A prospective, phase II, single-centre, cross-sectional, randomised study investigating Dehydroepiandrosterone supplementation and its Profile in Trauma: ADaPT.

INTRODUCTION: The improvements in short-term outcome after severe trauma achieved through early resuscitation and acute care can be offset over the following weeks by an acute systemic inflammatory response with immuneparesis leading to infection, multiorgan dysfunction/multiorgan failure (MOF) and death. Serum levels of the androgen precursor dehydroepiandrosterone (DHEA) and its sulfate ester DHEAS, steroids with immune-enhancing activity, are low after traumatic injury at a time when patients are catabolic and immunosuppressed. Addressing this deficit and restoring the DHEA(S) ratio to cortisol may provide a range of physiological benefits, including immune modulatory effects. OBJECTIVE: Our primary objective is to establish a dose suitable for DHEA supplementation in patients after acute trauma to raise circulating DHEA levels to at least 15 nmol/L. Secondary objectives are to assess if DHEA supplementation has any effect on neutrophil function, metabolic and cytokine profiles and which route of administration (oral vs sublingual) is more effective in restoring circulating levels of DHEA, DHEAS and downstream androgens. METHODS AND ANALYSIS: A prospective, phase II, single-centre, cross-sectional, randomised study investigating Dehydroepiandrosterone supplementation and its profile in trauma, with a planned recruitment between April 2019 and July 2021, that will investigate DHEA supplementation and its effect on serum DHEA, DHEAS and downstream androgens in trauma. A maximum of 270 patients will receive sublingual or oral DHEA at 50, 100 or 200 mg daily over 3 days. Females aged ≥50 years with neck of femur fracture and male and female major trauma patients, aged 16-50 years with an injury severity score ≥16, will be recruited. ETHICS AND DISSEMINATION: This protocol was approved by the West Midlands - Coventry and Warwickshire Research Ethics Committee (Reference 18/WM/0102) on 8 June 2018. Results will be disseminated via peer-reviewed publications and presented at national and international conferences. TRIAL REGISTRATION: This trial is registered with the European Medicines Agency (EudraCT: 2016-004250-15) and ISRCTN (12961998). It has also been adopted on the National Institute of Health Research portfolio (CPMS ID:38158). TRIAL PROGRESSION: The study recruited its first patient on 2 April 2019 and held its first data monitoring committee on 8 November 2019. DHEA dosing has increased to 100 mg in both male cohorts and remains on 50 mg in across all female groups.

Dynamic contrast-enhanced near-infrared spectroscopy using indocyanine green on moderate and severe traumatic brain injury: a prospective observational study.

BACKGROUND: The care given to moderate and severe traumatic brain injury (TBI) patients may be hampered by the inability to tailor their treatments according to their neurological status. Contrast-enhanced near-infrared spectroscopy (NIRS) with indocyanine green (ICG) could be a suitable neuromonitoring tool. METHODS: Monitoring the effective attenuation coefficients (EAC), we compared the ICG kinetics between five TBI and five extracranial trauma patients, following a venous-injection of 5 mL of 1 mg/mL ICG, using two commercially available NIRS devices. RESULTS: A significantly slower passage of the dye through the brain of the TBI group was observed in two parameters related to the first ICG inflow into the brain (P=0.04; P=0.01). This is likely related to the reduction of cerebral perfusion following TBI. Significant changes in ICG optical properties minutes after injection (P=0.04) were registered. The acquisition of valid optical data in a clinical environment was challenging. CONCLUSIONS: Future research should analyze abnormalities in the ICG kinetic following brain trauma, test how these values can enhance care in TBI, and adapt the current optical devices to clinical settings. Also, studies on the pattern in changes of ICG optical properties after venous injection can improve the accuracy of the values detected.

The Valsalva maneuver: an indispensable physiological tool to differentiate intra versus extracranial near-infrared signal.

Developing near-infrared spectroscopy (NIRS) parameter recovery techniques to more specifically resolve brain physiology from that of the overlying tissue is an important part of improving the clinical utility of the technology. The Valsalva maneuver (VM) involves forced expiration against a closed glottis causing widespread venous congestion within the context of a fall in cardiac output. Due to the specific anatomical confines and metabolic demands of the brain we believe a properly executed VM has the ability to separate haemodynamic activity of brain tissue from that of the overlying scalp as observed by NIRS, and confirmed by functional magnetic resonance imaging (fMRI). Healthy individuals performed a series of standing maximum effort VMs under separate observation by frequency domain near-infrared spectroscopy (FD-NIRS) and fMRI. Nine individuals completed the clinical protocol (6 males, age 21-40). During the VMs, brain and extracranial tissue targeted signal were significantly different (opposite direction of change) in both fMRI and NIRS (p=0.00025 and 0.00115 respectively), with robust cross correlation of parameters between modalities. Four of these individuals performed further VMs after infiltrating 2% xylocaine/1:100,000 epinephrine (vasoconstrictor) into scalp tissue beneath the probes. No significant difference in the cerebrally derived parameters was observed. The maximum effort VM has the ability to separate NIRS observable physiology of the brain from the overlying extracranial tissue. Observations made by this FD cerebral NIRS device are comparable with fMRI in this context.

Cerebral Oxygenation in Traumatic Brain Injury: Can a Non-Invasive Frequency Domain Near-Infrared Spectroscopy Device Detect Changes in Brain Tissue Oxygen Tension as Well as the Established Invasive Monitor?

The cost and highly invasive nature of brain monitoring modality in traumatic brain injury patients currently restrict its utility to specialist neurological intensive care settings. We aim to test the abilities of a frequency domain near-infrared spectroscopy (FD-NIRS) device in predicting changes in invasively measured brain tissue oxygen tension. Individuals admitted to a United Kingdom specialist major trauma center were contemporaneously monitored with an FD-NIRS device and invasively measured brain tissue oxygen tension probe. Area under the curve receiver operating characteristic (AUROC) statistical analysis was utilized to assess the predictive power of FD-NIRS in detecting both moderate and severe hypoxia (20 and 10 mm Hg, respectively) as measured invasively. Sixteen individuals were prospectively recruited to the investigation. Severe hypoxic episodes were detected in nine of these individuals, with the NIRS demonstrating a broad range of predictive abilities (AUROC 0.68-0.88) from relatively poor to good. Moderate hypoxic episodes were detected in seven individuals with similar predictive performance (AUROC 0.576-0.905). A variable performance in the predictive powers of this FD-NIRS device to detect changes in brain tissue oxygen was demonstrated. Consequently, this enhanced NIRS technology has not demonstrated sufficient ability to replace the established invasive measurement.

Traumatic dural venous sinus thrombosis; a challenge in management of head injury patients.

Venous sinus thrombosis secondary to traumatic brain injury and head trauma is increasingly detected following contrast enhanced cranial imaging in acute trauma. The presence of sinus thrombosis poses further challenges in the management of traumatic brain injury patients with cerebral contusions, intraparenchymal haemorrhages or subdural/extradural haemorrhages. The decision to anti-coagulate such trauma induced venous sinus thrombosis is controversial and requires further attention and research to delineate risks versus benefits of treatment. In this article we report 4 cases of venous sinus thrombosis following head trauma and review the literature on management of such patients.

Spinal arachnoid web-a review article.

The spinal arachnoid web is an abnormal formation of an arachnoid membrane in the subarachnoid space. It is a rare entity with some degree of uncertainty surrounding its etiology. It can result in a displacement of the spinal cord causing pain and neurological symptoms as well as blockage of cerebrospinal fluid (CSF) flow and subsequent syringomyelia. The syrinx resulting from the altered CSF flow dynamics has been described to assume variable positions relative to the web itself. The "scalpel sign" is regarded as a pathognomonic feature of a spinal arachnoid web. The arachnoid web, however, is relatively thin and may be elusive of routine radiological investigations. As such, a myriad of preoperative and intraoperative investigations have been postulated to improve the sensitivity of detecting this abnormality. Management of spinal arachnoid webs ranges from conservative management to surgical excision where in the latter, the extent of excision remains the subject of debate. The authors herein present a review of the available information on this rare topic.

Cranial Focal Nodular Haematopoietic Hyperplasia: A case report and literature review.

Focal Nodular Haematopoietic Hyperplasia (FNHH) is an uncommon, benign, osteolytic lesion and so far, has not been reported cranially. Here, we report the first cranial case of a patient with right frontal bone FNHH and describe the clinical history, management and follow up with review of the literature of this rare pathology.

S100B and Glial Fibrillary Acidic Protein as Indexes to Monitor Damage Severity in an In Vitro Model of Traumatic Brain Injury.

Traumatic brain injury (TBI) is a leading and rising cause of death and disability worldwide. There is great interest in S100B and Glial Fibrillary Acid Protein (GFAP) as candidate biomarkers of TBI for diagnosis, triage, prognostication and drug development. However, conflicting results especially on S100B hamper their routine application in clinical practice. To try to address this question, we mimicked TBI damage utilizing a well-validated, simplified in vitro model of graded stretch injury induced in rat organotypic hippocampal slice cultures (OHSC). Different severities of trauma, from mild to severe, have been tested by using an equi-biaxial stretch of the OHSCs at a specified Lagrangian strain of 0 (controls), 5, 10, 20 and 50 %. OHSC were analysed at 3, 6, 18, 24, 48 and 96 h post-injury. Cell death, gene expressions and release into the culture medium of S100B and GFAP were determined at each time point. Gene expression and release of S100B slightly increased only in 20 and 50 % stretched OHSC. GFAP over-expression occurred in 10, 20 and 50 % and was inversely correlated with time post-injury. GFAP release significantly increased with time at any level of injury (p < 0.01 with respect to controls). Consequently, the total amount of GFAP released showed a strong linear relationship with the severity of injury (R(2) = 0.7662; p < 0.001). Under these experimental conditions, S100B seems to be useful in diagnosing only moderate to severe TBI-like injuries. Differently, GFAP demonstrates adequate biomarker requisites since its cellular release is affected by all grades of injury severity.