Benefits of a prehospital stroke code system. Feasibility and efficacy in the first year of clinical practice in Barcelona, Spain

BACKGROUND AND OBJECTIVES: Hospital admission delay is a main limiting factor for effective thrombolytic therapy in stroke patients. We developed a stroke code system for rapid request of emergency transportation to the hospital and a priority availability of the attending neurologist on the patient's arrival at the Emergency Department (ED). METHODS: Over a 1-year period, a 24-hour telephone hotline between the attending neurologist and the Barcelona public emergency coordination service was established. Priority 1 (P1) was defined as a patient with symptoms suggestive of acute stroke with onset of less than 3 h, in which case immediate transportation service and rapid ED reception was organized. Data from patients in the P1 group (n = 39) and patients without activation of the stroke code (P0) (n = 181) were compared. RESULTS: There were significant differences between P1 and P0 groups in mean time from ED arrival to request for neurologic assessment (4.4 +/- 19.5 vs. 194.7 +/- 244.9 min, p < 0.001), from arrival to neurologic examination (12.6 +/- 21.1 vs. 225.3 +/- 258.2 min, p < 0.005), and from arrival to performance of brain CT scan (35.5 +/- 34.9 vs.120.3 +/- 143.2 min, p < 0.001), and also in the number of patients treated with thrombolytic agents (19 vs. 4.5%, p < 0.003). There were no differences between groups in the time elapsed from stroke onset to ED arrival. CONCLUSIONS: Activation of the stroke code was effective in increasing the percentage of patients treated with thrombolytic drugs and also in shortening the delay from ED arrival until neurologic assessment and from ED arrival until brain CT.     

Simple models to include influenza vaccination history when evaluating the effect of influenza vaccination

BackgroundMost reports of influenza vaccine effectiveness consider current-season vaccination only.AimWe evaluated a method to estimate the effect of influenza vaccinations (EIV) considering vaccination history.MethodsWe used a test-negative design with well-documented vaccination history to evaluate the average EIV over eight influenza seasons (2011/12–2018/19; n = 10,356). Modifying effect was considered as difference in effects of vaccination in current and previous seasons and current-season vaccination only. We also explored differences between current-season estimates excluding from the reference category people vaccinated in any of the five previous seasons and estimates without this exclusion or only for one or three previous seasons.ResultsThe EIV was 50%, 45% and 38% in people vaccinated in the current season who had previously received none, one to two and three to five doses, respectively, and it was 30% and 43% for one to two and three to five prior doses only. Vaccination in at least three previous seasons reduced the effect of current-season vaccination by 12 percentage points overall, 31 among outpatients, 22 in 9–65 year-olds, and 23 against influenza B. Including people vaccinated in previous seasons only in the unvaccinated category underestimated EIV by 9 percentage points on average (31% vs 40%). Estimates considering vaccination of three or five previous seasons were similar.ConclusionsVaccine effectiveness studies should consider influenza vaccination in previous seasons, as it can retain effect and is often an effect modifier. Vaccination status in three categories (current season, previous seasons only, unvaccinated) reflects the whole EIV.     

CB(1) cannabinoid receptors inhibit the glutamatergic component of KCl-evoked excitation of locus coeruleus neurons in rat brain slices

CB(1) cannabinoid receptors located at presynaptic sites suppress synaptic transmission in the rat brain. The aim of this work was to examine by single-unit extracellular techniques the effect of the synthetic cannabinoid receptor agonist WIN 55212-2 on KCl-evoked excitation of locus coeruleus neurons in rat brain slices. Short applications of KCl (30 mM) increased by 9-fold the firing rate of locus coeruleus cells. Perfusion with the GABA(A) receptor antagonist picrotoxin (100 microM) increased KCl-evoked effect, whereas NMDA and non-NMDA glutamate receptor antagonists (D-AP5 100 microM and CNQX 30 microM, respectively) were able to decrease KCl-evoked effect only in the presence of picrotoxin (100 microM). Bath application of WIN 55212-2 (10 microM) inhibited KCl-evoked effect; this inhibition was blocked by the CB(1) receptor antagonist AM 251 (1 microM). However, a lower concentration of WIN 55212-2 (1 microM) did not significantly change KCl effect. In the presence of picrotoxin (100 microM), perfusion with D-AP5 (100 microM) or CNQX (30 microM) blocked WIN 55212-2-induced inhibition, although picrotoxin (100 microM) itself failed to affect cannabinoid effect. In conclusion, GABAergic and glutamatergic components are both involved in KCl-evoked excitation of LC neurons, although CB(1) receptors only seem to inhibit the glutamatergic component of KCl effect in the locus coeruleus.     

Complete T2-Fogging of Pontomedullary Infarction in Locked-In Syndrome

We report a patient who was treated with intravenous thrombolysis, and subsequently developed a Locked-In Syndrome (LIS). After 2 days, magnetic resonance imaging showed a large bilateral pontomedullary infarction. However, in contrast to the patient’s clinical situation, the follow-up T2-weighted MR images up to day 26 did not display the infarction. This phenomenon is known as the so-called fogging effect. An erratum to this article can be found at     

Morphometric analysis of immunoselection against hyperploid cancer cells

An at least transient increase of ploidy, usually by whole genome duplication, is a frequent event in oncogenesis, explaining the cytogenetic features of at least 40% of solid cancers. Here, we show that fibrosarcomas induced by the carcinogen methylcholanthrene (MCA) are distinct with respect to their ploidy status when they arise in immunocompetent wild type versus severely immunodeficient Rag2^−/−γc^−/− mice. MCA-induced fibrosarcomas are particularly hyperploid if they develop in an immunodeficient setting, correlating with higher DNA content, increased nuclear surface, as well as hyperphosphorylation of eukaryotic initiation factor 2` (eIF2`), a biomarker indicating endoplasmic reticulum (ER) stress. Upon transfer of such cells into wild type mice, such hyperploid, ER-stressed cells (that originated in Rag2^−/−γc^−/− mice) fail to proliferate and actually induce a protective anticancer immune response. In contrast, such cells do form tumors in Rag2^−/−γc^−/− recipients (which lack T, B and NK cells) as well as in Rag2^−/− recipients (which only lack T and B lymphocytes) and conserve their hyperploidy as well as eIF2` hyperphosphorylation. To measure these parameters, we developed a morphometric analysis tool that is applicable to immunohistochemistry of formaldehyde-fixed, paraffin-embedded tissues. This software automatically identifies and quantifies the surface of nuclei and determines the intensity of eIF2` phosphorylation within a perinuclear region of interest. Comparative analyses performed on cultured cells and tissue sections validated the accuracy of this method, which can be used to investigate ploidy and ER stress in cancers in situ.