Strategies to Improve Drug Delivery Across the Blood-Brain Barrier for Glioblastoma.

PURPOSE OF REVIEW: Glioblastoma remains resistant to most conventional treatments. Despite scientific advances in the past three decades, there has been a dearth of effective new treatments. New approaches to drug delivery and clinical trial design are needed. RECENT FINDINGS: We discuss how the blood-brain barrier and tumor microenvironment pose challenges for development of effective therapies for glioblastoma. Next, we discuss treatments in development that aim to overcome these barriers, including novel drug designs such as nanoparticles and antibody-drug conjugates, novel methods of drug delivery, including convection-enhanced and intra-arterial delivery, and novel methods to enhance drug penetration, such as blood-brain barrier disruption by focused ultrasound and laser interstitial thermal therapy. Lastly, we address future opportunities, positing combination therapy as the best strategy for effective treatment, neoadjuvant and window-of-opportunity approaches to simultaneously enhance therapeutic effectiveness with interrogation of on-treatment biologic endpoints, and adaptive platform and basket trials as imperative for future trial design. New approaches to GBM treatment should account for the blood-brain barrier and immunosuppression by improving drug delivery, combining treatments, and integrating novel clinical trial designs.

Asleep triple-modality motor mapping for perirolandic gliomas: an update on outcomes.

OBJECTIVE: Maximal safe resection of gliomas near motor pathways is facilitated by intraoperative mapping. Here, the authors review their results with triple-modality asleep motor mapping with motor evoked potentials and bipolar and monopolar stimulation for cortical and subcortical mapping during glioma surgery in an expanded cohort. METHODS: This was a retrospective analysis of patients who underwent resection of a perirolandic glioma near motor pathways. Clinical and neuromonitoring data were extracted from the electronic medical records for review. All patients with new or worsened postoperative motor deficits were followed for at least 6 months. Regression analyses were performed to assess factors associated with a persistent motor deficit. RESULTS: Between January 2018 and December 2021, 160 operations were performed in 151 patients with perirolandic glioma. Sixty-four patients (40%) had preoperative motor deficits, and the median extent of resection was 98%. Overall, patients in 38 cases (23.8%) had new or worse immediate postoperative deficits by discharge, and persistent deficits by 6 months were seen in 6 cases (3.8%), all in patients with high-grade gliomas. There were no new persistent deficits in low-grade glioma patients (0%). The risk factors for a persistent deficit included an insular tumor component (OR 8.6, p = 0.01), preoperative motor weakness (OR 8.1, p = 0.03), intraoperative motor evoked potential (MEP) changes (OR 36.5, p < 0.0001), and peri-resection cavity ischemia (OR 7.5, p = 0.04). Most persistent deficits were attributable to ischemic injury despite structural preservation of the descending motor tracts. For patients with persistent motor deficits, there were 3 cases (50%) in which a change in MEP was noted but subsequent subcortical monopolar stimulation still elicited a response in the corresponding muscle groups, suggesting axonal activation distal to a point of injury. CONCLUSIONS: Asleep triple motor mapping results in a low rate of permanent deficits, especially for low-grade gliomas. Peri-resection cavity ischemia continues to be a significant risk factor for permanent deficit despite maintaining appropriate distance for subcortical tracts based on monopolar feedback.

Surgical management and outcome of newly diagnosed glioblastoma without contrast enhancement (low-grade appearance): a report of the RANO resect group.

BACKGROUND: Resection of the contrast-enhancing (CE) tumor represents the standard of care in newly diagnosed glioblastoma. However, some tumors ultimately diagnosed as glioblastoma lack contrast enhancement and have a 'low-grade appearance' on imaging (non-CE glioblastoma). We aimed to (a) volumetrically define the value of non-CE tumor resection in the absence of contrast enhancement, and to (b) delineate outcome differences between glioblastoma patients with and without contrast enhancement. METHODS: The RANO resect group retrospectively compiled a global, eight-center cohort of patients with newly diagnosed glioblastoma per WHO 2021 classification. The associations between postoperative tumor volumes and outcome were analyzed. Propensity score-matched analyses were constructed to compare glioblastomas with and without contrast enhancement. RESULTS: Among 1323 newly diagnosed IDH-wildtype glioblastomas, we identified 98 patients (7.4%) without contrast enhancement. In such patients, smaller postoperative tumor volumes were associated with more favorable outcome. There was an exponential increase in risk for death with larger residual non-CE tumor. Accordingly, extensive resection was associated with improved survival compared to lesion biopsy. These findings were retained on a multivariable analysis adjusting for demographic and clinical markers. Compared to CE glioblastoma, patients with non-CE glioblastoma had a more favorable clinical profile and superior outcome as confirmed in propensity score analyses by matching the patients with non-CE glioblastoma to patients with CE glioblastoma using a large set of clinical variables. CONCLUSIONS: The absence of contrast enhancement characterizes a less aggressive clinical phenotype of IDH-wildtype glioblastomas. Maximal resection of non-CE tumors has prognostic implications and translates into favorable outcome.

Socioeconomic differences between medically and surgically treated prolactinomas: a retrospective review of 598 patients.

OBJECTIVE: Socioeconomic status (SES) is known to affect presentations and outcomes in pituitary neuroendocrine tumor resections, but there is a paucity of literature examining its impact specifically on patients with prolactinomas, who may be treated medically or surgically. The authors sought to determine whether SES was associated with differences in treatment choice or outcomes for prolactinoma patients. METHODS: The authors retrospectively reviewed patient records at a high-volume academic pituitary center for prolactinoma diagnoses. Patients were split into medically and surgically treated cohorts. Race, ethnicity, insurance status, primary care physician (PCP) status, and zip code-based income data were collected and examined as socioeconomic covariates. Outcomes of interest included pretreatment likelihood of surgical cure, medical versus surgical treatment allocation, and posttreatment remission rates. RESULTS: The authors analyzed 568 prolactinoma patients (351 medically treated and 217 surgically treated). Patients receiving surgery were more likely to have Medicaid or private insurance (p < 0.001) and have lower incomes (p < 0.001) than medically treated patients. Lower-income surgical patients were more likely to require surgical intervention for an indication such as tumor decompression than higher-income patients (p = 0.023). Surgical patients with a PCP had a higher estimated likelihood of surgical cure (p = 0.008), while no SES-based differences in surgical remission likelihood existed in the medical cohort. After surgery, surgical patients who achieved remission had significantly higher income than those who did not (p < 0.001). Other SES factors were not associated with surgical remission, and among medically treated patients, remission rates were not affected by any SES factor. Income was inversely related to prolactinoma size in both cohorts (surgical, p < 0.001; medical, p = 0.005) but was associated more prominently in surgical patients (surgical, -0.65 mm per $10,000; medical, -0.37 mm per $10,000). CONCLUSIONS: While surgical prolactinoma patients were prone to income and PCP-related disparities, no SES disparities were found among medically treated patients. Income had a more pronounced association with tumor size in the surgical cohort and likely contributed to the increased need for surgical intervention seen in low-income surgical patients. Addressing socioeconomic healthcare disparities is needed among surgical prolactinoma patients to increase rates of early presentation and improve the outcomes of low-SES populations.

Patient-reported outcome measures in cerebrovascular neurosurgery.

OBJECTIVE: The object of this study was to describe the use of patient-reported outcome measures (PROMs) in cerebrovascular neurosurgery and to outline a framework for incorporating them into future cerebrovascular research. METHODS: Following the standardized PRISMA guidelines, the authors performed a search of the PubMed and Embase databases in February 2023 using filters to investigate six specific cerebrovascular pathologies/procedures: subarachnoid hemorrhage (SAH), intracranial hemorrhage, ischemic stroke, arteriovenous malformation, chronic subdural hematoma, and carotid artery stenosis. PROMs in the identified articles were distinguished and classified as generic, symptom specific, or disease specific. RESULTS: A total of 259 studies including 51 PROMs were eligible for inclusion in the review. Most of the PROMs were generic or symptom specific. Only 5 PROMs were disease specific, and all of these pertained to stroke or SAH. CONCLUSIONS: There are only a limited number of disease-specific PROMs available for cerebrovascular pathologies and outcomes. Further validation of existing measures in independent cohorts, expanded incorporation of disease-specific PROMs in prospective trials, and the development of new PROMs specific to cerebrovascular conditions are critical to a better understanding of the impact of cerebrovascular diseases and novel therapies on patient lives.

Middle meningeal artery embolization with polyvinyl alcohol particles in a patient with ophthalmic artery origin from middle meningeal artery: Case report and technical note.

This is a case report of an adult with chronic subdural hematoma (cSDH) who underwent endovascular treatment for middle meningeal artery (MMA) embolization. There was a prominent meningo-ophthalmic branch with an absence of an ophthalmic artery from the internal carotid artery. MMA embolization was performed utilizing particles with no complications and the resolution of the cSDH was within 4 months. This case report demonstrates that despite extreme variant anatomy, MMA embolization with particles is feasible, effective, and safe when appropriate techniques are used.

Prognostic evaluation of re-resection for recurrent glioblastoma using the novel RANO classification for extent of resection: A report of the RANO resect group.

BACKGROUND: The value of re-resection in recurrent glioblastoma remains controversial as a randomized trial that specifies intentional incomplete resection cannot be justified ethically. Here, we aimed to (1) explore the prognostic role of extent of re-resection using the previously proposed Response Assessment in Neuro-Oncology (RANO) classification (based upon residual contrast-enhancing (CE) and non-CE tumor), and to (2) define factors consolidating the surgical effects on outcome. METHODS: The RANO resect group retrospectively compiled an 8-center cohort of patients with first recurrence from previously resected glioblastomas. The associations of re-resection and other clinical factors with outcome were analyzed. Propensity score-matched analyses were constructed to minimize confounding effects when comparing the different RANO classes. RESULTS: We studied 681 patients with first recurrence of Isocitrate Dehydrogenase (IDH) wild-type glioblastomas, including 310 patients who underwent re-resection. Re-resection was associated with prolonged survival even when stratifying for molecular and clinical confounders on multivariate analysis; ≤1 cm3 residual CE tumor was associated with longer survival than non-surgical management. Accordingly, "maximal resection" (class 2) had superior survival compared to "submaximal resection" (class 3). Administration of (radio-)chemotherapy in the absence of postoperative deficits augmented the survival associations of smaller residual CE tumors. Conversely, "supramaximal resection" of non-CE tumor (class 1) was not associated with prolonged survival but was frequently accompanied by postoperative deficits. The prognostic role of residual CE tumor was confirmed in propensity score analyses. CONCLUSIONS: The RANO resect classification serves to stratify patients with re-resection of glioblastoma. Complete resection according to RANO resect classes 1 and 2 is prognostic.

Single-cell RNA sequencing and spatial transcriptomics reveal cancer-associated fibroblasts in glioblastoma with protumoral effects.

Cancer-associated fibroblasts (CAFs) were presumed absent in glioblastoma given the lack of brain fibroblasts. Serial trypsinization of glioblastoma specimens yielded cells with CAF morphology and single-cell transcriptomic profiles based on their lack of copy number variations (CNVs) and elevated individual cell CAF probability scores derived from the expression of 9 CAF markers and absence of 5 markers from non-CAF stromal cells sharing features with CAFs. Cells without CNVs and with high CAF probability scores were identified in single-cell RNA-Seq of 12 patient glioblastomas. Pseudotime reconstruction revealed that immature CAFs evolved into subtypes, with mature CAFs expressing actin alpha 2, smooth muscle (ACTA2). Spatial transcriptomics from 16 patient glioblastomas confirmed CAF proximity to mesenchymal glioblastoma stem cells (GSCs), endothelial cells, and M2 macrophages. CAFs were chemotactically attracted to GSCs, and CAFs enriched GSCs. We created a resource of inferred crosstalk by mapping expression of receptors to their cognate ligands, identifying PDGF and TGF-ß as mediators of GSC effects on CAFs and osteopontin and HGF as mediators of CAF-induced GSC enrichment. CAFs induced M2 macrophage polarization by producing the extra domain A (EDA) fibronectin variant that binds macrophage TLR4. Supplementing GSC-derived xenografts with CAFs enhanced in vivo tumor growth. These findings are among the first to identify glioblastoma CAFs and their GSC interactions, making them an intriguing target.

CDKN2A/B co-deletion is associated with increased risk of local and distant intracranial recurrence after surgical resection of brain metastases.

Background: While genetic alterations in brain metastases (BMs) have been previously explored, there are limited data examining their association with recurrence after surgical resection. This study aimed to identify genetic alterations within BMs associated with CNS recurrence after surgery across multiple cancer types. Methods: A retrospective, single-center study was conducted with patients who underwent resection of a BM with available clinical and gene sequencing data available. Local and remote CNS recurrence were the primary study outcomes. Next-generation sequencing of the coding regions in over 500 oncogenes was performed in brain metastasis specimens. Cox proportional hazards analyses were performed to identify clinical features and genomic alterations associated with CNS recurrence. Results: A total of 90 patients undergoing resection of 91 BMs composed the cohort. Genes most frequently mutated in the cohort included TP53 (64%), CDKN2A (37%), TERT (29%), CDKN2B (23%), NF1 (14%), KRAS (14%), and PTEN (13%), all of which occurred across multiple cancer types. CDKN2A/B co-deletion was seen in 21 (23.1%) brain metastases across multiple cancer types. In multivariate Cox proportional hazard analyses including patient, tumor, and treatment factors, CDKN2A/B co-deletion in the brain metastasis was associated with increased risk of local (HR 4.07, 95% CI 1.32-12.54, P = 0.014) and remote (HR 2.28, 95% CI 1.11-4.69, P = 0.025) CNS progression. Median survival and length of follow-up were not different based on CDKN2A/B mutation status. Conclusions: CDKN2A/B co-deletion detected in BMs is associated with increased CNS recurrence after surgical resection. Additional work is needed to determine whether more aggressive treatment in patients with this mutation may improve outcomes.

Prognostic validation of a new classification system for extent of resection in glioblastoma: A report of the RANO resect group.

BACKGROUND: Terminology to describe extent of resection in glioblastoma is inconsistent across clinical trials. A surgical classification system was previously proposed based upon residual contrast-enhancing (CE) tumor. We aimed to (1) explore the prognostic utility of the classification system and (2) define how much removed non-CE tumor translates into a survival benefit. METHODS: The international RANO resect group retrospectively searched previously compiled databases from 7 neuro-oncological centers in the USA and Europe for patients with newly diagnosed glioblastoma per WHO 2021 classification. Clinical and volumetric information from pre- and postoperative MRI were collected. RESULTS: We collected 1,008 patients with newly diagnosed IDHwt glioblastoma. 744 IDHwt glioblastomas were treated with radiochemotherapy per EORTC-26981/22981 (TMZ/RT→TMZ) following surgery. Among these homogenously treated patients, lower absolute residual tumor volumes (in cm3) were favorably associated with outcome: patients with "maximal CE resection" (class 2) had superior outcome compared to patients with "submaximal CE resection" (class 3) or "biopsy" (class 4). Extensive resection of non-CE tumor (≤5 cm3 residual non-CE tumor) was associated with better survival among patients with complete CE resection, thus defining class 1 ("supramaximal CE resection"). The prognostic value of the resection classes was retained on multivariate analysis when adjusting for molecular and clinical markers. CONCLUSIONS: The proposed "RANO categories for extent of resection in glioblastoma" are highly prognostic and may serve for stratification within clinical trials. Removal of non-CE tumor beyond the CE tumor borders may translate into additional survival benefit, providing a rationale to explicitly denominate such "supramaximal CE resection."

Posterior-based resection of spinal meningiomas: an institutional experience of 141 patients with an average of 28 months of follow-up.

OBJECTIVE: Spinal meningiomas pose unique challenges based on the location of their dural attachment. However, there is a paucity of literature investigating the role of dural attachment location on outcomes after posterior-based approach for spinal meningioma resection. The aim of this study was to investigate any differences in outcomes between dural attachment location subgroups in spinal meningioma patients who underwent posterior-based resection. METHODS: This was a single-institution review of patients who underwent resection of a spinal meningioma from 1997 to 2017. Surgical, oncological, and neurological outcomes were compared between patients with varying dural attachments. Multivariate analysis was utilized. RESULTS: A total of 141 patients were identified. The mean age was 62 years, and 110 women were included. The sites of dural attachments were as follows: 16 (11.3%) dorsal, 31 (22.0%) dorsolateral, 17 (12.1%) lateral, 40 (28.4%) ventral, and 37 (26.2%) ventrolateral. Most meningiomas were WHO grade I (92.2%) and in the thoracic spine (61.0%). All patients underwent a posterior approach for tumor resection. There were no differences between subgroups in terms of largest diameter of tumor resected (p = 0.201), gross-total resection (GTR) or subtotal resection (p = 0.362), Simpson grade of resection, perioperative complications (p = 0.116), long-term neurological deficit (p = 0.100), or postoperative radiation therapy (p = 0.971). Cervical spine location was associated with reduced incidence of GTR (OR 0.271, 95% CI 0.108-0.684, p = 0.006) on multivariate analysis. The overall incidence of recurrence/progression was 4.6%, with no difference (p = 0.800) between subgroups. Similarly, the average length of follow-up was 28.1 months, with no difference between subgroups (p = 0.413). CONCLUSIONS: Posterior-based approaches for resection of spinal meningiomas are safe and effective, regardless of dural attachment location, with similar surgical, oncological, and neurological outcomes. Comparison of long-term recurrence rates between dural attachment subgroups is required.

Anterolateral Thigh Free Flap Versus Thigh Split Thickness Skin Graft: Comparison of Morbidity in the First 30 Days.

Background: An anterior thigh split thickness skin graft (AT-STSG) is frequently needed to close the radial forearm free flap (RFFF) donor site, conferring morbidity to two extremities. The anterolateral thigh (ALT) free flap is virtually always closed primarily. Objective: To compare donor site pain, sensation, motor function, and cosmesis associated with the AT-STSG and the ALT. Methods: Patients undergoing an ALT or an RFFF with AT-STSG were enrolled in a prospective observational cohort study. Pain, tingling, numbness, lower extremity function, and subjective donor site cosmetic satisfaction were measured at 1 week and 1 month postoperation using validated instruments. Results: Forty-eight patients were included, with a mean age of 64.2 years (female 31.2%). There were no differences in age or medical comorbidities between the two groups. The average donor defect was 50 and 180 cm2 for the AT-STSG and ALT cohorts, respectively. At 1 week and 1 month postoperatively, we did not detect a difference in donor site pain, pruritus, numbness or tingling, lower extremity function, or subjective cosmetic satisfaction between the two cohorts. Conclusion: ALT primary donor site morbidity, including pain, sensory function, motor function, and cosmesis, is equivalent to RFFF secondary donor site morbidity at 1 week and 1 month postoperatively.

Novel intraoperative strategies for enhancing tumor control: Future directions.

Maximal safe surgical resection plays a key role in the care of patients with gliomas. A range of technologies have been developed to aid surgeons in distinguishing tumor from normal tissue, with the goal of increasing tumor resection and limiting postoperative neurological deficits. Technologies that are currently being investigated to aid in improving tumor control include intraoperative imaging modalities, fluorescent tumor makers, intraoperative cell and molecular profiling of tumors, improved microscopic imaging, intraoperative mapping, augmented and virtual reality, intraoperative drug and radiation delivery, and ablative technologies. In this review, we summarize the aforementioned advancements in neurosurgical oncology and implications for improving patient outcomes.

Correlation between tumor volume and serum prolactin and its effect on surgical outcomes in a cohort of 219 prolactinoma patients.

OBJECTIVE: Prolactinoma is the most common pituitary adenoma and can be managed medically or surgically. The authors assessed the correlation between tumor volume and prolactin level and its effect on surgical outcomes. METHODS: The authors reviewed 219 patients who underwent transsphenoidal prolactinoma resection at a single institution from 2012 to 2019. Outcomes were compared between patients with and without biochemical remission. Tumor volumes were quantified with BrainLab Smartbrush. Correlation analysis and linear regression were used to examine the association between tumor volume and serum prolactin level. Volume-adjusted prolactin level was defined as serum prolactin level divided by tumor volume. The authors utilized receiver operating characteristic (ROC) curve analysis to determine the thresholds for predicting biochemical remission status. RESULTS: The mean tumor volume was 5.66 cm3, and the mean preoperative prolactin level was 752.3 µg/L. Men had larger prolactinomas than women (mean volume 11.32 vs 2.54 cm3; p < 0.001), and women had a greater volume-adjusted prolactin level (mean 412.5 vs 175.9 µg/L/cm3, p < 0.001). In total, 66.7% of surgical patients achieved biochemical remission 6 weeks after surgery, whereas a similar cohort of medically treated patients during the same time frame demonstrated a 69.4% remission rate. Pearson correlation and linear regression analysis revealed a strong association between preoperative tumor volume and prolactin levels, with an increase in serum prolactin level of 101.31 µg/L per 1-cm3 increase in tumor volume (p < 0.001). This held true for men (R = 0.601, p < 0.001) and women (R = 0.935, p < 0.001), with women demonstrating a greater increase in prolactin level per 1-cm3 increase in volume (185.70 vs 79.77 µg/L, p < 0.001). Patients who achieved remission exhibited a 66.08-µg/L increase in preoperative prolactin level per 1 cm3 of preoperative tumor volume (p < 0.001), which was less than the 111.46-µg/L increase per 1 cm3 in patients without remission (p < 0.001). Patients who failed to achieve remission had residual tumors with a 77.77-µg/L increase in prolactin per 1 cm3 of remaining tumor volume after resection (p < 0.001). ROC curve analysis revealed significant thresholds that optimally predicted lack of postoperative remission on the basis of preoperative prolactin and tumor volume. These thresholds were rendered nonsignificant in patients with documented Knosp grade ≥ 3. CONCLUSIONS: Although the authors found a correlation between prolactinoma volume and serum prolactin level, patients without remission had a greater increase in serum prolactin level per increase in preoperative tumor volume than those who achieved remission, suggesting unique tumor composition. The authors also identified prolactin and tumor volume thresholds that optimally predicted biochemical remission status. The authors hope that their results can be used to identify prolactinomas for which surgery could achieve remission as an alternative to medical management.

Predictors of Extreme Hospital Length of Stay After Traumatic Brain Injury.

BACKGROUND: Hospital length of stay (HLOS) after traumatic brain injury (TBI) is an important metric of injury severity, resource utilization, and access to post-acute care services. Risk factors for protracted HLOS after TBI require further characterization. METHODS: Data regarding adult inpatients admitted to a single U.S. level 1 trauma center with a diagnosis of acute TBI between August 1, 2019, and April 1, 2022, were extracted from the electronic health record. Patients with extreme HLOS (XHLOS, >99th percentile of institutional TBI HLOS) were compared with those without XHLOS. Socioeconomic status (SES), clinical/injury factors, and discharge disposition were analyzed. RESULTS: In 1638 patients, the median HLOS was 3 days (interquartile range [IQR]: 2-8 days). XHLOS threshold was >70 days (N = 18; range: 72-146 days). XHLOS was associated with younger age (XHLOS/non-XHLOS: 50.4/59.6 years; P = 0.042) and greater proportions with severe TBI (55.6%/11.4%; P < 0.001), low SES (72.2%/31.4%; P < 0.001), and Medicaid insurance (77.8%/30.1%; P < 0.001). XHLOS patients were more likely to die in hospital (22.2%/8.1%) and discharge to post-acute facility (77.8%/16.3%; P < 0.001). No XHLOS patients were discharged to home. In XHLOS patients alive at discharge, medical stability was documented at median 39 days (IQR: 28-58 days) and were hospitalized for another 56 days (IQR: 26.5-78.5 days). CONCLUSIONS: XHLOS patients were more likely to have severe injuries, low SES, and Medicaid. XHLOS is associated with in-hospital mortality and need for post-acute placement. XHLOS patients often demonstrated medical stability long before placement, underscoring complex relationships between SES, health insurance, and outcome. These findings have important implications for quality improvement and resource utilization at acute care hospitals and await validation from larger trials.

Evacuation of a multi-loculated acute-on-chronic subdural hematoma using tandem bedside subdural evacuation port systems.

Background: Traumatic subdural hematomas (SDH) can have devastating neurologic consequences. Acute-on-chronic SDHs are more frequent in the elderly, who have increased comorbidities and perioperative risks. The subdural evacuation port system (SEPS) procedure consists of a twist drill hole connected to a single drain on suction, which can be performed at bedside to evacuate SDHs without requiring general anesthesia. However, a single SEPS can be limited due to inability to evacuate across septations between SDHs of different ages. Purpose: We present to our knowledge the first case of using tandem SEPS to evacuate a multi-loculated SDH. We discuss the technical nuances of the procedure as a treatment option for complex SDHs. Findings: An 86-year-old man with cognitive impairment and recurrent falls presented acutely after ground-level fall with worsening dysarthria and right hemiparesis. Computed tomography scan showed a 11 mm left holohemispheric mixed-density SDH with loculated acute and subacute/chronic components with 2 mm midline shift. Following two interval stability scans, the patient underwent drainage of a superficial chronic component, and a posterolateral acute/subacute component using two sequential SEPS drains at bedside in the intensive care unit. The patient's symptoms markedly improved, drains were removed, and the patient was discharged home with home health on post-procedure day 6. Conclusions: Judicious patient selection and pre-procedural planning can enable the use of tandem SEPS to evacuate multi-loculated SDHs under moderate sedation. Using multiple subdural ports to evacuate complex SDHs should be an option for proceduralists in settings where general anesthesia is not feasible.

Cardiac Complications After 3-Column Osteotomy for Adult Spinal Deformity Patients With Formal Cardiac Clearance: Identifying Key Risk Factors and Threshold Cutoffs Via Recursive Partitioning Analysis.

BACKGROUND: Despite formal cardiac clearance, a subset of 3-column osteotomy (3CO) patients still experience cardiac complications (CCs). OBJECTIVE: To define the incidence and risk factors for CC in 3CO patients who had formal cardiac clearance and assess the utility of the Revised Cardiac Risk Index (RCRI) and preoperative metabolic equivalent (MET) functional ability in predicting perioperative CC. METHODS: Patients with adult spinal deformity (ASD) who underwent 3CO deformity correction from 2006 to 2019 were retrospectively reviewed. Multivariate and recursive partitioning analyses were performed to assess risk factors. RESULTS: A total of 390 patients with ASD were included. The mean age was 64.6 years, and 60.3% were female. The CC rate was 9.7%. Patients with CCs were older ( P < .001), had an increased history of heart disease ( P = .001), and higher blood loss ( P = .045). RCRI score ( P = .646) or MET functional ability ( P = .493) were not associated with CC. On multivariate analysis, age ( P < .001), blood loss ( P = .008), and prior spinal fusion ( P = .025) were independent risk factors for CC. Patients age older than 81 years had a significantly higher CC rate than those younger than 81 years. In patients age 81 years and younger, if blood loss was >3900 mL, CC rate was significantly higher. Among patients age 81 years and younger and with >3900 mL blood loss, CC rate is significantly higher in patients with ejection fraction (EF) ≤54.5%. CONCLUSION: RCRI and MET functional ability are limited risk assessment tools in ASD 3CO patients with formal cardiac clearance. Patients older than 81 years are at high risk for CC. In younger patients, cardiac EF and blood loss are significant components to risk stratify for CC.