Svećenik Rudolf Mikec, mučenik za vjeru otaca : (jedno novigradsko sjećanje)

Background New-onset atrial fibrillation (AF) is the most common arrhythmia in critically ill patients. Although evidence base and expert consensus opinion for management have been summarised in several international guidelines, no specific considerations for critically ill patients have been included. We aimed to establish current practice of management of critically ill patients with new-onset AF. Methods We designed a short user-friendly online questionnaire. All members of the Intensive Care Society were invited via email containing a link to the questionnaire, which comprised 21 questions. The online survey was conducted between November 2016 and December 2016. Results The response rate was 397/3152 (12.6%). The majority of respondents (81.1%) worked in mixed Intensive Care Units and were consultants (71.8%). Most respondents (39.5%) would start intervention on patients with fast new-onset AF and stable blood pressure at a heart rate between 120 and 139 beats/min. However, 34.8% of participants would treat all patients who developed new-onset fast AF. Amiodarone and beta-blockers (80.9% and 11.6% of answers) were the most commonly used anti-arrhythmics. A total of 63.8% of respondents do not regularly anti-coagulate critically ill patients with new-onset fast AF, while 30.8% anti-coagulate within 72 hours. A total of 68.0% of survey respondents do not routinely use stroke risk scores in critically ill patients with new-onset AF. A total of 85.4% of participants would consider taking part in a clinical trial investigating treatment of new-onset fast AF in the critically ill. Discussion Our results suggest a considerable disparity between contemporary practice of management of new-onset AF in critical illness and treatment recommendations for the general patient population suffering from AF, particularly with regard to anti-arrhythmics and anti-coagulation used. Amongst intensivists, there is a substantial interest in research for management of new-onset AF in critically ill patients

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Identification of Morphine-6-glucuronide in Chromaffin Cell Secretory Granules

We report for the first time that morphine-6-glucuronide, a highly analgesic morphine-derived molecule, is present in adrenal chromaffin granules and secreted from chromaffin cells upon stimulation. We also demonstrate that phosphatidylethanolamine-binding protein (alternatively named Raf-1 kinase inhibitor protein or RKIP) acts as an endogenous morphine-6-glucuronide-binding protein. An UDP-glucuronosyltransferase 2B-like enzyme, described to transform morphine into morphine-6-glucuronide, has been immunodetected in the chromaffin granule matrix, and morphine-6-glucuronide de novo synthesis has been characterized, demonstrating the possible involvement of intragranular UDP-glucuronosyltransferase 2B-like enzyme in morphine-6-glucuronide metabolism. Once secreted into the circulation, morphine-6-glucuronide may mediate several systemic actions (e.g. on immune cells) based on its affinity for µ-opioid receptors. These activities could be facilitated by phosphatidylethanolamine-binding protein (PEBP), acting as a molecular shield and preventing morphine-6-glucuronide from rapid clearance. Taken together, our data represent an important observation on the role of morphine-6-glucuronide as a new endocrine factor