Influence of Preoperative Motor Score and Patient Comorbidities on Transcranial Motor-Evoked Potential Acquisition in Intracranial Surgery: A Retrospective Cohort Study.

BACKGROUND AND OBJECTIVES: Intraoperative neurophysiological monitoring plays a pivotal role in modern neurosurgery, aiding in real-time assessment of eloquent neural structures to mitigate iatrogenic neural injury. This study represents the largest retrospective series to date in monitoring corticospinal tract integrity during intracranial surgery with transcranial motor-evoked potentials (TCMEPs), focusing on the influence of demographic factors, comorbidities, and preoperative motor deficits on the reliability of intraoperative neurophysiological monitoring. While the impact of patient-specific factors affecting TCMEP monitoring in spine surgery is well-documented, similar insights for intracranial surgery are lacking. METHODS: A total of 420 craniotomy patients were retrospectively analyzed from electronic medical records from December 2017 to February 2023, excluding patients without preoperative Medical Research Council scores or medical histories. Using intrinsic hand muscles as a robust data set, 840 hand TCMEPs acquired during intracranial surgery were assessed. Demographic and clinical factors, including preoperative motor scores, were analyzed to identify associations with TCMEP acquisition and amplitude. Nonparametric statistics and multivariate regression analysis were employed. RESULTS: TCMEPs were successfully acquired in 734 (87.7%) patient hands, even in the presence of preoperative motor deficits in 13.9% of total patient hands. Preoperative motor scores did not predict the ability to acquire baseline TCMEPs (P = .6). Notably, older age (P < .001) and hypertension (P = .01) were independent predictors of lower TCMEP acquisition rates. Preoperative motor scores significantly influenced TCMEP amplitudes, with higher scores correlating with higher amplitudes (1771 [SD = 1550] eve vs 882 [SD = 856] µV, P < .0001). Older age (P < .001) and chronic kidney disease (P = .04) were also associated with reduced TCMEP amplitudes. CONCLUSION: Our investigation into TCMEPs during intracranial surgery demonstrated a notably high acquisition rate in hand muscles, irrespective of preoperative motor deficits. Preoperative motor scores reliably correlated with TCMEP amplitudes in a linear fashion while advanced age and renal disease emerged as independent predictors of lower TCMEP amplitudes.

Comparing U.S. and Canadian treatment patterns on venous thromboembolism outcomes in the GARFIELD-VTE registry.

BACKGROUND: Economically developed countries continue to find that venous thromboembolism (VTE) is a major cause of morbidity and mortality. OBJECTIVE: To compare baseline risk profiles and patient workflow patterns between the United States (U.S.) and Canadian management of VTE patients from 2014 to 2017. METHODS: The Global Anticoagulant Registry in the FIELD (GARFIELD-VTE) is a prospective, observational study of 10,679 patients with objectively confirmed VTE, followed for 3 years. In total 1101 patients enrolled in the U.S. and Canada were included in this analysis. RESULTS: Median age and body mass index were comparable between the U.S. (60.5; 30.2) and Canadian (59.7; 29) patients. A higher percentage of U.S. patients were black (n = 128, 24.1 %; n = 22, 3.9 %) and had a higher VTE-associated risk profile, including immobilization, hospitalization, and recent surgery. U.S. patients had a higher combined DVT and PE primary diagnoses (20.3 %) and were more likely to be treated in hospitals (77.2 %) than Canadians (13.3 %; 48.1 %). Direct oral anticoagulant therapy (DOAC) was nearly two-fold more frequent in Canadian patients (n = 218, 39.2 %) at the end of 3 years in comparison to the U.S. (n = 118, 23.0 %). Adjusted for sex, recent bleed event, heart failure, chronic immobilization, family history of VTE, history of cancer and prior VTE, and renal insufficiency, the risk of all-cause mortality was 51.9 % higher in patients from the U.S. compared to those in Canada after 3 years. Patients from the U.S. also had a higher likelihood of hospitalization, major bleeding, and recurrent VTE after controlling for prior history and comorbid conditions. CONCLUSION: Higher rates of adverse VTE-associated outcomes in the U.S. may be attributed to different baseline risk profiles, facility care, and distribution of specialists and their subsequent treatment strategies. TYPE OF RESEARCH: Global, multicentre, non-interventional, prospective registry titled Global Anticoagulant Registry in the FIELD - Venous Thromboembolism (GARFIELD-VTE). KEY FINDINGS: 531 U.S. and 557 Canadians patients included in study. DOAC use more frequent in Canadian patients after 3 years than U.S. (39.2 % vs. 23.0 %, respectively). Adjusted for sex, recent bleed event, heart failure, chronic immobilization, family history of VTE, history of cancer and prior VTE, and renal insufficiency, all-cause mortality risk remained higher in U.S. patients vs. Canadian patients after 3 years. U.S. patients had higher likelihood of hospitalization, major bleeding, and recurrent VTE. TAKE-HOME MESSAGE: Higher rates of adverse VTE-associated outcomes in the U.S. may be attributed to different baseline risk profiles, facility care, and composition of specialists and their subsequent treatment strategies. TABLE OF CONTENTS SUMMARY: Global, multicentre, non-interventional, prospective registry titled Global Anticoagulant Registry in the FIELD - Venous Thromboembolism (GARFIELD-VTE). Higher rates of adverse VTE-associated outcomes were observed in U.S. patients vs Canadian patients, which may be attributed to different baseline risk profiles, facility care, and distribution of specialists and their subsequent treatment strategies.

Calcium imaging and analysis of the jugular-nodose ganglia enables identification of distinct vagal sensory neuron subsets.

Objective.Sensory nerves of the peripheral nervous system (PNS) transmit afferent signals from the body to the brain. These peripheral nerves are composed of distinct subsets of fibers and associated cell bodies, which reside in peripheral ganglia distributed throughout the viscera and along the spinal cord. The vagus nerve (cranial nerve X) is a complex polymodal nerve that transmits a wide array of sensory information, including signals related to mechanical, chemical, and noxious stimuli. To understand how stimuli applied to the vagus nerve are encoded by vagal sensory neurons in the jugular-nodose ganglia, we developed a framework for micro-endoscopic calcium imaging and analysis.Approach.We developed novel methods forin vivoimaging of the intact jugular-nodose ganglion using a miniature microscope (Miniscope) in transgenic mice with the genetically-encoded calcium indicator GCaMP6f. We adapted the Python-based analysis package Calcium Imaging Analysis (CaImAn) to process the resulting one-photon fluorescence data into calcium transients for subsequent analysis. Random forest classification was then used to identify specific types of neuronal responders.Results.We demonstrate that recordings from the jugular-nodose ganglia can be accomplished through careful surgical dissection and ganglia stabilization. Using a customized acquisition and analysis pipeline, we show that subsets of vagal sensory neurons respond to different chemical stimuli applied to the vagus nerve. Successful classification of the responses with a random forest model indicates that certain calcium transient features, such as amplitude and duration, are important for encoding these stimuli by sensory neurons.Significance.This experimental approach presents a new framework for investigating how individual vagal sensory neurons encode various stimuli on the vagus nerve. Our surgical and analytical approach can be applied to other PNS ganglia in rodents and other small animal species to elucidate previously unexplored roles for peripheral neurons in a diverse set of physiological functions.

Transient Receptor Potential Ankyrin-1-expressing vagus nerve fibers mediate IL-1ß induced hypothermia and reflex anti-inflammatory responses.

BACKGROUND: Inflammation, the physiological response to infection and injury, is coordinated by the immune and nervous systems. Interleukin-1ß (IL-1ß) and other cytokines produced during inflammatory responses activate sensory neurons (nociceptors) to mediate the onset of pain, sickness behavior, and metabolic responses. Although nociceptors expressing Transient Receptor Potential Ankyrin-1 (TRPA1) can initiate inflammation, comparatively little is known about the role of TRPA1 nociceptors in the physiological responses to specific cytokines. METHODS: To monitor body temperature in conscious and unrestrained mice, telemetry probes were implanted into peritoneal cavity of mice. Using transgenic and tissue specific knockouts and chemogenetic techniques, we recorded temperature responses to the potent pro-inflammatory cytokine IL-1ß. Using calcium imaging, whole cell patch clamping and whole nerve recordings, we investigated the role of TRPA1 during IL-1ß-mediated neuronal activation. Mouse models of acute endotoxemia and sepsis were used to elucidate how specific activation, with optogenetics and chemogenetics, or ablation of TRPA1 neurons can affect the outcomes of inflammatory insults. All statistical tests were performed with GraphPad Prism 9 software and for all analyses, P ≤ 0.05 was considered statistically significant. RESULTS: Here, we describe a previously unrecognized mechanism by which IL-1ß activates afferent vagus nerve fibers to trigger hypothermia, a response which is abolished by selective silencing of neuronal TRPA1. Afferent vagus nerve TRPA1 signaling also inhibits endotoxin-stimulated cytokine storm and significantly reduces the lethality of bacterial sepsis. CONCLUSION: Thus, IL-1ß activates TRPA1 vagus nerve signaling in the afferent arm of a reflex anti-inflammatory response which inhibits cytokine release, induces hypothermia, and reduces the mortality of infection. This discovery establishes that TRPA1, an ion channel known previously as a pro-inflammatory detector of cold, pain, itch, and a wide variety of noxious molecules, also plays a specific anti-inflammatory role via activating reflex anti-inflammatory activity.