The Five-Factor Modified Frailty Index as a Predictor of Outcomes in Deep Brain Stimulation Surgery for Parkinson's Disease.

Introduction Parkinson's disease (PD) is one of the most common neurodegenerative diseases worldwide. Though there are many pharmacological therapeutics approved today for PD, surgical interventions such as deep brain stimulation (DBS) have shown convincing symptom mitigation and minimal complication rates in aggregate. Recently, the concept of frailty - defined as reduced physiologic reserve and function affecting multiple systems throughout the patient - has gained traction as a predictor of short-term postoperative morbidity and mortality. As such, the Modified Frailty Index-5 (mFI-5) is a postoperative morbidity predictor based on five factors and has been used in neurosurgical subspecialties such as tumor, vascular, and spine. Yet, there is minimal literature assessing frailty in the field of functional neurosurgery. With the prevalence of DBS in PD, this study evaluated the mFI-5 as a predictor of postoperative complications in a selected patient population. Methods The American College of Surgeons National Surgical Quality Improvement Program 2010-2019 Database was queried for Current Procedural Terminology (CPT) codes, as well as the International Classification of Diseases (ICD)-9 and ICD-10 codes pertaining to DBS procedures in PD patients. Each patient was scored by the mFI-5 protocol and stratified into groups of No Frailty (mFI-5=0), Moderate Frailty (mFI-5=1), and Significant Frailty (mFI-5≥2). The No Frailty group was used as a reference in multivariate and univariate analyses of the groups. Results A total of 1,645 subjects were included in the study and were subcategorized into groups of No Frailty (N=877), Moderate Frailty (N=561), and Significant Frailty (N=207) based on their frailty scores. The subjects' mean age was 65.8±9.4 years. Overall, 1,161 (70.6%) were male, while 484 (29.4%) were female. With reference to the No Frailty group in multivariate analysis, patients with moderate frailty experienced greater unplanned readmission (OR 2.613, 95% CI 1.143-5.973, p=0.023), while those with significant frailty experienced greater unplanned readmission (OR 3.723, 95% CI 1.376-10.073, p=0.010), any readmission (OR 2.396, 95% CI 1.098-5.230, p=0.028), non-home discharge (OR 4.317, 95% CI 1.765-10.562, p<0.001), and complications in aggregate (OR 2.211, 95% CI 1.285-3.806, p=0.004). Conclusions Until now, the available clinical tools were limited in providing accurate predictions with minimal information for postoperative outcomes in DBS for PD patients. Our data give clinicians insight into the relationship between frailty and surgical outcomes and will assist physicians in preparing for postoperative care by predicting outcomes of significantly frail PD patients receiving DBS therapy.

Comparison of 5-Item and 11-Item Modified Frailty Index as Predictors of Functional Independence in Patients With Spinal Cord Injury.

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.

The Anterior Versus Posterior Approach for Interbody Fusion in Patients Who Are Classified as Obese: A Retrospective Cohort Study of 9,021 Patients From a National Database.

Introduction Lumbar spine interbody fusions have been performed to relieve back pain and improve stability due to various underlying pathologies. Anterior interbody fusion and posterior interbody fusion approaches are two main approaches that are classically compared. In an attempt to compare these two approaches to the spine, large retrospective national database reviews have been performed to compare and predict 30-day postoperative outcomes; however, they have conflicting findings. Obesity, defined as having a body mass index (BMI) over 30 kg/m2, may also contribute to the extent of spine pathology and is associated with increased rates of postoperative complications. Complication rates in patients who are obese have yet to be thoroughly investigated using a large national database. Our present investigation aims to make this comparison using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. The goal of the present study is to utilize a nationwide prospective database to determine short-term differences in postoperative outcomes between posterior and anterior lumbar fusion in patients with obesity and relate these findings to previous studies in the general population. Methods A retrospective cohort analysis was conducted on 9,021 patient data from the ACS-NSQIP database from 2015 to 2019 who underwent an elective, single-level fusion via anterior or posterior surgical approach. This database captures over 150 clinical variables on individual patient cases, including demographic data, preoperative risk factors and laboratory values, intraoperative data, and significant events up to postoperative day 30. All outcome measures were included in this analysis with special attention to rates of deep venous thrombosis (DVT) and pulmonary embolism (PE), prolonged length of stay (LOS), reoperation, and operation time. Results Multivariable analysis controlling for age, BMI, sex, race, functional status, American Society of Anesthesiologists (ASA) class, and selected comorbidities with P < 0.05 demonstrated that the anterior approach was an independent predictor for all significant outcomes except prolonged length of stay. Compared to the posterior approach, the anterior approach had a shorter total operation time (B = -13.257, 95% confidence interval (CI) [-17.522, -8.992], P < 0.001), higher odds of deep vein thrombosis (odds ratio (OR) = 2.210, 95% CI [1.211, 4.033], P= 0.010), and higher odds of pulmonary embolism (OR = 2.679, 95% CI [1.311, 5.477], P = 0.007) and was protective against unplanned reoperation (OR = 0.702, 95% CI [0.548, 0.898], P = 0.005). Conclusions The obese population makes up a large and growing demographic of those undergoing spine surgery, and as such, it is pertinent to investigate the differences, advantages, and disadvantages of lumbar fusion approaches in this group. While anterior approaches may be protective of longer operation time and unplanned reoperation, this benefit may not be clinically significant when considering an increased risk of DVT and PE. Given the short-term nature of this dataset and the limitations inherent in large de-identified retrospective database studies, these findings are interpreted with caution. Longer-term follow-up studies accounting for confounding variables with spine-centered outcomes will be necessary to further elucidate these nuances.

Ventriculostomy Associated with Reduced Mortality in Severe Traumatic Brain Injury Compared to Parenchymal ICP Monitoring: A Propensity Score-Adjusted Analysis.

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.

The SLANT Score Predicts Poor Neurologic Outcome in Comatose Survivors of Cardiac Arrest: An External Validation Using a Retrospective Cohort.

BACKGROUND: Hypoxic brain injury is the leading cause of death in comatose patients following resuscitation from cardiac arrest. Neurological outcome can be difficult to prognosticate following resuscitation, and goals of care discussions are often informed by multiple prognostic tools. One tool that has shown promise is the SLANT score, which encompasses five metrics including initial nonshockable rhythm, leukocyte count after targeted temperature management, total adrenaline dose during resuscitation, lack of bystander cardiopulmonary resuscitation, and time to return of spontaneous circulation. This cohort study aimed to provide an external validation of this score by using a database of comatose cardiac arrest survivors from our institution. METHODS: We retrospectively queried our database of cardiac arrest survivors, selecting for patients with coma, sustained return of spontaneous circulation, and use of targeted temperature management to have a comparable sample to the index study. We calculated SLANT scores for each patient and separated them into risk levels, both according to the original study and according to a Youden index analysis. The primary outcome was poor neurologic outcome (defined by a cerebral performance category score of 3 or greater at discharge), and the secondary outcome was in-hospital mortality. Univariable and multivariable analyses, as well as a receiver operator characteristic curve, were used to assess the SLANT score for independent predictability and diagnostic accuracy for poor outcomes. RESULTS: We demonstrate significant association between a SLANT group with increased risk and poor neurologic outcome on univariable (p = 0.005) and multivariable analysis (odds ratio 1.162, 95% confidence interval 1.003-1.346, p = 0.046). A receiver operating characteristic analysis indicates that SLANT scoring is a fair prognostic test for poor neurologic outcome (area under the curve 0.708, 95% confidence interval 0.536-0.879, p = 0.024). Among this cohort, the most frequent SLANT elements were initial nonshockable rhythm (84.5%) and total adrenaline dose ≥ 5 mg (63.9%). There was no significant association between SLANT score and in-hospital mortality (p = 0.064). CONCLUSIONS: The SLANT score may independently predict poor neurologic outcome but not in-hospital mortality. Including the SLANT score as part of a multimodal approach may improve our ability to accurately prognosticate comatose survivors of cardiac arrest.

Respiratory plasticity following spinal cord injury: perspectives from mouse to man.

The study of respiratory plasticity in animal models spans decades. At the bench, researchers use an array of techniques aimed at harnessing the power of plasticity within the central nervous system to restore respiration following spinal cord injury. This field of research is highly clinically relevant. People living with cervical spinal cord injury at or above the level of the phrenic motoneuron pool at spinal levels C3-C5 typically have significant impairments in breathing which may require assisted ventilation. Those who are ventilator dependent are at an increased risk of ventilator-associated co-morbidities and have a drastically reduced life expectancy. Pre-clinical research examining respiratory plasticity in animal models has laid the groundwork for clinical trials. Despite how widely researched this injury is in animal models, relatively few treatments have broken through the preclinical barrier. The three goals of this present review are to define plasticity as it pertains to respiratory function post-spinal cord injury, discuss plasticity models of spinal cord injury used in research, and explore the shift from preclinical to clinical research. By investigating current targets of respiratory plasticity research, we hope to illuminate preclinical work that can influence future clinical investigations and the advancement of treatments for spinal cord injury.

AAV2-BDNF promotes respiratory axon plasticity and recovery of diaphragm function following spinal cord injury.

More than half of spinal cord injury (SCI) cases occur in the cervical region, leading to respiratory dysfunction due to damaged neural circuitry that controls critically important muscles such as the diaphragm. The C3-C5 spinal cord is the location of phrenic motor neurons (PhMNs) that are responsible for diaphragm activation; PhMNs receive bulbospinal excitatory drive predominately from supraspinal neurons of the rostral ventral respiratory group (rVRG). Cervical SCI results in rVRG axon damage, PhMN denervation, and consequent partial-to-complete paralysis of hemidiaphragm. In a rat model of C2 hemisection SCI, we expressed the axon guidance molecule, brain-derived neurotrophic factor (BDNF), selectively at the location of PhMNs (ipsilateral to lesion) to promote directed growth of rVRG axons toward PhMN targets by performing intraspinal injections of adeno-associated virus serotype 2 (AAV2)-BDNF vector. AAV2-BDNF promoted significant functional diaphragm recovery, as assessed by in vivo electromyography. Within the PhMN pool ipsilateral to injury, AAV2-BDNF robustly increased sprouting of both spared contralateral-originating rVRG axons and serotonergic fibers. Furthermore, AAV2-BDNF significantly increased numbers of putative monosynaptic connections between PhMNs and these sprouting rVRG and serotonergic axons. These findings show that targeting circuit plasticity mechanisms involving the enhancement of synaptic inputs from spared axon populations is a powerful strategy for restoring respiratory function post-SCI.-Charsar, B. A., Brinton, M. A., Locke, K., Chen, A. Y., Ghosh, B., Urban, M. W., Komaravolu, S., Krishnamurthy, K., Smit, R., Pasinelli, P., Wright, M. C., Smith, G. M., Lepore, A. C. AAV2-BDNF promotes respiratory axon plasticity and recovery of diaphragm function following spinal cord injury.