How common is acute pelvic fixation failure after adult spine surgery? A single-center study of 358 patients.

OBJECTIVE: There is a paucity of literature on pelvic fixation failure after adult spine surgery in the early postoperative period. The purpose of this study was to determine the incidence of acute pelvic fixation failure in a large single-center study and to describe the lessons learned. METHODS: The authors performed a retrospective review of adult (≥ 18 years old) patients who underwent spinal fusion with pelvic fixation (iliac, S2-alar-iliac [S2AI] screws) at a single academic medical center between 2015 and 2020. All patients had a minimum of 3 instrumented levels. The minimum follow-up was 6 months after the index spine surgery. Patients with prior pelvic fixation were excluded. Acute pelvic fixation failure was defined as revision of the pelvic screws within 6 months of the primary surgery. Patient demographics and operative, radiographic, and rod/screw parameters were collected. All rods were cobalt-chrome. All iliac and S2AI screws were closed-headed screws. RESULTS: In 358 patients, the mean age was 59.5 ± 13.6 years, and 64.0% (n = 229) were female. The mean number of instrumented levels was 11.5 ± 5.5, and 79.1% (n = 283) had ≥ 6 levels fused. Three-column osteotomies were performed in 14.2% (n = 51) of patients, and 74.6% (n = 267) had an L5-S1 interbody fusion. The mean diameter/length of pelvic screws was 8.5/86.6 mm. The mean number of pelvic screws was 2.2 ± 0.5, the mean rod diameter was 6.0 ± 0 mm, and 78.5% (n = 281) had > 2 rods crossing the lumbopelvic junction. Accessory rods extended to S1 (32.7%, n = 117) or S2/ilium (45.8%, n = 164). Acute pelvic fixation failure occurred in 1 patient (0.3%); this individual had a broken S2AI screw near the head-neck junction. This 76-year-old woman with degenerative lumbar scoliosis and chronic lumbosacral zone 1 fracture nonunion had undergone posterior instrumented fusion from T10 to pelvis with bilateral S2AI screws (8.5 × 90 mm); i.e., transforaminal lumbar interbody fusion L4-S1. The patient had persistent left buttock pain postoperatively, with radiographically confirmed breakage of the left S2AI screw 68 days after surgery. Revision included instrumentation removal at L2-pelvis and a total of 4 pelvic screws. CONCLUSIONS: The acute pelvic fixation failure rate was exceedingly low in adult spine surgery. This rate may be the result of multiple factors including the preference for multirod (> 2), closed-headed pelvic screw constructs in which large-diameter long screws are used. Increasing the number of rods and screws at the lumbopelvic junction may be important factors to consider, especially for patients with high risk for nonunion.

Incidence, mechanism, and protective strategies for 2-year pelvic fixation failure after adult spinal deformity surgery with a minimum six-level fusion.

OBJECTIVE: The purpose of this study was to determine the incidence, mechanism, and potential protective strategies for pelvic fixation failure (PFF) within 2 years after adult spinal deformity (ASD) surgery. METHODS: Data for ASD patients (age ≥ 18 years, minimum of six instrumented levels) with pelvic fixation (S2-alar-iliac [S2AI] and/or iliac screws) with a minimum 2-year follow-up were consecutively collected (2015-2019). Patients with prior pelvic fixation were excluded. PFF was defined as any revision to pelvic screws, which may include broken rods across the lumbosacral junction requiring revision to pelvic screws, pseudarthrosis across the lumbosacral junction requiring revision to pelvic screws, a broken or loose pelvic screw, or sacral/iliac fracture. Patient information including demographic data and health history (age, sex, BMI, smoking status, American Society of Anesthesiologists score, osteoporosis), operative (total instrumented levels [TIL], three-column osteotomy [3CO], interbody fusion), screw (iliac, S2AI, length, diameter), rod (diameter, kickstand), rod pattern (number crossing lumbopelvic junction, lowest instrumented vertebra [LIV] of accessory rod[s], lateral connectors, dual-headed screws), and pre- and postradiographic (lumbar lordosis, pelvic incidence, pelvic tilt, major Cobb angle, lumbosacral fractional curve, C7 coronal vertical axis [CVA], T1 pelvic angle, C7 sagittal vertical axis) parameters was collected. All rods across the lumbosacral junction were cobalt-chrome. All iliac and S2AI screws were closed-headed tulips. Both univariate and multivariate analyses were performed to determine risk factors for PFF. RESULTS: Of 253 patients (mean age 58.9 years, mean TIL 13.6, 3CO 15.8%, L5-S1 interbody 74.7%, mean pelvic screw diameter/length 8.6/87 mm), the 2-year failure rate was 4.3% (n = 11). The mechanisms of failure included broken rods across the lumbosacral junction (n = 4), pseudarthrosis across the lumbosacral junction requiring revision to pelvic screws (n = 3), broken pelvic screw (n = 1), loose pelvic screw (n = 1), sacral/iliac fracture (n = 1), and painful/prominent pelvic screw (n = 1). A higher number of rods crossing the lumbopelvic junction (mean 3.8 no failure vs 2.9 failure, p = 0.009) and accessory rod LIV to S2/ilium (no failure 54.2% vs failure 18.2%, p = 0.003) were protective for failure. Multivariate analysis demonstrated that accessory rod LIV to S2/ilium versus S1 (OR 0.2, p = 0.004) and number of rods crossing the lumbar to pelvis (OR 0.15, p = 0.002) were protective, while worse postoperative CVA (OR 1.5, p = 0.028) was an independent risk factor for failure. CONCLUSIONS: The 2-year PFF rate was low relative to what is reported in the literature, despite patients undergoing long fusion constructs for ASD. The number of rods crossing the lumbopelvic junction and accessory rod LIV to S2/ilium relative to S1 alone likely increase construct stiffness. Residual postoperative coronal malalignment should be avoided to reduce PFF.

Management of Anticoagulation/Antiplatelet Medication and Venous Thromboembolism Prophylaxis in Elective Spine Surgery: Concise Clinical Recommendations Based on a Modified Delphi Process.

STUDY DESIGN: Delphi method. OBJECTIVE: To gain consensus on the following questions: (1) When should anticoagulation/antiplatelet (AC/AP) medication be stopped before elective spine surgery?; (2) When should AC/AP medication be restarted after elective spine surgery?; (3) When, how, and in whom should venous thromboembolism (VTE) chemoprophylaxis be started after elective spinal surgery? SUMMARY OF BACKGROUND DATA: VTE can lead to significant morbidity after adult spine surgery, yet postoperative VTE prophylaxis practices vary considerably. The management of preoperative AC/AP medication is similarly heterogeneous. MATERIALS AND METHODS: Delphi method of consensus development consisting of three rounds (January 26, 2021, to June 21, 2021). RESULTS: Twenty-one spine surgeons were invited, and 20 surgeons completed all rounds of questioning. Consensus (>70% agreement) was achieved in 26/27 items. Group consensus stated that preoperative Direct Oral Anticoagulants should be stopped two days before surgery, warfarin stopped five days before surgery, and all remaining AC/AP medication and aspirin should be stopped seven days before surgery. For restarting AC/AP medication postoperatively, consensus was achieved for low-risk/medium-risk/high-risk patients in 5/5 risk factors (VTE history/cardiac/ambulation status/anterior approach/operation). The low/medium/high thresholds were POD7/POD5/POD2, respectively. For VTE chemoprophylaxis, consensus was achieved for low-risk/medium-risk/high-risk patients in 12/13 risk factors (age/BMI/VTE history/cardiac/cancer/hormone therapy/operation/anterior approach/staged separate days/staged same days/operative time/transfusion). The one area that did not gain consensus was same-day staged surgery. The low-threshold/medium-threshold/high-threshold ranges were postoperative day 5 (POD5) or none/POD3-4/POD1-2, respectively. Additional VTE chemoprophylaxis considerations that gained consensus were POD1 defined as the morning after surgery regardless of operating finishing time, enoxaparin as the medication of choice, and standardized, rather than weight-based, dose given once per day. CONCLUSIONS: In the first known Delphi study to address anticoagulation/antiplatelet recommendations for elective spine surgery (preoperatively and postoperatively); our Delphi consensus recommendations from 20 spine surgeons achieved consensus on 26/27 items. These results will potentially help standardize the management of preoperative AC/AP medication and VTE chemoprophylaxis after adult elective spine surgery.

A new modular radiographic classification of adult idiopathic scoliosis as an extension of the Lenke classification of adolescent idiopathic scoliosis.

PURPOSE: To propose and test the reliability of a radiographic classification system for adult idiopathic scoliosis. METHODS: A three-component radiographic classification for adult idiopathic scoliosis consisting of curve type, a lumbosacral modifier, and a global alignment modifier is presented. Twelve spine surgeons graded 30 pre-marked cases twice, approximately 1 week apart. Case order was randomized between sessions. RESULTS: The interrater reliability (Fleiss' kappa coefficient) for curve type was 0.660 and 0.798, for the lumbosacral modifier 0.944 and 0.965, and for the global alignment modifier 0.922 and 0.916, for round 1 and 2 respectively. Mean intrarater reliability was 0.807. CONCLUSIONS: This new radiographic classification of adult idiopathic scoliosis maintains the curve types from the Lenke classification and introduces the lumbosacral and global alignment modifiers. The reliability of the lumbosacral modifier and global alignment modifier shows near perfect agreement, and sets the foundation for further studies to validate the reliability, utility, and applicability of this classification system.

Dynamics of central and peripheral immunomodulation in a murine glioma model.

BACKGROUND: Immunosuppression by gliomas contributes to tumor progression and treatment resistance. It is not known when immunosuppression occurs during tumor development but it likely involves cross-talk among tumor cells, tumor-associated macrophages and microglia (TAMs), and peripheral as well as tumor-infiltrating lymphocytes (TILs). RESULTS: We have performed a kinetic study of this immunomodulation, assessing the dynamics of immune infiltration and function, within the central nervous system (CNS) and peripherally. PDGF-driven murine glioma cells were injected into the white matter of 13 mice. Four mice were sacrificed 13 days post-injection (dpi), four mice at 26 dpi, and five mice at 40 dpi. Using multiparameter flow cytometry, splenic T cells were assessed for FoxP3 expression to identify regulatory T cells (Tregs) and production of IFN-gamma and IL-10 after stimulation with PMA/ionomycin; within the CNS, CD4+ TILs were quantified, and TAMs were quantified and assessed for TNF-alpha and IL-10 production after stimulation with LPS. Peripheral changes associated with tumor development were noted prior to effects within the CNS. The percentage of FoxP3+ regulatory T cells (Tregs) increased by day 26, with elevated frequencies throughout the duration of the study. This early increase in Tregs was paralleled by an increase in IL-10 production from Tregs. At the final time points examined (tumor morbidity or 40 dpi), there was an increase in the frequency of TAMs with decreased capacity to secrete TNF-alpha. An increase in TIL frequency was also observed at these final time points. CONCLUSION: These data provide insight into the kinetics of the immunosuppressive state associated with tumor growth in a murine model of human gliomas. Functional impairment of TAMs occurs relatively late in the course of GBM tumor growth, potentially providing a window of opportunity for therapeutic strategies directed towards preventing their functional impairment.

Posterior dynamic stabilization of the lumbar spine: pedicle based stabilization with the AccuFlex rod system.

Posterior dynamic stabilization in the lumbar spine is performed in an attempt to reduce loading across the intervertebral disc for the purpose of relieving pain and limiting degeneration while preserving motion. The AccuFlex rod system (Globus Medical, Inc.), a first-generation device, achieves this by changing the properties of the rod within the Protex pedicle screw-based rigid rod system. Helical cuts that have been created in the standard 6.5-mm rod allow for a limited range of motion while providing a posterior tension band that relieves a significant amount of disc loading. The AccuFlex rod system has been approved by the Food and Drug Administration for single-level fusion when used in conjunction with an interbody graft. In a study involving 170 patients who underwent fusion surgery for back pain, the 54 who received the AccuFlex construct had statistically similar fusion rates and outcomes (as assessed by visual analog scale and Short Form-16 scores) when compared with 116 patients treated with rigid rod fixation after 1 year of follow up. Future clinical studies will examine and provide information regarding the impact of AccuFlex on the incidence of adjacent-level disease. Information gained through the clinical experience with AccuFlex will serve as a foundation for the development of a stand-alone dynamic construct.

Surgeon-Delivered Nerve Block for Reduction of Perioperative Pain and Opioid Use After Lumbosacral Spine Surgery.

This cohort study compares postoperative pain scores, opioid use, and length of hospital stay among adults undergoing noninstrumented lumbosacral surgery who received x-ray­guided dorsal ramus block vs those who did not.

Management of childhood spasticity: a neurosurgical perspective.

The management of childhood spasticity requires a multidisciplinary effort. With input from pediatricians, physical and occupational therapists, neurologists, orthotists, orthopedic surgeons, neurological surgeons, and other healthcare personnel, effective treatment for spasticity can be initiated and maintained that can lead to meaningful improvements in quality of life for vast numbers of children. Neurosurgical treatment of spasticity will continue to evolve and be refined as procedures and techniques are appropriately evaluated with reliable and validated outcome measures.

Severity of presentation is associated with time to recovery in spinal epidural lipomatosis.

We present a patient with prednisone-induced spinal epidural lipomatosis (SEL) and relatively acute neurologic deterioration followed by rapid recovery after surgical decompression. SEL is a rare disease characterized by hypertrophy of epidural fat, most commonly associated with exogenous steroid use. To our knowledge, an analysis of the dynamics of steroid dose related to time to onset has never been performed, or of patient presentation features with respect to patient outcome. We retrospectively reviewed the literature for English language series and case reports of SEL associated with prednisone use from 1975-2013. Data were compiled for 41 patients regarding the prescribed dose of prednisone and length of treatment, as well as the severity of symptoms on the Ranawat scale, time to onset, time to recovery, and degree of recovery of neurological symptoms. Fisher's exact test and analysis of variance were used for comparing proportions, and p values <0.05 were considered statistically significant. We found that the mean cumulative dose of prednisone trended towards an association with a lack of recovery (p=0.06) and may be related to rate of recovery. Prescribed prednisone dose varied inversely with the time before onset of neurological symptoms, but failed to reach statistical significance. Higher severity of presenting symptoms on the Ranawat scale were found to be associated with a higher likelihood of delayed recovery (p=0.035). Patients with symptoms lower on the Ranawat scale more frequently experienced complete neurologic recovery, though this did not reach significance. The acuity of neurological deterioration was not related to the time to recovery or ultimate degree of recovery. Severity of presentation on the Ranawat scale is associated with rate of recovery and may be related to degree of recovery in SEL patients. Cumulative dose of prednisone may be related to degree and rate of recovery. Prescribed dose of prednisone may be related to time to onset of neurological symptoms. Acuity of neurological deterioration is not related to rate or degree of recovery.

Cancer-testis and melanocyte-differentiation antigen expression in malignant glioma and meningioma.

Identification of well-defined glioma-specific antigens is a crucial and necessary step in developing immunotherapy for glioblastoma multiforme (GBM). In this study, we analyzed the composite expression of cancer-testis antigens (CTA) and melanocyte-differentiation antigens (MDA) in malignant glioma tissue and primary glioma cell lines and compared them with normal brain specimens and meningioma. CTA and MDA expression was assessed by the reverse transcription-polymerase chain reaction. The following primers were analyzed for CTA: LAGE-1, NY-ESO-1, MAGE-1, MAGE-3, MAGE-4, MAGE-10, CT-7, CT-10, HOM-MEL 40, BAGE, and SCP-1; and for MDA: tyrosinase, gp100, MELAN-A/MART-1, and TRP-2. The expression level was determined by ethidium bromide-stained agarose gel. Among malignant glioma tissue, the highest CTA and MDA expression rates were found for MAGE-3 (22%), MAGE-1 (16%), CT-7 (11%), gp100 (40%), and TRP-2 (29%). Among primary glioma cell lines, the highest levels of expression were: CT-10 (38%), gp100 (100%), and TRP-2 (31%). NY-ESO-1 was the only CTA demonstrated and seen in 12% of meningioma tissue specimens. TRP-2 and gp100 were expressed in 65% and 38% of meningioma tissue, respectively; gp100 and TRP-2 were expressed in 100% and 50% of meningioma cell lines. Of the nine normal brain specimens, all samples tested positive for TRP-2. All other CTA and MDA tested negative in normal brain. We conclude that CTA and MDA demonstrate low-to-variable levels of expression within GBM. However, two CTA (MAGE-1 and MAGE-3) and one MDA (gp100) may be considered candidate antigens based on their restricted expression in GBM. These results will greatly accelerate the development of novel, specific immunotherapeutic strategies.

Operative management of spinal hemangioblastoma.

Hemangioblastomas occur in 2% to 15% of reported series of intramedullary spinal cord tumors. They are benign, highly vascular tumors that can be cured with surgical resection. Complete removal of these tumors with low morbidity is possible with current microneurosurgical techniques and a thorough understanding of the typical relationship of the tumor to adjacent neural structures. We describe our experience with 16 intramedullary and 2 lumbosacral nerve root hemangioblastomas and review the relevant published literature. A detailed discussion of the operative technique is provided along with an operative video. Three illustrative cases are used to demonstrate clinical considerations that can arise with these tumors, including surgery during pregnancy, symptoms related to syrinx or syringomyelia, and postoperative consequences of neurological deficits.

The survival impact of postoperative infection in patients with glioblastoma multiforme.

OBJECTIVE: The capacity for local infection to prolong survival in patients with cancer is a widely accepted but unsubstantiated principle. The neurosurgical literature contains anecdotal reports of patients with malignant gliomas who experienced prolonged remission of their tumors after a bacterial infection. This association has not been explored in a larger series of patients with malignant glioma with postoperative infections. METHODS: A single-center operative experience accumulated over 10 years was examined to evaluate whether postoperative infections conferred a survival advantage in patients with glioblastoma multiforme. A total of 382 patients were examined, and 18 bacterial infections were identified. The vast majority (17 cases, 94%) of these were gram-positive infections. Cases were compared with age-matched controls. Survival differences were evaluated using Kaplan-Meier curves, and other differences were tested using the Mann-Whitney U test. RESULTS: Cases and controls were younger and survived longer than the overall study sample, but cases and controls were similar at baseline. A moderate, statistically insignificant survival advantage was seen in the case group (Kaplan-Meier P = 0.27). However, when patients with infections in the first quarter and first half of their postoperative survival were examined, this survival advantage disappeared. There was no significant survival difference in any subgroup analyzed, including deep infections, bone flap infections, or infections caused by any specific organism. CONCLUSION: In this single-center study, postoperative infection did not confer any survival advantage in patients with glioblastoma multiforme.

Lack of B7 expression, not human leukocyte antigen expression, facilitates immune evasion by human malignant gliomas.

OBJECTIVE: Lack of human leukocyte antigens and costimulatory molecules have been suggested as mechanisms by which human malignant gliomas avoid immune recognition and elimination. METHODS: Using quantitative multiparameter flow cytometric analysis, tumor cells from patients with glioblastoma multiforme (n = 18) were examined ex vivo for the expression of human leukocyte antigen Class I and II molecules and the costimulatory molecules B7-1 and B7-2. They were compared with reactive astrocytes from peritumoral brain metastases (n = 7), and astrocytes removed during nontumor surgery (n = 5). RESULTS: In contrast to the vast majority of solid peripheral human tumors, these results demonstrate that glioblastoma multiforme frequently express both human leukocyte antigen Class I and II molecules. Like most solid peripheral tumors, glioblastoma multiforme tumor cells express few or no B7 costimulatory molecules. Functional assays using heterogeneous ex vivo tumor preparations or pure populations of ex vivo tumor cells and microglia obtained using fluorescence-activated cell sorting indicate that CD4+ T-cells are activated by tumor cells only in the presence of exogenous B7 costimulation (provided by addition of soluble agonist anti-CD28 monoclonal antibody). CONCLUSION: Thus, in contrast to many solid peripheral tumors, failure to present tumor antigens is not a likely impediment to immunotherapeutic strategies against malignant gliomas. Rather, immunotherapeutic strategies need to overcome low levels of B7 costimulation.

Changes in the immunologic phenotype of human malignant glioma cells after passaging in vitro.

Although immunotherapeutic strategies against glioblastomas have been promising both in vitro and in animal models, similar successes have not been realized in human clinical trials. One reason may be that immunotherapeutic strategies are based on prior studies that primarily have used human glioblastoma cell lines passaged in vitro, which may not accurately reflect the in vivo properties of glioblastoma cells. In this report, we used flow cytometry to quantify the expression of immunological cell surface molecules on human glioblastomas directly ex vivo (prior to any in vitro culturing) and after varying passages in vitro. Furthermore, we used ELISA to quantitate cytokine secretion after various passages in vitro. We demonstrate that in vitro culturing of established cell lines led to increases in the cell surface expression of MHC class I and ICAM-1 and secretion of IL-6 and TGF-beta(2). Furthermore, there were significant changes in the expression of MHC class I, MHC class II, B7-2, ICAM-1, and FasL when comparing ex vivo tumor cells to those after a single passage in vitro. After passaging once in vitro, there were also significant changes in the secretion of TGF-beta(2) and IL-10. This report indicates that in vitro culturing leads to significant changes in both cell surface molecules and secreted cytokines, which are known to affect the ability of immune cells to initiate an anti-tumor immune response. These changes in the immunological phenotype of glioblastomas after in vitro culturing may in part explain the limited success of immunotherapeutic strategies against glioblastomas in human clinical trials.