G1m1 predominance of intrathecal virus-specific antibodies in multiple sclerosis

We have previously shown that plasmablasts of the G1m1 allotype of IgG1 are selectively enriched in the cerebrospinal fluid of G1m1/G1m3 heterozygous patients with multiple sclerosis, whereas both allotypes are equally used in neuroborreliosis. Here, we demonstrate a strong preference for the G1m1 allotype in the intrathecal humoral immune responses against measles, rubella, and varicella zoster virus in G1m1/G1m3 heterozygous multiple sclerosis patients. Conversely, intrathecally synthesized varicella zoster virus‐specific IgG1 in varicella zoster virus meningoencephalitis comprised both allotypes. This implies that G1m1 B cells are selected to the central nervous system of multiple sclerosis patients regardless of specificity and suggests that an antigen‐independent mechanism could drive the intrathecal humoral immune response.publishedVersio

Implementation of recommended trauma system criteria in south-eastern Norway: a cross-sectional hospital survey

<p>Abstract</p> <p>Background</p> <p>Formalized trauma systems have shown beneficial effects on patient survival and have harvested great recognition among health care professionals. In spite of this, the implementation of trauma systems is challenging and often met with resistance.</p> <p>Recommendations for a national trauma system in Norway were published in 2007. We wanted to assess the level of implementation of these recommendations.</p> <p>Methods</p> <p>A survey of all acute care hospitals that receive severely injured patients in the south-eastern health region of Norway was conducted. A structured questionnaire based on the 2007 national recommendations was used in a telephone interview of hospital trauma personnel between January 17 and 21, 2011. Seventeen trauma system criteria were identified from the recommendations.</p> <p>Results</p> <p>Nineteen hospitals were included in the study and these received more than 2000 trauma patients annually via their trauma teams. Out of the 17 criteria that had been identified, the hospitals fulfilled a median of 12 criteria. Neither the size of the hospitals nor the distance between the hospitals and the regional trauma centre affected the level of trauma resources available. The hospitals scored lowest on the criteria for transfer of patients to higher level of care and on the training requirements for members of the trauma teams.</p> <p>Conclusion</p> <p>Our study identifies a major shortcoming in the efforts of regionalizing trauma in our region. The findings indicate that training of personnel and protocols for inter-hospital transfer are the major deficiencies from the national trauma system recommendations. Resources for training of personnel partaking in trauma teams and development of inter-hospital transfer agreements should receive immediate attention.</p

Pre-hospital advanced airway management by anaesthetist and nurse anaesthetist critical care teams: a prospective observational study of 2028 pre-hospital tracheal intubations

Background: Pre-hospital tracheal intubation success and complication rates vary considerably among provider categories. The purpose of this study was to estimate the success and complication rates of pre-hospital tracheal intubation performed by physician anaesthetist or nurse anaesthetist pre-hospital critical care teams. Methods: Data were prospectively collected from critical care teams staffed with a physician anaesthetist or a nurse anaesthetist according to the Utstein template for pre-hospital advanced airway management. The patients served by six ambulance helicopters and six rapid response vehicles in Denmark, Finland, Norway, and Sweden from May 2015 to November 2016 were included. Results: The critical care teams attended to 32 007 patients; 2028 (6.3%) required pre-hospital tracheal intubation. The overall success rate of pre-hospital tracheal intubation was 98.7% with a median intubation time of 25 s and an on-scene time of 25 min. The majority (67.0%) of the patients' tracheas were intubated by providers who had performed >2500 tracheal intubations. The success rate of tracheal intubation on the first attempt was 84.5%, and 95.9% of intubations were completed after two attempts. Complications related to pre-hospital tracheal intubation were recorded in 10.9% of the patients. Intubations after rapid sequence induction had a higher success rate compared with intubations without rapid sequence induction (99.4% vs 98.1%; P=0.02). Physicians had a higher tracheal intubation success rate than nurses (99.0% vs 97.6%; P=0.03). Conclusions: When performed by experienced physician anaesthetists and nurse anaesthetists, pre-hospital tracheal intubation was completed rapidly with high success rates and a low incidence of complications.Peer reviewe

Single-cell transcriptomics combined with proteomics of intrathecal IgG reveal transcriptional heterogeneity of oligoclonal IgG-secreting cells in multiple sclerosis

The phenotypes of B lineage cells that produce oligoclonal IgG in multiple sclerosis have not been unequivocally determined. Here, we utilized single-cell RNA-seq data of intrathecal B lineage cells in combination with mass spectrometry of intrathecally synthesized IgG to identify its cellular source. We found that the intrathecally produced IgG matched a larger fraction of clonally expanded antibody-secreting cells compared to singletons. The IgG was traced back to two clonally related clusters of antibody-secreting cells, one comprising highly proliferating cells, and the other consisting of more differentiated cells expressing genes associated with immunoglobulin synthesis. These findings suggest some degree of heterogeneity among cells that produce oligoclonal IgG in multiple sclerosis

Pediatric Emergencies in Helicopter Emergency Medical Services:A National Population-Based Cohort Study From Denmark

Study objective: To examine the diagnostic pattern, level of severity of illness or injuries, and mortality among children for whom a physician-staffed helicopter emergency medical service (HEMS) was dispatched. Methods: Population-based cohort study including patients aged less than 16 years treated by the Danish national HEMS from October 1, 2014, to September 30, 2018. Diagnoses were retrieved from inhospital medical records, and the severity of illness or injuries was assessed by a severity score on scene, administration of advanced out-of-hospital care, need for intensive care in a hospital, and mortality. Results: In total, 651 HEMS missions included pediatric patients aged less than 1 year (9.2%), 1 to 2 years (29.0%), 3 to 7 years (28.3%), and 8 to 15 years (33.5%). A third of the patients had critical emergencies (29.6%), and for 20.1% of the patients, 1 or more out-of-hospital interventions were performed: intubation, mechanical chest compressions, intraosseous vascular access, blood transfusion, chest tube insertion, and/or ultrasound examination. Among the 525 patients with hospital follow-up, the most frequent hospital diagnoses were injuries (32.2%), burns (11.2%), and respiratory diseases (7.8%). Within 24 hours of the mission, 18.1% of patients required intensive care. Twenty-nine patients (5.1%, 95% confidence interval [CI] 3.6 to 7.3) died either on or within 1 day of the mission, and the cumulative 30-day mortality was 35 of 565 (6.2%, 95% CI 4.5 to 8.5) (N¼565 first-time missions). Conclusion: On Danish physician-staffed HEMS missions, 1 in 5 pediatric patients required advanced out-of-hospital care. Among hospitalized patients, nearly one-fifth of the patients required immediate intensive care and 6.2% died within 30 days of the mission.publishedVersio

Patients Referred to a Norwegian Trauma Centre: effect of transfer distance on injury patterns, use of resources and outcomes

Background Triage and interhospital transfer are central to trauma systems. Few studies have addressed transferred trauma patients. This study investigated transfers of variable distances to OUH (Oslo University Hospital, Ullevål), one of the largest trauma centres in Europe. Methods Patients included in the OUH trauma registry from 2001 to 2008 were included in the study. Demographic, injury, management and outcome data were abstracted. Patients were grouped according to transfer distance: ≤20 km, 21-100 km and > 100 km. Results Of the 7.353 included patients, 5.803 were admitted directly, and 1.550 were transferred. The number of transfers per year increased, and there was no reduction in injury severity during the study period. Seventy-six per cent of the transferred patients were severely injured. With greater transfer distances, injury severity increased, and there were larger proportions of traffic injuries, polytrauma and hypotensive patients. With shorter distances, patients were older, and head injuries and injuries after falls were more common. The shorter transfers less often activated the trauma team: ≤20 km -34%; 21-100 km -51%; > 100 km -61%, compared to 92% of all directly admitted patients. The mortality for all transferred patients was 11%, but was unequally distributed according to transfer distance. Conclusion This study shows heterogeneous characteristics and high injury severity among interhospital transfers. The rate of trauma team assessment was low and should be further examined. The mortality differences should be interpreted with caution as patients were in different phases of management. The descriptive characteristics outlined may be employed in the development of triage protocols and transfer guidelines

The civilian validation of the Modified Physiological Triage Tool (MPTT): an evidence-based approach to primary major incident triage

INTRODUCTION: Triage is a key principle in the effective management of a major incident. Existing triage tools have demonstrated limited performance at predicting need for life-saving intervention (LSI). Derived on a military cohort, the Modified Physiological Triage Tool (MPTT) has demonstrated improved performance. Using a civilian trauma registry, this study aimed to validate the MPTT in a civilian environment. METHODS: Retrospective database review of the Trauma Audit and Research Network (TARN) database for all adult patients (>18 years) between 2006 and 2014. Patients were defined as Priority One if they received one or more LSIs from a previously defined list. Only patients with complete physiological data were included. Patients were categorised by the MPTT and existing triage tools using first recorded hospital physiology. Performance characteristics were evaluated using sensitivity, specificity and area under receiver operating characteristic (AUROC). RESULTS: During the study period, 218 985 adult patients were included in the TARN database. 127 233 (58.1%) had complete data: 55.6% male, aged 61.4 (IQR 43.1-80.0) years, Injury Severity Score 9 (IQR 9-16), 96.5% suffered blunt trauma and 24 791 (19.5%) were Priority One. The MPTT (sensitivity 57.6%, specificity 71.5%) outperformed all existing triage methods with a 44.7% absolute reduction in undertriage compared with existing UK civilian methods. AUROC comparison supported the use of the MPTT over other tools (p<0.001.) CONCLUSION: Within a civilian trauma registry population, the MPTT demonstrates improved performance at predicting need for LSI, with the lowest rates of undertriage and an appropriate level of overtriage. We suggest the MPTT be considered as an alternative to existing triage tools

Domes and semi-capsules as model systems for infrared microspectroscopy of biological cells.

It is well known that infrared microscopy of micrometer sized samples suffers from strong scattering distortions, attributed to Mie scattering. The state-of-the-art preprocessing technique for modelling and removing Mie scattering features from infrared absorbance spectra of biological samples is built on a meta model for perfect spheres. However, non-spherical cell shapes are the norm rather than the exception, and it is therefore highly relevant to evaluate the validity of this preprocessing technique for deformed spherical systems. Addressing these cases, we investigate both numerically and experimentally the absorbance spectra of 3D-printed individual domes, rows of up to five domes, two domes with varying distance, and semi-capsules of varying lengths as model systems of deformed individual cells and small cell clusters. We find that coupling effects between individual domes are small, corroborating previous related literature results for spheres. Further, we point out and illustrate with examples that, while optical reciprocity guarantees the same extinction efficiency for top vs. bottom illumination, a scatterer's internal field may be vastly different in these two situations. Finally, we demonstrate that the ME-EMSC model for preprocessing infrared spectra from spherical biological systems is valid also for deformed spherical systems

Stopping Antiepileptic Drugs: When and Why?

After a patient has initiated an antiepileptic drug (AED) and achieved a sustained period of seizure freedom, the bias towards continuing therapy indefinitely can be substantial. Studies show that the rate of seizure recurrence after AED withdrawal is about two to three times the rate in patients who continue AEDs, but there are many benefits to AED withdrawal that should be evaluated on an individualized basis. AED discontinuation may be considered in patients whose seizures have been completely controlled for a prolonged period, typically 1 to 2 years for children and 2 to 5 years for adults. For children, symptomatic epilepsy, adolescent onset, and a longer time to achieve seizure control are associated with a worse prognosis. In adults, factors such as a longer duration of epilepsy, an abnormal neurologic examination, an abnormal EEG, and certain epilepsy syndromes are known to increase the risk of recurrence. Even in patients with a favorable prognosis, however, the risk of relapse can be as high as 20% to 25%. Before withdrawing AEDs, patients should be counseled about their individual risk for relapse and the potential implications of a recurrent seizure, particularly for safety and driving

EEG in fitness to drive evaluations in people with epilepsy - Considerable variations across Europe

PURPOSE: Epilepsy patients consider driving issues to be one of their most serious concerns. Ideally, decisions regarding fitness to drive should be based upon thorough evaluations by specialists in epilepsy care. In 2009, an EU directive was published aiming to harmonize evaluation practices within European countries, but, despite these recommendations, whether all epileptologists use the same criteria is unclear. We therefore conducted this study to investigate routine practices on how epileptologists at European epilepsy centers evaluate fitness to drive. METHODS: A questionnaire was sent to 63 contact persons identified through the European Epi-Care and the E-pilepsy network. The questionnaire addressed how fitness-to-drive evaluations were conducted, the involvement of different professionals, the use and interpretation of EEG, and opinions on existing regulations and guidelines. RESULTS: The questionnaire was completed by 35 participants (56 % response rate). Results showed considerable variation regarding test routines and the emphasis placed on the occurrence and extent of epileptiform discharges revealed by EEG. 82 % of the responders agreed that there was a need for more research on how to better evaluate fitness-to-drive in people with epilepsy, and 89 % agreed that regulations on fitness to drive evaluations should be internationally coordinated. CONCLUSION: Our survey showed considerable variations among European epileptologists regarding use of EEG and how findings of EEG pathology should be assessed in fitness-to-drive evaluations. There is a clear need for more research on this issue and international guidelines on how such evaluations should be carried out would be of value