Collection Of Biomaterials Research Articles

Inflammatory Neuropathy Consortium base (INCbase): a protocol of a global prospective observational cohort study for the development of a prediction model for treatment response in chronic inflammatory demyelinating polyneuropathy

BackgroundINCbase is an international, multicenter prospective observational study using a customizable web-based modular registry to study the clinical, biological and electrophysiological variation and boundaries of chronic inflammatory demyelinating polyneuropathy (CIDP). The primary objective of INCbase is to develop and validate a clinical prediction model for treatment response.MethodsAll patients meeting clinical criteria for CIDP can be included in INCbase. Collected data include demographics, clinical history, diagnostics and various domains of clinical outcomes. Data is collected at a minimum of every 6 months for two years, and more frequently at the discretion of the investigational site to allow for assessment of unexpected changes in treatment response or clinical status. Participants can be enrolled in various sub-studies designed to capture data relevant to specific groups of interest. Data is entered directly into the web-based data entry system by local investigators and/or participants. Collection and local storage of biomaterial is optional. To develop a clinical prediction model for treatment response, newly diagnosed patients with active disease warranting start of first-line treatment will be included. The study population will be split into a development and validation cohort. Univariate and multivariate logistic regression analysis will be used to identify and combine predictors at start of treatment for treatment response at six months. Model performance will be assessed through discrimination and calibration in an external validation cohort. The externally validated prediction model will be made available to researchers and clinicians on the INCbase website.DiscussionWith this study, we aim to create a clinically relevant and implementable prediction model for treatment response to first line treatments in CIDP. INCbase enrollment started in April 2021, with 29 centers across 8 countries and 303 patients participating to date. This collaborative effort between academia, patient advocacy organizations and pharmaceutical industry will deepen our understanding of how to diagnose and treat CIDP.

Necropsy in Mouse Research.

Necropsy is the postmortem examination of an animal's body. Experiments on laboratory animals are performed to gather scientific data relevant to basic and, even more often, translational research, mainly in the field of translational medicine. A necropsy conducted on laboratory animals subjected to experimental research provides an opportunity to exhaustively explore pathological processes that took place during life. In order to achieve that goal, procedures of biomaterial collection should be performed timely, bearing in mind the inevitable process of postmortem tissue decay, and precisely, to avoid mechanical tissue damage.In this chapter, procedures of collecting organs and tissue in a way that ensures the preservation of the organ structure, tissue organization, morphological characteristics of cells, and last but not least, intracellular protein and nucleic acid content and chromosome organization are going to be described step by step.

Awareness of biobanking among patients and doctors: experience of the Tomsk Oblast

Aim. To assess awareness of biobanking among patients and healthcare professionals, and to identify factors influencing willingness to become donors and participate in the collection of biological material.Material and methods. A qualitative study was conducted based on semi-structured interviews of doctors (n=11) and patients (n=11) of Tomsk medical organizations. The results obtained were processed using lexical and comparative analysis techniques.Results. The experience of participation in biobanking was extremely limited among both patients and doctors, but those who had previous experience evaluated it positively. Patients and doctors had not received information about biobanks from official sources, but intuitively understood their functions and roles in biomedical research. Patients were willing to donate biomaterials, while doctors were willing to collect them, but both parties emphasized the importance of understanding the purpose and future use of the biomaterials. Patients wanted to ensure the safety of the collection procedures and the confidentiality of their personal data. The main motives for donating biomaterial were contribution to scientific development, potential attractiveness for the descendants of donors, social origin and material reward.Conclusion. Popularizing biobanking and increasing the awareness of donors and healthcare professionals about the regulatory framework governing biobanking activities can help establish trust and enhance readiness for donation, even regarding invasive biomaterial collection procedures.

The Cantabria Cohort, a protocol for a population-based cohort in northern Spain

Cantabria Cohort stems from a research and action initiative lead by researchers from Valdecilla Research Institute (IDIVAL), Marqués de Valdecilla University Hospital and University of Cantabria, supported by the regional Goverment. Its aim is to identify and follow up a cohort that would provide information to improve the understanding of the etiology and prognosis of different acute and chronic diseases. The Cantabria Cohort will recruit between 40,000–50,000 residents aged 40–69 years at baseline, representing 10–20% of the target population. Currently, more than 30,000 volunteers have been enrolled. All participants will be invited for a re-assessment every three years, while the overall duration is planned for twenty years. The repeated collection of biomaterials combined with broad information from participant questionnaires, medical examinations, actual health system records and other secondary public data sources is a major strength of its design, which will make it possible to address biological pathways of disease development, identify new factors involved in health and disease, design new strategies for disease prevention, and advance precision medicine. It is conceived to allow access to a large number of researchers worldwide to boost collaboration and medical research.

Deciphering the genetic basis of immune thrombocytopenia: current evidence for genetic predisposition in adult ITP.

Immune thrombocytopenia (ITP) is the consequence of a complex, still incompletely understood immunological dysregulation. Proposed mechanisms include autoantibody-induced platelet destruction, impaired platelet production as well as abnormalities in T-cell immunity, such as T helper cells (Th1) polarization, a high proportion of Th17 cells, and a reduced number of regulatory T cells. Although the etiology of ITP is incompletely understood and considered multifactorial in most cases, genetic variants are thought to play a key role in susceptibility to ITP, especially in persistent or chronic ITP. Efforts are currently underway to uncover possible predisposing genetic factors for the development of ITP. Single-nucleotide polymorphisms and copy number variations have been identified in several immune-related genes, such as cytokine genes, Fcγ receptor genes or T-cell costimulation genes, and have been associated with patients' susceptibility to ITP. However, because of the clinical heterogeneity and low incidence of ITP it remains challenging to perform genetic analyses with sufficiently large sample size within informative patient populations, highlighting the need for collection of well-annotated biomaterials in clinical trials or registry projects. Another significant challenge is to go beyond performing association studies alone and to establish genotype-phenotype associations, thus proving causality between a genetic alteration and ITP pathogenesis. This review summarizes our current knowledge on genetic alterations identified as potential predisposing factors for the development of ITP in adults, thereby addressing signaling pathways considered critical for ITP pathogenesis.

PREVALENCE OF GASTROINTESTINAL TRACT PATHOLOGY AND HELICOBACTERIOSIS IN HORSES

This article presents information on the prevalence of helicobacteriosis in horses of different age groups. It has been found that gastrointestinal tract (GIT) pathology is widely prevalent in horses, ranging from 50% to 80%. The main conditions among GIT pathologies in horses are gastrophylosis, erosions, ulcers, and helicobacteriosis. Helico-bacteriosis is registered in 66.7% to 100% of the investigated adult population and in 20% to 66.7% of the young horses. Stomach examinations using endoscopy and video gastroscopy provide a clear picture of the mucous membrane's condition in different parts of the stomach and allow for the collection of biomaterials for additional research. The percentage of animals affected by helicobacteriosis increases with age. Animals suf-fering from helicobacteriosis experience significantly reduced productivity, delayed growth and development in young horses, leading to premature culling. It is incorrect to only test suspicious animals with indications for helicobacteriosis, as not all carriers of Helicobacter pylori show symptoms of the disease. The use of the drug Domosedan at a dose of 0.5 μg per kilogram of body weight, or Combistress at a rate of 0.5 cm3 per 100 kg of body weight, effectively calmed the an-imals, fully relaxed the GIT, and facilitated successful endoscopy and video gastroscopy examinations.

Cohort profile: the Norwegian Registry of Persons Assessed for Cognitive Symptoms (NorCog) – a national research and quality registry with a biomaterial collection

PurposeThe Norwegian Registry of Persons Assessed for Cognitive Symptoms (NorCog) was established to harmonise and improve the quality of diagnostic practice across clinics assessing persons with cognitive symptoms in Norwegian...

ОЦЕНКА КУЛЬТУРОМА ОТДЕЛЯЕМОГО ВЕРХНИХ ДЫХАТЕЛЬНЫХ ПУТЕЙ И СОДЕРЖИМОГО ТОЛСТОЙ КИШКИ У ПАЦИЕНТОВ С АТОПИЧЕСКИМ ДЕРМАТИТОМ

Aim. The aim of the study is to study the species diversity of the microflora of the discharge of the nose, oropharynx and the contents of the colon in atopic dermatitis. Material and methods. The study included 80 patients with atopic dermatitis. Patients are divided into 3 groups depending on the severity of AD (Focusing on the SCORAD scale). The patients underwent collection of biomaterials from the oral and nasal cavities and intestines. Sowing of the material was carried out on an extended list of nutrient media. As a result of the MALDI-ToF mass spectrometry on the Microflex LT (Bruker, Germany), the resulting microorganisms were recognized by direct and extended deposition using formic acid. Results and discussion. When seeding feces patients from all groups, statistically significant differences were revealed for the following microorganisms, depending on the severity: Enterococcus faecium (61%), Streptococcus anginosus (16.7%), Parabacteroides distasonis (22.2%) were found in remission; at the stage of exacerbation with exacerbation of atopic dermatitis in the form of a limited form - Enterococcus faecalis (39.3%), Lactobacillus fermentum (16.1%), Streptococcus parasanguinis (9%);with a common form of exacerbation, Klebsiella pneumonia (50%), Klebsiella oxytoca (50%), Enterococcus mundtii (16.7%), Echerichia vulneris (16.7%), Lactobacillus salivarius (83.3%), Raoultella ornithinolytica(16.7%), Enterococcus avium (50%), Enterobacter asburie (16.7%), Citr obacter braaki (33.3%), Bacteroides vulgates (33.3%), Bifidobacterium adolescentis(16.7%), Enterococcus durans (16.7%), Lactobacillus crispatus (16.7%), Corynebacterium amycolatum (33.3%), Streptococcus sanguinis (16.7%). Inoculation of oropharyngeal discharge from patients with atopic dermatitis revealed statistically significant differences for the following microorganisms, depending on the severity: Streptococcus australis (11.1%) was detected in remission; in the stage of exacerbation with a limited form of atopic dermatitis, Rothia mucalaginosa (19.6%), Streptococcus saliverius (39.3%) were identified; in the stage of exacerbation with a widespread form of atopic dermatitis, Streptococcus anginosus (16.7%;), Candida albicans (33.3%), Streptococcus gordonii (16.7%), Staphylococcus haemolyticus (16.7%), Neisseria oralis (33.3%), Corynebacterium amycolatum (16.7%), Kocuria rhizophila (33.3%), Lactobacillus rhamnosus (16.7%). Inoculation of nasal discharge from patients with atopic dermatitis revealed statistically significant differences for the following microorganisms, depending on the severity: Staphylococcus haemolyticus (16.7%), Staphylococcus lugdunensis (11.1%), Staphylococcus copitis (11.1%) were found in remission. At the stage of exacerbation with a widespread form of atopic dermatitis, Proteus mirabilis (16.7%), Streptococcus vestibularis (16.7%), Streptococcus sobrinus (16.7%), Staphylococcus warneri (16.7%), Corynebacterium coyleae (16.7%), Lactobacillus plantarum (16.7%). Conclusion. Our results indicate enzymatic deficiency and significant changes in the qualitative composition of the microbiota in people with atopic dermatitis, which violates the body's immunomodulating function.

Alternative and promising targets of biochemical analysis in sport (review of literature).

Current literature review provides an evaluation of advantages and limitations of biochemical control objects representing functional state of athletes as well as the outlook for using alternative targets regarding sports medicine. Traditionally, invasive procedures (venous blood collection, muscle biopsy) have been known as the gold standard for analyzing a wide range of biomarkers which could be employed as effective diagnostic tools to control the course of adaptation processes, monitor performance, overtraining and physical well-being of athletes, but these techniques are painful, time-consuming and place demands on storage and shipment. In this behalf finding an alternative objects for biochemical research that does not have disadvantages given above is the question of present interest. Saliva and dry blood spots (DBS) could serve as equally informative and promising targets for monitoring athletes' condition. The non-invasive nature of saliva collection allows to shorten sample collection time, reduce stress hormones levels and possible infection contamination. Moreover, collecting saliva process does not require special equipment and trained medical staff which is particularly important when athletes are at training camps. The DBS method has successfully proven itself with regard to neonatal screening and pharmacokinetics studies. Its key benefits are simplicity, small volume of bioliquid, enhanced stability of adsorbed biomarkers on the card surface, lack of special storage and transportation requirements and low costs for samples shipment to the laboratory. Taken together outlined advantages will provide the opportunity to increase the frequency of biomaterial collection to perform selective observation of training loads effects on various systems of athletes' body. The combination of DBS with immunochemical and mass-spectrometric approaches could serve as an efficient instrument to investigate the role of various biomarkers in monitoring the functional state of athletes. We searched for articles in MedLine database with the key words «dry blood spots», «saliva», «sports medicine», «sample collection», «sports biochemistry».

Comparison of the Physical Properties and Effectiveness of Medical Swabs for Sampling Biomaterials.

The COVID-19 pandemic has induced a sharp rise in demand for consumables for laboratory diagnosis and, in particular, for swabs for sampling biomaterials. Test quality depends strongly on swab quality. The aim of this work was to run experimental studies to evaluate the physical and operational properties of fiber-type medical swabs. This study compared swabs from leading manufacturers traditionally regarded as the quality standard on the Russian market in the premium sector: Copan Diagnostics (Italy), Puritan Medical Products (PMP) (USA), and PharmMedPolis (PhMP) (Russia). The following properties were studied: absorption, zeta potential, and surface morphology (by scanning electron microscopy). The techniques for biomaterial collection and release were also considered. Experiments using Streptomyces pneumoniae cultures as an example showed that the Copan Diagnostics swab had a recovery rate (RR) of 78.3%, compared with 84.15% for the Puritan Medical Products swab, 87.49% for the PhMP swab, and 93.72% for the HydraFlock® swab. The HydraFlock® swab was found to be especially effective due to its high ability to absorb water and protein and its high bacterial recovery rate. The second best results were for the PharmMedPolis® swab, followed by the Copan swab and the nylon swab from Puritan Medical Products.

Three-Dimensional Printability of an ECM-Based Gelatin Methacryloyl (GelMA) Biomaterial for Potential Neuroregeneration.

The current study introduces two novel, smart polymer three-dimensional (3D)-printable interpenetrating polymer network (IPN) hydrogel biomaterials with favorable chemical, mechanical, and morphological properties for potential applications in traumatic brain injury (TBI) such as potentially assisting in the restoration of neurological function through closure of the wound deficit and neural tissue regeneration. Additionally, removal of injury matter to allow for the appropriate scaffold grafting may assist in providing a TBI treatment. Furthermore, due to the 3D printability of the IPN biomaterials, complex structures can be designed and fabricated to mimic the native shape and structure of the injury sight, which can potentially assist with neural tissue regeneration after TBI. In this study, a peptide-only approach was employed, wherein collagen and elastin in a blend with gelatin methacryloyl were prepared and crosslinked using either Irgacure or Irgacure and Genipin to form either a semi or full IPN hydrogel 3D-printable neuromimicking platform system, respectively. The scaffolds displayed favorable thermal stability and were amorphous in nature with high full width at half-maximum values. Furthermore, no alteration to the peptide secondary structure was noted using Fourier transform infrared spectroscopy. The IPN biomaterials have a stiffness of around 600 Pa and are suitable for softer tissue engineering applications—that is, the brain. Scanning electron micrographs indicated that the IPN biomaterials had a morphological structure with a significant resemblance to the native rat cortex. Both biomaterial scaffolds were shown to support the growth of PC12 cells over a 72 h period. Furthermore, the increased nuclear eccentricity and nuclear area were shown to support the postulation that the IPN biomaterials maintain the cells in a healthy state encouraging cellular mitosis and proliferation. The Genipin component of the full IPN was further shown to exhibit antimicrobial properties and this suggests that Genipin can prevent the growth of pathogens associated with postsurgical brain infections. In addition to these findings, the study presents an anomaly, wherein the full IPN is found to be more brittle than the semi IPN, a finding that is in contradiction with the literature. This research, therefore, contributes to the collection of potential biomaterials for TBI applications coupled with 3D printing and can assist in the progression of neural treatments toward patient-specific scaffolds through the development of custom scaffolds.

Role of biobanking in managing large-scale epidemiological studies

The success and quality of large-scale epidemiological studies depends entirely on biomaterial quality. Therefore, when arranging the third Epidemiology of Cardiovascular Diseases and their Risk Factors in Regions of Russian Federation (ESSE-RF-3) study, increased attention was paid to specifics of collection, processing and further transportation of biological samples and related clinical and anthropometric data of participants from regional collection centers to Biobank.Aim. To develop a methodology for collection of high-quality biomaterials within the large-scale epidemiological study, involving the sampling, processing, freezing of blood and its derivatives (serum, plasma) in the regions, followed by transportation and storage of obtained biomaterial in the Biobank of National Medical Research Center for Therapy and Preventive Medicine (Moscow).Material and methods. To conduct the ESSE-RF-3 study, a design was developed, according to which the collection of venous blood samples in a total volume of 29,5 ml from each participant is planned in all participating regions in order to obtain and store samples of whole blood, serum and two types of plasma.Results. On the basis of international biobanking standards, ethical norms, experience from ESSE-RF and ESSE-RF-2, and literature data, a protocol for biobanking of blood and its derivatives was developed. The type and number of serum and plasma aliquots obtained, the required standard technical means and consumables, as well as logistic biomaterial requirements were determined. Training programs for regional participants were developed. By the beginning of August 2021, 180 thousand samples of whole blood, serum and plasma from more than 23 thousand participants from 28 Russian regions were collected, processed and stored.Conclusion. The presented work made it possible to assess and confirm the compliance of developed biobanking protocol with quality requirements. However, due to the coronavirus disease 2019 pandemic, by August 2021, the Biobank did not reach the maximum effectiveness predicted for the ESSE-RF-3 project.

A Collection of Biomaterials and Biomechanical Experiments and Analysis Methods

A Collection Of Biomaterials And Biomechanical Experiments And Analysis Methods - Video. JoVE publishes peer-reviewed scientific video protocols to accelerate biological, medical, chemical and physical research. Watch our scientific video articles. JoVE is the world-leading producer and provider of science videos with the mission to improve scientific research, scientific journals, and education. Millions of scientists, educators and students at thousands of universities, colleges, hospitals and biopharmaceutical companies worldwide use JoVE for their research, teaching and learning.

A Collection of Biomaterials and Biomechanical Experiments and Analysis Methods

A Collection Of Biomaterials And Biomechanical Experiments And Analysis Methods - Video. JoVE publishes peer-reviewed scientific video protocols to accelerate biological, medical, chemical and physical research. Watch our scientific video articles. JoVE is the world-leading producer and provider of science videos with the mission to improve scientific research, scientific journals, and education. Millions of scientists, educators and students at thousands of universities, colleges, hospitals and biopharmaceutical companies worldwide use JoVE for their research, teaching and learning.

Abstract CT251: MEDOCC-CrEATE trial in progress: effectiveness of adjuvant chemotherapy in stage II colon cancer patients with positive circulating tumor DNA

Abstract Background Accurate detection of patients with minimal residual disease (MRD) after resection of localized colon cancer remains an unmet clinical need as these patients might benefit from adjuvant chemotherapy (ACT). For stage II colon cancer, ACT is only indicated in patients with a pT4 tumor without a deficient mismatch repair system (dMMR), according to Dutch guidelines. However, recurrence rate (RR) in stage II colon cancer is still 15-20%. Circulating tumor DNA (ctDNA), consisting of small fragments of DNA containing tumor-specific mutations, has been shown to be a promising biomarker for MRD and a strong predictor for recurrent disease when detectable after resection. The MEDOCC-CrEATE trial investigates how many stage II colon cancer patients with detectable ctDNA after surgery will accept ACT and whether ACT reduces RR in these patients. Methods The MEDOCC-CrEATE study follows the ‘trials within cohorts' (TwiCs) design. Patients with colorectal cancer are included in the Prospective Dutch ColoRectal Cancer (PLCRC) cohort study and give informed consent for collection of clinical data and biomaterials, including tissue and blood samples. Additionally, patients are invited to give their consent for future randomization without being informed when allocated to the control group receiving standard of care. In MEDOCC-CrEATE 1320 stage II colon cancer patients without an indication for ACT will be included and randomized 1:1 into an experimental and a control arm. In the experimental arm, tissue and blood samples are analyzed after surgery for tissue-informed detection of plasma ctDNA, using the PGDx elio™ Platform. Patients with detectable ctDNA after surgery will be offered ACT consisting of 8 cycles of capecitabine plus oxaliplatin. Patients in the experimental arm without detectable ctDNA and patients in the control arm receive standard follow-up. The primary endpoint is the proportion of patients accepting ACT when ctDNA is detectable after resection. Most important secondary endpoint is 2-year RR, but also includes 5-year RR, disease free and overall survival, time to recurrence, quality of life and cost-effectiveness of the ctDNA-based treatment strategy. Data will be analyzed by intention to treat. To our knowledge, MEDOCC-CrEATE is the first trial in which a ctDNA guided strategy for adjuvant chemotherapy in colon cancer is investigated. The first patient was enrolled in August 2020. MEDOCC-CrEATE is now open for inclusion in 8 hospitals in the Netherlands. So far, 9 patients have been randomized. The number of participating hospitals will be expanded to 20-25 hospitals to include all 1320 patients within 3 years. MEDOCC-CrEATE has been registered in the Netherlands Trial Register: NL6281/NTR6455. Citation Format: Suzanna J. Schraa, Karlijn L. Van Rooijen, Dave E. Van Der Kruijssen, Carmen Rubio Alarcón, Jillian Phallen, John Simmons, Sam Angiuoli, Amy E. Greer, Veerle M. Coupé, Helma M. Van Grevenstein, Sjoerd Elias, Helena M. Verkooijen, Miranda M. Van Dongen, Linda J. Bosch, Daan Van Den Broek, Gerrit A. Meijer, Victor E. Velculescu, Remond J. Fijneman, Geraldine R. Vink, Miriam Koopman. MEDOCC-CrEATE trial in progress: effectiveness of adjuvant chemotherapy in stage II colon cancer patients with positive circulating tumor DNA [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT251.

DescribePSP and ProPSP: German Multicenter Networks for Standardized Prospective Collection of Clinical Data, Imaging Data, and Biomaterials of Patients With Progressive Supranuclear Palsy.

Background: The German research networks DescribePSP and ProPSP prospectively collect comprehensive clinical data, imaging data and biomaterials of patients with a clinical diagnosis of progressive supranuclear palsy. Progressive supranuclear palsy is a rare, adult-onset, neurodegenerative disease with striking clinical heterogeneity. Since now, prospective natural history data are largely lacking. Clinical research into treatment strategies has been limited due to delay in clinical diagnosis and lack of natural history data on distinct clinical phenotypes.Methods: The DescribePSP network is organized by the German Center for Neurodegenerative Diseases. DescribePSP is embedded in a larger network with parallel cohorts of other neurodegenerative diseases and healthy controls. The DescribePSP network is directly linked to other Describe cohorts with other primary diagnoses of the neurodegenerative and vascular disease spectrums and also to an autopsy program for clinico-pathological correlation. The ProPSP network is organized by the German Parkinson and Movement Disorders Society. Both networks follow the same core protocol for patient recruitment and collection of data, imaging and biomaterials. Both networks host a web-based data registry and a central biorepository. Inclusion/exclusion criteria follow the 2017 Movement Disorder Society criteria for the clinical diagnosis of progressive supranuclear palsy.Results: Both networks started recruitment of patients by the end of 2015. As of November 2020, N = 354 and 269 patients were recruited into the DescribePSP and the ProPSP studies, respectively, and N = 131 and 87 patients received at least one follow-up visit.Conclusions: The DescribePSP and ProPSP networks are ideal resources for comprehensive natural history data of PSP, including imaging data and biological samples. In contrast to previous natural history studies, DescribePSP and ProPSP include not only patients with Richardson's syndrome, but also variant PSP phenotypes as well as patients at very early disease stages, before a diagnosis of possible or probable PSP can be made. This will allow for identification and evaluation of early biomarkers for diagnosis, prognosis, and progression.

Thoracic radiotherapy PLUS durvalumab in elderly and/or frail NSCLC stage III patients unfit for chemotherapy: Employing optimized (hypofractionated) radiotherapy to foster durvalumab efficacy—The TRADE-hypo trial.

TPS8585 Background: Non-small cell lung cancer (NSCLC) is the most common cause of cancer death worldwide highlighting the importance of improving current therapeutic options. In particular, elderly and frail patients are not only underrepresented in clinical trials, but also frequently do not receive standard treatment regimens due to comorbidities. For example, patients with unresectable stage III NSCLC who are unfit for chemotherapy (CHT) do not benefit from the recent seminal therapy algorithm change for this disease, i.e. consolidation therapy with the immune checkpoint inhibitor (ICI) durvalumab after combined radiochemotherapy (RChT). Instead, these patients are treated with radiotherapy only, raising the serious concern of undertreatment. This issue is addressed by the TRADE-hypo clinical trial that investigates a novel therapy option for NSCLC stage III patients not capable of receiving CHT. To this end, thoracic radiotherapy (TRT) is administered together with durvalumab, employing the synergism created by the combination of restoring anti-tumor immune response by the ICI with the induction of immunogenicity by irradiation. The latter effect has been suggested to be further boosted by hypofractionated radiotherapy, which could also be more practicable for the patient. Taken these considerations into account, the TRADE-hypo trial addresses safety and efficacy of durvalumab therapy combined with either conventional or hypofractionated TRT. Methods: The TRADE-hypo trial is a prospective, randomized, open-label, multicentric phase II trial. Eligible patients are diagnosed with unresectable stage III NSCLC and not capable of receiving sequential RChT due to high vulnerability as reflected by a poor performance status (ECOG 2 or ECOG1 and CCI≥ 1) and/or high age (≥ 70)]. Two treatment groups are evaluated: Both receive durvalumab (1,5000 mg, Q4W) for up to 12 months. In the CON-group this is combined with conventionally fractionated TRT (30 x 2 Gy), while in the HYPO-group patients are treated with hypofractionated TRT (20 x 2.75 Gy). In the HYPO-arm, a safety stop-and-go lead-in phase precedes full enrollment. Here, patients are closely monitored with regard to toxicity (i.e., pneumonitis grade ≥ 3 within 8 weeks after TRT) in small cohorts of 6. The primary objective of the trial is safety and tolerability. As a primary efficacy endpoint, the objective response rate after 3 months will be evaluated. Further endpoints are additional parameters of safety and efficacy, as well as the comprehensive collection of biomaterials to be analyzed regarding treatment-induced changes and potential novel biomarkers. As of February 10, 2021, 9 patients of planned 88 patients have been enrolled in the TRADE-hypo trial. Clinical trial information: NCT04351256.

Circulating tumor DNA analysis of genomic alterations in metastatic urothelial carcinoma from NCT03113266 study.

486 Background: Recent studies have suggested the predictive value of liquid biopsies for immune checkpoint inhibitors. NCT03113266 is a multicenter phase II trial to evaluate the safety and efficacy of toripalimab (anti-PD-1) in metastatic urothelial carcinoma (mUC). Here we report the initial circulating tumor DNA (ctDNA) analysis of genomic alterations from a single-institution biomarker cohort. Methods: Twenty-seven mUC patients receiving toripalimab (3 mg/kg Q2W) at Ren Ji Hospital were enrolled and consented to Institutional Review Board-approved protocols permitting biomaterial collection and genetic sequencing. Serial plasma specimens were obtained at baseline and every two cycles. The 600-gene panel (PredicineATLAS) liquid biopsy assay was applied to assess somatic variants and blood tumor mutational burden (bTMB). Results: The ctDNA assays were performed successfully for 100% of baseline samples (n = 27) with average read depth of 24,389 (range 14,000-31,700). A total of 571 non-synonymous mutations were identified, demonstrating prevalent aberrations in TP53 (63%), TERT promoter (30%), KDM2D (26%), PPM1D (26%), and KDM6A (26%). In 5 patients, FGFR3 variants were detected, including 6 missense sites and 4 FGFR3- TACC3 fusion events. Copy number gain ( FGFR1, ERBB2) and loss ( PTEN, BRCA2, CDKN2A) were pinpointed. TMB estimation revealed one case with an exceptionally high bTMB (62.6 mutations/Mb) and genomic features of microsatellite instability (MSI). Concordance with tumor-based genotyping and ctDNA kinetics during toripalimab treatment are being determined. Conclusions: Prospective ctDNA analysis using the PredicineATLAS liquid biopsy assay is feasible and represents a minimally invasive approach to detecting cancer-specific genetic landscape and potentially guiding personalized therapeutic decisions in mUC patients. Clinical trial information: NCT03113266 . Research Sponsor: Shanghai Junshi BioSciences; Huidu Shanghai Medical Sciences Ltd

A developed treatment method for superficial and partial thickness localized burns: Clinical and morphological assessment

Objectives to prove the effectiveness of the new developed method of treatment of patients with localized superficial and partial thickness burns (gel and silver coating plus ultraviolet radiation of the wound and magnetic therapy).
 Material and methods.The treatment of local burn wound infection was analyzed in 29 patients with I-II degree localized burns during the all phases of the wound healing process. The wound material was obtained in accordance with the requirements of the Guidelines МУ 4.2.2039-05 "The technique of collection and transportation of biomaterials in microbiological laboratories". The material was delivered to the laboratory in test tubes with a transport medium under isothermal conditions at a temperature of 2022C within a day after collection.
 Results.The tests revealed no significant differences in the studied characteristics between the compared groups (р0.05, р=0.55,2=3.841).
 Conclusion.We consider the developed method of local treatment of superficial and partial thickness localized burns as a rather promising, feasible method having its own significance and intended for the prevention and treatment of local wound infection in all phases of the wound healing process.

Methodological aspects of formation of parsipative direction of medicine on example of using various types of biomaterial for COVID-19diagnosis

The development of laboratory diagnostics is carried out not only by technological modernization, but also by the expansion of the volume of non-invasive studies with the active participation of patients in the collection of biomaterials. According to the results of the study with 68 patients the most effective verification of SARS-CoV-2 is carried out with the active participation of the patient in the collection of biomaterials. Increasing the information content of research is being developed by methods of logical analysis, which allow obtaining new knowledge about the subject area.