Subsidence after lateral lumbar interbody fusion using a 3D-printed porous titanium interbody cage: single-institution case series.

OBJECTIVE: Cage subsidence is a well-known phenomenon after lateral lumbar interbody fusion (LLIF), occurring in 10%-20% of cases. A 3D-printed porous titanium (pTi) cage has a stiffness that mimics the modulus of elasticity of native vertebrae, which reduces stress at the bone-hardware interface, lowering the risk of subsidence. In this study, the authors evaluated their institutional rate of subsidence and resultant reoperation in patients who underwent LLIF using a 3D-printed pTi interbody cage. METHODS: This is a retrospective case series of consecutive adult patients who underwent LLIF using pTi cages from 2018 to 2020. Demographic and clinical characteristics including age, sex, bone mineral density, smoking status, diabetes, steroid use, number of fusion levels, posterior instrumentation, and graft size were collected. The Marchi subsidence grade was determined at the time of last follow-up. Outcome measures of interest were subsidence and resultant reoperation. Univariable logistic regression analysis was performed to assess the extent to which clinical and operative characteristics were associated with Marchi grade I-III subsidence. Significance was assessed at p < 0.05. RESULTS: Fifty-five patients (38 with degenerative disc disease and 17 with adult spinal deformity) were treated with 97 pTi interbody cages with a mean follow-up of 18 months. The mean age was 63.6 ± 10.1 years, 60% of patients were female, and 36% of patients had osteopenia or osteoporosis. Patients most commonly underwent single-level LLIF (58.2%). Sixteen patients (29.1%) had posterior instrumentation. The subsidence grade distribution was as follows: 89 (92%) grade 0, 5 (5%) grade I, 2 (2%) grade II, and 1 (1%) grade III. No patients who were active or prior smokers and no patients with posterior instrumentation experienced graft subsidence. No clinical or operative characteristics were significantly associated with graft subsidence. One patient (1.8%) required reoperation because of subsidence. CONCLUSIONS: In this institutional case series, subsidence of pTi intervertebral cages after LLIF occurred in 8% of operated levels, 3% of which were grade II or III. Only 1 patient required reoperation. These reported rates are lower than those reported for polyetheretherketone implants. Further studies are necessary to compare the impact of these cage materials on subsidence after LLIF.

Computed Tomography Hounsfield Units as a Predictor of Reoperation and Graft Subsidence After Standalone and Multilevel Lateral Lumbar Interbody Fusion.

BACKGROUND: Standalone single and multilevel lateral lumbar interbody fusion (LLIF) have been increasingly applied to treat degenerative spinal conditions in a less invasive fashion. Graft subsidence following LLIF is a known complication and has been associated with poor bone mineral density (BMD). Previous research has demonstrated the utility of computed tomography (CT) Hounsfield units (HUs) as a surrogate for BMD. In the present study, we investigated the relationship between the CT HUs and subsidence and reoperation after standalone and multilevel LLIF. METHODS: A prospectively maintained single-institution database was retrospectively reviewed for LLIF patients from 2017 to 2020, including single and multilevel standalone cases with and without supplemental posterior fixation. Data on demographics, graft parameters, BMD determined by dual-energy x-ray absorptiometry, preoperative mean segmental CT HUs, and postoperative subsidence and reoperation were collected. We used 36-in. standing radiographs to measure the preoperative global sagittal alignment and disc height and subsidence at last follow-up. Subsidence was classified using the Marchi grading system corresponding to disc height loss: grade 0, 0%-24%; grade I, 25%-49%; grade II, 50%-74%; and grade III, 75%-100%. RESULTS: A total of 89 LLIF patients had met the study criteria, with a mean follow-up of 19.9 ± 13.9 months. Of the 54 patients who had undergone single-level LLIF, the mean segmental HUs were 152.0 ± 8.7 for 39 patients with grade 0 subsidence, 136.7 ± 10.4 for 9 with grade I subsidence, 133.9 ± 23.1 for 3 with grade II subsidence, and 119.9 ± 30.9 for 3 with grade III subsidence (P = 0.032). Of the 96 instrumented levels in the 35 patients who had undergone multilevel LLIF, 85, 9, 1, and 1 level had had grade 0, grade I, grade II, and grade III subsidence, with no differences in the HU levels. On multivariate logistic regression, increased CT HU levels were independently associated with a decreased risk of reoperation after both single-level and multilevel LLIF (odds ratio, 0.98; 95% confidence interval, 0.97-0.99; P = 0.044; and odds ratio, 0.97; 95% confidence interval, 0.94-0.99; P = 0.017, respectively). Overall, the BMD determined using dual-energy x-ray absorptiometry was not associated with graft subsidence or reoperation. Using a receiver operating characteristic curve to separate the patients who had and had not required reoperation, the threshold HU level determined for single-level and multilevel LLIF was 131.4 (sensitivity, 0.62; specificity 0.65) and 131.0 (sensitivity, 0.67; specificity, 0.63), respectively. CONCLUSIONS: Lower CT HUs were independently associated with an increased risk of graft subsidence after single-level LLIF. In addition, lower CT HUs significantly increased the risk of reoperation after both single and multilevel LLIF with a critical threshold of 131 HUs. The determination of the preoperative CT HUs might provide a more robust gauge of local bone quality and the likelihood of graft subsidence requiring reoperation following LLIF than overall BMD.

The Effect of Sacroiliac Fusion and Pelvic Fixation on Rod Strain in Thoracolumbar Fusion Constructs: A Biomechanical Investigation.

STUDY DESIGN: In vitro biomechanical study. OBJECTIVE: Investigate effects of sacroiliac joint (SIJ) fusion and iliac fixation on distal rod strain in thoracolumbar fusions. SUMMARY OF BACKGROUND DATA: Instrument failure is a multifactorial, challenging problem frequently encountered by spinal surgeons. Increased rod strain may lead to instrumentation failure and rod fracture. METHODS: Seven fresh frozen human cadaveric specimens (T9-pelvis) used. Six operative constructs tested to investigate changes in rod strain at L5-S1 and S1-Ilium rods, posterior pedicle screws/rods from T10-S1 (PS), PS + bilateral iliac screw fixation, PS + unilateral iliac screw fixation (UIS), PS+UIS+3 unilateral SIJ screws, PS + 3 unilateral SIJ screws, and PS +6 bilateral SIJ screws. Uniaxial strain gauges were used to measure surface strain of rods during flexion-extension. RESULTS: In flexion-extension, bilateral iliac screws added significant strain to L5-S1 compared with long fusion constructs ending at S1 (PS) (P < 0.05). Unilateral iliac fixation exhibited highest strain to L5-S1 ipsilateral rod, was significantly higher compared with bilateral iliac fixation and PS construct. Unilateral and bilateral SIJ fusion did not significantly change L5-S1 rod strain compared with PS. When measuring S1-Ilium rod strain, unilateral pelvic fixation had highest reported rod strain, approached significance compared with bilateral iliac screws (P = 0.054). Addition of contralateral SIJ fusion did not affect rod strain at S1-ilium on side with unilateral fixation. CONCLUSION: Results showed additional fixation below S1 to pelvis added significant rod strain. Unilateral pelvic screws had highest rod strain; SIJ fusion did not affect rod strain. Findings can help guide surgeons when associated risk of rod failure is a consideration.Level of Evidence: N/A.

Radiculopathy with concomitant sacroiliac dysfunction and lumbosacral degenerative disease: illustrative case.

BACKGROUND: The sacroiliac joint (SIJ) is an important cause of low back pain and referred leg pain (RLP). Pain from SIJ dysfunction may occur in isolation or may result from a combination with lumbosacral area-mediated pain. SIJ fusion is one treatment modality for medically refractory symptoms and may also have a role in the treatment of RLP. OBSERVATIONS: The authors present a challenging case of concomitant lumbosacral degenerative disease and SIJ dysfunction in a patient with radiculopathy. They provide clinical characteristics and imaging findings and discuss difficulties in dealing with the intersection of these two distinct diagnoses. In addition, the authors offer a review of the relevant literature, elucidating the role of SIJ dysfunction in causing radicular lower extremity pain, the relationship to concomitant lumbosacral degenerative disease, and outcome data for SIJ fusion as it relates to RLP. LESSONS: With increasing numbers of patients undergoing spinal instrumentation in the setting of degenerative lumbosacral arthritis, as well as randomized controlled trial data demonstrating the efficacy of SIJ fusion for medically refractory SIJ dysfunction, it is important to recognize the challenges in understanding how both of these patient groups may present with radiculopathy. Failure to do so may result in incorrect patient selection, poor outcomes, and increased morbidity for at-risk patients.

The Effect of Elevated Mean Arterial Blood Pressure in Cervical Traumatic Spinal Cord Injury with Hemorrhagic Contusion.

OBJECTIVE: Hemorrhagic contusion in cervical spinal cord injury (CSCI) is poorly understood. We investigated hemorrhagic expansion in patients with CSCI with an assigned elevated mean arterial pressure (MAP) goal of >85 mm Hg. The change in hemorrhagic area and long-term follow-up data ≥6 months after injury was studied. METHODS: A retrospective review was performed from 2005 to 2016 to identify patients with motor complete CSCI with 2 cervical magnetic resonance imaging (MRI) scans within 7 days of injury showing evidence of hemorrhagic contusion and assigned a MAP goal of >85 mm Hg for 7 days. T2-weighted MRI was used to calculate the hemorrhagic surface area in the sagittal plane. A calculated MAP was recorded for each blood pressure measure between the initial and follow-up MRI scans. The American Spinal Injury Association impairment scale (AIS) and American Spinal Injury Association motor scores were recorded at the final follow-up examination at ≥6 months. RESULTS: A total of 193 patients were identified. The mean change in the hemorrhagic area was 24.0 mm2. Of the 193 patients, the AIS grade was A for 114 and B for 79 patients. Multiple logistic regression analysis demonstrated that the MAP and systolic blood pressure were nonsignificant predictors of hemorrhagic contusion expansion. An increased hemorrhagic contusion area on the follow-up MRI scan was associated with a reduced odds of AIS improvement of ≥1 and ≥2 points (odds ratio, 0.97; 95% confidence interval, 0.87-0.97; P = 0.028; and odds ratio, 0.92; 95% confidence interval, 0.99-1.13; P = 0.008, respectively) at the final ≥6-month follow-up examination. CONCLUSION: The present study investigated the clinical safety of elevated MAP goals for patients with CSCI and hemorrhagic contusion. Elevated MAPs did not significantly increase the risk of hemorrhagic expansion in those with CSCI. We have also reported the use of hemorrhagic contusion size as a potential radiographic biomarker for neurological outcomes.

CNTF receptor subunit α as a marker for glioma tumor-initiating cells and tumor grade: laboratory investigation.

OBJECT: Tumor-initiating cells are uniquely resilient to current treatment modalities and play an important role in tumor resistance and recurrence. The lack of specific tumor-initiating cell markers to identify and target these cells presents a major obstacle to effective directed therapy. METHODS: To identify tumor-initiating cell markers in primary brain tumors, the authors compared the proteomes of glioma tumor-initiating cells to their differentiated progeny using a novel, nongel/shotgun-based, multidimensional liquid-chromatography protein separation technique. An in vivo xenograft model was used to demonstrate the tumorigenic and stem cell properties of these cells. Western blot and immunofluorescence analyses were used to confirm findings of upregulated ciliary neurotrophic factor receptor subunit-α (CNTFRα) in undifferentiated tumor-initiating cells and gliomas of increasing tumor grade. Sequencing of the CNTFRα coding regions was performed for mutation analysis. Finally, antibody-dependent cell-mediated cytotoxicity was used to establish the role of CNTFRα as a potential immunotherapeutic target. RESULTS: Ciliary neurotrophic factor receptor subunit-α expression was increased in tumor-initiating cells and was decreased in the cells' differentiated progeny, and expression levels increased with glioma grade. Mutations of CNTFRα are not common in gliomas. Functional studies using CNTF treatment in glioma tumor-initiating cells showed induction of differentiation through the CNTFRα pathway. Treatment with anti-CNTFRα antibody resulted in increased antibody-dependent cell-mediated cytotoxicity in CNTFRα expressing DAOY cells but not in cell lines that lack CNTFRα. CONCLUSIONS: These data indicate that CNTFRα plays a role in the formation or maintenance of tumor-initiating cells in gliomas, is a marker that correlates with histological grade, may underlie treatment resistance in some cases, and is a potential therapeutic target.

MyD88 inhibition amplifies dendritic cell capacity to promote pancreatic carcinogenesis via Th2 cells.

The transition of chronic pancreatic fibroinflammatory disease to neoplasia is a primary example of the paradigm linking inflammation to carcinogenesis. However, the cellular and molecular mediators bridging these entities are not well understood. Because TLR4 ligation can exacerbate pancreatic inflammation, we postulated that TLR4 activation drives pancreatic carcinogenesis. In this study, we show that lipopolysaccharide accelerates pancreatic tumorigenesis, whereas TLR4 inhibition is protective. Furthermore, blockade of the MyD88-independent TRIF pathway is protective against pancreatic cancer, whereas blockade of the MyD88-dependent pathway surprisingly exacerbates pancreatic inflammation and malignant progression. The protumorigenic and fibroinflammatory effects of MyD88 inhibition are mediated by dendritic cells (DCs), which induce pancreatic antigen-restricted Th2-deviated CD4(+) T cells and promote the transition from pancreatitis to carcinoma. Our data implicate a primary role for DCs in pancreatic carcinogenesis and illustrate divergent pathways in which blockade of TLR4 signaling via TRIF is protective against pancreatic cancer and, conversely, MyD88 inhibition exacerbates pancreatic inflammation and neoplastic transformation by augmenting the DC-Th2 axis.