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Article ; Online: Thrombosis pathways in COVID-19 vs. influenza-associated ARDS: A targeted proteomics approach.

Rademaker, Emma / Doorduijn, Dennis J / Kusadasi, Nuray / Maas, Coen / Drylewicz, Julia / Huisman, Albert / Hoefer, Imo E / Bonten, Marc J M / Derde, Lennie P G / Rooijakkers, Suzan H M / Cremer, Olaf L

Journal of thrombosis and haemostasis : JTH

2022 Volume 20, Issue 5, Page(s) 1206–1212

Abstract: Background: Pulmonary embolism (PE) occurs in one-third of critically-ill COVID-19 patients. Although prior studies identified several pathways contributing to thrombogenicity, it is unknown whether this is COVID-19-specific or also occurs in ARDS ... ...

Abstract	Background: Pulmonary embolism (PE) occurs in one-third of critically-ill COVID-19 patients. Although prior studies identified several pathways contributing to thrombogenicity, it is unknown whether this is COVID-19-specific or also occurs in ARDS patients with another infection. Objective: To compare pathway activity among patients having COVID-19 with PE (C19PE+), COVID-19 without PE (C19PE-), and influenza-associated ARDS (IAA) using a targeted proteomics approach. Methods: We exploited an existing biorepository containing daily plasma samples to carefully match C19PE+ cases to C19PE- and IAA controls on mechanical ventilation duration, PEEP, FiO2, and cardiovascular-SOFA (n = 15 per group). Biomarkers representing various thrombosis pathways were measured using proximity extension- and ELISA-assays. Summed z-scores of individual biomarkers were used to represent total pathway activity. Results: We observed no relevant between-group differences among 22 biomarkers associated with activation of endothelium, platelets, complement, coagulation, fibrinolysis or inflammation, except sIL-1RT2 and sST2, which were lower in C19PE- than IAA (log2-Foldchange -0.67, p = .022 and -1.78, p = .022, respectively). However, total pathway analysis indicated increased activation of endothelium (z-score 0.2 [-0.3-1.03] vs. 0.98 [-2.5--0.3], p = .027), platelets (1.0 [-1.3-3.0] vs. -3.3 [-4.1--0.6], p = .023) and coagulation (0.8 [-0.5-2.0] vs. -1.0 [-1.6-1.0], p = .023) in COVID-19 patients (C19PE+/C19PE- groups combined) compared to IAA. Conclusion: We observed only minor differences between matched C19PE+, C19PE-, and IAA patients, which suggests individual biomarkers mostly reflect disease severity. However, analysis of total pathway activity suggested upregulation of some distinct processes in COVID-19 could be etiologically related to increased PE-risk.
MeSH term(s)	Biomarkers ; COVID-19/complications ; Humans ; Influenza, Human/complications ; Influenza, Human/diagnosis ; Proteomics ; Pulmonary Embolism/diagnosis ; Respiratory Distress Syndrome ; SARS-CoV-2 ; Thrombosis
Chemical Substances	Biomarkers
Language	English
Publishing date	2022-02-27
Publishing country	England
Document type	Journal Article
ZDB-ID	2112661-6
ISSN	1538-7836 ; 1538-7933
ISSN (online)	1538-7836
ISSN	1538-7933
DOI	10.1111/jth.15671
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Article: Prognostic Value of [

Pullen, Lieke C E / Noortman, Wyanne A / Triemstra, Lianne / de Jongh, Cas / Rademaker, Fenna J / Spijkerman, Romy / Kalisvaart, Gijsbert M / Gertsen, Emma C / de Geus-Oei, Lioe-Fee / Tolboom, Nelleke / de Steur, Wobbe O / Dantuma, Maura / Slart, Riemer H J A / van Hillegersberg, Richard / Siersema, Peter D / Ruurda, Jelle P / van Velden, Floris H P / Vegt, Erik / On Behalf Of The Plastic Study Group

Cancers

2023 Volume 15, Issue 11

Abstract: Aim: To improve identification of peritoneal and distant metastases in locally advanced gastric cancer using [: Methods: [: Results: None of the models could identify metastases with low AUCs of 0.59, 0.51, and 0.56, for the clinical, radiomic, ... ...

Abstract	Aim: To improve identification of peritoneal and distant metastases in locally advanced gastric cancer using [ Methods: [ Results: None of the models could identify metastases with low AUCs of 0.59, 0.51, and 0.56, for the clinical, radiomic, and clinicoradiomic model, respectively. Subgroup analysis of intestinal and mixed-type tumours resulted in low AUCs of 0.67 and 0.60 for the clinical and radiomic models, and a moderate AUC of 0.71 in the clinicoradiomic model. Subgroup analysis of diffuse-type tumours did not improve the classification performance. Conclusion: Overall, [
Language	English
Publishing date	2023-05-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15112874
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Article ; Online: Lupus anticoagulant associates with thrombosis in patients with COVID-19 admitted to intensive care units: A retrospective cohort study.

Noordermeer, Tessa / Schutgens, Roger E G / Visser, Chantal / Rademaker, Emma / de Maat, Moniek P M / Jansen, A J Gerard / Limper, Maarten / Cremer, Olaf L / Kruip, Marieke J H A / Endeman, Henrik / Maas, Coen / de Laat, Bas / Urbanus, Rolf T

Research and practice in thrombosis and haemostasis

2022 Volume 6, Issue 6, Page(s) e12809

Abstract: Background: Thrombosis is a frequent and severe complication in patients with coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU). Lupus anticoagulant (LA) is a strong acquired risk factor for thrombosis in various diseases and ...

Abstract	Background: Thrombosis is a frequent and severe complication in patients with coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU). Lupus anticoagulant (LA) is a strong acquired risk factor for thrombosis in various diseases and is frequently observed in patients with COVID-19. Whether LA is associated with thrombosis in patients with severe COVID-19 is currently unclear. Objective: To investigate if LA is associated with thrombosis in critically ill patients with COVID-19. Patients/methods: The presence of LA and other antiphospholipid antibodies was assessed in patients with COVID-19 admitted to the ICU. LA was determined with dilute Russell's viper venom time (dRVVT) and LA-sensitive activated partial thromboplastin time (aPTT) reagents. Results: Of 169 patients with COVID-19, 116 (69%) tested positive for at least one antiphospholipid antibody upon admission to the ICU. Forty (24%) patients tested positive for LA; of whom 29 (17%) tested positive with a dRVVT, 19 (11%) tested positive with an LA-sensitive aPTT, and 8 (5%) tested positive on both tests. Fifty-eight (34%) patients developed thrombosis after ICU admission. The odds ratio (OR) for thrombosis in patients with LA based on a dRVVT was 2.5 (95% confidence interval [CI], 1.1-5.7), which increased to 4.5 (95% CI, 1.4-14.3) in patients at or below the median age in this study (64 years). LA positivity based on a dRVVT or LA-sensitive aPTT was only associated with thrombosis in patients aged less than 65 years (OR, 3.8; 95% CI, 1.3-11.4) and disappeared after adjustment for C-reactive protein. Conclusion: Lupus anticoagulant on admission is strongly associated with thrombosis in critically ill patients with COVID-19, especially in patients aged less than 65 years.
Language	English
Publishing date	2022-09-16
Publishing country	United States
Document type	Journal Article
ISSN	2475-0379
ISSN (online)	2475-0379
DOI	10.1002/rth2.12809
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Article ; Online: High-salt intake affects retinal vascular tortuosity in healthy males: an exploratory randomized cross-over trial.

Wenstedt, Eliane F E / Beugelink, Lisanne / Schrooten, Esmee M / Rademaker, Emma / Rorije, Nienke M G / Wouda, Rosa D / Schlingemann, Reinier O / Wong, Tien Y / Vogt, Liffert

Scientific reports

2021 Volume 11, Issue 1, Page(s) 801

Abstract: The retinal microcirculation is increasingly receiving credit as a relatively easily accessible microcirculatory bed that correlates closely with clinical cardiovascular outcomes. The effect of high salt (NaCl) intake on the retinal microcirculation is ... ...

Abstract	The retinal microcirculation is increasingly receiving credit as a relatively easily accessible microcirculatory bed that correlates closely with clinical cardiovascular outcomes. The effect of high salt (NaCl) intake on the retinal microcirculation is currently unknown. Therefore, we performed an exploratory randomized cross-over dietary intervention study in 18 healthy males. All subjects adhered to a two-week high-salt diet and low-salt diet, in randomized order, after which fundus photographs were taken and assessed using a semi-automated computer-assisted program (SIVA, version 4.0). Outcome parameters involved retinal venular and arteriolar tortuosity, vessel diameter, branching angle and fractal dimension. At baseline, participants had a mean (SD) age of 29.8 (4.4) years and blood pressure of 117 (9)/73 (5) mmHg. Overall, high-salt diet significantly increased venular tortuosity (12.2%, p = 0.001). Other retinal parameters were not significantly different between diets. Changes in arteriolar tortuosity correlated with changes in ambulatory systolic blood pressure (r = - 0.513; p = 0.04). In conclusion, high-salt diet increases retinal venular tortuosity, and salt-induced increases in ambulatory systolic blood pressure associate with decreases in retinal arteriolar tortuosity. Besides potential eye-specific consequences, both phenomena have previously been associated with hypertension and other cardiovascular risk factors, underlining the deleterious microcirculatory effects of high salt intake.
MeSH term(s)	Adult ; Arterioles/drug effects ; Cross-Over Studies ; Diagnostic Techniques, Ophthalmological ; Healthy Volunteers ; Heart Disease Risk Factors ; Humans ; Hypertension/chemically induced ; Hypertension/physiopathology ; Male ; Microcirculation ; Retinal Vessels/drug effects ; Retinal Vessels/physiopathology ; Sodium Chloride, Dietary/pharmacology ; Venules/drug effects
Chemical Substances	Sodium Chloride, Dietary
Language	English
Publishing date	2021-01-12
Publishing country	England
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-020-79753-6
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Article ; Online: High-salt intake affects retinal vascular tortuosity in healthy males

Eliane F. E. Wenstedt / Lisanne Beugelink / Esmee M. Schrooten / Emma Rademaker / Nienke M. G. Rorije / Rosa D. Wouda / Reinier O. Schlingemann / Tien Y. Wong / Liffert Vogt

Scientific Reports, Vol 11, Iss 1, Pp 1-

an exploratory randomized cross-over trial

2021 Volume 8

Abstract: Abstract The retinal microcirculation is increasingly receiving credit as a relatively easily accessible microcirculatory bed that correlates closely with clinical cardiovascular outcomes. The effect of high salt (NaCl) intake on the retinal ... ...

Abstract	Abstract The retinal microcirculation is increasingly receiving credit as a relatively easily accessible microcirculatory bed that correlates closely with clinical cardiovascular outcomes. The effect of high salt (NaCl) intake on the retinal microcirculation is currently unknown. Therefore, we performed an exploratory randomized cross-over dietary intervention study in 18 healthy males. All subjects adhered to a two-week high-salt diet and low-salt diet, in randomized order, after which fundus photographs were taken and assessed using a semi-automated computer-assisted program (SIVA, version 4.0). Outcome parameters involved retinal venular and arteriolar tortuosity, vessel diameter, branching angle and fractal dimension. At baseline, participants had a mean (SD) age of 29.8 (4.4) years and blood pressure of 117 (9)/73 (5) mmHg. Overall, high-salt diet significantly increased venular tortuosity (12.2%, p = 0.001). Other retinal parameters were not significantly different between diets. Changes in arteriolar tortuosity correlated with changes in ambulatory systolic blood pressure (r = − 0.513; p = 0.04). In conclusion, high-salt diet increases retinal venular tortuosity, and salt-induced increases in ambulatory systolic blood pressure associate with decreases in retinal arteriolar tortuosity. Besides potential eye-specific consequences, both phenomena have previously been associated with hypertension and other cardiovascular risk factors, underlining the deleterious microcirculatory effects of high salt intake.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
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Article ; Online: Virtual reality training of lucid dreaming.

Philosophical transactions of the Royal Society of London. Series B, Biological sciences

2020 Volume 376, Issue 1817, Page(s) 20190697

Abstract: Metacognitive reflections on one's current state of mind are largely absent during dreaming. Lucid dreaming as the exception to this rule is a rare phenomenon; however, its occurrence can be facilitated through cognitive training. A central idea of ... ...

Abstract	Metacognitive reflections on one's current state of mind are largely absent during dreaming. Lucid dreaming as the exception to this rule is a rare phenomenon; however, its occurrence can be facilitated through cognitive training. A central idea of respective training strategies is to regularly question one's phenomenal experience: is the currently experienced world
MeSH term(s)	Dreams ; Humans ; Virtual Reality
Language	English
Publishing date	2020-12-14
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	208382-6
ISSN	1471-2970 ; 0080-4622 ; 0264-3839 ; 0962-8436
ISSN (online)	1471-2970
ISSN	0080-4622 ; 0264-3839 ; 0962-8436
DOI	10.1098/rstb.2019.0697
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Article ; Online: High-salt intake affects sublingual microcirculation and is linked to body weight change in healthy volunteers: a randomized cross-over trial.

Rorije, Nienke M G / Rademaker, Emma / Schrooten, Esmee M / Wouda, Rosa D / Homan Van Der Heide, Jacob J / Van Den Born, Bert-Jan H / Vogt, Liffert

Journal of hypertension

2018 Volume 37, Issue 6, Page(s) 1254–1261

Abstract: Background: The pathophysiology of salt-sensitive hypertension remains uncertain, but may involve microvascular alterations. High-salt intake decreases microvascular density in hypertensive patients, but due to lack of studies in normotensive patients ... ...

Abstract	Background: The pathophysiology of salt-sensitive hypertension remains uncertain, but may involve microvascular alterations. High-salt intake decreases microvascular density in hypertensive patients, but due to lack of studies in normotensive patients the causal pathway remains unclear. We studied whether high-salt intake decreases sublingual microvascular density in normotensive individuals and assessed the influence of body weight on changes in microvascular density. Methods: In an open label randomized cross-over trial 18 healthy men were included to study the effect of a 2-week high-salt (>12 g/day) and low-salt (<3 g/day) diet on microvascular (diameter <20 μm) density with sublingual sidestream darkfield imaging. We used sublingual nitroglycerin (NTG) to recruit microvessels. Results: There was no significant difference in microvascular density between diets (0.96 ± 3.88 mm/mm; P = 0.31, following NTG; and -0.03 ± 1.64 mm/mm; P = 0.95, without NTG). Increased salt intake was correlated with a decrease in microvascular density following NTG (r = -0.47; P = 0.047), but not without NTG (r = 0.06; P = 0.800). The decrease in microvascular density following high-salt intake was significantly larger for those with a large change in body weight as compared with those with a small changer in body weight (-0.79 ± 1.35 and 0.84 ± 1.56 mm/mm respectively, P = 0.031). Conclusion: We demonstrate in healthy volunteers that higher salt intake is correlated with decreased sublingual microvascular density following administration of NTG and; larger changes in body weight following high-salt intake coincide with a larger decrease in microvascular density. Changes in microvascular density occurred without blood pressure effects, indicating that high-salt load as such contributes to microvascular changes, and may precede hypertension development.
MeSH term(s)	Adult ; Blood Pressure ; Body Weight ; Cross-Over Studies ; Healthy Volunteers ; Humans ; Hypertension/chemically induced ; Male ; Microcirculation/drug effects ; Microvessels/drug effects ; Mouth Floor/blood supply ; Nitroglycerin ; Sodium Chloride/pharmacology ; Sodium Chloride, Dietary/pharmacology ; Time Factors ; Young Adult
Chemical Substances	Sodium Chloride, Dietary ; Sodium Chloride (451W47IQ8X) ; Nitroglycerin (G59M7S0WS3)
Language	English
Publishing date	2018-12-21
Publishing country	England
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	605532-1
ISSN	1473-5598 ; 0263-6352 ; 0952-1178
ISSN (online)	1473-5598
ISSN	0263-6352 ; 0952-1178
DOI	10.1097/HJH.0000000000002015
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Article ; Online: Salt increases monocyte CCR2 expression and inflammatory responses in humans.

Wenstedt, Eliane Fe / Verberk, Sanne Gs / Kroon, Jeffrey / Neele, Annette E / Baardman, Jeroen / Claessen, Nike / Pasaoglu, Özge T / Rademaker, Emma / Schrooten, Esmee M / Wouda, Rosa D / de Winther, Menno Pj / Aten, Jan / Vogt, Liffert / Van den Bossche, Jan

JCI insight

2019 Volume 4, Issue 21

Abstract: Inflammation may play a role in the link between high salt intake and its deleterious consequences. However, it is unknown whether salt can induce proinflammatory priming of monocytes and macrophages in humans. We investigated the effects of salt on ... ...

Abstract	Inflammation may play a role in the link between high salt intake and its deleterious consequences. However, it is unknown whether salt can induce proinflammatory priming of monocytes and macrophages in humans. We investigated the effects of salt on monocytes and macrophages in vitro and in vivo by performing a randomized crossover trial in which 11 healthy human subjects adhered to a 2-week low-salt and high-salt diet. We demonstrate that salt increases monocyte expression of CCR2, a chemokine receptor that mediates monocyte infiltration in inflammatory diseases. In line with this, we show a salt-induced increase of plasma MCP-1, transendothelial migration of monocytes, and skin macrophage density after high-salt diet. Macrophages demonstrate signs of an increased proinflammatory phenotype after salt exposure, as represented by boosted LPS-induced cytokine secretion of IL-6, TNF, and IL-10 in vitro, and by increased HLA-DR expression and decreased CD206 expression on skin macrophages after high-salt diet. Taken together, our data open up the possibility for inflammatory monocyte and macrophage responses as potential contributors to the deleterious effects of high salt intake.
MeSH term(s)	Adult ; Cross-Over Studies ; Cytokines/metabolism ; Female ; Humans ; Inflammation/metabolism ; Male ; Monocytes/drug effects ; Monocytes/metabolism ; Receptors, CCR2/metabolism ; Sodium Chloride, Dietary/metabolism ; Sodium Chloride, Dietary/pharmacology ; Young Adult
Chemical Substances	CCR2 protein, human ; Cytokines ; Receptors, CCR2 ; Sodium Chloride, Dietary
Language	English
Publishing date	2019-11-01
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.130508
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Article: The combination of intravenous bevacizumab and metronomic oral cyclophosphamide is an effective regimen for platinum-resistant recurrent ovarian cancer.

Barber, Emma L / Zsiros, Emese / Lurain, John R / Rademaker, Alfred / Schink, Julian C / Neubauer, Nikki L

Journal of gynecologic oncology

2013 Volume 24, Issue 3, Page(s) 258–264

Abstract: Objective: To determine the efficacy, progression-free survival (PFS) and overall survival (OS) for the combination of intravenous bevacizumab and oral cyclophosphamide in heavily pretreated patients with recurrent ovarian carcinoma.: Methods: A ... ...

Abstract	Objective: To determine the efficacy, progression-free survival (PFS) and overall survival (OS) for the combination of intravenous bevacizumab and oral cyclophosphamide in heavily pretreated patients with recurrent ovarian carcinoma. Methods: A retrospective review was performed for all patients with recurrent ovarian carcinoma treated with intravenous bevacizumab 10 mg/kg every 14 days and oral cyclophosphamide 50 mg daily between January 2006 and December 2010. Response to treatment was determined by Response Evaluation Criteria in Solid Tumors criteria and/or CA-125 levels. Results: Sixty-six eligible patients were identified. Median age was 53 years. Fifty-five patients (83%) had undergone optimal cytoreduction. All patients were primarily or secondarily platinum resistant at the time of administration of bevacizumab and cyclophosphamide. The median number of prior chemotherapy treatments was 6.5 (range, 3 to 16). Eight patients (12.1%) had side effects which required discontinuation of bevacizumab and cyclophosphamide. There was one bowel perforation (1.5%). Overall response rate was 42.4%, including, complete response in 7 patients (10.6%), and partial response in 21 patients (31.8%), while 15 patients (22.7%) had stable disease and 23 patients (34.8%) had disease progression. Median PFS for responders was 5 months (range, 2 to 14 months). Median OS from initiation of bevacizumab and cyclophosphamide was 20 months (range, 2 to 56 months) for responders and 9 months (range, 2 to 51 months) for non-responders (p=0.004). Conclusion: Bevacizumab and cyclophosphamide is an effective, well-tolerated chemotherapy regimen in heavily pretreated patients with recurrent ovarian carcinoma. This combination significantly improved PFS and OS in responders. Response rates were similar and favorable to the rates reported for similar patients receiving other commonly used second-line chemotherapeutic agents.
Language	English
Publishing date	2013-07-04
Publishing country	Korea (South)
Document type	Journal Article
ZDB-ID	2478405-9
ISSN	2005-0399 ; 2005-0380
ISSN (online)	2005-0399
ISSN	2005-0380
DOI	10.3802/jgo.2013.24.3.258
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Article ; Online: Growth and prevalence of feeding difficulties in children with Robin sequence: a retrospective cohort study.

Paes, Emma C / de Vries, Iris A C / Penris, Wouter M / Hanny, Karlijn H / Lavrijsen, Selma W / van Leerdam, Elselien K / Rademaker, Maaike M / Veldhoen, Esther S / Eijkemans, Rene M J C / Kon, Moshe / Breugem, Corstiaan C

Clinical oral investigations

2017 Volume 21, Issue 6, Page(s) 2063–2076

Abstract: Objectives: In addition to breathing problems, patients with Robin sequence (RS) often encounter feeding difficulties (FD). Data regarding the occurrence of FD and possible influencing factors are scarce. The study aim was to elucidate these factors to ... ...

Abstract	Objectives: In addition to breathing problems, patients with Robin sequence (RS) often encounter feeding difficulties (FD). Data regarding the occurrence of FD and possible influencing factors are scarce. The study aim was to elucidate these factors to improve treatment strategies. Material and methods: A retrospective comparative cohort study was conducted, consisting of 69 infants diagnosed with both RS and a cleft palate and 64 isolated cleft palate only (iCPO) infants. Data regarding FD, growth, and airway intervention were collected during the first 2 years of life. A systematic review of the literature was conducted to identify reported FD in RS patients. Results: RS patients had more FD (91 %) than iCPO patients (72 %; p = 0.004). Also, nasogastric (NG)-tube feeding was necessary more frequently and for a longer period (both p < 0.001). Growth was lower in RS than iCPO infants (p = 0.008) and was not affected by the kind of airway management (conservative/surgical; p = 0.178), cleft palate grade (p = 0.308), or associated disorders (p = 0.785). By contrast, surgical intervention subtype did significantly affect growth. Mean reported FD for RS in the literature is 80 % (range = 47-100 %), and 55 % (range = 11-100 %) of infants need NG-tube feeding. Conclusions: FD is present in a large proportion of infants with RS, which indicates the need for early recognition and proper treatment to ensure optimal growth. Growth during the first 2 years of life is significantly lower in RS patients than iCPO patients, which indicates the need for careful attention and long-term follow-up. Clinical relevance: This study indicates the need for early recognition and proper treatment of FD in RS to ensure optimal growth. In addition, growth needs careful attention and long-term follow-up.
Language	English
Publishing date	2017-07
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1364490-7
ISSN	1436-3771 ; 1432-6981
ISSN (online)	1436-3771
ISSN	1432-6981
DOI	10.1007/s00784-016-1996-8
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