The Swedish Research Council, Swedish Heart-Lung Foundation, Swedish Society for Medical Research, Strategic Research Program in Epidemiology at Karolinska Institutet, and Danish Council for Independent Research.

Aims/hypotheses Cardiovascular autonomic neuropathy is associated with increased morbidity in patients with type 1 diabetes. Although it is conventionally considered to be an organic, irreversible disorder, we previously demonstrated in patients with short-duration type 1 diabetes that reduced baroreflex sensitivity (BRS) could be corrected by slow, deep breathing, indicating a functional component to the disorder. We have now tested whether autonomic abnormalities in long-term diabetes progress to a stage that cannot be modified by functional manoeuvres, indicating a switch towards predominantly organic dysfunction. Methods We studied 117 patients with a short duration (8.9± 0.1 years) and 37 patients with a long duration (33.7± 0.5 years) of type 1 diabetes, 73 healthy controls and 12 hearttransplanted participants (surgical heart denervation). An autonomic score was calculated from autonomic function tests. Spectral analysis of heart rate and blood pressure variability, and BRS, were obtained from recordings during normal (15 breaths per min) and slow, deep (six breaths per min) controlled breathing. Results BRS was reduced in all patients, but more in patients with a long duration of diabetes or with increasing autonomic involvement, although the effect of duration disappeared after adjustment for age. Slow breathing increased the BRS to the level of the control participants at a normal rate of breathing (15 per min) in all patients except those with an abnormal autonomic score. Conclusions/interpretation Patients with type 1 diabetes have a blunted BRS that in the majority of patients can be restored by slow breathing, irrespective of disease duration. Even after a long duration of diabetes, the abnormal BRS is at least in part of functional origin.

Aims Left ventricular (LV) dysfunction can be triggered by non‐cardiac disease, such as sepsis, hypoxia, major haemorrhage, or severe stress (Takotsubo syndrome), but its clinical importance is not established. In this study, we evaluate the incidence and impact on mortality of LV dysfunction associated with critical illness. Methods and results In this single‐centre, observational study, consecutive patients underwent an echocardiographic examination within 24 h of intensive care unit (ICU) admission. LV systolic dysfunction was defined as an ejection fraction (EF) < 50% and/or regional wall motion abnormalities (RWMA). A cardiologist assessed patients with LV dysfunction for the presence of an acute or chronic cardiac disease, and coronary angiography was performed in high‐risk patients. Of the 411 patients included, 100 patients (24%) had LV dysfunction and in 52 (13%) of these patients, LV dysfunction was not attributed to a cardiac disease. Patients with LV dysfunction and non‐cardiac disease had higher mortality risk score (Simplified Acute Physiologic Score 3 score), heart rate, noradrenaline doses, and lactate levels as well as decreased EF, stroke volume, and cardiac output compared with patients with normal LV function. Diagnoses most commonly associated with LV dysfunction and non‐cardiac disease were sepsis, respiratory insufficiency, major haemorrhage, and neurological disorders. RWMA (n = 40) with or without low EF was more common than global hypokinesia (n = 12) and was reversible in the majority of cases. Twelve patients had a circumferential pattern of RWMA in concordance with Takotsubo syndrome. Crude 30 day mortality was higher in patients with LV dysfunction and non‐cardiac disease compared with patients with normal LV function (33% vs. 18%, P = 0.023), but not after risk adjustment (primary outcome) {odds ratio [OR] 1.56 [confidence interval (CI) 0.75–3.39], P = 0.225}. At 90 days, crude mortality was 44% and 22% (P = 0.002), respectively, in these groups. This difference was also significant after risk adjustment [OR 2.40 (CI 1.18–4.88), P = 0.016]. Conclusions Left ventricular systolic dysfunction is commonly triggered by critical illness, is frequently seen as regional hypokinesia, and is linked to an increased risk of death. The prognostic importance of LV dysfunction in critical illness might be underestimated.

Background:The prevalence and importance of cardiac dysfunction in critically ill patients with COVID-19 in Sweden is not yet established. The aim of the study was to assess the prevalence of cardiac dysfunction and elevated pulmonary artery pressure (PAP), and its influence on mortality in patients with COVID-19 in intensive care in Sweden. Methods:This was a multicentre observational study performed in five intensive care units (ICUs) in Sweden. Patients admitted to participating ICU with COVID-19 were examined with echocardiography within 72 h from admission and again after 4 to 7 days. Cardiac dysfunction was defined as left ventricular (LV) dysfunction (ejection fraction <50% and/or regional hypokinesia) or right ventricular (RV) dysfunction (defined as TAPSE <17 mm or visually assessed moderate/severe RV dysfunction). Results:We included 132 patients, of whom 127 (96%) were intubated. Cardiac dysfunction was found in 42 (32%) patients. Most patients had cardiac dysfunction at the first assessment (n = 35) while a few developed cardiac dysfunction later (n = 7) and some changed type of dysfunction (n = 3). LV dysfunction was found in 21 and | 607 HOLMQVIST eT aL.

BACKGROUND Creutzfeldt‐Jakob disease (CJD) is an uncommon, invariably fatal, neurodegenerative disorder that presents as progressive dementia with concurrent motor symptoms and myoclonia. The pathophysiology involves prion protein misfolding and spreading in a self‐catalyzed manner. It has been shown to be transmissible through tissue transplants. Variant CJD (vCJD), a subtype of the disease is also transmissible through transfusion of blood products. This study aims to corroborate the scarce data that suggest that sporadic CJD (sCJD) is not transmitted via blood transfusion. METHODS AND STUDY DESIGN A retrospective cohort study was performed, using data from the bi‐national Scandinavian Donations and Transfusions (SCANDAT2) database containing data on blood donors, donations, transfusions, and transfused patients in Sweden and Denmark since 1968 and 1982, respectively. Mortality and medical data were collected from nationwide health care and population registries. Donors with subsequent CJD were identified, as well as recipients of blood products from these donors. A second analysis was performed, screening for clustering of CJD cases from donors without a CJD diagnosis. RESULTS We identified 39 donors with a subsequent diagnosis of sCJD. No cases of CJD occurred among the 883 recipients of blood products from these donors. A total of 89 CJD cases were identified among recipients of transfusions. No clustering of cases from the same donor occurred. DISCUSSION Using data from a large, bi‐national database of transfused patients, we find no evidence of sCJD transmission. Our data adds to the growing body of evidence indicating that sCJD is not transfusion transmitted.

Background Intensive care unit (ICU) patients are transfused with blood products for a number of reasons, from massive ongoing hemorrhage, to mild anemia following blood sampling, combined with bone marrow depression due to critical illness. There's a paucity of data on transfusions in ICUs and most studies are based on audits or surveys. The aim of this study was to provide a complete picture of ICU‐related transfusions in Sweden. Methods We conducted a register based retrospective cohort study with data on all adult patient admissions from 82 of 84 Swedish ICUs between 2010 and 2018, as recorded in the Swedish Intensive Care Register. Transfusions were obtained from the SCANDAT‐3 database. Descriptive statistics were computed, characterizing transfused and nontransfused patients. The distribution of blood use comparing different ICUs was investigated by computing the observed proportion of ICU stays with a transfusion, as well as the expected proportion. Results In 330,938 ICU episodes analyzed, at least one transfusion was administered for 106,062 (32%). For both red‐cell units and plasma, the fraction of patients who were transfused decreased during the study period from 31.3% in 2010 to 24.6% in 2018 for red‐cells, and from 16.6% in 2010 to 9.4% in 2018 for plasma. After adjusting for a range of factors, substantial variation in transfusion frequency remained, especially for plasma units. Conclusion Despite continuous decreases in utilization, transfusions remain common among Swedish ICU patients. There is considerable unexplained variation in transfusion rates. More research is needed to establish stronger critiera for when to transfuse ICU patients.

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Introduction: The importance of cardiac dysfunction in critically ill patients with COVID-19 is not well studied. The aim of the study was to assess the incidence, clinical risk factors, and prognosis of cardiac dysfunction in critical illness caused by COVID-19, and to evaluate if cardiac biomarkers can detect this condition.Methods: This was a multicentre observational study performed in five intensive care units (ICUs) in Sweden. Patients admitted to participating ICU with COVID-19 were examined with echocardiography within 72 hours from admission to the ICU and again after four to seven days. Cardiac biomarkers and clinical data were collected at the time of echocardiography. Cardiac dysfunction was defined as either left ventricular (LV) dysfunction (having an ejection fraction < 50% and/or regional hypokinesia) or right ventricular (RV) dysfunction (having a tricuspid annular plane systolic excursion (TAPSE) < 17mm or a moderate/severe RV dysfunction assessed visually).Results: We included 132 patients of whom 94 (71%) were included prospectively. The vast majority were intubated (n=127). At the time of admission to ICU, 35 (27%) patients had cardiac dysfunction and 7 patients (5%) had cardiac dysfunction detected later in the ICU-period. LV dysfunction was found in 18 patients and RV dysfunction in 17 patients, 7 patients had both RV and LV dysfunction. Noradrenaline > 0.20µg/kg/min was the only clinical variable associated with a higher risk of cardiac dysfunction. RV dysfunction was associated with an increased risk of death in a risk-adjusted model (OR 3.98, p = 0.013). Troponin and N-terminal pro b-type natriuretic peptide (NTproBNP) had moderate values in detecting cardiac dysfunction (AUC 0.729 and AUC 0.744, respectively). A combination of troponin < 1.44 times the upper reference limit and NTproBNP < 857ng/L had 85% probability of excluding cardiac dysfunction.Conclusions: Cardiac dysfunction is common in critically ill patients with COVID-19. Although not easily detected with clinical variables, cardiac biomarkers might be helpful. RV dysfunction is associated with an increased risk of death, these patients might benefit from further investigation or treatments. Trial registration: Registered on 24 Aug 2020 at Clinicaltrials.gov; registration number NCT04524234.