The attainment of a patient acceptable symptom state in patients undergoing revision spine fusion.

INTRODUCTION: Revision lumbar fusion is most commonly due to nonunion, adjacent segment disease (ASD), or recurrent stenosis, but it is unclear if diagnosis affects patient outcomes. The primary aim of this study was to assess whether patients achieved the patient acceptable symptom state (PASS) or minimal clinically important difference (MCID) after revision lumbar fusion and assess whether this was influenced by the indication for revision. METHODS: We retrospectively identified all 1-3 level revision lumbar fusions at a single institution. Oswestry Disability Index (ODI) was collected at preoperative, three-month postoperative, and one-year postoperative time points. The MCID was calculated using a distribution-based method at each postoperative time point. PASS was set at the threshold of ≤ 22. RESULTS: We identified 197 patients: 56% with ASD, 28% with recurrent stenosis, and 15% with pseudarthrosis. The MCID for ODI was 10.05 and 10.23 at three months and one year, respectively. In total, 61% of patients with ASD, 52% of patients with nonunion, and 65% of patients with recurrent stenosis achieved our cohort-specific MCID at one year postoperatively with ASD (p = 0.78). At one year postoperatively, 33.8% of ASD patients, 47.8% of nonunion patients, and 37% of patients with recurrent stenosis achieved PASS without any difference between indication (p = 0.47). CONCLUSIONS: The majority of patients undergoing revision spine fusion experience significant postoperative improvements regardless of the indication for revision. However, a large proportion of these patients do not achieve the patient acceptable symptom state. While revision spine surgery may offer substantial benefits, these results underscore the need to manage patient expectations.

Radiology Reports Do Not Accurately Portray the Severity of Cervical Neural Foraminal Stenosis.

STUDY DESIGN: Retrospective study. OBJECTIVE: (1) To compare cervical magnetic resonance imaging (MRI) radiology reports to a validated grading system for cervical foraminal stenosis (FS) and (2) to evaluate whether the severity of cervical neural FS on MRI correlates to motor weakness or patient-reported outcomes. BACKGROUND: Radiology reports of cervical spine MRI are often reviewed to assess the degree of neural FS. However, research looking at the association between these reports and objective MRI findings, as well as clinical symptoms, is lacking. PATIENTS AND METHODS: We retrospectively identified all adult patients undergoing primary 1 or 2-level anterior cervical discectomy and fusion at a single academic center for an indication of cervical radiculopathy. Preoperative MRI was assessed for neural FS severity using the grading system described by Kim and colleagues for each level of fusion, as well as adjacent levels. Neural FS severity was recorded from diagnostic radiologist MRI reports. Motor weakness was defined as an examination grade <4/5 on the final preoperative encounter. Regression analysis was conducted to evaluate whether the degree of FS by either classification was related to patient-reported outcome measure severity. RESULTS: A total of 283 patients were included in the study, and 998 total levels were assessed. There were significant differences between the MRI grading system and the assessment by radio-logists (P< 0.001). In levels with moderate stenosis, 28.9% were classified as having no stenosis by radiology. In levels with severe stenosis, 29.7% were classified as having mild-moderate stenosis or less. Motor weakness was found similarly often in levels of moderate or severe stenosis (6.9% and 9.2%, respectively). On regression analysis, no associations were found between baseline patient-reported outcome measures and stenosis severity assessed by radiologists or MRI grading systems. CONCLUSION: Radiology reports on the severity of cervical neural FS are not consistent with a validated MRI grading system. These radiology reports underestimated the severity of neural foraminal compression and may be inappropriate when used for clinical decision-making. LEVEL OF EVIDENCE: Level III.

Preoperative Oswestry Disability Index Should not be Utilized to Determine Surgical Eligibility for Patients Requiring Lumbar Fusion for Degenerative Lumbar Spine Disease.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To evaluate how preoperative Oswestry Disability Index (ODI) thresholds might affect minimal clinically important difference (MCID) achievement following lumbar fusion. SUMMARY OF BACKGROUND DATA: As payers invest in alternative payment models, some are suggesting threshold cutoffs of patient-reported outcomes (PROMs) in reimbursement approvals for orthopedic procedures. The feasibility of this has not been investigated in spine surgery. MATERIALS/METHODS: We included all adult patients undergoing one to three-level primary lumbar fusion at a single urban tertiary academic center from 2014 to 2020. ODI was collected preoperatively and one year postoperatively. We implemented theoretical threshold cutoffs at increments of 10. MCID was set at 14.3. The percent of patients meeting MCID were determined among patients "approved" or "denied" at each threshold. At each threshold, the positive predictive value (PPV) for MCID attainment was calculated. RESULTS: A total 1368 patients were included and 62.4% (N=364) achieved MCID. As the ODI thresholds increased, a greater percent of patients in each group reached the MCID. At the lowest ODI threshold, 6.58% (N=90) of patients would be denied, rising to 20.2%, 39.5%, 58.4%, 79.9%, and 91.4% at ODI thresholds of 30, 40, 50, 60, and 70, respectively. The PPV increased from 0.072 among patients with ODI>20 to 0.919 at ODI>70. The number of patients denied a clinical improvement in the denied category per patient achieving the MCID increased at each threshold (ODI>20: 1.96; ODI>30: 2.40; ODI>40: 2.75; ODI>50: 3.03; ODI>60: 3.54; ODI>70: 3.75). CONCLUSION: Patients with poorer preoperative ODI are significantly more likely to achieve MCID following lumbar spine fusion at all ODI thresholds. Setting a preoperative ODI threshold for surgical eligibility will restrict access to patients who may benefit from spine fusion despite ODI>20 demonstrating the lowest predictive value for MCID achievement. LEVEL OF EVIDENCE: 3.

Subfascial Lumbar Spine Drain Output Does Not Affect Outcomes After Incidental Durotomies in Elective Spine Surgery.

OBJECTIVE: Postoperative drains have long been regarded as a preventive measure to mitigate the risks of complications such as neurological impairment by reducing fluid accumulation following spine surgery. Our study aims to contribute to the existing body of knowledge by examining the effects of postoperative drain output on the 90-day postoperative outcomes for patients who experienced an incidental durotomy after lumbar decompression procedures, with or without fusion. METHODS: All patients aged ≥18 years with an incidental durotomy from spinal decompression with or without fusion surgery between 2017 and 2021 were retrospectively identified. The patient demographics, surgical characteristics, method of dural tear repair (DuraSeal, suture, and/or DuraGen), surgical outcomes, and drain data were collected via medical record review. Patients were grouped by readmission status and final 8-hour drain output. Those with a final 8-hour drain output of ≥40 mL were included in the high drain output (HDO) group and those with <40 mL were in the low drain output (LDO) group. RESULTS: There were no statistically significant differences in preoperative patient demographics, surgical characteristics, method of dural tear repair, length of stay (HDO, 4.02 ± 1.90 days; vs. LDO, 4.26 ± 2.10 days; P = 0.269), hospital readmissions (HDO, 10.6%; vs. LDO, 7.96%; P = 0.744), or occurrence of reoperation during readmission (HDO, 6.06%; vs. LDO, 2.65%; P = 0.5944) between the 2 groups. CONCLUSIONS: For patients undergoing primary lumbar decompression with or without fusion and experiencing an incidental durotomy, no significant association was found between the drain output and 90-day patient outcomes. Adequate fascial closure and the absence of symptoms may be satisfactory criteria for standard patient discharge regardless of drain output.

NRF2/ARE mediated antioxidant response to glaucoma: role of glia and retinal ganglion cells.

Glaucoma, the second leading cause of irreversible blindness worldwide, is associated with age and sensitivity to intraocular pressure (IOP). We have shown that elevated IOP causes an early increase in levels of reactive oxygen species (ROS) in the microbead occlusion mouse model. We also detected an endogenous antioxidant response mediated by Nuclear factor erythroid 2-Related Factor 2 (NRF2), a transcription factor that binds to the antioxidant response element (ARE) and increases transcription of antioxidant genes. Our previous studies show that inhibiting this pathway results in earlier and greater glaucoma pathology. In this study, we sought to determine if this endogenous antioxidant response is driven by the retinal ganglion cells (RGCs) or glial cells. We used Nrf2fl/fl mice and cell-type specific adeno-associated viruses (AAVs) expressing Cre to alter Nrf2 levels in either the RGCs or glial cells. Then, we quantified the endogenous antioxidant response, visual function and optic nerve histology after IOP elevation. We found that knock-down of Nrf2 in either cell type blunts the antioxidant response and results in earlier pathology and vision loss. Further, we show that delivery of Nrf2 to the RGCs is sufficient to provide neuroprotection. In summary, both the RGCs and glial cells contribute to the antioxidant response, but treatment of the RGCs alone with increased Nrf2 is sufficient to delay onset of vision loss and axon degeneration in this induced model of glaucoma.

Intraocular Sustained Release of EPO-R76E Mitigates Glaucoma Pathogenesis by Activating the NRF2/ARE Pathway.

Erythropoietin (EPO) is neuroprotective in multiple models of neurodegenerative diseases, including glaucoma. EPO-R76E retains the neuroprotective effects of EPO but diminishes the effects on hematocrit. Treatment with EPO-R76E in a glaucoma model increases expression of antioxidant proteins and is neuroprotective. A major pathway that controls the expression of antioxidant proteins is the NRF2/ARE pathway. This pathway is activated endogenously after elevation of intraocular pressure (IOP) and contributes to the slow onset of pathology in glaucoma. In this study, we explored if sustained release of EPO-R76E in the eye would activate the NRF2/ARE pathway and if this pathway was key to its neuroprotective activity. Treatment with PLGA.EPO-E76E prevented increases in retinal superoxide levels in vivo, and caused phosphorylation of NRF2 and upregulation of antioxidants. Further, EPO-R76E activates NRF2 via phosphorylation by the MAPK pathway rather than the PI3K/Akt pathway, used by the endogenous antioxidant response to elevated IOP.

cGMP Signaling in the Neurovascular Unit-Implications for Retinal Ganglion Cell Survival in Glaucoma.

Glaucoma is a progressive age-related disease of the visual system and the leading cause of irreversible blindness worldwide. Currently, intraocular pressure (IOP) is the only modifiable risk factor for the disease, but even as IOP is lowered, the pathology of the disease often progresses. Hence, effective clinical targets for the treatment of glaucoma remain elusive. Glaucoma shares comorbidities with a multitude of vascular diseases, and evidence in humans and animal models demonstrates an association between vascular dysfunction of the retina and glaucoma pathology. Integral to the survival of retinal ganglion cells (RGCs) is functional neurovascular coupling (NVC), providing RGCs with metabolic support in response to neuronal activity. NVC is mediated by cells of the neurovascular unit (NVU), which include vascular cells, glial cells, and neurons. Nitric oxide-cyclic guanosine monophosphate (NO-cGMP) signaling is a prime mediator of NVC between endothelial cells and neurons, but emerging evidence suggests that cGMP signaling is also important in the physiology of other cells of the NVU. NO-cGMP signaling has been implicated in glaucomatous neurodegeneration in humans and mice. In this review, we explore the role of cGMP signaling in the different cell types of the NVU and investigate the potential links between cGMP signaling, breakdown of neurovascular function, and glaucoma pathology.