Biofluid Biomarkers in the Prognosis of Amyotrophic Lateral Sclerosis: Recent Developments and Therapeutic Applications

Amyotrophic lateral sclerosis; Biomarker; PrognosisEsclerosi lateral amiotròfica; Biomarcador; PronòsticEsclerosis lateral amiotrófica; Biomarcador; PronósticoAmyotrophic lateral sclerosis is a neurodegenerative disease characterized by the degeneration of motor neurons for which effective therapies are lacking. One of the most explored areas of research in ALS is the discovery and validation of biomarkers that can be applied to clinical practice and incorporated into the development of innovative therapies. The study of biomarkers requires an adequate theoretical and operational framework, highlighting the “fit-for-purpose” concept and distinguishing different types of biomarkers based on common terminology. In this review, we aim to discuss the current status of fluid-based prognostic and predictive biomarkers in ALS, with particular emphasis on those that are the most promising ones for clinical trial design and routine clinical practice. Neurofilaments in cerebrospinal fluid and blood are the main prognostic and pharmacodynamic biomarkers. Furthermore, several candidates exist covering various pathological aspects of the disease, such as immune, metabolic and muscle damage markers. Urine has been studied less often and should be explored for its possible advantages. New advances in the knowledge of cryptic exons introduce the possibility of discovering new biomarkers. Collaborative efforts, prospective studies and standardized procedures are needed to validate candidate biomarkers. A combined biomarkers panel can provide a more detailed disease status.This study has been funded by Instituto de Salud Carlos III through the project “PI19/0593” (co-funded by European Regional Development Fund: “A way to make Europe “)

International standardisation work on the measurement of radon in air and water

Radon is considered to be the main source of human exposure to natural radiation. As stated by the World Health Organization, the exposure due to the inhalation of indoor radon is much greater than the one via the ingestion of water as radon degasses from water during handling. In response to these concerns about the universal presence of radon, environmental assessment studies are regularly commissioned to assess the radon exposure of public and workers. The credibility of such studies relies on the quality and reliability of radon analysis as well as on the sample representativeness of the radiological situation. The standard-setting approach, based on consensus, seemed to lend itself to a settlement of technical aspects of potential comparison. At present, two Working Groups of the International Standardization Organization are focussing on drafting standards on radon and its decay products measurement in air and water. These standards, which aim for a set of rigorous metrology practices, will be useful for persons in charge of the initial characterisation of a site with respect to natural radioactivity as well as to those performing the routine surveillance of specific site

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients. the DecubICUs study

Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and fac‐ tors associated with ICU‐acquired pressure injuries in adult ICU patients. Methods: International 1‐day point‐prevalence study; follow‐up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU‐acquired pressure injury and hospital mortality were assessed by generalised linear mixed‐effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU‐acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU‐acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU‐acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score < 19, ICU stay > 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower‐middle income‐economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3)

A school-based physical activity promotion intervention in children: rationale and study protocol for the PREVIENE Project

The lack of physical activity and increasing time spent in sedentary behaviours during childhood place importance on developing low cost, easy-toimplement school-based interventions to increase physical activity among children. The PREVIENE Project will evaluate the effectiveness of five innovative, simple, and feasible interventions (active commuting to/from school, active Physical Education lessons, active school recess, sleep health promotion, and an integrated program incorporating all 4 interventions) to improve physical activity, fitness, anthropometry, sleep health, academic achievement, and health-related quality of life in primary school children. The PREVIENE Project will provide the information about the effectiveness and implementation of different school-based interventions for physical activity promotion in primary school children.The PREVIENE Project was funded by the Spanish Ministry of Economy and Competitiveness (DEP2015-63988-R, MINECO-FEDER). MAG is supported by grants from the Spanish Ministry of Economy and Competitivenes

A preliminary randomized double blind placebo-controlled trial of intravenous immunoglobulin for Japanese encephalitis in Nepal

BACKGROUND: Japanese encephalitis (JE) virus (JEV) is a mosquito-borne flavivirus found across Asia that is closely related to West Nile virus. There is no known antiviral treatment for any flavivirus. Results from in vitro studies and animal models suggest intravenous immunoglobulin (IVIG) containing virus-specific neutralizing antibody may be effective in improving outcome in viral encephalitis. IVIG's anti-inflammatory properties may also be beneficial. METHODOLOGY/PRINCIPAL FINDINGS: We performed a pilot feasibility randomized double-blind placebo-controlled trial of IVIG containing anti-JEV neutralizing antibody (ImmunoRel, 400mg/kg/day for 5 days) in children with suspected JE at two sites in Nepal; we also examined the effect on serum neutralizing antibody titre and cytokine profiles. 22 children were recruited, 13 of whom had confirmed JE; 11 received IVIG and 11 placebo, with no protocol violations. One child (IVIG group) died during treatment and two (placebo) subsequently following hospital discharge. Overall, there was no difference in outcome between treatment groups at discharge or follow up. Passive transfer of anti-JEV antibody was seen in JEV negative children. JEV positive children treated with IVIG had JEV-specific neutralizing antibody titres approximately 16 times higher than those treated with placebo (p=0.2), which was more than could be explained by passive transfer alone. IL-4 and IL-6 were higher in the IVIG group. CONCLUSIONS/SIGNIFICANCE: A trial of IVIG for JE in Nepal is feasible. IVIG may augment the development of neutralizing antibodies in JEV positive patients. IVIG appears an appealing option for JE treatment that warrants further study. TRIAL REGISTRATION: ClinicalTrials.gov NCT01856205

Certified reference materials for radionuclides in Bikini Atoll sediment (IAEA-410) and Pacific Ocean sediment (IAEA-412)

The preparation and characterization of certified reference materials (CRMs) for radionuclide content in sediments collected offshore of Bikini Atoll (IAEA-410) and in the open northwest Pacific Ocean (IAEA-412) are described and the results of the certification process are presented. The certified radionuclides include: 40K, 210Pb (210Po), 226Ra, 228Ra, 228Th, 232Th, 234U, 238U, 239Pu, 239+240Pu and 241Am for IAEA-410 and 40K, 137Cs, 210Pb (210Po), 226Ra, 228Ra, 228Th, 232Th, 235U, 238U, 239Pu, 240Pu and 239+240Pu for IAEA-412. The CRMs can be used for quality assurance and quality control purposes in the analysis of radionuclides in sediments, for development and validation of analytical methods and for staff training

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study.

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat