Brain temperature regulation in poor-grade subarachnoid hemorrhage patients – A multimodal neuromonitoring study

Elevated body temperature (Tcore) is associated with poor outcome after subarachnoid hemorrhage (SAH). Brain temperature (Tbrain) is usually higher than Tcore. However, the implication of this difference (Tdelta) remains unclear. We aimed to study factors associated with higher Tdelta and its association with outcome. We included 46 SAH patients undergoing multimodal neuromonitoring, for a total of 7879 h of averaged data of Tcore, Tbrain, cerebral blood flow, cerebral perfusion pressure, intracranial pressure and cerebral metabolism (CMD). Three-months good functional outcome was defined as modified Rankin Scale ≤2. Tbrain was tightly correlated with Tcore (r = 0.948, p < 0.01), and was higher in 73.7% of neuromonitoring time (Tdelta +0.18°C, IQR −0.01 – 0.37°C). A higher Tdelta was associated with better metabolic state, indicated by lower CMD-glutamate ( p = 0.003) and CMD-lactate ( p < 0.001), and lower risk of mitochondrial dysfunction (MD) (OR = 0.2, p < 0.001). During MD, Tdelta was significantly lower (0°C, IQR −0.2 – 0.1; p < 0.001). A higher Tdelta was associated with improved outcome (OR = 7.7, p = 0.002). Our study suggests that Tbrain is associated with brain metabolic activity and exceeds Tcore when mitochondrial function is preserved. Further studies are needed to understand how Tdelta may serve as a surrogate marker for brain function and predict clinical course and outcome after SAH

Preclinical evaluation of two 68Ga-siderophores as potential radiopharmaceuticals for Aspergillus fumigatus infection imaging

PURPOSE: Invasive pulmonary aspergillosis is mainly caused by Aspergillus fumigatus, and is one of the major causes of morbidity and mortality in immunocompromised patients. The mortality associated with invasive pulmonary aspergillosis remains high, mainly due to the difficulties and limitations in diagnosis. We have shown that siderophores can be labelled with (68)Ga and can be used for PET imaging of A. fumigatus infection in rats. Here we report on the further evaluation of the most promising (68)Ga-siderophore candidates, triacetylfusarinine (TAFC) and ferrioxamine E (FOXE). METHODS: Siderophores were labelled with (68)Ga using acetate buffer. Log P, protein binding and stability values were determined. Uptake by A. fumigatus was studied in vitro in cultures with high and low iron loads. In vivo biodistribution was determined in normal mice and an infection model was established using neutropenic rats inoculated with A. fumigatus. Static and dynamic muPET imaging was performed and correlated with CT images, and lung infection was evaluated ex vivo. RESULTS: (68)Ga-siderophores were labelled with high radiochemical purity and specific activity. (68)Ga-TAFC and (68)Ga-FOXE showed high uptake by A. fumigatus in iron-deficient cultures. In normal mice, (68)Ga-TAFC and (68)Ga-FOXE showed rapid renal excretion with high metabolic stability. In the rat infection model focal lung uptake was detected by muPET with both compounds and increased with severity of the infection, correlating with abnormal CT images. CONCLUSION: (68)Ga-TAFC and (68)Ga-FOXE displayed excellent in vitro stability and high uptake by A. fumigatus. Both compounds showed excellent pharmacokinetics, highly selective accumulation in infected lung tissue and good correlation with severity of disease in a rat infection model, which makes them promising agents for A. fumigatus infection imaging

Clinical autonomic nervous system laboratories in Europe: a joint survey of the European Academy of Neurology and the European Federation of Autonomic Societies

© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.Background and purpose: Disorders of the autonomic nervous system (ANS) are common conditions, but it is unclear whether access to ANS healthcare provision is homogeneous across European countries. The aim of this study was to identify neurology-driven or interdisciplinary clinical ANS laboratories in Europe, describe their characteristics and explore regional differences. Methods: We contacted the European national ANS and neurological societies, as well as members of our professional network, to identify clinical ANS laboratories in each country and invite them to answer a web-based survey. Results: We identified 84 laboratories in 22 countries and 46 (55%) answered the survey. All laboratories perform cardiovascular autonomic function tests, and 83% also perform sweat tests. Testing for catecholamines and autoantibodies are performed in 63% and 56% of laboratories, and epidermal nerve fiber density analysis in 63%. Each laboratory is staffed by a median of two consultants, one resident, one technician and one nurse. The median (interquartile range [IQR]) number of head-up tilt tests/laboratory/year is 105 (49-251). Reflex syncope and neurogenic orthostatic hypotension are the most frequently diagnosed cardiovascular ANS disorders. Thirty-five centers (76%) have an ANS outpatient clinic, with a median (IQR) of 200 (100-360) outpatient visits/year; 42 centers (91%) also offer inpatient care (median 20 [IQR 4-110] inpatient stays/year). Forty-one laboratories (89%) are involved in research activities. We observed a significant difference in the geographical distribution of ANS services among European regions: 11 out of 12 countries from North/West Europe have at least one ANS laboratory versus 11 out of 21 from South/East/Greater Europe (p = 0.021). Conclusions: This survey highlights disparities in the availability of healthcare services for people with ANS disorders across European countries, stressing the need for improved access to specialized care in South, East and Greater Europe.info:eu-repo/semantics/publishedVersio

EFAS/EAN survey on the influence of the COVID-19 pandemic on European clinical autonomic education and research

© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.Purpose: To understand the influence of the coronavirus disease 2019 (COVID-19) pandemic on clinical autonomic education and research in Europe. Methods: We invited 84 European autonomic centers to complete an online survey, recorded the pre-pandemic-to-pandemic percentage of junior participants in the annual congresses of the European Federation of Autonomic Societies (EFAS) and European Academy of Neurology (EAN) and the pre-pandemic-to-pandemic number of PubMed publications on neurological disorders. Results: Forty-six centers answered the survey (55%). Twenty-nine centers were involved in clinical autonomic education and experienced pandemic-related didactic interruptions for 9 (5; 9) months. Ninety percent (n = 26/29) of autonomic educational centers reported a negative impact of the COVID-19 pandemic on education quality, and 93% (n = 27/29) established e-learning models. Both the 2020 joint EAN-EFAS virtual congress and the 2021 (virtual) and 2022 (hybrid) EFAS and EAN congresses marked higher percentages of junior participants than in 2019. Forty-one respondents (89%) were autonomic researchers, and 29 of them reported pandemic-related trial interruptions for 5 (2; 9) months. Since the pandemic begin, almost half of the respondents had less time for scientific writing. Likewise, the number of PubMed publications on autonomic topics showed the smallest increase compared with other neurological fields in 2020-2021 and the highest drop in 2022. Autonomic research centers that amended their trial protocols for telemedicine (38%, n = 16/41) maintained higher clinical caseloads during the first pandemic year. Conclusions: The COVID-19 pandemic had a substantial negative impact on European clinical autonomic education and research. At the same time, it promoted digitalization, favoring more equitable access to autonomic education and improved trial design.info:eu-repo/semantics/publishedVersio

A plea for equitable global access to COVID‐19 diagnostics, vaccination and therapy: The NeuroCOVID‐19 Task Force of the European Academy of Neurology

Coronavirus disease 2019 (COVID‐19), a multi‐organ disease caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), continues to challenge health and care systems around the globe. The pandemic has disrupted acute neurology services and routine patient care and has impacted the clinical course in patients with chronic neurological disease. COVID‐19 appears to have exposed inequalities of societies and healthcare systems and had a disproportionate impact on already vulnerable communities. The next challenge will be to set up initiatives to stop disparities in all aspects related to COVID‐19. From the medical perspective, there is a need to consider inequalities in prevention, treatment and long‐term consequences. Some of the issues of direct relevance to neurologists are summarised. With this appraisal, the European Academy of Neurology NeuroCOVID‐19 Task Force intends to raise awareness of the potential impact of COVID‐19 on inequalities in healthcare and calls for action to prevent disparity at individual, national and supranational levels

Diploids in the Cryptococcus neoformans Serotype A Population Homozygous for the α Mating Type Originate via Unisexual Mating

The ubiquitous environmental human pathogen Cryptococcus neoformans is traditionally considered a haploid fungus with a bipolar mating system. In nature, the α mating type is overwhelmingly predominant over a. How genetic diversity is generated and maintained by this heterothallic fungus in a largely unisexual α population is unclear. Recently it was discovered that C. neoformans can undergo same-sex mating under laboratory conditions generating both diploid intermediates and haploid recombinant progeny. Same-sex mating (α-α) also occurs in nature as evidenced by the existence of natural diploid αADα hybrids that arose by fusion between two α cells of different serotypes (A and D). How significantly this novel sexual style contributes to genetic diversity of the Cryptococcus population was unknown. In this study, ∼500 natural C. neoformans isolates were tested for ploidy and close to 8% were found to be diploid by fluorescence flow cytometry analysis. The majority of these diploids were serotype A isolates with two copies of the α MAT locus allele. Among those, several are intra-varietal allodiploid hybrids produced by fusion of two genetically distinct α cells through same-sex mating. The majority, however, are autodiploids that harbor two seemingly identical copies of the genome and arose via either endoreplication or clonal mating. The diploids identified were isolated from different geographic locations and varied genotypically and phenotypically, indicating independent non-clonal origins. The present study demonstrates that unisexual mating produces diploid isolates of C. neoformans in nature, giving rise to populations of hybrids and mixed ploidy. Our findings underscore the importance of same-sex mating in shaping the current population structure of this important human pathogenic fungus, with implications for mechanisms of selfing and inbreeding in other microbial pathogens

Low-resolution pressure reactivity index and its derived optimal cerebral perfusion pressure in adult traumatic brain injury: a CENTER-TBI study

Abstract: Background: After traumatic brain injury (TBI), brain tissue can be further damaged when cerebral autoregulation is impaired. Managing cerebral perfusion pressure (CPP) according to computed “optimal CPP” values based on cerebrovascular reactivity indices might contribute to preventing such secondary injuries. In this study, we examined the discriminative value of a low-resolution long pressure reactivity index (LPRx) and its derived “optimal CPP” in comparison to the well-established high-resolution pressure reactivity index (PRx). Methods: Using the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study dataset, the association of LPRx (correlation between 1-min averages of intracranial pressure and arterial blood pressure over a moving time frame of 20 min) and PRx (correlation between 10-s averages of intracranial pressure and arterial blood pressure over a moving time frame of 5 min) to outcome was assessed and compared using univariate and multivariate regression analysis. “Optimal CPP” values were calculated using a multi-window algorithm that was based on either LPRx or PRx, and their discriminative ability was compared. Results: LPRx and PRx were both significant predictors of mortality in univariate and multivariate regression analysis, but PRx displayed a higher discriminative ability. Similarly, deviations of actual CPP from “optimal CPP” values calculated from each index were significantly associated with outcome in univariate and multivariate analysis. “Optimal CPP” based on PRx, however, trended towards more precise predictions. Conclusions: LPRx and its derived “optimal CPP” which are based on low-resolution data were significantly associated with outcome after TBI. However, they did not reach the discriminative ability of the high-resolution PRx and its derived “optimal CPP.” Nevertheless, LPRx might still be an interesting tool to assess cerebrovascular reactivity in centers without high-resolution signal monitoring. Trial registration: ClinicalTrials.gov Identifier: NCT02210221. First submitted July 29, 2014. First posted August 6, 2014

Quality indicators for patients with traumatic brain injury in European intensive care units

Background: The aim of this study is to validate a previously published consensus-based quality indicator set for the management of patients with traumatic brain injury (TBI) at intensive care units (ICUs) in Europe and to study its potential for quality measur

Changing care pathways and between-center practice variations in intensive care for traumatic brain injury across Europe

Purpose: To describe ICU stay, selected management aspects, and outcome of Intensive Care Unit (ICU) patients with traumatic brain injury (TBI) in Europe, and to quantify variation across centers. Methods: This is a prospective observational multicenter study conducted across 18 countries in Europe and Israel. Admission characteristics, clinical data, and outcome were described at patient- and center levels. Between-center variation in the total ICU population was quantified with the median odds ratio (MOR), with correction for case-mix and random variation between centers. Results: A total of 2138 patients were admitted to the ICU, with median age of 49 years; 36% of which were mild TBI (Glasgow Coma Scale; GCS 13–15). Within, 72 h 636 (30%) were discharged and 128 (6%) died. Early deaths and long-stay patients (> 72 h) had more severe injuries based on the GCS and neuroimaging characteristics, compared with short-stay patients. Long-stay patients received more monitoring and were treated at higher intensity, and experienced worse 6-month outcome compared to short-stay patients. Between-center variations were prominent in the proportion of short-stay patients (MOR = 2.3, p < 0.001), use of intracranial pressure (ICP) monitoring (MOR = 2.5, p < 0.001) and aggressive treatme

Machine learning algorithms performed no better than regression models for prognostication in traumatic brain injury

Objective: We aimed to explore the added value of common machine learning (ML) algorithms for prediction of outcome for moderate and severe traumatic brain injury. Study Design and Setting: We performed logistic regression (LR), lasso regression, and ridge regression with key baseline predictors in the IMPACT-II database (15 studies, n = 11,022). ML algorithms included support vector machines, random forests, gradient boosting machines, and artificial neural networks and were trained using the same predictors. To assess generalizability of predictions, we performed internal, internal-external, and external validation on the recent CENTER-TBI study (patients with Glasgow Coma Scale <13, n = 1,554). Both calibration (calibration slope/intercept) and discrimination (area under the curve) was quantified. Results: In the IMPACT-II database, 3,332/11,022 (30%) died and 5,233(48%) had unfavorable outcome (Glasgow Outcome Scale less than 4). In the CENTER-TBI study, 348/1,554(29%) died and 651(54%) had unfavorable outcome. Discrimination and calibration varied widely between the studies and less so between the studied algorithms. The mean area under the curve was 0.82 for mortality and 0.77 for unfavorable outcomes in the CENTER-TBI study. Conclusion: ML algorithms may not outperform traditional regression approaches in a low-dimensional setting for outcome prediction after moderate or severe traumatic brain injury. Similar to regression-based prediction models, ML algorithms should be rigorously validated to ensure applicability to new populations