Design and 3D printing of novel titanium spine rods with lower flexural modulus and stiffness profile with optimised imaging compatibility.

PURPOSE: To manufacture and test 3D printed novel design titanium spine rods with lower flexural modulus and stiffness compared to standard solid titanium rods for use in metastatic spine tumour surgery (MSTS) and osteoporosis. METHODS: Novel design titanium spine rods were designed and 3D printed. Three-point bending test was performed to assess mechanical performance of rods, while a French bender was used to assess intraoperative rod contourability. Furthermore, 3D printed spine rods were tested for CT & MR imaging compatibility using phantom setup. RESULTS: Different spine rod designs generated includes shell, voronoi, gyroid, diamond, weaire-phelan, kelvin, and star. Tests showed 3D printed rods had lower flexural modulus with reduction ranging from 2 to 25% versus standard rod. Shell rods exhibited highest reduction in flexural modulus of 25% (~ 77.4 GPa) and star rod exhibited lowest reduction in flexural modulus of 2% (100.8GPa). 3D printed rod showed reduction in stiffness ranging from 40 to 59%. Shell rod displayed highest reduction in stiffness of 59% (179.9 N/mm) and gyroid had least reduction in stiffness of 40% (~ 259.2 N/mm). Rod bending test showed that except gyroid, other rod designs demonstrated lesser bending difficulty versus standard rod. All 3D printed rods demonstrated improved CT/MR imaging compatibility with reduced artefacts versus standard rod. CONCLUSION: By utilising novel design approach, we successfully generated a spine rod design portfolio with lower flexural modulus/stiffness profile and better CT/MR imaging compatibility for potential use in MSTS/other conditions such as osteoporosis. Thus, exploration of new rod designs in surgical application could enhance treatment outcome and improve quality of life for patients.

The Utility of 'Minimal Access and Separation Surgery' in the Management of Metastatic Spine Disease.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: To compare outcomes of percutaneous pedicle screw fixation (PPSF) to open posterior stabilization (OPS) in spinal instability patients and minimal access separation surgery (MASS) to open posterior stabilization and decompression (OPSD) in metastatic spinal cord compression (MSCC) patients. METHODS: We analysed patients who underwent surgery for thoracolumbar metastatic spine disease (MSD) from Jan 2011 to Oct 2017. Patients were divided into minimally invasive spine surgery (MISS) and open spine surgery (OSS) groups. Spinal instability patients were treated with PPSF/OPS with pedicle screws. MSCC patients were treated with MASS/OPSD. Outcomes measured included intraoperative blood loss, operative time, duration of hospital stay and ASIA-score improvement. Time to initiate radiotherapy and perioperative surgical/non-surgical complications was recorded. Propensity scoring adjustment analysis was utilised to address heterogenicity of histological tumour subtypes. RESULTS: Of 200 eligible patients, 61 underwent MISS and 139 underwent OSS for MSD. There was no significant difference in baseline characteristics between MISS and OSS groups. In the MISS group, 28 (45.9%) patients were treated for spinal instability and 33 (54.1%) patients were treated for MSCC. In the OSS group, 15 (10.8%) patients were treated for spinal instability alone and 124 (89.2%) were treated for MSCC. Patients who underwent PPSF had significantly lower blood loss (95 mL vs 564 mL; P < .001) and surgical complication rates(P < .05) with shorter length of stay approaching significance (6 vs 19 days; P = .100) when compared to the OPS group. Patients who underwent MASS had significantly lower blood loss (602 mL vs 1008 mL) and shorter length of stay (10 vs 18 days; P = .098) vs the OPSD group. CONCLUSION: This study demonstrates the benefits of PPSF and MASS over OPS and OPSD for the treatment of MSD with spinal instability and MSCC, respectively.

ProDisc-C versus anterior cervical discectomy and fusion for the surgical treatment of symptomatic cervical disc disease: two-year outcomes of Asian prospective randomized controlled multicentre study.

PURPOSE: Our study aimed to evaluate non-inferiority of ProDisc-C to anterior cervical discectomy and fusion (ACDF) in terms of clinical outcomes and incidence of adjacent segment disease (ASD) at 24-months post-surgery in Asian patients with symptomatic cervical disc disease (SCDD). METHODS: This multicentre, prospective, randomized controlled trial was initiated after ethics committee approval at nine centres (China/Hong Kong/Korea/Singapore/Taiwan). Patients with single-level SCDD involving C3-C7-vertebral segments were randomized (2:1) into: group-A treated with ProDisc-C and group-B with ACDF. Assessments were conducted at baseline, 6-weeks, 3/6/12/18/24-months post-surgery and annually thereafter till 84-months. Primary endpoint was overall success at 24-months, defined as composite of: (1) ≥ 20% improvement in neck disability index (NDI); (2) maintained/improved neurologic parameters; (3) no implant removal/revision/re-operation at index level; and (4) no adverse/severe/life-threatening events. RESULTS: Of 120 patients (80ProDisc-C,40ACDF), 76 and 37 were treated as per protocol (PP). Overall success (PP) was 76.5% in group-A and 81.8% in group-B at 24-months (p = 0.12), indicating no clear non-inferiority of ProDisc-C to ACDF. Secondary outcomes improved for both groups with no significant inter-group differences. Occurrence of ASD was higher in group-B with no significant between-group differences. Range of motion (ROM) was sustained with ProDisc-C but lost with ACDF at 24-months. CONCLUSION: Cervical TDR with ProDisc-C is feasible, safe, and effective for treatment of SCDD in Asians. No clear non-inferiority was demonstrated between ProDisc-C and ACDF. However, patients treated with ProDisc-C demonstrated significant improvement in NDI, neurologic success, pain scores, and 36-item-short-form survey, along with ROM preservation at 24-months. Enrolment difficulties resulted in inability to achieve pre-planned sample size to prove non-inferiority. Future Asian-focused, large-scale studies are needed to establish unbiased efficacy of ProDisc-C to ACDF.

Analysis of Short-Term versus Long-Term Readmission-Free Survival After Metastatic Spine Tumor Surgery.

BACKGROUND: Readmission-free survival (ReAFS) is a novel clinical and quality metric after metastatic spine tumor surgery (MSTS). We believe that factors influencing ReAFS after index MSTS vary based on time. We considered 2 time frames and defined short-term ReAFS as survival without an unplanned hospital readmission up to 90 days and long-term ReAFS as survival without unplanned hospital readmission up to 1 year after MSTS. METHODS: We retrospectively analyzed 266 patients who underwent MSTS between 2005 and 2016. All relevant oncologic, surgical and follow-up data were collected. Multivariate logistic regression analysis was used to analyze prognostic factors associated with higher probability of short-term ReAFS and long-term ReAFS. RESULTS: Multivariate analysis showed that Eastern Cooperative Oncology Group score ≤2 (P = 0.011), preoperative hemoglobin (Hb) level >12 g/dL (P = 0.008), ≤3 comorbidities (P = 0.052), shorter index length of stay ≤10 days (P = 0.007), and absence of neurologic/hematologic complications during index stay (P = 0.015) significantly increased the probability of short-term ReAFS, whereas preoperative Hb level >12 g/dL (P = 0.003) or tumor primaries with advanced treatment modalities such as breast (P = 0.012), hematologic (P = 0.006), prostate (P = 0.004), and renal/thyroid (P = 0.038) as opposed to aggressive lung tumor primaries were associated with significantly higher probability of long-term ReAFS. CONCLUSIONS: Patient and treatment factors predominantly influence ReAFS up to 90 days, whereas primary tumor-related factors alongside general health influence ReAFS beyond 90 days after index MSTS. Awareness of these factors may help oncologists and surgeons optimize treatment planning. The clinical significance of this study will continue to evolve, because we have been witnessing over the past decade that patients are becoming more involved in both their general health and understanding the natural history of the diseases that affect them.

Evolution of materials for implants in metastatic spine disease till date - Have we found an ideal material?

"Metastatic Spine Disease" (MSD) often requires surgical intervention and instrumentation with spinal implants. Ti6Al4V is widely used in metastatic spine tumor surgery (MSTS) and is the current implant material of choice due to improved biocompatibility, mechanical properties, and compatibility with imaging modalities compared to stainless steel. However, it is still not the ideal implant material due to the following issues. Ti6Al4V implants cause stress-shielding as their Young's modulus (110 gigapascal [GPa]) is higher than cortical bone (17-21 GPa). Ti6Al4V also generates artifacts on CT and MRI, which interfere with the process of postoperative radiotherapy (RT), including treatment planning and delivery. Similarly, charged particle therapy is hindered in the presence of Ti6Al4V. In addition, artifacts on CT and MRI may result in delayed recognition of tumor recurrence and postoperative complications. In comparison, polyether-ether-ketone (PEEK) is a promising alternative. PEEK has a low Young's modulus (3.6 GPa), which results in optimal load-sharing and produces minimal artifacts on imaging with less hinderance on postoperative RT. However, PEEK is bioinert and unable to provide sufficient stability in the immediate postoperative period. This issue may possibly be mitigated by combining PEEK with other materials to form composites or through surface modification, although further research is required in these areas. With the increasing incidence of MSD, it is an opportune time for the development of spinal implants that possess all the ideal material properties for use in MSTS. Our review will explore whether there is a current ideal implant material, available alternatives and whether these require further investigation.

Is there a place for surgical repair in adults with spondylolysis or grade-I spondylolisthesis-a systematic review and treatment algorithm.

OBJECTIVES: Pars repair is less explored in adults due to associated disc degeneration with advancing age. The aim of our systematic review was to define optimal characteristics of adults with spondylolysis/grade-I spondylolisthesis suitable for pars repair and evaluate the feasibility, effectiveness, and safety of standard repair techniques in these adults. METHODS: This systematic review is reported in line with PRISMA-P and protocol is registered with PROSPERO (CRD42020189208). Electronic searches were conducted in PubMed, Embase, Scopus, and Web of Science in June 2020 using systematic search strategy. Studies involving adults aged ≥18-years with spondylolysis/grade-1 isthmic spondylolisthesis treated with standard pars repair techniques were considered eligible. A two-staged (titles/abstracts and full-text) screening was conducted independently by three authors followed by quality assessment using the Joanna Briggs Institute critical appraisal checklist for selection of final articles for narrative synthesis. RESULTS: A total of 5,813-articles were retrieved using systematic search strategy. First screening followed by removal of duplicates resulted in 111-articles. Second (full-text) screening resulted in exclusion of 64-articles. A final 47-articles were considered for data extraction after quality assessment. A total of 590-adults were enrolled across 47-studies; 93% were 'young adults' (18-35 years); 82% were males. Persistent low back pain was the common presenting complaint. Lysis defect was primarily bilateral (96.4%) and L5 was the most involved level (68.5%). Majority had no disc degeneration (83.5%) and had spondylolysis as the primary diagnosis (86%); only 14% had grade-I spondylolisthesis. Pars infiltration test was conducted in 22-studies and discography in 8-studies. Duration of prior conservative therapy was 3 to 72-months. Buck's repair was the commonest technique (27-studies, 372-adults). Successful repair was reported in 86% of patients treated with Buck's and ≥90% treated with Scott's, Morscher's and pedicle-screw-based techniques. Improvement in pain/functional outcomes, union rate and rate-of-return to sports/activity was high and comparable across all techniques. Intraoperative blood loss was low with minimally invasive versus traditional repair. The overall complication rate was 11.9%, with implant failure being the major complication. CONCLUSIONS: Our systematic review establishes a definite place for lysis repair in carefully selected adults with spondylolysis/grade-I spondylolisthesis. We propose a treatment algorithm for optimizing patient selection and outcomes. We conclude that adults with age 18 to 45 years, no/mild disc or facet degenerative changes, positive diagnostic infiltration test, and normal preoperative discography will have successful outcomes with pars repair, regardless of the technique.

Can Polyether Ether Ketone Dethrone Titanium as the Choice Implant Material for Metastatic Spine Tumor Surgery?

Instrumentation during metastatic spine tumor surgery (MSTS) provides stability to the spinal column in patients with pathologic fracture or iatrogenic instability produced while undergoing extensive decompression. Titanium is the current implant material of choice in MSTS. However, it hinders radiotherapy planning and generates artifacts, with magnetic resonance imaging and computed tomography scans used for postoperative evaluation of tumor recurrence and/or complications. The high modulus of elasticity of titanium (110 GPa) results in stress shielding, which may lead to construct failure at the bone-implant interface. Polyether ether ketone (PEEK), a thermoplastic polymer, is an emerging alternative to titanium for use in MSTS. The modulus of elasticity of PEEK (3.6 GPa) is close to that of cortical bone (17-21 GPa), resulting in minimal stress shielding. Its radiolucent and nonmetallic properties cause minimal interference with magnetic resonance imaging and computed tomography scans. PEEK also causes low-dose perturbation for radiotherapy planning. However, PEEK has reduced bioactivity with bone and lacks sufficient rigidity to be used as rods in MSTS. The reduced bioactivity of PEEK may be addressed by 1) surface modification (introducing porosity or bioactive coating with hydroxyapatite [HA] or titanium) and 2) forming composites with HA/titanium. The mechanical properties of PEEK may be improved by forming composites with HA or carbon fiber. Despite these modifications, all PEEK and PEEK-based implants are difficult to handle and contour intraoperatively. Our review provides a comprehensive overview of PEEK and modified PEEK implants, with a description of their properties and limitations, potentially serving as a basis for their future development and use in MSTS.

Analysis of unplanned hospital readmissions up to 2-years after metastatic spine tumour surgery.

PURPOSE: The aim of this study was to investigate rates, causes, and risk factors of unplanned hospital readmissions (UHR) within 30 days, 90 days, 1 year and 2 years after metastatic spine tumour surgery (MSTS) to augment multi-disciplinary treatment planning and improve patient education. METHODS: We retrospectively reviewed 272-patients who underwent MSTS between 2005 and 2016. Hospital records were utilised to obtain demographics, oncological, procedural details, and postoperative outcomes. All UHR within 2 years were reviewed. Primary outcomes were rates, causes, and risk factors of UHR. Risk factors for UHR were evaluated utilising multivariate logistic regression analysis. RESULTS: Thirty-day, 90 day, 1 year, and 2 year UHR-rates after MSTS were 17.2%, 31.1%, 46.2%, and 52.7%, respectively. Lung cancer primaries had the highest UHR-events (24.7%) whilst renal/thyroid displayed the least (6.6%). Disease-related causes (16.2%) were the most common reason for readmissions across all timeframes, followed by respiratory (13.7%) and progression of metastatic spine disease (12.7%). Urological conditions accounted for majority of readmissions within 30-days; disease-related causes, symptomatic spinal metastases, and respiratory conditions represented the most common causes at 30-90 days, 90 days-1 year, and 1-2 years, respectively. An ECOG >1 (p = 0.057), CCI >7 (p = 0.01), and primary lung tumour (p = 0.02) significantly increased UHR-risk on multivariate analysis. CONCLUSION: Seventy-four percent of patients had at least one UHR within 2 years of MSTS and majority were secondary to disease-related causes. Majority of first UHR occurred between 30 and 90 days post-surgery. Local disease progression and overall disease progression account for the highest UHR-events at 90 days-1 year and 1-2 year timeframes, respectively. We define UHR in specific timeframes, thus enabling better surveillance and reducing unnecessary morbidity.

Readmission-Free Survival Analysis in Metastatic Spine Tumour Surgical Patients: A Novel Concept.

BACKGROUND: Outcomes commonly used to ascertain success of metastatic spine tumour surgery (MSTS) are 30-day complications/mortality and overall/disease-free survival. We believe a new, effective outcome indicator after MSTS would be the absence of unplanned hospital readmission (UHR) after index discharge. We introduce the concept of readmission-free survival (ReAFS), defined as 'the time duration between hospital discharge after index operation and first UHR or death'. The aim of this study is to identify factors influencing ReAFS in MSTS patients. PATIENTS AND METHODS: We retrospectively analysed 266 consecutive patients who underwent MSTS between 2005 and 2016. Demographics, oncological characteristics, procedural, preoperative and postoperative details were collected. ReAFS of patients within 2 years or until death was reviewed. Perioperative factors predictive of reduced ReAFS were evaluated using multivariate regression analysis. RESULTS: Of 266 patients, 230 met criteria for analysis. A total of 201 had UHR, whilst 1 in 8 (29/230) had no UHR. Multivariate analysis revealed that haemoglobin ≥ 12 g/dL, ECOG score of ≤ 2, primary prostate, breast and haematological cancers, comorbidities ≤ 3, absence of preoperative radiotherapy and shorter postoperative length of stay significantly prolonged the time to first UHR. CONCLUSIONS: Readmission-free survival is a novel concept in MSTS, which relies on patients' general condition, appropriateness of interventional procedures and underlying disease burden. Additionally, it may indicate the successful combination of a multi-disciplinary treatment approach. This information will allow oncologists and surgeons to identify patients who may benefit from increased surveillance following discharge to increase ReAFS. We envisage that ReAFS is a concept that can be extended to other surgical oncological fields.

Is there an optimal timing between radiotherapy and surgery to reduce wound complications in metastatic spine disease? A systematic review.

PURPOSE: Surgery with radiation therapy (RT) is more effective in treating spinal metastases, than RT alone. However, RT when administered in close proximity to surgery may predispose to wound complications. There exist limited guidelines on the optimal timing between RT and surgery. The purpose of this systematic review is to: (1) address whether pre-operative RT (preop-RT) and/or post-operative RT (postop-RT) is associated with wound complications and (2) define the safe interval between RT and surgery or vice versa. METHODS: PubMed, Embase and Scopus databases were systematically searched for articles dealing with spinal metastases, treated with surgery and RT, and discussing wound status. RESULTS: We obtained 2332 articles from all databases, and after applying exclusion criteria, removing duplicates and reading the full text, we identified 27 relevant articles. Fourteen additional articles were identified by hand-search, leading to a total of 41 articles. All 41 mentioned wound complications/healing. Sixteen articles discussed preop-RT, 8 postop-RT, 15 both, and 2 mentioned intraoperative-RT with additional pre/postop-RT. Twenty studies mentioned surgery-RT time interval; one concluded that wound complications were higher when RT-surgery interval was ≤ 7 days. Seven studies reported significant association between preop-RT and wound complications. CONCLUSIONS: Evidence is insufficient to draw definitive conclusion about optimal RT-surgery interval. However, based on published literature and expert opinions, we conclude that an interval of 2 weeks, the minimum being 7 days, is optimum between RT-surgery or vice versa; this can be reduced further by postop-stereotactic body RT. If RT-surgery window is > 12 months, wound-complications rise. Postop-RT has fewer wound complications versus preop-RT.

A comparison of the biological activity of 2 formulations of enoxaparin in 12 healthy volunteers.

INTRODUCTION: India is one of the few countries where biosimilar enoxaparin is available for clinical use. Despite availability since past 4 to 5 years, there is a paucity of published literature regarding their biological activity. The aim of the current study is to compare the biological activity of an endogenously developed formulation of enoxaparin with the branded formulation. MATERIALS AND METHODS: Twelve healthy male volunteers received 1 subcutaneous injection of 2 different formulations of enoxaparin in a randomized, open-label, balanced, 2-treatment, 2-period, 2-sequence, cross-over study. The test formulation was Injection Troynoxa (enoxaparin sodium 40 mg/0.4 mL, Troikaa Pharmaceuticals Ltd., India) and reference formulation was Injection Clexane (enoxaparin sodium 40 mg/ 0.4 mL, Sanofi-Aventis, UK). The plasma anti-Xa activity and activated partial thromboplastin time (aPTT) were estimated on fully automated coagulometer predose and at 2, 4, 6, 8, and 10 hours following dosing with 40 mg/0.4 mL of enoxaparin. RESULTS: The results of mixed model analysis of repeated measures analysis of variance (ANOVA) for estimating difference between least square means of test and reference formulations, at all time points, showed no significant differences in anti-Xa activity and plasma aPTT levels. Both formulations were well tolerated and there were no bleeding episodes. CONCLUSION: After a single-dose injection in healthy participants, anti-Xa activities of 2 formulations of LMWH enoxaparin were comparable. No significant difference was observed in the mean plasma aPTT. It remains to be seen whether the 2 formulations would show comparable clinical efficacy.