Novel Use of Bilateral Prone Transpsoas Approach for the Treatment of Transforaminal Interbody Fusion Pseudarthrosis and Interbody Cage Subsidence.

BACKGROUND AND OBJECTIVES: Pseudarthrosis is a complication after transforaminal lumbar interbody fusion (TLIF) that leads to recurrent symptoms and potential revision surgery. Subsidence of the interbody adds to the complexity of surgical revision. In addition, we report a novel technique for the treatment of TLIF pseudarthrosis with subsidence and propose an approach algorithm for TLIF cage removal. METHODS: Cases of reoperation for TLIF pseudarthrosis were reviewed. We report a novel technique using a bilateral prone transpsoas (PTP) approach to remove a subsided TLIF cage and place a new lateral cage. An approach algorithm was developed based on the experience of TLIF cage removal. The patient was placed in the prone position with somatosensory evoked potential and electromyography monitoring. A PTP retractor was placed using standard techniques on the ipsilateral side of the previous TLIF. After the discectomy, the subsided TLIF cage was visualized but unable to be removed. The initial dilator was closed, and a second PTP retractor was placed on the contralateral side. After annulotomy and discectomy to circumferentially isolate the subsided cage, a box cutter was used to push and mobilize the TLIF cage from this contralateral side, which could then be pulled out from the ipsilateral side. A standard lateral interbody cage was then placed. RESULTS: Retractor time was less than 10 minutes on each side. The patient's symptoms resolved postoperatively. We review illustrative cases of various approaches for TLIF cage removal spanning the lumbosacral spine and recommend an operative approach based on the lumbar level, degree of subsidence, and mobility of the interbody. CONCLUSION: Bilateral PTP retractors for TLIF cage removal may be effectively used in cases of pseudarthrosis with severe cage subsidence. Careful consideration of various factors, including patient surgical history, body habitus, and intraoperative findings, is essential in determining the appropriate treatment for these complex cases.

Dehydrated human amnion/chorion membrane use in emergent craniectomies shows minimal dural adhesions.

Decompressive craniectomies (DCs) are routinely performed neurosurgical procedures to emergently treat increased intracranial pressure secondary to multiple aetiologies, such as subdural haematoma, epidural haematoma, or malignant oedema in the setting of acute infarction. The DC procedure typically induces epidural fibrosis post-cranial resection, resulting in adherence of the dura to both the brain internally and skin flap externally. This becomes especially problematic in the setting of skull flap replacement for cranioplasty as adherences can lead to bridging vein tear, damage to the underlying brain cortex, and other postoperative complications. Dural adjuvants, which can contribute to decreased rate of adherence formation, can thereby reduce both postoperative cranioplasty complications and operative duration. Dehydrated human amnion/chorion membrane (DHACM) allografts (AMNIOFIX, MIMEDX Group Inc., US) have been shown to reduce the rate of dural scar tissue formation in re-exploration of posterior lumbar interbody fusion operations which require entry into the epidural space. The purpose of this study was to evaluate whether or not the use of DHACM in the setting of emergent craniectomies decreased the rate of dural adhesion formation and subsequent cranioplasty complications. Patients (n=7) who underwent emergent craniectomy and intraoperative placement of DHACM were evaluated during replacement of either an autologous skull cap or a custom-made implant, at which point the degree of adhesions was qualitatively assessed. Placement of DHACM below and on top of the dura resulted in negligible adhesion being found during the defect exposure, and there were no intraoperative complications during cranioplasties. Reported estimated blood loss across the seven patients averaged 64.2ml, total operative time averaged 79.2 minutes, and time dedicated to exposing defect for bone flap placement was <3 minutes.

Benign Brain and Spinal Tumors Originating from Bone or Cartilage.

Benign osseocartilaginous tumors of the spine are overall uncommon, representing between 1 and 13% of all primary bone tumors and less than 10% of all spinal tumors. Tumors in this category include osteoblastic lesions such as the related osteoid osteoma and osteoblastoma, and cartilage-forming lesions including osteochondroma, chondroma, and chondroblastoma. Aneurysmal bone cysts, giant cell tumors of bone, and eosinophilic granulomas also comprise benign tumors of the spine arising from bone. There is significant heterogeneity in the epidemiology, molecular biology, imaging features, and optimal treatment of these lesions. For example, osteoid osteoma is characterized by high expression of the cyclooxygenase enzymes, making it amenable to treatment with anti-inflammatory drugs initially, whereas other lesions such as osteoblastoma may require intralesional curettage or en bloc resection sooner. Generally, en bloc resection is preferred when possible to minimize risk of recurrence. Further, some tumors may arise in the setting of syndromic conditions, such as multiple chondromas arising in Ollier disease or Maffucci syndrome, or as part of genetic disorders, such as osteochondromas in the context of hereditary multiple exostosis. These lesions may present with local pain, cause neurological compromise or be discovered incidentally on routine imaging. The Enneking classification and Weinstein-Boriani-Biagini system are routinely used to classify lesions and assist in surgical planning. More novel techniques such as radiofrequency ablation and laser photocoagulation have been applied for the treatment of osteoid osteoma and may have utility in the treatment of other lesion types. A multidisciplinary approach is critical in the management of benign lesions of the spine, and both chemotherapeutic and surgical approaches are routinely used.

Complications of the Prone Transpsoas Lateral Lumbar Interbody Fusion for Degenerative Lumbar Spine Disease: A Multicenter Study.

BACKGROUND AND OBJECTIVES: The prone transpsoas (PTP) approach for lateral lumbar interbody fusion (LLIF) is a novel technique for degenerative lumbar spine disease. However, there is a paucity of information in the literature on the complications of this procedure, with all published data consisting of small samples. We aimed to report the intraoperative and postoperative complications of PTP in the largest study to date. METHODS: A retrospective electronic medical record review was conducted at 11 centers to identify consecutive patients who underwent LLIF through the PTP approach between January 1, 2021, and December 31, 2021. The following data were collected: intraoperative characteristics (operative time, estimated blood loss [EBL], intraoperative complications [anterior longitudinal ligament (ALL) rupture, cage subsidence, vascular and visceral injuries]), postoperative complications, and hospital stay. RESULTS: A total of 365 patients were included in the study. Among these patients, 2.2% had ALL rupture, 0.3% had cage subsidence, 0.3% had a vascular injury, 0.3% had a ureteric injury, and no other visceral injuries were reported. Mean operative time was 226.2 ± 147.9 minutes. Mean EBL was 138.4 ± 215.6 mL. Mean hospital stay was 2.7 ± 2.2 days. Postoperative complications included new sensory symptoms-8.2%, new lower extremity weakness-5.8%, wound infection-1.4%, cage subsidence-0.8%, psoas hematoma-0.5%, small bowel obstruction and ischemia-0.3%, and 90-day readmission-1.9%. CONCLUSION: In this multicenter case series, the PTP approach was well tolerated and associated with a satisfactory safety profile.

Cerebrospinal Fluid Drainage in Patients with Acute Spinal Cord Injury: A Multi-Center Randomized Controlled Trial.

OBJECTIVE: The secondary phase of spinal cord injury (SCI) is characterized by ischemic injury. Spinal cord perfusion pressure (SCPP), calculated as the difference between mean arterial pressure (MAP) and intrathecal pressure (ITP), has arisen as a therapeutic target for improving outcomes. Cerebrospinal fluid drainage (CSFD) may reduce ITP and thereby increase SCPP. Randomized controlled trial to evaluate the safety and feasibility of CSFD to improve SCPP and outcomes after acute SCI. METHODS: Inclusion criteria included acute cervical SCI within 24 hours of presentation. All patients received lumbar drain placement and appropriate decompressive surgery. Patients randomized to the control group received MAP elevation only. Patients in the experimental group received MAP elevation and CSFD to achieve ITP <10 mmHg for 5 days. ITP and MAP were recorded hourly. Adverse events were documented and patients underwent functional assessments at enrollment, 72 hours, 90 days, and 180 days post-injury. RESULTS: Eleven patients were enrolled; 4 were randomized to receive CSFD. CSFD patients had a mean ITP of 5.3 ± 2.5 mmHg versus. 15 ± 3.0 mmHg in the control group. SCPP improved significantly, from 77 ± 4.5 mmHg in the control group to 101 ± 6.3 mmHg in the CSFD group (P < 0.01). Total motor scores improved by 15 ± 8.4 and 57 ± 24 points in the control and CSFD groups, respectively, over 180 days. No adverse events were attributable to CSFD. CONCLUSIONS: CSFD is a safe, effective mechanism for reducing ITP and improving SCPP in the acute period post-SCI. The favorable safety profile and preliminary efficacy should help drive recruitment in future studies.

Creation and preclinical evaluation of a novel mussel-inspired, biomimetic, bioactive bone graft scaffold: direct comparison with Infuse bone graft using a rat model of spinal fusion.

OBJECTIVE: Infuse bone graft is a widely used osteoinductive adjuvant; however, the simple collagen sponge scaffold used in the implant has minimal inherent osteoinductive properties and poorly controls the delivery of the adsorbed recombinant human bone morphogenetic protein-2 (rhBMP-2). In this study, the authors sought to create a novel bone graft substitute material that overcomes the limitations of Infuse and compare the ability of this material with that of Infuse to facilitate union following spine surgery in a clinically translatable rat model of spinal fusion. METHODS: The authors created a polydopamine (PDA)-infused, porous, homogeneously dispersed solid mixture of extracellular matrix and calcium phosphates (BioMim-PDA) and then compared the efficacy of this material directly with Infuse in the setting of different concentrations of rhBMP-2 using a rat model of spinal fusion. Sixty male Sprague Dawley rats were randomly assigned to each of six equal groups: 1) collagen + 0.2 µg rhBMP-2/side, 2) BioMim-PDA + 0.2 µg rhBMP-2/side, 3) collagen + 2.0 µg rhBMP-2/side, 4) BioMim-PDA + 2.0 µg rhBMP-2/side, 5) collagen + 20 µg rhBMP-2/side, and 6) BioMim-PDA + 20 µg rhBMP-2/side. All animals underwent posterolateral intertransverse process fusion at L4-5 using the assigned bone graft. Animals were euthanized 8 weeks postoperatively, and their lumbar spines were analyzed via microcomputed tomography (µCT) and histology. Spinal fusion was defined as continuous bridging bone bilaterally across the fusion site evaluated via µCT. RESULTS: The fusion rate was 100% in all groups except group 1 (70%) and group 4 (90%). Use of BioMim-PDA with 0.2 µg rhBMP-2 led to significantly greater results for bone volume (BV), percentage BV, and trabecular number, as well as significantly smaller trabecular separation, compared with the use of the collagen sponge with 2.0 µg rhBMP-2. The same results were observed when the use of BioMim-PDA with 2.0 µg rhBMP-2 was compared with the use of the collagen sponge with 20 µg rhBMP-2. CONCLUSIONS: Implantation of rhBMP-2-adsorbed BioMim-PDA scaffolds resulted in BV and bone quality superior to that afforded by treatment with rhBMP-2 concentrations 10-fold higher implanted on a conventional collagen sponge. Using BioMim-PDA (vs a collagen sponge) for rhBMP-2 delivery could significantly lower the amount of rhBMP-2 required for successful bone grafting clinically, improving device safety and decreasing costs.

Radiographic alignment outcomes after the single-position prone transpsoas approach: a multi-institutional retrospective review of 363 cases.

OBJECTIVE: The aim of this paper was to evaluate the changes in radiographic spinopelvic parameters in a large cohort of patients undergoing the prone transpsoas approach to the lumbar spine. METHODS: A multicenter retrospective observational cohort study was performed for all patients who underwent lateral lumber interbody fusion via the single-position prone transpsoas (PTP) approach. Spinopelvic parameters from preoperative and first upright postoperative radiographs were collected, including lumbar lordosis (LL), pelvic incidence (PI), and pelvic tilt (PT). Functional indices (visual analog scale score), and patient-reported outcomes (Oswestry Disability Index) were also recorded from pre- and postoperative appointments. RESULTS: Of the 363 patients who successfully underwent the procedure, LL after fusion was 50.0° compared with 45.6° preoperatively (p < 0.001). The pelvic incidence-lumbar lordosis mismatch (PI-LL) was 10.5° preoperatively versus 2.9° postoperatively (p < 0.001). PT did not significantly change (0.2° ± 10.7°, p > 0.05). CONCLUSIONS: The PTP approach allows significant gain in lordotic augmentation, which was associated with good functional results at follow-up.

In-Human Report of S2 Alar-Iliac Screw Placement Using Augmented Reality Assistance.

BACKGROUND: S2 alar-iliac (S2AI) screws provide spinopelvic fixation with the advantages of minimized dissection, easier rod contouring, and decreased symptomatic screw-head prominence. However, placement of S2AI screws may be challenging because of the anatomy of the lumbosacral junction. Augmented reality is a nascent technology that may enhance placement of S2AI screws. OBJECTIVE: To report the first in-human placement of augmented reality (AR)-assisted S2 alar-iliac screws and evaluate the accuracy of screw placement. METHODS: A retrospective review was performed of patients who underwent AR-assisted S2AI screw placement. All surgeries were performed by 2 neurosurgeons using an AR head-mounted display (Xvision, Augmedics). Screw accuracy was analyzed in a blinded fashion by an independent neuroradiologist using the cortical breach grading scale. RESULTS: Twelve patients underwent AR-assisted S2AI screw placement for a total of 23 screws. Indications for surgery included deformity, degenerative disease, and tumor. Twenty-two screws (95.6%) were accurate-defined as grade 0 or grade 1. Twenty-one screws (91.3%) were classified as grade 0, 1 screw (4.3%) was grade 1, and 1 screw (4.3%) was grade 3. All breaches were asymptomatic. CONCLUSION: AR-assisted S2AI screw placement had an overall accuracy rate of 95.6% (grade 0 and grade 1 screws) in a cohort of 12 patients and 23 screws. This compares favorably with freehand and robotic placement. 1,2 AR enables spine surgeons to both better visualize anatomy and accurately place spinal instrumentation. Future studies are warranted to research the learning curve and cost analysis of AR-assisted spine surgery.

Treatment of Spinal Arteriovenous Malformation and Fistula.

With the rapid advancements in endovascular therapy over previous decades, the treatment of spinal arteriovenous malformations (AVMs) continues to evolve. The decision to use endovascular versus surgical therapy largely depends on the type of lesion and its anatomic location. Recent studies demonstrate that endovascular treatment is effective for extradural arteriovenous fistulas (AVFs), intradural ventral (perimedullary) AVMs, and intramedullary spinal AVMs. Treatment of intradural dorsal (dural) AVFs remains largely surgical because of lower recurrence rates, although recent studies demonstrate equivocal outcomes. Extradural-intradural (juvenile) AVMs and conus AVMs remain difficult-to-treat lesions.

Octogenarians Are Independently Associated With Extended LOS and Non-Routine Discharge After Elective ACDF for CSM.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The aim of this study was to determine the impact age has on LOS and discharge disposition following elective ACDF for cervical spondylotic myelopathy (CSM). METHODS: A retrospective cohort study was performed using the National Inpatient Sample (NIS) database from 2016 and 2017. All adult patients >50 years old undergoing ACDF for CSM were identified using the ICD-10-CM diagnosis and procedural coding system. Patients were then stratified by age: 50 to 64 years-old, 65 to 79 years-old, and greater than or equal to 80 years-old. Weighted patient demographics, comorbidities, perioperative complications, LOS, discharge disposition, and total cost of admission were assessed. RESULTS: A total of 14 865 patients were identified. Compared to the 50-64 and 65-79 year-old cohorts, the 80+ years cohort had a significantly higher rate of postoperative complication (50-64 yo:10.2% vs. 65-79 yo:12.6% vs. 80+ yo:18.9%, P = 0.048). The 80+ years cohort experienced significantly longer hospital stays (50-64 yo: 2.0 ± 2.4 days vs. 65-79 yo: 2.2 ± 2.8 days vs. 80+ yo: 2.3 ± 2.1 days, P = 0.028), higher proportion of patients with extended LOS (50-64 yo:18.3% vs. 65-79 yo:21.9% vs. 80+ yo:28.4%, P = 0.009), and increased rates of non-routine discharges (50-64 yo:15.1% vs. 65-79 yo:23.0% vs. 80+ yo:35.8%, P < 0.001). On multivariate analysis, age 80+ years was found to be a significant independent predictor of extended LOS [OR:1.97, 95% CI:(1.10,3.55), P = 0.023] and non-routine discharge [OR:2.46, 95% CI:(1.44,4.21), P = 0.001]. CONCLUSIONS: Our study demonstrates that octogenarian age status is a significant independent risk factor for extended LOS and non-routine discharge after elective ACDF for CSM.

Clinical accuracy and initial experience with augmented reality-assisted pedicle screw placement: the first 205 screws.

OBJECTIVE: Augmented reality (AR) is a novel technology which, when applied to spine surgery, offers the potential for efficient, safe, and accurate placement of spinal instrumentation. The authors report the accuracy of the first 205 pedicle screws consecutively placed at their institution by using AR assistance with a unique head-mounted display (HMD) navigation system. METHODS: A retrospective review was performed of the first 28 consecutive patients who underwent AR-assisted pedicle screw placement in the thoracic, lumbar, and/or sacral spine at the authors' institution. Clinical accuracy for each pedicle screw was graded using the Gertzbein-Robbins scale by an independent neuroradiologist working in a blinded fashion. RESULTS: Twenty-eight consecutive patients underwent thoracic, lumbar, or sacral pedicle screw placement with AR assistance. The median age at the time of surgery was 62.5 (IQR 13.8) years and the median body mass index was 31 (IQR 8.6) kg/m2. Indications for surgery included degenerative disease (n = 12, 43%); deformity correction (n = 12, 43%); tumor (n = 3, 11%); and trauma (n = 1, 4%). The majority of patients (n = 26, 93%) presented with low-back pain, 19 (68%) patients presented with radicular leg pain, and 10 (36%) patients had documented lower extremity weakness. A total of 205 screws were consecutively placed, with 112 (55%) placed in the lumbar spine, 67 (33%) in the thoracic spine, and 26 (13%) at S1. Screw placement accuracy was 98.5% for thoracic screws, 97.8% for lumbar/S1 screws, and 98.0% overall. CONCLUSIONS: AR depicted through a unique HMD is a novel and clinically accurate technology for the navigated insertion of pedicle screws. The authors describe the first 205 AR-assisted thoracic, lumbar, and sacral pedicle screws consecutively placed at their institution with an accuracy of 98.0% as determined by a Gertzbein-Robbins grade of A or B.

Ramifications of Postoperative Dysphagia on Health Care Resource Utilization Following Elective Anterior Cervical Discectomy and Interbody Fusion for Cervical Spondylotic Myelopathy.

STUDY DESIGN: This is a retrospective cohort study. OBJECTIVE: The aim of this study was to investigate patient risk factors and health care resource utilization associated with postoperative dysphagia following elective anterior cervical discectomy and fusion (ACDF) for cervical spondylotic myelopathy. SUMMARY OF BACKGROUND DATA: There is a paucity of data on factors predisposing patients to dysphagia and the burden this complication has on health care resource utilization following ACDF. METHODS: A retrospective cohort study was performed using the Nationwide Inpatient Sample (NIS) database from 2016 to 2017. All adult (above 18 y old) patients undergoing ACDF for cervical spondylotic myelopathy were identified using the ICD-10-CM diagnosis and procedural coding system. Patients were then categorized by whether they had a recorded postoperative dysphagia or no dysphagia. Weighted patient demographics, comorbidities, perioperative complications, length of hospital stay (LOS), discharge disposition, and total cost of admission were assessed. A multivariate stepwise logistic regression was used to determine both the odds ratio for risk-adjusted postoperative dysphagia as well as extended LOS. RESULTS: A total of 17,385 patients were identified, of which 1400 (8.1%) experienced postoperative dysphagia. Compared with the No-Dysphagia cohort, the Dysphagia cohort had a greater proportion of patients experiencing a complication (P=0.004), including 1 complication (No-Dysphagia: 2.9% vs. Dysphagia: 6.8%), and >1 complication (No-Dysphagia: 0.3% vs. Dysphagia: 0.4%). The Dysphagia cohort experienced significantly longer hospital stays (No-Dysphagia: 1.9±2.1 d vs. Dysphagia: 4.2±4.3 d, P<0.001), higher total cost of admission (No-Dysphagia: $19,441±10,495 vs. Dysphagia: $25,529±18,641, P<0.001), and increased rates of nonroutine discharge (No-Dysphagia: 16.5% vs. Dysphagia: 34.3%, P<0.001). Postoperative dysphagia was found to be a significant independent risk factor for extended LOS on multivariate analysis, with an odds ratio of 5.37 (95% confidence interval: 4.09, 7.05, P<0.001). CONCLUSION: Patients experiencing postoperative dysphagia were found to have significantly longer hospital LOS, higher total cost of admission, and increased nonroutine discharge when compared with the patients who did not. LEVEL OF EVIDENCE: Level III.

Impact of race on nonroutine discharge, length of stay, and postoperative complications after surgery for spinal metastases.

OBJECTIVE: Previous studies have suggested the possibility of racial disparities in surgical outcomes for patients undergoing spine surgery, although this has not been thoroughly investigated in those with spinal metastases. Given the increasing prevalence of spinal metastases requiring intervention, knowledge about potential discrepancies in outcomes would benefit overall patient care. The objective in the present study was to investigate whether race was an independent predictor of postoperative complications, nonroutine discharge, and prolonged length of stay (LOS) after surgery for spinal metastasis. METHODS: The authors retrospectively examined patients at a single comprehensive cancer center who had undergone surgery for spinal metastasis between April 2013 and April 2020. Demographic information, primary pathology, preoperative clinical characteristics, and operative outcomes were collected. Factors achieving p values < 0.15 on univariate regression were entered into a stepwise multivariable logistic regression to generate predictive models. Nonroutine discharge was defined as a nonhome discharge destination and prolonged LOS was defined as LOS greater than the 75th percentile for the entire cohort. RESULTS: Three hundred twenty-eight patients who had undergone 348 operations were included: 240 (69.0%) White and 108 (31.0%) Black. On univariable analysis, cohorts significantly differed in age (p = 0.02), marital status (p < 0.001), insurance status (p = 0.03), income quartile (p = 0.02), primary tumor type (p = 0.04), and preoperative Karnofsky Performance Scale (KPS) score (p < 0.001). On multivariable analysis, race was an independent predictor for nonroutine discharge: Black patients had significantly higher odds of nonroutine discharge than White patients (adjusted odds ratio [AOR] 2.24, 95% confidence interval [CI] 1.28-3.92, p = 0.005). Older age (AOR 1.06 per year, 95% CI 1.03-1.09, p < 0.001), preoperative KPS score ≤ 70 (AOR 3.30, 95% CI 1.93-5.65, p < 0.001), preoperative Frankel grade A-C (AOR 3.48, 95% CI 1.17-10.3, p = 0.02), insurance status (p = 0.005), being unmarried (AOR 0.58, 95% CI 0.35-0.97, p = 0.04), number of levels (AOR 1.17 per level, 95% CI 1.05-1.31, p = 0.004), and thoracic involvement (AOR 1.71, 95% CI 1.02-2.88, p = 0.04) were also predictive of nonroutine discharge. However, race was not independently predictive of postoperative complications or prolonged LOS. Higher Charlson Comorbidity Index (AOR 1.22 per point, 95% CI 1.04-1.43, p = 0.01), low preoperative KPS score (AOR 1.84, 95% CI 1.16-2.92, p = 0.01), and number of levels (AOR 1.15 per level, 95% CI 1.05-1.27, p = 0.004) were predictive of complications, while insurance status (p = 0.05), income quartile (p = 0.01), low preoperative KPS score (AOR 1.64, 95% CI 1.03-2.72, p = 0.05), and number of levels (AOR 1.16 per level, 95% CI 1.05-1.30, p = 0.004) were predictive of prolonged LOS. CONCLUSIONS: Race, insurance status, age, baseline functional status, and marital status were all independently associated with nonroutine discharge. This suggests that a combination of socioeconomic factors and functional status, rather than medical comorbidities, may best predict postdischarge disposition in patients treated for spinal metastases. Further investigation in a prospective cohort is merited.

Synergy between glutamate modulation and anti-programmed cell death protein 1 immunotherapy for glioblastoma.

OBJECTIVE: Immune checkpoint inhibitors such as anti-programmed cell death protein 1 (anti-PD-1) have shown promise for the treatment of cancers such as melanoma, but results for glioblastoma (GBM) have been disappointing thus far. It has been suggested that GBM has multiple mechanisms of immunosuppression, indicating a need for combinatorial treatment strategies. It is well understood that GBM increases glutamate in the tumor microenvironment (TME); however, the significance of this is not well understood. The authors posit that glutamate upregulation in the GBM TME is immunosuppressive. The authors utilized a novel glutamate modulator, BHV-4157, to determine synergy between glutamate modulation and the well-established anti-PD-1 immunotherapy for GBM. METHODS: C57BL/6J mice were intracranially implanted with luciferase-tagged GL261 glioma cells. Mice were randomly assigned to the control, anti-PD-1, BHV-4157, or combination anti-PD-1 plus BHV-4157 treatment arms, and median overall survival was assessed. In vivo microdialysis was performed at the tumor site with administration of BHV-4157. Intratumoral immune cell populations were characterized with immunofluorescence and flow cytometry. RESULTS: The BHV-4157 treatment arm demonstrated improved survival compared with the control arm (p < 0.0001). Microdialysis demonstrated that glutamate concentration in TME significantly decreased after BHV-4157 administration. Immunofluorescence and flow cytometry demonstrated increased CD4+ T cells and decreased Foxp3+ T cells in mice that received BHV-4157 treatment. No survival benefit was observed when CD4+ or CD8+ T cells were depleted in mice prior to BHV-4157 administration (p < 0.05). CONCLUSIONS: In this study, the authors showed synergy between anti-PD-1 immunotherapy and glutamate modulation. The authors provide a possible mechanism for this synergistic benefit by showing that BHV-4157 relies on CD4+ and CD8+ T cells. This study sheds light on the role of excess glutamate in GBM and provides a basis for further exploring combinatorial approaches for the treatment of this disease.

Neuroprotective Role of Acidosis in Ischemia: Review of the Preclinical Evidence.

Efforts to develop effective neuroprotective therapies for ischemic stroke have had little success to date. One promising approach to neuroprotection is ischemic postconditioning, which utilizes brief bouts of ischemia after acute ischemic stroke to elicit neuroprotection, although the mechanism is largely unknown. As the primary components of transient ischemia are local hypoxia and acidosis, and hypoxic postconditioning has had little success, it is possible that the acidosis component may be the primary driver. To address the evidence behind this, we performed a systematic review of preclinical studies focused on the neuroprotective role of transient acidosis after ischemia. Animal studies demonstrated that mild-to-moderate acidosis after ischemic events led to better functional neurologic outcomes with reduced infarct volumes, while severe acidosis often led to cerebral edema and worse functional outcomes. In vitro studies demonstrated that mild-to-moderate acidosis improves neuronal survival largely through two means: (1) inhibition of harmful superoxide formation in the excitotoxic pathway and (2) remodeling neuronal mitochondria to allow for efficient ATP production (i.e., oxidative phosphorylation), even in the absence of oxygen. Similar to the animal studies, acidotic postconditioning in humans would entail short cycles of carbon dioxide inhalation, which has already been demonstrated to be safe as part of a hypercapnic challenge when measuring cerebrovascular reactivity. Due to the preclinical efficacy of acidotic postconditioning, its relatively straightforward translation into humans, and the growing need for neuroprotective therapies, future preclinical studies should focus on filling the current knowledge gaps that are currently restricting the development of phase I/II clinical trials.

Influence of tranexamic acid use on venous thromboembolism risk in patients undergoing surgery for spine tumors.

OBJECTIVE: Patients with spine tumors are at increased risk for both hemorrhage and venous thromboembolism (VTE). Tranexamic acid (TXA) has been advanced as a potential intervention to reduce intraoperative blood loss in this surgical population, but many fear it is associated with increased VTE risk due to the hypercoagulability noted in malignancy. In this study, the authors aimed to 1) develop a clinical calculator for postoperative VTE risk in the population with spine tumors, and 2) investigate the association of intraoperative TXA use and postoperative VTE. METHODS: A retrospective data set from a comprehensive cancer center was reviewed for adult patients treated for vertebral column tumors. Data were collected on surgery performed, patient demographics and medical comorbidities, VTE prophylaxis measures, and TXA use. TXA use was classified as high-dose (≥ 20 mg/kg) or low-dose (< 20 mg/kg). The primary study outcome was VTE occurrence prior to discharge. Secondary outcomes were deep venous thrombosis (DVT) or pulmonary embolism (PE). Multivariable logistic regression was used to identify independent risk factors for VTE and the resultant model was deployed as a web-based calculator. RESULTS: Three hundred fifty patients were included. The mean patient age was 57 years, 53% of patients were male, and 67% of surgeries were performed for spinal metastases. TXA use was not associated with increased VTE (14.3% vs 10.1%, p = 0.37). After multivariable analysis, VTE was independently predicted by lower serum albumin (odds ratio [OR] 0.42 per g/dl, 95% confidence interval [CI] 0.23-0.79, p = 0.007), larger mean corpuscular volume (OR 0.91 per fl, 95% CI 0.84-0.99, p = 0.035), and history of prior VTE (OR 2.60, 95% CI 1.53-4.40, p < 0.001). Longer surgery duration approached significance and was included in the final model. Although TXA was not independently associated with the primary outcome of VTE, high-dose TXA use was associated with increased odds of both DVT and PE. The VTE model showed a fair fit of the data with an area under the curve of 0.77. CONCLUSIONS: In the present cohort of patients treated for vertebral column tumors, TXA was not associated with increased VTE risk, although high-dose TXA (≥ 20 mg/kg) was associated with increased odds of DVT or PE. Additionally, the web-based clinical calculator of VTE risk presented here may prove useful in counseling patients preoperatively about their individualized VTE risk.

A Web-Based Calculator for Predicting the Occurrence of Wound Complications, Wound Infection, and Unplanned Reoperation for Wound Complications in Patients Undergoing Surgery for Spinal Metastases.

BACKGROUND: In the present study, we identified the risk factors for wound complications, wound infection, and reoperation for wound complications after spine metastasis surgery and deployed the resultant model as a web-based calculator. METHODS: Patients treated at a single comprehensive cancer center during a 7-year period were included. The demographics, pathology, comorbidities, laboratory values, and operative details were collected. Factors with P < 0.15 on univariable regression were entered into multivariable logistic regression to generate predictive models internally validated using 1000 bootstrapped samples. RESULTS: Of the 330 patients included, 29 (7.6%) had experienced a surgical site infection. The independent predictive factors for wound-related complications were a higher Charlson comorbidity index (CCI; odds ratio [OR], 1.41 per point; P < 0.01), Karnofsky performance scale score ≤70 (OR, 2.14; P = 0.04), lower platelet count (OR, 0.49 per 105/µL; P < 0.01), revision versus index surgery (OR, 3.10; P = 0.02), and increased incision length (OR, 1.21 per level; P = 0.02). Wound infection was associated with a higher CCI (OR, 1.60 per point; P < 0.01), a lower platelet count (OR, 0.35 per 105/µL; P < 0.01), revision surgery (OR, 4.63; P = 0.01), and a longer incision length (OR, 1.25 per level; P = 0.03). Unplanned reoperation for wound complications was predicted by a higher CCI (OR, 1.39 per point; P = 0.003), prior irradiation (OR, 2.52; P = 0.04), a lower platelet count (OR, 0.57 per 105/µL; P = 0.02), and revision surgery (OR, 3.34; P = 0.03), The optimism-corrected areas under the curve were 0.75, 0.81, and 0.72 for the wound complication, infection, and reoperation models, respectively. CONCLUSIONS: Low platelet counts, poorer health status, more invasive surgery, and revision surgery all independently predicted the risk of wound complications, including infection and unplanned reoperation for infection. Validation of the calculators in a prospective study is merited.

Interrater and Intrarater Reliability of the Vertebral Bone Quality Score.

BACKGROUND: Vertebral bone quality had a significant impact on postoperative outcomes in spinal fusion surgery. New magnetic resonance imaging-based measures, such as the Vertebral Bone Quality (VBQ) score, may allow for bone quality assessment without the radiation associated with conventional testing. In the present study, we sought to assess the intrarater and interrater reliability of VBQ scores calculated by medical professionals and trainees. METHODS: Thirteen reviewers of various specialties and levels of training were recruited and asked to calculate VBQ scores for 30 patients at 2 time points separated by 2 months. Scored volumes were acquired from patients treated for both degenerative and oncologic indications. Intrarater and interrater agreement, quantified by intraclass correlation coefficient (ICC), was assessed using 2-way random effects modeling. Square-weight Cohen κ and Kendall Tau-b were used to determine whether raters assigned similar scores during both evaluations. RESULTS: All raters showed moderate to excellent reliability for VBQ score (ICC 0.667-0.957; κ0.648-0.921) and excellent reliability for all constituent components used to calculate VBQ score (ICC all ≥0.97). Interrater reliability was also found to be good for VBQ score on both the first (ICC = 0.818) and second (ICC = 0.800) rounds of assessment; scores for the constituent component all had ICC values ≥0.97 for the constituent components. CONCLUSIONS: The VBQ score appears to have both good intrarater and interrater reliability. In addition, there appeared to be no correlation between score reliability and level of training. External validation and further investigations of its ability to accurately model bone biomechanical properties are necessary.

Removal of instrumentation for postoperative spine infection: systematic review.

OBJECTIVE: Currently, no consensus exists as to whether patients who develop infection of the surgical site after undergoing instrumented fusion should have their implants removed at the time of wound debridement. Instrumentation removal may eliminate a potential infection nidus, but removal may also destabilize the patient's spine. The authors sought to summarize the existing evidence by systematically reviewing published studies that compare outcomes between patients undergoing wound washout and instrumentation removal with outcomes of patients undergoing wound washout alone. The primary objectives were to determine 1) whether instrumentation removal from an infected wound facilitates infection clearance and lowers morbidity, and 2) whether the chronicity of the underlying infection affects the decision to remove instrumentation. METHODS: PRISMA guidelines were used to review the PubMed/MEDLINE, Embase, Cochrane Library, Scopus, Web of Science, and ClinicalTrials.gov databases to identify studies that compared patients with implants removed and patients with implants retained. Outcomes of interest included mortality, rate of repeat wound washout, and loss of correction. RESULTS: Fifteen articles were included. Of 878 patients examined in these studies, 292 (33%) had instrumentation removed. Patient populations were highly heterogeneous, and outcome data were limited. Available data suggested that rates of reoperation, pseudarthrosis, and death were higher in patients who underwent instrumentation removal at the time of initial washout. Three studies recommended that instrumentation be uniformly removed at the time of wound washout. Five studies favored retaining the original instrumentation. Six studies favored retention in early infections but removal in late infections. CONCLUSIONS: The data on this topic remain heterogeneous and low in quality. Retention may be preferred in the setting of early infection, when the risk of underlying spine instability is still high and the risk of mature biofilm formation on the implants is low. However, late infections likely favor instrumentation removal. Higher-quality evidence from large, multicenter, prospective studies is needed to reach generalizable conclusions capable of guiding clinical practice.

Impact of Multidisciplinary Intraoperative Teams on Thirty-Day Complications After Sacral Tumor Resection.

OBJECTIVE: To evaluate the impact of multidisciplinary intraoperative teams on surgical complications in patients undergoing sacral tumor resection. METHODS: We reviewed all patients with primary or metastatic sacral tumors managed at a single comprehensive cancer center over a 7-year period. Perioperative complication rates were compared between those treated by an unassisted spinal oncologist and those treated with the assistance of at least 1 other surgical specialty. Statistical analysis involved univariable and stepwise multivariable logistic regression models to identify predictors of multidisciplinary management and 30-day complications. RESULTS: A total of 107 patients underwent 132 operations for sacral tumors; 92 operations involved multidisciplinary teams, including 54% of metastatic tumor operations and 74% of primary tumor operations. Patients receiving multidisciplinary management had higher body mass indexes (29.8 vs. 26.3 kg/m2; P = 0.008), larger tumors (258 vs. 55 cm³; P < 0.001), and higher American Society of Anesthesiologists scores (3 vs. 2; P = 0.049). Only larger tumor volume (odds ratio [OR], 1.007 per cm³; P < 0.001) and undergoing treatment for a malignant primary versus a metastatic tumor (OR, 23.4; P < 0.001) or benign primary tumor (OR, 29.3; P < 0.001) were predictive of multidisciplinary management. Although operations involving multidisciplinary teams were longer (467 vs. 231 minutes; P < 0.001) and had higher blood loss (1698 vs. 774 mL; P = 0.004), 30-day complication rates were similar (37 vs. 27%; P = 0.39). On multivariable analysis, only larger tumor volume (OR, 1.004 per cm³; P = 0.005) and longer surgical duration (OR, 1.002 per minute; P = 0.03) independently predicted higher 30-day complications. CONCLUSIONS: Although patients managed with multidisciplinary teams had larger tumors and worse baseline health, 30-day complications were similar. This finding suggests that the use of multidisciplinary teams may help to mitigate surgical morbidity in those with high baseline risk.