Brain injury in COVID-19 is associated with dysregulated innate and adaptive immune responses.

COVID-19 is associated with neurological complications including stroke, delirium and encephalitis. Furthermore, a post-viral syndrome dominated by neuropsychiatric symptoms is common, and is seemingly unrelated to COVID-19 severity. The true frequency and underlying mechanisms of neurological injury are unknown, but exaggerated host inflammatory responses appear to be a key driver of COVID-19 severity. We investigated the dynamics of, and relationship between, serum markers of brain injury [neurofilament light (NfL), glial fibrillary acidic protein (GFAP) and total tau] and markers of dysregulated host response (autoantibody production and cytokine profiles) in 175 patients admitted with COVID-19 and 45 patients with influenza. During hospitalization, sera from patients with COVID-19 demonstrated elevations of NfL and GFAP in a severity-dependent manner, with evidence of ongoing active brain injury at follow-up 4 months later. These biomarkers were associated with elevations of pro-inflammatory cytokines and the presence of autoantibodies to a large number of different antigens. Autoantibodies were commonly seen against lung surfactant proteins but also brain proteins such as myelin associated glycoprotein. Commensurate findings were seen in the influenza cohort. A distinct process characterized by elevation of serum total tau was seen in patients at follow-up, which appeared to be independent of initial disease severity and was not associated with dysregulated immune responses unlike NfL and GFAP. These results demonstrate that brain injury is a common consequence of both COVID-19 and influenza, and is therefore likely to be a feature of severe viral infection more broadly. The brain injury occurs in the context of dysregulation of both innate and adaptive immune responses, with no single pathogenic mechanism clearly responsible.

Can compliment and complaint data inform the care of individuals with chronic subdural haematoma (cSDH)?

OBJECTIVES: To explore the frequency and nature of complaints and compliments reported to Patient Advice and Liaison (PALS) in individuals undergoing surgery for a chronic subdural haematoma (cSDH). DESIGN: A retrospective study of PALS user interactions. SUBJECTS: Individuals undergoing treatment for cSDH between 2014 and 2019. METHODS: PALS referrals from patients with cSDH between 2014 and 2019 were identified. Case records were reviewed and data on the frequency, nature and factors leading up to the complaint were extracted and coded according to Healthcare Complaints Analysis Tool (HCAT). RESULTS: Out of 531 patients identified, 25 (5%) had a PALS interaction, of which 15 (3%) were complaints and 10 (2%) were compliments. HCAT coding showed 8/15 (53%) of complaints were relationship problems, 6/15 (33%) a management problem and 1/15 (7%) other. Of the relationship problems, 6 (75%) were classed as problems with communication and 2 (25%) as a problem with listening. Of the compliments, 9/10 (90%) related to good clinical quality and 1/10 (10%) to staff-patient relationship. Patients were more likely to register a compliment than family members, who in turn were more likely to register a complaint (p<0.005). Complaints coded as a relationship problem had 2/8 (25%) submitted by a patient and 6/8 (75%) submitted by a relative. CONCLUSIONS: Using the HCAT, routinely collected PALS data can easily be coded to quantify and provide unique perspective on tertiary care, such as communication. It is readily suited to quality improvement and audit initiatives.

Identification of factors associated with morbidity and postoperative length of stay in surgically managed chronic subdural haematoma using electronic health records: a retrospective cohort study.

INTRODUCTION: Chronic subdural haematoma (cSDH) tends to occur in older patients, often with significant comorbidity. The incidence and effect of medical complications as well as the impact of intraoperative management strategies are now attracting increasing interest. OBJECTIVES: We used electronic health record data to study the profile of in-hospital morbidity and examine associations between various intraoperative events and postoperative stay. DESIGN, SETTING AND PARTICIPANTS: Single-centre, retrospective cohort of 530 cases of cSDH (2014-2019) surgically evacuated under general anaesthesia at a neurosciences centre in Cambridge, UK. METHODS AND OUTCOME DEFINITION: Complications were defined using a modified Electronic Postoperative Morbidity Score. Association between complications and intraoperative care (time with mean arterial pressure <80 mm Hg, time outside of end-tidal carbon dioxide (ETCO2) range of 3-5 kPa, maintenance anaesthetic, operative time and opioid dose) on postoperative stay was assessed using Cox regression. RESULTS: 53 (10%) patients suffered myocardial injury, while 24 (4.5%) suffered acute renal injury. On postoperative day 3 (D3), 280 (58% of remaining) inpatients suffered at least 1 complication. D7 rate was comparable (57%). Operative time was the only intraoperative event associated with postoperative stay (HR for discharge: 0.97 (95% CI: 0.95 to 0.99)). On multivariable analysis, postoperative complications (0.61 (0.55 to 0.68)), anticoagulation (0.45 (0.37 to 0.54)) and cognitive impairment (0.71 (0.58 to 0.87)) were associated with time to discharge. CONCLUSIONS: There is a high postoperative morbidity burden in this cohort, which was associated with postoperative stay. We found no evidence of an association between intraoperative events and postoperative stay.

Neuro-critical care: a valuable placement during foundation and early neurosurgical training.

INTRODUCTION: Neurosciences critical care units (NCCUs) present a unique opportunity to junior trainees in neurosurgery as well as foundation trainees looking to gain experience in the management of critically ill patients with neurological conditions. Placements in NCCUs are undertaken in the early years of neurosurgical training or during neurosciences themed foundation programmes. We sought to quantify the educational benefits of such placements from the trainee perspective. METHODS: Thirty-two trainees who had undertaken placements at Foundation Year 2 (FY2) to Specialty Trainee Year 3 (ST3) level between August 2009 and April 2013 were invited to take part in an online questionnaire survey. Competence in individual skills was self-rated on a ranked scale from one (never observed) to five (performed unsupervised) both before and after the placement. Trainees were also asked a series of questions pertaining to their ability to manage common neurosurgical conditions, as well as the perceived educational rigour of their placement. RESULTS: Twenty-three responses were received. Eighteen responses were from FY2s and seven were from ST1-3 level trainees. Following their placements, 100% of respondents felt better equipped to deal with neurosurgical and neurological emergencies and cranial trauma. Most felt better equipped to manage hydrocephalus (95.7%), polytrauma patients (95.7%), spontaneous intracranial haemorrhage (91.3%) and spinal trauma (82.6%). Significant increases were seen in experience in all practical skills assessed. These included central venous catheterisation (p < 0.001), intracranial pressure (ICP) bolt insertion (p < 0.001), ICP bolt removal (p < 0.001), external ventricular drain (EVD) insertion (p = 0.001) and tapping of EVD for cerebrospinal fluid sample (p < 0.001). CONCLUSION: Our results clearly demonstrate the educational benefits of NCCU placements in the early stages of a neurosurgical training programme as well as in the Foundation Programme. This supports the incorporation of a four- to six-month NCCU rotation in early years training as educationally valuable.

Strategies to prevent ventilation-associated pneumonia: the effect of cuff pressure monitoring techniques and tracheal tube type on aspiration of subglottic secretions: an in-vitro study.

BACKGROUND: Ventilation-associated pneumonia (VAP) is the commonest nosocomial infection in intensive care. Implementation of a VAP prevention care bundle is a proven method to reduce its incidence. The UK care bundle recommends maintenance of the tracheal tube cuff pressure at 20 to 30  cmH2O with 4-hourly pressure checks and use of tracheal tubes with subglottic aspiration ports in patients admitted for more than 72  h. OBJECTIVE: To evaluate the effects of tracheal tube type and cuff pressure monitoring technique on leakage of subglottic secretions past the tracheal tube cuff. DESIGN: Bench-top study. SETTING: Laboratory. INTERVENTIONS: A model adult trachea with simulated subglottic secretions was intubated with a tracheal tube with the cuff inflated to 25  cmH2O. Experiments were conducted using a Portex Profile Soft Seal tracheal tube with three cuff pressure monitoring strategies and using a Portex SACETT tracheal tube with intermittent cuff pressure checks. OUTCOME MEASURES: Rate of simulated secretion leakage past the tracheal tube cuff. RESULTS: Mean ±â€ŠSD leakage of fluid past the Profile Soft Seal tracheal tube cuff was 2.25 ±â€Š1.49  ml  min⁻¹ with no monitoring of cuff pressure, 2.98 ±â€Š1.63  ml  min⁻¹ with intermittent cuff pressure monitoring and 3.83 ±â€Š2.17  ml  min⁻¹ with continuous cuff pressure monitoring (P <0.001). Using a SACETT tracheal tube with a subglottic aspiration port and aspirating the simulated secretions prior to intermittent cuff pressure checks reduced the leakage rate to 0.50 ±â€Š0.48  ml  min⁻¹ (P <0.001). CONCLUSION: Subglottic secretions leaked past the tracheal tube cuff with all tube types and cuff pressure monitoring strategies in this model. Significantly higher rates were observed with continuous cuff pressure monitoring and significantly lower rates were observed when using a tracheal tube with a subglottic aspiration port. Further evaluation of medical device performance is needed in order to design more effective VAP prevention strategies.

Perioperative care of a patient with stroke.

Strokes and TIAs, with their high cumulative mortality and morbidity rates, are occurring with increasing frequency in western population 14. As such, it is vital for clinicians to provide optimal medical management in the perioperative period for those patients with this common neurological problem. This review aims to highlight the importance of the perioperative period and the stages of pre-optimization that can be taken by the multi-disciplinary team to aid this 171819. The evidence suggests that there are significant physiological advantages to early invasive monitoring and high dependency care in these complex patients. These cohort of patients are at increased risk of development of respiratory, gastrointestinal, nutritional and electrolyte disturbances so a constant vigil should be exercised in early recognition and treatment.

Molecular mechanisms of traumatic brain injury: the missing link in management.

Head injury is common, sometimes requires intensive care unit admission, and is associated with significant mortality and morbidity. A gap still remains in the understanding of the molecular mechanism of this condition. This review is aimed at providing a general overview of the molecular mechanisms involved in traumatic brain injury to a busy clinician. It will encompass the pathophysiology in traumatic brain injury including apoptosis, the role of molecules and genes, and a brief mention of possible pharmacological therapies.

Gene expression changes in long term expanded human neural progenitor cells passaged by chopping lead to loss of neurogenic potential in vivo.

Numerous cell culture protocols have been described for the proliferation of multipotent human neural progenitor cells (HNPCs). The mitogen combinations used to expand HNPCs vary, and it is not clear to what extent this may affect the subsequent differentiation of these cells. In this study human foetal cortical tissue was cultured in the presence of either EGF, or FGF-2, or a combination of both using a unique chopping method in which cell to cell contact is maintained. The differentiation potential of neurospheres following mitogen withdrawal was assessed at early (8 weeks) and late (20 weeks) times of expansion, both in vitro and in vivo. In addition, changes in gene expression with time were analysed by microarray experiments. Results show that the presence of FGF-2 was highly predictive of neuronal differentiation after short term culture both in vitro and in vivo. In addition, time in culture had a significant effect on transplant size and neural constituents suggesting that cells have a limited life span and restricted lineage potential. Array analysis confirms that following extensive time in culture cells are entering growth arrest with fundamental expression changes in genes associated with cell cycle regulation, apoptosis and immune functions.

Differentiation and migration of long term expanded human neural progenitors in a partial lesion model of Parkinson's disease.

Human neural progenitor cells (HNPCs) can be expanded in large numbers for significant periods of time to provide a reliable source of neural cells for transplantation in neurodegenerative disorders such as Parkinson's disease (PD). In the present study, HNPCs isolated from embryonic cortex were expanded as neurospheres in cell culture for 10 months. Just prior to transplantation, a proportion of the HNPCs were treated in a "predifferentiation" protocol in combination with the neurotropic factor NT4, in order to yield significant numbers of neurons. For transplantation, either undifferentiated HNPCs, or predifferentiated HNPCs were transplanted into the substantia nigra of a rat model of Parkinson's disease. At 12 weeks, there was good survival with proliferation of transplanted HNPCs occurring after transplantation but ceasing before the animals were sacrificed. Transplants of predifferentiated cells contained a higher proportion of neurons. The presence of a lesion in the striatum had a significant influence on the migration of transplanted cells from the substantia nigra into the striatum. There was no significant behavioural recovery or effect of transplanted HNPCs on the loss of dopaminergic cells from the host brain. In conclusion, HNPCs may provide a source of cells for use in the treatment of Parkinson's disease.