A Nuclear Localization of the Infectious Haematopoietic Necrosis Virus NV Protein Is Necessary for Optimal Viral Growth

The nonvirion (NV) protein of infectious hematopoietic necrosis virus (IHNV) has been previously reported to be essential for efficient growth and pathogenicity of IHNV. However, little is known about the mechanism by which the NV supports the viral growth. In this study, cellular localization of NV and its role in IHNV growth in host cells was investigated. Through transient transfection in RTG-2 cells of NV fused to green fluorescent protein (GFP), a nuclear localization of NV was demonstrated. Deletion analyses showed that the 32EGDL35 residues were essential for nuclear localization of NV protein, and fusion of these 4 amino acids to GFP directed its transport to the nucleus. We generated a recombinant IHNV, rIHNV-NV-ΔEGDL in which the 32EGDL35 was deleted from the NV. rIHNVs with wild-type NV (rIHNV-NV) or with the NV gene replaced with GFP (rIHNV-ΔNV-GFP) were used as controls. RTG-2 cells infected with rIHNV-ΔNV-GFP and rIHNV-NV-ΔEGDL yielded 12- and 5-fold less infectious virion, respectively, than wild type rIHNV-infected cells at 48 h post-infection (p.i.). While treatment with poly I∶C at 24 h p.i. did not inhibit replication of wild-type rIHNVs, replication rates of rIHNV-ΔNV-GFP and rIHNV-NV-ΔEGDL were inhibited by poly I∶C. In addition, both rIHNV-ΔNV and rIHNV-NV-ΔEGDL induced higher levels of expressions of both IFN1 and Mx1 than wild-type rIHNV. These data suggest that the IHNV NV may support the growth of IHNV through inhibition of the INF system and the amino acid residues of 32EGDL35 responsible for nuclear localization are important for the inhibitory activity of NV

Managing accidental hypothermia: a UK-wide survey of prehospital and search and rescue providers

Aim The management of hypothermic casualties is a challenge faced by all prehospital and search and rescue (SAR) teams. It is not known how the practice of these diverse teams compare. The aim of this study was to review prehospital hypothermia management across a wide range of SAR providers in the UK. Methods A survey of ground ambulances (GAs), air ambulances (AAs), mountain rescue teams (MRTs, including Ministry of Defence), lowland rescue teams (LRTs), cave rescue teams (CRTs), and lifeboats and lifeguard organisations (LLOs) across the UK was conducted between May and November 2017. In total, 189 teams were contacted. Questions investigated packaging methods, temperature measurement and protocols for managing hypothermic casualties. Results Response rate was 59%, comprising 112 teams from a wide range of organisations. Heavyweight (>3 kg) casualty bags were used by all CRTs, 81% of MRTs, 29% of LRTs, 18% of AAs and 8% of LLOs. Specially designed lightweight (<0.5 kg) blankets or wraps were used by 93% of LRTs, 85% of LLOs, 82% of GAs, 71% of AAs and 50% of MRTs. Bubble wrap was used mainly by AAs, with 35% of AAs reporting its use. Overall, 94% of packaging methods incorporated both insulating and vapour-tight layers. Active warming by heated pads or blankets was used by 65% of AAs, 60% of CRTs, 54% of MRTs, 29% of LRTs and 9% of GAs, with no LLO use. Temperature measurement was reported by all AAs and GAs, 93% of LRTs, 80% of CRTs, 75% of MRTs and 31% of LLOs. The favoured anatomical site for temperature measurement was tympanic. Protocols for packaging hypothermic casualties were reported by 73% of services. Conclusions This survey describes current practice in prehospital hypothermia management, comparing the various methods used by different teams, and provides a basis to direct further education and research. https://emj.bmj.com/content/35/11/652.long This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ http://dx.doi.org/10.1136/emermed-2017-20717

Mortality of civilian patients with suspected traumatic haemorrhage receiving pre-hospital transfusion of packed red blood cells compared to pre-hospital crystalloid

Background Major haemorrhage is a leading cause of mortality following major trauma. Increasingly, Helicopter Emergency Medical Services (HEMS) in the United Kingdom provide pre-hospital transfusion with blood products, although the evidence to support this is equivocal. This study compares mortality for patients with suspected traumatic haemorrhage transfused with pre-hospital packed red blood cells (PRBC) compared to crystalloid. Methods A single centre retrospective observational cohort study between 1 January 2010 and 1 February 2015. Patients triggering a pre-hospital Code Red activation were eligible. The primary outcome measure was all-cause mortality at 6 hours and 28 days, including a sub-analysis of patients receiving a major and massive transfusion. Multivariable regression models predicted mortality. Multiple Imputation (MI) was employed, and logistic regression models were constructed for all imputed datasets. Results The crystalloid (n= 103) and PRBC (n= 92) group were comparable for demographics, Injury Severity Score (p= 0.67) and mechanism of injury (p= 0.74). Observed 6 hour mortality was smaller in the PRBC group (n= 10, 10%) compared to crystalloid group (n= 19, 18%). Adjusted OR was not statistically significant (OR 0.48, CI 0.19-1.19, p= 0.11). Observed mortality at 28 days was smaller in the PRBC group (n= 21, 27%) compared to crystalloid group (n= 31, 40%), p= 0.09. Adjusted OR was not statistically significant (OR 0.66, CI 0.32-1.35, p= 0.26). A statistically significant greater proportion of the crystalloid group required a major transfusion (n= 62, 63%) compared to the PRBC group (n= 41, 46%), p= 0.02. For patients requiring a massive transfusion observed mortality was smaller in the PRBC group at 28 days (p= 0.07). Conclusion In a single centre UK HEMS study, in patients with suspected traumatic haemorrhage who received a PRBC transfusion there was an observed, but non-significant, reduction in mortality at 6 hours and 28 days, also reflected in a massive transfusion subgroup. Patients receiving pre-hospital PRBC were significantly less likely to require an in-hospital major transfusion. Further adequately powered multi-centre prospective research is required to establish the optimum strategy for pre-hospital volume replacement in patients with traumatic haemorrhage.</p

Head injury in older adults presenting to the ambulance service: who do we convey to the emergency department, and what clinical variables are associated with an intracranial bleed? A retrospective case–control study

Abstract Objective Most older adults with traumatic brain injuries (TBI) reach the emergency department via the ambulance service. Older adults, often with mild TBI symptoms, risk being under-triaged and facing poor outcomes. This study aimed to identify whether sufficient information is available on the scene to an ambulance clinician to identify an older adult at risk of an intracranial haemorrhage following a head injury. Methods This was a retrospective case–control observational study involving one regional ambulance service in the UK and eight emergency departments. 3545 patients aged 60 years and over presented to one regional ambulance service with a head injury between the 1st of January 2020 and the 31st of December 2020. The primary outcome was an acute intracranial haemorrhage on head computed tomography (CT) scan in patients conveyed to the emergency department (ED). A secondary outcome was factors associated with conveyance to the ED by the ambulance clinician. Results In 2020, 2111 patients were conveyed to the ED and 162 patients were found to have an intracranial haemorrhage on their head CT scan. Falls from more than 2 m (adjusted odds ratio (aOR) 3.45, 95% CI 1.78–6.40), chronic kidney disease (CKD) (aOR 2.80, 95% CI 1.25–5.75) and Clopidogrel (aOR 1.98, 95% CI 1.04–3.59) were associated with an intracranial haemorrhage. Conveyance to the ED was associated with patients taking anticoagulant and antiplatelet medication or a visible head injury or head injury symptoms. Conclusion This study highlights that while most older adults with a head injury are conveyed to the ED, only a minority will have an intracranial haemorrhage following their head injury. While mechanisms of injury such as falls from more than 2 m remain a predictor, this work highlights that Clopidogrel and CKD are also associated with an increased odds of tICH in older adults following a head injury. These findings may warrant a review of current ambulance head injury guidelines

Lessons learned from the first 50 COVID-19 critical care transfer missions conducted by a civilian UK Helicopter Emergency Medical Service team

BackgroundThe COVID-19 pandemic has placed exceptional demand on Intensive Care Units, necessitating the critical care transfer of patients on a regional and national scale. Performing these transfers required specialist expertise and involved moving patients over significant distances. Air Ambulance Kent Surrey Sussex created a designated critical care transfer team and was one of the first civilian air ambulances in the United Kingdom to move ventilated COVID-19 patients by air. We describe the practical set up of such a service and the key lessons learned from the first 50 transfers.MethodsRetrospective review of air critical care transfer service set up and case review of first 50 transfers.ResultsWe describe key elements of the critical care transfer service, including coordination and activation; case interrogation; workforce; training; equipment; aircraft modifications; human factors and clinical governance. A total of 50 missions are described between 18 December 2020 and 1 February 2021. 94% of the transfer missions were conducted by road. The mean age of these patients was 58 years (29–83). 30 (60%) were male and 20 (40%) were female. The mean total mission cycle (time of referral until the time team declared free at receiving hospital) was 264 min (range 149–440 min). The mean time spent at the referring hospital prior to leaving for the receiving unit was 72 min (31–158). The mean transfer transit time between referring and receiving units was 72 min (9–182).ConclusionCritically ill COVID-19 patients have highly complex medical needs during transport. Critical care transfer of COVID-19-positive patients by civilian HEMS services, including air transfer, can be achieved safely with specific planning, protocols and precautions. Regional planning of COVID-19 critical care transfers is required to optimise the time available of critical care transfer teams

Mortality of civilian patients with suspected traumatic haemorrhage receiving pre-hospital transfusion of packed red blood cells compared to pre-hospital crystalloid

Abstract Background Major haemorrhage is a leading cause of mortality following major trauma. Increasingly, Helicopter Emergency Medical Services (HEMS) in the United Kingdom provide pre-hospital transfusion with blood products, although the evidence to support this is equivocal. This study compares mortality for patients with suspected traumatic haemorrhage transfused with pre-hospital packed red blood cells (PRBC) compared to crystalloid. Methods A single centre retrospective observational cohort study between 1 January 2010 and 1 February 2015. Patients triggering a pre-hospital Code Red activation were eligible. The primary outcome measure was all-cause mortality at 6 hours (h) and 28 days (d), including a sub-analysis of patients receiving a major and massive transfusion. Multivariable regression models predicted mortality. Multiple Imputation was employed, and logistic regression models were constructed for all imputed datasets. Results The crystalloid (n = 103) and PRBC (n = 92) group were comparable for demographics, Injury Severity Score (p = 0.67) and mechanism of injury (p = 0.73). Observed 6 h mortality was smaller in the PRBC group (n = 10, 10%) compared to crystalloid group (n = 19, 18%). Adjusted OR was not statistically significant (OR 0.48, CI 0.19–1.19, p = 0.11). Observed mortality at 28 days was smaller in the PRBC group (n = 21, 26%) compared to crystalloid group (n = 31, 40%), p = 0.09. Adjusted OR was not statistically significant (OR 0.66, CI 0.32–1.35, p = 0.26). A statistically significant greater proportion of the crystalloid group required a major transfusion (n = 62, 60%) compared to the PRBC group (n = 41, 40%), p = 0.02. For patients requiring a massive transfusion observed mortality was smaller in the PRBC group at 28 days (p = 0.07). Conclusion In a single centre UK HEMS study, in patients with suspected traumatic haemorrhage who received a PRBC transfusion there was an observed, but non-significant, reduction in mortality at 6 h and 28 days, also reflected in a massive transfusion subgroup. Patients receiving pre-hospital PRBC were significantly less likely to require an in-hospital major transfusion. Further adequately powered multi-centre prospective research is required to establish the optimum strategy for pre-hospital volume replacement in patients with traumatic haemorrhage

Occult tension pneumothorax discovered following imaging for adult trauma patients in the modern major trauma system: a multicentre observational study.

BACKGROUND Tension pneumothorax following trauma is a life-threatening emergency and radiological investigation is normally discouraged prior to treatment in traditional trauma doctrines such as ATLS. Some trauma patients may be physiologically stable enough for diagnostic imaging and occult tension pneumothorax is discovered radiologically. We assessed the outcomes of these patients and compared them with those with clinical diagnosis of tension pneumothorax prior to imaging. METHODS A multicentre civilian-military collaborative network of six major trauma centres in the UK collected observational data from adult patients who had a diagnosis of traumatic tension pneumothorax during a 33-month period. Patients were divided into (diagnosis following CT/CXR) or (no prior CT/CXR) groups. The effect of radiological diagnosis on survival was analysed using multivariable logistic regression that included the covariates of age, gender, comorbidities and Injury Severity Score. RESULTS There were 133 patients, with a median age of 41 (IQR 24-61); 108 (81%) were male. Survivors included 49 of 59 (83%) in the radiological group and 59 of 74 (80%) in the clinical group (p=0.487). Multivariable logistic regression showed no significant association between radiological diagnosis and survival (OR 2.40, 95% CI 0.80 to 7.95; p=0.130). There was no significant difference in mortality between the groups. CONCLUSION Radiological imaging may be appropriate for selected trauma patients at risk of tension pneumothorax if they are considered haemodynamically stable. Trauma patients may be physiologically stable enough for radiological imaging but have occult tension pneumothorax because they did not have the typical clinical presentation. The historical dogma of the no longer applies to such patients