors for 30-day infection to create the Pediatric Scoliosis Infection Risk Score (PSIR Score). ROC curve analysis, predicted probabilities, and Hosmer Lemeshow goodness-of-fit test were done to assess the scoring system on a validation cohort. RESULTS: A total of 31,742 patients were included in the study. The mean age was 13.8 years and 68.7% were female. The 30-day infection rate was 2.2%. Reoperation rate in patients who had a post-operative infection was 59.4%. Patients who had post-operative infection had a higher likelihood of non-home discharge (X2 = 124.8, p < 0.001). In our multivariable regression analysis, high BMI (OR = 1.01, p < 0.001), presence of open wound (OR = 3.18, p < 0.001), presence of ostomy (OR = 1.51, p < 0.001), neuromuscular etiology (OR = 1.56, p = 0.009), previous operation (OR = 1.74, p < 0.001), increasing ASA class (OR = 1.43, p < 0.001), increasing operation time in hours (OR = 1.11, p < 0.001), and use of only minimally invasive techniques (OR = 4.26, p < 0.001) were associated with increased risk of 30-day post-operative infection. Idiopathic etiology (OR = 0.53, p < 0.001) and intraoperative topical antibiotic use (B = 0.71, p = 0.003) were associated with reduced risk of 30-day postoperative infection. The area under the curve was 0.780 and 0.740 for the derivation cohort and validation cohort, respectively. CONCLUSIONS: To our knowledge, this is the largest study of risk factors for infection in pediatric spinal deformity surgery. We found 5 patient factors (BMI, ASA, osteotomy, etiology, and previous surgery, and 3 surgeon-controlled factors (surgical time, antibiotics, MIS) associated with risk. The Pediatric Scoliosis Infection Risk Score (PSIR) Score can be applied for risk stratification and to investigate implementation of novel protocols to reduce infection rates in high-risk patients.

Cervical kyphosis after posterior cervical laminectomy with and without fusion.

BACKGROUND: Cervical posterior instrumentation and fusion is often performed to avoid post-laminectomy kyphosis. However, larger comparative analyses of cervical laminectomy with or without fusion are sparse. METHODS: A retrospective, two-center, comparative cohort study included patients after stand-alone dorsal laminectomy with (n = 91) or without (n = 46) additional fusion for degenerative cervical myelopathy with a median follow-up of 59 (interquartile range (IQR) 52) months. The primary outcome was the C2-7 Cobb angle and secondary outcomes were Neck Disability Index (NDI), modified Japanese Orthopaedic Association (mJOA) scale, revision rates, T1 slope and C2-7 sagittal vertical axis (C2-7 SVA) at final follow-up. Logistic regression analysis adjusted for potential confounders (i.e. age, operated levels, and follow-up). RESULTS: Preoperative C2-7 Cobb angle and T1 slope were higher in the laminectomy group, while the C2-7 SVA was similar. The decrease in C2-7 Cobb angle from pre- to postoperatively was more pronounced in the laminectomy group (- 6° (IQR 20) versus -1° (IQR 7), p = 0.002). When adjusting for confounders, the decrease in C2-7 Cobb angle remained higher in the laminectomy group (coefficient - 12 (95% confidence interval (CI) -18 to -5), p = 0.001). However, there were no adjusted differences for postoperative NDI (- 11 (- 23 to 2), p = 0.10), mJOA, revision rates, T1 slope and C2-7 SVA. CONCLUSION: Posterior cervical laminectomy without fusion is associated with mild loss of cervical lordosis of around 6° in the mid-term after approximately five years, however without any clinical relevance regarding NDI or mJOA in well-selected patients (particularly in shorter segment laminectomies of < 3 levels).

Translational Relevance of Secondary Intracellular Signaling Cascades Following Traumatic Spinal Cord Injury.

Traumatic spinal cord injury (SCI) is a life-threatening and life-altering condition that results in debilitating sensorimotor and autonomic impairments. Despite significant advances in the clinical management of traumatic SCI, many patients continue to suffer due to a lack of effective therapies. The initial mechanical injury to the spinal cord results in a series of secondary molecular processes and intracellular signaling cascades in immune, vascular, glial, and neuronal cell populations, which further damage the injured spinal cord. These intracellular cascades present promising translationally relevant targets for therapeutic intervention due to their high ubiquity and conservation across eukaryotic evolution. To date, many therapeutics have shown either direct or indirect involvement of these pathways in improving recovery after SCI. However, the complex, multifaceted, and heterogeneous nature of traumatic SCI requires better elucidation of the underlying secondary intracellular signaling cascades to minimize off-target effects and maximize effectiveness. Recent advances in transcriptional and molecular neuroscience provide a closer characterization of these pathways in the injured spinal cord. This narrative review article aims to survey the MAPK, PI3K-AKT-mTOR, Rho-ROCK, NF-κB, and JAK-STAT signaling cascades, in addition to providing a comprehensive overview of the involvement and therapeutic potential of these secondary intracellular pathways following traumatic SCI.

Lived experience-centred word clouds may improve research uncertainty gathering in priority setting partnerships.

INTRODUCTION: AO Spine RECODE-DCM was a multi-stakeholder priority setting partnership (PSP) to define the top ten research priorities for degenerative cervical myelopathy (DCM). Priorities were generated and iteratively refined using a series of surveys administered to surgeons, other healthcare professionals (oHCP) and people with DCM (PwDCM). The aim of this work was to utilise word clouds to enable the perspectives of people with the condition to be heard earlier in the PSP process than is traditionally the case. The objective was to evaluate the added value of word clouds in the process of defining research uncertainties in National Institute for Health Research (NIHR) James Lind Alliance (JLA) Priority Setting Partnerships. METHODS: Patient-generated word clouds were created for the four survey subsections of the AO Spine RECODE-DCM PSP: diagnosis, treatment, long-term management and other issues. These were then evaluated as a nested methodological study. Word-clouds were created and iteratively refined by an online support group of people with DCM, before being curated by the RECODE-DCM management committee and expert healthcare professional representatives. The final word clouds were embedded within the surveys administered at random to 50% of participants. DCM research uncertainties suggested by participants were compared pre- and post-word cloud presentation. RESULTS: A total of 215 (50.9%) participants were randomised to the word cloud stream, including 118 (55%) spinal surgeons, 52 (24%) PwDCM and 45 (21%) oHCP. Participants submitted 434 additional uncertainties after word cloud review: word count was lower and more uniform across each survey subsections compared to pre-word cloud uncertainties. Twenty-three (32%) of the final 74 PSP summary questions did not have a post-word cloud contribution and no summary question was formed exclusively on post-word cloud uncertainties. There were differences in mapping of pre- and post-word cloud uncertainties to summary questions, with greater mapping of post-word cloud uncertainties to the number 1 research question priority: raising awareness. Five of the final summary questions were more likely to map to the research uncertainties suggested by participants after having reviewed the word clouds. CONCLUSIONS: Word clouds may increase the perspective of underrepresented stakeholders in the research question gathering stage of priority setting partnerships. This may help steer the process towards research questions that are of highest priority for people with the condition.

Using Clinical Vignettes and a Modified Expert Delphi Panel to Determine Parameters for Identifying Non-Traumatic Spinal Cord Injury in Health Administrative and Electronic Medical Record Databases.

OBJECTIVE: To obtain expert consensus on the parameters and etiologic conditions required to retrospectively identify cases of non-traumatic spinal cord injury (NTSCI) in health administrative and electronic medical record (EMR) databases based on the rating of clinical vignettes. DESIGN: A modified Delphi process included 2 survey rounds and 1 remote consensus panel. The surveys required the rating of clinical vignettes, developed after chart reviews and expert consultation. Experts who participated in survey rounds were invited to participate in the Delphi Consensus Panel. SETTING: An international collaboration using an online meeting platform. PARTICIPANTS: Thirty-one expert physicians and/or clinical researchers in the field of spinal cord injury (SCI). MAIN OUTCOME MEASURE(S): Agreement on clinical vignettes as NTSCI. Parameters to classify cases of NTSCI in health administrative and EMR databases. RESULTS: In health administrative and EMR databases, cauda equina syndromes should be considered SCI and classified as a NTSCI or TSCI based on the mechanism of injury. A traumatic event needs to be listed for injury to be considered TSCI. To be classified as NTSCI, neurologic sufficient impairments (motor, sensory, bowel, and bladder) are required, in addition to an etiology. It is possible to have both a NTSCI and a TSCI, as well as a recovered NTSCI. If information is unavailable or missing in health administrative and EMR databases, the case may be listed as "unclassifiable" depending on the purpose of the research study. CONCLUSION: The Delphi panel provided guidelines to appropriately classify cases of NTSCI in health administrative and EMR databases.

Hospital spending and length of stay attributable to perioperative adverse events for inpatient hip, knee, and spine surgery: a retrospective cohort study.

BACKGROUND: The incremental hospital cost and length of stay (LOS) associated with adverse events (AEs) has not been well characterized for planned and unplanned inpatient spine, hip, and knee surgeries. METHODS: Retrospective cohort study of hip, knee, and spine surgeries at an academic hospital in 2011-2012. Adverse events were prospectively collected for 3,063 inpatient cases using the Orthopaedic Surgical AdVerse Event Severity (OrthoSAVES) reporting tool. Case costs were retrospectively obtained and inflated to equivalent 2021 CAD values. Propensity score methodology was used to assess the cost and LOS attributable to AEs, controlling for a variety of patient and procedure factors. RESULTS: The sample was 55% female and average age was 64; 79% of admissions were planned. 30% of cases had one or more AEs (82% had low-severity AEs at worst). The incremental cost and LOS attributable to AEs were $8,500 (95% confidence interval [CI]: 5100-11,800) and 4.7 days (95% CI: 3.4-5.9) per admission. This corresponded to a cumulative $7.8 M (14% of total cohort cost) and 4,290 bed-days (19% of cohort bed-days) attributable to AEs. Incremental estimates varied substantially by (1) admission type (planned: $4,700/2.4 days; unplanned: $20,700/11.5 days), (2) AE severity (low: $4,000/3.1 days; high: $29,500/11.9 days), and (3) anatomical region (spine: $19,800/9 days; hip: $4,900/3.8 days; knee: $1,900/1.5 days). Despite only 21% of admissions being unplanned, adverse events in these admissions cumulatively accounted for 59% of costs and 62% of bed-days attributable to AEs. CONCLUSIONS: This study comprehensively demonstrates the considerable cost and LOS attributable to AEs in orthopaedic and spine admissions. In particular, the incremental cost and LOS attributable to AEs per admission were almost five times as high among unplanned admissions compared to planned admissions. Mitigation strategies focused on unplanned surgeries may result in significant quality improvement and cost savings in the healthcare system.

Spinal Meningiomas.

Spinal meningiomas are relatively rare, but account for a significant proportion of primary spinal tumors in adults. These meningiomas can be found anywhere along the spinal column and their diagnosis is often delayed due to their slow growth and the lack of significant neurological symptoms until they reach a critical size, at which point signs of spinal cord or nerve root compression generally manifest and progress. If left untreated, spinal meningiomas can cause severe neurological deficits including rendering patients paraplegic or tetraplegic. In this chapter we will review the clinical features of spinal meningiomas, their surgical management, and detail molecular features that differentiate them from intracranial meningiomas.

Early surgical intervention for acute spinal cord injury: time is spine.

Acute traumatic spinal cord injury (tSCI) is a devastating occurrence that significantly contributes to global morbidity and mortality. Surgical decompression with stabilization is the most effective way to minimize the damaging sequelae that follow acute tSCI. In recent years, strong evidence has emerged that supports the rationale that early surgical intervention, within 24 h following the initial injury, is associated with a better prognosis and functional outcomes. In this review, we have summarized the evidence and elaborated on the nuances of this concept. Additionally, we have reviewed further concepts that stem from "time is spine," including earlier cutoffs less than 24 h and the challenging entity of central cord syndrome, as well as the emerging concept of adequate surgical decompression. Lastly, we identify barriers to early surgical care for acute tSCI, a key aspect of spine care that needs to be globally addressed via research and policy on an urgent basis.

Degenerative cervical myelopathy: Where have we been? Where are we now? Where are we going?

Degenerative cervical myelopathy (DCM), a recently coined term, encompasses a group of age-related and genetically associated pathologies that affect the cervical spine, including cervical spondylotic myelopathy and ossification of the posterior longitudinal ligament (OPLL). Given the significant contribution of DCM to global disease and disability, there are worldwide efforts to promote research and innovation in this area. An AO Spine effort termed 'RECODE-DCM' was initiated to create an international multistakeholder consensus group, involving patients, caregivers, physicians and researchers, to focus on launching actionable discourse on DCM. In order to improve the management, treatment and results for DCM, the RECODE-DCM consensus group recently identified ten priority areas for translational research. The current article summarizes recent advancements in the field of DCM. We first discuss the comprehensive definition recently refined by the RECODE-DCM group, including steps taken to arrive at this definition and the supporting rationale. We then provide an overview of the recent advancements in our understanding of the pathophysiology of DCM and modalities to clinically assess and diagnose DCM. A focus will be set on advanced imaging techniques that may offer the opportunity to improve characterization and diagnosis of DCM. A summary of treatment modalities, including surgical and nonoperative options, is then provided along with future neuroprotective and neuroregenerative strategies. This review concludes with final remarks pertaining to the genetics involved in DCM and the opportunity to leverage this knowledge toward a personalized medicine approach.

In-hospital mortality rate in subaxial cervical spinal cord injury patients: a systematic review and meta-analysis.

PURPOSE: To determine existing trends concerning in-hospital mortality in patients with traumatic subaxial cervical spinal cord injury (SCI) over the last four decades. METHODS: We searched MEDLINE and EMBASE to assess the role of the following factors on in-hospital mortality over the last four decades: neurological deficit, age, surgical decompression, use of computed tomography (CT) and magnetic resonance imaging (MRI), use of methylprednisolone in the acute post-injury period, and study location (developing versus developed countries). RESULTS: Among 3333 papers after deduplication, 21 studies met the eligibility criteria. The mortality rate was 17.88% [95% confidence interval (CI): 12.9-22.87%]. No significant trend in mortality rate was observed over the 42-year period (meta-regression coefficient = 0.317; p = 0.372). Subgroup analysis revealed no significant association between acute subaxial cervical SCI-related mortality when stratified by use of surgery, administration of methylprednisolone, use of MRI and CT imaging, study design (prospective versus retrospective study), and study location. The mortality rate was significantly higher in complete SCI (20.66%, p = 0.002) and American Spinal Injury Association impairment scale (AIS) A (20.57%) and B (9.28%) (p = 0.028). CONCLUSION: A very low level of evidence showed that in-hospital mortality in patients with traumatic subaxial cervical SCI did not decrease over the last four decades despite diagnostic and therapeutic advancements. The overall acute mortality rate following subaxial cervical SCI is 17.88%. We recommend reporting a stratified mortality rate according to key factors such as treatment paradigms, age, and severity of injury in future studies.

Adopting and adapting clinical practice guidelines for timing of decompressive surgery in acute spinal cord injury from a developed world context to a developing region.

PURPOSE: The proper application of high-quality clinical practice guidelines improves trauma patients' care and outcomes. This study aimed to adopt and adapt guidelines on the timing of decompressive surgery in acute spinal cord injury (SCI) in Iranian clinical settings. METHODS: This study followed a systematic search and review of the literature to enter them into the selection process. The source guidelines' clinical suggestions were converted into clinical scenarios for clinical questions on the timing of decompressive surgery. After summarizing the scenarios, we prepared an initial list of recommendations based on the status of the Iranian patients and the health system. The ultimate conclusion was reached with the help of a national interdisciplinary expert panel comprising 20 experts throughout the country. RESULTS: A total of 408 records were identified. After title and abstract screening, 401 records were excluded, and the full texts of the remaining seven records were reviewed. Based on our screening process, only one guideline included recommendations on the topic of interest. All of the recommendations were accepted by the expert panel with slight changes due to resource availability in Iran. The final two recommendations were the consideration of early surgery (≤24 h) as a treatment option in adult patients with traumatic central cord syndrome and in adult patients with acute SCI regardless of the level of injury. CONCLUSION: Considering early surgery for adult patients with acute traumatic SCI regardless of the level of injury was the final recommendation for Iran. Although most of the recommendations are adoptable in developing countries, issues with infrastructure and availability of resources are the limitations.