Implant and construct decision-making in metastatic spine tumour surgery: a review of current concepts with a decision-making algorithm.

STUDY DESIGN: Narrative Review. OBJECTIVE: Metastatic spine tumour surgery (MSTS) is an important treatment modality of metastatic spinal disease (MSD). Increase in MSTS has been due to improvements in our oncological treatment, as patients have increased longevity and even those with poorer comorbidities are now being considered for surgery. However, there is currently no guideline on how MSTS surgeons should select the appropriate levels to instrument, and which type of implants should be utilised. METHODS: The current literature on MSTS was reviewed to study implant and construct decision making factors, with a view to write this narrative review. All studies that were related to instrumentation in MSTS were included. RESULTS: A total of 58 studies were included in this review. We discuss novel decision-making models that should be taken into account when planning for surgery in patients undergoing MSTS. These factors include the quality of bone for instrumentation, the extent of the construct required for MSTS patients, the use of cement augmentation and the choice of implant. Various studies have advocated for the use of these modalities and demonstrated better outcomes in MSTS patients when used appropriately. CONCLUSION: We have established a new instrumentation algorithm that should be taken into consideration for patients undergoing MSTS. It serves as an important guide for surgeons treating MSTS, with the continuous evolvement of our treatment capacity in MSD.

White matter disturbances in major depressive disorder: a coordinated analysis across 20 international cohorts in the ENIGMA MDD working group.

Alterations in white matter (WM) microstructure have been implicated in the pathophysiology of major depressive disorder (MDD). However, previous findings have been inconsistent, partially due to low statistical power and the heterogeneity of depression. In the largest multi-site study to date, we examined WM anisotropy and diffusivity in 1305 MDD patients and 1602 healthy controls (age range 12-88 years) from 20 samples worldwide, which included both adults and adolescents, within the MDD Working Group of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium. Processing of diffusion tensor imaging (DTI) data and statistical analyses were harmonized across sites and effects were meta-analyzed across studies. We observed subtle, but widespread, lower fractional anisotropy (FA) in adult MDD patients compared with controls in 16 out of 25 WM tracts of interest (Cohen's d between 0.12 and 0.26). The largest differences were observed in the corpus callosum and corona radiata. Widespread higher radial diffusivity (RD) was also observed (all Cohen's d between 0.12 and 0.18). Findings appeared to be driven by patients with recurrent MDD and an adult age of onset of depression. White matter microstructural differences in a smaller sample of adolescent MDD patients and controls did not survive correction for multiple testing. In this coordinated and harmonized multisite DTI study, we showed subtle, but widespread differences in WM microstructure in adult MDD, which may suggest structural disconnectivity in MDD.

Is high pressure postdilation safe in bioresorbable vascular scaffolds? Optical coherence tomography observations after noncompliant balloons inflated at more than 24 atmospheres.

OBJECTIVES: Optical coherence tomography (OCT) was used to investigate integrity and expansion of bioresorbable drug-eluting scaffolds (BVS) after high-pressure postdilation (HPPD). BACKGROUND: Because of concerns about the risk of BVS damage, postdilation was not recommended and applied in the existing randomized studies and most registries. Recent real world data suggest incomplete BVS expansion cause higher rates of thrombosis. In vivo confirmation of the safety of high pressure postdilation is of paramount importance. METHODS: Data from final OCT examination of consecutive implanted BVS, postdilated with noncompliant (NC) balloons at pressure ≥24 atm were analyzed. The following stent performance indices were assessed with OCT: mean and minimal lumen and scaffold area, residual area stenosis (RAS), incomplete strut apposition (ISA), tissue prolapse, eccentricity index (EI), symmetry index (SI), strut fractures, and edge dissections. RESULT: Twenty-two BVS postdilated at high pressure were analyzed. The average maximal postdilation balloon inflation (maxPD) was 28 ± 3 atm. High pressure OPN NC Balloon (SIS Medical AG, Winterthur Switzerland) was used in 41% of postdilations with a maximal PD of 30 ± 4.7 atm. Final mean and minimal lumen area were 6.8 ± 1.4 and 5.5 ± 1.4 mm(2) , respectively. OCT showed low percentage of RAS (16 ± 9.6%), and low percentage of ISA (1.8 ± 2.4%). Mean EI was 0.86 ± 0.02 and SI 0.35 ± 0.14. OCT analysis showed one edge dissection and no scaffold fractures. CONCLUSIONS: BVS deployment optimization using HPPD does not cause BVS disruption and is associated with a good BVS expansion, low rate of strut malapposition and edge dissections.

Vacuum assisted closure and local drug delivery systems in spinal infections: A review of current evidence.

Background: Spinal infections are still showing increased incidence throughout the years as our surgical capabilities increase, coupled with an overall aging population with greater number of chronic comorbidities. The management of spinal infection is of utmost importance, due to high rates of morbidity and mortality, on top of the general difficulty in eradicating spinal infection due to the ease of hematogenous spread in the spine. We aim to summarize the utility of vacuum-assisted closure (VAC) and local drug delivery systems (LDDS) in the management of spinal infections. Methods: A narrative review was conducted. All studies that were related to the use of VAC and LDDS in Spinal Infections were included in the study. Results: A total of 62 studies were included in this review. We discussed the utility of VAC as a tool for the management of wounds requiring secondary closure, as well as how it is increasingly being used after primary closure as prophylaxis for surgical site infections in high-risk wounds of patients undergoing spinal surgery. The role of LDDS in spinal infections was also discussed, with preliminary studies showing good outcomes when patients were treated with various novel LDDS. Conclusions: We have summarized and given our recommendations for the use of VAC and LDDS for spinal infections. A treatment algorithm has also been established, to act as a guide for spine surgeons to follow when tackling various spinal infections in day-to-day clinical practice.

Trends in surgical management of spinal metastases in a Singaporean tertiary referral center: a 17-year retrospective review.

Introduction: Surgical treatment is increasingly the treatment of choice in cancer patients with epidural spinal cord compression and spinal instability. There has also been an evolution in surgical treatment with the advent of minimally invasive surgical (MIS) techniques and separation surgery. This paper aims to investigate the changes in epidemiology, surgical technique, outcomes and complications in the last 17 years in a tertiary referral center in Singapore. Methods: This is a retrospective study of 383 patients with surgically treated spinal metastases treated between January 2005 to January 2022. Patients were divided into 3 groups, patients treated between 2005 - 2010, 2011-2016, and 2017- 2021. Demographic, oncological, surgical, patient outcome and survival data were collected. Statistical analysis with univariate analysis was performed to compare the groups. Results: There was an increase in surgical treatment (87 vs 105 vs 191). Lung, Breast and prostate cancer were the most common tumor types respectively. There was a significant increase in MIS(p<0.001) and Separation surgery (p<0.001). There was also a significant decrease in mean blood loss (1061ml vs 664 ml vs 594ml) (p<0.001) and total transfusion (562ml vs 349ml vs 239ml) (p<0.001). Group 3 patients were more likely to have improved or normal neurology (p=<0.001) and independent ambulatory status(p=0.012). There was no significant change in overall survival. Conclusion: There has been a significant change in our surgical practice with decreased blood loss, transfusion and improved neurological and functional outcomes. Patients should be managed in a multidisciplinary manner and surgical treatment should be recommended when indicated.

Outcomes and Complications of Surgery for Symptomatic Spinal Metastases; a Comparison Between Patients Aged ≥ 70 and <70.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: Physicians may be deterred from operating on elderly patients due to fears of poorer outcomes and complications. We aimed to compare the outcomes of surgical treatment of spinal metastases patients aged ≥70-yrs and <70-yrs. MATERIALS AND METHODS: This is a retrospective study of patients surgically treated for metastatic epidural spinal cord compression and spinal instability between January-2005 to December-2021. Follow-up was till death or minimum 1-year post-surgery. Outcomes included post-operative neurological status, ambulatory status, medical and surgical complications. Two Sample t-test/Mann Whitney U test were used for numerical variables and Pearson Chi-Squared or Fishers Exact test for categorical variables. Survival was presented with a Kaplan-Meier curve. P < .05 was significant. RESULTS: We identified 412 patients of which 29 (7.1%) patients were excluded due to loss to follow-up and previous surgical treatment. 79 (20.6%) were ≥70-yrs. Age ≥70-yrs patients had poorer ECOG scores (P = .0017) and Charlson Comorbidity Index (P < .001). No significant difference in modified Tokuhashi score (P = .393) was observed with significantly more ≥ prostate (P < .001) and liver (P = .029) cancer in ≥70-yrs. Improved or maintained normal neurological function (P = .934), independent ambulatory status (P = .171), and survival at 6 months (P = .119) and 12 months (P = .659) was not significantly different between both groups. Medical (P = .528) or surgical (P = .466) complication rates and readmission rates (P = .800) were similar. CONCLUSION: ≥70-yrs patients have comparable outcomes to <70-yr old patients with no significant increase in complication rates. Age should not be a determining factor in deciding surgical management of spinal metastases.

Illness remission status and commissural and associative brain white matter fiber changes in schizophrenia.

There is a paucity of studies clarifying biological basis of illness remission in schizophrenia related to white matter abnormalities, hence this study aimed to examine brain white matter anomalies via combinatorial diffusion tensor imaging (DTI) indices between remitted and nonremitted patients and evaluate predictors of remission. We examined DTI data of 178 patients who met the DSM-IV criteria for schizophrenia (120 nonremitted, 58 remitted) and 111 healthy controls. Remission was determined using Global Assessment of Functioning (GAF) and Positive and Negative Syndrome Scale (PANSS) scores. Analysis of covariance identified significantly different white matter tracts between groups, whilst covarying for clinical variables. Correlation and regression analyses were performed to determine clinical-imaging predictors of remission. Compared to controls, both nonremitted and remitted patients had reduced fractional anisotropy in the body of corpus callosum (BCC) and posterior thalamic radiation. Nonremitted patients had higher axial diffusivity (AD)/mean diffusivity (MD) values in the right cingulum than remitted patients after controlling for duration of illness, number of hospitalizations, and daily total chlorpromazine equivalents. The MD and AD of right cingulum correlated positively with the severity of psychotic psychopathology in nonremitted subjects. In addition, female sex and longer duration of illness were also significant predictors of remission. Specific DTI indices reflecting axonal processes and inflammation/edema of associative fibers (right cingulum) differentiated nonremitted from remitted patients, and together with relevant clinical factors, could serve as potential prognostic markers in schizophrenia.

Disruption of brain anatomical networks in schizophrenia: A longitudinal, diffusion tensor imaging based study.

Despite convergent neuroimaging evidence indicating a wide range of brain abnormalities in schizophrenia, our understanding of alterations in the topological architecture of brain anatomical networks and how they are modulated over time, is still rudimentary. Here, we employed graph theoretical analysis of longitudinal diffusion tensor imaging data (DTI) over a 5-year period to investigate brain network topology in schizophrenia and its relationship with clinical manifestations of the illness. Using deterministic tractography, weighted brain anatomical networks were constructed from 31 patients experiencing schizophrenia and 28 age- and gender-matched healthy control subjects. Although the overall small-world characteristics were observed at both baseline and follow-up, a scan-point independent significant deficit of global integration was found in patients compared to controls, suggesting dysfunctional integration of the brain and supporting the notion of schizophrenia as a disconnection syndrome. Specifically, several brain regions (e.g., the inferior frontal gyrus and the bilateral insula) that are crucial for cognitive and emotional integration were aberrant. Furthermore, a significant group-by-longitudinal scan interaction was revealed in the characteristic path length and global efficiency, attributing to a progressive aberration of global integration in patients compared to healthy controls. Moreover, the progressive disruptions of the brain anatomical network topology were associated with the clinical symptoms of the patients. Together, our findings provide insights into the substrates of anatomical dysconnectivity patterns for schizophrenia and highlight the potential for connectome-based metrics as neural markers of illness progression and clinical change with treatment.

Early coverage of drug-eluting stents analysed by optical coherence tomography: evidence of the impact of stent apposition and strut characteristics on the neointimal healing process.

AIMS: Previous studies have associated issues such as incomplete stent apposition with delayed healing and adverse events (stent thrombosis). The aim of this study was to evaluate the impact of strut apposition and stent type on the progression of stent strut coverage. METHODS AND RESULTS: We evaluated in vivo in porcine models the follow-up response and coverage characteristics of well-apposed and malapposed segments of drug-eluting stents (DES) (CYPHER, PROMUS Element and Orsiro) and the Absorb bioresorbable vascular scaffold (BVS) by optical coherence tomography (OCT) sequentially, at baseline, and at one week and four weeks of follow-up. Supporting results were provided by histological analysis performed at four-week follow-up and computer simulation describing the shear characteristics around apposed and non-apposed struts. A total of 325 cross-sections containing 3,166 struts were analysed. The extent of malapposition decreased over time as a result of neointimal healing (from 7.1% at baseline to 0% at four weeks; p=0.03). At one week, 13.6% of struts in well-apposed segments were still uncovered versus 19.2% of struts in malapposed cross-sections and 77.8% of NASB struts (p<0.01). At four-week follow-up, 3.1% of struts were uncovered in well-apposed cross-sections vs. 1.6% in malapposed cross-sections and 35.7% of NASB struts (p<0.01). A comparison of the apposed segments revealed that the thin-strut Orsiro had only 1.3% of uncovered struts at one week while PROMUS Element, CYPHER and BVS had 6.6%, 48.4% and 16.2% of struts still uncovered, respectively. CONCLUSIONS: This study shows that early coverage is influenced by stent apposition as well as platform strut characteristics (stent type). At four weeks, NASB struts remained a focus of delayed endothelialisation.

Bioabsorbable vascular scaffold overexpansion: insights from in vitro post-expansion experiments.

AIMS: While bioresorbable vascular scaffolds (BVS) are increasingly used in clinical practice, their behaviour when post-dilated beyond their recommended maximum overexpansion diameter remains sparsely documented. We aimed to test the overexpansion of the BVS scaffold in vitro and evaluate the impact of excessive scaffold oversizing on focal point support. METHODS AND RESULTS: We examined the post-expansion behaviour of the bioresorbable vascular scaffold (3.0 mm and 3.5 mm Absorb BVS; Abbott Vascular, Santa Clara, CA, USA) after overexpansion with non-compliant (NC) balloons of increasing diameters. After each oversizing step, the scaffolds were measured and inspected for strut disruption using microscope and optical coherence tomography imaging. Point force mechanical measurements on single scaffold struts were also performed to evaluate the impact of excessive scaffold overstretching on focal mechanical support. 3.0 mm and 3.5 mm scaffold sizes could be post-expanded up to 1 mm above their nominal diameters without any strut fracture when deployed without an external constraining model. Importantly, when overexpansion of both scaffold sizes was repeated using a constraining silicone lesion model, only post-expansion with an NC balloon size 0.5 mm larger than the scaffold nominal sizes could be performed without strut fractures. Point force compression analysis on single struts shows that overstretched struts with fractures provided lower focal strength compared to overexpanded ring segments without fractures and normal segments expanded at nominal pressure. CONCLUSIONS: In our experiments, only overexpansion with an NC balloon 0.5 mm larger than the BVS size was feasible for BVS deployed inside an arterial lesion model. Overexpansion of the BVS scaffold beyond recommended post-dilation limits can lead to strut disconnections and focal loss of mechanical support.

Bioresorbable vascular scaffold radial expansion and conformation compared to a metallic platform: insights from in vitro expansion in a coronary artery lesion model.

AIMS: This study aimed to compare the acute expansion behaviour of a polymer-based bioresorbable scaffold and a second-generation metallic DES platform in a realistic coronary artery lesion model. Experimental mechanical data with conventional methods have so far shown little difference between metallic stents and currently available polymer-based bioresorbable scaffolds (BRS). Nevertheless, differences in acute results have been observed in clinical studies comparing BRS directly with metallic DES platforms. METHODS AND RESULTS: We examined the expansion behaviour of the bioresorbable vascular scaffold (3.0×18 mm Absorb BVS; Abbott Vascular, Santa Clara, CA, USA) and a metallic DES (3.0×18 mm XIENCE Prime; Abbott Vascular) after expansion at 37°C using identical coronary artery stenosis models (in total 12 experiments were performed). Device expansion was compared during balloon inflation and after deflation using microscopy to allow assessment of plaque recoil. Minimal lumen diameter (MLD) and minimal lumen area (MLA) and stent eccentricity were quantified from optical coherence tomography (OCT) imaging at nominal diameter and after post-dilation at 18 atm. The MLA in the models with BVS deployed was 4.92±0.17 mm² while in the metallic DES it was 5.40±0.13 mm2 (p=0.02) at nominal pressure (NP), and 5.41±0.20 and 6.07±0.25 mm2 (p=0.02), respectively, after expansion at 18 atm. Stent eccentricity index at the MLA was 0.71±0.02 in BVS compared to 0.81±0.02 in the metal stent at NP (p=0.004), and 0.73±0.03 compared to 0.75±0.02 at 18 atm (p=0.39). CONCLUSIONS: Results obtained in this in vitro lesion model were comparable to the results in randomised clinical trials comparing BVS and XIENCE stents in vivo. Such models may be useful in future BRS developments to predict their acute response in vivo in eccentric lesions.

Progressive gender differences of structural brain networks in healthy adults: a longitudinal, diffusion tensor imaging study.

Sexual dimorphism in the brain maturation during childhood and adolescence has been repeatedly documented, which may underlie the differences in behaviors and cognitive performance. However, our understanding of how gender modulates the development of structural connectome in healthy adults is still not entirely clear. Here we utilized graph theoretical analysis of longitudinal diffusion tensor imaging data over a five-year period to investigate the progressive gender differences of brain network topology. The brain networks of both genders showed prominent economical "small-world" architecture (high local clustering and short paths between nodes). Additional analysis revealed a more economical "small-world" architecture in females as well as a greater global efficiency in males regardless of scan time point. At the regional level, both increased and decreased efficiency were found across the cerebral cortex for both males and females, indicating a compensation mechanism of cortical network reorganization over time. Furthermore, we found that weighted clustering coefficient exhibited significant gender-time interactions, implying different development trends between males and females. Moreover, several specific brain regions (e.g., insula, superior temporal gyrus, cuneus, putamen, and parahippocampal gyrus) exhibited different development trajectories between males and females. Our findings further prove the presence of sexual dimorphism in brain structures that may underlie gender differences in behavioral and cognitive functioning. The sex-specific progress trajectories in brain connectome revealed in this work provide an important foundation to delineate the gender related pathophysiological mechanisms in various neuropsychiatric disorders, which may potentially guide the development of sex-specific treatments for these devastating brain disorders.

Impact of stent strut design in metallic stents and biodegradable scaffolds.

Advances in the understanding of healing mechanisms after stent implantation have led to the recognition of stent strut thickness as an essential factor affecting re-endothelialization and overall long term vessel healing response after Percutaneous Coronary Interventions (PCI). Emergence of Drug-eluting stents (DESs) with anti-proliferative coating has contributed to reducing the incidence of restenosis and Target Lesion Revascularization (TVR), while progress and innovations in stent materials have in the meantime facilitated the design of newer platforms with more conformability and thinner struts, producing lesser injury and improving integration into the vessel wall. Recent advances in biodegradable metal and polymer materials now also allow for the design of fully biodegradable platforms, which are aimed at scaffolding the vessel only temporarily to prevent recoil and constrictive remodeling of the vessel during the initial period required, and are then progressively resorbed thereby avoiding the drawback of leaving an unnecessary implant permanently in the vessel. The aim of this article is to review recent evolution in stent material and stent strut design while understanding their impact on PCI outcomes. The article describes the different metallic alloys and biodegradable material properties and how these have impacted the evolution of stent strut thickness and ultimately outcomes in patients.

Structural connectivity analysis reveals topological aberrations in patients with schizophrenia.

Topological analysis and the associated parameters allow elucidation of brain networks in health and illness. Evidently useful measures for defining network competency such as small-worldness can potentially improve understanding of brain connectivity and their disruptions underlying neuropsychiatric conditions such as schizophrenia. In the current study, we assessed the structural differences of brain networks in schizophrenia patients as compared with healthy controls. As proof of concept investigation, diffusion tensor imaging recordings from 2 schizophrenia patients and 2, gender and age matched, control subjects were subjected to analysis using several graph network distance metrics. Among them, those that appeared to have the ability to encode and highest sensitivity in shedding light about anatomical changes in neuron deficiency were the shortest path length and clustering coefficient parameters. Schizophrenia patients displayed comparatively lower clustering coefficient, longer path lengths and hence reduced small-worldness. These results suggest aberrant topological architecture in the structural brain networks of patients with schizophrenia, which may impact the psychopathological and cognitive manifestations of this potentially crippling illness.