Elke Smits

Bio: Elke Smits is an academic researcher from University of Antwerp. The author has contributed to research in topics: Biobank & Cancer. The author has an hindex of 4, co-authored 10 publications receiving 93 citations.

Cachexia in cancer: what is in the definition?

Abstract: Objective This study aimed to provide evidence-based results on differences in overall survival (OS) rate to guide the diagnosis of cancer cachexia. Design Data collection and clinical assessment was performed every 3 months (5 visits): baseline data, muscle strength, nutritional and psychosocial status. 2 definitions on cachexia using different diagnostic criteria were applied for the same patient population. Fearon et al's definition is based on weight loss, body mass index (BMI) and sarcopenia. Evans et al nuances the contribution of sarcopenia and attaches additional attention to abnormal biochemistry parameters, fatigue and anorexia. The mean OS rates were compared between patients with and without cachexia for both definitions. Results Based on the population of 167 patients who enrolled, 70% developed cachexia according to Fearon et al's definition and 40% according to Evans et al's definition. The OS in the cachectic population is 0.97 and 0.55 years, respectively. The difference in OS between pat...

Towards Harmonized Biobanking for Biomonitoring: A Comparison of Human Biomonitoring-Related and Clinical Biorepositories.

Abstract: Human biomonitoring (HBM) depends on high-quality human samples to identify status and trends in exposure and ensure comparability of results. In this context, much effort has been put into the development of standardized processes and quality assurance for sampling and chemical analysis, while effects of sample storage and shipment on sample quality have been less thoroughly addressed. To characterize the currently applied storage and shipment procedures within the consortium of the European Human Biomonitoring Initiative (HBM4EU), which aims at harmonization of HBM in Europe, a requirement analysis based on data from an online survey was conducted. In addition, the online survey was addressed to professionals in clinical biobanking represented by members of the European, Middle Eastern and African Society for Biopreservation and Biobanking (ESBB) to identify the current state-of-the-art in terms of sample storage and shipment. Results of this survey conducted in these two networks were compared to detect processes with potential for optimization and harmonization. In general, many similarities exist in sample storage and shipment procedures applied by ESBB members and HBM4EU partners and many requirements for ensuring sample quality are already met also by HBM4EU partners. Nevertheless, a need for improvement was identified for individual steps in sample storage, shipment, and related data management with potential impact on sample and data quality for HBM purposes. Based on these findings, recommendations for crucial first steps to further strengthen sample quality, and thus foster advancement in HBM on a pan-European level are given.

Global Biobank Week: Toward Harmonization in Biobanking

Abstract: As we reflect on the activities of 2017, one of the greatest achievements in the field of biobanking has been the initiation, planning, and holding the first Global Biobank Week (GBW) in Stockholm, Sweden, from September 13 to 15, 2017. The event attracted a total of 857 participants and vendors from 53 countries, including 53 participants from lowand middle-income countries. The congress supported seven travel awardees. The attendees came from biobanks, clinical organizations, biological resource centers, industrial partners, policy-making organizations, ministries, and advocacy groups. This meeting was a close collaboration between three organizations, the European and Middle Eastern and African Society for Biopreservation and Biobanking (ESBB); the Biobanking and Biomolecular Research Infrastructure–European Research Infrastructure Consortium (BBMRI-ERIC); and the International Society for Biological and Environmental Repositories (ISBER). This first-time collaboration was the brainchild of Jan-Eric Litton, the now former Director General of BBMRI-ERIC. The first meeting of the GBW Steering Committee was held in Vienna, Austria, at the time of the Europe Biobank Week (EBW) in 2016 during which the framework for the meeting planning was established. The steering committee was chaired by Jan-Eric Litton and vice-chaired by Brent Schacter, now Past President of ISBER (Fig. 1). Steering committee members included Elke Smits (ESBB Past President), Outi Törnwall (BBMRI-ERIC), Markus Pasterk (BBMRI-ERIC), Michaela Th. Mayrhofer (BBMRI-ERIC), Erik Steinfelder (Director General, BBMRI-ERIC), Balwir (Bal) Mathroo-Ball (ESBB President), Marianne Henderson (ISBER OAC Chair), Zisis Kozlakidis (ISBER President), Ana Torres (ISBER), Samantha Wale (ISBER), Gunnel Tybring (KI), Robert Hewitt (ESBB), and Nadia Taleb (Congress organizer). Marianne Henderson, was named the co-Chair of the Programme Committee (PC) along with Balwir Matharoo-Ball. The PC was assembled from representatives of all three organizations to allow the planning of the 30 excellent scientific sessions included in the GBW. The PC members came from six continents, only missing Antarctica in its reach! The GBW theme, ‘‘Toward Harmonization in Biobanking,’’ highlights a critical role that biospecimen and data harmonization plays in moving scientific discovery from the donor to the laboratory and back to the bedside. The more collaboration a biobank establishes, the higher the volume of requests for harmonization. The lack of a comprehensive methodology for linking information across data providers globally reduces the ability of researchers to combine data from disparate sources. Scientific integrity and the speed of discovery in science and technology require that we harmonize our processes and procedures for collecting, processing, storing, and annotating our biospecimens so that the data collected will be reproducible. It has become clear to the biobanking community that the biobank is a key resource for future research and that quality biospecimens will contribute to the reproducibility, validity, and rapidity of scientific discovery. Toward that end, the GBW provided a global platform for comprehensive discussion and collaboration on improving and harmonizing biobanking and biopreservation of samples and data for research. The GBW was preceded by a two-part initial training workshop that focused on ‘‘How to build a Modern Biobank’’ and ‘‘IT for Biobanks.’’ Both workshops were fully subscribed and were well attended by a globally diverse audience. The feedback from these sessions reflected the need for continued biobanking education on ELSI, IRB applications, IT, and sustainability. In addition, there is a need for professional continued development of biobank technicians, managers, and directors. The feedback also emphasized how our biobanks need to educate through our management and operational structure on the value of quality biobanking to their overall scientific infrastructure. The GBW was inaugurated by a representative from the Swedish government, Agneta Karlsson. Thereafter, Swedish folk songs were performed by Anna Johansson and at the piano Alexander Nordvall.

Biobanking for Viral Hepatitis Research.

Abstract: Introduction Viral hepatitis is a worldwide, important health issue. The optimal management of viral hepatitis infections faces numerous challenges. In this paper, we describe how biobanking of biological samples derived from viral hepatitis patients collected both in-hospital and during community outreach screenings provides a unique collection of samples. Materials and Methods All samples and materials were provided with a study code within the SLIMS system Study protocols and an informed consent form were approved by the Antwerp University Hospital/University of Antwerp Ethical Committee. Systematic biobanking was initiated in October 2014. Collected sample types include: 1) serum and plasma of all newly diagnosed HBV, HCV, HDV and HEV positive patients; 2) left-over serum and plasma samples from all PCR analyses for HBV, HCV and HEV performed in the context of routine clinical care; 3) left-over liver tissue not needed for routine histological diagnosis after liver biopsy; and 4) additional virus-specific, appropriate sample types using a scientific rationale-based approach. A community outreach screening program was performed in three major Belgian cities. Serum, EDTA, Tempus Blood RNA and BD Vacutainer CPT were collected. CPT tubes were centrifuged on-site and mononuclear cells collected within 24 hours. Results Concerning community screening: 298 individuals supplied all 4 sample types. Samples were stored at -150°C and were logged in the biobank SLIMS database. Samples were used for HBV-related immunological and biomarker studies. DNA isolated from plasma samples derived from chronic HBV patients was used to investigate Single Nucleotide Polymorphism rs 1790008. Serum samples collected from chronic hepatitis C patients were used to assess the efficacy of HCV treatment. Peripheral Blood Mononuclear Cells (PBMC) isolated from chronic HBV patients and healthy controls were used for different immunological study purposes. Virus isolated from biobanked stool of a chronic hepatitis E patient was used to establish a mouse model for Hepatitis E infections, allowing further HEV virology studies. Conclusion The establishment of a biobank with samples collected both in-hospital and during community-outreach screening resulted in a unique, continuously expanding collection of biological samples which provides an excellent platform for prompt answers to clinically and translational relevant research questions.

Tumorbank@uza: A Collection of Tissue, Fluid Samples and Associated Data of Oncology Patients for the Use in Translational Research

Abstract: Tumorbank@UZA is an academic hospital integrated biobank that collects tissue, blood and urine samples from oncology patients. We work according to a quality management system and have established SOPs for all work procedures in the biobank. Tumorbank@UZA is funded by the National Cancer Plan, an initiative from the Belgian government since 2009. Samples from our biobank are available for both academic as well as commercial researchers, through a well-established access procedure. Currently the collection consists of more than 85.000 samples of more than 8000 patients. Funding statement: Tumorbank@UZA is funded by the National Cancer Plan (initiative 27) from the Ministry of Health of the Belgian Federal Government.

Cancer cachexia: Diagnosis, assessment, and treatment.

Abstract: Cancer cachexia is a multi-factorial syndrome, which negatively affects quality of life, responsiveness to chemotherapy, and survival in advanced cancer patients. Our understanding of cachexia has grown greatly in recent years and the roles of many tumor-derived and host-derived compounds have been elucidated as mediators of cancer cachexia. However, cancer cachexia remains an unmet medical need and attempts towards a standard treatment guideline have been unsuccessful. This review covers the diagnosis, assessment, and treatment of cancer cachexia; the elements impeding the formulation of a standard management guideline; and future directions of research for the improvement and standardization of current treatment procedures.

GLIM Criteria Using Hand Grip Strength Adequately Predict Six-Month Mortality in Cancer Inpatients.

Abstract: Protein-calorie malnutrition is very frequent in cancer patients and is associated with an increase in morbidity and mortality. Recently, the Global Leadership Initiative on Malnutrition (GLIM) criteria were proposed to standardize the diagnosis of malnutrition. Nevertheless, these criteria were not validated in prospective studies. Our objective is to determine the prevalence of malnutrition in cancer inpatients using different diagnostic classifications, including GLIM criteria, and to establish their association with length of stay and mortality. Hence, we designed a prospective study. Within the first 24 hours of admission to the Inpatient Oncology Unit, subjective global assessment (SGA) was carried out, and anthropometric data (body mass index (BMI), mid-arm circumference (MAC), arm muscle circumference (AMC), fat-free mass index (FFMI)) and hand grip strength (HGS) were obtained to assess the reduction of muscle mass according to GLIM criteria. Length of stay, biomarkers (albumin, prealbumin, C-reactive protein (CRP)), and in-hospital and six-month mortality were evaluated. Regarding the 282 patients evaluated, their mean age was 60.4 ± 12.6 years, 55.7% of them were male, and 92.9% had an advanced-stage tumor (17.7% stage III, 75.2% stage IV). According to SGA, 81.6% of the patients suffered from malnutrition (25.5% moderate malnutrition, and 56.1% severe malnutrition), and, based on GLIM criteria, malnutrition rate was between 72.2 and 80.0% depending on the used tool. Malnourished patients (regardless of the tool used) showed significantly worse values concerning BMI, length of stay, and levels of CRP/albumin, albumin, and prealbumin than normally nourished patients. In logistic regression, adjusted for confounding variables, the odds ratio of death at six months was significantly associated with malnutrition by SGA (odds ratio 2.73, confidence interval (CI) 1.35–5.52, p = 0.002), and by GLIM criteria calculating muscle mass with HGS (odds ratio 2.72, CI 1.37–5.40, p = 0.004) and FFMI (odds ratio 1.87, CI 1.01–3.48, p = 0.047), but not by MAC or AMC. The prevalence of malnutrition in advanced-stage cancer inpatients is very high. SGA and GLIM criteria, especially with HGS, are useful tools to diagnose malnutrition and have a similar predictive value regarding six-month mortality in cancer inpatients.

A Narrative Review of Cancer-Related Fatigue (CRF) and Its Possible Pathogenesis.

Abstract: Many cancer patients suffer from severe fatigue when treated with chemotherapy or radiotherapy; however, the etiology and pathogenesis of this kind of fatigue remains unknown. Fatigue is associated with cancer itself, as well as adjuvant therapies and can persist for a long time. Cancer patients present a high degree of fatigue, which dramatically affects the quality of their everyday life. There are various clinical research studies and reviews that aimed to explore the mechanisms of cancer-related fatigue (CRF). However, there are certain limitations in these studies: For example, some studies have only blood biochemical texts without histopathological examination, and there has been insufficient systemic evaluation of the dynamic changes in relevant indexes. Thus, we present this narrative review to summarize previous studies on CRF and explore promising research directions. Plenty of evidence suggests a possible association between CRF and physiological dysfunction, including skeletal muscular and mitochondrial dysfunction, peripheral immune activation and inflammation dysfunction, as well as central nervous system (CNS) disorder. Mitochondrial DNA (mtDNA), mitochondrial structure, oxidative pressure, and some active factors such as ATP play significant roles that lead to the induction of CRF. Meanwhile, several pro-inflammatory and anti-inflammatory cytokines in the peripheral system, even in the CNS, significantly contribute to the occurrence of CRF. Moreover, CNS function disorders, such as neuropeptide, neurotransmitter, and hypothalamic-pituitary-adrenal (HPA) axis dysfunction, tend to amplify the sense of fatigue in cancer patients through various signaling pathways. There have been few accurate animal models established to further explore the molecular mechanisms of CRF due to different types of cancer, adjuvant therapy schedules, living environments, and physical status. It is imperative to develop appropriate animal models that can mimic human CRF and to explore additional mechanisms using histopathological and biochemical methods. Therefore, the main purpose of this review is to analyze the possible pathogenesis of CRF and recommend future research that will clarify CRF pathogenesis and facilitate the formulation of new treatment options.

Ultrafiltration and size exclusion chromatography combined with asymmetrical-flow field-flow fractionation for the isolation and characterisation of extracellular vesicles from urine

Abstract: Extracellular vesicles (EVs) have a great potential in clinical applications. However, their isolation from different bodily fluids and their characterisation are currently not optimal or standardised. Here, we report the results of examining the performance of ultrafiltration combined with size exclusion chromatography (UF-SEC) to isolate EVs from urine. The results reveal that UF-SEC is an efficient method and provides high purity. Furthermore, we introduce asymmetrical-flow field-flow fractionation coupled with a UV detector and multi-angle light-scattering detector (AF4/UV-MALS) as a characterisation method and compare it with current methods. We demonstrate that AF4/UV-MALS is a straightforward and reproducible method for determining size, amount and purity of isolated urinary EVs.

Clinical and virological heterogeneity of hepatitis delta in different regions world-wide: The Hepatitis Delta International Network (HDIN)

Abstract: Background & Aims Chronic hepatitis D (delta) is a major global health burden Clinical and virological characteristics of patients with hepatitis D virus (HDV) infection and treatment approaches in different regions world-wide are poorly defined Methods The Hepatitis Delta International Network (HDIN) registry was established in 2011 with centres in Europe, Asia, North- and South America Here, we report on clinical/ virological characteristics of the first 1576 patients with ongoing or past HDV infection included in the database until October 2016 and performed a retrospective outcome analysis The primary aim was to investigate if the region of origin was associated with HDV replication and clinical outcome Results The majority of patients was male (n = 979, 62%) and the mean age was 367 years (range 1-79, with 9% of patients younger than 20 years) Most patients were HBeAg-negative (77%) and HDV-RNA positive (85%) Cirrhosis was reported in 487% of cases which included 13% of patients with previous or ongoing liver decompensation Hepatocellular carcinoma (HCC) developed in 30 patients (25%) and 44 (36%) underwent liver transplantation Regions of origin were independently associated with clinical endpoints and detectability of HDV RNA Antiviral therapy was administered to 356 patients with different treatment uptakes in different regions Of these, 264 patients were treated with interferon-a and 92 were treated with HBV-Nucs only Conclusions The HDIN registry confirms the severity of hepatitis delta but also highlights the heterogeneity of patient characteristics and clinical outcomes in different regions There is an urgent need for novel treatment options for HDV infection