Publications by authors named "J W A Smit"

1,817 Publications

  • Page 1 of 1

IGF2 is a potential factor in RAI-refractory differentiated thyroid cancer.

Oncol Lett 2021 Aug 6;22(2):590. Epub 2021 Jun 6.

Department of Pathology, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands.

Differentiated thyroid cancer (DTC) is the most frequent endocrine tumor with a good prognosis after primary treatment in most cases. By contrast, 30-40% of patients with metastatic DTC are unresponsive to I radioactive iodide (RAI) treatment due to tumor dedifferentiation. Currently, underlying molecular mechanisms of dedifferentiation remain elusive and predictive biomarkers are lacking. Therefore, the present study aimed to identify molecular biomarkers in primary tumors associated with RAI refractoriness. A retrospective cohort was gathered consisting of RAI-sensitive patients with DTC and RAI-refractory patients with poorly DTC. In all patients, extensive intratumoral mutation profiling, gene fusions analysis, telomerase reverse transcriptase (TERT) promoter mutation analysis and formalin-fixed paraffin-embedded-compatible RNA sequencing were performed. Genetic analyses revealed an increased mutational load in RAI-refractory DTC, including mutations in and promoter. Transcriptomic analyses revealed profound differential expression of insulin-like growth factor 2 (), with up to 100-fold higher expression in RAI-refractory DTC compared with in RAI-sensitive DTC cases. ELISA revealed significant lower IGF2 plasma concentrations after surgery and subsequent I RAI therapy in patients with DTC compared with pretreatment baseline. Overall, the current findings suggested that the tumor-promoting growth factor IGF2 may have a potential role in acquiring RAI refractoriness.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/ol.2021.12851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200939PMC
August 2021

Lipid biomarkers in statin users with coronary artery disease annotated by coronary computed tomography angiography.

Sci Rep 2021 Jun 18;11(1):12899. Epub 2021 Jun 18.

Istituto di Fisiologia Clinica-CNR, via Giuseppe Moruzzi 1, 56124, Pisa, Italy.

Molecular markers are suggested to improve the diagnostic and prognostic accuracy in patients with coronary artery disease (CAD) beyond current clinical scores based on age, gender, symptoms and traditional risk factors. In this context, plasma lipids are emerging as predictors of both plaque composition and risk of future events. We aim to identify plasma lipid biomarkers associated to CAD indexes of stenosis severity, plaque lipid content and a comprensive score of CAD extent and its risk. We used a simple high performance liquid chromatography-tandem mass spectrometry method to identify 69 plasma lipids in 132 subjects referred to Coronary Computed Tomography Angiography (CCTA) for suspected CAD, all under statin treatment. Patients were stratified in groups using three different CCTA-based annotations: CTA-risk score, lipid plaque prevalence (LPP) ratio and the coronary artery disease-reporting and data system (CAD-RADS). We identified a common set of lipid biomarkers composed of 7 sphingomyelins and 3 phosphatidylethanolamines, which discriminates between high risk CAD patients and controls regardless of the CAD annotations used (CTA score, LPP ratio, or CAD-RADS). These results highlight the potential of circulating lipids as biomarkers of stenosis severity, non calcified plaque composition and overall plaque risk of events.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-92339-0DOI Listing
June 2021

Incorporating oral PrEP into standard prevention services for South African women: a nested interrupted time-series study.

Lancet HIV 2021 Jun 11. Epub 2021 Jun 11.

University of Washington, Seattle, WA, USA; Gilead Sciences, Foster City, CA, USA.

Background: As oral pre-exposure prophylaxis (PrEP) becomes the standard of prevention globally, its potential effect on HIV incidence in clinical trials of new prevention interventions is unknown, particularly for trials among women. In a trial measuring HIV incidence in African women, oral PrEP was incorporated into the standard of prevention in the trial's last year. We assessed the effect of on-site access to PrEP on HIV incidence in this natural experiment.

Methods: We did a nested interrupted time-series study using data from the ECHO trial. At 12 sites in four countries (Eswatini, Kenya, South Africa, and Zambia), women (aged 16-35 years) were randomly assigned to receive one of three contraceptives between Dec 14, 2015, and Sept 12, 2017, and followed up quarterly for up to 18 months to determine the effect of contraceptive method on HIV acquisition. Women were eligible if they wanted long-acting contraception, were medically qualified to receive study contraceptives, and had not used any of the study contraceptives in the past 6 months. The present analyses are limited to nine South African sites where on-site access to oral PrEP was implemented between March 13 and June 12, 2018. Using an interrupted time-series design, we compared HIV incidence before versus after PrEP access, limited to quarterly study visits at which on-site PrEP access was available to at least some participants and, in a sensitivity analysis, to the 180 days before and after access. The outcome was incident HIV infection, detected using two rapid HIV tests done in parallel for each participant at every scheduled follow-up visit. This study is registered on ClinicalTrials.gov, NCT02550067.

Findings: 2124 women were followed up after on-site PrEP access began, of whom 543 (26%) reported PrEP use. A total of 12 HIV seroconversions were observed in 556 person-years (incidence 2·16%) after on-site PrEP access, compared with 133 HIV seroconversions in 2860 person-years (4·65%) before PrEP access (adjusted incidence rate ratio [IRR] 0·45, 95% CI 0·25-0·82, p=0·0085). Similar results were also observed when limiting the analysis to 180 days before versus after PrEP access. A total of 46 HIV seroconversions were observed in 919 person-years within 180 days before PrEP access, compared with 11 seroconversions in 481 person-years in the 180 days following PrEP access (incidence 5·00 vs 2·29 per 100 person-years; IRR 0·43, 95% CI 0·22-0·88, p=0·012).

Interpretation: On-site access to PrEP as part of standard of prevention in a clinical trial among women in South Africa was associated with halving HIV incidence, when approximately a quarter of women started PrEP. Providing access to on-site PrEP could decrease incidence in HIV prevention trials. These data are also among the first to show in any setting that access to PrEP is associated with decreased HIV acquisition among South African women.

Funding: Bill & Melinda Gates Foundation, United States Agency for International Development, President's Emergency Plan for AIDS Relief, the Swedish International Development Cooperation Agency, South African Medical Research Council, and United Nations Population Fund.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2352-3018(21)00048-5DOI Listing
June 2021

Acceptability of an Intervention to Promote Viral Suppression and Serostatus Disclosure for Men Living with HIV in South Africa: Qualitative Findings.

AIDS Behav 2021 Jun 7. Epub 2021 Jun 7.

University of Alabama at Birmingham (UAB), Division of Infectious Disease, Birmingham, Alabama, USA.

Men living with HIV (MLWH) often have reproductive goals that can increase HIV-transmission risks to their pregnancy partners. We developed a safer conception intervention for MLWH in South Africa employing cognitive behavioral skills to promote serostatus disclosure, ART uptake, and viral suppression. MLWH were recruited from an HIV clinic near Durban, South Africa, and encouraged to include partners in follow-up visits. Exit in-depth interviews were conducted with eleven men and one female partner. The emerging over-arching theme is that safer conception care mitigates internalized and community-level HIV-stigma among MLWH. Additional related sub-themes include: (1) safer conception care acceptability is high but structural barriers challenge participation; (2) communication skills trainings helped overcome barriers to disclose serostatus; (3) feasibility and perceived effectiveness of strategies informed safer conception method selection. Our findings suggest that offering safer conception care to MLWH is a novel stigma-reducing strategy for motivating HIV prevention and treatment and serostatus disclosure to partners.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10461-021-03278-wDOI Listing
June 2021

Comparative angiotomographic study of swine vascular anatomy: contributions to research and training models in vascular and endovascular surgery.

J Vasc Bras 2021 May 14;20:e20200086. Epub 2021 May 14.

Universidade Federal de São Paulo - UNIFESP, Programa de Ciência Cirúrgica Interdisciplinar, São Paulo, SP, Brasil.

Background: Medium and large animal models allow researchers to evaluate the efficacy and safety of cardiovascular procedures in systems that resemble human anatomy and can be used to simulate scenarios for training purposes. Although porcine models have been used extensively, many physiological and anatomical features remain unknown or only superficially described.

Objectives: To describe the normal porcine vascular anatomy on computed tomography scans, compare it to human vascular anatomy, and discuss the application of porcine models for open and endovascular procedures.

Methods: Three male Landrace pigs underwent computed tomography. The vascular anatomy of the neck, thorax, abdomen, and limbs was analyzed and described; relevant similarities and differences between porcine and human vascular anatomies and the implications for vascular procedures in pigs are highlighted.

Results: The carotid territory, aortic arch, and terminal aorta branches all show marked differences in pigs compared to their human counterparts. Compressions of both left renal and common iliac veins were detected, analogous to those seen in human Nutcracker and May-Thurner syndromes. Vascular measurements (diameters, lengths, and angles) of several different porcine territories are presented.

Conclusions: The data presented should be useful for planning preclinical trials and basic research and for refining surgical training using porcine models in vascular fields.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1590/1677-5449.200086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147709PMC
May 2021