Publications by authors named "Alexander P J Vlaar"

118 Publications

Targeted Temperature Management in Out-of-Hospital Cardiac Arrest With Shockable Rhythm: A Post Hoc Analysis of the Coronary Angiography After Cardiac Arrest Trial.

Crit Care Med 2021 Sep 22. Epub 2021 Sep 22.

Department of Cardiology, Amsterdam University Medical Center, location VUmc, Amsterdam, The Netherlands. Department of Cardiology, Erasmus Medical Center, Rotterdam, The Netherlands. Department of Intensive Care Medicine, Erasmus Medical Center, Rotterdam, The Netherlands. Department of Cardiology, Amphia Hospital, Breda, The Netherlands. Department of Intensive Care Medicine, Amphia Hospital, Breda, The Netherlands. Department of Cardiology, Rijnstate Hospital, Arnhem, The Netherlands. Department of Intensive Care Medicine, Rijnstate Hospital, Arnhem, The Netherlands. Department of Cardiology, HAGA Hospital, Den Haag, The Netherlands. Department of Intensive Care Medicine, HAGA Hospital, Den Haag, The Netherlands. Department of Cardiology, Maasstad Hospital, Rotterdam, The Netherlands. Department of Cardiology, University Medical Centre Utrecht, Utrecht, The Netherlands. Department of Intensive Care Medicine, Maasstad Hospital, Rotterdam, The Netherlands. Department of Intensive Care Medicine, Amsterdam University Medical Center, location VUmc, Amsterdam, The Netherlands. Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands. Department of Intensive Care Medicine, Maastricht University Medical Center, University Maastricht, Maastricht, The Netherlands. Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht, The Netherlands. Department of Intensive Care Medicine, Medisch Spectrum Twente, Enschede, The Netherlands. Department of Cardiology, Medisch Spectrum Twente, Enschede, The Netherlands. Department of Cardiology, Radboud University Medical Center, Nijmegen, The Netherlands. Department of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, The Netherlands. Department of Cardiology, Amsterdam University Medical Center, location AMC, Amsterdam, The Netherlands. Department of Intensive Care Medicine, Amsterdam University Medical Center, location AMC, Amsterdam, The Netherlands. Department of Cardiology, OLVG, Amsterdam, The Netherlands. Department of Intensive Care Medicine, OLVG, Amsterdam, The Netherlands. Department of Cardiology, Noord West Ziekenhuisgroep, Alkmaar, The Netherlands. Department of Intensive Care Medicine, Noord West Ziekenhuisgroep, Alkmaar, The Netherlands. Department of Cardiology, Maastricht University Medical Center, Maastricht, The Netherlands. Department of Cardiology, Scheper Hospital, Emmen, The Netherlands. Department of Cardiology, Haaglanden Medical Center, Den Haag, The Netherlands. Department of Cardiology, Isala Hospital, Zwolle, The Netherlands. Department of Cardiology, Tergooi Hospital, Blaricum, The Netherlands. Department of Cardiology, Elisabeth-Tweesteden Hospital, Tilburg, The Netherlands. Department of Epidemiology and Data Science, Amsterdam University Medical Center, location VUmc, Amsterdam, The Netherlands.

Objectives: The optimal targeted temperature in patients with shockable rhythm is unclear, and current guidelines recommend targeted temperature management with a correspondingly wide range between 32°C and 36°C. Our aim was to study survival and neurologic outcome associated with targeted temperature management strategy in postarrest patients with initial shockable rhythm.

Design: Observational substudy of the Coronary Angiography after Cardiac Arrest without ST-segment Elevation trial.

Setting: Nineteen hospitals in The Netherlands.

Patients: The Coronary Angiography after Cardiac Arrest trial randomized successfully resuscitated patients with shockable rhythm and absence of ST-segment elevation to a strategy of immediate or delayed coronary angiography. In this substudy, 459 patients treated with mild therapeutic hypothermia (32.0-34.0°C) or targeted normothermia (36.0-37.0°C) were included. Allocation to targeted temperature management strategy was at the discretion of the physician.

Interventions: None.

Measurements And Main Results: After 90 days, 171 patients (63.6%) in the mild therapeutic hypothermia group and 129 (67.9%) in the targeted normothermia group were alive (hazard ratio, 0.86 [95% CI, 0.62-1.18]; log-rank p = 0.35; adjusted odds ratio, 0.89; 95% CI, 0.45-1.72). Patients in the mild therapeutic hypothermia group had longer ICU stay (4 d [3-7 d] vs 3 d [2-5 d]; ratio of geometric means, 1.32; 95% CI, 1.15-1.51), lower blood pressures, higher lactate levels, and increased need for inotropic support. Cerebral Performance Category scores at ICU discharge and 90-day follow-up and patient-reported Mental and Physical Health Scores at 1 year were similar in the two groups.

Conclusions: In the context of out-of-hospital cardiac arrest with shockable rhythm and no ST-elevation, treatment with mild therapeutic hypothermia was not associated with improved 90-day survival compared with targeted normothermia. Neurologic outcomes at 90 days as well as patient-reported Mental and Physical Health Scores at 1 year did not differ between the groups.
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http://dx.doi.org/10.1097/CCM.0000000000005271DOI Listing
September 2021

The recipe for TACO: A narrative review on the pathophysiology and potential mitigation strategies of transfusion-associated circulatory overload.

Blood Rev 2021 Oct 2:100891. Epub 2021 Oct 2.

Department of Intensive Care, University of Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands; Laboratory for Experimental Intensive Care and Anesthesiology (L.E.I.C.A.), University of Amsterdam, Amsterdam UMC, the Netherlands. Electronic address:

Transfusion associated circulatory overload (TACO) is one of the leading causes of transfusion related morbidity and mortality. TACO is the result of hydrostatic pulmonary edema following transfusion. However, up to 50% of all TACO cases appear after transfusion of a single unit, suggesting other factors, aside from volume, play a role in its pathophysiology. TACO follows a two-hit model, in which the first hit is an existing disease or comorbidity that renders patients volume incompliant, and the second hit is the transfusion. First hit factors include, amongst others, cardiac and renal failure. Blood product factors, setting TACO apart from crystalloid overload, include colloid osmotic pressure effects, viscosity, pro-inflammatory mediators and storage lesion byproducts. Differing hemodynamic changes, glycocalyx injury, endothelial damage and inflammatory reactions can all contribute to developing TACO. This narrative review explores pathophysiological mechanisms for TACO, discusses related therapeutic and preventative measures, and identifies areas of interest for future research.
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http://dx.doi.org/10.1016/j.blre.2021.100891DOI Listing
October 2021

Perioperative Care Standards in Cardiac Surgery Patients Aiming at Enhancing Recovery: A Nationwide Survey in the Netherlands and Belgium.

J Cardiothorac Vasc Anesth 2021 Sep 5. Epub 2021 Sep 5.

Department of Anesthesiology, Amsterdam University Medical Center (UMC), Location AMC, the Netherlands.

Objective: The aim of this survey was to describe existing perioperative care standards and best practices in the Netherlands and Belgium.

Design: An online survey was followed up by an in-depth personal interview. The main outcomes were the existing standards of perioperative care for patients undergoing cardiac surgery.

Setting: The online survey and subsequent interviews were targeted to one representative in the intensive care unit (ICU), cardiac surgery, and anesthesiology department from each cardiac surgical center in the Netherlands and Belgium.

Participants: A representative intensive care physician, cardiac surgeon, and cardiac anesthesiologist.

Interventions: None.

Measurements And Main Results: The response rate was 60% (71% for the Netherlands, and 44% in Belgium). Agreement across centers was found for discontinuation of proton-pump inhibitors (80%) and avoiding intra- and postoperative (92%) nonsteroidal antiinflammatory drugs. Additionally, 98% of respondents stated that physiotherapy should be started immediately in the ICU. Major divergence was found for elements such as the discontinuation of angiotensin-converting enzyme inhibitors (55%) or the postoperative use of chest support vests (44%).

Conclusions: The authors demonstrated a wide range of different local protocols. Strategies differed among disciplines, hospitals, and countries. This emphasized the need for the implementation of a more universal protocol to further reduce variance and improve recovery practices. This nationwide survey was the first of its kind simultaneously studying best practices for cardiac surgery through the entire care pathway at the advent of Enhanced Recovery After Surgery (ERAS) Cardiac implementation. A multinational randomized controlled trial to test the implementation of an evidence-based ERAS Cardiac protocol is the next step to pave the way for further outcome improvements in this high-risk population.
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http://dx.doi.org/10.1053/j.jvca.2021.08.106DOI Listing
September 2021

Time since SARS-CoV-2 infection and humoral immune response following BNT162b2 mRNA vaccination.

EBioMedicine 2021 Sep 24;72:103589. Epub 2021 Sep 24.

Department of Internal Medicine, Amsterdam UMC, Amsterdam Institute for Infection and Immunity, Vrije Universiteit Amsterdam, De Boelelaan 1117, Amsterdam 1081 HV, the Netherlands. Electronic address:

Background: To optimise the use of available SARS-CoV-2 vaccines, some advocate delaying second vaccination for individuals infected within six months. We studied whether post-vaccination immune response is equally potent in individuals infected over six months prior to vaccination.

Methods: We tested serum IgG binding to SARS-CoV-2 spike protein and neutralising capacity in 110 healthcare workers, before and after both BNT162b2 messenger RNA (mRNA) vaccinations. We compared outcomes between participants with more recent infection (n = 18, median two months, IQR 2-3), with infection-vaccination interval over six months (n = 19, median nine months, IQR 9-10), and to those not previously infected (n = 73).

Findings: Both recently and earlier infected participants showed comparable humoral immune responses after a single mRNA vaccination, while exceeding those of previously uninfected persons after two vaccinations with 2.5 fold (p = 0.003) and 3.4 fold (p < 0.001) for binding antibody levels, and 6.4 and 7.2 fold for neutralisation titres, respectively (both p < 0.001). The second vaccine dose yielded no further substantial improvement of the humoral response in the previously infected participants (0.97 fold, p = 0.92), while it was associated with a 4 fold increase in antibody binding levels and 18 fold increase in neutralisation titres in previously uninfected participants (both p < 0.001). Adjustment for potential confounding of sex and age did not affect these findings.

Interpretation: Delaying the second vaccination in individuals infected up to ten months prior may constitute a more efficient use of limited vaccine supplies.

Funding: Netherlands Organization for Health Research and Development ZonMw; Corona Research Fund Amsterdam UMC; Bill & Melinda Gates Foundation.
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http://dx.doi.org/10.1016/j.ebiom.2021.103589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8461365PMC
September 2021

Ipsilateral and contralateral validation of continuous noninvasive finger blood pressure: does side matter?

Br J Anaesth 2021 Nov 15;127(5):e149-e151. Epub 2021 Sep 15.

Department of Anaesthesiology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.

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http://dx.doi.org/10.1016/j.bja.2021.07.032DOI Listing
November 2021

Sex steroid hormones are associated with mortality in COVID-19 patients: Level of sex hormones in severe COVID-19.

Medicine (Baltimore) 2021 Aug;100(34):e27072

Amsterdam UMC, University of Amsterdam, Department of Neurology, Amsterdam Neuroscience, Meibergdreef 9, Amsterdam, the Netherlands.

Abstract: In patients with coronavirus disease 2019 (COVID-19), men are more severely affected than women. Multiple studies suggest that androgens might play a role in this difference in disease severity. Our objective was to assess the association between sex hormone levels and mortality in patients with severe COVID-19.We selected patients from the Amsterdam University Medical Centers COVID-19 Biobank, in which patients admitted to hospital in March and April 2020, with reverse transcription-polymerase chain reaction proven severe acute respiratory syndrome-coronavirus-2 infection, were prospectively included. Specifically, we included postmenopausal women (>55 years) and age-matched men, with a mortality of 50% in each group. Residual plasma samples were used to measure testosterone, estradiol, sex hormone binding globulin (SHBG), and albumin. We investigated the association of the levels of these hormones with mortality in men and women.We included 16 women and 24 men in March and April 2020 of whom 7 (44%) and 13 (54%), respectively, died. Median age was 69 years (interquartile range [IQR] 64-75). In men, both total and free testosterone was significantly lower in deceased patients (median testosterone 0.8 nmol/L [IQR 0.4-1.9] in deceased patients vs 3.2 nmol/L [IQR 2.1-7.5] in survivors; P < .001, and median free testosterone 33.2 pmol/L [IQR 15.3-52.2] in deceased patients vs 90.3 pmol/L [IQR 49.1-209.7] in survivors; P = .002). SHBG levels were significantly lower in both men and women who died (18.5 nmol/L [IQR 11.3-24.3] in deceased patients vs 34.0 nmol/L [IQR 25.0-48.0] in survivors; P < .001). No difference in estradiol levels was found between deceased and surviving patients.Low SHBG levels were associated with mortality rate in patients with COVID-19, and low total and free testosterone levels were associated with mortality in men. The role of testosterone and SHBG and potential of hormone replacement therapy needs further exploration in COVID-19.
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http://dx.doi.org/10.1097/MD.0000000000027072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389969PMC
August 2021

Differential effects of speed and volume on transfusion-associated circulatory overload: A randomized study in rats.

Vox Sang 2021 Aug 15. Epub 2021 Aug 15.

Department of Intensive Care, Amsterdam UMC, Amsterdam, The Netherlands.

Background And Objectives: Transfusion-associated circulatory overload (TACO) is the primary cause of transfusion-related mortality. Speed and volume of transfusion are major risk factors. The aim of this study was to investigate the interaction of red blood cell (RBC) transfusion speed and volume on the development of TACO.

Materials And Methods: A validated model for TACO in anaemic Lewis rats with an acute myocardial infarction was used. The effect on pulmonary hydrostatic pressure of one, two or four units of packed RBCs transfused in either 30 or 60 min was evaluated (3.3-26.6 ml·kg ·hr ). Pulmonary capillary pressure was measured as left ventricular end-diastolic pressure (LVEDP). Cardiac stress biomarkers atrial natriuretic-peptide (ANP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured 1-h post-transfusion.

Results: Thirty animals were included (n = 5 per group). Transfusion of RBCs increased LVEDP in a volume-dependent manner (ΔLVEDP [mmHg]: -0.95, +0.50, +6.26, p < 0.001). Fast transfusion increased overall ΔLVEDP by +3.5 mmHg and up to +11.8 mmHg in the four units' group (p = 0.016). Doubling transfusion speed increased ΔLVEDP more than doubling volume in the larger volume groups. No difference in ANP or NT-proBNP were seen in high transfusion volume or groups.

Conclusion: Transfusion volume dose-dependently increased LVEDP, with speed of transfusion rapidly elevating LVEDP at higher transfusion volumes. ANP and NT-proBNP were not impacted by transfusion volume or speed in this model. TACO is seen as purely volume overload, however, this study emphasizes that limiting transfusion speed, as a modifiable risk factor, might aid in preventing TACO.
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http://dx.doi.org/10.1111/vox.13191DOI Listing
August 2021

Assessment of Lung Reaeration at 2 Levels of Positive End-expiratory Pressure in Patients With Early and Late COVID-19-related Acute Respiratory Distress Syndrome.

J Thorac Imaging 2021 Sep;36(5):286-293

Departments of Intensive Care.

Purpose: Patients with novel coronavirus disease (COVID-19) frequently develop acute respiratory distress syndrome (ARDS) and need invasive ventilation. The potential to reaerate consolidated lung tissue in COVID-19-related ARDS is heavily debated. This study assessed the potential to reaerate lung consolidations in patients with COVID-19-related ARDS under invasive ventilation.

Materials And Methods: This was a retrospective analysis of patients with COVID-19-related ARDS who underwent chest computed tomography (CT) at low positive end-expiratory pressure (PEEP) and after a recruitment maneuver at high PEEP of 20 cm H2O. Lung reaeration, volume, and weight were calculated using both CT scans. CT scans were performed after intubation and start of ventilation (early CT), or after several days of intensive care unit admission (late CT).

Results: Twenty-eight patients were analyzed. The median percentages of reaerated and nonaerated lung tissue were 19% [interquartile range, IQR: 10 to 33] and 11% [IQR: 4 to 15] for patients with early and late CT scans, respectively (P=0.049). End-expiratory lung volume showed a median increase of 663 mL [IQR: 483 to 865] and 574 mL [IQR: 292 to 670] after recruitment for patients with early and late CT scans, respectively (P=0.43). The median decrease in lung weight attributed to nonaerated lung tissue was 229 g [IQR: 165 to 376] and 171 g [IQR: 81 to 229] after recruitment for patients with early and late CT scans, respectively (P=0.16).

Conclusions: The majority of patients with COVID-19-related ARDS undergoing invasive ventilation had substantial reaeration of lung consolidations after recruitment and ventilation at high PEEP. Higher PEEP can be considered in patients with reaerated lung consolidations when accompanied by improvement in compliance and gas exchange.
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http://dx.doi.org/10.1097/RTI.0000000000000600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386391PMC
September 2021

Survival of patients with acute pulmonary embolism treated with venoarterial extracorporeal membrane oxygenation: A systematic review and meta-analysis.

J Crit Care 2021 08 24;64:245-254. Epub 2021 Mar 24.

Department of Intensive Care Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands. Electronic address:

Background: To examine whether venoarterial extracorporeal membrane oxygenation (VA-ECMO) improves survival of patients with acute pulmonary embolism (PE).

Methods: Following the PRISMA guidelines, a systematic search was conducted up to August 2019 of the databases: PubMed/MEDLINE, EMBASE and Cochrane. All studies reporting the survival of adult patients with acute PE treated with VA-ECMO and including four patients or more were included. Exclusion criteria were: correspondences, reviews and studies in absence of a full text, written in other languages than English or Dutch, or dating before 1980. Short-term (hospital or 30-day) survival data were pooled and presented with relative risks (RR) and 95% confidence intervals (95% CI). Also, the following pre-defined factors were evaluated for their association with survival in VA-ECMO treated patients: age > 60 years, male sex, pre-ECMO cardiac arrest, surgical embolectomy, catheter directed therapy, systemic thrombolysis, and VA-ECMO as single therapy.

Results: A total of 29 observational studies were included (N = 1947 patients: VA-ECMO N = 1138 and control N = 809). There was no difference in short-term survival between VA-ECMO treated patients and control patients (RR 0.91, 95% CI 0.71-1.16). In acute PE patients undergoing VA-ECMO, age > 60 years was associated with lower survival (RR 0.72, 95% CI 0.52-0.99), surgical embolectomy was associated with higher survival (RR 1.96, 95% CI 1.39-2.76) and pre-ECMO cardiac arrest showed a trend toward lower survival (RR 0.88, 95% CI 0.77-1.01). The other evaluated factors were not associated with a difference in survival.

Conclusions: At present, there is insufficient evidence that VA-ECMO treatment improves short-term survival of acute PE patients. Low quality evidence suggest that VA-ECMO patients aged ≤60 years or who received SE have higher survival rates. Considering the limited evidence derived from the present data, this study emphasizes the need for prospective studies.

Protocol Registration: PROSPERO CRD42019120370.
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http://dx.doi.org/10.1016/j.jcrc.2021.03.006DOI Listing
August 2021

Clinical features and prognostic factors in Covid-19: A prospective cohort study.

EBioMedicine 2021 May 14;67:103378. Epub 2021 May 14.

From the Department of Intensive Care, University of Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.

Background: Mortality rates are high among hospitalized patients with COVID-19, especially in those intubated on the ICU. Insight in pathways associated with unfavourable outcome may lead to new treatment strategies.

Methods: We performed a prospective cohort study of patients with COVID-19 admitted to general ward or ICU who underwent serial blood sampling. To provide insight in the pathways involved in disease progression, associations were estimated between outcome risk and serial measurements of 64 biomarkers in potential important pathways of COVID-19 infection (inflammation, tissue damage, complement system, coagulation and fibrinolysis) using joint models combining Cox regression and linear mixed-effects models. For patients admitted to the general ward, the primary outcome was admission to the ICU or mortality (unfavourable outcome). For patients admitted to the ICU, the primary outcome was 12-week mortality.

Findings: A total of 219 patients were included: 136 (62%) on the ward and 119 patients (54%) on the ICU; 36 patients (26%) were included in both cohorts because they were transferred from general ward to ICU. On the general ward, 54 of 136 patients (40%) had an unfavourable outcome and 31 (23%) patients died. On the ICU, 54 out of 119 patients (45%) died. Unfavourable outcome on the general ward was associated with changes in concentrations of IL-6, IL-8, IL-10, soluble Receptor for Advanced Glycation End Products (sRAGE), vascular cell adhesion molecule 1 (VCAM-1) and Pentraxin-3. Death on the ICU was associated with changes in IL-6, IL-8, IL-10, sRAGE, VCAM-1, Pentraxin-3, urokinase-type plasminogen activator receptor, IL-1-receptor antagonist, CD14, procalcitonin, tumor necrosis factor alfa, tissue factor, complement component 5a, Growth arrest-specific 6, angiopoietin 2, and lactoferrin. Pathway analysis showed that unfavourable outcome on the ward was mainly driven by chemotaxis and interleukin production, whereas death on ICU was associated with a variety of pathways including chemotaxis, cell-cell adhesion, innate host response mechanisms, including the complement system, viral life cycle regulation, angiogenesis, wound healing and response to corticosteroids.

Interpretation: Clinical deterioration in patients with severe COVID-19 involves multiple pathways, including chemotaxis and interleukin production, but also endothelial dysfunction, the complement system, and immunothrombosis. Prognostic markers showed considerable overlap between general ward and ICU patients, but we identified distinct differences between groups that should be considered in the development and timing of interventional therapies in COVID-19.

Funding: Amsterdam UMC, Amsterdam UMC Corona Fund, and Dr. C.J. Vaillant Fonds.
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http://dx.doi.org/10.1016/j.ebiom.2021.103378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8118723PMC
May 2021

Complement inhibition in severe COVID-19 - Blocking C5a seems to be key.

EClinicalMedicine 2021 May 24;35:100722. Epub 2021 Apr 24.

Department of Neurology, Amsterdam Neuroscience, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands.

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http://dx.doi.org/10.1016/j.eclinm.2021.100722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099654PMC
May 2021

High titers and low fucosylation of early human anti-SARS-CoV-2 IgG promote inflammation by alveolar macrophages.

Sci Transl Med 2021 06 11;13(596). Epub 2021 May 11.

Department of Immunopathology, Sanquin Research and Landsteiner Laboratory Academic Medical Centre, Plesmanlaan 125, 1066 CX Amsterdam, Netherlands.

Patients diagnosed with coronavirus disease 2019 (COVID-19) become critically ill primarily around the time of activation of the adaptive immune response. Here, we provide evidence that antibodies play a role in the worsening of disease at the time of seroconversion. We show that early-phase severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) spike protein-specific immunoglobulin G (IgG) in serum of critically ill COVID-19 patients induces excessive inflammatory responses by human alveolar macrophages. We identified that this excessive inflammatory response is dependent on two antibody features that are specific for patients with severe COVID-19. First, inflammation is driven by high titers of anti-spike IgG, a hallmark of severe disease. Second, we found that anti-spike IgG from patients with severe COVID-19 is intrinsically more proinflammatory because of different glycosylation, particularly low fucosylation, of the antibody Fc tail. Low fucosylation of anti-spike IgG was normalized in a few weeks after initial infection with SARS-CoV-2, indicating that the increased antibody-dependent inflammation mainly occurs at the time of seroconversion. We identified Fcγ receptor (FcγR) IIa and FcγRIII as the two primary IgG receptors that are responsible for the induction of key COVID-19-associated cytokines such as interleukin-6 and tumor necrosis factor. In addition, we show that anti-spike IgG-activated human macrophages can subsequently break pulmonary endothelial barrier integrity and induce microvascular thrombosis in vitro. Last, we demonstrate that the inflammatory response induced by anti-spike IgG can be specifically counteracted by fostamatinib, an FDA- and EMA-approved therapeutic small-molecule inhibitor of Syk kinase.
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http://dx.doi.org/10.1126/scitranslmed.abf8654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158960PMC
June 2021

Intramuscular adipose tissue at level Th12 is associated with survival in COVID-19.

J Cachexia Sarcopenia Muscle 2021 May 3. Epub 2021 May 3.

Department of Radiology and Nuclear Medicine, Amsterdam Movement Sciences, Amsterdam University Medical Centers, location AMC, Amsterdam, The Netherlands.

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http://dx.doi.org/10.1002/jcsm.12696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200446PMC
May 2021

The effect of immediate coronary angiography after cardiac arrest without ST-segment elevation on left ventricular function. A sub-study of the COACT randomised trial.

Resuscitation 2021 07 28;164:93-100. Epub 2021 Apr 28.

Department of Intensive care medicine, Noord West Ziekenhuisgroep, Alkmaar, The Netherlands.

Background: The effect of immediate coronary angiography and percutaneous coronary intervention (PCI) in patients who are successfully resuscitated after cardiac arrest in the absence of ST-segment elevation myocardial infarction (STEMI) on left ventricular function is currently unknown.

Methods: This prespecified sub-study of a multicentre trial evaluated 552 patients, successfully resuscitated from out-of-hospital cardiac arrest without signs of STEMI. Patients were randomized to either undergo immediate coronary angiography or delayed coronary angiography, after neurologic recovery. All patients underwent PCI if indicated. The main outcomes of this analysis were left ventricular ejection fraction and end-diastolic and systolic volumes assessed by cardiac magnetic resonance imaging or echocardiography.

Results: Data on left ventricular function was available for 397 patients. The mean (± standard deviation) left ventricular ejection fraction was 45.2% (±12.8) in the immediate angiography group and 48.4% (±13.2) in the delayed angiography group (mean difference: -3.19; 95% confidence interval [CI], -6.75 to 0.37). Median left ventricular end-diastolic volume was 177 ml in the immediate angiography group compared to 169 ml in the delayed angiography group (ratio of geometric means: 1.06; 95% CI, 0.95-1.19). In addition, mean left ventricular end-systolic volume was 90 ml in the immediate angiography group compared to 78 ml in the delayed angiography group (ratio of geometric means: 1.13; 95% CI 0.97-1.32).

Conclusion: In patients successfully resuscitated after out-of-hospital cardiac arrest and without signs of STEMI, immediate coronary angiography was not found to improve left ventricular dimensions or function compared with a delayed angiography strategy.

Clinical Trial Registration: Netherlands Trial Register number, NTR4973.
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http://dx.doi.org/10.1016/j.resuscitation.2021.04.020DOI Listing
July 2021

Clinical performance of a machine-learning algorithm to predict intra-operative hypotension with noninvasive arterial pressure waveforms: A cohort study.

Eur J Anaesthesiol 2021 Jun;38(6):609-615

From the Department of Anaesthesiology (MW, BvdS, BFG, FdB, CB, DE, MWH, DPV) and Department of Intensive Care, Amsterdam UMC, location AMC, Amsterdam, The Netherlands (APJV).

Background: Intra-operative hypotension is associated with adverse postoperative outcomes. A machine-learning-derived algorithm developed to predict hypotension based on arterial blood pressure (ABP) waveforms significantly reduced intra-operative hypotension. The algorithm calculates the likelihood of hypotension occurring within minutes, expressed as the Hypotension Prediction Index (HPI) which ranges from 0 to 100. Currently, HPI is only available for patients monitored with invasive ABP, which is restricted to high-risk procedures and patients. In this study, the performance of HPI, employing noninvasive continuous ABP measurements, is assessed.

Objectives: The first aim was to compare the performance of the HPI algorithm, using noninvasive versus invasive ABP measurements, at a mathematically optimal HPI alarm threshold (Youden index). The second aim was to assess the performance of the algorithm using a HPI alarm threshold of 85 that is currently used in clinical trials. Hypotension was defined as a mean arterial pressure (MAP) below 65 mmHg for at least 1 min. The predictive performance of the algorithm at different HPI alarm thresholds (75 and 95) was studied.

Design: Observational cohort study.

Setting: Tertiary academic medical centre.

Patients: Five hundred and seven adult patients undergoing general surgery.

Results: The performance of the algorithm with invasive and noninvasive ABP input was similar. A HPI alarm threshold of 85 showed a median [IQR] time from alarm to hypotension of 2.7 [1.0 to 7.0] min with a sensitivity of 92.7 (95% confidence interval [CI], 91.2 to 94.3), specificity of 87.6 (95% CI, 86.2 to 89.0), positive predictive value of 79.9 (95% CI, 77.7 to 82.1) and negative predictive value of 95.8 (95% CI, 94.9 to 96.7). A HPI alarm threshold of 75 provided a lower positive predictive value but a prolonged time from prediction to actual hypotension.

Conclusion: This study demonstrated that the algorithm can be employed using continuous noninvasive ABP waveforms. This opens up the potential to predict and prevent hypotension in a larger patient population.

Trial Registration: Clinical trials registration number NCT03533205.
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http://dx.doi.org/10.1097/EJA.0000000000001521DOI Listing
June 2021

Extracorporeal Membrane Oxygenation in Patients With COVID-19: An International Multicenter Cohort Study.

J Intensive Care Med 2021 Aug 7;36(8):910-917. Epub 2021 Apr 7.

Department of Intensive Care, Amsterdam University Medical Centers, Location Academic Medical Center (26066AMC), Amsterdam, the Netherlands.

Background: To report and compare the characteristics and outcomes of COVID-19 patients on extracorporeal membrane oxygenation (ECMO) to non-COVID-19 acute respiratory distress syndrome (ARDS) patients on ECMO.

Methods: We performed an international retrospective study of COVID-19 patients on ECMO from 13 intensive care units from March 1 to April 30, 2020. Demographic data, ECMO characteristics and clinical outcomes were collected. The primary outcome was to assess the complication rate and 28-day mortality; the secondary outcome was to compare patient and ECMO characteristics between COVID-19 patients on ECMO and non-COVID-19 related ARDS patients on ECMO (non-COVID-19; January 1, 2018 until July 31, 2019).

Results: During the study period 71 COVID-19 patients received ECMO, mostly veno-venous, for a median duration of 13 days (IQR 7-20). ECMO was initiated at 5 days (IQR 3-10) following invasive mechanical ventilation. Median PaO/FiO ratio prior to initiation of ECMO was similar in COVID-19 patients (58 mmHg [IQR 46-76]) and non-COVID-19 patients (53 mmHg [IQR 44-66]), the latter consisting of 48 patients. 28-day mortality was 37% in COVID-19 patients and 27% in non-COVID-19 patients. However, Kaplan-Meier curves showed that after a 100-day follow-up this non-significant difference resolves. Non-surviving COVID-19 patients were more acidotic prior to initiation ECMO, had a shorter ECMO run and fewer received muscle paralysis compared to survivors.

Conclusions: No significant differences in outcomes were found between COVID-19 patients on ECMO and non-COVID-19 ARDS patients on ECMO. This suggests that ECMO could be considered as a supportive therapy in case of refractory respiratory failure in COVID-19.
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http://dx.doi.org/10.1177/08850666211007063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267077PMC
August 2021

Coronavirus disease 2019 is associated with catheter-related thrombosis in critically ill patients: A multicenter case-control study.

Thromb Res 2021 04 26;200:87-90. Epub 2021 Jan 26.

Department of Intensive Care Medicine, Amsterdam University Medical Centers, VU University, Amsterdam, the Netherlands; Amsterdam Cardiovascular Sciences Research Institute, Amsterdam University Medical Centers, Amsterdam, the Netherlands; Amsterdam Leiden Intensive care Focused Echography (ALIFE, www.alifeofpocus.com), the Netherlands.

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http://dx.doi.org/10.1016/j.thromres.2021.01.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835604PMC
April 2021

Efficacy matters: broadening complement inhibition in COVID-19 - Authors' reply.

Lancet Rheumatol 2021 Feb 14;3(2):e95-e96. Epub 2020 Dec 14.

Department of Neurology, Amsterdam Neuroscience, Amsterdam UMC, University of Amsterdam, Amsterdam 1100DD, Netherlands.

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http://dx.doi.org/10.1016/S2665-9913(20)30424-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834467PMC
February 2021

Afucosylated IgG characterizes enveloped viral responses and correlates with COVID-19 severity.

Science 2021 02 23;371(6532). Epub 2020 Dec 23.

Department of Rheumatology and Clinical Immunology, Amsterdam UMC, Amsterdam Rheumatology and Immunology Center, Amsterdam, Netherlands.

Immunoglobulin G (IgG) antibodies are crucial for protection against invading pathogens. A highly conserved N-linked glycan within the IgG-Fc tail, which is essential for IgG function, shows variable composition in humans. Afucosylated IgG variants are already used in anticancer therapeutic antibodies for their increased activity through Fc receptors (FcγRIIIa). Here, we report that afucosylated IgG (approximately 6% of total IgG in humans) are specifically formed against enveloped viruses but generally not against other antigens. This mediates stronger FcγRIIIa responses but also amplifies brewing cytokine storms and immune-mediated pathologies. Critically ill COVID-19 patients, but not those with mild symptoms, had high concentrations of afucosylated IgG antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), amplifying proinflammatory cytokine release and acute phase responses. Thus, antibody glycosylation plays a critical role in immune responses to enveloped viruses, including COVID-19.
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http://dx.doi.org/10.1126/science.abc8378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919849PMC
February 2021

One of the first validations of an artificial intelligence algorithm for clinical use: The impact on intraoperative hypotension prediction and clinical decision-making.

Surgery 2021 06 11;169(6):1300-1303. Epub 2020 Dec 11.

Amsterdam UMC, University of Amsterdam, Department of Anesthesiology, Amsterdam, Netherlands.

This review describes the steps and conclusions from the development and validation of an artificial intelligence algorithm (the Hypotension Prediction Index), one of the first machine learning predictive algorithms used in the operating room environment. The algorithm has been demonstrated to reduce intraoperative hypotension in two randomized controlled trials via real-time prediction of upcoming hypotensive events prompting anesthesiologists to act earlier, more often, and differently in managing impending hypotension. However, the algorithm entails no dynamic learning process that evolves from use in clinical patient care, meaning the algorithm is fixed, and furthermore provides no insight into the decisional process that leads to an early warning for intraoperative hypotension, which makes the algorithm a "black box." Many other artificial intelligence machine learning algorithms have these same disadvantages. Clinical validation of such algorithms is relatively new and requires more standardization, as guidelines are lacking or only now start to be drafted. Before adaptation in clinical practice, impact of artificial intelligence algorithms on clinical behavior, outcomes and economic advantages should be studied too.
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http://dx.doi.org/10.1016/j.surg.2020.09.041DOI Listing
June 2021

Data on sex differences in one-year outcomes of out-of-hospital cardiac arrest patients without ST-segment elevation.

Data Brief 2020 Dec 12;33:106521. Epub 2020 Nov 12.

Department of Intensive care medicine, Maastricht University Medical Center, University Maastricht, Maastricht, the Netherlands.

Sex differences in out-of-hospital cardiac arrest (OHCA) patients are increasingly recognized. Although it has been found that post-resuscitated women are less likely to have significant coronary artery disease (CAD) than men, data on follow-up in these patients are limited. Data for this data in brief article was obtained as a part of the randomized controlled Coronary Angiography after Cardiac Arrest without ST-segment elevation (COACT) trial. The data supplements the manuscript "Sex differences in out-of-hospital cardiac arrest patients without ST-segment elevation: A COACT trial substudy" were it was found that women were less likely to have significant CAD including chronic total occlusions, and had worse survival when CAD was present. The dataset presented in this paper describes sex differences on interventions, implantable-cardioverter defibrillator (ICD) shocks and hospitalizations due to heart failure during one-year follow-up in patients successfully resuscitated after OHCA. Data was derived through a telephone interview at one year with the patient or general practitioner. Patients in this randomized dataset reflects a homogenous study population, which can be valuable to further build on research regarding long-term sex differences and to further improve cardiac care.
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http://dx.doi.org/10.1016/j.dib.2020.106521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691722PMC
December 2020

Sex differences in patients with out-of-hospital cardiac arrest without ST-segment elevation: A COACT trial substudy.

Resuscitation 2021 01 12;158:14-22. Epub 2020 Nov 12.

Department of Intensive care medicine, Maastricht University Medical Centre, University Maastricht, Maastricht, the Netherlands.

Background: Whether sex is associated with outcomes of out-of-hospital cardiac arrest (OHCA) is unclear.

Objectives: This study examined sex differences in survival in patients with OHCA without ST-segment elevation myocardial infarction (STEMI).

Methods: Using data from the randomized controlled Coronary Angiography after Cardiac Arrest (COACT) trial, the primary point of interest was sex differences in OHCA-related one-year survival. Secondary points of interest included the benefit of immediate coronary angiography compared to delayed angiography until after neurologic recovery, angiographic and clinical outcomes.

Results: In total, 522 patients (79.1% men) were included. Overall one-year survival was 59.6% in women and 63.4% in men (HR 1.18; 95% CI: 0.76-1.81;p = 0.47). No cardiovascular risk factors were found that modified survival. Women less often had significant coronary artery disease (CAD) (37.0% vs. 71.3%;p < 0.001), but when present, they had a worse prognosis than women without CAD (HR 3.06; 95% CI 1.31-7.19;p = 0.01). This was not the case for men (HR 1.05; 95% CI 0.67-1.65;p = 0.83). In both sexes, immediate coronary angiography did not improve one-year survival compared to delayed angiography (women, odds ratio (OR) 0.87; 95% CI 0.58-1.30;p = 0.49; vs. men, OR 0.97; 95% CI 0.45-2.09;p = 0.93).

Conclusion: In OHCA patients without STEMI, we found no sex differences in overall one-year survival. Women less often had significant CAD, but when CAD was present they had worse survival than women without CAD. This was not the case for men. Both sexes did not benefit from a strategy of immediate coronary angiography as compared to delayed strategy with respect to one-year survival.

Clinical Trial Registration Number: Netherlands trial register (NTR) 4973.
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http://dx.doi.org/10.1016/j.resuscitation.2020.10.026DOI Listing
January 2021

Transfusion in the mechanically ventilated patient.

Intensive Care Med 2020 12 12;46(12):2450-2457. Epub 2020 Nov 12.

Department of Intensive Care, Erasme University Hospital, Université Libre de Bruxelles, Route de Lennik 808, 1070, Brussels, Belgium.

Red blood cell transfusions are a frequent intervention in critically ill patients, including in those who are receiving mechanical ventilation. Both these interventions can impact negatively on lung function with risks of transfusion-related acute lung injury (TRALI) and other forms of acute respiratory distress syndrome (ARDS). The interactions between transfusion, mechanical ventilation, TRALI and ARDS are complex and other patient-related (e.g., presence of sepsis or shock, disease severity, and hypervolemia) or blood product-related (e.g., presence of antibodies or biologically active mediators) factors also play a role. We propose several strategies targeted at these factors that may help limit the risks of associated lung injury in critically ill patients being considered for transfusion.
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http://dx.doi.org/10.1007/s00134-020-06303-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658306PMC
December 2020

PRactice of VENTilation in Patients with Novel Coronavirus Disease (PRoVENT-COVID): rationale and protocol for a national multicenter observational study in The Netherlands.

Ann Transl Med 2020 Oct;8(19):1251

Department of Intensive Care, Amsterdam UMC location AMC, The Netherlands.

Background: The coronavirus disease 2019 (COVID-19) pandemic is rapidly expanding across the world, with more than 100,000 new cases each day as of end-June 2020. Healthcare workers are struggling to provide the best care for COVID-19 patients. Approaches for invasive ventilation vary widely between and within countries and new insights are acquired rapidly. We aim to investigate invasive ventilation practices and outcome in COVID-19 patients in the Netherlands.

Methods: PRoVENT-COVID ('study of PRactice of VENTilation in COVID-19') is an investigator-initiated national, multicenter observational study to be undertaken in intensive care units (ICUs) in The Netherlands. Consecutive COVID-19 patients aged 18 years or older, who are receiving invasive ventilation in the participating ICUs, are to be enrolled during a 10-week period, with a daily follow-up of 7 days. The primary outcome is ventilatory management (including tidal volume expressed as mL/kg predicted body weight and positive end-expiratory pressure expressed as cmHO) during the first 3 days of ventilation. Secondary outcomes include other ventilatory variables, use of rescue therapies for refractory hypoxemia such as prone positioning and extracorporeal membrane oxygenation, use of sedatives, vasopressors and inotropes; daily cumulative fluid balances; acute kidney injury; ventilator-free days and alive at day 28 (VFD-28), duration of ICU and hospital stay, and ICU, hospital and 90-day mortality.

Discussion: PRoVENT-COVID will be the largest observational study to date, with high density ventilatory data and major outcomes. There is urgent need for a better understanding of ventilation practices, and the effects of ventilator settings on outcomes in COVID-19 patients. The results of PRoVENT-COVID will be rapidly disseminated through electronic presentations, such as webinars and electronic conferences, and publications in international peer-reviewed journals. Access to source data will be made available through local, regional and national anonymized datasets on request, and after agreement of the PRoVENT-COVID steering committee.

Trial Registration: PRoVENT-COVID is registered at clinicaltrials.gov (identifier NCT04346342).
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http://dx.doi.org/10.21037/atm-20-5107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7607125PMC
October 2020

Ventilation management and clinical outcomes in invasively ventilated patients with COVID-19 (PRoVENT-COVID): a national, multicentre, observational cohort study.

Lancet Respir Med 2021 02 23;9(2):139-148. Epub 2020 Oct 23.

Department of Intensive Care, Amsterdam University Medical Centers location Academic Medical Center, Amsterdam, Netherlands; ACHIEVE, Centre of Applied Research, Amsterdam University of Applied Sciences, Faculty of Health, Amsterdam, Netherlands.

Background: Little is known about the practice of ventilation management in patients with COVID-19. We aimed to describe the practice of ventilation management and to establish outcomes in invasively ventilated patients with COVID-19 in a single country during the first month of the outbreak.

Methods: PRoVENT-COVID is a national, multicentre, retrospective observational study done at 18 intensive care units (ICUs) in the Netherlands. Consecutive patients aged at least 18 years were eligible for participation if they had received invasive ventilation for COVID-19 at a participating ICU during the first month of the national outbreak in the Netherlands. The primary outcome was a combination of ventilator variables and parameters over the first 4 calendar days of ventilation: tidal volume, positive end-expiratory pressure (PEEP), respiratory system compliance, and driving pressure. Secondary outcomes included the use of adjunctive treatments for refractory hypoxaemia and ICU complications. Patient-centred outcomes were ventilator-free days at day 28, duration of ventilation, duration of ICU and hospital stay, and mortality. PRoVENT-COVID is registered at ClinicalTrials.gov (NCT04346342).

Findings: Between March 1 and April 1, 2020, 553 patients were included in the study. Median tidal volume was 6·3 mL/kg predicted bodyweight (IQR 5·7-7·1), PEEP was 14·0 cm HO (IQR 11·0-15·0), and driving pressure was 14·0 cm HO (11·2-16·0). Median respiratory system compliance was 31·9 mL/cm HO (26·0-39·9). Of the adjunctive treatments for refractory hypoxaemia, prone positioning was most often used in the first 4 days of ventilation (283 [53%] of 530 patients). The median number of ventilator-free days at day 28 was 0 (IQR 0-15); 186 (35%) of 530 patients had died by day 28. Predictors of 28-day mortality were gender, age, tidal volume, respiratory system compliance, arterial pH, and heart rate on the first day of invasive ventilation.

Interpretation: In patients with COVID-19 who were invasively ventilated during the first month of the outbreak in the Netherlands, lung-protective ventilation with low tidal volume and low driving pressure was broadly applied and prone positioning was often used. The applied PEEP varied widely, despite an invariably low respiratory system compliance. The findings of this national study provide a basis for new hypotheses and sample size calculations for future trials of invasive ventilation for COVID-19. These data could also help in the interpretation of findings from other studies of ventilation practice and outcomes in invasively ventilated patients with COVID-19.

Funding: Amsterdam University Medical Centers, location Academic Medical Center.
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http://dx.doi.org/10.1016/S2213-2600(20)30459-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7584441PMC
February 2021

Development of a SARS-CoV-2 Total Antibody Assay and the Dynamics of Antibody Response over Time in Hospitalized and Nonhospitalized Patients with COVID-19.

J Immunol 2020 12 30;205(12):3491-3499. Epub 2020 Oct 30.

Department of Immunopathology, Sanquin Research and Landsteiner Laboratory Academic Medical Centre, 1066 CX Amsterdam, the Netherlands;

Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infections often cause only mild disease that may evoke relatively low Ab titers compared with patients admitted to hospitals. Generally, total Ab bridging assays combine good sensitivity with high specificity. Therefore, we developed sensitive total Ab bridging assays for detection of SARS-CoV-2 Abs to the receptor-binding domain (RBD) and nucleocapsid protein in addition to conventional isotype-specific assays. Ab kinetics was assessed in PCR-confirmed, hospitalized coronavirus disease 2019 (COVID-19) patients ( = 41) and three populations of patients with COVID-19 symptoms not requiring hospital admission: PCR-confirmed convalescent plasmapheresis donors ( = 182), PCR-confirmed hospital care workers ( = 47), and a group of longitudinally sampled symptomatic individuals highly suspect of COVID-19 ( = 14). In nonhospitalized patients, the Ab response to RBD is weaker but follows similar kinetics, as has been observed in hospitalized patients. Across populations, the RBD bridging assay identified most patients correctly as seropositive. In 11/14 of the COVID-19-suspect cases, seroconversion in the RBD bridging assay could be demonstrated before day 12; nucleocapsid protein Abs emerged less consistently. Furthermore, we demonstrated the feasibility of finger-prick sampling for Ab detection against SARS-CoV-2 using these assays. In conclusion, the developed bridging assays reliably detect SARS-CoV-2 Abs in hospitalized and nonhospitalized patients and are therefore well suited to conduct seroprevalence studies.
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http://dx.doi.org/10.4049/jimmunol.2000767DOI Listing
December 2020

A Higher Fluid Balance in the Days After Septic Shock Reversal Is Associated With Increased Mortality: An Observational Cohort Study.

Crit Care Explor 2020 Oct 23;2(10):e0219. Epub 2020 Sep 23.

Department of Intensive Care Medicine, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam, The Netherlands.

Objectives: Previous studies demonstrated that extensive fluid loading and consequently positive fluid balances during sepsis resuscitation are associated with adverse outcome. Yet, the association between fluid balance and mortality after reversal of shock, that is, during deresuscitation, is largely unappreciated. Our objective was to investigate the effects of fluid balance on mortality in the days after septic shock reversal.

Design: Retrospective observational cohort study.

Setting: ICUs of two university-affiliated hospitals in The Netherlands.

Patients: Adult patients admitted with septic shock followed by shock reversal. Reversal of septic shock was defined based on Sepsis-3 criteria as the first day that serum lactate was less than or equal to 2 mmol/L without vasopressor requirement.

Interventions: None.

Measurements And Main Results: Reversal of septic shock occurred in 636 patients, of whom 20% died in the ICU. Mixed-effects logistic regression modeling, adjusted for possible confounders, showed that fluid balance in the days after reversal of septic shock (until discharge or death) was an independent predictor of ICU mortality: odds ratio 3.18 (1.90-5.32) per 10 mL/kg increase in daily fluid balance. Similar results were found for 30-day, 90-day, hospital, and 1-year mortality: odds ratios 2.09 (1.64-2.67); 1.79 (1.38-2.32); 1.70 (1.40-2.07); and 1.53 (1.17-2.01), respectively. Positive cumulative fluid balances vs. neutral or negative fluid balances on the final day in the ICU were associated with increased ICU, hospital, 30-day, and 90-day mortality: odds ratios 3.46 (2.29-5.23); 3.39 (2.35-4.9); 5.33 (3.51-8.08); and 3.57 (2.49-5.12), respectively. Using restricted cubic splines, we found a dose-response relationship between cumulative fluid balance after shock reversal and ICU mortality.

Conclusions: A higher fluid balance in the days after septic shock reversal was associated with increased mortality. This stresses the importance of implementing restrictive and deresuscitative fluid management strategies after initial hemodynamic resuscitation. Prospective interventional studies are needed to confirm our results.
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http://dx.doi.org/10.1097/CCE.0000000000000219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523767PMC
October 2020

Blood Transfusion Threshold in Patients Receiving Extracorporeal Membrane Oxygenation Support for Cardiac and Respiratory Failure-A Systematic Review and Meta-Analysis.

J Cardiothorac Vasc Anesth 2021 Apr 10;35(4):1192-1202. Epub 2020 Sep 10.

Department of Cardiovascular Sciences, University of Leicester, Clinical Sciences Wing, Glenfield Hospital, Leicester, United Kingdom.

Objective: To review studies that have evaluated the effects of liberal or restrictive red cell transfusion thresholds on clinical outcomes in patients requiring extracorporeal membrane oxygenation (ECMO) support for cardiac or respiratory failure.

Design: A systematic review and meta-analysis.

Setting And Participants: The study comprised 1,070 patients from observational studies and randomized controlled trials analyzing transfusion policies in venoarterial (VA) and venovenous (VV) ECMO adult populations.

Measurements And Main Results: Eligible studies were identified by searching the Cochrane Central Register of Controlled Trials, Medline, and EMBASE until March 4, 2020, using a combination of subject headings and text words. Risk of bias assessment was performed to assess study quality according to the ROBINS-I tool and the case series studies appraisal checklist. There was high risk of bias in the studies analyzed, and none had methodologic adequacy. Three studies analyzed VA ECMO and VV ECMO patients separately. Five datasets were related exclusively or mostly to VA ECMO. Four were retrospective analyses, and one was conducted as a prospective observational study; the median transfusion threshold reported was 8 g/dL, with a mean mortality of 52%. Eight datasets were related either exclusively or mostly to VV ECMO. Six were retrospective and two were prospective observational studies; the median transfusion threshold was 8 g/dL, and the mean mortality rate was 33%.

Conclusions: The present study did not resolve uncertainty as to transfusion management in ECMO, although several studies (most of them in VV ECMO) demonstrated that a restrictive threshold has acceptable outcomes in single-center cohorts.
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http://dx.doi.org/10.1053/j.jvca.2020.08.068DOI Listing
April 2021

Treating critically ill anemic patients with erythropoietin: less is more.

Intensive Care Med 2021 02 9;47(2):256-257. Epub 2020 Oct 9.

Department of Intensive Care Medicine, Amsterdam UMC, Location AMC, Room, C3-430, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.

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http://dx.doi.org/10.1007/s00134-020-06259-0DOI Listing
February 2021
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