A Clinical Practice Guideline on the Timing of Surgical Decompression and Hemodynamic Management of Acute Spinal Cord Injury and the Prevention, Diagnosis, and Management of Intraoperative Spinal Cord Injury: Introduction, Rationale, and Scope.

STUDY DESIGN: Protocol for the development of clinical practice guidelines following the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) standards. OBJECTIVES: Acute SCI or intraoperative SCI (ISCI) can have devastating physical and psychological consequences for patients and their families. The treatment of SCI has dramatically evolved over the last century as a result of preclinical and clinical research that has addressed important knowledge gaps, including injury mechanisms, disease pathophysiology, medical management, and the role of surgery. In an acute setting, clinicians are faced with critical decisions on how to optimize neurological recovery in patients with SCI that include the role and timing of surgical decompression and the best strategies for hemodynamic management. The lack of consensus surrounding these treatments has prevented standardization of care across centers and has created uncertainty with respect to how to best manage patients with SCI. ISCI is a feared complication that can occur in the best of hands. Unfortunately, there are no systematic reviews or clinical practice guidelines to assist spine surgeons in the assessment and management of ISCI in adult patients undergoing spinal surgery. Given these limitations, it is the objective of this initiative to develop evidence-based recommendations that will inform the management of both SCI and ISCI. This protocol describes the rationale for developing clinical practice guidelines on (i) the timing of surgical decompression in acute SCI; (ii) the hemodynamic management of acute SCI; and (iii) the prevention, identification, and management of ISCI in patients undergoing surgery for spine-related pathology. METHODS: Systematic reviews were conducted according to PRISMA standards in order to summarize the current body of evidence and inform the guideline development process. The guideline development process followed the approach proposed by the GRADE working group. Separate multidisciplinary, international groups were created to perform the systematic reviews and formulate the guidelines. All potential conflicts of interest were vetted in advance. The sponsors exerted no influence over the editorial process or the development of the guidelines. RESULTS: This process resulted in both systematic reviews and clinical practice guidelines/care pathways related to the role and timing of surgery in acute SCI; the optimal hemodynamic management of acute SCI; and the prevention, diagnosis and management of ISCI. CONCLUSIONS: The ultimate goal of this clinical practice guideline initiative was to develop evidence-based recommendations for important areas of controversy in SCI and ISCI in hopes of improving neurological outcomes, reducing morbidity, and standardizing care across settings. Throughout this process, critical knowledge gaps and future directions were also defined.

Accuracy of Intraoperative Neuromonitoring in the Diagnosis of Intraoperative Neurological Decline in the Setting of Spinal Surgery-A Systematic Review and Meta-Analysis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVES: In an effort to prevent intraoperative neurological injury during spine surgery, the use of intraoperative neurophysiological monitoring (IONM) has increased significantly in recent years. Using IONM, spinal cord function can be evaluated intraoperatively by recording signals from specific nerve roots, motor tracts, and sensory tracts. We performed a systematic review and meta-analysis of diagnostic test accuracy (DTA) studies to evaluate the efficacy of IONM among patients undergoing spine surgery for any indication. METHODS: The current systematic review and meta-analysis was performed using the Preferred Reporting Items for a Systematic Review and Meta-analysis statement for Diagnostic Test Accuracy Studies (PRISMA-DTA) and was registered on PROSPERO. A comprehensive search was performed using MEDLINE, EMBASE and SCOPUS for all studies assessing the diagnostic accuracy of neuromonitoring, including somatosensory evoked potential (SSEP), motor evoked potential (MEP) and electromyography (EMG), either on their own or in combination (multimodal). Studies were included if they reported raw numbers for True Positives (TP), False Negatives (FN), False Positives (FP) and True Negative (TN) either in a 2 × 2 contingency table or in text, and if they used postoperative neurologic exam as a reference standard. Pooled sensitivity and specificity were calculated to evaluate the overall efficacy of each modality type using a bivariate model adapted by Reitsma et al, for all spine surgeries and for individual disease groups and regions of spine. The risk of bias (ROB) of included studies was assessed using the quality assessment tool for diagnostic accuracy studies (QUADAS-2). RESULTS: A total of 163 studies were included; 52 of these studies with 16,310 patients reported data for SSEP, 68 studies with 71,144 patients reported data for MEP, 16 studies with 7888 patients reported data for EMG and 69 studies with 17,968 patients reported data for multimodal monitoring. The overall sensitivity, specificity, DOR and AUC for SSEP were 71.4% (95% CI 54.8-83.7), 97.1% (95% CI 95.3-98.3), 41.9 (95% CI 24.1-73.1) and .899, respectively; for MEP, these were 90.2% (95% CI 86.2-93.1), 96% (95% CI 94.3-97.2), 103.25 (95% CI 69.98-152.34) and .927; for EMG, these were 48.3% (95% CI 31.4-65.6), 92.9% (95% CI 84.4-96.9), 11.2 (95% CI 4.84-25.97) and .773; for multimodal, these were found to be 83.5% (95% CI 81-85.7), 93.8% (95% CI 90.6-95.9), 60 (95% CI 35.6-101.3) and .895, respectively. Using the QUADAS-2 ROB analysis, of the 52 studies reporting on SSEP, 13 (25%) were high-risk, 10 (19.2%) had some concerns and 29 (55.8%) were low-risk; for MEP, 8 (11.7%) were high-risk, 21 had some concerns and 39 (57.3%) were low-risk; for EMG, 4 (25%) were high-risk, 3 (18.75%) had some concerns and 9 (56.25%) were low-risk; for multimodal, 14 (20.3%) were high-risk, 13 (18.8%) had some concerns and 42 (60.7%) were low-risk. CONCLUSIONS: These results indicate that all neuromonitoring modalities have diagnostic utility in successfully detecting impending or incident intraoperative neurologic injuries among patients undergoing spine surgery for any condition, although it is clear that the accuracy of each modality differs.PROSPERO Registration Number: CRD42023384158.

An Update of a Clinical Practice Guideline for the Management of Patients With Acute Spinal Cord Injury: Recommendations on the Role and Timing of Decompressive Surgery.

STUDY DESIGN: Clinical practice guideline development. OBJECTIVES: Acute spinal cord injury (SCI) can result in devastating motor, sensory, and autonomic impairment; loss of independence; and reduced quality of life. Preclinical evidence suggests that early decompression of the spinal cord may help to limit secondary injury, reduce damage to the neural tissue, and improve functional outcomes. Emerging evidence indicates that "early" surgical decompression completed within 24 hours of injury also improves neurological recovery in patients with acute SCI. The objective of this clinical practice guideline (CPG) is to update the 2017 recommendations on the timing of surgical decompression and to evaluate the evidence with respect to ultra-early surgery (in particular, but not limited to, <12 hours after acute SCI). METHODS: A multidisciplinary, international, guideline development group (GDG) was formed that consisted of spine surgeons, neurologists, critical care specialists, emergency medicine doctors, physical medicine and rehabilitation professionals, as well as individuals living with SCI. A systematic review was conducted based on accepted methodological standards to evaluate the impact of early (within 24 hours of acute SCI) or ultra-early (in particular, but not limited to, within 12 hours of acute SCI) surgery on neurological recovery, functional outcomes, administrative outcomes, safety, and cost-effectiveness. The GRADE approach was used to rate the overall strength of evidence across studies for each primary outcome. Using the "evidence-to-recommendation" framework, recommendations were then developed that considered the balance of benefits and harms, financial impact, patient values, acceptability, and feasibility. The guideline was internally appraised using the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool. RESULTS: The GDG recommended that early surgery (≤24 hours after injury) be offered as the preferred option for adult patients with acute SCI regardless of level. This recommendation was based on moderate evidence suggesting that patients were 2 times more likely to recover by ≥ 2 ASIA Impairment Score (AIS) grades at 6 months (RR: 2.76, 95% CI 1.60 to 4.98) and 12 months (RR: 1.95, 95% CI 1.26 to 3.18) if they were decompressed within 24 hours compared to after 24 hours. Furthermore, patients undergoing early surgery improved by an additional 4.50 (95% 1.70 to 7.29) points on the ASIA Motor Score compared to patients undergoing surgery after 24 hours post-injury. The GDG also agreed that a recommendation for ultra-early surgery could not be made on the basis of the current evidence because of the small sample sizes, variable definitions of what constituted ultra-early in the literature, and the inconsistency of the evidence. CONCLUSIONS: It is recommended that patients with an acute SCI, regardless of level, undergo surgery within 24 hours after injury when medically feasible. Future research is required to determine the differential effectiveness of early surgery in different subpopulations and the impact of ultra-early surgery on neurological recovery. Moreover, further work is required to define what constitutes effective spinal cord decompression and to individualize care. It is also recognized that a concerted international effort will be required to translate these recommendations into policy.

Definition, Frequency and Risk Factors for Intra-Operative Spinal Cord Injury: A Knowledge Synthesis.

STUDY DESIGN: Mixed-methods approach. OBJECTIVES: Intra-operative spinal cord injury (ISCI) is a devastating complication of spinal surgery. Presently, a uniform definition for ISCI does not exist. Consequently, the reported frequency of ISCI and important risk factors vary in the existing literature. To address these gaps in knowledge, a mixed-methods knowledge synthesis was undertaken. METHODS: A scoping review was conducted to review the definitions used for ISCI and to ascertain the frequency of ISCI. The definition of ISCI underwent formal review, revision and voting by the Guidelines Development Group (GDG). A systematic review of the literature was conducted to determine the risk factors for ISCI. Based on this systematic review and GDG input, a table was created to summarize the factors deemed to increase the risk for ISCI. All reviews were done according to PRISMA standards and were registered on PROSPERO. RESULTS: The frequency of ISCI ranged from 0 to 61%. Older age, male sex, cardiovascular disease including hypertension, severe myelopathy, blood loss, requirement for osteotomy, coronal deformity angular ratio, and curve magnitude were associated with an increased risk of ISCI. Better pre-operative neurological status and use of intra-operative neuromonitoring (IONM) were associated with a decreased risk of ISCI. The risk factors for ISCI included a rigid thoracic curve with high deformity angular ratio, revision congenital deformity with significant cord compression and myelopathy, extrinsic intradural or extradural lesions with cord compression and myelopathy, intramedullary spinal cord tumor, unstable spine fractures (bilateral facet dislocation and disc herniation), extension distraction injury with ankylosing spondylitis, ossification of posterior longitudinal ligament (OPLL) with severe cord compression, and moderate to severe myelopathy. CONCLUSIONS: ISCI has been defined as "a new or worsening neurological deficit attributable to spinal cord dysfunction during spine surgery that is diagnosed intra-operatively via neurophysiologic monitoring or by an intraoperative wake-up test, or immediately post-operatively based on clinical assessment". This paper defines clinical and imaging factors which increase the risk for ISCI and that could assist clinicians in decision making.

A Clinical Practice Guideline for Prevention, Diagnosis and Management of Intraoperative Spinal Cord Injury: Recommendations for Use of Intraoperative Neuromonitoring and for the Use of Preoperative and Intraoperative Protocols for Patients Undergoing Spine Surgery.

STUDY DESIGN: Development of a clinical practice guideline following the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) process. OBJECTIVE: The objectives of this study were to develop guidelines that outline the utility of intraoperative neuromonitoring (IONM) to detect intraoperative spinal cord injury (ISCI) among patients undergoing spine surgery, to define a subset of patients undergoing spine surgery at higher risk for ISCI and to develop protocols to prevent, diagnose, and manage ISCI. METHODS: All systematic reviews were performed according to PRISMA standards and registered on PROSPERO. A multidisciplinary, international Guidelines Development Group (GDG) reviewed and discussed the evidence using GRADE protocols. Consensus was defined by 80% agreement among GDG members. A systematic review and diagnostic test accuracy (DTA) meta-analysis was performed to synthesize pooled evidence on the diagnostic accuracy of IONM to detect ISCI among patients undergoing spinal surgery. The IONM modalities evaluated included somatosensory evoked potentials (SSEPs), motor evoked potentials (MEPs), electromyography (EMG), and multimodal neuromonitoring. Utilizing this knowledge and their clinical experience, the multidisciplinary GDG created recommendations for the use of IONM to identify ISCI in patients undergoing spine surgery. The evidence related to existing care pathways to manage ISCI was summarized and based on this a novel AO Spine-PRAXIS care pathway was created. RESULTS: Our recommendations are as follows: (1) We recommend that intraoperative neurophysiological monitoring be employed for high risk patients undergoing spine surgery, and (2) We suggest that patients at "high risk" for ISCI during spine surgery be proactively identified, that after identification of such patients, multi-disciplinary team discussions be undertaken to manage patients, and that an intraoperative protocol including the use of IONM be implemented. A care pathway for the prevention, diagnosis, and management of ISCI has been developed by the GDG. CONCLUSION: We anticipate that these guidelines will promote the use of IONM to detect and manage ISCI, and promote the use of preoperative and intraoperative checklists by surgeons and other team members for high risk patients undergoing spine surgery. We welcome teams to implement and evaluate the care pathway created by our GDG.

Interventions to Optimize Spinal Cord Perfusion in Patients With Acute Traumatic Spinal Cord Injury: An Updated Systematic Review.

STUDY DESIGN: Systematic review update. OBJECTIVES: Interventions that aim to optimize spinal cord perfusion are thought to play an important role in minimizing secondary ischemic damage and improving outcomes in patients with acute traumatic spinal cord injuries (SCIs). However, exactly how to optimize spinal cord perfusion and enhance neurologic recovery remains controversial. We performed an update of a recent systematic review (Evaniew et al, J. Neurotrauma 2020) to evaluate the effects of Mean Arterial Pressure (MAP) support or Spinal Cord Perfusion Pressure (SCPP) support on neurological recovery and rates of adverse events among patients with acute traumatic SCI. METHODS: We searched PubMed/MEDLINE, EMBASE and ClinicalTrials.gov for new published reports. Two reviewers independently screened articles, extracted data, and evaluated risk of bias. We implemented the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach to rate confidence in the quality of the evidence. RESULTS: From 569 potentially relevant new citations since 2019, we identified 9 new studies for inclusion, which were combined with 19 studies from a prior review to give a total of 28 studies. According to low or very low quality evidence, the effect of MAP support on neurological recovery is uncertain, and increased SCPP may be associated with improved neurological recovery. Both approaches may involve risks for specific adverse events, but the importance of these adverse events to patients remains unclear. Very low quality evidence failed to yield reliable guidance about particular monitoring techniques, perfusion ranges, pharmacological agents, or durations of treatment. CONCLUSIONS: This update provides an evidence base to support the development of a new clinical practice guideline for the hemodynamic management of patients with acute traumatic SCI. While avoidance of hypotension and maintenance of spinal cord perfusion are important principles in the management of an acute SCI, the literature does not provide high quality evidence in support of a particular protocol. Further prospective, controlled research studies with objective validated outcome assessments are required to examine interventions to optimize spinal cord perfusion in this setting.

Prevention, Diagnosis, and Management of Intraoperative Spinal Cord Injury in the Setting of Spine Surgery: A Proposed Care Pathway.

STUDY DESIGN: This study is a mixed methods approach. OBJECTIVES: Intraoperative spinal cord injury (ISCI) is a challenging complication in spine surgery. Intra-operative neuromonitoring (IONM) has been developed to detect changes in neural function. We report on the first multidisciplinary, international effort through AO Spine and the Praxis Spinal Cord Institute to develop a comprehensive guideline and care pathway for the prevention, diagnosis, and management of ISCI. METHODS: Three literature reviews were registered on PROSPERO (CRD 42022298841) and performed according to PRISMA guidelines: (1) Definitions, frequency, and risk factors for ISCI, (2) Meta-analysis of the accuracy of IONM for diagnosis of ISCI, (3) Reported management approaches for ISCI and related events. The results were presented in a consensus session to decide the definition of IONM and recommendation of its use in high-risk cases. Based on a literature review of management strategies for ISCI, an intra-operative checklist and overall care pathway was developed by the study team. RESULTS: An operational definition and high-risk patient categories for ISCI were established. The reported incidence of deficits was documented to be higher in intramedullary tumour spine surgery. Multimodality IONM has a high sensitivity and specificity. A guideline recommendation of IONM to be employed for high-risk spine cases was made. The different sections of the intraoperative checklist include surgery, anaesthetic and neurophysiology. The care pathway includes steps (1) initial clinical assessment, (2) pre-operative planning, (3) surgical/anaesthetic planning, (4) intra-operative management, and (5) post-operative management. CONCLUSIONS: This is the first evidence based comprehensive guideline and care pathway for ISCI using the GRADE methodology. This will facilitate a reduction in the incidence of ISCI and improved outcomes from this complication. We welcome the wide implementation and validation of these guidelines and care pathways in prospective, multicentre studies.

The 2023 AO Spine-Praxis Guidelines in Acute Spinal Cord Injury: What Have We Learned? What Are the Critical Knowledge Gaps and Barriers to Implementation?

STUDY DESIGN: Narrative summary of the 2023 AO Spine-Praxis clinical practice guidelines for management in acute spinal cord injury (SCI). OBJECTIVES: The objective of this article is to summarize the key findings of the clinical practice guidelines for the optimal management of traumatic and intraoperative SCI (ISCI). This article will also highlight potential knowledge translation opportunities for each recommendation and discuss important knowledge gaps and areas of future research. METHODS: Systematic reviews were conducted according to accepted methodological standards to evaluate the current body of evidence and inform the guideline development process. The summarized evidence was reviewed by a multidisciplinary guidelines development group that consisted of international multidisciplinary stakeholders. The Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach was used to rate the certainty of the evidence for each critical outcome and the "evidence to recommendation" framework was used to formulate the final recommendations. RESULTS: The key recommendations regarding the timing of surgical decompression, hemodynamic management, and the prevention, diagnosis, and management of ISCI are summarized. While a strong recommendation was made for early surgery, further prospective research is required to define what constitutes sufficient surgical decompression, examine the role of ultra-early surgery, and assess the impact of early surgery in different SCI phenotypes, including central cord syndrome. Furthermore, additional investigation is required to evaluate the impact of mean arterial blood pressure targets on neurological recovery and to determine the utility of spinal cord perfusion pressure measurements. Finally, there is a need to examine the role of neuroprotective agents for the treatment of ISCI and to prospectively validate the new AO Spine-Praxis care pathway for the prevention, diagnosis, and management of ISCI. To optimize the translation of these guidelines into practice, important barriers to their implementation, particularly in underserved areas, need to be explored. Ultimately, these recommendations will help to establish more personalized approaches to care for SCI patients. CONCLUSIONS: The recommendations from the 2023 AO Spine-Praxis guidelines not only highlight the current best practice in the management of SCI, but reveal critical knowledge gaps and barriers to implementation that will help to guide further research efforts in SCI.

The Management of Intraoperative Spinal Cord Injury - A Scoping Review.

STUDY DESIGN: Scoping Review. OBJECTIVE: To review the literature and summarize information on checklists and algorithms for responding to intraoperative neuromonitoring (IONM) alerts and management of intraoperative spinal cord injuries (ISCIs). METHODS: MEDLINE® was searched from inception through January 26, 2022 as were sources of grey literature. We attempted to obtain guidelines and/or consensus statements from the following sources: American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM), American Academy of Neurology (AAN), American Clinical Neurophysiology Society, NASS (North American Spine Society), and other spine surgery organizations. RESULTS: Of 16 studies reporting on management strategies for ISCIs, two were publications of consensus meetings which were conducted according to the Delphi method and eight were retrospective cohort studies. The remaining six studies were narrative reviews that proposed intraoperative checklists and management strategies for IONM alerts. Of note, 56% of included studies focused only on patients undergoing spinal deformity surgery. Intraoperative considerations and measures taken in the event of an ISCI are divided and reported in three categories of i) Anesthesiologic, ii) Neurophysiological/Technical, and iii) Surgical management strategies. CONCLUSION: There is a paucity of literature on comparative effectiveness and harms of management strategies in response to an IONM alert and possible ISCI. There is a pressing need to develop a standardized checklist and care pathway to avoid and minimize the risk of postoperative neurologic sequelae.

A Clinical Practice Guideline for the Management of Patients With Acute Spinal Cord Injury: Recommendations on Hemodynamic Management.

STUDY DESIGN: Clinical practice guideline development following the GRADE process. OBJECTIVES: Hemodynamic management is one of the only available treatment options that likely improves neurologic outcomes in patients with acute traumatic spinal cord injury (SCI). Augmenting mean arterial pressure (MAP) aims to improve blood perfusion and oxygen delivery to the injured spinal cord in order to minimize secondary ischemic damage to neural tissue. The objective of this guideline was to update the 2013 AANS/CNS recommendations on the hemodynamic management of patients with acute traumatic SCI, acknowledging that much has been published in this area since its publication. Specifically, we sought to make recommendations on 1. The range of mean arterial pressure (MAP) to be maintained by identifying an upper and lower MAP limit; 2. The duration of such MAP augmentation; and 3. The choice of vasopressor. Additionally, we sought to make a recommendation on spinal cord perfusion pressure (SCPP) targets. METHODS: A multidisciplinary guideline development group (GDG) was formed that included health care professionals from a wide range of clinical specialities, patient advocates, and individuals living with SCI. The GDG reviewed the 2013 AANS/CNS guidelines and voted on whether each recommendation should be endorsed or updated. A systematic review of the literature, following PRISMA standards and registered in PROSPERO, was conducted to inform the guideline development process and address the following key questions: (i) what are the effects of goal-directed interventions to optimize spinal cord perfusion on extent of neurological recovery and rates of adverse events at any time point of follow-up? and (ii) what are the effects of particular monitoring techniques, perfusion ranges, pharmacological agents, and durations of treatment on extent of neurological recovery and rates of adverse events at any time point of follow-up? The GDG combined the information from this systematic review with their clinical expertise in order to develop recommendations on a MAP target range (specifically an upper and lower limit to target), the optimal duration for MAP augmentation, and the use of vasopressors or inotropes. Using methods outlined by the GRADE working group, recommendations were formulated that considered the balance of benefits and harms, financial impact, acceptability, feasibility and patient preferences. RESULTS: The GDG suggested that MAP should be augmented to at least 75-80 mmHg as the "lower limit," but not actively augmented beyond an "upper limit" of 90-95 mmHg in order to optimize spinal cord perfusion in acute traumatic SCI. The quality of the evidence around the "target MAP" was very low, and thus the strength of this recommendation is weak. For duration of hemodynamic management, the GDG "suggested" that MAP be augmented for a duration of 3-7 days. Again, the quality of the evidence around the duration of MAP support was very low, and thus the strength of this recommendation is also weak. The GDG felt that a recommendation on the choice of vasopressor or the use of SCPP targets was not warranted, given the dearth of available evidence. CONCLUSION: We provide new recommendations for blood pressure management after acute SCI that acknowledge the limitations of the current evidence on the relationship between MAP and neurologic recovery. It was felt that the low quality of existing evidence and uncertainty around the relationship between MAP and neurologic recovery justified a greater range of MAP to target, and for a broader range of days post-injury than recommended in previous guidelines. While important knowledge gaps still remain regarding hemodynamic management, these recommendations represent current perspectives on the role of MAP augmentation for acute SCI.

An Overview of the Methodology Used to Develop Clinical Practice Guidelines for the Management of Acute and Intraoperative Spinal Cord Injury.

STUDY DESIGN: An overview of the methods used to develop clinical practice guidelines (CPGs). OBJECTIVES: Acute spinal cord injury (SCI) and intraoperative SCI (ISCI) can have devastating physical and psychological consequences for patients and their families. To date, there are several studies that have discussed the diagnostic and management strategies for both SCI and ISCI. CPGs in SCI help to distill and translate the current evidence into actionable recommendations, standardize care across centers, optimize patient outcomes, and reduce costs and unnecessary interventions. Furthermore, they can be used by patients to assist in making decisions about certain treatments and by policy makers to inform allocation of resources. The objective of this article is to summarize the methods used to develop CPGs for the timing of surgery and hemodynamic management of acute SCI, as well as the identification and treatment of ISCI. METHODS: The CPGs were developed using standards established by the Institute of Medicine (now the National Academy of Medicine), the Guideline International Network and several other organizations. Systematic reviews were conducted according to accepted methodological standards (eg, Institute of Medicine, Agency for Healthcare Research and Quality and Patient-Centered Outcomes Research Institute) in order to summarize the current body of evidence and inform the guideline development process. Protocols for each guideline were created. A multidisciplinary guideline development group (GDG) was formed that included individuals living with SCI as well as clinicians from the broad range of specialties that encounter patients with SCI: spine or trauma surgeons, critical care physicians, rehabilitation specialists, neurologists, anesthesiologists and other healthcare professionals. Individuals living with SCI were also included in the GDG. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach was used to rate the certainty of the evidence for each critical outcome. The "evidence to recommendation" framework was then used to translate the evidence obtained from the systematic review to an actionable recommendation. This framework provides structure when assessing the body of evidence and considers several additional factors when rating the strength of the recommendation, including the magnitude of benefits and harms, patient preferences, resource use, health equities, acceptability and feasibility. Finally, the CPGs were appraised both internally and externally. RESULTS: The results of the CPGs for SCI are provided in separate articles in this focus issue. CONCLUSIONS: Development of these CPGs for SCI followed the methodology proposed by the Institute of Medicine the Guideline International Network and the GRADE Working Group. It is anticipated that these CPGs will assist clinicians implement the best evidence into practice and facilitate shared-decision making with patients.

Timing of Decompressive Surgery in Patients With Acute Spinal Cord Injury: Systematic Review Update.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: Surgical decompression is a cornerstone in the management of patients with traumatic spinal cord injury (SCI); however, the influence of the timing of surgery on neurological recovery after acute SCI remains controversial. This systematic review aims to summarize current evidence on the effectiveness, safety, and cost-effectiveness of early (≤24 hours) or late (>24 hours) surgery in patients with acute traumatic SCI for all levels of the spine. Furthermore, this systematic review aims to evaluate the evidence with respect to the impact of ultra-early surgery (earlier than 24 hours from injury) on these outcomes. METHODS: A systematic search of the literature was performed using the MEDLINE database (PubMed), Cochrane database, and EMBASE. Two reviewers independently screened the citations from the search to determine whether an article satisfied predefined inclusion and exclusion criteria. For all key questions, we focused on primary studies with the least potential for bias and those that controlled for baseline neurological status and specified time from injury to surgery. Risk of bias of each article was assessed using standardized tools based on study design. Finally, the overall strength of evidence for the primary outcomes was assessed using the GRADE approach. Data were synthesized both qualitatively and quantitively using meta-analyses. RESULTS: Twenty-one studies met inclusion and exclusion criteria and formed the evidence base for this review update. Seventeen studies compared outcomes between patients treated with early (≤24 hours from injury) compared to late (>24 hours) surgical decompression. An additional 4 studies evaluated even earlier time frames: <4, <5, <8 or <12 hours. Based on moderate evidence, patients were 2 times more likely to recover by ≥ 2 grades on the ASIA Impairment Score (AIS) at 6 months (RR: 2.76, 95% CI 1.60 to 4.98) and 12 months (RR: 1.95, 95% CI 1.26 to 3.18) if they were decompressed within 24 hours compared to after 24 hours. Furthermore, moderate evidence suggested that patients receiving early decompression had an additional 4.50 (95% CI 1.70 to 7.29) point improvement on the ASIA motor score. With respect to administrative outcomes, there was low evidence that early decompression may decrease acute hospital length of stay. In terms of safety, there was moderate evidence that suggested the rate of major complications does not differ between patients undergoing early compared to late surgery. Furthermore, there was no difference in rates of mortality, surgical device-related complications, sepsis/systemic infection or neurological deterioration based on timing of surgery. Firm conclusions were not possible with respect to the impact of ultra-early surgery on neurological, functional or safety outcomes given the poor-quality studies, imprecision and the overlap in the time frames examined. CONCLUSIONS: This review provides an evidence base to support the update on clinical practice guidelines related to the timing of surgical decompression in acute SCI. Overall, the strength of evidence was moderate that early surgery (≤24 hours from injury) compared to late (>24 hours) results in clinically meaningful improvements in neurological recovery. Further studies are required to delineate the role of ultra-early surgery in patients with acute SCI.

AO Spine/Praxis Clinical Practice Guidelines for the Management of Acute Spinal Cord Injury: An Introduction to a Focus Issue.

STUDY DESIGN: Narrative overview and summary. OBJECTIVES: The objective of this introductory manuscript is to provide an overview of the effort that was undertaken to establish clinical practice guidelines for a number of important topics in spinal cord injury (SCI). These topics included: 1. The role and timing of surgical decompression after acute traumatic SCI; 2. The hemodynamic management of acute traumatic SCI; and 3. The definition, diagnosis, and management of intra-operative SCI. Here, we introduce the rationale for the guidelines, the methodology utilized, and summarize how the topics are addressed within various manuscripts of this Focus Issue. METHODS: The key clinical questions were defined using the PICO format for treatment reviews (patient; intervention; comparison; outcomes) or PPO format (patient, prognostic factor, outcomes) for risk factor review. Multi-disciplinary, international guideline development groups (GDGs) were established to evaluate and collate the available evidence in a rigorous, systematic manner, followed by a review of systematically obtained evidence within the framework of the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) criteria and application of the Evidence to Decision process. Consensus meetings, using a modified Delphi approach, were held with the multidisciplinary, international GDGs using online video-conferencing technology and anonymous voting to develop the final recommendations for each of the topics addressed. All systematic review protocols followed PRISMA standards and were registered on PROSPERO; all potential conflicts were vetted in an open and transparent manner. The funders (AO Spine and Praxis Spinal Cord Institute) had no influence over editorial content or the guidelines process). RESULTS: Updated guidelines were established for the timing of surgical decompression after acute SCI, with surgical decompression within 24 hours of injury now "recommended" as a treatment option. Updated guidelines were also established for hemodynamic management, with an expanded target range for mean arterial pressure (MAP) of 75-80 to 90-95 mmHg for between 3 to 7 days post-injury now "suggested" as a treatment option. The available literature mandated scoping and systematic reviews on the topic of intra-operative SCI, and this resulted in manuscripts to address the definition, frequency, and risk factors, to define the role of intra-operative neuromonitoring, and to suggest an evidence-based care pathway for management. CONCLUSION: A rigorous process following GRADE standards was undertaken to review the available evidence and establish guideline recommendations around the role and timing of surgery in acute SCI, optimal hemodynamic management of acute SCI and the prevention, diagnosis and management of intraoperative SCI. This effort also identified key knowledge gaps and future directions for study, which will serve to refine these recommendations in the future.

Respectful Maternity Care : A Systematic Review.

BACKGROUND: Severe maternal morbidity and mortality are worse in the United States than in all similar countries, with the greatest effect on Black women. Emerging research suggests that disrespectful care during childbirth contributes to this problem. PURPOSE: To conduct a systematic review on definitions and valid measurements of respectful maternity care (RMC), its effectiveness for improving maternal and infant health outcomes for those who are pregnant and postpartum, and strategies for implementation. DATA SOURCES: Systematic searches of Ovid Medline, CINAHL, Embase, Cochrane Central Register of Controlled Trials, PsycInfo, and SocINDEX for English-language studies (inception to July 2023). STUDY SELECTION: Randomized controlled trials and nonrandomized studies of interventions of RMC versus usual care for effectiveness studies; additional qualitative and noncomparative validation studies for definitions and measurement studies. DATA EXTRACTION: Dual data abstraction and quality assessment using established methods, with resolution of disagreements through consensus. DATA SYNTHESIS: Thirty-seven studies were included across all questions, of which 1 provided insufficient evidence on the effectiveness of RMC to improve maternal outcomes and none studied RMC to improve infant outcomes. To define RMC, authors identified 12 RMC frameworks, from which 2 main concepts were identified: disrespect and abuse and rights-based frameworks. Disrespect and abuse components focused on recognizing birth mistreatment; rights-based frameworks incorporated aspects of reproductive justice, human rights, and antiracism. Five overlapping framework themes include freedom from abuse, consent, privacy, dignity, communication, safety, and justice. Twelve tools to measure RMC were validated in 24 studies on content validity, construct validity, and internal consistency, but lack of a gold standard limited evaluation of criterion validity. Three tools specific for RMC had at least 1 study demonstrating consistency internally and with an intended construct relevant to U.S. settings, but no single tool stands out as the best measure of RMC. LIMITATIONS: No studies evaluated other health outcomes or RMC implementation strategies. The lack of definition and gold standard limit evaluation of RMC tools. CONCLUSION: Frameworks for RMC are well described but vary in their definitions. Tools to measure RMC demonstrate consistency but lack a gold standard, requiring further evaluation before implementation in U.S. settings. Evidence is lacking on the effectiveness of implementing RMC to improve any maternal or infant health outcome. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. (PROSPERO: CRD42023394769).

Risk factors for C5 palsy: a systematic review and multivariate analysis.

OBJECTIVE: Postoperative C5 palsy (C5P) is a known complication in cervical spine surgery. However, its exact pathophysiology is unclear. The authors aimed to provide a review of the current understanding of C5P by performing a comprehensive, systematic review of the existing literature and conducting a critical appraisal of existing evidence to determine the risk factors of C5P. METHODS: A systematic search of PubMed/MEDLINE (January 1, 2019, to July 2, 2021), EMBASE (inception to July 2, 2021), and Cochrane (inception to July 2, 2021) databases was conducted. Preestablished criteria were used to evaluate studies for inclusion. Studies that adjusted for one or more of the following factors were considered: preoperative foraminal diameter (FD) at C4/5, posterior spinal cord shift at C4/5, preoperative anterior-posterior diameter (APD) at C4/5, preoperative spinal cord rotation, and change in C2-7 Cobb angle. Studies were rated as good, fair, or poor based on the Quality in Prognosis Studies (QUIPS) tool. Random effects meta-analyses were done using methods outlined by Cochrane methodologists for pooling of prognostic studies. Overall quality (strength) of evidence was based on Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methods for prognostic studies. The protocol for this review was published on the PROSPERO (CRD264358) website. RESULTS: Of 303 potentially relevant citations of studies, 12 met the inclusion criteria set a priori. These works provide moderate-quality evidence that preoperative FD substantially increases the odds of C5P in patients undergoing posterior cervical surgery. Pooled estimates across 7 studies in which various surgical approaches were used indicate that the odds of C5P approximately triple for each millimeter decrease in preoperative FD (OR 3.05, 95% CI 2.07-4.49). Preoperative APD increases the odds of C5P, but the confidence is low. Across 3 studies, each using different surgical approaches, each millimeter decrease in preoperative APD was associated with a more than 2-fold increased odds of C5P (pooled OR 2.51, 95% CI 1.69-3.73). Confidence that there is an association with postoperative C5P and posterior spinal cord shift, change in sagittal Cobb angle, and preoperative spinal cord rotation is very low. CONCLUSIONS: The exact pathophysiological process resulting in postoperative C5P remains an enigma but there is a clear association with foraminal stenosis, especially when performing posterior procedures. C5P is also related to decreased APD but the association is less clear. The overall quality (strength) of evidence provided by the current literature is low to very low for most factors. Systematic review registration no.: CRD264358 (https://www.crd.york.ac.uk/prospero/).

Inclusion of nonrandomized studies of interventions in systematic reviews of interventions: updated guidance from the Agency for Health Care Research and Quality Effective Health Care program.

OBJECTIVES: We developed guidance to inform decisions regarding the inclusion of nonrandomized studies of interventions (NRSIs) in systematic reviews (SRs) of the effects of interventions. STUDY DESIGN AND SETTING: The guidance workgroup comprised SR experts and used an informal consensus generation method. RESULTS: Instead of recommending NRSI inclusion only if randomized controlled trials (RCTs) are insufficient to address the SR key question, different topics may require different decisions regarding NRSI inclusion. We identified important considerations to inform such decisions from topic refinement through protocol development. During topic scoping and refinement, considerations were related to the clinical decisional dilemma, adequacy of RCTs to address the key questions, risk of bias in NRSIs, and the extent to which NRSIs are likely to complement RCTs. When NRSIs are included, during SR team formation, familiarity with topic-specific data sources and advanced analytic methods for NRSIs should be considered. During protocol development, the decision regarding NRSI inclusion or exclusion should be justified, and potential implications explained. When NRSIs are included, the protocol should describe the processes for synthesizing evidence from RCTs and NRSIs and determining the overall strength of evidence. CONCLUSION: We identified specific considerations for decisions regarding NRSI inclusion in SRs and highlight the importance of flexibility and transparency.

Physical Activity and the Health of Wheelchair Users: A Systematic Review in Multiple Sclerosis, Cerebral Palsy, and Spinal Cord Injury.

OBJECTIVE: To understand the benefits and harms of physical activity in people who may require a wheelchair with a focus on people with multiple sclerosis (MS), cerebral palsy (CP), and spinal cord injury (SCI). DATA SOURCES: Searches were conducted in MEDLINE, Cumulative Index to Nursing and Allied Health, PsycINFO, Cochrane CENTRAL, and Embase (January 2008 through November 2020). STUDY SELECTION: Randomized controlled trials, nonrandomized trials, and cohort studies of observed physical activity (at least 10 sessions on 10 days) in participants with MS, CP, and SCI. DATA EXTRACTION: We conducted dual data abstraction, quality assessment, and strength of evidence. Measures of physical functioning are reported individually where sufficient data exist and grouped as "function" where data are scant. DATA SYNTHESIS: No studies provided evidence for prevention of cardiovascular conditions, development of diabetes, or obesity. Among 168 included studies, 44% enrolled participants with MS (38% CP, 18% SCI). Studies in MS found walking ability may be improved with treadmill training and multimodal exercises; function may be improved with treadmill, balance exercises, and motion gaming; balance is likely improved with balance exercises and may be improved with aquatic exercises, robot-assisted gait training (RAGT), motion gaming, and multimodal exercises; activities of daily living (ADL), female sexual function, and spasticity may be improved with aquatic therapy; sleep may be improved with aerobic exercises and aerobic fitness with multimodal exercises. In CP, balance may be improved with hippotherapy and motion gaming; function may be improved with cycling, treadmill, and hippotherapy. In SCI, ADL may be improved with RAGT. CONCLUSIONS: Depending on population and type of exercise, physical activity was associated with improvements in walking, function, balance, depression, sleep, ADL, spasticity, female sexual function, and aerobic capacity. Few harms of physical activity were reported in studies. Future studies are needed to address evidence gaps and to confirm findings.

Outpatient Cervical Ripening: A Systematic Review and Meta-analysis.

OBJECTIVE: To assess the comparative effectiveness and potential harms of cervical ripening in the outpatient compared with the inpatient setting, or different methods of ripening in the outpatient setting alone. DATA SOURCES: Searches for articles in English included MEDLINE, EMBASE, CINAHL, Cochrane Library, ClinicalTrials.gov, and reference lists (up to August 2020). METHODS OF STUDY SELECTION: Using predefined criteria and DistillerSR software, 10,853 citations were dual-reviewed for randomized controlled trials (RCTs) and cohort studies of outpatient cervical ripening using prostaglandins and mechanical methods in pregnant women at or beyond 37 weeks of gestation. TABULATION, INTEGRATION, AND RESULTS: Using prespecified criteria, study data abstraction and risk of bias assessment were conducted by two reviewers, random-effects meta-analyses were conducted and strength of evidence was assessed. We included 30 RCTs and 10 cohort studies (N=9,618) most generalizable to women aged 25-30 years with low-risk pregnancies. All findings were low or insufficient strength of evidence and not statistically significant. Incidence of cesarean delivery was not different for any comparison of inpatient and outpatient settings, or comparisons of different methods in the outpatient setting (most evidence available for single-balloon catheters and dinoprostone). Harms were inconsistently reported or inadequately defined. Differences were not found for neonatal infection (eg, sepsis) with outpatient compared with inpatient dinoprostone, birth trauma (eg, cephalohematoma) with outpatient compared with inpatient single-balloon catheter, shoulder dystocia with outpatient dinoprostone compared with placebo, maternal infection (eg, chorioamnionitis) with outpatient compared with inpatient single-balloon catheters or outpatient prostaglandins compared with placebo, and postpartum hemorrhage with outpatient catheter compared with inpatient dinoprostone. Evidence on misoprostol, hygroscopic dilators, and other outcomes (eg, perinatal mortality and time to vaginal birth) was insufficient. CONCLUSION: In women with low-risk pregnancies, outpatient cervical ripening with dinoprostone or single-balloon catheters did not increase cesarean deliveries. Although there were no clear differences in harms when comparing outpatient with inpatient cervical ripening, the certainty of evidence is low or insufficient to draw definitive conclusions. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42020167406.

Autologous Stem Cells in Cervical Spine Fusion.

STUDY DESIGN: Systematic review. OBJECTIVES: To systematically review, critically appraise and synthesize evidence on use of stem cells from autologous stem cells from bone marrow aspirate, adipose, or any other autologous sources for fusion in the cervical spine compared with other graft materials. METHODS: A systematic search of PubMed/MEDLINE was conducted for literature published through October 31, 2018 and through February 20, 2020 for EMBASE and ClinicalTrials.gov comparing autologous cell sources for cervical spine fusion to other graft options. RESULTS: From 36 potentially relevant citations identified, 10 studies on cervical fusion met the inclusion criteria set a priori. Two retrospective cohort studies, one comparing cancellous bone marrow (CBM) versus hydroxyapatite (HA) and the other bone marrow aspirate (BMA) combined with autograft and HA versus autograft and HA alone, were identified. No statistical differences were seen between groups in either study for improvement in function, symptoms, or fusion; however, in the study evaluating BMA, the authors reported a statistically greater fusion rate and probability of fusion over time in the BMA versus the non-BMA group. Across case series evaluating BMA, authors reported improved function and pain and fusion ranged from 84% to 100% across the studies. In general, complications were poorly reported. CONCLUSIONS: The overall quality (strength) of evidence of effectiveness and safety of autologous BMA for cervical arthrodesis in the current available literature was very low. Based on currently available data, firm conclusions regarding the effectiveness or safety of BMA in cervical fusions cannot be made.

Spine Treatment Appraisal Report (STAR): Bone Marrow-Derived Stem Cells Improve Neurological Recovery in Participants With Spinal Cord Injury.

Srivastava RN, Agrahari AK, Singh A, Chandra T, Raj S. Effectiveness of bone marrow-derived mononuclear stem cells for neurological recovery in participants with spinal cord injury: a randomized controlled trial. Asian J Transfus Sci. 2019;13(2):120-128.