Uncovering the origin of Z-configured double bonds in polyketides: intermediate E-double bond formation during borrelidin biosynthesis

Formation of Z-configured double bonds in reduced polyketides is uncommon and their origins have not been extensively studied. To investigate the origin of the Z-configured double bond in the macrolide borrelidin, the recombinant dehydratase domains BorDH2 and B0rDH3 were assayed with a synthetic analogue of the predicted tetraketide substrate. The configuration of the dehydrated products was determined to be E in both cases by comparison to synthetic standards. Detailed NMR spectroscopic analysis of the biosynthetic intermediate pre-borrelidin confirmed the E,E-configuration of the fulllength polyketide synthase product. In contrast to a previously-proposed hypothesis, our results show that in this case the Z-configured double bond is not formed via dehydration from a 3 L-configured precursor, but rather as the result of a later isomerization process.Marie Curie programme of the European UnionEmmy Noether programme of the Deutsche ForschungsgemeinschaftDAA

Sacral Fractures and Associated Injuries.

STUDY DESIGN: Literature review. OBJECTIVE: The aim of this review is to describe the injuries associated with sacral fractures and to analyze their impact on patient outcome. METHODS: A comprehensive narrative review of the literature was performed to identify the injuries associated with sacral fractures. RESULTS: Sacral fractures are uncommon injuries that result from high-energy trauma, and that, due to their rarity, are frequently underdiagnosed and mistreated. Only 5% of sacral fractures occur in isolation. Injuries most often associated with sacral fractures include neurologic injuries (present in up to 50% of sacral fractures), pelvic ring disruptions, hip and lumbar spine fractures, active pelvic/ abdominal bleeding and the presence of an open fracture or significant soft tissue injury. Diagnosis of pelvic ring fractures and fractures extending to the lumbar spine are key factors for the appropriate management of sacral fractures. Importantly, associated systemic (cranial, thoracic, and abdominopelvic) or musculoskeletal injuries should be promptly assessed and addressed. These associated injuries often dictate the management and eventual outcome of sacral fractures and, therefore, any treatment algorithm should take them into consideration. CONCLUSIONS: Sacral fractures are complex in nature and often associated with other often-missed injuries. This review summarizes the most relevant associated injuries in sacral fractures and discusses on their appropriate management

AOSpine—Spine Trauma Classification System: The Value of Modifiers: A Narrative Review With Commentary on Evolving Descriptive Principles

Study Design: Narrative review. Objectives: To describe the current AOSpine Trauma Classification system for spinal trauma and highlight the value of patient-specific modifiers for facilitating communication and nuances in treatment. Methods: The classification for spine trauma previously developed by The AOSpine Knowledge Forum is reviewed and the importance of case modifiers in this system is discussed. Results: A successful classification system facilitates communication and agreement between physicians while also determining injury severity and provides guidance on prognosis and treatment. As each injury may be unique among different patients, the importance of considering patient-specific characteristics is highlighted in this review. In the current AOSpine Trauma Classification, the spinal column is divided into 4 regions: the upper cervical spine (C0-C2), subaxial cervical spine (C3-C7), thoracolumbar spine (T1-L5), and the sacral spine (S1-S5, including coccyx). Each region is classified according to a hierarchical system with increasing levels of injury or instability and represents the morphology of the injury, neurologic status, and clinical modifiers. Specifically, these clinical modifiers are denoted starting with M followed by a number. They describe unique conditions that may change treatment approach such as the presence of significant soft tissue damage, uncertainty about posterior tension band injury, or the presence of a critical disc herniation in a cervical bilateral facet dislocation. These characteristics are described in detail for each spinal region. Conclusions: Patient-specific modifiers in the AOSpine Trauma Classification highlight unique clinical characteristics for each injury and facilitate communication and treatment between surgeons

Variation in global treatment for subaxial cervical spine isolated unilateral facet fractures.

PURPOSE To determine the variation in the global treatment practices for subaxial unilateral cervical spine facet fractures based on surgeon experience, practice setting, and surgical subspecialty. METHODS A survey was sent to 272 members of the AO Spine Subaxial Injury Classification System Validation Group worldwide. Questions surveyed surgeon preferences with regard to diagnostic work-up and treatment of fracture types F1-F3, according to the AO Spine Subaxial Cervical Spine Injury Classification System, with various associated neurologic injuries. RESULTS A total of 161 responses were received. Academic surgeons use the facet portion of the AO Spine classification system less frequently (61.6%) compared to hospital-employed and private practice surgeons (81.1% and 81.8%, respectively) (p = 0.029). The overall consensus was in favor of operative treatment for any facet fracture with radicular symptoms (N2) and for any fractures categorized as F2N2 and above. For F3N0 fractures, significantly less surgeons from Africa/Asia/Middle East (49%) and Europe (59.2%) chose operative treatment than from North/Latin/South America (74.1%) (p = 0.025). For F3N1 fractures, significantly less surgeons from Africa/Asia/Middle East (52%) and Europe (63.3%) recommended operative treatment than from North/Latin/South America (84.5%) (p = 0.001). More than 95% of surgeons included CT in their work-up of facet fractures, regardless of the type. No statistically significant differences were seen in the need for MRI to decide treatment. CONCLUSION Considerable agreement exists between surgeon preferences with regard to unilateral facet fracture management with few exceptions. F2N2 fracture subtypes and subtypes with radiculopathy (N2) appear to be the threshold for operative treatment

Health professionals’ perspective on the applicability of AO Spine PROST (patient reported outcome Spine trauma) in people with a motor-complete traumatic or non-traumatic spinal cord injury

Purpose: The AO Spine PROST (Patient Reported Outcome Spine Trauma) was developed for people with spine trauma and minor or no neurological impairment. The purpose is to investigate health professionals’ perspective on the applicability of the AO Spine PROST for people with motor-complete traumatic or non-traumatic spinal cord injury (SCI), using a discussion meeting and international survey study. Methods: A discussion meeting with SCI rehabilitation physicians in the Netherlands was performed, followed by a worldwide online survey among the AO Spine International community, involved in the care of people with SCI. Participants rated the comprehensibility, relevance, acceptability, feasibility and completeness of the AO Spine PROST on a 1–5 point scale (5 most positive). Comments could be provided per question. Results: The discussion meeting was attended by 13 SCI rehabilitation physicians. The survey was completed by 196 participants. Comprehensibility (mean ± SD: 4.1 ± 0.8), acceptability (4.0 ± 0.8), relevance (3.9 ± 0.8), completeness (3.9 ± 0.8), and feasibility (4.1 ± 0.7) of the AO Spine PROST were rated positively for use in people with motor-complete traumatic or non-traumatic SCI. Only a few participants questioned the relevance of items on the lower extremities (e.g., walking) or missed items on pulmonary functioning and complications. Some recommendations were made for improvement in instructions, terminology and examples of the tool. Conclusion: Health professionals found the AO Spine PROST generally applicable for people with motor-complete traumatic or non-traumatic SCI. This study provides further evidence for the use of the AO Spine PROST in spine trauma care, rehabilitation and research, as well as suggestions for its further development.</p

Establishing the Injury Severity of Subaxial Cervical Spine Trauma: Validating the Hierarchical Nature of the AO Spine Subaxial Cervical Spine Injury Classification System.

STUDY DESIGN Global cross-sectional survey. OBJECTIVE To validate the AO Spine Subaxial Cervical Spine Injury Classification by examining the perceived injury severity by surgeon across AO geographical regions and practice experience. SUMMARY OF BACKGROUND DATA Previous subaxial cervical spine injury classifications have been limited by subpar interobserver reliability and clinical applicability. In an attempt to create a universally validated scheme with prognostic value, AO Spine established a subaxial cervical spine injury classification involving four elements: (1) injury morphology, (2) facet injury involvement, (3) neurologic status, and (4) case-specific modifiers. METHODS A survey was sent to 272 AO Spine members across all geographic regions and with a variety of practice experience. Respondents graded the severity of each variable of the classification system on a scale from zero (low severity) to 100 (high severity). Primary outcome was to assess differences in perceived injury severity for each injury type over geographic regions and level of practice experience. RESULTS A total of 189 responses were received. Overall, the classification system exhibited a hierarchical progression in subtype injury severity scores. Only three subtypes showed a significant difference in injury severity score among geographic regions: F3 (floating lateral mass fracture, p:0.04), N3 (incomplete spinal cord injury, p:0.03), and M2 (critical disk herniation, p:0.04). When stratified by surgeon experience, pairwise comparison showed only 2 morphological subtypes, B1 (bony posterior tension band injury, p:0.02) and F2 (unstable facet fracture, p:0.03), and one neurologic subtype (N3, p:0.02) exhibited a significant difference in injury severity score. CONCLUSIONS The AO Spine Subaxial Cervical Spine Injury Classification System has shown to be reliable and suitable for proper patient management. The study shows this classification is substantially generalizable by geographic region and surgeon experience; and provides a consistent method of communication among physicians while covering the majority of subaxial cervical spine traumatic injuries.Level of Evidence: 4

Management of Acute Traumatic Central Cord Syndrome: A Narrative Review.

Study Design Narrative review. Objectives To provide an updated overview of the management of acute traumatic central cord syndrome (ATCCS). Methods A comprehensive narrative review of the literature was done to identify evidence-based treatment strategies for patients diagnosed with ATCCS. Results ATCCS is the most commonly encountered subtype of incomplete spinal cord injury and is characterized by worse sensory and motor function in the upper extremities compared with the lower extremities. It is most commonly seen in the setting of trauma such as motor vehicles or falls in elderly patients. The operative management of this injury has been historically variable as it can be seen in the setting of mechanical instability or preexisting cervical stenosis alone. While each patient should be evaluated on an individual basis, based on the current literature, the authors' preferred treatment is to perform early decompression and stabilization in patients that have any instability or significant neurologic deficit. Surgical intervention, in the appropriate patient, is associated with an earlier improvement in neurologic status, shorter hospital stay, and shorter intensive care unit stay. Conclusions While there is limited evidence regarding management of ATCCS, in the presence of mechanical instability or ongoing cord compression, surgical management is the treatment of choice. Further research needs to be conducted regarding treatment strategies and patient outcomes

Effect of surgical experience and spine subspecialty on the reliability of the AO Spine Upper Cervical Injury Classification System.

OBJECTIVE The objective of this paper was to determine the interobserver reliability and intraobserver reproducibility of the AO Spine Upper Cervical Injury Classification System based on surgeon experience ( 20 years) and surgical subspecialty (orthopedic spine surgery, neurosurgery, and "other" surgery). METHODS A total of 11,601 assessments of upper cervical spine injuries were evaluated based on the AO Spine Upper Cervical Injury Classification System. Reliability and reproducibility scores were obtained twice, with a 3-week time interval. Descriptive statistics were utilized to examine the percentage of accurately classified injuries, and Pearson's chi-square or Fisher's exact test was used to screen for potentially relevant differences between study participants. Kappa coefficients (κ) determined the interobserver reliability and intraobserver reproducibility. RESULTS The intraobserver reproducibility was substantial for surgeon experience level ( 20 years: 0.70) and surgical subspecialty (orthopedic spine: 0.71 vs neurosurgery: 0.69 vs other: 0.68). Furthermore, the interobserver reliability was substantial for all surgical experience groups on assessment 1 ( 20 years: 0.62), and only surgeons with > 20 years of experience did not have substantial reliability on assessment 2 ( 20 years: 0.59). Orthopedic spine surgeons and neurosurgeons had substantial intraobserver reproducibility on both assessment 1 (0.64 vs 0.63) and assessment 2 (0.62 vs 0.63), while other surgeons had moderate reliability on assessment 1 (0.43) and fair reliability on assessment 2 (0.36). CONCLUSIONS The international reliability and reproducibility scores for the AO Spine Upper Cervical Injury Classification System demonstrated substantial intraobserver reproducibility and interobserver reliability regardless of surgical experience and spine subspecialty. These results support the global application of this classification system

The AO spine upper cervical injury classification system: Do work setting or trauma center affiliation affect classification accuracy or reliability?

PURPOSE To assess the accuracy and reliability of the AO Spine Upper Cervical Injury Classification System based on a surgeons' work setting and trauma center affiliation. METHODS A total of 275 AO Spine members participated in a validation of 25 upper cervical spine injuries, which were evaluated by computed tomography (CT) scans. Each participant was grouped based on their work setting (academic, hospital-employed, or private practice) and their trauma center affiliation (Level I, Level II or III, and Level IV or no trauma center). The classification accuracy was calculated as percent of correct classifications, while interobserver reliability, and intraobserver reproducibility were evaluated based on Fleiss' Kappa coefficient. RESULTS The overall classification accuracy for surgeons affiliated with a level I trauma center was significantly greater than participants affiliated with a level II/III center or a level IV/no trauma center on assessment one (p1<0.0001) and two (p2 = 0.0003). On both assessments, surgeons affiliated with a level I or a level II/III trauma center were significantly more accurate at identifying IIIB injury types (p1 = 0.0007; p2 = 0.0064). Academic surgeons and hospital employed surgeons were significantly more likely to correctly classify type IIIB injuries on assessment one (p1 = 0.0146) and two (p2 = 0.0015). When evaluating classification reliability, the largest differences between work settings and trauma center affiliations was identified in type IIIB injuries. CONCLUSION Type B injuries are the most difficult injury type to correctly classify. They are classified with greater reliability and classification accuracy when evaluated by academic surgeons, hospital-employed surgeons, and surgeons associated with higher-level trauma centers (I or II/III)

Regional and experiential differences in surgeon preference for the treatment of cervical facet injuries: a case study survey with the AO Spine Cervical Classification Validation Group

Purpose The management of cervical facet dislocation injuries remains controversial. The main purpose of this investigation was to identify whether a surgeon’s geographic location or years in practice infuences their preferred management of traumatic cervical facet dislocation injuries. Methods A survey was sent to 272 AO Spine members across all geographic regions and with a variety of practice experience. The survey included clinical case scenarios of cervical facet dislocation injuries and asked responders to select preferences among various diagnostic and management options. Results A total of 189 complete responses were received. Over 50% of responding surgeons in each region elected to initiate management of cervical facet dislocation injuries with an MRI, with 6 case exceptions. Overall, there was considerable agreement between American and European responders regarding management of these injuries, with only 3 cases exhibiting a signifcant diference. Additionally, results also exhibited considerable management agreement between those with≤10 and>10 years of practice experience, with only 2 case exceptions noted. Conclusion More than half of responders, regardless of geographical location or practice experience, identifed MRI as a screening imaging modality when managing cervical facet dislocation injuries, regardless of the status of the spinal cord and prior to any additional intervention. Additionally, a majority of surgeons would elect an anterior approach for the surgical management of these injuries. The study found overall agreement in management preferences of cervical facet dislocation injuries around the globe. Keywords Cervical spine · Trauma · Spinal injuries · Joint dislocations · Neck injuries · Spinal disease