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Background: Transfusion‐associated circulatory overload (TACO) is an often underdiagnosed pulmonary transfusion complication. A biomarker could aid with the diagnosis. To date, B‐type natriuretic peptide (BNP) and N‐terminal prohormone B‐type natriuretic peptide (NT‐proBNP) seem the most promising biomarkers in the general hospital population. The aim was to evaluate NT‐proBNP as a biomarker for TACO in a critically ill patient population and explore syndecan‐1 and cytokines as other potential biomarkers. Study Design and Methods: A retrospective study was performed using samples and clinical data collected during a prospective observational study. Adult patients admitted to the intensive care and transfused with a single red blood cell unit were included. TACO cases were retrospectively identified using a case definition based on the current TACO definition. The primary biomarker was NT‐proBNP, also we measured syndecan‐1 IL‐6, IL‐8, and IL‐10. All markers were measured directly before transfusion, 1 and 24 h after transfusion. Results: Our cohort included 64 patients, 12 of which were identified as TACO patients. TACO patients had a lower PaO2/FiO2 ratio and were more often ventilated following transfusion compared to non‐TACO patients. There was no significant difference in NT‐proBNP between pre‐ and post‐transfusion levels nor between TACO and non‐TACO patients. Syndecan‐1 was significantly elevated in TACO patients both pre‐ and post‐transfusion compared to non‐TACO patients. Discussion: NT‐proBNP was not associated with TACO in this critically ill patient population. Interestingly, levels of syndecan‐1 were increased in TACO patients at baseline. More research is needed to clarify this association and its possibilities as a biomarker to predict patients at risk for TACO. [ABSTRACT FROM AUTHOR]

Objective: Intravenous antimicrobial therapy within 1 h of the diagnosis of septic shock is recommended in international sepsis guidelines. We aimed to evaluate the association between antimicrobial timing and mortality in patients presenting to the ED with septic shock. Methods: Post‐hoc analysis of 1587 adult participants enrolled in the Australasian Resuscitation in Sepsis Evaluation (ARISE) multicentre trial of early goal‐directed therapy for whom the time of initial antimicrobial therapy was recorded. We compared participants who had initiation of antimicrobials within the first hour (early) or later (delayed) of ED presentation. A propensity score model using inverse probability of treatment weighting was constructed to account for confounding baseline covariates. The primary outcome was 90‐day mortality. Results: The median (interquartile range) time to initiating antimicrobials was 69 (39–112) min with 712 (44.9%) participants receiving the first dose within the first hour of ED presentation. Compared with delayed therapy, early administration was associated with increased baseline illness severity score and greater intensity of resuscitation pre‐randomisation (fluid volumes, vasopressors, invasive ventilation). All‐cause 90‐day mortality was also higher; 22.6% versus 15.5%; unadjusted odds ratio (OR) 1.58 (95% confidence interval [CI] 1.16–2.15), P = 0.004. After inverse probability of treatment weighting, the mortality difference was non‐significant; OR 1.30 (95% CI 0.95–1.76), P = 0.1. Live discharge rates from ICU (OR 0.81, 95% CI 0.72–0.91; P = 0.80) and hospital (OR 0.93, 95% CI 0.82–1.06; P = 0.29) were also not different between groups. Conclusion: In this post‐hoc analysis of the ARISE trial, early antimicrobial therapy was associated with increased illness severity, but 90‐day adjusted mortality was not reduced. [ABSTRACT FROM AUTHOR]

Objective: In pancreatic cancer, which is therapy resistant due to its hypoxic microenvironment, hyperthermia may enhance the effect of radio(chemo)therapy. The aim of this systematic review is to investigate the validity of the hypothesis that hyperthermia added to radiotherapy and/or chemotherapy improves treatment outcome for pancreatic cancer patients. Methods and materials: We searched MEDLINE and Embase, supplemented by handsearching, for clinical studies involving hyperthermia in pancreatic cancer patients. The quality of studies was evaluated using the Oxford Centre for Evidence-Based Medicine levels of evidence. Primary outcome was treatment efficacy; we calculated overall response rate and the weighted estimate of the population median overall survival (mp) and compared these between hyperthermia and control cohorts. Results: Overall, 14 studies were included, with 395 patients with locally advanced and/or metastatic pancreatic cancer of whom 248 received hyperthermia. Patients were treated with regional (n = 189), intraoperative (n = 39) or whole-body hyperthermia (n = 20), combined with chemotherapy, radiotherapy or both. Quality of the studies was low, with level of evidence 3 (five studies) and 4. The six studies including a control group showed a longer mp in the hyperthermia groups than in the control groups (11.7 vs. 5.6 months). Overall response rate, reported in three studies with a control group, was also better for the hyperthermia groups (43.9% vs. 35.3%). Conclusions: Hyperthermia, when added to chemotherapy and/or radiotherapy, may positively affect treatment outcome for patients with pancreatic cancer. However, the quality of the reviewed studies was limited and future randomised controlled trials are needed to establish efficacy. [ABSTRACT FROM AUTHOR]

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) targets multiple organs and causes severe coagulopathy. Histopathological organ changes might not only be attributable to a direct virus-induced effect, but also the immune response. The aims of this study were to assess the duration of viral presence, identify the extent of inflammatory response, and investigate the underlying cause of coagulopathy., Methods: This prospective autopsy cohort study was done at Amsterdam University Medical Centers (UMC), the Netherlands. With informed consent from relatives, full body autopsy was done on 21 patients with COVID-19 for whom autopsy was requested between March 9 and May 18, 2020. In addition to histopathological evaluation of organ damage, the presence of SARS-CoV-2 nucleocapsid protein and the composition of the immune infiltrate and thrombi were assessed, and all were linked to disease course., Findings: Our cohort (n=21) included 16 (76%) men, and median age was 68 years (range 41-78). Median disease course (time from onset of symptoms to death) was 22 days (range 5-44 days). In 11 patients tested for SARS-CoV-2 tropism, SARS-CoV-2 infected cells were present in multiple organs, most abundantly in the lungs, but presence in the lungs became sporadic with increased disease course. Other SARS-CoV-2-positive organs included the upper respiratory tract, heart, kidneys, and gastrointestinal tract. In histological analyses of organs (sampled from nine to 21 patients per organ), an extensive inflammatory response was present in the lungs, heart, liver, kidneys, and brain. In the brain, extensive inflammation was seen in the olfactory bulbs and medulla oblongata. Thrombi and neutrophilic plugs were present in the lungs, heart, kidneys, liver, spleen, and brain and were most frequently observed late in the disease course (15 patients with thrombi, median disease course 22 days [5-44]; ten patients with neutrophilic plugs, 21 days [5-44]). Neutrophilic plugs were observed in two forms: solely composed of neutrophils with neutrophil extracellular traps (NETs), or as aggregates of NETs and platelets.., Interpretation: In patients with lethal COVID-19, an extensive systemic inflammatory response was present, with a continued presence of neutrophils and NETs. However, SARS-CoV-2-infected cells were only sporadically present at late stages of COVID-19. This suggests a maladaptive immune response and substantiates the evidence for immunomodulation as a target in the treatment of severe COVID-19., Funding: Amsterdam UMC Corona Research Fund., (© 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license.)