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Alexander F. Haddad, Jacob S. Young, and Manish K. Aghi

The treatment for glioblastoma (GBM) has not seen significant improvement in over a decade. Immunotherapies target the immune system against tumor cells and have seen success in various cancer types. However, the efficacy of immunotherapies in GBM thus far has been limited. Systemic immunotherapies also carry with them concerns surrounding systemic toxicities as well as penetration of the blood-brain barrier. These concerns may potentially limit their efficacy in GBM and preclude the use of combinatorial immunotherapy, which may be needed to overcome the severe multidimensional immune suppression seen in GBM patients. The use of viral vectors to deliver immunotherapies directly to tumor cells has the potential to improve immunotherapy delivery to the CNS, reduce systemic toxicities, and increase treatment efficacy. Indeed, preclinical studies investigating the delivery of immunomodulators to GBM using viral vectors have demonstrated significant promise. In this review, the authors discuss previous studies investigating the delivery of local immunotherapy using viral vectors. They also discuss the future of these treatments, including the reasoning behind immunomodulator and vector selection, patient safety, personalized therapies, and the need for combinatorial treatment.

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Darryl Lau, Alexander F. Haddad, Vedat Deviren, and Christopher P. Ames

OBJECTIVE

Rigid multiplanar thoracolumbar adult spinal deformity (ASD) cases are challenging and many require a 3-column osteotomy (3CO), specifically asymmetrical pedicle subtraction osteotomy (APSO). The outcomes and additional risks of performing APSO for the correction of concurrent sagittal-coronal deformity have yet to be adequately studied.

METHODS

The authors performed a retrospective review of all ASD patients who underwent 3CO during the period from 2006 to 2019. All cases involved either isolated sagittal deformity (patients underwent standard PSO) or concurrent sagittal-coronal deformity (coronal vertical axis [CVA] ≥ 4.0 cm; patients underwent APSO). Perioperative and 2-year follow-up outcomes were compared between patients with isolated sagittal imbalance who underwent PSO and those with concurrent sagittal-coronal imbalance who underwent APSO.

RESULTS

A total of 390 patients were included: 338 who underwent PSO and 52 who underwent APSO. The mean patient age was 64.6 years, and 65.1% of patients were female. APSO patients required significantly more fusions with upper instrumented vertebrae (UIV) in the upper thoracic spine (63.5% vs 43.3%, p = 0.007). Radiographically, APSO patients had greater deformity with more severe preoperative sagittal and coronal imbalance: sagittal vertical axis (SVA) 13.0 versus 10.7 cm (p = 0.042) and CVA 6.1 versus 1.2 cm (p < 0.001). In APSO cases, significant correction and normalization were achieved (SVA 13.0–3.1 cm, CVA 6.1–2.0 cm, lumbar lordosis [LL] 26.3°–49.4°, pelvic tilt [PT] 38.0°–20.4°, and scoliosis 25.0°–10.4°, p < 0.001). The overall perioperative complication rate was 34.9%. There were no significant differences between PSO and APSO patients in rates of complications (overall 33.7% vs 42.3%, p = 0.227; neurological 5.9% vs 3.9%, p = 0.547; medical 20.7% vs 25.0%, p = 0.482; and surgical 6.5% vs 11.5%, p = 0.191, respectively). However, the APSO group required significantly longer stays in the ICU (3.1 vs 2.3 days, p = 0.047) and hospital (10.8 vs 8.3 days, p = 0.002). At the 2-year follow-up, there were no significant differences in mechanical complications, including proximal junctional kyphosis (p = 0.352), pseudarthrosis (p = 0.980), rod fracture (p = 0.852), and reoperation (p = 0.600).

CONCLUSIONS

ASD patients with significant coronal imbalance often have severe concurrent sagittal deformity. APSO is a powerful and effective technique to achieve multiplanar correction without higher risk of morbidity and complications compared with PSO for sagittal imbalance. However, APSO is associated with slightly longer ICU and hospital stays.

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nlm-article

Darryl Lau, Alexander F. Haddad, Vedat Deviren, and Christopher P. Ames

OBJECTIVE

There is an increased recognition of disproportional lumbar lordosis (LL) and artificially high pelvic incidence (PI) as a cause for positive sagittal imbalance and spinal pelvic mismatch. For such cases, a sacral pedicle subtraction osteotomy (PSO) may be indicated, although its morbidity is not well described. In this study, the authors evaluate the specific complication risks associated with S1 PSO.

METHODS

A retrospective review of all adult spinal deformity patients who underwent a 3-column osteotomy (3CO) for thoracolumbar deformity from 2006 to 2019 was performed. Demographic, clinical baseline, and radiographic parameters were recorded. The primary outcome of interest was perioperative complications (surgical, neurological, and medical). Secondary outcomes of interest included case length, blood loss, and length of stay. Multivariate analysis was used to assess the risk of S1 PSO compared with 3CO at other levels.

RESULTS

A total of 405 patients underwent 3CO in the following locations: thoracic (n = 55), L1 (n = 25), L2 (n = 29), L3 (n = 141), L4 (n = 129), L5 (n = 17), and S1 (n = 9). After S1 PSO, there were significant improvements in the sagittal vertical axis (14.8 cm vs 6.7 cm, p = 0.004) and PI-LL mismatch (31.7° vs 9.6°, p = 0.025) due to decreased PI (80.3° vs 65.9°, p = 0.006). LL remained unchanged (48.7° vs 57.8°, p = 0.360). The overall complication rate was 27.4%; the surgical, neurological, and medical complication rates were 7.7%, 6.2%, and 20.0%, respectively. S1 PSO was associated with significantly higher rates of overall complications: thoracic (29.1%), L1 (32.0%), L2 (31.0%), L3 (19.9%), L4 (32.6%), L5 (11.8%), and S1 (66.7%) (p = 0.018). Similarly, an S1 PSO was associated with significantly higher rates of surgical (thoracic [9.1%], L1 [4.0%], L2 [6.9%], L3 [5.7%], L4 [10.9%], L5 [5.9%], and S1 [44.4%], p = 0.006) and neurological (thoracic [9.1%], L1 [0.0%], L2 [6.9%], L3 [2.8%], L4 [7.0%], L5 [5.9%], and S1 [44.4%], p < 0.001) complications. On multivariate analysis, S1 PSO was independently associated with higher odds of overall (OR 7.93, p = 0.013), surgical (OR 20.66, p = 0.010), and neurological (OR 14.75, p = 0.007) complications.

CONCLUSIONS

S1 PSO is a powerful technique for correction of rigid sagittal imbalance due to an artificially elevated PI in patients with rigid high-grade spondylolisthesis and chronic sacral fractures. However, the technique and intraoperative corrective maneuvers are challenging and associated with high surgical and neurological complications. Additional investigations into the learning curve associated with S1 PSO and complication prevention are needed.

Free access

nlm-article

Rushikesh S. Joshi, Darryl Lau, Alexander F. Haddad, Vedat Deviren, and Christopher P. Ames

OBJECTIVE

Correction of rigid cervical deformities can be associated with high complication rates and result in prolonged intensive care unit (ICU) and hospital stays. In this study, the authors aimed to examine the risk factors contributing to length of stay (LOS) in both the hospital and ICU following adult cervical deformity (ACD) surgery and to identify severe adverse events that occurred in this setting.

METHODS

A retrospective review of ACD patients who underwent posterior-based osteotomies for deformity correction from 2010 to 2019 was performed. Inclusion criteria were cervical kyphosis > 20° and/or cervical sagittal vertical axis (cSVA) > 4 cm. Multivariate analysis was used to identify risk factors independently associated with ICU and hospital LOS.

RESULTS

A total of 107 patients were included. The mean age was 63.5 years, and 61.7% were female. Over half (52.3%) underwent 3-column osteotomies, while 47.7% underwent posterior column osteotomies. There was significant correction of all cervical parameters: cSVA (6.0 vs 3.6 cm, p < 0.001), cervical lordosis (8.2° vs −5.3°, p < 0.001), cervical scoliosis (6.5° vs 2.2°, p < 0.001), and T1-slope (40.2° vs 34.5°, p < 0.001). There were also reciprocal changes to the distal spine: thoracic kyphosis (54.4° vs 46.4°, p < 0.001), lumbar lordosis (49.9° vs 45.8°, p = 0.003), and thoracolumbar scoliosis (13.9° vs 11.1°, p = 0.009). Overall, 4 patients (3.7%) suffered aspiration-related complications, 3 patients (2.8%) experienced dysphagia requiring a feeding tube, and 4 patients (3.7%) had compromised airways, with 1 resulting in death. The mean ICU and hospital LOS were 2.8 days and 7.9 days, respectively. Multivariate analysis identified three factors independently associated with longer ICU LOS: female sex (3.0 vs 2.4 days, p = 0.004), ≥ 12 segments fused (3.5 vs 1.9 days, p = 0.002), and postoperative complication (4.0 vs 1.9 days, p = 0.017). These same factors were independently associated with longer hospital LOS as well: female sex (8.3 vs 7.3 days, p = 0.013), ≥ 12 segments fused (9.4 vs 6.2 days, p = 0.001), and complication (9.7 vs 6.7 days, p = 0.026).

CONCLUSIONS

Posterior-based osteotomies are very effective for the correction of ACD, but postoperative hospital stays are relatively longer than those following surgery for degenerative disease. Risk factors for prolonged ICU and hospital LOS consist of both nonmodifiable (female sex) and modifiable (≥ 12 segments fused and presence of complication) risk factors. Additional multicenter prospective studies will be needed to validate these findings.

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Qiunan Lyu, Darryl Lau, Alexander F. Haddad, Vedat Deviren, and Christopher P. Ames

OBJECTIVE

The purpose of this study was to compare rod fracture (RF) rates among three types of rod constructs (RCs) following lumbar pedicle subtraction osteotomy (PSO) for adult spinal deformity (ASD).

METHODS

A retrospective review of consecutive patients with adult spinal deformity who were treated with lumbar PSO between 2007 and 2017 was performed. The minimum follow-up was 2 years. Three RCs were compared: standard (2 main rods), satellite (2 main rods with satellite rod), and nested (2 main rods and 2 short rods spanning osteotomy). Outcomes examined included RF rate, time to RF, pseudarthrosis, and reoperation. Multivariate analysis was used.

RESULTS

A total of 141 patients were included 55 with standard, 23 with satellite, and 63 with nested RCs. The mean age was 65.2 years and 34.8% of patients were male. Radiographic preoperative and postoperative results were as follows: sagittal vertical axis (11.0 vs 3.9 cm), lumbar lordosis (28.5° vs 57.1°), pelvic tilt (30.6° vs 21.0°), pelvic incidence (61.5° vs 60.0°), distance between central sacral vertical line and C7 plumb line (2.2 vs 1.5 cm), and scoliosis (18.9° vs 11.3°). The average time to RF was 12.4 months. Overall RF, bilateral RF, pseudarthrosis, and reoperation rates were 22.7%, 5.0%, 20.6%, and 17.7%, respectively. Standard RCs had a significantly higher RF (36.4% vs 13.0% vs 14.3%, p = 0.008), bilateral RF (35.0% vs 0.0% vs 0.0%, p = 0.021), pseudarthrosis (34.5% vs 8.7% vs 12.7%, p = 0.004), and reoperation (30.9% vs 4.3% vs 11.1%, p = 0.004) rates. Satellite RCs (OR 0.21, p = 0.015), nested RCs (OR 0.24, p = 0.003), and bone morphogenetic protein–2 (OR 0.28, p = 0.005) were independently associated with lower odds of RF.

CONCLUSIONS

Use of multiple rods in the satellite RC and nested RC groups was associated with lower rates of RF, pseudarthrosis, and reoperations following lumbar PSO. Bone morphogenetic protein–2 was associated with a reduction in RF rate as well.

Open access

nlm-article

Ramin A. Morshed, Alexander F. Haddad, Kunal P. Raygor, Mary Jue Xu, Charles J. Limb, and Philip V. Theodosopoulos

Intravestibular schwannomas are rare tumors within the intralabyrinthine region and involve different management considerations compared to more common vestibular schwannomas. In this report, the authors review a case of a 52-year-old woman who presented with hearing loss and vestibular symptoms and was found to have a left intravestibular schwannoma. Given her debilitating vestibular symptoms, she underwent microsurgical resection. In this video, the authors review the relevant anatomy, surgical technique, and management considerations in these patients.

The video can be found here: https://stream.cadmore.media/r10.3171/2021.7.FOCVID2187

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Michael M. Safaee, Alexander F. Haddad, Marissa Fury, Patrick R. Maloney, Justin K. Scheer, Darryl Lau, Vedat Deviren, and Christopher P. Ames

OBJECTIVE

Proximal junctional kyphosis (PJK) and proximal junctional failure (PJF) are well-recognized complications of long-segment spinal fusion. Previous studies have suggested that ligament augmentation can decrease rates of PJF by reducing junctional stress and strengthening upper instrumented vertebrae (UIVs) and adjacent segments. However, there is a paucity of long-term data on the efficacy of ligament augmentation in preventing PJF. In this study, the authors sought to determine the effect of ligament augmentation on rates of PJF in a cohort of adult spinal deformity patients with at least 1 year of follow-up.

METHODS

They conducted a retrospective analysis of ligament augmentation in a consecutive series of surgical patients with adult spinal deformity. Data on patient demographics, surgical characteristics, and surgery for PJF were collected. The minimum follow-up was 12 months. Univariate and multivariate analyses were performed to identify factors associated with reoperation for PJF.

RESULTS

The authors identified a total of 242 patients (166 women [68.6%]) with ligament augmentation whose mean age was 66 years. The mean number of fused levels was 10, with a UIV distribution as follows: 90 upper thoracic UIVs (37.2%) and 152 lower thoracic UIVs (62.8%). Compared to a historical cohort of 77 patients treated before implementation of ligament augmentation, reoperation for PJF was significantly lower with ligament augmentation (15.6% vs 3.3%, p < 0.001). In a multivariate model, only ligament augmentation (OR 0.184, 95% CI 0.071–0.478, p = 0.001) and number of fused levels (OR 0.762, 95% CI 0.620–0.937, p = 0.010) were associated with reductions in reoperation for PJF.

CONCLUSIONS

Ligament augmentation was associated with significant reductions in the rate of reoperation for PJF at 12 months in a cohort of adult spinal deformity patients. The most dramatic reduction was seen among patients with lower thoracic UIV. These data suggest that in appropriately selected patients, ligament augmentation may be a valuable adjunct for PJF reduction; however, long-term follow-up is needed.

Free access

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Enrique Vargas, Dennis T. Lockney, Praveen V. Mummaneni, Alexander F. Haddad, Joshua Rivera, Xiao Tan, Alysha Jamieson, Yasmine Mahmoudieh, Sigurd Berven, Steve E. Braunstein, and Dean Chou

OBJECTIVE

Within the Spine Instability Neoplastic Score (SINS) classification, tumor-related potential spinal instability (SINS 7–12) may not have a clear treatment approach. The authors aimed to examine the proportion of patients in this indeterminate zone who later required surgical stabilization after initial nonoperative management. By studying this patient population, they sought to determine if a clear SINS cutoff existed whereby the spine is potentially unstable due to a lesion and would be more likely to require stabilization.

METHODS

Records from patients treated at the University of California, San Francisco, for metastatic spine disease from 2005 to 2019 were retrospectively reviewed. Seventy-five patients with tumor-related potential spinal instability (SINS 7–12) who were initially treated nonoperatively were included. All patients had at least a 1-year follow-up with complete medical records. A univariate chi-square test and Student t-test were used to compare categorical and continuous outcomes, respectively, between patients who ultimately underwent surgery and those who did not. A backward likelihood multivariate binary logistic regression model was used to investigate the relationship between clinical characteristics and surgical intervention. Recursive partitioning analysis (RPA) and single-variable logistic regression were performed as a function of SINS.

RESULTS

Seventy-five patients with a total of 292 spinal metastatic sites were included in this study; 26 (34.7%) patients underwent surgical intervention, and 49 (65.3%) did not. There was no difference in age, sex, comorbidities, or lesion location between the groups. However, there were more patients with a SINS of 12 in the surgery group (55.2%) than in the no surgery group (44.8%) (p = 0.003). On multivariate analysis, SINS > 11 (OR 8.09, CI 1.96–33.4, p = 0.004) and Karnofsky Performance Scale (KPS) score < 60 (OR 0.94, CI 0.89–0.98, p = 0.008) were associated with an increased risk of surgery. KPS score was not correlated with SINS (p = 0.4). RPA by each spinal lesion identified an optimal cutoff value of SINS > 10, which were associated with an increased risk of surgical intervention. Patients with a surgical intervention had a higher incidence of complications on multivariable analysis (OR 2.96, CI 1.01–8.71, p = 0.048).

CONCLUSIONS

Patients with a mean SINS of 11 or greater may be at increased risk of mechanical instability requiring surgery after initial nonoperative management. RPA showed that patients with a KPS score of 60 or lower and a SINS of greater than 10 had increased surgery rates.

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Justin K. Scheer, Alexander F. Haddad, Andrew K. Chan, Charles M. Eichler, Bobby Tay, Shane Burch, Dean Chou, Christopher P. Ames, and Praveen V. Mummaneni

OBJECTIVE

Anterior lumbar interbody fusion (ALIF) is an effective surgical modality for many lumbar degenerative pathologies, but a rare and infrequently reported complication is postoperative lymphocele. The goals of the present study were to review a large consecutive series of patients who underwent ALIF at a high-volume institution, estimate the rate of lymphocele occurrence after ALIF, and investigate the outcomes of patients who developed lymphocele after ALIF.

METHODS

A retrospective review of the electronic medical record was completed, identifying all patients (≥ 18 years old) who underwent at a minimum a single-level ALIF from 2012 through 2019. Postoperative spinal and abdominal images, as well as radiologist reports, were reviewed for mention of lymphocele. Clinical data were collected and reported.

RESULTS

A total of 1322 patients underwent a minimum 1-level ALIF. Of these patients, 937 (70.9%) had either postoperative abdominal or lumbar spine images, and the resulting lymphocele incidence was 2.1% (20/937 patients). The mean ± SD age was 67 ± 10.9 years, and the male/female ratio was 1:1. Patients with lymphocele were significantly older than those without lymphocele (66.9 vs 58.9 years, p = 0.006). In addition, patients with lymphocele had a greater number of mean levels fused (2.5 vs 1.8, p < 0.001) and were more likely to have undergone ALIF at L2–4 (95.0% vs 66.4%, p = 0.007) than patients without lymphocele. On subsequent multivariate analysis, age (OR 1.07, 95% CI 1.01–1.12, p = 0.013), BMI (OR 1.10, 95% CI 1.01–1.18, p = 0.021), and number of levels fused (OR 1.82, 95% CI 1.05–3.14, p = 0.032) were independent prognosticators of postoperative lymphocele development. Patients with symptomatic lymphocele were successfully treated with either interventional radiology (IR) drainage and/or sclerosis therapy and achieved radiographic resolution. The mean ± SD length of hospital stay was 9.1 ± 5.2 days. Ten patients (50%) were postoperatively discharged to a rehabilitation center: 8 patients (40%) were discharged to home, 1 (5%) to a skilled nursing facility, and 1 (5%) to a long-term acute care facility.

CONCLUSIONS

After ALIF, 2.1% of patients were diagnosed with radiographically identified postoperative lymphocele and had risk factors such as increased age, BMI, and number of levels fused. Most patients presented within 1 month postoperatively, and their clinical presentations included abdominal pain, abdominal distension, and/or wound complications. Of note, 25% of identified lymphoceles were discovered incidentally. Patients with symptomatic lymphocele were successfully treated with either IR drainage and/or sclerosis therapy and achieved radiographic resolution.

Free access

nlm-article

Vijay Letchuman, Nitin Agarwal, Valli P. Mummaneni, Michael Y. Wang, Saman Shabani, Arati Patel, Joshua Rivera, Alexander F. Haddad, Vivian Le, Joyce M. Chang, Dean Chou, Seema Gandhi, and Praveen V. Mummaneni

OBJECTIVE

There is a learning curve for surgeons performing “awake” spinal surgery. No comprehensive guidelines have been proposed for the selection of ideal candidates for awake spinal fusion or decompression. The authors sought to formulate an algorithm to aid in patient selection for surgeons who are in the startup phase of awake spinal surgery.

METHODS

The authors developed an algorithm for selecting patients appropriate for awake spinal fusion or decompression using spinal anesthesia supplemented with mild sedation and local analgesia. The anesthetic protocol that was used has previously been reported in the literature. This algorithm was formulated based on a multidisciplinary team meeting and used in the first 15 patients who underwent awake lumbar surgery at a single institution.

RESULTS

A total of 15 patients who underwent decompression or lumbar fusion using the awake protocol were reviewed. The mean patient age was 61 ± 12 years, with a median BMI of 25.3 (IQR 2.7) and a mean Charlson Comorbidity Index of 2.1 ± 1.7; 7 patients (47%) were female. Key patient inclusion criteria were no history of anxiety, 1 to 2 levels of lumbar pathology, moderate stenosis and/or grade I spondylolisthesis, and no prior lumbar surgery at the level where the needle is introduced for anesthesia. Key exclusion criteria included severe and critical central canal stenosis or patients who did not meet the inclusion criteria. Using the novel algorithm, 14 patients (93%) successfully underwent awake spinal surgery without conversion to general anesthesia. One patient (7%) was converted to general anesthesia due to insufficient analgesia from spinal anesthesia. Overall, 93% (n = 14) of the patients were assessed as American Society of Anesthesiologists class II, with 1 patient (7%) as class III. The mean operative time was 115 minutes (± 60 minutes) with a mean estimated blood loss of 46 ± 39 mL. The median hospital length of stay was 1.3 days (IQR 0.1 days). No patients developed postoperative complications and only 1 patient (7%) required reoperation. The mean Oswestry Disability Index score decreased following operative intervention by 5.1 ± 10.8.

CONCLUSIONS

The authors propose an easy-to-use patient selection algorithm with the aim of assisting surgeons with patient selection for awake spinal surgery while considering BMI, patient anxiety, levels of surgery, and the extent of stenosis. The algorithm is specifically intended to assist surgeons who are in the learning curve of their first awake spinal surgery cases.