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Study Design: Retrospective Cohort Study., Objectives: To determine the ability of early vital sign abnormalities to predict functional independence in patients with SCI that required surgery., Methods: A retrospective analysis of data extracted from the Pennsylvania Trauma Outcome Study database. Inclusion criteria were patients >18 years with a diagnosis of SCI who required urgent spine surgery in Pennsylvania from 1/1/2010-12/31/2020 and had complete records available., Results: A total of 644 patients met the inclusion criteria. The mean age was 47.1 ± 14.9 years old and the mean injury severity score (ISS) was 22.3 ± 12.7 with the SCI occurring in the cervical, thoracic, and lumbar spine in 61.8%, 19.6% and 18.0%, respectively. Multivariable logistic regression analyses for predictors of functional independence at discharge showed that higher HR at the scene (OR 1.016, 95% CI 1.006-1.027, P = .002) and lower ISS score (OR .894, 95% CI .870-.920, P < .001) were significant predictors of functional independence. Similarly, higher admission HR (OR 1.015, 95% CI 1.004-1.027, P = .008) and lower ISS score (OR .880, 95% CI 0.864-.914, P < .001) were significant predictors of functional independence. Peak Youden indices showed that patients with HR at scene >70 and admission HR ≥83 were more likely to achieve functional independence., Conclusions: Early heart rate is a strong predictor of functional independence in patients with SCI. HR at scene >70 and admission HR ≥83 is associated with improved outcomes, suggesting lack of neurogenic shock., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Study Design: Retrospective Cohort Study., Introduction: The 11-item modified Frailty index (mFI-11) by the ACS-NSQIP database was used to predict which patients are high risk for complications and inpatient mortality. ACS-NSQIP now has switched to the 5-item MFI. However, there are no studies on how these frailty indices fare against each other and their prognostic value of functional independence in patients with spinal cord injury (SCI)., Objective: To compare the mFI-5 and mFI-11 in order to standardize frailty assessment in the SCI population., Methods: Retrospective analysis of 272,174 patients with SCI from 2010 to 2020 from the Pennsylvania Trauma Systems Foundation (PTSF) registry. Multivariable logistic regression was used to determine the predictive value of mFI for functional independence as determined by locomotion and transfer mobility., Results: A total of 1907 patients were included with a mean age of 46.9 ± 15.1 years. The 3 most common MFI factors were hypertension (32.2%), diabetes mellitus (13.7%) and chronic obstructive pulmonary disease (8.5%). Multivariable logistic regression analyses using MFI-5 and MFI-11 showed that a higher frailty score in MFI-5 (OR 1.375, P < .001) and in MFI-11 (OR 1.366, P < .001) were each predictive of poor functional status at discharge. ROC curves for the MFI-5 (AUC = .818, P < .001) and MFI-11 (AUC = .819, P < .001) demonstrated excellent diagnostic accuracy., Conclusion: The new MFI-5 is equivalent to its predecessor, the MFI-11, and predictive of functional outcomes in patients with SCI. MFI-5 can serve as the preferred frailty index at the point of care and in research contexts., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Author ContributionsNM, TL, and JJ designed the study. NM, TL were involved with data collection and analysis. NM, TL, CY, KL, DF, KH, KL were involved with data collection, manuscript preparation, critical revision, and data interpretation. AS, SP, JH, JSH, JJ were responsible for manuscript preparation, and critical revision.

Background: There is a lack of data on whether intracranial pressure (ICP)-guided therapy with an intraparenchymal fiberoptic monitor (IPM) or an external ventricular drain (EVD) leads to superior outcomes. Our goal is to determine the relationship between ICP-guided therapy with an EVD or IPM and mortality., Methods: Retrospective analysis of severe traumatic brain injury cases that required IPM or EVD placement for ICP-guided therapy from January 1, 2010 to December 31, 2020. The data were obtained from the Pennsylvania Trauma Systems Foundation registry., Results: A total of 2305 patients met the inclusion criteria, with 1048 (45.5%) IPM and 1257 (54.5%) EVD placed. Inpatient mortality occurred in 337 (32.2%) and 334 (26.6%) patients in the IPM and EVD cohorts, respectively (P = 0.003). Even among those treated medically only, inpatient mortality occurred in 171 (30.8%) of those with an IPM and in 100 (23.4%) of those with an EVD (P = 0.010). Multivariable logistic regression analysis showed that older age (odds ratio [OR] 1.03, P < 0.001), lower Glasgow Coma Scale (GCS) score (OR 1.16, P < 0.001), requiring surgery (OR 1.22, P = 0.049), and an IPM (OR 1.40, P = 0.001) were significant predictors of mortality. Propensity score-adjusted analysis using inverse probability of treatment weighted method revealed a 28% decrease in mortality and a 14% decrease in length of hospital stay with EVD use when adjusting for age, sex, GCS, Injury Severity Score, surgery, and Hispanic ethnicity., Conclusions: A significant mortality benefit was associated with the use of EVD compared to IPM. This mortality benefit was observed regardless of whether patients required surgery or not., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Although not a technically difficult operation, cranioplasty is associated with high rates of complications. The optimal timing of cranioplasty to mitigate complications remains the subject of debate., Objective: To report outcomes between patients undergoing cranioplasty at ultra-early (0-6 weeks), intermediate (6 weeks to 6 months), and late (>6 months) time frames. We report a novel craniectomy contour classification (CCC) as a radiographic parameter to assess readiness for cranioplasty., Methods: A single-institution retrospective analysis of patients undergoing cranioplasty was performed. Patients were stratified into ultra-early (within 6 weeks of index craniectomy), intermediate (6 weeks to 6 months), and late (>6 months) cranioplasty cohorts. We have devised CCC scores, A, B, and C, based on radiographic criteria, where A represents those with a sunken brain/flap, B with a normal parenchymal contour, and C with "full" parenchyma., Results: A total of 119 patients were included. There was no significant difference in postcranioplasty complications, including return to operating room ( P = .212), seizures ( P = .556), infection ( P = .140), need for shunting ( P = .204), and deep venous thrombosis ( P = .066), between the cohorts. Univariate logistic regression revealed that ultra-early cranioplasty was significantly associated with higher rate of functional independence at >6 months (odds ratio 4.32, 95% CI 1.39-15.13, P = .015) although this did not persist when adjusting for patient selection features (odds ratio 2.90, 95% CI 0.53-19.03, P = .234)., Conclusion: In appropriately selected patients, ultra-early cranioplasty is not associated with increased rate of postoperative complications and is a viable option. The CCC may help guide decision-making on timing of cranioplasty., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Background: Euglycemic diabetic ketoacidosis is a metabolic condition characterized by relative euglycemia, ketonemia, and metabolic acidosis that occurs through mechanisms resembling starvation. Pancreaticoduodenectomy is a complex abdominal operation that subjects patients to a prolonged fasting and an inflammatory state. This study examined the incidence of euglycemic diabetic ketoacidosis and potential opportunities for early diagnosis and management in patients undergoing pancreaticoduodenectomy., Methods: A single-institution retrospective review of 350 patients who underwent pancreaticoduodenectomy between 2017 and 2020 was performed. Primary endpoints were peak beta-hydroxybutyrate levels, peak lactate levels, lowest pH, peak base deficits, and urinary output within the first 24 hours, postoperatively. Additional endpoints included incidence of postoperative pancreatic fistula, delayed gastric emptying, total complications, postoperative hospital length of stay, readmission rates, and changes in insulin regimen at discharge., Results: Of the 350 cases reviewed, 39 (11.1%) patients developed euglycemic diabetic ketoacidosis. Male sex and pancreatic cancer were associated with a risk for euglycemic diabetic ketoacidosis (P < .05). Patients with euglycemic diabetic ketoacidosis had significantly higher peak beta-hydroxybutyrate levels than patients without euglycemic diabetic ketoacidosis (mean difference = 19.8 mg/dL, 95% confidence interval = 14.7-24.9, P < .001), and were nearly four times more likely to require insulin at discharge (odds ratio 3.8, 95% confidence interval = 1.1-13.0, P < .05)., Conclusion: This is the first large descriptive study that investigates euglycemic diabetic ketoacidosis after pancreaticoduodenectomy. Euglycemic diabetic ketoacidosis after pancreaticoduodenectomy is associated with significantly higher beta-hydroxybutyrate levels and new or increased insulin requirement at discharge. Our study demonstrates potential markers for euglycemic diabetic ketoacidosis after pancreaticoduodenectomy, offering an opportunity to identify and successfully treat this disease in a timely manner., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Anaplastic meningioma are rare, cancerous tumors of the central nervous system that often require multimodal therapy for tumor control. Both laser interstitial thermal therapy (LITT) and brachytherapy with implanted cesium-131 metallic seeds have demonstrated efficacy in the treatment of recurrent and resistant anaplastic meningioma; however, their safety as a dual therapy has never been reported., Observations: In this report, the authors present a case of a 53-year-old female who received LITT in combination with brachytherapy after surgical and radiation treatment options had been exhausted. The authors discuss the unique safety concern of thermal injury with this treatment combination and demonstrate their method for the safe administration of these treatments together. Furthermore, the authors provide a review of the literature on LITT as an emerging therapy for anaplastic meningioma., Lessons: The use of LITT in combination with brachytherapy remains an option for salvage therapy in patients with recurrent meningioma that provides durable local control of tumor.

Introduction: Dural tails are thickened contrast-enhancing portions of dura associated with some meningiomas. Prior studies have demonstrated the presence of tumor cells within the dural tail, however their inclusion in radiation treatment fields remains controversial. We evaluated the role of including the dural tail when treating a meningioma with stereotactic radiation and the impact on tumor recurrence., Methods: This is a retrospective, single-institution, cohort study of patients with intracranial World Health Organization (WHO) grade 1 meningioma and identified dural tail who were treated with stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) from January 2012 to December 2018. SRS and FSRT subgroups were categorized based on coverage or non-coverage of the dural tail by the radiation fields, as determined independently by a radiation oncologist and a neurosurgeon. Demographics, tumor characteristics, radiation plans, and outcomes were evaluated. High grade tumors were analyzed separately., Results: A total of 187 WHO grade 1 tumors from 177 patients were included in the study (median age: 62 years, median follow-up: 40 months, 78.1% female) with 104 receiving SRS and 83 receiving FSRT. The dural tail was covered in 141 (75.4%) of treatment plans. There was no difference in recurrence rates (RR) or time to recurrence (TTR) between non-coverage or coverage of dural tails (RR: 2.2% vs 3.5%, P  = 1.0; TTR: 34 vs 36 months, P  = 1.00). There was no difference in the rate of radiation side effects between dural tail coverage or non-coverage groups. These associations remained stable when SRS and FSRT subgroups were considered separately, as well as in a high grade cohort of 16 tumors., Conclusion: Inclusion of the dural tail in the SRS or FSRT volumes for meningioma treatment does not seem to reduce recurrence rate. Improved understanding of dural tail pathophysiology, tumor grade, tumor spread, and radiation response is needed to better predict the response of meningiomas to radiotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Piper, Yu, Taghvaei, Fernandez, Mouchtouris, Smit, Yudkoff, Collopy, Reyes, Lavergne, Karsy, Prashant, Shi and Evans.)

Leber congenital amaurosis type 10 is a severe retinal dystrophy caused by mutations in the CEP290 gene 1,2 . We developed EDIT-101, a candidate genome-editing therapeutic, to remove the aberrant splice donor created by the IVS26 mutation in the CEP290 gene and restore normal CEP290 expression. Key to this therapeutic, we identified a pair of Staphylococcus aureus Cas9 guide RNAs that were highly active and specific to the human CEP290 target sequence. In vitro experiments in human cells and retinal explants demonstrated the molecular mechanism of action and nuclease specificity. Subretinal delivery of EDIT-101 in humanized CEP290 mice showed rapid and sustained CEP290 gene editing. A comparable surrogate non-human primate (NHP) vector also achieved productive editing of the NHP CEP290 gene at levels that met the target therapeutic threshold, and demonstrated the ability of CRISPR/Cas9 to edit somatic primate cells in vivo. These results support further development of EDIT-101 for LCA10 and additional CRISPR-based medicines for other inherited retinal disorders.