Anthony Ray Absalom

Late motor responses, including F-waves and H-reflexes, are commonly recorded during electrophysiological diagnostic evaluation in awake patients. Although these responses could offer added value during intraoperative neurophysiological monitoring, their use has not yet been widely adopted. This systematic review aims to assess current knowledge on how anesthetic and surgical factors influence the recording and monitoring of spinal late responses during surgery. The authors searched PubMed and EMBASE for relevant articles on studies of late response recording. Studies were considered eligible if the influence of one or more of the following parameters on late responses were assessed: (1) ventilation and metabolic parameters, (2) volatile agents, (3) intravenous agents, (4) neuromuscular blocking agents, (5) epidural or intrathecal agents, or (6) surgical factors. The QUADAS-2 tool was used to assess the risk of bias and concerns regarding applicability. Sixty-two studies were included. Respiratory conditions like hypercapnia reduced H-reflex amplitude, whereas hyperoxia and intermittent hypoxia had limited impact. Volatile agents, including isoflurane, sevoflurane, and nitrous oxide decreased late response amplitudes, with dose-dependent effects. Most intravenous anesthetics, particularly propofol, reduced H-reflex amplitude and F-wave persistence in a dose-dependent manner. Conversely, ketamine was found to increase H-reflex amplitude. During spinal and vascular surgeries, H-reflex monitoring proved feasible and provided valuable supplementary data to the conventional motor evoked potential (MEP) and somatosensory evoked potential (SSEP) modalities. This systematic review demonstrates that H-reflexes and F-waves are significantly influenced by anesthetic factors. The reviewed studies indicate that intravenous and volatile anesthetics significantly affect late responses, by reducing H-reflex and F-wave amplitudes, whereas latencies appear unaffected. The methodological quality varied significantly across the included studies and affects the interpretation of their conclusions. These findings support the potential integration of late response monitoring into intraoperative neurophysiological monitoring (IONM) protocols, provided that anesthetic management and surgical context are carefully considered.

Background: Postoperative delirium (POD) is a fluctuating confusional state occurring early after surgery. Given its fluctuating nature, POD detection is influenced by the frequency and timing of screening. Sparse assessments potentially underestimate the true incidence reported in individual studies, subsequently influencing the weight of studies in meta-analyses, and the results and precision of these meta-analyses. Objective: To develop a method to evaluate the robustness of meta-analyses to the variation in the frequency and timing of POD assessment across included studies. Methods: We developed an expert-based scoring system to rate studies according to the confidence that a patient reported not to have POD in the study truly did not, based on the reported timing and frequency of POD assessments. We describe how to use the system to generate hypothetical event rates for studies if the frequency and timing of POD assessment were optimal and how to use these rates in a sensitivity analysis of meta-analyses including these studies. We illustrate the method applying it to two meta-analyses as work examples, one of observational studies and one of randomized controlled trials (RCTs). Results: In our work examples, the expert-based score for the individual studies ranged from 33–77% for the observational and 22–70% for RCTs meta-analysis. Sensitivity analyses showed a change in the pooled effect size, heterogeneity, and precision compared to the original estimates. Conclusion: We present a method to evaluate the robustness of a meta-analysis of studies having POD as an outcome, when there is variation across individual studies in the frequency and timing of POD assessment. The confidence score acts as a preliminary index of the robustness of meta-analyses. Through work examples, we showed that the robustness depends on the characteristics of individual studies included.

Melatonin (MEL) is an endogenous hormone that regulates circadian rhythm, immune function and oxidative stress responses. Norepinephrine (NE), an endogenous catecholamine, increases blood pressure through the sympathetic nervous system and is commonly administered intraoperatively or in the clinically ill patient for hemodynamic support. Although endogenous NE is known to stimulate MEL synthesis, the effects of exogenous intravenous NE on plasma MEL concentration, particularly under general anaesthesia (GA), remain poorly characterised. This study examined the influence of intravenous NE on plasma MEL concentrations in healthy volunteers, both awake and under general anaesthesia. A secondary analysis was conducted using data from a prospective, single‐centre, cross‐over study involving volunteers who received stepwise NE infusions while awake and under total intravenous general anaesthesia. Arterial blood samples were collected to determine plasma MEL and NE concentrations. Linear mixed‐effects modelling was used to assess the relationship between NE and MEL concentrations. A total of 36 healthy volunteers were enroled, yielding 417 MEL‐NE samples. Intravenous NE administration was significantly associated with higher plasma MEL concentration, corresponding to an estimated 26% increase in MEL per 1 standard‐deviation increase in NE concentration (Estimate = 0.230, p < 0.001). MEL concentrations were approximately 43% higher in the awake phase compared to GA (Estimate = 0.356, p < 0.001). GA did not significantly modify the NE‐MEL association (Estimate = −0.02877, p = 0.528). Substantial positive correlation was observed between baseline MEL concentrations and the magnitude of the response to NE administration ( r = 0.74). In conclusion, intravenous NE increases plasma MEL concentrations in both awake and anaesthetised individuals. Substantial interindividual variation in MEL response suggests underlying physiological differences. Future studies should explore the long‐term effects of NE administration on MEL concentrations. Trial Registration: The study is registered in the Dutch Trial Register (NL9312).

T-cell activation may be contributing to severe psychiatric disorders. Soluble CD27 (sCD27) - a marker for T-cell activation and disease activity in several autoimmune diseases - was evaluated as a tool for distinguishing T-cell activity in selected patients with severe psychiatric disorders, multiple sclerosis (MS), and controls. We hypothesise that elevated sCD27 levels will be associated with comorbid autoimmune disease (AID). sCD27 was measured in cerebrospinal fluid (CSF) and blood from a population enriched for suspected immunological comorbidity: the Immunopsychiatry Cohort (IP; n=115) and patients with MS (n=37), where levels in both groups were higher when compared with age matched controls undergoing surgery (n=154). Positive sCD27 (sCD27+), was defined as values >97.5% of controls. In IP, 23% were CSF sCD27+ and 15% blood sCD27+, compared to patients with MS where 88% were CSF sCD27+ and 22% were blood sCD27+. CSF-sCD27+ was confirmed as a sensitive marker for MS. In IP, CSF-sCD27+ was associated with comorbid AID (X2=4.847, p =0.028;) and AID disease activity (OR=5.14, p=0.029). Associations with AID were stronger when CSF and/or blood sCD27+ were combined (X2=8.559, p=0.003). CSF-sCD27+ in IP was also associated with pleocytosis, CSF-Total-tau, and CSF-NfL. In patients with severe psychiatric disorders, the sCD27+ cases were more likely to have comorbid AID and established markers for neuroinflammation in CSF. Combining analyses of CSF and blood improved sensitivity and specificity for AID suggesting compartmentalized T-cell activation. Psychiatric symptoms may precede somatic symptoms - or be the prominent symptom - of AID and sCD27 is a candidate marker for identification of this subgroup.

Background/Objectives: Severe traumatic brain injury (TBI) carries high mortality, and outcomes are particularly poor when prehospital cardiopulmonary resuscitation (CPR) is required. Because these patients are often excluded from research, epidemiological data and prognostic insights are limited. This study aimed to describe characteristics and outcomes of patients with suspected severe TBI who received prehospital CPR. Methods: We performed a sub-analysis of the prospectively collected multicenter BRAIN-PROTECT registry, including all patients with suspected severe TBI who underwent prehospital CPR and were transported to a participating trauma center. Results: A total of 256 patients with suspected severe TBI who received prehospital CPR were included. Early mortality was high, with 22.6% declared dead in the emergency department and an additional 28.9% within 24 h, resulting in 48.5% 24 h survival. Thirty-day mortality was 79.9%. Among survivors, 45.7% achieved moderate disability or good recovery at discharge. Outcomes, 30-day mortality, and neurological status at discharge did not differ between isolated and non-isolated TBI. Characteristics often seen in survivors included shockable initial rhythm, reactive pupils, and lack of anisocoria. All patients without prehospital return of spontaneous circulation died. Conclusions: Although overall 30-day mortality was high, survival among patients for whom resuscitation was attempted and who reached hospital care was not negligible, and a substantial proportion of the survivors achieved moderate to good neurological recovery. Prehospital ROSC and shockable rhythms were associated with better outcomes, suggesting that resuscitation may be valuable and warranted in selected patients with potentially reversible conditions. Further studies are needed to better define prognostic factors and guide management in this highly vulnerable population.

Helmet use is widely accepted to reduce head injury severity by absorbing impact forces, but the specific effect on the presence of radiologically detected intracranial injuries remains unclear. To examine the relationship between helmet use and Rotterdam CT score components, craniocervical fractures, and short-term mortality in cyclists and motorcyclists with severe TBI. This is a secondary analysis of data from the BRAIN-PROTECT dataset, a prospective observational study of 2,589 subjects with severe traumatic brain injury in the Netherlands. Logistic regression analysis was used, with helmet use as the independent variable, and Rotterdam score components, craniocervical fractures, and 30-day mortality as outcome measures. Among 499 severe TBI patients analyzed (median age 43 years), helmet use significantly reduced epidural mass (OR 0.25, 95% CI 0.10-0.60, p = 0.008) and skull fractures (OR 0.37, 95% CI 0.25-0.56, p = 0.004). However, helmeted patients had higher odds of cervical fractures (OR 2.94, 95% CI 1.74-4.98, p = 0.004), which persisted after adjusting for age and motor GCS component. Among patients with severe TBI, those wearing helmets showed epidural mass lesions and skull fractures less frequently, but more often had cervical fractures than those not wearing helmets.