Publications by authors named "Jeanette Tas"

12 Publications

  • Page 1 of 1

In-Depth Investigation of Conjunctival Swabs and Tear Fluid of Symptomatic COVID-19 Patients, an Observational Cohort Study.

Transl Vis Sci Technol 2021 10;10(12):32

University Eye Clinic Maastricht, Maastricht University Medical Center, Maastricht, the Netherlands.

Purpose: The putative presence of SARS-CoV-2 in ocular specimen puts healthcare workers at risk. We thoroughly examined conjunctival swabs and tear fluid in a large cohort of COVID-19 patients.

Methods: A total of 243 symptomatic laboratory-confirmed COVID-19 patients were included in this observational multicenter study. Conjunctival swabs were analyzed by reverse transcription polymerase chain reaction for detection of SARS-CoV-2 RNA. Next-generation sequencing and phylogenetic analysis were performed to identify viral strains and to determine tissue tropism. Schirmer tear samples from 43 hospitalized COVID-19 patients and 25 healthy controls were analyzed by multiplex cytokine immunoassays.

Results: Viral SARS-CoV-2 RNA was detected in conjunctival swabs from 17 (7.0%) of 243 COVID-19 patients. Conjunctival samples were positive for viral SARS-CoV-2 RNA as long as 12 days after disease onset. Cycle threshold (Ct) values for conjunctival swabs (mean 34.5 ± 5.1) were significantly higher than nasopharyngeal swabs (mean 16.7 ± 3.6). No correlation between Ct values of conjunctival and nasopharyngeal swabs was observed. The majority of positive conjunctival samples were detected only once and primarily during the first visit. Next-generation sequencing analysis revealed that the virus strain found in the conjunctiva was most often identical to the one found in the nasopharynx. Tear cytokine levels IL-1β and IL-6 were elevated in COVID-19 patients compared to healthy controls.

Conclusions: Conjunctival samples that were positive for SARS-CoV-2 RNA contained the same viral strain as the nasopharynx.

Translational Relevance: The presence of SARS-CoV-2 viral RNA and elevated cytokines in tear fluid confirm the involvement of the ocular surface in COVID-19 disease.
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http://dx.doi.org/10.1167/tvst.10.12.32DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8543390PMC
October 2021

Targeting Autoregulation-Guided Cerebral Perfusion Pressure after Traumatic Brain Injury (COGiTATE): A Feasibility Randomized Controlled Clinical Trial.

J Neurotrauma 2021 Oct 16;38(20):2790-2800. Epub 2021 Aug 16.

Department of Intensive Care Medicine, University Maastricht (KEMTA), Maastricht University Medical Center+, Maastricht, The Netherlands.

Managing traumatic brain injury (TBI) patients with a cerebral perfusion pressure (CPP) near to the cerebral autoregulation (CA)-guided "optimal" CPP (CPPopt) value is associated with improved outcome and might be useful to individualize care, but has never been prospectively evaluated. This study evaluated the feasibility and safety of CA-guided CPP management in TBI patients requiring intracranial pressure monitoring and therapy (TBIicp patients). The CPPopt Guided Therapy: Assessment of Target Effectiveness (COGiTATE) parallel two-arm feasibility trial took place in four tertiary centers. TBIicp patients were randomized to either the Brain Trauma Foundation (BTF) guideline CPP target range (control group) or to the individualized CA-guided CPP targets (intervention group). CPP targets were guided by six times daily software-based alerts for up to 5 days. The primary feasibility end-point was the percentage of time with CPP concordant (±5 mm Hg) with the set CPP targets. The main secondary safety end-point was an increase in therapeutic intensity level (TIL) between the control and intervention group. Twenty-eight patients were randomized to the control and 32 patients to the intervention group. CPP in the intervention group was in the target range for 46.5% (interquartile range, 41.2-58) of the monitored time, significantly higher than the feasibility target specified in the published protocol (36%;  < 0.001). There were no significant differences between groups for TIL or for other safety end-points. Conclusively, targeting an individual and dynamic CA-guided CPP is feasible and safe in TBIicp patients. This encourages a prospective trial powered for clinical outcomes.
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http://dx.doi.org/10.1089/neu.2021.0197DOI Listing
October 2021

Optimal Cerebral Perfusion Pressure Assessed with a Multi-Window Weighted Approach Adapted for Prospective Use: A Validation Study.

Acta Neurochir Suppl 2021 ;131:181-185

Brain Physics Laboratory, Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.

Background: Pressure reactivity index (PRx)-cerebral perfusion pressure (CPP) relationships over a given time period can be used to detect a value of CPP at which PRx shows the best autoregulation (optimal CPP, or CPPopt). Algorithms for continuous assessment of CPPopt in traumatic brain injury (TBI) patients reached the desired high yield with a multi-window approach (CPPopt_MA). However, the calculations were tested on retrospective manually cleaned datasets. Moreover, CPPopt false-positive values can be generated from non-physiological variations of intracranial pressure (ICP) and arterial blood pressure (ABP). Therefore, the algorithm robustness was improved, making it suitable for prospective bedside application (COGiTATE trial).

Objective: To validate the CPPopt revised algorithm in a large single-centre retrospective cohort of TBI patients.

Methods: 840 TBI patients were included. CPPopt yield, stability and ability to discriminate outcome groups were compared to CPPopt_MA and the Brain Trauma Foundation (BTF) guideline reference.

Results: CPPopt yield was lower than CPPopt_MA yield (85% and 90%, p < 0.001), but, importantly, with increased stability (p < 0.0001). The ∆(CPP-CPPopt) could distinguish the mortality and survival outcome (t = -6.7, p < 0.0001) with a statistical significance higher than the ∆CPP calculated with the guideline reference (CPP-60) (t = -4.5, p < 0.0001).

Conclusion: This study validates, on a large cohort of patients, the new algorithm proposed for prospective use of CPPopt as a CPP target at bedside.
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http://dx.doi.org/10.1007/978-3-030-59436-7_36DOI Listing
June 2021

Patient's Clinical Presentation and CPPopt Availability: Any Association?

Acta Neurochir Suppl 2021 ;131:167-172

Department of Intensive Care, University Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands.

Background: The 'optimal' CPP (CPPopt) concept is based on the vascular pressure reactivity index (PRx). The feasibility and effectiveness of CPPopt guided therapy in severe traumatic brain injury (TBI) patients is currently being investigated prospectively in the COGiTATE trial. At the moment there is no clear evidence that certain admission and treatment characteristics are associated with CPPopt availability (yield).

Objective: To test the relation between patients' admission and treatment characteristics and the average CPPopt yield.

Methods: Retrospective analysis of 230 patients from the CENTER-TBI high-resolution database with intracranial pressure (ICP) measured using an intraparenchymal probe. CPPopt was calculated using the algorithm set for the COGiTATE study. CPPopt yield was defined as the percentage of CPP monitored time (%) when CPPopt is available. The variables in the statistical model included age, admission Glasgow Coma Scale (GCS), gender, pupil response, hypoxia and hypotension at the scene, Marshall computed tomography (CT) score, decompressive craniectomy, injury severity score score and 24-h therapeutic intensity level (TIL) score.

Results: The median CPPopt yield was 80.7% (interquartile range 70.9-87.4%). None of the selected variables showed a significant statistical correlation with the CPPopt yield.

Conclusion: In this retrospective multicenter study, none of the selected admission and treatment variables were related to the CPPopt yield.
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http://dx.doi.org/10.1007/978-3-030-59436-7_34DOI Listing
June 2021

An Update on the COGiTATE Phase II Study: Feasibility and Safety of Targeting an Optimal Cerebral Perfusion Pressure as a Patient-Tailored Therapy in Severe Traumatic Brain Injury.

Acta Neurochir Suppl 2021 ;131:143-147

Department of Intensive Care Medicine, University of Maastricht, Maastricht University Medical Centre, Maastricht, The Netherlands.

Introduction: Monitoring of cerebral autoregulation (CA) in patients with a traumatic brain injury (TBI) can provide an individual 'optimal' cerebral perfusion pressure (CPP) target (CPPopt) at which CA is best preserved. This potentially offers an individualized precision medicine approach. Retrospective data suggest that deviation of CPP from CPPopt is associated with poor outcomes. We are prospectively assessing the feasibility and safety of this approach in the COGiTATE [CPPopt Guided Therapy: Assessment of Target Effectiveness] study. Its primary objective is to demonstrate the feasibility of individualizing CPP at CPPopt in TBI patients. The secondary objectives are to investigate the safety and physiological effects of this strategy.

Methods: The COGiTATE study has included patients in four European hospitals in Cambridge, Leuven, Nijmegen, and Maastricht (coordinating centre). Patients with severe TBI requiring intracranial pressure (ICP)-directed therapy are allocated into one of two groups. In the intervention group, CPPopt is calculated using a published (modified) algorithm. In the control group, the CPP target recommended in the Brain Trauma Foundation guidelines (CPP 60-70 mmHg) is used.

Results: Patient recruitment started in February 2018 and will continue until 60 patients have been studied. Fifty-one patients (85% of the intended total) have been recruited in October 2019. The first results are expected early 2021.

Conclusion: This prospective evaluation of the feasibility, safety and physiological implications of autoregulation-guided CPP management is providing evidence that will be useful in the design of a future phase III study in severe TBI patients.
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http://dx.doi.org/10.1007/978-3-030-59436-7_29DOI Listing
June 2021

Semi-automated Computed Tomography Volumetry as a Proxy for Intracranial Pressure in Patients with Severe Traumatic Brain Injury: Clinical Feasibility Study.

Acta Neurochir Suppl 2021 ;131:17-21

Department of Intensive Care, Maastricht University Medical Centre, Maastricht, The Netherlands.

Introduction: Traumatic brain injury (TBI) is associated with high mortality due to intracranial pressure (ICP). Whether computed tomography (CT) scanning of the brain within the first 24 h is indicative of intracranial hypertension is largely unknown. We assessed the feasibility of semi-automated CT segmentation in comparison with invasive ICP measurements.

Relevance: CT volumetry of the brain might provide ICP data when invasive monitoring is not possible or is undesirable.

Methods: We identified 33 patients with TBI who received a CT scan at admission and ICP monitoring within 24 h. Semi-automated segmentation of CT images in Matlab yielded cerebrospinal fluid (CSF) and intracranial volume (ICV) data. The ratio CSF/ICV × 100 (expressed as a percentage) was used as a proxy for ICP. The association between invasive ICP and the CSF/ICV ratio was evaluated using a simple linear regression model and a mono-exponential function derived from previous research in animals.

Results: ICP is moderately but significantly associated with the CSF/ICV ratio (r = -0.44, p = 0.01). The mono-exponential function provided a better fit of the relationship between ICP and the CSF/ICV ratio than the linear model.

Conclusion: Our feasibility TBI data show that cross-sectional volumetric CT measures are associated with ICP. This non-invasive method can be used in future studies to monitor patients who are not candidates for invasive monitoring or to evaluate therapy effects objectively.
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http://dx.doi.org/10.1007/978-3-030-59436-7_4DOI Listing
June 2021

The "sex gap" in COVID-19 trials: a scoping review.

EClinicalMedicine 2020 Dec 30;29:100652. Epub 2020 Nov 30.

Department of Obstetrics and Gynaecology, Maastricht University Medical Centre (MUMC+), Maastricht, the Netherlands.

Background: Many studies investigate the role of pharmacological treatments on disease course in Corona Virus Disease 2019 (COVID-19). Sex disparities in genetics, immunological responses, and hormonal mechanisms may underlie the substantially higher fatality rates reported in male COVID-19 patients. To optimise care for COVID-19 patients, prophylactic and therapeutic studies should include sex-specific design and analyses. Therefore, in this scoping review, we investigated whether studies on pharmacological treatment in COVID-19 were performed based on a priori sex-specific design or post-hoc sex-specific analyses.

Methods: We systematically searched PubMed, EMBASE, UpToDate, clinical trial.org, and MedRxiv for studies on pharmacological treatment for COVID-19 until June 6th, 2020. We included case series, randomized controlled trials, and observational studies in humans (≥18 years) investigating antiviral, antimalarial, and immune system modulating drugs. Data were collected on 1) the proportion of included females, 2) whether sex stratification was performed (a priori by design or post-hoc), and 3) whether effect modification by sex was investigated.

Findings: 30 studies were eligible for inclusion, investigating remdesivir ( = 2), lopinavir/ritonavir ( = 5), favipiravir ( = 1), umifenovir ( = 1), hydroxychloroquine/chloroquine ( = 8), convalescent plasma ( = 6), interleukin-6 (IL-6) pathway inhibitors ( = 5), interleukin-1 (IL-1) pathway inhibitors ( = 1) and corticosteroids ( = 3). Only one study stratified its data based on sex in a post-hoc analysis, whereas none did a priori by design. None of the studies investigated effect modification by sex. A quarter of the studies included twice as many males as females.

Interpretation: Analyses assessing potential interference of sex with (side-)effects of pharmacological therapy for COVID-19 are rarely reported. Considering sex differences in case-fatality rates and genetic, immunological, and hormonal mechanisms, studies should include sex-specific analyses in their design to optimise COVID-19 care.

Funding: None.
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http://dx.doi.org/10.1016/j.eclinm.2020.100652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7701906PMC
December 2020

Decreased serial scores of severe organ failure assessments are associated with survival in mechanically ventilated patients; the prospective Maastricht Intensive Care COVID cohort.

J Crit Care 2021 04 17;62:38-45. Epub 2020 Nov 17.

Department of Intensive Care, Maastricht University Medical Centre+, P. Debyelaan 25, 6202 AZ Maastricht, the Netherlands; Care and Public Health Research Institute (CAPHRI), Maastricht University, Universiteitssingel 40, 6229 ER Maastricht, the Netherlands. Electronic address:

Background: The majority of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are admitted to the Intensive Care Unit (ICU) for mechanical ventilation. The role of multi-organ failure during ICU admission as driver for outcome remains to be investigated yet.

Design And Setting: Prospective cohort of mechanically ventilated critically ill with SARS-CoV-2 infection.

Participants And Methods: 94 participants of the MaastrICCht cohort (21% women) had a median length of stay of 16 days (maximum of 77). After division into survivors (n = 59) and non-survivors (n = 35), we analysed 1555 serial SOFA scores using linear mixed-effects models.

Results: Survivors improved one SOFA score point more per 5 days (95% CI: 4-8) than non-survivors. Adjustment for age, sex, and chronic lung, renal and liver disease, body-mass index, diabetes mellitus, cardiovascular risk factors, and Acute Physiology and Chronic Health Evaluation II score did not change this result. This association was stronger for women than men (P-interaction = 0.043).

Conclusions: The decrease in SOFA score associated with survival suggests multi-organ failure involvement during mechanical ventilation in patients with SARS-CoV-2. Surviving women appeared to improve faster than surviving men. Serial SOFA scores may unravel an unfavourable trajectory and guide decisions in mechanically ventilated patients with SARS-CoV-2.
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http://dx.doi.org/10.1016/j.jcrc.2020.11.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7669472PMC
April 2021

Serial measurements in COVID-19-induced acute respiratory disease to unravel heterogeneity of the disease course: design of the Maastricht Intensive Care COVID cohort (MaastrICCht).

BMJ Open 2020 09 29;10(9):e040175. Epub 2020 Sep 29.

Department of Intensive Care, Maastricht University Medical Center+, Maastricht, The Netherlands.

Introduction: The course of the disease in SARS-CoV-2 infection in mechanically ventilated patients is unknown. To unravel the clinical heterogeneity of the SARS-CoV-2 infection in these patients, we designed the prospective observational Maastricht Intensive Care COVID cohort (MaastrICCht). We incorporated serial measurements that harbour aetiological, diagnostic and predictive information. The study aims to investigate the heterogeneity of the natural course of critically ill patients with a SARS-CoV-2 infection.

Methods And Analysis: Mechanically ventilated patients admitted to the intensive care with a SARS-CoV-2 infection will be included. We will collect clinical variables, vital parameters, laboratory variables, mechanical ventilator settings, chest electrical impedance tomography, ECGs, echocardiography as well as other imaging modalities to assess heterogeneity of the course of a SARS-CoV-2 infection in critically ill patients. The MaastrICCht is also designed to foster various other studies and registries and intends to create an open-source database for investigators. Therefore, a major part of the data collection is aligned with an existing national intensive care data registry and two international COVID-19 data collection initiatives. Additionally, we create a flexible design, so that additional measures can be added during the ongoing study based on new knowledge obtained from the rapidly growing body of evidence. The spread of the COVID-19 pandemic requires the swift implementation of observational research to unravel heterogeneity of the natural course of the disease of SARS-CoV-2 infection in mechanically ventilated patients. Our study design is expected to enhance aetiological, diagnostic and prognostic understanding of the disease. This paper describes the design of the MaastrICCht.

Ethics And Dissemination: Ethical approval has been obtained from the medical ethics committee (Medisch Ethische Toetsingscommissie 2020-1565/3 00 523) of the Maastricht University Medical Centre+ (Maastricht UMC+), which will be performed based on the Declaration of Helsinki. During the pandemic, the board of directors of Maastricht UMC+ adopted a policy to inform patients and ask their consent to use the collected data and to store serum samples for COVID-19 research purposes. All study documentation will be stored securely for fifteen years after recruitment of the last patient. The results will be published in peer-reviewed academic journals, with a preference for open access journals, while particularly considering deposition of the manuscripts on a preprint server early.

Trial Registration Number: The Netherlands Trial Register (NL8613).
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http://dx.doi.org/10.1136/bmjopen-2020-040175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526030PMC
September 2020

Anti-decubitus bed mattress may interfere with cerebrovascular pressure reactivity measures due to induced ICP and ABP cyclic peaks.

J Clin Monit Comput 2021 04 8;35(2):423-425. Epub 2020 Feb 8.

Department of Intensive Care, University of Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands.

Severe traumatic brain injury (TBI) patients are monitored with continuous arterial blood pressure (ABP) and intracranial pressure (ICP). The pressure reactivity index (PRx) is a frequently used correlation coefficient between ABP and ICP to inform clinicians at the bedside about trends in global cerebrovascular pressure regulation status. We present an unexpected influence of cyclic anti-decubitus mattress inflations and deflations on invasive ICP, ABP and PRx calculations in our TBI patients. This might affect autoregulation guided management. In our database, 23% (9/39) of the patients show recurrent peaks in the monitoring signals. We hypothesize that these peaks are caused by (a combination) of hydrostatic change, local (cervical) compression and/or incorrect sensor zeroing due to positional changes induced by the anti-decubitus mattress. This warrants further investigation by the manufacturer and exploration of data filters.
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http://dx.doi.org/10.1007/s10877-020-00471-5DOI Listing
April 2021

Feasibility of individualised severe traumatic brain injury management using an automated assessment of optimal cerebral perfusion pressure: the COGiTATE phase II study protocol.

BMJ Open 2019 09 20;9(9):e030727. Epub 2019 Sep 20.

Division of Anaesthesia, University of Cambridge, Cambridge, UK.

Introduction: Individualising therapy is an important challenge for intensive care of patients with severe traumatic brain injury (TBI). Targeting a cerebral perfusion pressure (CPP) tailored to optimise cerebrovascular autoregulation has been suggested as an attractive strategy on the basis of a large body of retrospective observational data. The objective of this study is to prospectively assess the feasibility and safety of such a strategy compared with fixed thresholds which is the current standard of care from international consensus guidelines.

Methods And Analysis: CPPOpt Guided Therapy: Assessment of Target Effectiveness (COGiTATE) is a prospective, multicentre, non-blinded randomised, controlled trial coordinated from Maastricht University Medical Center, Maastricht (The Netherlands). The other original participating centres are Cambridge University NHS Foundation Trust, Cambridge (UK), and University Hospitals Leuven, Leuven (Belgium). Adult severe TBI patients requiring intracranial pressure monitoring are randomised within the first 24 hours of admission in neurocritical care unit. For the control arm, the CPP target is the Brain Trauma Foundation guidelines target (60-70 mm Hg); for the intervention group an automated CPP target is provided as the CPP at which the patient's cerebrovascular reactivity is best preserved (CPPopt). For a maximum of 5 days, attending clinicians review the CPP target 4-hourly. The main hypothesis of COGiTATE are: (1) in the intervention group the percentage of the monitored time with measured CPP within a range of 5 mm Hg above or below CPPopt will reach 36%; (2) the difference in between groups in daily therapy intensity level score will be lower or equal to 3.

Ethics And Dissemination: Ethical approval has been obtained for each participating centre. The results will be presented at international scientific conferences and in peer-reviewed journals.

Trial Registration Number: NCT02982122.
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http://dx.doi.org/10.1136/bmjopen-2019-030727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6756360PMC
September 2019

Dynamic cerebral autoregulation estimates derived from near infrared spectroscopy and transcranial Doppler are similar after correction for transit time and blood flow and blood volume oscillations.

J Cereb Blood Flow Metab 2020 01 24;40(1):135-149. Epub 2018 Oct 24.

Department of Neurology, University Medical Center Groningen, Groningen, The Netherlands.

We analysed mean arterial blood pressure, cerebral blood flow velocity, oxygenated haemoglobin and deoxygenated haemoglobin signals to estimate dynamic cerebral autoregulation. We compared macrovascular (mean arterial blood pressure-cerebral blood flow velocity) and microvascular (oxygenated haemoglobin-deoxygenated haemoglobin) dynamic cerebral autoregulation estimates during three different conditions: rest, mild hypocapnia and hypercapnia. Microvascular dynamic cerebral autoregulation estimates were created by introducing the constant time lag plus constant phase shift model, which enables correction for transit time, blood flow and blood volume oscillations (TT-BF/BV correction). After TT-BF/BV correction, a significant agreement between mean arterial blood pressure-cerebral blood flow velocity and oxygenated haemoglobin-deoxygenated haemoglobin phase differences in the low frequency band was found during rest (left: intraclass correlation=0.6, median phase difference 29.5° vs. 30.7°, right: intraclass correlation=0.56, median phase difference 32.6° vs. 39.8°) and mild hypocapnia (left: intraclass correlation=0.73, median phase difference 48.6° vs. 43.3°, right: intraclass correlation=0.70, median phase difference 52.1° vs. 61.8°). During hypercapnia, the mean transit time decreased and blood volume oscillations became much more prominent, except for very low frequencies. The transit time related to blood flow oscillations was remarkably stable during all conditions. We conclude that non-invasive microvascular dynamic cerebral autoregulation estimates are similar to macrovascular dynamic cerebral autoregulation estimates, after TT-BF/BV correction is applied. These findings may increase the feasibility of non-invasive continuous autoregulation monitoring and guided therapy in clinical situations.
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http://dx.doi.org/10.1177/0271678X18806107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927073PMC
January 2020
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