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Article ; Online: Reply to Author.

Walk, Jona / Janssen, Rob / Dofferhoff, Anton S M

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

2021 Volume 73, Issue 7, Page(s) 1325

Language	English
Publishing date	2021-03-18
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	1099781-7
ISSN	1537-6591 ; 1058-4838
ISSN (online)	1537-6591
ISSN	1058-4838
DOI	10.1093/cid/ciab166
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Article ; Online: Ernstige bijwerkingen van fluorochinolonen.

Boes, J / Dofferhoff, A S M / Fleuren, H W H A / Kramers, C

Nederlands tijdschrift voor geneeskunde

2020 Volume 164

Abstract: Fluoroquinolones are frequently prescribed antibiotics. Recently, the Dutch medicines evaluation board CBG warned about the risk of aortic aneurysms and dissections with the use of fluoroquinolones. We reviewed the three articles used in this warning. We ...

Title translation	Serious side effects of fluoroquinolones: low risk of connective tissue-related disorders such as aneurysms.
Abstract	Fluoroquinolones are frequently prescribed antibiotics. Recently, the Dutch medicines evaluation board CBG warned about the risk of aortic aneurysms and dissections with the use of fluoroquinolones. We reviewed the three articles used in this warning. We consider that the evidence for a causal relationship is limited. The hazard ratio for the association with fluoroquinolones and aortic aneurysms was around 2. The absolute risk is low given the low prevalence in the general population. However, aortic aneurysms and dissections are life-threatening conditions and must be taken serious. We advise what to do in case of known aortic aneurysms or the presence of multiple risk factors.
MeSH term(s)	Aged ; Aneurysm, Dissecting/chemically induced ; Anti-Bacterial Agents/adverse effects ; Aortic Aneurysm/chemically induced ; Fluoroquinolones/adverse effects ; Humans ; Male ; Risk Factors
Chemical Substances	Anti-Bacterial Agents ; Fluoroquinolones
Language	Dutch
Publishing date	2020-11-19
Publishing country	Netherlands
Document type	Case Reports ; Journal Article
ZDB-ID	82073-8
ISSN	1876-8784 ; 0028-2162
ISSN (online)	1876-8784
ISSN	0028-2162
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Article ; Online: COVID-19-associated pulmonary aspergillosis: a prospective single-center dual case series.

Meijer, Eelco F J / Dofferhoff, Anton S M / Hoiting, Oscar / Meis, Jacques F

Mycoses

2021 Volume 64, Issue 4, Page(s) 457–464

Abstract: Background: COVID-19-associated pulmonary aspergillosis (CAPA) has emerged as an invasive fungal disease, often affecting previously immunocompetent, mechanically ventilated, intensive care unit (ICU) patients. Incidence rates of 3.8%-33.3% have been ... ...

Abstract	Background: COVID-19-associated pulmonary aspergillosis (CAPA) has emerged as an invasive fungal disease, often affecting previously immunocompetent, mechanically ventilated, intensive care unit (ICU) patients. Incidence rates of 3.8%-33.3% have been reported depending on the geographic area, with high (47%) mortality. Objectives: Here, we describe a single-centre prospective case series with CAPA cases from both the first (March-May, n = 5/33) and second (mid-September through mid-December, n = 8/33) COVID-19 wave at a 500-bed teaching hospital in the Netherlands. Patients/methods: In the first COVID-19 wave, a total of 265 SARS-CoV-2 PCR-positive patients were admitted to our hospital of whom 33 needed intubation and mechanical ventilation. In the second wave, 508 SARS-CoV-2 PCR-positive patients were admitted of whom 33 needed mechanical ventilation. Data were prospectively collected. Results: We found a significant decrease in COVID-19 patients needing mechanical ventilation in the ICU in the second wave (p < .01). From these patients, however, a higher percentage were diagnosed with CAPA (24.2% vs 15.2%), although not significant (p = .36). All CAPA patients encountered in the second wave received dexamethasone. Mortality between both groups was similarly high (40%-50%). Moreover, we found environmental TR Conclusions: In this series, 19.7% (n = 13/66) of mechanically ventilated SARS-CoV-2 patients were diagnosed with CAPA. In addition, we found a significant reduction in COVID-19 patients needing mechanical ventilation on the ICU in the second wave. Numbers are too small to determine whether there is a true difference in CAPA incidence in mechanically ventilated patients between the two waves, and whether it could be attributed to dexamethasone SARS-CoV-2 therapy.
MeSH term(s)	Aged ; COVID-19/complications ; COVID-19/diagnosis ; Cohort Studies ; Female ; Humans ; Intensive Care Units ; Male ; Netherlands/epidemiology ; Polymerase Chain Reaction ; Prospective Studies ; Pulmonary Aspergillosis/complications ; Pulmonary Aspergillosis/epidemiology ; Pulmonary Aspergillosis/etiology ; Pulmonary Aspergillosis/mortality ; Respiration, Artificial ; Respiratory Insufficiency/etiology ; Respiratory Insufficiency/therapy ; SARS-CoV-2/genetics ; SARS-CoV-2/isolation & purification
Language	English
Publishing date	2021-02-16
Publishing country	Germany
Document type	Journal Article
ZDB-ID	392487-7
ISSN	1439-0507 ; 0933-7407
ISSN (online)	1439-0507
ISSN	0933-7407
DOI	10.1111/myc.13254
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Article ; Online: Azole-Resistant COVID-19-Associated Pulmonary Aspergillosis in an Immunocompetent Host: A Case Report.

Meijer, Eelco F J / Dofferhoff, Anton S M / Hoiting, Oscar / Buil, Jochem B / Meis, Jacques F

Journal of fungi (Basel, Switzerland)

2020 Volume 6, Issue 2

Abstract: COVID-19-associated pulmonary aspergillosis (CAPA) is a recently described disease entity affecting patients with severe pulmonary abnormalities treated in intensive care units. Delays in diagnosis contribute to a delayed start of antifungal therapy. In ... ...

Abstract	COVID-19-associated pulmonary aspergillosis (CAPA) is a recently described disease entity affecting patients with severe pulmonary abnormalities treated in intensive care units. Delays in diagnosis contribute to a delayed start of antifungal therapy. In addition, the emergence of resistance to triazole antifungal agents puts emphasis on early surveillance for azole-resistant
Keywords	covid19
Language	English
Publishing date	2020-06-06
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2784229-0
ISSN	2309-608X ; 2309-608X
ISSN (online)	2309-608X
ISSN	2309-608X
DOI	10.3390/jof6020079
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Article ; Online: Vitamin K metabolism as the potential missing link between lung damage and thromboembolism in Coronavirus disease 2019.

Janssen, Rob / Visser, Margot P J / Dofferhoff, Anton S M / Vermeer, Cees / Janssens, Wim / Walk, Jona

The British journal of nutrition

2020 Volume 126, Issue 2, Page(s) 191–198

Abstract: ... in the liver and the activation of extrahepatically synthesised protein S which seems to be important in local ... We therefore expect that vitamin K-dependent endothelial protein S activation is also compromised, which would be ... induced vitamin K depletion, leading to a decrease in activated MGP and protein S, aggravating pulmonary ...

Abstract	Coronavirus disease 2019 (Covid-19), caused by severe acute respiratory syndrome coronavirus (SARS-CoV)-2, exerts far-reaching effects on public health and socio-economic welfare. The majority of infected individuals have mild to moderate symptoms, but a significant proportion develops respiratory failure due to pneumonia. Thrombosis is another frequent manifestation of Covid-19 that contributes to poor outcomes. Vitamin K plays a crucial role in the activation of both pro- and anticlotting factors in the liver and the activation of extrahepatically synthesised protein S which seems to be important in local thrombosis prevention. However, the role of vitamin K extends beyond coagulation. Matrix Gla protein (MGP) is a vitamin K-dependent inhibitor of soft tissue calcification and elastic fibre degradation. Severe extrahepatic vitamin K insufficiency was recently demonstrated in Covid-19 patients, with high inactive MGP levels correlating with elastic fibre degradation rates. This suggests that insufficient vitamin K-dependent MGP activation leaves elastic fibres unprotected against SARS-CoV-2-induced proteolysis. In contrast to MGP, Covid-19 patients have normal levels of activated factor II, in line with previous observations that vitamin K is preferentially transported to the liver for activation of procoagulant factors. We therefore expect that vitamin K-dependent endothelial protein S activation is also compromised, which would be compatible with enhanced thrombogenicity. Taking these data together, we propose a mechanism of pneumonia-induced vitamin K depletion, leading to a decrease in activated MGP and protein S, aggravating pulmonary damage and coagulopathy, respectively. Intervention trials should be conducted to assess whether vitamin K administration plays a role in the prevention and treatment of severe Covid-19.
MeSH term(s)	COVID-19/complications ; COVID-19/pathology ; Calcium-Binding Proteins/metabolism ; Extracellular Matrix Proteins/metabolism ; Humans ; Lung/physiopathology ; Protein S/metabolism ; SARS-CoV-2 ; Thromboembolism/etiology ; Thromboembolism/prevention & control ; Thrombosis/etiology ; Thrombosis/prevention & control ; Vitamin K/antagonists & inhibitors ; Vitamin K/metabolism ; Vitamin K Deficiency/etiology ; Vitamin K Deficiency/metabolism ; Matrix Gla Protein
Chemical Substances	Calcium-Binding Proteins ; Extracellular Matrix Proteins ; Protein S ; Vitamin K (12001-79-5)
Keywords	covid19
Language	English
Publishing date	2020-10-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	280396-3
ISSN	1475-2662 ; 0007-1145
ISSN (online)	1475-2662
ISSN	0007-1145
DOI	10.1017/S0007114520003979
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Article: Vitamin K metabolism as the potential missing link between lung damage and thromboembolism in Covid-19

Janssen, R. / Visser, M. P. J. / Dofferhoff, A. S. M. / Vermeer, C. / Janssens, W. / Walk, J.

Br J Nutr

Abstract: ... S which seems to be important in local thrombosis prevention However, the role of vitamin K extends ... of procoagulant factors We therefore expect that vitamin K-dependent endothelial protein S activation is also ... a mechanism of pneumonia-induced vitamin K depletion, leading to a decrease in activated MGP and protein S ...

Abstract	Coronavirus disease 2019 (Covid-19), caused by SARS-CoV-2, exerts far-reaching effects on public health and socioeconomic welfare The majority of infected individuals have mild to moderate symptoms but a significant proportion develops respiratory failure due to pneumonia Thrombosis is another frequent manifestation of Covid-19 that contributes to poor outcomes Vitamin K plays a crucial role in activation of both pro- and anticlotting factors in the liver, and the activation of extrahepatically synthesised protein S which seems to be important in local thrombosis prevention However, the role of vitamin K extends beyond coagulation Matrix Gla protein (MGP) is a vitamin K-dependent inhibitor of soft tissue calcification and elastic fibre degradation Severe extrahepatic vitamin K insufficiency was recently demonstrated in Covid-19 patients, with high inactive MGP levels correlating with elastic fibre degradation rates This suggests that insufficient vitamin K-dependent MGP activation leaves elastic fibres unprotected against SARS-CoV-2 induced proteolysis In contrast to MGP, Covid-19 patients have normal levels of activated factor II, in line with previous observations that vitamin K is preferentially transported to the liver for activation of procoagulant factors We therefore expect that vitamin K-dependent endothelial protein S activation is also compromised, which would be compatible with enhanced thrombogenicity Taking these data together, we propose a mechanism of pneumonia-induced vitamin K depletion, leading to a decrease in activated MGP and protein S, aggravating pulmonary damage and coagulopathy, respectively Intervention trials should be conducted to assess whether vitamin K administration plays a role in prevention and treatment of severe Covid-19
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #834834
Database	COVID19

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Article ; Online: Azole-Resistant COVID-19-Associated Pulmonary Aspergillosis in an Immunocompetent Host

Meijer, E.F.J. / Dofferhoff, A.S.M. / Hoiting, O. / Buil, J.B. / Meis, J.F.

Journal of Fungi, vol. 6, iss. 2

A Case Report.

2020

Abstract: Contains fulltext : 220218.pdf (publisher's version ) (Open Access) ... COVID-19-associated pulmonary aspergillosis (CAPA) is a recently described disease entity affecting patients with severe pulmonary abnormalities treated in intensive care units. Delays ...

Abstract	Contains fulltext : 220218.pdf (publisher's version ) (Open Access) COVID-19-associated pulmonary aspergillosis (CAPA) is a recently described disease entity affecting patients with severe pulmonary abnormalities treated in intensive care units. Delays in diagnosis contribute to a delayed start of antifungal therapy. In addition, the emergence of resistance to triazole antifungal agents puts emphasis on early surveillance for azole-resistant Aspergillus species. We present a patient with putative CAPA due to Aspergillus fumigatus with identification of a triazole-resistant isolate during therapy. We underline the challenges faced in the management of these cases, the importance of early diagnosis and need for surveillance given the emergence of triazole resistance.
Keywords	Radboudumc 4: lnfectious Diseases and Global Health RIHS: Radboud Institute for Health Sciences ; Radboudumc 4: lnfectious Diseases and Global Health RIMLS: Radboud Institute for Molecular Life Sciences ; covid19
Subject code	610
Publishing country	nl
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Vitamin D - contrary to vitamin K - does not associate with clinical outcome in hospitalized COVID-19 patients

Walk, J. / Dofferhoff, A. S. / van den Ouweland, J. M. / van Daal, H. / Janssen, R.

Abstract: SARS-CoV-2 causes remarkably variable disease from asymptomatic individuals to respiratory insufficiency and coagulopathy. Vitamin K deficiency was recently found to associate with clinical outcome in a cohort of COVID-19 patients. Vitamin D has been ... ...

Abstract	SARS-CoV-2 causes remarkably variable disease from asymptomatic individuals to respiratory insufficiency and coagulopathy. Vitamin K deficiency was recently found to associate with clinical outcome in a cohort of COVID-19 patients. Vitamin D has been hypothesized to reduce disease susceptibility by modulating inflammation, yet little is known about its role in disease severity. Considering the critical interaction between vitamin K and vitamin D in calcium and elastic fiber metabolism, we determined vitamin D status in the same cohort of 135 hospitalized COVID-19 patients by measuring blood 25(OH)D levels. We found no difference in vitamin D status between those with good and poor outcome (defined as intubation and/or death). Instead, we found vitamin D sufficient persons (25(OH)D >50 nmol/L) had accelerated elastic fiber degradation compared to those with mild deficiency (25(OH)D 25-50 nmol/L). Based on these findings, we hypothesize that vitamin D might have both favorable anti-inflammatory and unfavorable pro-calcification effects during COVID-19 and that vitamin K might compensate for the latter.
Keywords	covid19
Publisher	MedRxiv; WHO
Document type	Article ; Online
DOI	10.1101/2020.11.07.20227512
Database	COVID19

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Article: Corrigendum: Effects of Vitamin D and K on Interleukin-6 in COVID-19.

Visser, Margot P J / Dofferhoff, Anton S M / van den Ouweland, Jody M W / van Daal, Henny / Kramers, Cornelis / Schurgers, Leon J / Janssen, Rob / Walk, Jona

Frontiers in nutrition

2022 Volume 9, Page(s) 868324

Abstract: This corrects the article DOI: 10.3389/fnut.2021.761191.]. ...

Abstract	[This corrects the article DOI: 10.3389/fnut.2021.761191.].
Language	English
Publishing date	2022-03-08
Publishing country	Switzerland
Document type	Published Erratum
ZDB-ID	2776676-7
ISSN	2296-861X
ISSN	2296-861X
DOI	10.3389/fnut.2022.868324
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Article: Effects of Vitamin D and K on Interleukin-6 in COVID-19.

Visser, Margot P J / Dofferhoff, Anton S M / van den Ouweland, Jody M W / van Daal, Henny / Kramers, Cornelis / Schurgers, Leon J / Janssen, Rob / Walk, Jona

Frontiers in nutrition

2022 Volume 8, Page(s) 761191

Abstract: Background: Pathology during COVID-19 infection arises partly from an excessive inflammatory response with a key role for interleukin (IL)-6. Both vitamin D and K have been proposed as potential modulators of this process.: Methods: We assessed ... ...

Abstract	Background: Pathology during COVID-19 infection arises partly from an excessive inflammatory response with a key role for interleukin (IL)-6. Both vitamin D and K have been proposed as potential modulators of this process. Methods: We assessed vitamin D and K status by measuring circulating 25-hydroxyvitamin D (25(OH)D) and desphospho-uncarboxylated Matrix Gla-Protein (dp-ucMGP), respectively in 135 hospitalized COVID-19 patients in relation to inflammatory response, elastic fiber degradation and clinical outcomes. Results: Comparing good and poor disease outcomes of COVID-19 patients, vitamin 25(OH)D levels were not significantly different. IL-6 levels, however, were significantly higher in patients with poor outcome, compared to patients with good outcome (30.3 vs. 153.0 pg/mL; Conclusions: Dp-ucMGP associates with IL-6 as a central component of the destructive inflammatory processes in COVID-19. An intervention trial may provide insight whether vitamin K administration, either or not in combination with vitamin D, improves clinical outcome of COVID-19.
Language	English
Publishing date	2022-01-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2776676-7
ISSN	2296-861X
ISSN	2296-861X
DOI	10.3389/fnut.2021.761191
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