Neutrophil-Derived Peptidyl Arginine Deiminase Activity Contributes to Pulmonary Emphysema by Enhancing Elastin Degradation.

In chronic obstructive pulmonary disease (COPD), inflammation gives rise to protease-mediated degradation of the key extracellular matrix protein, elastin, which causes irreversible loss of pulmonary function. Intervention against proteolysis has met with limited success in COPD, due in part to our incomplete understanding of the mechanisms that underlie disease pathogenesis. Peptidyl arginine deiminase (PAD) enzymes are a known modifier of proteolytic susceptibility, but their involvement in COPD in the lungs of affected individuals is underexplored. In this study, we showed that enzyme isotypes PAD2 and PAD4 are present in primary granules of neutrophils and that cells from people with COPD release increased levels of PADs when compared with neutrophils of healthy control subjects. By examining bronchoalveolar lavage and lung tissue samples of patients with COPD or matched smoking and nonsmoking counterparts with normal lung function, we reveal that COPD presents with markedly increased airway concentrations of PADs. Ex vivo, we established citrullinated elastin in the peripheral airways of people with COPD, and in vitro, elastin citrullination significantly enhanced its proteolytic degradation by serine and matrix metalloproteinases, including neutrophil elastase and matrix metalloprotease-12, respectively. These results provide a mechanism by which neutrophil-released PADs affect lung function decline, indicating promise for the future development of PAD-based therapeutics for preserving lung function in patients with COPD.

Iliac crest bone graft versus cell-based grafts to augment spinal fusion: a systematic review and meta-analysis.

INTRODUCTION: Despite successful fusion rates with iliac crest bone graft (ICBG), donor-site morbidity and increased operating time remain a considerable limitation and drive the search for alternatives. In this systematic review, grafts with additional cellular supplementation were compared with ICBG for spinal arthrodesis. We compared safety, efficacy and long-term outcomes, thus providing the current and relevant evidence for orthopaedic surgeons to make informed choices regarding this rapidly developing field. METHODS: An electronic literature search was conducted according to the PRISMA guidelines by two independent reviewers for articles published up to 1st March 2023 using PubMed, EMBASE and the Cochrane Central Register of Controlled Trial. Cellular allografts were not included. The following data were extracted: Number of patients, type of graft, fusion assessment method, follow-up duration, fusion rates, clinical outcomes and complications. The methodological quality of evidence (MQOE) was assessed using the Risk of Bias 2 (RoB-2) tool and Risk of Bias In Non-Randomised Studies (ROBINS) tool developed by Cochrane for evaluating bias in randomised and non-randomised studies. RESULTS: Ten studies fulfiled the inclusion criteria, including 465 patients. The mean number of patients per study was 43.8 (std dev. 28.81, range 12-100). Two studies demonstrated cell-based therapy to be significantly more successful in terms of fusion rates compared to ICBG. However, the remaining eight demonstrated equivocal results. No study found that cell-based therapy was inferior. No difference was seen between the two groups in three studies who focused on degenerative cohorts. No difference in functional outcome scores was seen between the groups. A number of different preparation techniques for cell-based grafts were used throughout the studies. CONCLUSION: Cell-based therapy offers a promising alternative to ICBG in spinal fusion surgery, which could help reduce the associated morbidity to patients. This review found that cell-based therapy is non-inferior to iliac crest bone graft and may offer patients an alternative treatment option with fewer complications and reduced post-operative pain. However, the literature to date is limited by heterogeneity of the cell preparation and grafting process. Future research with a unified approach to the cell preparation process is required to fully delineate the potential advantages of this technology.

Accuracy of augmented reality-assisted pedicle screw placement: a systematic review.

OBJECTIVE: Conventional freehand methods of pedicle screw placement are associated with significant complications due to close proximity to neural and vascular structures. Recent advances in augmented reality surgical navigation (ARSN) have led to its adoption into spine surgery. However, little is known regarding its overall accuracy. The purpose of this study is to delineate the overall accuracy of ARSN pedicle screw placement across various models. METHODS: A systematic review was conducted of Medline/PubMed, Cochrane and Embase Library databases according to the PRISMA guidelines. Relevant data extracted included reports of pedicle screw placement accuracy and breaches, as defined by the Gertzbein-Robbins classification, in addition to deviation from pre-planned trajectory and entry point. Accuracy was defined as the summation of grade 0 and grade 1 events per the Gertzbein-Robbins classification. RESULTS: Twenty studies reported clinically accurate placed screws. The range of clinically accurate placed screws was 26.3-100%, with 2095 screws (93.1%) being deemed clinically accurate. Furthermore, 5.4% (112/2088) of screws were reported as grade two breaches, 1.6% (33/2088) grade 3 breaches, 3.1% (29/926) medial breaches and 2.3% (21/926) lateral breaches. Mean linear deviation ranged from 1.3 to 5.99 mm, while mean angular/trajectory deviation ranged 1.6°-5.88°. CONCLUSION: The results of this study highlight the overall accuracy of ARSN pedicle screw placement. However, further robust prospective studies are needed to accurately compare to conventional methods of pedicle screw placement.

Outcomes following spinal instrumented fusions in patients with parkinson's disease: a systematic review and meta-analysis.

BACKGROUND: Parkinson's Disease (PD) patients represent challenging spinal surgery candidates due to associated frailty and deformity. This study consolidates the literature concerning spinal surgery outcomes in PD versus non-PD patients, to evaluate if PD predisposes patients to worse post-operative outcomes, so that treatment protocols can be optimised. METHODS: A systematic review and meta-analysis was conducted of PubMed/Medline, Embase, and Google Scholar databases per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies of interest included comparative (PD versus non-PD) cohorts undergoing spinal instrumented fusions. Post-operative clinical outcomes were collated and compared for significance between cohorts. Further analysis was made on outcomes based on the different surgical procedures performed (Anterior Cervical Discectomy and Fusion (ACDF), Thoracolumbar or Lumbar fusions, Thoracolumbar or Lumbar fusions without Osteoporotic Vertebral Compression fracture (OVCF) patients). All statistical analysis was performed using The R Project for Statistical Computing (version 4.1.2), with a p-value of < 0.05 deemed statistically significant. RESULTS: In total, 2,323,650 patients were included across 16 studies. Of those, 2,308,949 (99.37%) were patients without PD (non-PD), while 14,701 (0.63%) patients had PD at time of surgery. The collective mean age was 68.23 years (PD: 70.14 years vs non-PD: 64.86 years). Comparatively, there were 844,641 males (PD: 4,574; non-PD: 840,067) and 959,908 females (PD: 3,213; non-PD: 956,695). Overall, there were more post-operative complications in the PD cohort. Specifically, PD patients experienced significantly more surgical site infections (p = 0.01), increased rates of revision surgeries (p = 0.04) and increased venous thromboembolic events (p = 0.02) versus the non-PD cohort. In thoracolumbar/lumbar spinal fusions without OVCF patients, the PD cohort had increased rates of revision surgeries (p < 0.01) in comparison to the non-PD cohort. However, when including OVCF patients in thoracolumbar/lumbar spinal fusions, the PD cohort had significantly higher amounts of postoperative complications (p = 0.01), pneumonia (p = 0.02), and revision surgeries (p < 0.01) when compared to the non-PD cohort. CONCLUSION: Although more robust prospective studies are needed, the results of this study highlight the need for advanced wound care management in the postoperative period, both in-hospital and in the community, in addition to comprehensive multidisciplinary care from allied health professionals, with potential for the use of Enhanced Recovery After Surgery (ERAS) protocols in PD patients undergoing spinal instrumented fusions.

Isolated C1 arch fractures: C1-2 fusion vs. C1 osteosynthesis - surgical strategies for potentially unstable injuries.

STUDY DESIGN: Narrative Review. OBJECTIVES: The premise of this review is to provide a review of the literature pertaining to studies describing outcomes of surgical cohorts when implementing C1 osteosynthesis for arch fractures with or without transverse atlantal ligamentous (TAL) injury. METHODS: A comprehensive search strategy was implemented across several search engines to identify studies which evaluate the outcomes of C1 osteosynthesis for patients with C1 arch fractures with and without TAL injury. RESULTS: Ten studies were identified. Parameters reported included osteosynthesis fusion rates, deformity correction, preservation of motion segments, patient reported outcome measures and overall complications. Overall, C1 osteosynthesis showed excellent fusion rates with complications comparable to traditional techniques denoted in literature. Furthermore, the osteosynthesis technique depicted good overall deformity correction and preservation of motion segments, in addition to good patient reported outcomes. CONCLUSION: It appears C1 osteosynthesis offers a safe and efficacious alternative option for the surgical treatment of C1 fractures with TAL rupture. It has the potential to reduce deformity, increase ROM, improve PROMs and has complication rates comparable with those of fusion techniques. However more robust prospective evidence is required.

The diagnostic and prognostic utility of oxidative stress circulatory biomarkers in traumatic brain injury patients: a systematic review.

OBJECTIVE: The objective of this review is to qualitatively appraise the available literature to evaluate the efficacy of circulatory systemic oxidative stress markers (OSMx) in determining the diagnosis and outcome of TBI. METHODS: A systematic review was conducted of PubMed/Medline, Embase and Google Scholar databases per the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) for studies which employed serum or plasma OSMx analysis for diagnostic or prognostic purposes in patients with TBI. RESULTS: Eight studies were included. There were 654 patients across the eight studies, of which 518 (79.2%) patients had sustained a TBI. The heterogeneity between studies in terms of OSMxs analyzed ultimately made collective analysis inappropriate. Nevertheless, several studies highlighted the potential role of circulatory OSMx levels in determining the diagnosis (presence and severity) and prognosis (functional outcome and mortality) of TBI. CONCLUSION: The care for patients with TBI remains a complex clinical challenge with a high morbidity and mortality profile. Evidenced by this review, circulatory OSMxs appear to have the potential to supplement current diagnostic measures, in addition to identifying new treatment strategies and monitoring recovery. Despite early promise, the evidence for such markers remains in its infancy and robust prospective studies are needed.

The correlation between altmetric score and traditional measures of article impact for studies published within the Surgeon Journal.

Alternative metrics, or altmetrics, have emerged as a promising tool for measuring the social impact of research, which is increasingly important in today's digital and social media-driven world. Altmetric Attention Score (AAS) is a weighted count of all the online attention garnered by a study, and it is currently unclear whether a relationship with traditional bibliometrics exists. The purpose of this article was to retrospectively review articles published in the Surgeon Journal from 2003 to 2020 to compare AAS with bibliometric parameters using an Independent t-test and Pearson's correlation analysis. There were statistically significant weakly positive relationships between AAS and sample size, number of reads, and number of citations. There was no statistically significant relationship between AAS and number of authors, H-index, or level of evidence. This study highlights the potential value of altmetrics by measuring the social impact of research as altmetrics can provide valuable information not captured by traditional metrics. It is currently unclear what the optimal balance of social and academic impact is in evaluating research impact and how altmetrics can be integrated into existing research frameworks.

Retrospective case series of vertebral artery injuries associated with cervical spine trauma.

BACKGROUND: Vertebral artery injuries (VAI) can occur due to cervical spine trauma. VAI can prove a serious complication and potentially compromise vascular supply to the posterior aspect of the brain. Currently, there is a paucity of evidence with regards to incidence, management, and outcomes for these patients. The purpose of this study is to investigate and elucidate the incidence of VAI associated with cervical trauma at a national tertiary referral centre for spinal pathology, their respective management, and associated outcomes. METHODS: A retrospective review was conducted from 2012 to 2021 to identify patients with VAI secondary to cervical spine trauma. Demographic, clinical, and radiological data was collected to identify common traits in injury characteristics and management. RESULTS: 1013 spine patients presented to our institution across the 10-year period. 739/1013 (72.9 %) were trauma patients. 42/739 (5.7 %) were imaged for suspected VAI secondary to trauma. There were 14/739 (1.9 %) confirmed VAI. All patients had CT-angiography for diagnosis. Four of the confirmed VAI patients (28.6 %) had additional MR-angiography imaging. Right-side was the most common side of VAI injury (7/14; 50 %), followed by left (5/14; 35.7 %) and bilateral (2/14; 14.3 %) injuries. 8/14 (57.1 %) patients were prescribed anti-thrombotic therapy. Acute mortality within 3-months was noted to be 2/14 (14.3 %) and occurred at 49 days and 57 days respectively. CONCLUSION: VAI associated with cervical spine injury is rare in occurrence. However, it can be associated with high morbidity and mortality. As such, a multi-disciplinary approach to care is integral to ensuring good outcomes in these patients.

Comparative surgical outcomes of navigated vs non-navigated posterior spinal fusions in ankylosing spondylitis patients.

INTRODUCTION: Ankylosing Spondylitis (AS) patients with acute spinal fractures represent a challenge for practicing spine surgeons due to difficult operative anatomy and susceptibility to complications. RESEARCH QUESTION: Does intraoperative CT-navigation improve outcomes in patients with ankylosing spondylitis undergoing surgery? METHODS: A retrospective review was carried out at our centre from 05/2016-06/2021 to identify AS patients presenting with a traumatic spinal fracture, managed surgically with posterior spinal fusion (PSF). Cohorts were categorised and compared for outcomes based on those who underwent PSF with intraoperative CT-navigation versus those surgically managed with traditional intraoperative fluoroscopy. RESULTS: 37 AS patients were identified. 29/37 (78.4%) underwent PSF. Intraoperative navigation was used in 14 (48.3%) cases. Mean age of the entire cohort was 67.6 years. No difference existed between the navigated and non-navigated groups for mean levels fused (5.35 vs 5.07; p â€‹= â€‹0.31), length of operation (217.9mins vs 175.3mins; p â€‹= â€‹0.07), overall length-of-stay (12 days vs 21.9 days; p â€‹= â€‹0.16), patients requiring HDU (3/14 vs 5/15; p â€‹= â€‹0.09) or ICU (5/14 vs 9/15; p â€‹= â€‹0.10), postoperative neurological improvement (1/14 vs 1/15; p â€‹= â€‹0.48) or deterioration (1/14 vs 0/15; p â€‹= â€‹0.15), intraoperative complications (2/14 vs 3/15; p â€‹= â€‹0.34), postoperative complications 4/14 vs 4/15; p â€‹= â€‹0.46), revision surgeries (3/14 vs 1/15; p â€‹= â€‹0.16) and 30-day mortality (0/14 vs 0/15). CONCLUSION: This is the first study that compares surgical outcomes of navigated vs non-navigated PSFs for AS patients with an acute spinal fracture. Although limited by its retrospective design and sample size, this study highlights the non-inferiority of intraoperative navigation as a surgical aid in a challenging cohort.

Risk factors for distal junctional failure in long-construct instrumentation for adult spinal deformity.

PURPOSE: The aim of this study is to identify risk factors associated with postoperative DJF in long constructs for ASD. METHODS: A retrospective review was performed at a tertiary referral spine centre from 01/01/2007 to 31/12/2016. Demographic, clinical and radiographic parameters were collated for patients with DJF in the postoperative period and compared to those without DJF. Survival analyses were performed using univariate logistic regression to identify variables with a p value < 0.05 for inclusion in multivariate analysis. Spearman's correlations were performed where applicable. RESULTS: One hundred two patients were identified. 41 (40.2%) suffered DJF in the postoperative period, with rod fracture being the most common sign of DJF (13/65; 20.0%). Mean time to failure was 32.4 months. On univariate analysis, pedicle subtraction osteotomy (p = 0.03), transforaminal lumbar interbody fusion (p < 0.001), pre-op LL (p < 0.01), pre-op SVA (p < 0.01), pre-op SS (p = 0.02), postop LL (p = 0.03), postop SVA (p = 0.01), postop PI/LL (p < 0.001), LL correction (p < 0.001), SVA correction (p < 0.001), PT correction (p = 0.03), PI/LL correction (p < 0.001), SS correction (p = 0.03) all proved significant. On multivariate analysis, pedicle subtraction osteotomy (OR 27.3; p = 0.03), postop SVA (p < 0.01) and LL correction (p = 0.02) remained statistically significant as independent risk factors for DJF. CONCLUSION: Recently, DJF has received recognition as its own entity due to a notable postoperative incidence. Few studies to date have evaluated risk factors for DJF. The results of our study highlight that pedicle subtraction osteotomy, poor correction of lumbar lordosis, and sagittal vertical axis are significantly associated with postoperative occurrence of DJF.