Publications by authors named "H Rogier Van Doorn"

242 Publications

Evaluation of Immunohistochemical Markers, CK17 and SOX2, as Adjuncts to p53 for the Diagnosis of Differentiated Vulvar Intraepithelial Neoplasia (dVIN).

Pharmaceuticals (Basel) 2021 Apr 2;14(4). Epub 2021 Apr 2.

Department of Pathology, Erasmus MC, University Medical Centre Rotterdam, 3015 GD Rotterdam, The Netherlands.

Histological diagnosis of differentiated vulvar intraepithelial neoplasia (dVIN), the precursor of human papillomavirus (HPV)-independent vulvar squamous cell carcinoma (VSCC), can be challenging, as features of dVIN may mimic those of non-dysplastic dermatoses. To aid the diagnosis, p53-immunohistochemistry (IHC) is commonly used, and mutant expression patterns are used to support a histological diagnosis of dVIN. However, a proportion of dVIN can show wild-type p53-expression, which is characteristic of non-dysplastic dermatoses. Furthermore, recent research has identified a novel precursor of HPV-independent VSCC-the p53-wild-type differentiated exophytic vulvar intraepithelial lesion (de-VIL). Currently, there are no established diagnostic IHC-markers for p53-wild-type dVIN or de-VIL. We evaluated IHC-markers, cytokeratin 17 (CK17), and SRY-box 2 (SOX2), as diagnostic adjuncts for dVIN. For this, IHC-expression of CK17, SOX2, and p53 was studied in dVIN ( = 56), de-VIL ( = 8), and non-dysplastic vulvar tissues ( = 46). For CK17 and SOX2, the percentage of cells showing expression, and the intensity and distribution of expression were recorded. We also performed next generation targeted sequencing (NGTS) on a subset of dVIN ( = 8) and de-VIL ( = 8). With p53-IHC, 74% of dVIN showed mutant patterns and 26% showed wild-type expression. Median percentage of cells expressing CK17 or SOX2 was significantly higher in dVIN (p53-mutant or p53-wild-type) and de-VIL than in non-dysplastic tissues ( < 0.01). Diffuse, moderate-to-strong, full epithelial expression of CK17 or SOX2 was highly specific for dVIN and de-VIL. With NGTS, mutations were detected in both dVIN and de-VIL. We infer that immunohistochemical markers CK17 and SOX2, when used along with p53, may help support the histological diagnosis of dVIN.
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http://dx.doi.org/10.3390/ph14040324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066509PMC
April 2021

Nuclear factor IB is downregulated in vulvar squamous cell carcinoma (VSCC): Unravelling differentially expressed genes in VSCC through gene expression dataset analysis.

Oncol Lett 2021 May 16;21(5):381. Epub 2021 Mar 16.

Department of Pathology, Erasmus MC, University Medical Center Rotterdam, 3000CA Rotterdam, The Netherlands.

Vulvar squamous cell carcinoma (VSCC) comprises two distinct etiopathological subtypes: i) Human papilloma virus (HPV)-related VSCC, which arises via the precursor high grade squamous intraepithelial lesion (HSIL); and ii) HPV-independent VSCC, which arises via precursor, differentiated vulvar intraepithelial neoplasia (dVIN), driven by mutations. However, the mechanism of carcinogenesis of VSCC is poorly understood. The current study aimed to gain insight into VSCC carcinogenesis by identifying differentially expressed genes (DEGs) for each VSCC subtype. The expression of certain DEGs was then further assessed by performing immunohistochemistry (IHC) on whole tissue sections of VSCC and its precursors. Statistical analysis of microarrays was performed on two independent gene expression datasets (GSE38228 and a study from Erasmus MC) on VSCC and normal vulva. DEGs were identified that were similarly (up/down) regulated with statistical significance in both datasets. For HPV-related VSCCs, this constituted 88 DEGs, and for HPV-independent VSCCs, this comprised 46 DEGs. IHC was performed on VSCC (n=11), dVIN (n=6), HSIL (n=6) and normal vulvar tissue (n=7) with i) signal transducer and activator of transcription 1 (STAT1; an upregulated DEGs); ii) nuclear factor IB (NFIB; a downregulated DEG); iii) p16 (to determine the HPV status of tissues); and iv) p53 (to confirm the histological diagnoses). Strong and diffuse NFIB expression was observed in the basal and para-basal layers of normal vulvar tissue, whereas NFIB expression was minimal or completely negative in dVIN and in both subtypes of VSCC. In contrast, no discernable difference was observed in STAT1 expression among normal vulvar tissue, dVIN, HSIL or VSCC. By leveraging bioinformatics, the current study identified DEGs that can facilitate research into VSCC carcinogenesis. The results suggested that NFIB is downregulated in VSCC and its relevance as a diagnostic/prognostic biomarker deserves further exploration.
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http://dx.doi.org/10.3892/ol.2021.12642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020388PMC
May 2021

: High Prevalence and Possibly Chronic Shedding in Human Respiratory Tract, But No Zoonotic Transmission.

Viruses 2021 03 24;13(4). Epub 2021 Mar 24.

Emerging Infection Group, Oxford University Clinical Research Unit, Ho Chi Minh City 7000, Vietnam.

is a recently discovered DNA virus family consisting of two species, and . Here we used PCR amplification and sequencing to characterize redondoviruses in nasal/throat swabs collected longitudinally from a cohort of 58 individuals working with animals in Vietnam. We additionally analyzed samples from animals to which redondovirus DNA-positive participants were exposed. Redondoviruses were detected in approximately 60% of study participants, including 33% (30/91) of samples collected during episodes of acute respiratory disease and in 50% (29/58) of baseline samples (with no respiratory symptoms). Vientovirus (73%; 24/33) was detected more frequently in samples than brisaviruses (27%; 9/33). In the 23 participants with at least 2 redondovirus-positive samples among their longitudinal samples, 10 (43.5%) had identical redondovirus replication-gene sequences detected (sampling duration: 35-132 days). We found no identical redondovirus replication genes in samples from different participants, and no redondoviruses were detected in 53 pooled nasal/throat swabs collected from domestic animals. Phylogenetic analysis described no large-scale geographical clustering between viruses from Vietnam, the US, Spain, and China, indicating that redondoviruses are highly genetically diverse and have a wide geographical distribution. Collectively, our study provides novel insights into the family in humans, describing a high prevalence, potentially associated with chronic shedding in the respiratory tract with lack of evidence of zoonotic transmission from close animal contacts. The tropism and potential pathogenicity of this viral family remain to be determined.
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http://dx.doi.org/10.3390/v13040533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063800PMC
March 2021

Human infection with an unknown species of Dracunculus in Vietnam.

Int J Infect Dis 2021 Apr 15;105:739-742. Epub 2021 Mar 15.

National Hospital for Tropical Diseases 2, Hanoi, Vietnam. Electronic address:

Guinea worm (GW) disease, caused by Dracunculus medinensis, is an almost eradicated waterborne zoonotic disease. The World Health Organization (WHO) currently lists GW as endemic in only five African countries. In July 2020, the Vietnamese public health surveillance system detected a hanging worm in a 23-year-old male patient, who did not report any travel to Africa or any country previously endemic for GW. The patient was hospitalized with symptoms of fatigue, anorexia, muscle aches, and abscesses, with worms hanging out of the skin in the lower limbs. The worms were retrieved from the lesions and microscopically examined in Vietnam, identifying structures compatible with Dracunculus spp. and L1-type larvae. A section of this parasite was sent to the Centers for Disease Control and Prevention (CDC) in Atlanta, United States, for confirmatory diagnosis of GW. The adult worm had cuticle structures compatible with Dracunculus parasites, although the length of L1 larvae was about 339 μm, substantially shorter than D. medinensis. DNA sequence analysis of the 18S small subunit rRNA gene confirmed that this parasite was not GW, and determined that the sample belonged to a Dracunculus sp. not previously reported in GenBank that clustered with the animal-infective Dracunculus insignis and Dracunculus lutrae, located in a different clade than D. medinensis. This study highlights the importance of effective public health surveillance systems and the collaborative work of local public health authorities from Vietnam with the WHO and CDC in efforts to achieve the eradication of GW.
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http://dx.doi.org/10.1016/j.ijid.2021.02.018DOI Listing
April 2021

Community-based antibiotic access and use in six low-income and middle-income countries: a mixed-method approach.

Lancet Glob Health 2021 May 10;9(5):e610-e619. Epub 2021 Mar 10.

MRC-Wits Rural Public Health and Health Transitions Research Unit (Agincourt), University of the Witwatersrand, Johannesburg, South Africa.

Background: Antimicrobial misuse is common in low-income and middle-income countries (LMICs), and this practice is a driver of antibiotic resistance. We compared community-based antibiotic access and use practices across communities in LMICs to identify contextually specific targets for interventions to improve antibiotic use practices.

Methods: We did quantitative and qualitative assessments of antibiotic access and use in six LMICs across Africa (Mozambique, Ghana, and South Africa) and Asia (Bangladesh, Vietnam, and Thailand) over a 2·5-year study period (July 1, 2016-Dec 31, 2018). We did quantitative assessments of community antibiotic access and use through supplier mapping, customer exit interviews, and household surveys. These quantitative assessments were triangulated with qualitative drug supplier and consumer interviews and discussions.

Findings: Vietnam and Bangladesh had the largest proportions of non-licensed antibiotic dispensing points. For mild illness, drug stores were the most common point of contact when seeking antibiotics in most countries, except South Africa and Mozambique, where public facilities were most common. Self-medication with antibiotics was found to be widespread in Vietnam (55·2% of antibiotics dispensed without prescription), Bangladesh (45·7%), and Ghana (36·1%), but less so in Mozambique (8·0%), South Africa (1·2%), and Thailand (3·9%). Self-medication was considered to be less time consuming, cheaper, and overall, more convenient than accessing them through health-care facilities. Factors determining where treatment was sought often involved relevant policies, trust in the supplier and the drug, disease severity, and whether the antibiotic was intended for a child. Confusion regarding how to identify oral antibiotics was revealed in both Africa and Asia.

Interpretation: Contextual complexities and differences between countries with different incomes, policy frameworks, and cultural norms were revealed. These contextual differences render a single strategy inadequate and instead necessitate context-tailored, integrated intervention packages to improve antibiotic use in LMICs as part of global efforts to combat antibiotic resistance.

Funding: Wellcome Trust and Volkswagen Foundation.
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http://dx.doi.org/10.1016/S2214-109X(21)00024-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050200PMC
May 2021