The effect of institutional case volume on post-operative outcomes after endarterectomy and stenting for symptomatic carotid stenosis.

OBJECTIVE: To investigate the effects of yearly institutional case volume for carotid endarterectomy (CEA) and stenting (CAS) among symptomatic carotid stenosis patients on the rates of postoperative stroke and inpatient mortality. MATERIALS AND METHODS: Patients with prior stroke ("symptomatic") undergoing CEA or CAS during an inpatient stay were identified from the National Inpatient Sample for years 2012-2015. The primary variable was volume of CEA or CAS performed annually by each institution. The primary outcome was a composite variable for in-hospital death or postoperative stroke. RESULTS: A total of 5,628 patients with symptomatic carotid stenosis underwent CEA, while 245 underwent CAS. In the symptomatic CEA population, 519 (9.2 %) patients experienced postoperative stroke or mortality, and were more likely to be treated at centers with a lower yearly institutional volume (median 10 [IQR 5-15] versus 10 [7-20] cases, p < 0.001). In the symptomatic CAS population, 32 (13.1 %) patients experienced stroke or mortality, and these patients were also more likely to undergo treatment at hospitals with a lower yearly institutional volume (median 5 [IQR 5-7] versus 5 [5-10] cases, p = 0.044). Thresholds for yearly institutional volume found differences in adverse outcome between 0-9, 10-29, and ≥30 cases/year (11.7 % vs 8.4 % vs 6.0 %, p < 0.001) for CEA, and differences in postoperative stroke between 0-9 and ≥10 cases/year for CAS (11.0 % vs 1.4 %, p = 0.028). CONCLUSIONS: Hospitals performing higher volumes of CEA or CAS have fewer postoperative strokes. The threshold reported herein is ≥30 CEA procedures or ≥10 CAS procedures annually for appreciably improved outcomes.

First United States multicenter experience with the new-generation FRED X surface-modified flow diversion stent: feasibility, safety, and short-term efficacy.

OBJECTIVE: Flow diversion created a paradigm shift in the treatment of intracranial aneurysms. The new flow redirection endoluminal device with X technology (FRED X) is the latest update of the recent Food and Drug Administration-approved FRED. The FRED X is engineered to reduce material thrombogenicity and enhance vessel healing. In this study, the authors aimed to evaluate the feasibility and early safety and efficacy of the new FRED X. METHODS: The authors retrospectively collected and analyzed data from patients who had undergone flow diversion with the new FRED X at four tertiary cerebrovascular centers in the United States from February 2022 through July 2022. RESULTS: Forty-four patients with 45 aneurysms treated using 46 devices comprised the overall study cohort and were divided into two groups: 39 patients with unruptured aneurysms and 5 patients with ruptured aneurysms. The mean patient age was 57.7 ± 9.1 years, and most patients were female (84%). Ninety-one percent of the aneurysms were saccular, with the majority (93%) located in the anterior circulation, specifically the posterior communicating (27%) and carotid ophthalmic (27%) territories. The mean maximum aneurysm diameter was 5.6 ± 4.6 mm, and 20% of the lesions had been previously treated. The mean procedure time was 61.6 minutes, with a mean cumulative fluoroscopy time of 24.6 minutes. Additionally, 7% of the lesions received adjunct treatment. Stent placement was successful in 100% of cases, achieving good wall apposition and complete neck coverage. Further, immediate aneurysm contrast stasis > 90% was observed in 61% of cases. Symptomatic postoperative complications occurred in 3 patients in the unruptured cohort and 1 patient in the ruptured cohort. All patients in the study were discharged on dual antiplatelet regimens with a modified Rankin Scale score of 0. At 6 months after treatment, 89% of cases had adequate occlusion, with < 6% of cases having asymptomatic in-stent stenosis. All patients had excellent functional outcomes. CONCLUSIONS: FRED X for the treatment of an intracranial aneurysm is technically feasible alone or in conjunction with intrasaccular embolization. In addition, the study results showed very promising early safety and efficacy. Follow-up studies should establish the long-term safety and efficacy profiles of this new stent.

Predictors of recurrence after surgical resection of parafalcine and parasagittal meningiomas.

PURPOSE: Owing to their vicinity near the superior sagittal sinus, parasagittal and parafalcine meningiomas are challenging tumors to surgically resect. In this study, we investigate key factors that portend increased risk of recurrence after surgery. METHODS: This is a retrospective study of patients who underwent resection of parasagittal and parafalcine meningiomas at our institution between 2012 and 2018. Relevant clinical, radiographic, and histopathological variables were selected for analysis as predictors of tumor recurrence. RESULTS: A total of 110 consecutive subjects (mean age: 59.4 ± 15.2 years, 67.3% female) with 74 parasagittal and 36 parafalcine meningiomas (92 WHO grade 1, 18 WHO grade 2/3), are included in the study. A total of 37 patients (33.6%) exhibited recurrence with median follow-up of 42 months (IQR: 10-71). In the overall cohort, parasagittal meningiomas exhibited shorter progression-free survival compared to parafalcine meningiomas (Kaplan-Meier log-rank p = 0.045). On univariate analysis, predictors of recurrence include WHO grade 2/3 vs. grade 1 tumors (p < 0.001), higher Ki-67 indices (p < 0.001), partial (p = 0.04) or complete sinus invasion (p < 0.001), and subtotal resection (p < 0.001). Multivariable Cox regression analysis revealed high-grade meningiomas (HR: 3.62, 95% CI: 1.60-8.22; p = 0.002), complete sinus invasion (HR: 3.00, 95% CI: 1.16-7.79; p = 0.024), and subtotal resection (HR: 3.10, 95% CI: 1.38-6.96; p = 0.006) as independent factors that portend shorter time to recurrence. CONCLUSION: This study identifies several pertinent factors that confer increased risk of recurrence after resection of parasagittal and parafalcine meningiomas, which can be used to devise appropriate surgical strategy to achieve improved patient outcomes.

Blood Loss and Transfusion in a Pediatric Scoliosis Surgery Cohort in the Antifibrinolytic Era.

Children and adolescents undergoing posterior spinal fusion for scoliosis experience high rates of bleeding and blood product transfusion. Antifibrinolytic therapy is one key strategy to decrease blood loss and transfusion in pediatric scoliosis surgery. Here we review 172 pediatric scoliosis patients (birth to 21 y) who underwent posterior spinal fusion at our institution from 2017 to 2018. We reported rates of blood loss and transfusion, compared patients receiving tranexamic acid to a ε-aminocaproic acid, and evaluated antifibrinolytic agent and laboratory parameters as predictors of blood loss and transfusion. Intraoperatively, 62% received tranexamic acid and 38% received ε-aminocaproic acid. Overall, blood loss (mean intraoperative estimated blood loss=14.9±9.7 mL/kg, 22% with clinically significant blood loss [>20 mL/kg], and mean calculated hemoglobin mass loss=175.9±70.1 g) and transfusion rates (15% with intraoperative allogeneic red blood cell transfusion and mean intraoperative allogeneic red blood cell transfusion volume=12.5±7.1 mL/kg) were similar to previous cohorts studying intraoperative antifibrinolytics. There was no difference in intraoperative estimated blood loss, clinically significant blood loss, calculated hemoglobin mass loss, or transfusion rates between the antifibrinolytic groups. Antifibrinolytic choice was not predictive of blood loss or transfusion. Routine hematologic laboratory parameters and antifibrinolytic choice were insufficient to predict blood loss or other outcomes. Future prospective laboratory-based studies may provide a more comprehensive model of surgical-induced coagulopathy in scoliosis surgery and provide a better tool for predicting blood loss and improving outcomes.

Statins as a Medical Adjunct in the Surgical Management of Chronic Subdural Hematomas.

BACKGROUND: By stabilizing immature leaky vessel formation in neomembranes, statin drugs have been suggested as a nonsurgical treatment option for chronic subdural hematomas (cSDH). Statin therapy seems to reduce conservatively managed cSDH volume. However, the usefulness of these medications in supplementing surgical treatment is unknown. OBJECTIVE: To investigate the effect of concurrent statin therapy on outcomes after surgical treatment of cSDH. METHODS: A retrospective single-institution cohort study of surgically managed patients with convexity cSDH between 2009 and 2019 was conducted. Patients receiving this diagnosis who underwent surgical decompression were included, and those without follow-up scans were excluded. Demographic, clinical, and radiographic variables were collected. cSDH size was defined as maximum radial thickness in millimeters on axial computed tomography of the head. Multivariable linear regression was performed to identify factors (including statin use) that were associated with preoperative to follow-up cSDH size change. RESULTS: Overall, 111 patients, including 36 patients taking statins on admission, were evaluated. Median time to follow-up postoperative imaging was 30 days (interquartile range, 17-42 days). Patients on statins were older (median, 75 years, range, 68-78.25 years vs. 69 years, range, 59-7 years; P = 0.006) and reported more antiplatelet use (67% vs. 28%; P < 0.001). Median change in follow-up size was 13 mm in both statin and nonstatin groups. Adjusting for other clinical covariates, statin use was associated with greater reduction in cSDH size (CE = -6.72 mm, 95% confidence interval, -13.18 to -0.26 mm; P = 0.042). CONCLUSIONS: Statin use is associated with improved cSDH size postoperatively. Statin drugs might represent a low-cost and low-risk supplement to the surgical management for patients with cSDH.

Predicting for Lost to Follow-up in Surgical Management of Patients with Chronic Subdural Hematoma.

BACKGROUND: Lost to follow-up (LTF) represents an understudied barrier to effective management of chronic subdural hematoma (cSDH). Understanding the factors associated with LTF after surgical treatment of cSDH could uncover pathways for quality improvement efforts and modify discharge planning. We sought to identify the demographic and clinical factors associated with patient LTF. METHODS: A single-institution, retrospective cohort study of patients treated surgically for convexity cSDH from 2009 to 2019 was conducted. The primary outcome was LTF, with neurosurgical readmission as the secondary outcome. Univariate analysis was conducted using the student-t test and χ2 test. Multivariate logistic regression was performed to identify the factors associated with LTF and neurosurgical readmission. RESULTS: A total of 139 patients were included, 29% of whom were LTF. The mean first postoperative follow-up duration was 60 days. On univariate analysis, uninsured/Medicaid coverage was associated with increased LTF compared with private insurance/Medicare coverage (62.5% vs. 41.4%; P = 0.039). A higher discharge modified Rankin scale score was also associated with LTF (3.7 vs. 3.5; P < 0.001). On multivariate analysis, uninsured/Medicaid patients had a significantly greater risk of LTF compared with private insurance/Medicare patients (odds ratio, 2.44; 95% confidence interval, 1.13-5.23; P = 0.022). LTF was independently associated with an increased risk of neurosurgical readmission (odds ratio, 1.94; 95% confidence interval, 1.17-3.24; P = 0.011). CONCLUSIONS: Uninsured and Medicaid patients had a greater likelihood of LTF compared with private insurance and Medicare patients. LTF was further associated with an increased risk of neurosurgical readmission. The results from the present study emphasize the need to address barriers to follow-up to reduce readmission after surgery for cSDH. These findings could inform improved discharge planning, such as predischarge repeat imaging studies and postdischarge contact.

Impact of insurance type on national variation in cost of endovascular treatment for unruptured cerebral aneurysms.

BACKGROUND: Identifying drivers of nationwide variation in healthcare costs could help reduce overall cost. Endovascular treatment for unruptured cerebral aneurysms (ETUCR) is an elective neurointerventional procedure that allows for detailed analysis of cost variation. This study aimed to investigate the role of insurance type in cost variation of ETUCR. METHODS: A retrospective analysis of patients undergoing ETUCR was done. Demographic and hospital data were obtained from the National Inpatient Sample 2012-2015. Multivariate analysis was done using a generalized linear model. Oaxaca-Blinder decomposition was performed to identify factors driving cost variation. RESULTS: There was a significant difference in median cost ($25 331.82 vs $25 825.25, respectively, P<0.001) as well as length of stay (P<0.001) and complications (P<0.001) between patients with private insurance and Medicare. In multivariate analysis, insurance type was not predictive of increased cost. Among patients aged 65-75 years there was a higher median cost with private insurance compared to Medicare ($28 373.85 vs $25 558.25, respectively, P<0.001) but no difference in complications or length of stay. Oaxaca-Blinder decomposition showed higher marginal costs associated with private insurance patients at hospitals with greater endovascular operative volume (P=0.015). CONCLUSIONS: In patients aged 65-75 years, private insurance is associated with higher costs compared to Medicare; however, insurance type is not predictive of increased cost in multivariate analysis. Differential treatment of private insurance and Medicare patients at hospitals with greater operative volume seems to influence this difference, likely due to differential reimbursement schemes that lead to weaker cost controls.

Hyperoxemia and Cerebral Vasospasm in Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Cerebral vasospasm is a major contributor to disability and mortality after aneurysmal subarachnoid hemorrhage. Oxidation of cell-free hemoglobin plays an integral role in neuroinflammation and is a suggested source of tissue injury after aneurysm rupture. This study sought to determine whether patients with subarachnoid hemorrhage and cerebral vasospasm were more likely to have been exposed to early hyperoxemia than those without vasospasm. METHODS: This single-center retrospective cohort study included adult patients presenting with aneurysmal subarachnoid hemorrhage to Vanderbilt University Medical Center between January 2007 and December 2017. Patients with an ICD-9/10 diagnosis of aneurysmal subarachnoid hemorrhage were initially identified (N = 441) and subsequently excluded if they did not have intracranial imaging, arterial PaO2 values or died within 96 h post-rupture (N = 96). The final cohort was 345 subjects. The degree of hyperoxemia was defined by the highest PaO2 measured within 72 h after aneurysmal rupture. The primary outcome was development of cerebral vasospasm, which included asymptomatic vasospasm and delayed cerebral ischemia (DCI). Secondary outcomes were mortality and modified Rankin Scale. RESULTS: Three hundred and forty five patients met inclusion criteria; 218 patients (63%) developed vasospasm. Of those that developed vasospasm, 85 were diagnosed with delayed cerebral ischemia (DCI, 39%). The average patient age of the cohort was 55 ± 13 years, and 68% were female. Ninety percent presented with Fisher grade 3 or 4 hemorrhage (N = 310), while 42% presented as Hunt-Hess grade 4 or 5 (N = 146). In univariable analysis, patients exposed to higher levels of PaO2 by quintile of exposure had a higher mortality rate and were more likely to develop vasospasm in a dose-dependent fashion (P = 0.015 and P = 0.019, respectively). There were no statistically significant predictors that differentiated asymptomatic vasospasm from DCI and no significant difference in maximum PaO2 between these two groups. In multivariable analysis, early hyperoxemia was independently associated with vasospasm (OR = 1.15 per 50 mmHg increase in PaO2 [1.03, 1.28]; P = 0.013), but not mortality (OR = 1.10 [0.97, 1.25]; P = 0.147) following subarachnoid hemorrhage. CONCLUSIONS: Hyperoxemia within 72 h post-aneurysmal rupture is an independent predictor of cerebral vasospasm, but not mortality in subarachnoid hemorrhage. Hyperoxemia is a variable that can be readily controlled by adjusting the delivered FiO2 and may represent a modifiable risk factor for vasospasm.

Prehospital care of trauma patients in Tanzania: medical knowledge assessment and proposal for safe transportation of neurotrauma patients.

STUDY DESIGN: A descriptive, cross-sectional survey of individuals involved in prehospital transportation of neurotrauma patients was performed. OBJECTIVES: Little is known about prehospital care of neurotrauma patients in low- and middle-income countries. This study sought to assess the knowledge of prehospital transporters in Tanzania and propose an educational intervention to help identify patients with severe neurotrauma. SETTING: Dar es Salaam, Tanzania. METHODS: Surveys assessed demographic information and medical knowledge with three outcomes of identifying signs of a deceased, sick, or clinically deteriorating patient. Predictors of increased medical knowledge were investigated with univariate and multivariate logistic regression (MLR). RESULTS: The survey included 501 participants, who were predominantly young (mean: 36.7 years) and male (84.0%). More than 70% of participants self-reported being able to recognize a deceased or sick patient, yet fewer than 20% correctly listed more than two signs of a deceased, sick, or clinically deteriorating patient. MLR showed that first aid training (Odds ratio (OR): 2.3; 95% confidence interval (CI): 1.3, 3.9; p = 0.002) was predictive of identifying a deceased patient, being employed (OR: 0.5; 95% CI: 0.3, 0.9; p = 0.021) was a negative predictor of identifying a sick patient, and higher education level (OR: 2.3; 95% CI: 1.1, 4.8; p = 0.032) was predictive of identifying a clinically deteriorating patient. CONCLUSION: In a survey of prehospital transporters of neurotrauma patients in Tanzania, higher education level and first aid training were associated with higher medical knowledge scores. An educational flier was created to identify severe neurotrauma patients. Additional education of prehospital transporters in Tanzania may improve morbidity and mortality of neurotrauma patients.

Repeat Surgery After Decompressive Craniectomy for Traumatic Intracranial Hemorrhage: Outcomes and Predictors.

INTRODUCTION: Repeat surgery (RS) after decompressive craniectomy/craniotomy (DC) for traumatic intracranial hemorrhage (TICH) is a devastating complication. In patients undergoing DC for TICH, we sought to 1) describe the population requiring RS, 2) compare outcomes of those requiring RS with those who did not, and 3) discern RS predictors. METHODS: A single-institution retrospective case-control study was conducted from 2000 to 2015. Inclusion criteria were DC for acute supratentorial TICH (subdural hemorrhage, epidural hemorrhage, and intraparenchymal hemorrhage) and ≥7 day survival. Patients underwent RS within 7 days of DC; controls did not require RS. Outcomes and predictors of RS were evaluated with univariate and multivariate logistic regression (MLR). RESULTS: Of 201 patients requiring DC, 28 (14%) underwent RS. Common mechanisms were ground-level fall (45%) and motor vehicle collision (29%). Anticoagulation/antiplatelet medication was used by 44 patients (21%). Subdural hemorrhage was the most common hemorrhage (64%). Using MLR, those requiring RS were more likely to experience major complications (odds ratio [OR], 22.6; 95% confidence interval [CI], 5.06-101.35; P < 0.001) and in-hospital mortality (OR, 2.76; 95% CI, 1.02-7.43; P = 0.045) and be dead/dependent at 6 months (OR, 2.50; 95% CI, 1.08-5.82; P = 0.033) and 2 years (OR, 2.44; 95% CI, 0.99-6.00; P = 0.051). Predictors of undergoing RS identified by MLR were smaller hemorrhage (OR, 0.32; 95% CI, 0.13-0.78; P = 0.012), larger midline shift (OR, 4.40; 95% CI, 1.43-13.51; P = 0.010), and better preoperative Glasgow Coma Scale score (OR, 1.28; 95% CI, 1.13-1.46; P < 0.001). CONCLUSIONS: Patients requiring RS after DC represent a heterogenous population with worse outcomes. Although the identified risk factors for RS are not modifiable, surgeons should be aware of these factors during the initial surgery.

Toxic expanded GGGGCC repeat transcription is mediated by the PAF1 complex in C9orf72-associated FTD.

An expanded GGGGCC hexanucleotide of more than 30 repeats (termed (G4C2)30+) within C9orf72 is the most prominent mutation in familial frontotemporal degeneration (FTD) and amyotrophic lateral sclerosis (ALS) (termed C9+). Through an unbiased large-scale screen of (G4C2)49-expressing Drosophila we identify the CDC73/PAF1 complex (PAF1C), a transcriptional regulator of RNA polymerase II, as a suppressor of G4C2-associated toxicity when knocked-down. Depletion of PAF1C reduces RNA and GR dipeptide production from (G4C2)30+ transgenes. Notably, in Drosophila, the PAF1C components Paf1 and Leo1 appear to be selective for the transcription of long, toxic repeat expansions, but not shorter, nontoxic expansions. In yeast, PAF1C components regulate the expression of both sense and antisense repeats. PAF1C is upregulated following (G4C2)30+ expression in flies and mice. In humans, PAF1 is also upregulated in C9+-derived cells, and its heterodimer partner, LEO1, binds C9+ repeat chromatin. In C9+ FTD, PAF1 and LEO1 are upregulated and their expression positively correlates with the expression of repeat-containing C9orf72 transcripts. These data indicate that PAF1C activity is an important factor for transcription of the long, toxic repeat in C9+ FTD.

The Proline/Arginine Dipeptide from Hexanucleotide Repeat Expanded C9ORF72 Inhibits the Proteasome.

An intronic hexanucleotide repeat expansion (HRE) mutation in the C9ORF72 gene is the most common cause of familial ALS and frontotemporal dementia (FTD) and is found in ∼7% of individuals with apparently sporadic disease. Several different diamino acid peptides can be generated from the HRE by noncanonical translation (repeat-associated non-ATG translation, or RAN translation), and some of these peptides can be toxic. Here, we studied the effects of two arginine containing RAN translation products [proline/arginine repeated 20 times (PR20) and glycine/arginine repeated 20 times (GR20)] in primary rat spinal cord neuron cultures grown on an astrocyte feeder layer. We find that PR20 kills motor neurons with an LD50 of 2 µM, but in contrast to the effects of other ALS-causing mutant proteins (i.e., SOD or TDP43), PR20 does not evoke the biochemical signature of mitochondrial dysfunction, ER stress, or mTORC down-regulation. PR20 does result in a time-dependent build-up of ubiquitylated substrates, and this is associated with a reduction of flux through both autophagic and proteasomal degradation pathways. GR20, however, does not have these effects. The effects of PR20 on the proteasome are likely to be direct because (1) PR20 physically associates with proteasomes in biochemical assays, and (2) PR20 inhibits the degradation of a ubiquitylated test substrate when presented to purified proteasomes. Application of a proteasomal activator (IU1) blocks the toxic effects of PR20 on motor neuron survival. This work suggests that proteasomal activators have therapeutic potential in individuals with C9ORF72 HRE.