Association between cerebrovascular reactivity in adult traumatic brain injury and improvement in patient outcome over time: an exploratory analysis.

BACKGROUND: Impaired cerebrovascular reactivity following moderate/severe traumatic brain injury (TBI) has emerged as a key potential driver of morbidity and mortality. However, the major contributions to the literature so far have been solely focused on single point measures of long-term outcome. Therefore, it remains unknown whether cerebrovascular reactivity impairment, during the acute phase of TBI, is associated with failure to improve in outcome across time. METHODS: Cerebrovascular reactivity was measured using three intracranial pressure-based surrogate metrics. For each patient, % time spent above various literature-defined thresholds was calculated. Patients were dichotomized based on outcome transition into Improved vs Not Improved between 1 and 3 months, 3 and 6 months, and 1 and 6 months, based on the Glasgow Outcome Scale-Extended (GOSE). Univariate and multivariable logistic regression analyses were performed, adjusting for the International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) variables. RESULTS: Seventy-eight patients from the Winnipeg Acute TBI Database were included in this study. On univariate logistic regression analysis, higher % time with cerebrovascular reactivity metrics above clinically defined thresholds was associated with a lack of clinical improvement between 1 and 3 months and 1 and 6 months post injury (p < 0.05). These relationships held true on multivariable logistic regression analysis. CONCLUSION: Our study demonstrates that impaired cerebrovascular reactivity, during the acute phase of TBI, is associated with failure to improve clinically over time. These preliminary findings highlight the significance that cerebrovascular reactivity monitoring carries in outcome recovery association in moderate/severe TBI.

Endovascular and Antithrombotic Treatment in Blunt Cerebrovascular Injuries: A Systematic Review and Meta-Analysis.

OBJECTIVES: Ischemic stroke has been estimated to occur in up to 26% of patients with blunt cerebrovascular injury (BCVI). Antithrombotic therapy (AT) may be used for stroke prevention, but the role of endovascular treatment (ET) remains unclear. We systematically reviewed the literature on AT and ET for the treatment of patients with BCVIs. MATERIALS AND METHODS: PubMed, EMBASE, Web of Science, and Cochrane were searched upon the PRISMA guidelines to include studies reporting the use of ET in BCVI patients. Post-ET neurologic outcomes, radiographic responses, and complication rates were assessed. A fixed-effect model meta-analysis was performed to compare treatment-related post-BCVI ischemic stroke rates between AT and ET protocols. RESULTS: We included 16 studies comprising 352 patients undergoing ET for BCVI. Mean post-ET rates of good neurologic outcomes and radiologic responses were 86.9% (range, 63.6-100%) and 94.0% (range 57.1-100%), respectively. Mean post-ET complication rate was 5.2% (range, 0-66.7%). Seven studies compared the roles of AT (delivered in 805 patients) and ET (performed in 235 patients) for preventing the onset of post-BCVI ischemic strokes. No significant difference in rates of post-BCVI ischemic stroke was found between patients receiving AT vs patients undergoing ET (OR 0.71, 95% CI: 0.35-1.42, p = 0.402). CONCLUSION: AT and ET may be comparable in preventing the occurrence of ischemic stroke following BCVIs. AT may be preferred as the less-invasive first-line therapy, but ET showed favorable rates of post-treatment clinical and radiologic outcomes, coupled with low rates of treatment-related complications.

Generation of optically synchronized pump-signal beams for ultrafast OPCPA via the optical Kerr effect.

In recent years, multi-petawatt laser installations have achieved unprecedented peak powers, opening new horizons to laser-matter interaction studies. Ultra-broadband and extreme temporal contrast pulse requirements make optical parametric chirped pulse amplification (OPCPA) in the few-picosecond regime the key technology in these systems. To guarantee high fidelity output, however, OPCPA requires excellent synchronization between pump and signal pulses. Here, we propose a new highly versatile architecture for the generation of optically synchronized pump-signal pairs based on the Kerr shutter effect. We obtained >550µJ pump pulses of 12 ps duration at 532 nm optically synchronized with a typical ultrashort CPA source at 800 nm. As a proof-of-principle demonstration, our system was also used for amplification of ∼20µJ ultra-broadband pulses based on an OPCPA setup.

Improvement in the temporal contrast in the tens of ps range of the multi-PW Apollon laser front-end.

We demonstrate the impact of the optics roughness in Öffner stretchers used in chirped pulse amplification laser chains and how it is possible to improve the temporal contrast ratio in the temporal range of 10-100 ps by adequately choosing the optical quality of the key components. Experimental demonstration has been realized in the front-end source of the multi-petawatt (PW) laser facility Apollon, resulting in an enhancement of the contrast ratio by two to three orders of magnitude.

Correction to: Postoperative isolated lower extremity supplementary motor area syndrome: case report and review of the literature.

The original version of this article unfortunately contained an error. The author apologizes for having provided an incorrect name: "Ali Moghadammjou" should be "Ali Moghaddamjou". Given in this article is the correct author name.

Postoperative isolated lower extremity supplementary motor area syndrome: case report and review of the literature.

The supplementary motor area (SMA) syndrome is characterized by transient weakness and akinesia contralateral to the side of the affected hemisphere. The underlying pathology of the syndrome is not fully understood but is thought to be related to lesions in the SMA, residing principally in the mesial superior frontal gyrus (Broadmann's area 6c). Although the SMA syndrome a well-characterized clinical entity, we report herein, to our knowledge, the first case of isolated lower extremity SMA syndrome in the literature. This case highlights the importance of considering this rare clinical entity in the context of new or worsening postoperative neurologic deficits. Moreover, early studies did not support somatotopic organization of the SMA as in the primary motor cortex; emerging evidence suggests that delicate somatotopic representation may underlie distinct presentations like that reported in the present case.

Relationship Between Measures of Cerebrovascular Reactivity and Intracranial Lesion Progression in Acute TBI Patients: an Exploratory Analysis.

BACKGROUND: Failure of cerebral autoregulation and progression of intracranial lesion have both been shown to contribute to poor outcome in patients with acute traumatic brain injury (TBI), but the interplay between the two phenomena has not been investigated. Preliminary evidence leads us to hypothesize that brain tissue adjacent to primary injury foci may be more vulnerable to large fluctuations in blood flow in the absence of intact autoregulatory mechanisms. The goal of this study was therefore to assess the influence of cerebrovascular reactivity measures on radiological lesion expansion in a cohort of patients with acute TBI. METHODS: We conducted a retrospective cohort analysis on 50 TBI patients who had undergone high-frequency multimodal intracranial monitoring and for which at least two brain computed tomography (CT) scans had been performed in the acute phase of injury. We first performed univariate analyses on the full cohort to identify non-neurophysiological factors (i.e., initial lesion volume, timing of scan, coagulopathy) associated with traumatic lesion growth in this population. In a subset analysis of 23 patients who had intracranial recording data covering the period between the initial and repeat CT scan, we then correlated changes in serial volumetric lesion measurements with cerebrovascular reactivity metrics derived from the pressure reactivity index (PRx), pulse amplitude index (PAx), and RAC (correlation coefficient between the pulse amplitude of intracranial pressure and cerebral perfusion pressure). Using multivariate methods, these results were subsequently adjusted for the non-neurophysiological confounders identified in the univariate analyses. RESULTS: We observed significant positive linear associations between the degree of cerebrovascular reactivity impairment and progression of pericontusional edema. The strongest correlations were observed between edema progression and the following indices of cerebrovascular reactivity between sequential scans: % time PRx > 0.25 (r = 0.69, p = 0.002) and % time PAx > 0.25 (r = 0.64, p = 0.006). These associations remained significant after adjusting for initial lesion volume and mean cerebral perfusion pressure. In contrast, progression of the hemorrhagic core and extra-axial hemorrhage volume did not appear to be strongly influenced by autoregulatory status. CONCLUSIONS: Our preliminary findings suggest a possible link between autoregulatory failure and traumatic edema progression, which warrants re-evaluation in larger-scale prospective studies.

Intraosseous schwannoma of the occipital bone: a case report.

OBJECT: Intraosseous schwanomma of the calvarium METHODS: This paper reports the case of a 7-year-old boy who presented with an intraosseous schwanomma involving the occipital bone and provides a brief overview of the literature. RESULTS: The patient presented with a mass in the midline occipital region. Neuroimaging revealed a lytic lesion in the occipital bone with lack of enhancement on gadolinium MRI sequences. A gross total resection was performed, and histopathological analysis confirmed the diagnosis of schwannoma. CONCLUSION: Intraosseous schwanomma should be considered in the differential diagnosis of skull vault lesions in the pediatric population and can be successfully managed with surgical excision.

Exploring the expectation-actuality discrepancy: a systematic review of the impact of preoperative expectations on satisfaction and patient reported outcomes in spinal surgery.

Quality in healthcare is increasingly graded through a patient-centric lens, using reports of satisfaction and self-perceived outcome. Preestablished expectations have been recognized to influence these measures. With this review, we aim to examine the impact of expectations on satisfaction and patient-reported outcomes (PRO) for individuals undergoing elective spine surgery. We systematically searched MEDLINE, EMBASE, CINAHL, and Cochrane Library electronic databases from inception to July 2015 for studies examining the relationship between expectations and satisfaction/PROs in the context of elective spinal surgery. Qualitative synthesis centered around three key questions: (1) Does the magnitude of preoperative expectations impact patient satisfaction and/or PRO after surgery? (2) Does the underlying spinal pathology influence this relationship? (3) What is the impact of unmet expectations on satisfaction? A total of 1489 citations were retrieved. Nineteen met our inclusion criteria. These comprised 3383 patients; 3200 had lumbar and only 183 had cervical spine surgery. Three findings prevailed: (1) high preoperative expectations appear to be associated with higher satisfaction and PROs after surgery for focal lumbar disc herniation, but not for lumbar spinal stenosis; (2) patient expectations frequently exceed actual outcome, creating an "expectation-actuality discrepancy" (E-AD); and (3) high-quality studies suggest a larger E-AD portends lower satisfaction. Limitations to the data include heterogeneous study populations and surgical indications, along with the use of non-validated assessment tools, particularly for satisfaction. Our findings highlight the potential importance of establishing realistic expectations prior to surgery and may serve to direct future research efforts.

Concussion education in Canadian medical schools: a 5 year follow-up survey.

BACKGROUND: Despite concussion now being recognized as a public health priority in Canada, recent studies-including our 2012 survey of Canadian medical schools-have revealed major gaps in concussion education at the undergraduate medical school level. METHODS: We re-surveyed all 17 Canadian medical schools using a questionnaire divided in two categories: (1) concussion-specific education (2) head injury education incorporating a concussion component to determine whether there have been any improvements in concussion education at the medical school level during the last five years. For each year of medical school, respondents were asked to provide the estimated number of hours and teaching format for each category. RESULTS: We received replies from 13 of the 17 medical schools (76%). 11 of the 13 (85%) medical schools now reported providing concussion-specific education compared to 29% in our 2012 survey. The mean number of hours dedicated to category 1 learning in 2017 was 2.65 h compared to 0.57 in 2012, and the mean number of hours of category 2 increased to 7.5 from 1.54. CONCLUSION: Our follow-up study reveals increased exposure to concussion-related teaching in Canadian medical schools during the last five years. Persistent deficiencies in a minority of schools are highlighted. These should be addressed by reiterating the importance of concussion education for undergraduate medical students and by developing clear concussion-specific objectives at the national licensure level.

A Pilot Placebo Controlled Randomized Trial of Dexamethasone for Chronic Subdural Hematoma.

BACKGROUND: Current opinions regarding the use of dexamethasone in the treatment of chronic subdural hematomas (CSDH) are only based on observational studies. Moreover, the use of corticosteroids in asymptomatic or minimally symptomatic patient with this condition remains controversial. Here, we present data from a prospective randomized pilot study of CSDH patients treated with dexamethasone or placebo. METHODS: Twenty patients with imaging-confirmed CSDH were recruited from a single center and randomized to receive dexamethasone (12 mg/day for 3 weeks followed by tapering) or placebo as a conservative treatment. Patients were followed for 6 months and the rate of success of conservative treatment with dexamethasone versus placebo was measured. Parameters such as hematoma thickness and clinical changes were also compared before and after treatment with chi-square tests. Adverse events and complications were documented. RESULTS: During the 6-month follow-up, one of ten patients treated with corticosteroids had to undergo surgical drainage and three of ten patients were treated surgically after placebo treatment. At the end of the study, all remaining patients had complete radiological resolution. No significant differences were observed in terms of hematoma thickness profile and impression of change; however, patients experienced more severe side effects when treated with steroids as compared with placebo. Dexamethasone contributed to many serious adverse events. CONCLUSIONS: Given the small sample size, these preliminary results have not shown a clear beneficial effect of dexamethasone against placebo in our patients. However, the number of secondary effects reported was much greater for corticosteroids, and dexamethasone treatment was responsible for significant complications.

Admitting Hospital Influences on Withdrawal of Life-Sustaining Treatment Decision for Patients With Severe Traumatic Brain Injury.

BACKGROUND AND OBJECTIVES: Withdrawal of life-sustaining treatment (WLST) in severe traumatic brain injury (TBI) is complex, with a paucity of standardized guidelines. We aimed to assess the variability in WLST practices between trauma centers in North America. METHODS: This retrospective study used data from trauma centers through the American College of Surgeons Trauma Quality Improvement Program between 2017 and 2020. We included adult patients (>16 years) with severe TBI and a documented decision for WLST. We constructed a series of hierarchical logistic regression models to adjust for patient, injury, and hospital attributes influencing WLST; residual between-center variability was characterized using the median odds ratio. The impact of disparate WLST practices was further assessed by ranking centers by their conditional random intercept and assessing mortality, length of stay, and WLST between quartiles. RESULTS: We identified a total of 85 511 subjects with severe TBI treated across 510 trauma centers, of whom 20 300 (24%) had WLST. Patient-level factors associated with increased likelihood of WLST were advanced age, White race, self-pay, or Medicare insurance status (compared with private insurance). Black race was associated with reduced tendency for WLST. Treatment in nonprofit centers and higher-severity intracranial and extracranial injuries, midline shift, and pupil asymmetry also increased the likelihood for WLST. After adjustment for patient and hospital attributes, the median odds ratio was 1.45 (1.41-1.49 95% CI), suggesting residual variation in WLST between centers. When centers were grouped into quartiles by their propensity for WLST, there was increased adjusted mortality and shorter length of stay in fourth compared with first quartile centers. CONCLUSION: We highlighted the presence of contextual phenomena associated with disparate WLST practice patterns between trauma centers after adjustment for case-mix and hospital attributes. These findings highlight a need for standardized WLST guidelines to improve equity of care provision for patients with severe TBI.

Quantifying the Association Between Surgical Spine Approach and Tracheostomy Timing After Traumatic Cervical Spinal Cord Injury.

BACKGROUND AND OBJECTIVES: Recent evidence suggests earlier tracheostomy is associated with fewer complications in patients with complete cervical spinal cord injury (SCI). This study aims to evaluate the influence of spine surgical approach on the association between tracheostomy timing and in-hospital adverse events treating patients with complete cervical SCI. METHODS: This retrospective cohort study was performed using Trauma Quality Improvement Program data from 2017 to 2020. All patients with acute complete (American Spinal Injury Association-A) cervical SCI who underwent tracheostomy and spine surgery were included. Tracheostomy timing was dichotomized to early (within 1 week after surgery) and delayed (more than 1 week after surgery). Primary outcome was the occurrence of major in-hospital complications. Secondary outcomes included occurrences of immobility-related complications, surgical-site infection, hospital and intensive care unit length of stay, and time on mechanical ventilation. RESULTS: The study included 1592 patients across 358 trauma centers. Mean time to tracheostomy from surgery was 8.6 days. A total of 495 patients underwent anterior approach, 670 underwent posterior approach, and 427 underwent combined anterior and posterior approach. Patients who underwent anterior approach were significantly more likely to have delayed tracheostomy compared with posterior approach (53% vs 40%, P < .001). Early tracheotomy significantly reduced major in-hospital complications (odds ratio 0.67, 95% CI 0.53-0.84) and immobility complications (odds ratio = 0.78, 95% CI 0.6-1.0). Those undergoing early tracheostomy spent 6.0 (95% CI -8.47 to -3.43) fewer days in hospital, 5.7 (95% CI -7.8 to -3.7) fewer days in the intensive care unit, and 5.9 (95% CI -8.2 to -3.7) fewer days ventilated. Surgical approach had no significant negative effect on the association between tracheostomy timing and the outcomes of interest. CONCLUSION: Earlier tracheostomy for patients with cervical SCI is associated with reduced complications, length of stay, and ventilation time. This relationship appears independent of the surgical approach. These findings emphasize that tracheostomy need not be delayed because of the SCI treatment approach.

Vision Transformer-based Decision Support for Neurosurgical Intervention in Acute Traumatic Brain Injury: Automated Surgical Intervention Support Tool.

Purpose To develop an automated triage tool to predict neurosurgical intervention for patients with traumatic brain injury (TBI). Materials and Methods A provincial trauma registry was reviewed to retrospectively identify patients with TBI from 2005 to 2022 treated at a specialized Canadian trauma center. Model training, validation, and testing were performed using head CT scans with binary reference standard patient-level labels corresponding to whether the patient received neurosurgical intervention. Performance and accuracy of the model, the Automated Surgical Intervention Support Tool for TBI (ASIST-TBI), were also assessed using a held-out consecutive test set of all patients with TBI presenting to the center between March 2021 and September 2022. Results Head CT scans from 2806 patients with TBI (mean age, 57 years ± 22 [SD]; 1955 [70%] men) were acquired between 2005 and 2021 and used for training, validation, and testing. Consecutive scans from an additional 612 patients (mean age, 61 years ± 22; 443 [72%] men) were used to assess the performance of ASIST-TBI. There was accurate prediction of neurosurgical intervention with an area under the receiver operating characteristic curve (AUC) of 0.92 (95% CI: 0.88, 0.94), accuracy of 87% (491 of 562), sensitivity of 87% (196 of 225), and specificity of 88% (295 of 337) on the test dataset. Performance on the held-out test dataset remained robust with an AUC of 0.89 (95% CI: 0.85, 0.91), accuracy of 84% (517 of 612), sensitivity of 85% (199 of 235), and specificity of 84% (318 of 377). Conclusion A novel deep learning model was developed that could accurately predict the requirement for neurosurgical intervention using acute TBI CT scans. Keywords: CT, Brain/Brain Stem, Surgery, Trauma, Prognosis, Classification, Application Domain, Traumatic Brain Injury, Triage, Machine Learning, Decision Support Supplemental material is available for this article. © RSNA, 2024 See also commentary by Haller in this issue.

Automatic localisation and per-region quantification of traumatic brain injury on head CT using atlas mapping.

Rationale and objectives: To develop a method for automatic localisation of brain lesions on head CT, suitable for both population-level analysis and lesion management in a clinical setting. Materials and methods: Lesions were located by mapping a bespoke CT brain atlas to the patient's head CT in which lesions had been previously segmented. The atlas mapping was achieved through robust intensity-based registration enabling the calculation of per-region lesion volumes. Quality control (QC) metrics were derived for automatic detection of failure cases. The CT brain template was built using 182 non-lesioned CT scans and an iterative template construction strategy. Individual brain regions in the CT template were defined via non-linear registration of an existing MRI-based brain atlas.Evaluation was performed on a multi-centre traumatic brain injury dataset (TBI) (n = 839 scans), including visual inspection by a trained expert. Two population-level analyses are presented as proof-of-concept: a spatial assessment of lesion prevalence, and an exploration of the distribution of lesion volume per brain region, stratified by clinical outcome. Results: 95.7% of the lesion localisation results were rated by a trained expert as suitable for approximate anatomical correspondence between lesions and brain regions, and 72.5% for more quantitatively accurate estimates of regional lesion load. The classification performance of the automatic QC showed an AUC of 0.84 when compared to binarised visual inspection scores. The localisation method has been integrated into the publicly available Brain Lesion Analysis and Segmentation Tool for CT (BLAST-CT). Conclusion: Automatic lesion localisation with reliable QC metrics is feasible and can be used for patient-level quantitative analysis of TBI, as well as for large-scale population analysis due to its computational efficiency (<2 min/scan on GPU).

Intracranial Pressure-Derived Cerebrovascular Reactivity Indices, Chronological Age, and Biological Sex in Traumatic Brain Injury: A Scoping Review.

To date, there has been limited literature exploring the association between age and sex with cerebrovascular reactivity (CVR) in moderate/severe traumatic brain injury (TBI). Given the known link between age, sex, and cerebrovascular function, knowledge of the impacts on continuously assessed CVR is critical for the development of future therapeutics. We conducted a scoping review of the literature for studies that had a direct statistical interrogation of the relationship between age, sex, and continuous intracranial pressure (ICP)-based indices of CVR in moderate/severe TBI. The ICP-based indices researched included: pressure reactivity index (PRx), pulse amplitude index (PAx), and RAC. MEDLINE, BIOSIS, EMBASE, SCOPUS, Global Health, and the Cochrane library were searched from inception to June 2021 for relevant articles. A total of 10 original studies fulfilled our inclusion criteria. Nine of the articles documented a correlation between advanced age and worse CVR, with eight using PRx (2192 total patients), three using PAx (978 total patients), and one using RAC (358 total patients), p < 0.05; R ranging from 0.17 to 0.495 for all indices across all studies. Three articles (1256 total patients) displayed a correlation between biological sex and PRx, with females trending towards higher PRx values (p < 0.05) in the limited available literature. However, no literature exists comparing PAx or RAC with biological sex. Findings showed that aging was associated with impaired CVR. We observed a trend between female sex and worse PRx values, but the literature was limited and statistical significance was borderline. The identified studies were few in number, carried significant population heterogeneity, and utilized grand averaging of large epochs of physiology during statistical comparisons with age and biological sex. Because of the heterogeneous nature of TBI populations and limited focus on the effects of age and sex on outcomes in TBI, it is challenging to highlight the differences between the indices and patient age groups and sex. The largest study showing an association between PRx and age was done by Zeiler and colleagues, where 165 patients were studied noting that patients with a mean PRx value above zero had a mean age above 51.4 years versus a mean age of 41.4 years for those with a mean PRx value below zero (p = 0.0007). The largest study showing an association between PRx and sex was done by Czosnyka and colleagues, where 469 patients were studied noting that for patients <50 years of age, PRx was worse in females (0.11 ± 0.047) compared to males (0.044 ± 0.031), p < 0.05. The findings from these 10 studies provide preliminary data, but are insufficient to definitively characterize the impact of age and sex on CVR in moderate/severe TBI. Future work in the field should focus on the impact of age and sex on multi-modal cerebral physiological monitoring.

The Quantitative Associations Between Near Infrared Spectroscopic Cerebrovascular Metrics and Cerebral Blood Flow: A Scoping Review of the Human and Animal Literature.

Cerebral blood flow (CBF) is an important physiologic parameter that is vital for proper cerebral function and recovery. Current widely accepted methods of measuring CBF are cumbersome, invasive, or have poor spatial or temporal resolution. Near infrared spectroscopy (NIRS) based measures of cerebrovascular physiology may provide a means of non-invasively, topographically, and continuously measuring CBF. We performed a systematically conducted scoping review of the available literature examining the quantitative relationship between NIRS-based cerebrovascular metrics and CBF. We found that continuous-wave NIRS (CW-NIRS) was the most examined modality with dynamic contrast enhanced NIRS (DCE-NIRS) being the next most common. Fewer studies assessed diffuse correlation spectroscopy (DCS) and frequency resolved NIRS (FR-NIRS). We did not find studies examining the relationship between time-resolved NIRS (TR-NIRS) based metrics and CBF. Studies were most frequently conducted in humans and animal studies mostly utilized large animal models. The identified studies almost exclusively used a Pearson correlation analysis. Much of the literature supported a positive linear relationship between changes in CW-NIRS based metrics, particularly regional cerebral oxygen saturation (rSO2), and changes in CBF. Linear relationships were also identified between other NIRS based modalities and CBF, however, further validation is needed.

Optimal bispectral index level of sedation and cerebral oximetry in traumatic brain injury: a non-invasive individualized approach in critical care?

BACKGROUND: Impaired cerebral autoregulation has been linked with worse outcomes, with literature suggesting that current therapy guidelines fail to significantly impact cerebrovascular reactivity. The cerebral oximetry index (COx_a) is a surrogate measure of cerebrovascular reactivity which can in theory be obtained non-invasively using regional brain tissue oxygen saturation and arterial blood pressure. The goal of this study was to assess the relationship between objectively measured depth of sedation through BIS and autoregulatory capacity measured through COx_a. METHODS: In a prospectively maintained observational study, we collected continuous regional brain tissue oxygen saturation, intracranial pressure, arterial blood pressure and BIS in traumatic brain injury patients. COx_a was obtained using the Pearson's correlation between regional brain tissue oxygen saturation and arterial blood pressure and ranges from - 1 to 1 with higher values indicating impairment of cerebrovascular reactivity. Using BIS values and COx_a, a curve-fitting method was applied to determine the minimum value for the COx_a. The associated BIS value with the minimum COx_a is called BISopt. This BISopt was both visually and algorithmically determined, which were compared and assessed over the whole dataset. RESULTS: Of the 42 patients, we observed that most had a parabolic relationship between BIS and COx_a. This suggests a potential "optimal" depth of sedation where COx_a is the most intact. Furthermore, when comparing the BISopt algorithm with visual inspection of BISopt, we obtained similar results. Finally, BISopt % yield (determined algorithmically) appeared to be independent from any individual sedative or vasopressor agent, and there was agreement between BISopt found with COx_a and the pressure reactivity index (another surrogate for cerebrovascular reactivity). CONCLUSIONS: This study suggests that COx_a is capable of detecting disruption in cerebrovascular reactivity which occurs with over-/under-sedation, utilizing a non-invasive measure of determination and assessment. This technique may carry implications for tailoring sedation in patients, focusing on individualized neuroprotection.

Pre-Injury Antiplatelet Therapy and Risk of Adverse Outcomes after Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

There is an increasing number of trauma patients presenting on pre-injury antiplatelet (AP) agents attributable to an aging population and expanding cardio- or cerebrovascular indications for antithrombotic therapy. The effects of different AP regimens on outcomes after traumatic brain injury (TBI) have yet to be elucidated, despite the implications on patient/family counseling and the potential need for better reversal strategies. The goal of this systematic review and meta-analysis was to assess the impact of different pre-injury AP regimens on outcomes after TBI. In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the OVID Medline, Embase, BIOSIS, Scopus, and Cochrane databases were searched from inception to February 2022 using a combination of terms pertaining to TBI and use of AP agents. Baseline demographics and study characteristics as well as outcome data pertaining to intracerebral hematoma (ICH) progression, need for neurosurgical intervention, hospital length of stay, mortality, and functional outcome were extracted. Pooled odds ratios (ORs) and mean differences comparing groups were calculated using random-effects models. Thirteen observational studies, totaling 1244 patients receiving single AP therapy with acetylsalicylic acid or clopidogrel, 413 patients on dual AP therapy, and 3027 non-AP users were included. No randomized controlled trials were identified. There were significant associations between dual AP use and ICH progression (OR, 2.81; 95% confidence interval [CI], 1.19-6.61; I 2, 85%; p = 0.02) and need for neurosurgical intervention post-TBI (OR, 1.61; 95% CI, 1.15-2.28; I 2, 15%; p = 0.006) compared to non-users, but not between single AP therapy and non-users. There were no associations between AP use and hospital length of stay or mortality after trauma. Pre-injury dual AP use, but not single AP use, is associated with higher rates of ICH progression and neurosurgical intervention post-TBI. However, the overall quality of studies was low, and this association should be further investigated in larger studies.

Natural history of adolescent-onset cystinosis.

Cystinosis is a rare autosomal recessive disease caused by mutations of the CTNS gene in which cystine accumulates throughout the body as a result of a defective efflux of cystine from lysosomes. Three phenotypic forms have been described according to the age of onset and the severity of the clinical symptoms: infantile, intermediate, and ocular non-nephropathic cystinosis. Here we report the natural history of cystinosis in a 55-year-old man with intermediate nephropathic cystinosis diagnosed at 9 years of age. Although tubulopathy was unnoticed in the early years, he required transplantation at age 16. Sequencing analysis of all the CTNS exons revealed that the proband is homozygous for a 21-bp in-frame deletion in exon 5 (c. 198_218del21), resulting in an in-frame deletion of 7 amino acids from the N-terminal domain of the cystinosin protein. Our patient has had relatively mild extra-renal disease despite lack of early cysteamine therapy. He has been able to attend university and pursue a professional career into the 6th decade.