冰岛国家大学医院

BACKGROUND:Intraoperative hypotension is a common occurrence in patients undergoing anaesthesia, although there is no standardised definition of hypotension. International consensus statements provide some guidelines for the management of intraoperative hypotension, but general clinical practice is unknown. We aimed to survey anaesthesiologists' values and preferences regarding intraoperative blood pressure management, including whether they would support future research on this topic. METHODS:We conducted an international, online survey of routine practice and opinion. The target population was anaesthesiologists who regularly anaesthetise adult patients. Results are reported descriptively and in accordance with the Consensus-Based Checklist for Reporting of Survey Studies (CROSS) checklist. RESULTS:A total of 1640 anaesthesiologists from 11 European countries participated in the survey. The majority of respondents were specialists (1322 of 1640, 80.6%, 95% CI 78.7-82.6). Almost all respondents worked in public hospitals (1613 of 1640, 98.4%). The overall response rate was 22.7%. Most respondents reported using absolute mean arterial pressure as their main unit of measurement to quantify hypotension (1098 of 1640, 67.0%, 95% CI 64.6-69.2). Respondents were most likely to initiate vasoactive treatment at a mean arterial pressure below 60 or 65 mmHg. Chronic arterial hypertension, traumatic brain injury and surgical procedures involving head-up positioning of the patient were the three most common scenarios where respondents would raise their threshold for treatment. Most respondents considered the establishment of safe intraoperative blood pressure thresholds a critical research question, and almost all respondents (1509 of 1640, 92.0%) indicated a willingness to randomise patients to specific blood pressure targets. For 72.9% (1196 of 1640), the lowest acceptable mean arterial pressure for randomisation was 60 mmHg. Respondents were also interested in the comparison of efficacy and safety of vasoactive agents, and the most sought-after comparison was phenylephrine versus noradrenaline (1252 of 1640, 76.3%). The willingness of respondents to administer these agents in peripheral venous access differed according to geography. CONCLUSION:In this international survey, mean arterial pressures of 60 or 65 mmHg were the most commonly reported blood pressure thresholds leading to initiation of treatment with vasoactive agents. Almost all respondents indicated patient groups for whom they would alter their treatment threshold, namely those suffering from chronic arterial hypertension, those undergoing surgery in a head-up position, and patients with traumatic brain injury. The majority of respondents supported future trials establishing optimal mean arterial pressure threshold and choice of vasoactive agent. We noticed a geographical variation in willingness to administer vasoactive agents in peripheral venous access. EDITORIAL COMMENT:This survey of anaesthesiologists from European countries queried practitioner perceptions of blood pressure management in adults during anaesthesia with focus on hypotension. Queries and responses also concerned circumstances and blood pressure levels which clinicians report being willing to treat actively, and how they might do this practically.

Hereditary cystatin C amyloid angiopathy (HCCAA) is a familial form of cerebral amyloid angiopathy (CAA), a progressive disease that causes recurrent, often severe intracerebral hemorrhages and premature death in young adults. It is caused by a mutation in the CST3 gene that results in production of an aggregation-prone cystatin C protein. Basement membrane (BM) remodeling is implicated in the disease in both cerebral vessels and the skin. Here, we examined relationships between BM remodeling, vascular cellular alterations, signaling-associated markers, and cystatin C aggregation in HCCAA brain tissue using immunohistochemical analyses of cystatin C, α-smooth muscle actin (α-SMA), vimentin, collagen IV (COL IV), fibronectin 1 (FN1), SMAD2/3, phosphorylated SMAD2/3 (pSMAD2/3), and WNT-1. BM remodeling was prominent, COL IV and FN1 immunoreactivity was markedly increased, consistent with BM thickening, with FN1 immunoreactivity 71

BackgroundIn pediatric intensive care units, pain, sedation, delirium, and iatrogenic withdrawal syndrome (IWS) must be managed as interrelated conditions. Although clinical practice guidelines (CPGs) exist, new evidence needs to be incorporated, gaps in recommendations addressed, and recommendations adapted to the European context. ObjectiveThis protocol describes the development of the first patient- and family-informed European guideline for managing pain, sedation, delirium, and IWS by the European Society of Paediatric and Neonatal Intensive Care. MethodsThis guideline will follow the Grading of Recommendations Assessment, Development, and Evaluation ADOLOPMENT approach across seven phases: (1) setup—establish 3 groups, namely a steering committee, development panel (experts and patient and family partners), and patient and family partner advisory panel, to define guideline scope through voting and consensus; (2) preparation—vote on 30 summary recommendations compiled from existing CPGs of medium quality or above; prioritize new research questions; update the search for CPGs to match new research questions with recommendations using population, intervention, comparator, and outcome elements; prioritize outcomes for effectiveness questions using a 9-point Likert scale; with validation from patient and family partners; (3) evidence identification, analysis, and data extraction—develop individualized search strategies for each research question (2 independent appraisers will select and appraise studies and conduct data extraction); (4) evidence synthesis—expert pairs will summarize findings in evidence profiles and evidence-to-decision (EtD) frameworks (in the absence of evidence, the expert panel will be surveyed to assess current practices); (5) guideline development—expert pairs will draft recommendations, then topic-specific subgroups will reach consensus before full development panel voting (>80% approval needed; subgroups will determine the need for additional supporting content); (6) review—conduct internal, society-level, and external international expert reviews using surveys with Likert scales and open-ended comments; and (7) issue and update—publish the guideline and monitor literature to assess the need for updates before 5 years. ResultsIn phase 1, a total of 21 clinical experts and 17 patient and family partners were recruited, and the guideline scope was finalized with 80% to 100% agreement. In phase 2, a total of 23 summary recommendations and 17 new research questions (total=40) were selected. The updated CPG search identified 2 low-quality CPGs, which were excluded from recommendation matching. Of the 17 new research questions, 4 matched existing recommendations. Of the 3 effectiveness questions, one had 7 prioritized outcomes, whereas two had 9 outcomes for inclusion in EtD frameworks. The final CPG is expected by spring 2026, with search strategies, EtD frameworks, and recommendations included. ConclusionsThis protocol ensures a transparent Grading of Recommendations Assessment, Development, and Evaluation–based development process, leading to a trustworthy and credible guideline tailored to the European context for managing pain, sedation, delirium, and IWS in children who are critically ill. International Registered Report Identifier (IRRID)DERR1-10.2196/67930

Most clinical laboratories measure total magnesium (tMg) which includes both the ionized (iMg) and bound forms. Only the ionized component is biologically active, and it may be influenced by acid-base status, plasma protein concentrations and electrolyte disturbances, potentially altering how well tMg reflects iMg. This multicenter observational study evaluated the relationship between tMg and iMg using paired samples collected within a 2-hour window. Association was assessed with linear regression and Pearson's correlation coefficient, and agreement with Bland-Altman analysis. Ionized magnesium constituted 77.9% of tMg (95% CI 77.5%-78.4%). There was a strong correlation between iMg and tMg (r = 0.916, p < 0.0001). Bland-Altman analysis showed that tMg was, on average, 0.20 mmol/L higher than iMg (95% LoA 0.03-0.37 mmol/L). Proportional bias was observed (slope = 0.22, p < 0.001), with increasing discrepancies at higher concentrations. Stepwise multiple linear regression analysis including acid-base parameters, albumin and electrolytes, was used to identify variables independently associated with ionized and total magnesium concentrations. In this multivariable model, pH and ionized calcium were independently associated with both ionized and total magnesium. In conclusion, ionized and total magnesium were strongly correlated. However, proportional bias indicated that total magnesium increasingly deviates from the biologically active ionized fraction at higher concentrations. Therefore, derived equations to estimate one measure from the other are not reliable for clinical use.

OBJECTIVES:Occupational exposures may contribute to the development of COPD, a leading cause of morbidity and mortality globally. Using an exposome approach in a follow-up design, we aimed to examine the association between the occupational exposome and new-onset COPD in 2 population-based cohorts: the European Community Respiratory Health Survey (ECRHS) with 2 follow-ups (n = 4,087; observations = 6,224) and the CONSTANCES cohort with 1 follow-up (n = 8,255). METHODS:COPD was defined by respiratory symptom(s) and forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC) below the lower limit of normal. Occupational exposures were assessed through long-term job histories linked to 6 job exposure matrices representing 49 different chemical, ergonomic, and physical exposures. Cumulative occupational exposures until baseline were assigned to each participant. Three analytical approaches were used: Exposome-Wide Association Study (ExWAS), Least Absolute Shrinkage and Selection Operator (LASSO), and Boruta Random Forest. RESULTS:In ECRHS, across the 3 analytical approaches, the most important exposures associated with increased COPD were heavy lifting, forward-bent posture, gases and fumes, mineral dust, house dust mites, and kneeling/squatting. In CONSTANCES, the most important exposures were diesel exhaust fumes, respirable crystalline silica, other solvents, organic solvents, indoor cleaning, and mineral dust. Differences in follow-up time and cohort characteristics may explain cohort discrepancies. CONCLUSION:We confirmed the importance of several chemical occupational exposures for COPD and observed new associations between ergonomic and physical occupational exposures and COPD. These associations more likely reflect broader occupational exposure patterns than independent effects and should be interpreted in that context. Despite complexities in interpretation, the results underline the importance of implementing new analytical approaches, as it provide opportunities to identify the interplay of occupational exposures in an occupational exposome context.