Candidates For Fusion Research Articles

Comparison of Vicious Effect of Oral Pantoprazole and Famotidine on New Bone Formation in Patients With Lumbar Spine Fusion Surgery: A Randomized Control Trial

Background and Aim: Due to the increasing use of proton pump inhibitors (PPIs) and their side effects for bone repair and the high percentage of therapy failure in lumbar fusion surgery, especially in various animal studies, the goal of this study was to appraise the consequence of pantoprazole and famotidine on new bone formation in patients experiencing spinal fusion surgery. Methods and Materials/Patients: In this double-blind clinical trial, eighty patients participated based on the inclusion and exclusion criteria, of whom 40 cases received pantoprazole (group P) and 40 received famotidine (group F) for eight weeks. They were followed up for three, six, and twelve months after surgery for cage subsidence, screw loosening, and visual analogue scale (VAS), Oswestry disability index (ODI), Brantigan, Steffee, Fraser (BSF), and Lenke classification for grading their bone formation. A P<0.05 was considered significant. Results: The rate of fusion based on the Lenke score was lower in the group receiving pantoprazole six and 12 months after the surgery compared to group F (the frequency of Lenke grades C and D were 35% and 25% compared to the famotidine group 12.5% and 12.5%, respectively; P=0.042). The VAS Mean±SD score in group F was lower than group P after 12 months (2.48±1.06 and 1.83±0.55, respectively; P=0.008). There was no pharmacologically significant association between subsidence (P=0.43), loosening (P=0.13), ODI (P=0.31), and BSF (P=0.77) 3, 6 and 12 months post-operation. Conclusion: Affording to the preliminary conclusions of this study, the use of pump inhibitors, such as pantoprazole is more destructive for the ossification process in candidates for spinal fusion requiring the chronic use of drugs for controlling their gastric acid secretion, and H2-blocking drugs, such as famotidine are preferable in this situation after further investigations.

Decoding Metastasis: From Cell Death to Fusion in Cancer Progression.

Metastasis is one of the key concepts in modern oncology, which connects the movement of cancer cells in the body with changes in their characteristics and functions. The review examines the main aspects of metastasis, including theories, facts and discoveries that help to better understand this phenomenon and develop new approaches to its treatment. In this article, we also proposed the theory of cell fusion with the formation of hybrid cells as one of the factors of metastasis. We believe that the fusion of tumor cells with other types of motile cells (leukocytes and bone marrow progenitor cells) may represent an additional mechanism of tumor spread. Cells of bone marrow origin, including cells of the myeloid and macrophage lineages, are the best candidates for heterotypic fusion in regenerative conditions. Events such as cell fusion may play a role in tumor dedifferentiation and progression. We presented a number of arguments and data from our own research that speak in favor of the proposed theory. It should be noted that if the fusion of a normal cell with a tumor cell is one of the possible triggers of tumorigenesis and cancer spread, the mechanisms underlying this process may provide possible new targets for treatment. Therefore, their analysis will expand our arsenal of therapeutic tools by adding completely new targets - cell signaling molecules - and will provide the impetus for reconsidering the tumor microenvironment from a different angle.

Mental Health Rather than Mental Disorders as a Predictor of Immediate Postoperative Recovery Following Elective Lumbar Fusion

Study Design. Retrospective comparative cohort Objective. Investigate how a patient’s mental health, as measured using the PROMIS-10 Global Mental Health T-Score (MHT), influences their in-hospital recovery following elective one to two level lumbar fusion. Summary of Background Data. The intersection of mental and physical health among candidates for lumbar fusion has increased. While there is strong evidence to suggest mental disorders can influence a patient’s postoperative recovery, there is a paucity of information detailing the association between unrecognized low mental health and surgical outcomes. The MHT may provide a more nuanced insight to a patient’s preoperative mental health status. Methods. 637 patients that underwent one or two level elective lumbar fusion between April 2020 and June 2023 were analyzed for this study. Patients were stratified by their MHT (Above Average [AA] >50, control 40-50, Below Average [BA] <40) regardless of mental illness diagnosis. Outcome measures including: pain scores both during activity and at rest, opioid consumption during the in-hospital stay, and ambulation distance were compared among groups using both univariate and multivariate models to control for confounders. Results. The majority of patients reported average (41.4%) to above average (35.3%) mental health. After controlling for confounders, findings suggested that patients in the BA group reported higher pain, consumed more opioids, and had shorter ambulation distances than patients in the AA group (P=0.004, P-0.008, and P=0.020 respectively). Patients in the AA group were 84% less likely to be discharged to a facility compared to the BA group (P=0.001). Conclusion. The MHT was an independent predictor of immediate postsurgical recovery, while a mental disorder diagnosis was not. A preoperative MHT<40, may represent and additional risk factor that has not previously been identified in patients undergoing elective lumbar fusion.

Abstract 3361: Surfaceome and cancer testis antigen profiling of lung adenocarcinoma by large-scale transcriptomic analysis

Abstract Background: The emergence of improved modalities to target tumor specific and tumor associated antigens in solid tumors (e.g. antibody-drug conjugates, bi-specific antibodies, and adoptive cell therapy) underscores the need to efficiently identify and validate new therapeutic targets. Methods: We examined differential expression of surfaceome genes (Fonseca et al., 2016) and cancer testis (CT) antigen genes (Almeida et al., 2009) among major lung adenocarcinoma genomic subtypes; conducting comprehensive surfaceome/CT antigen profiling of 9002 NSCLC adenocarcinoma samples using data generated by RNA sequencing (whole transcriptome) at Caris Life Sciences (Phoenix, AZ). NSCLC tumors were stratified into 5 subgroups based on the presence of specific driver mutations: ALK fusion (N=325), EGFR mutant (N=1739), KRAS mutant (no STK11 or KEAP1 mutation; N=2561), KRAS + STK or KEAP1 mutation (N=1264), and Pan-WT (no mutation in ALK, EGFR, KRAS, STK11, or KEAP1 detected; N=3113). Fold-change in expression was calculated by dividing the median value for a specific subgroup by the median of all other groups combined. Significance was tested by Mann-Whitney U test, with p-values adjust for multiple hypothesis testing (Benjamini-Hochberg). Results: Surfaceome genes with the highest median expression overall included CD74, TMBIM6, and CD44, while the highest median expression among CT antigens was observed for SPAG9, KIAA0100, and RQCD1, yet the expression of these genes across the 5 driver mutation-based subgroups was similar (fold-changes ranged 0.93-1.06). To identify driver-associated candidate genes with relatively high expression, genes with subgroup-specific median expression >75th-percentile and with significant differences when compared to all other groups were ranked by fold-change. While several candidate surfaceome genes were associated with a specific subgroup, CLDN10 was identified among the top 3 candidates for both ALK fusion and KRAS + STK11/KEAP1 mutant subgroups: ALK fusion (GRIN2A, 3.03-fold; CLDN10, 2.53-fold; SLITRK6, 1.86-fold), EGFR mutant (SFTPC, 3.82-fold; MUC21, 1.99-fold; ATP13A4, 1.60-fold), KRAS mutant (VSIG1, 1.86-fold; AREG, 1.47-fold; C15orf48, 1.25-fold), and KRAS + STK11/KEAP1 mutant (ABCC2, 4.03-fold; MUC13, 3.21-fold; CLDN10, 3.00-fold). The top driver-associated CT antigen candidates included LEMD1 (1.42-fold) in ALK fusion, TMEM108 (1.27-fold) in EGFR mutant, XAGE1D (1.7-fold) in KRAS mutant, and CABYR (1.52-fold) in KRAS + STK11/KEAP1 mutant subgroups. Conclusion: Our analysis revealed several surfaceome and CT antigen candidate genes with relatively high expression across lung adenocarcinoma, as well as differential expression of candidate genes within specific genomic subtypes. These findings can help prioritize the validation and development of novel therapeutic targets in lung adenocarcinoma. Citation Format: Swartz Andrew, Andrew Elliott, George W. Sledge, Stephen V. Liu, Balazs Halmos, Vincent K. Lam, Taofeek K. Owonikoko. Surfaceome and cancer testis antigen profiling of lung adenocarcinoma by large-scale transcriptomic analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3361.

Updated Criteria for Fusion Level Selection in Adolescent Idiopathic Scoliosis Including Use of Three-Dimensional Analysis.

The development of new technologies and an enhanced understanding of the three-dimensional deformity in adolescent idiopathic scoliosis has led to advances in surgical management of adolescent idiopathic scoliosis. Posterior spinal approaches with pedicle screw constructs are now standard of care because they allow for powerful rotation maneuvers with three-column deformity correction. Selective fusion of the main curve while allowing for spontaneous correction of compensatory curves should be attempted whenever possible in the interest of limiting fusion size and preserving spinal mobility. Recent research provides updated criteria to determine optimal candidates for selective fusion. These criteria must be weighed against patient goals and patient-specific factors to limit complications and maximize chances of successful deformity correction.

Chronic Opioid Use Prior to ACDF Surgery Is Associated with Inferior Postoperative Outcomes: A Propensity-Matched Study of 17,443 Chronic Opioid Users

Candidates for anterior cervical discectomy and fusion (ACDF) have a higher rate of opioid use than does the public, but studies on preoperative opioid use have not been conducted. We aimed to understand how preoperative opioid use affects post-ACDF outcomes. The MarketScan Database was queried from 2007 to 2015 to identify adult patients who underwent an ACDF. Patients were classified into separate cohorts based on the number of separate opioid prescriptions in the year before their ACDF. Ninety-day postoperative complications, postoperative readmission, reoperation, and total inpatient costs were compared between opioid strata. Propensity score-matched patient cohorts were calculated to balance comorbidities across groups. Of 81,671 ACDF patients, 31,312 (38.3%) were nonusers, 30,302 (37.1%) were mild users, and 20,057 (24.6%) were chronic users. Chronic opioid users had a higher comorbidity burden, on average, than patients with less frequent opioid use (P < 0.001). Chronic opioid users had higher rates of postoperative complications (9.1%) than mild opioid users (6.0%) and nonusers (5.3%) (P < 0.001) and higher rates of readmission and reoperation. After balancing opioid nonusers versus chronic opioid users along with demographic characteristics, preoperative comorbidity, and operative characteristics, postoperative complications remained elevated for chronic opioid users relative to opioid nonusers (8.6% vs. 5.7%; P < 0.001), as did rates of readmission and reoperation. Chronic opioid users had more comorbidities than opioid nonusers and mild opioid users, longer hospitalizations, and higher rates of postoperative complication, readmission, and reoperation. After balancing patients across covariates, the outcome differences persisted, suggesting a durable association between preoperative opioid use and negative postoperative outcomes.

Irradiation damage concurrent challenges with RAFM and ODS steels for fusion reactor first-wall/blanket: a review

Reduced activation ferritic martensitic (RAFM) and oxide dispersion strengthened (ODS) steels are the most promising candidates for fusion first-wall/blanket (FW/B) structures. The performance of these steels will deteriorate during service due to neutron damage and transmutation-induced gases, such as helium/hydrogen, at elevated operating temperatures. Here, after highlighting the operating conditions of fusion reactor concepts and a brief overview, the main irradiation-induced degradation challenges associated with RAFM/ODS steels are discussed. Their long-term degradation scenarios such as (a) low-temperature hardening embrittlement (LTHE)—including dose-temperature dependent yield stress, tensile elongations, necking ductility, test temperature effect on hardening, Charpy impact ductile-to-brittle transition temperature and fracture toughness, (b) intermediate temperature cavity swelling, (c) the effect of helium on LTHE and cavity swelling, (d) irradiation creep and (e) tritium management issues are reviewed. The potential causes of LTHE are discussed, which highlights the need for advanced characterisation techniques. The mechanical properties, including the tensile/Charpy impact of RAFM and ODS steels, are compared to show that the current generation of ODS steels also suffers from LTHE, and shows irradiation hardening up to high temperatures of ∼400 °C–500 °C. To minimise this, future ODS steel development for FW/B-specific application should target materials with a lower Cr concentration (to minimise α′), and minimise other elements that could form embrittling phases under irradiation. RAFM steel-designing activities targeting improvements in creep and LTHE are reviewed. The need to better understand the synergistic effects of helium on the thermo-mechanical properties in the entire temperature range of FW/B is highlighted. Because fusion operating conditions will be complex, including stresses due to the magnetic field, primary loads like coolant pressure, secondary loads from thermal gradients, and due to spatial variation in damage levels and gas production rates, an experimentally validated multiscale modelling approach is suggested as a pathway to future reactor component designing such as for the fusion neutron science facility.

Symptomatic Sagittal Imbalance and Severe Degeneration of Paraspinal Muscle Predispose Suboptimal Outcomes After Lumbar Short Fusion Surgery for Degenerative Lumbar Spinal Stenosis

We sought to investigate the risk factors of suboptimal postoperative outcomes after short-segment surgery for degenerative lumbar spinal stenosis and severe sagittal imbalance and to recommend the appropriate candidates for the short fusion. A total of 101 elderly subjects who underwent short-segment surgery were included. Preoperative sagittal vertical axis decreased to ≤50 mm was determined as sagittal compensation; otherwise, it was determined as sagittal decompensation. At the latest follow-up, 64 patients with sagittal decompensation and 14 patients with proximal junctional kyphosis (PJK) were detected. Sagittal imbalance with the related symptoms was named as symptomatic sagittal imbalance. Preoperative clinical data and spinopelvic parameters were collected and compared between different groups. Symptomatic sagittal imbalance and severe degeneration of paravertebral muscle were revealed to be the risk factors for sagittal decompensation and PJK. More sagittal decompensations (100%) and PJKs (60%) were observed in patients with both of these risk factors. On the contrary, postoperative outcomes were superior with less sagittal decompensation (46.9%) and PJK (0%) in those with neither of the 2 factors. Symptomatic sagittal imbalance and severe degeneration of paraspinal muscle are the risk factors predisposing suboptimal surgical outcomes after lumbar short-segment decompression and fusion for degenerative lumbar spinal stenosis. We believe essential spinal function and substantial quality of paraspinal muscle are the keys to long-lasting good outcomes.

Important controversies in lumbar spine surgery: which patients benefit from lumbar spinal fusion and who should be fused?

Considering the rising tendency in the application of lumbar spine devices, a rigorous selection of candidates for lumbar spinal fusion must follow the benefit of the patient in terms of a better outcome than classical techniques or conservatory treatment. We pulled essential information from scientific sources regarding the clinical results of patients who underwent fusion surgery to sift patients who do better from fusion.&#x0D; We found out that imagistic proof of instability such as spondylolisthesis associated with lumbar spinal stenosis and refractory pain takes the most from spinal fusion procedures. Oswestry disability index improvement along with restoring the function and reduction of pain remained the postoperative desires of a successful fusion. Clinical amelioration with bracing test prior to intervention was a predictor of better results after fusion. Exclusion criteria like psychiatric disorders and prior lumbar spine surgery were highlighted since studies demonstrated that they are bad predictors of outcome in spinal fusion surgery.&#x0D; Laminectomy was nowhere implemented in the literature as to be urgently fused since only about 20% of patients manifest instability after this classical procedure. Iatrogenic segmental instability after laminectomy, radiologically proven should be a candidate for spinal fusion. These procedures have high costs and high rates of complications putting the patient’s functional status and quality of life at uncertainty since there is still a lot of debate in this area of spinal neurosurgery.

Awake spinal surgery: simplifying the learning curve with a patient selection algorithm.

There is a learning curve for surgeons performing "awake" spinal surgery. No comprehensive guidelines have been proposed for the selection of ideal candidates for awake spinal fusion or decompression. The authors sought to formulate an algorithm to aid in patient selection for surgeons who are in the startup phase of awake spinal surgery. The authors developed an algorithm for selecting patients appropriate for awake spinal fusion or decompression using spinal anesthesia supplemented with mild sedation and local analgesia. The anesthetic protocol that was used has previously been reported in the literature. This algorithm was formulated based on a multidisciplinary team meeting and used in the first 15 patients who underwent awake lumbar surgery at a single institution. A total of 15 patients who underwent decompression or lumbar fusion using the awake protocol were reviewed. The mean patient age was 61 ± 12 years, with a median BMI of 25.3 (IQR 2.7) and a mean Charlson Comorbidity Index of 2.1 ± 1.7; 7 patients (47%) were female. Key patient inclusion criteria were no history of anxiety, 1 to 2 levels of lumbar pathology, moderate stenosis and/or grade I spondylolisthesis, and no prior lumbar surgery at the level where the needle is introduced for anesthesia. Key exclusion criteria included severe and critical central canal stenosis or patients who did not meet the inclusion criteria. Using the novel algorithm, 14 patients (93%) successfully underwent awake spinal surgery without conversion to general anesthesia. One patient (7%) was converted to general anesthesia due to insufficient analgesia from spinal anesthesia. Overall, 93% (n = 14) of the patients were assessed as American Society of Anesthesiologists class II, with 1 patient (7%) as class III. The mean operative time was 115 minutes (± 60 minutes) with a mean estimated blood loss of 46 ± 39 mL. The median hospital length of stay was 1.3 days (IQR 0.1 days). No patients developed postoperative complications and only 1 patient (7%) required reoperation. The mean Oswestry Disability Index score decreased following operative intervention by 5.1 ± 10.8. The authors propose an easy-to-use patient selection algorithm with the aim of assisting surgeons with patient selection for awake spinal surgery while considering BMI, patient anxiety, levels of surgery, and the extent of stenosis. The algorithm is specifically intended to assist surgeons who are in the learning curve of their first awake spinal surgery cases.

Advanced Age Does Not Impact Outcomes After 1-level or 2-level Lateral Lumbar Interbody Fusion.

This was a retrospective comparative study. The objective of this study was to assess the effect of increased age on perioperative and postoperative complication rates, reoperation rates, and patient-reported pain and disability scores after lateral lumbar interbody fusion (LLIF). LLIF was developed to minimize soft tissue trauma and reduce the risk of vascular injury; however, there is little evidence regarding the effect of advanced age on outcomes of LLIF. Patients who underwent LLIF from 2009 to 2019 at one institution with a minimum 6-month follow-up were retrospectively reviewed. Patients less than 18 years old with musculoskeletal tumor or trauma were excluded. The primary outcome was the preoperative to postoperative change in the Numeric Pain Rating Scale (NPRS) for back pain. Operative time, estimated blood loss, length of stay, perioperative and 90-day complications, unplanned readmissions, reoperations, and change in Oswestry Disability Index were also evaluated. Relationships with age were assessed both with age as a continuous variable and segmenting by age below 70 versus 70+. In total, 279 patients were included. The median age was 65±13 years and 159 (57%) were female. Age was not related to improvements in back NPRS and Oswestry Disability Index. Operative time, estimated blood loss, length of stay, perioperative and 90-day complications, unplanned readmissions, reoperations, and radiographic fusion rate also were not related to age. After multivariable risk adjustment, increasing age was associated with greater improvements in back NPRS. The decrease in back NPRS was 0.68 (95% confidence interval: 0.14, 1.22; P=0.014) points greater for every 10-year increase in age. Age was not associated with rates of complication, readmission, or reoperation. LLIF is a safe and effective procedure in the elderly population. Advanced age is associated with larger improvements in preoperative back pain. Surgeons should consider the benefits of LLIF and other minimally invasive techniques when evaluating elderly candidates for lumbar fusion. Level III.

262. Does preoperative bone mineral density impact fusion success in anterior cervical spine surgery: a prospective cohort study

<h3>BACKGROUND CONTEXT</h3> Patients with osteoporosis have an imbalance in anabolic versus catabolic bone homeostasis. It has been theorized that osteoporosis may impact fusion rates in lumbar spine surgery. However, to our knowledge this has not been investigated in cervical spine surgery. As our population ages, we are encountering ever increasing numbers of patients with osteoporosis and osteopenia coming in for elective surgery. <h3>PURPOSE</h3> The purpose of this study is to identify risk factors for pseudarthrosis in patients undergoing anterior cervical spine surgery. <h3>STUDY DESIGN/SETTING</h3> This was a prospective, single-center study conducted at an academic medical center between 2002 and 2018. <h3>PATIENT SAMPLE</h3> Seventy-nine patients who underwent 1-4 level anterior cervical spine fusions between the years of 2002-2018, and had a bone mineral density examination performed preoperatively, completed the study with one year of clinical and radiographic follow-up. <h3>OUTCOME MEASURES</h3> Bone density as measured by T-score, Hounsfield units and fusion status were measured. <h3>METHODS</h3> We prospectively collected and analyzed data on patients undergoing anterior cervical spine fusions involving between 1-4 levels between the years of 2002-2018 in which a bone mineral density (BMD) examination was clinically indicated. Based on the World Health Organization (WHO) classification using DEXA scan for measurement of BMD, normal bone density was defined as T-score greater than or equal to -1 SD, osteopenia as having a T-score less than -1 and greater than -2.5 SD, and osteoporosis as having a T-score less than or equal to -2.5 SD. Patients were followed for a minimum of one year. CT scans performed postoperatively were used to evaluate fusion. Three Hounsfield unit measurements were obtained on the vertebrae above and below the fusion levels and averaged. A total of 79 patients completed the study with one-year of clinical and radiographic follow-up. BMD, number of levels fused, smoking status, age, sex and ACE inhibitors/ARBs were analyzed to assess their impact on fusion success. Fusion was established when there was continuous bone bridging between the vertebrae on CT scan. Multivariate analysis was performed to identify potential risk factors for pseudarthrosis utilizing JMP 10.0.0 statistical software. (SAS Institute Inc, Carey, North Carolina). <h3>RESULTS</h3> Fourteen patients (18%) developed pseudarthrosis at one-year postoperatively. The mean age at surgery was 58.8 ±10.5 (30 to 84 years). The mean BMD was -0.45 ±1.4 (-3 to 4). Osteopenia and osteoporosis were identified as risk factors for pseudarthorsis at a minimum of 1 year follow up. Number of levels fused, smoking status, Hounsfield units, ACE/ARB medications, age or gender were not statistically significant risk factors correlated with development of pseudarthrosis although the study may have been underpowered to detect these differences. <h3>CONCLUSIONS</h3> This study suggests that preoperative osteopenia or osteoporosis may be correlated with a higher incidence of pseudarthrosis in anterior cervical spine surgery, even more so than smoking or number of levels fused. While the number of patients enrolled in this study is small, the results are convincing enough to warrant screening and treatment of osteoporosis as well as the optimization of preoperative bone stock in all potential candidates for cervical spine fusion. <h3>FDA DEVICE/DRUG STATUS</h3> This abstract does not discuss or include any applicable devices or drugs.

Temperature-Dependent Cavity Swelling in Dual-Ion Irradiated Fe and Fe-Cr Ferritic Alloys

Fe-Cr ferritic-martensitic (FM) steels are promising structural material candidates for fusion and advanced fission reactors due to their attractive mechanical properties and volumetric swelling resistance. However, significant discrepancies exist regarding the effect of solutes and irradiation temperature on cavity swelling under ion versus neutron irradiation conditions. In this study, simultaneous dual ion irradiations (8 MeV Ni3+ ions and energy-degraded 3.5 MeV He2+ ions) were used to quantify the cavity swelling behavior in ultra-high purity Fe and Fe-Cr alloys (3-14 wt.% Cr), Fe-10 wt.% Cr-780 wt.ppm C, and Eurofer97 FM steel. The irradiations were conducted over a wide temperature range (400-550 °C) with a mid-range dose of ~30 displacements per atom (dpa) and 0.1 appm/dpa He implantation rate. Using state-of-the-art transmission electron microscopy (TEM), we reveal that pure Fe has a ~50 °C lower peak swelling temperature than Fe-Cr alloys, which is attributed to higher vacancy mobility in pure Fe. Chromium solute appears to strongly suppress cavity swelling in Fe-Cr alloys for temperatures below ~470 °C, but seems to have little effect or slightly enhances swelling above ~470 °C. Cavities were observed in all the irradiated samples between 400-550 °C. This indicates that the narrow temperature range of observable cavities reported in prior ion irradiated Fe-Cr ferritic alloy studies is likely an artefact associated with the use of low ion energies (<5 MeV), which leads to pronounced near-surface and implanted ion effects that suppress cavity swelling even at midrange depths (particularly at high temperatures).

Early Colorectal Responses to HIV-1 and Modulation by Antiretroviral Drugs.

Innate responses during acute HIV infection correlate with disease progression and pathogenesis. However, limited information is available about the events occurring during the first hours of infection in the mucosal sites of transmission. With an ex vivo HIV-1 challenge model of human colorectal tissue we assessed the mucosal responses induced by R5- and X4-tropic HIV-1 isolates in the first 24 h of exposure. Microscopy studies demonstrated virus penetration of up to 39 μm into the lamina propia within 6 h of inoculation. A rapid, 6 h post-challenge, increase in the level of secretion of inflammatory cytokines, chemokines, interferon- γ (IFN-γ), and granulocyte-macrophage colony-stimulating factor (GM-CSF) was observed following exposure to R5- or X4-tropic isolates. This profile persisted at the later time point measured of 24 h. However, exposure to the X4-tropic isolate tested induced greater changes at the proteomic and transcriptomic levels than the R5-tropic. The X4-isolate induced greater levels of CCR5 ligands (RANTES, MIP-1α and MIP-1β) secretion than R5-HIV-1. Potential drugs candidates for colorectal microbicides, including entry, fusion or reverse transcriptase inhibitors demonstrated differential capacity to modulate these responses. Our findings indicate that in colorectal tissue, inflammatory responses and a Th1 cytokine profile are induced in the first 24 h following viral exposure.

Temperature-dependent cavity swelling in dual-ion irradiated Fe and Fe-Cr ferritic alloys

Fe-Cr ferritic-martensitic (FM) steels are promising structural material candidates for fusion and advanced fission reactors due to their attractive mechanical properties and volumetric swelling resistance. However, significant discrepancies exist regarding the effect of solutes and irradiation temperature on cavity swelling under ion versus neutron irradiation conditions. In this study, simultaneous dual ion irradiations (8 MeV Ni3+ ions and energy-degraded 3.5 MeV He2+ ions) were used to quantify the cavity swelling behavior in ultra-high purity Fe and Fe-Cr alloys (3-14 wt.% Cr), Fe-10 wt.% Cr-780 wt.ppm C, and Eurofer97 FM steel. The irradiations were conducted over a wide temperature range (400-550°C) with a mid-range dose of ~30 displacements per atom (dpa) and 0.1 appm/dpa He implantation rate. Using state-of-the-art transmission electron microscopy (TEM), we reveal that pure Fe has a ~50°C lower peak swelling temperature difference than Fe-Cr alloys, which is attributed to higher vacancy mobility in pure Fe. Chromium solute appears to strongly suppress cavity swelling in Fe-Cr alloys for temperatures below ~470°C, but seems to have little effect or slightly enhances swelling above ~470°C. Cavities were observed in all the irradiated samples between 400-550°C. This indicates that the narrow temperature range of observable cavities reported in prior ion irradiated Fe-Cr ferritic alloy studies is likely an artifact associated with the use of low ion energies (<5 MeV), which leads to pronounced near-surface and implanted ion effects that suppress cavity swelling even at midrange depths (particularly at high temperatures).

Outcomes following discectomy for lumbar disc herniation in patients with substantial back pain

OBJECTIVEPatients with lumbar disc herniation (LDH) typically present with lower-extremity radiculopathy. However, there are patients who have concomitant substantial back pain (BP) and are considered candidates for fusion. The purpose of this study was to determine if patients with LDH and substantial BP improve with discectomy alone.METHODSThe DaneSpine database was used to identify 2399 patients with LDH and baseline BP visual analog scale (VAS) scores ≥ 50 who underwent a lumbar discectomy at one of 3 facilities between June 2010 and December 2017. Standard demographic and surgical variables and patient-reported outcomes, including BP and leg pain (LP) VAS scores (0–100), Oswestry Disability Index (ODI), and European Quality of Life–5 Dimensions Questionnaire (EQ-5D) at baseline and 12 months postoperatively, were collected.RESULTSA total of 1654 patients (69%) had 12-month data available, with a mean age of 48.7 years; 816 (49%) were male and the mean BMI was 27 kg/m2. At 12 months postoperatively, there were statistically significant improvements (p &lt; 0.0001) in BP (72.6 to 36.9), LP (74.8 to 32.6), ODI (50.9 to 25.1), and EQ-5D (0.25 to 0.65) scores.CONCLUSIONSPatients with LDH and LP and concomitant substantial BP can be counseled to expect improvement in their BP 12 months after surgery after a discectomy alone, as well as improvement in their LP.

Can fusion to S1 maintain favorable surgical outcomes following one-level pedicle subtraction osteotomy in patients with thoracolumbar kyphosis secondary to ankylosing spondylitis?

To compare the surgical outcomes between ankylosing spondylitis (AS)-related thoracolumbar kyphosis patients with the lowest instrumented vertebra (LIV) at S1 or above following one-level pedicle subtraction osteotomy (PSO). One hundred and two AS patients undergoing one-level PSO with a minimum of 2-year follow-up were included. Twenty-two patients were in group S1 (LIV at S1), and eighty were in group non-S1 (LIV above S1). Radiographic parameters including lumbar lordosis (LL), sacral slope (SS), pelvic incidence (PI), and sagittal vertical axis (SVA) were measured. Oswestry Disability Index (ODI) and visual analog scale (VAS) were applied for clinical assessment. In both S1 and non-S1 groups, the radiographic parameters and clinical outcomes were significantly improved after surgery (P < 0.05). Patients undergoing distal fusion to S1 had significantly larger preoperative PI-LL mismatch, SVA, and smaller preoperative LL and SS compared to those in group non-S1 (P < 0.05). No significant difference was found between the two groups regarding preoperative and final follow-up ODI and VAS (P > 0.05), as well as the improvement in ODI and VAS (P > 0.05). The incidence of overall complications and each type of complication including the implant failure was similar between group S1 and non-S1 (P > 0.05). Selecting S1 as the LIV without pelvic fixation following one-level PSO in thoracolumbar kyphosis caused by AS could achieve satisfactory surgical outcomes and might not increase the complications. Patients with relatively severe sagittal imbalance, loss of LL, PI-LL mismatch, and small SS might be the potential candidates for distal fusion to S1 following one-level PSO.

59. Outcomes following discectomy for lumbar disc herniation in patients with substantial back pain

BACKGROUND CONTEXT Patients with LDH typically present with lower extremity radiculopathy. However, some patients with substantial back pain are considered by some surgeons to be candidates for fusion. The purpose of this study is to determine if LDH patients with substantial back pain improve with a discectomy alone. PURPOSE To determine if back pain in patients with lumbar disc herniation (LDH) improves after discectomy alone without fusion. STUDY DESIGN/SETTING Longitudinal observational cohort. PATIENT SAMPLE Patients enrolled in DaneSpine. OUTCOME MEASURES Back and Leg pain VAS (0-100), Oswestry Disability Index (ODI), and EuroQoL 5D (EQ-5D). METHODS The DaneSpine database was used to identify 2,399 patients with LDH and baseline back pain VAS ≥ 50 who underwent a lumbar discectomy. Standard demographic and surgical variables and patient-reported outcomes including back and leg pain VAS (0-100), Oswestry Disability Index (ODI), and EuroQoL 5D (EQ-5D) at baseline and 12 months postoperatively were collected. RESULTS A total of 1,654 (69%) cases had 12-month data available, with a mean age of 48.7 years; 816 (49%) were male and mean BMI was 27 kg/m2. At 12 months postoperatively, there were statistically significant (p CONCLUSIONS Patients with LDH who have substantial back pain can be counseled to expect improvement in their back pain 12 months after surgery after a discectomy alone. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

294. Coupled rotation patterns in cervical axial rotation can change when the head is kept level

BACKGROUND CONTEXT Axial rotation of the cervical spine with the cranium held level occurs during certain daily activities such as looking over one's shoulder when walking or driving. These activities require rotation from the suboccipital and subaxial cervical spine. The literature on cervical spine axial rotation and coupled rotations has been obtained from experiments where the segmental axis of rotation is aligned with the global axis of rotation. In looking over one's shoulder, the segmental rotation axes may not be aligned with the global and primarily vertical rotation axis due to curvature of the spine. Furthermore, fusion may limit the amount of rotation that can be obtained from the subaxial spine and reduce the facility with which the daily activities are performed. PURPOSE (1) To define the rotation of the intact subaxial spine during horizontal axial rotation of the cranium, and (2) To measure the effect of C5-C7 fusion on the rotation of the subaxial spine during horizontal axial rotation of the cranium. STUDY DESIGN/SETTING Biomechanical experiment. PATIENT SAMPLE Five C0-T1 cadaveric spine specimens (38-54 years old, 3 female and 2 male). OUTCOME MEASURES Rotation of the subaxial cervical spine in response to applied axial rotation moment. METHODS A left and right axial rotation moment of 1Nm was applied to specimens mounted in an apparatus that held the cranium in an orientation consistent with horizontal gaze (horizontal Frankfort line). The axial rotation axis passed through the midpoint between the two external auditory meatuses. Rotations of the individual vertebrae before and after C5-C7 fusion using lateral mass screws and posterior rods were measured using an optoelectronic motion measurement system. RESULTS C5-C7 fusion reduced the C3-T1 axial rotation range of motion from a mean of 31±5° to 22±5°. In the nonfused levels, the axial rotation range of motion changed less than half a degree. Holding the cranium level (horizontal gaze) changes the segmental and overall coupled rotation behavior of the cervical spine during axial rotation. In 3 specimens, left axial rotation induced both right lateral bending in the lower segments and left lateral bending in upper segments, and vice versa with right axial rotation. In the three specimens in which both left and right lateral bending was induced by axial rotation, there was a 0.1° to 3.7° reduction in the coupled C3-C4 lateral bending range of motion. In the other two specimen, C3-C4 lateral bending range of motion increased by 0.8° to 1.8°. C5-C7 fusion changed the amount but not the direction of coupled lateral bending of unfused segments. CONCLUSIONS Without the horizontal gaze constraint, right axial rotation has been shown to induce right lateral bending in the cervical spine. There are various activities of daily living, such as looking over one's shoulder, that involve holding the gaze horizontal while axially rotating the cervical spine. In this biomechanical experiment, a constrained horizontal axial rotation resulted in specimen-specific coupled rotation of the subaxial cervical spine. In three of the specimen, axial rotation induced left and right segmental lateral bending regardless of the axial rotation direction.This specimen-specific difference in the coupled lateral bending and in the ability to perform constrained axial rotation after C5-C7 fusion leads us to wonder whether there may also be a patient-specific difference. This difference would have clinical implications for patients who are candidates for C5-C7 fusion. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

A Cost-Effectiveness Analysis of the Integration of Robotic Spine Technology in Spine Surgery.

ObjectiveWe investigate the cost-effectiveness of adding robotic technology in spine surgery to an active neurosurgical practice. MethodsThe time of operative procedures, infection rates, revision rates, length of stay, and possible conversion of open to minimally invasive spine surgery (MIS) secondary to robotic image guidance technology were calculated using a combination of institution-specific and national data points. This cost matrix was subsequently applied to 1 year of elective clinical case volume at an academic practice with regard to payor mix, procedural mix, and procedural revenue. ResultsA total of 1,985 elective cases were analyzed over a 1-year period; of these, 557 thoracolumbar cases (28%) were analyzed. Fifty-eight (10.4%) were MIS fusions. Independent review determined an additional ~10% cases (50) to be candidates for MIS fusion. Furthermore, 41.4% patients had governmental insurance, while 58.6% had commercial insurance. The weighted average diagnosis-related group reimbursement for thoracolumbar procedures for the hospital system was calculated to be $25,057 for Medicare and $42,096 for commercial insurance. Time savings averaged 3.4 minutes per 1-level MIS procedure with robotic technology, resulting in annual savings of $5,713. Improved pedicle screw accuracy secondary to robotic technology would have resulted in 9.47 revisions being avoided, with cost savings of $314,661. Under appropriate payor mix components, robotic technology would have converted 31 Medicare and 18 commercial patients from open to MIS. This would have resulted in 140 fewer total hospital admission days ($251,860) and avoided 2.3 infections ($36,312). Robotic surgery resulted in immediate conservative savings estimate of $608,546 during a 1-year period at an academic center performing 557 elective thoracolumbar instrumentation cases. ConclusionApplication of robotic spine surgery is cost-effective, resulting in lesser revision surgery, lower infection rates, reduced length of stay, and shorter operative time. Further research is warranted, evaluating the financial impact of robotic spine surgery.