Vascular allografts for clinical application in Europe: assessment of 30 years of experience with vascular tissue banking in Brussels.

Vascular tissue banking has been carried out in Brussels for over 30 years in compliance with EU and Swiss tissue banking regulations. A total of 2.765 vascular tissue donations were performed in Belgian, French, Netherlands and Suisse transplant centres: 547(20%), 1.013(37%) and 1.205(43%) during the first, second and third periods, respectively. 85% and 18% increase in donations during the second and third decades compared to previous one, were remarkable. Of the 7.066 evaluated vascular tissues, 2.407(227, 921 and 1.259) were discarded (34.1%), whereas 4.659(523, 1.861 and 2.275) accepted (65.9%) during the respective period. Of the 92 donated veins, 44(47.8%) were discarded and 48(52.2%) accepted. Allografts available for clinical application were stored in vapours of liquid nitrogen. A total of 4.636 allografts were delivered and transplanted for cases of infection (58%), critical limb ischaemia (16%) and congenital cardiac surgery (15%). Thirty veins were implanted. The progressive increases in donations of 20%, 37% and 43% and in transplantations of 20.8%, 34.6% and 45% during the first, second and third periods, respectively, were remarkable. Complications were reported after transplantation and these included acute rejection of two femoral arteries one month after transplantation. We conclude that the donation and transplantation of cryopreserved vascular allografts was stable with a progressive increase over time. Allografts were used predominantly for the treatment of infection, limb salvage for critical ischaemia and for neonates and infants with congenital cardiac malformation. Immune related rejection was observed. This should be a subject of future investigation.

Microbiological assessment of arterial allografts processed in a tissue bank.

The transmission of microbial infection through tissue allografts is one of the main risks that must be controlled in tissue banks. Therefore, microbiological monitoring controls and validated protocols for the decontamination of tissues during processing have been implemented. This study is based on the evaluation of data from microbiological cultures of arteries (mainly long peripheral arteries) processed in the tissue bank of Valencia (Spain). Donors' profile, pre- and post-disinfection tissue samples were assessed. The presence of residual antibiotics in disinfected tissues was determined and the antimicrobial potential of these tissues was tested. Our overall contamination rate was 23.69%, with a disinfection rate (after antibiotic incubation) of 87.5%. Most (76.09%) of the microbial contaminants were identified as Gram positive. Arterial allografts collected from body sites affected by prior organ removal showed higher risk of contamination. Only vancomycin was detected as tissue release. The antimicrobial effect on Candida albicans was lower than that for bacterial species. Risk assessment for microbial contamination suggested the donor's skin and the environment during tissue collection as the main sources for allograft contamination. Antibiotic-disinfected arterial allografts showed antimicrobial potential.

Evaluation of the Suitability of an Existing Job-Exposure Matrix for the Assessment of Exposure of UK Biobank Participants to Dust, Fumes, and Diesel Exhaust Particulates.

Many epidemiological studies have shown an association between outdoor particulate air pollutants and increased morbidity and mortality. Inhalation of ambient aerosols can exacerbate or promote the development of cardiovascular and pulmonary diseases as well as other diseases, such as type 2 diabetes mellitus (T2DM) and neurodegenerative diseases. Occupational exposure to dust, fumes and diesel exhaust particulates can also cause adverse health outcomes and there are numerous occupations where workers are exposed to airborne particles that are similar to ambient air pollution. An individual's job title has normally been identified as a major determinant of workplace exposure in epidemiological studies. This has led to the development of Job-Exposure Matrices (JEMs) as a way of characterising specific workplace exposures. One JEM for airborne chemical exposures is the Airborne Chemical Exposure Job-Exposure Matrix (ACE JEM), developed specifically for the UK Biobank cohort. The objective of this paper is to evaluate the suitability of the ACE JEM in assessing occupational aerosol exposure of participants in the UK Biobank. We searched the scientific literature to identify exposure data linked to selected jobs in the ACE JEM and compared these data with the JEM assessments. Additionally, we carried out an independent expert-based assessment of exposure to compare with the JEM estimates. There is good published evidence to substantiate the high dust and biological dust assignments in the JEM and more limited evidence for diesel exhaust particulates. There is limited evidence in the published literature to substantiate moderate or low exposure assignments in the JEM. The independent expert-based assessment found good agreement at the two extremes of exposure in the JEM (high and no exposure), with uncertainty in all other classifications. The ACE JEM assignments are probably reliable for highly exposed jobs and for jobs assigned as unexposed. However, the assignments for medium and low exposures are less reliable. The ACE JEM is likely to be a good tool to examine associations between occupational exposures to particulates and chronic disease, although it should be used with caution. Further efforts should be made to improve the reliability of the ACE JEM.

Making the most of small samples: Optimization of tissue allocation of pediatric solid tumors for clinical and research use.

INTRODUCTION: Tissue from pediatric solid tumors is in high demand for use in high-impact research studies, making the allocation of tissue from an anatomic pathology laboratory challenging. We designed, implemented, and assessed an interdepartmental process to optimize tissue allocation of pediatric solid tumors for both clinical care and research. METHODS: Oncologists, pathologists, surgeons, interventional radiologists, pathology technical staff, and clinical research coordinators participated in the workflow design. Procedures were created to address patient identification and consent, prioritization of protocols, electronic communication of requests, tissue preparation, and distribution. Pathologists were surveyed about the value of the new workflow. RESULTS: Over a 5-year period, 644 pediatric solid tumor patients consented to one or more studies requesting archival or fresh tissue. Patients had a variety of tumor types, with many rare and singular diagnoses. Sixty-seven percent of 1768 research requests were fulfilled. Requests for archival tissue were fulfilled at a significantly higher rate than those for fresh tissue (P > .001), and requests from resection specimens were fulfilled at a significantly higher rate than those from biopsies (P > .0001). In an anonymous survey, seven of seven pathologists reported that the process had improved since the introduction of the electronic communication model. CONCLUSIONS: A collaborative and informed model for tissue allocation is successful in distributing archival and fresh tissue for clinical research studies. Our workflows and policies have gained pathologists' approval and streamlined our processes. As clinical and research programs evolve, a thoughtful tissue allocation process will facilitate ongoing research.

Banking of corneal stromal lenticules: a risk-analysis assessment with the EuroGTP II interactive tool.

We evaluated the feasibility and performed a risk-benefit analysis of the storage and widespread distribution of stromal lenticules for clinical application using a new systematic tool (European Good Tissue and cells Practices II-EuroGTP II tool), specifically designed for assessing the risk, safety and efficacy of substances of human origin. Three types of potential tissue preparations for human stromal lenticules were evaluated: cryopreserved, dehydrated and decellularized. The tool helps to identify an overall risk score (0-2: negligible; 2-6: low; 6-22: moderate; > 22: high) and suggests risk reduction strategies. For all the three types of products, we found the level of risk to be as "moderate". A process validation, pre-clinical in vitro and in vivo evaluations and a clinical study limited to a restricted number of patients should therefore be performed in order to mitigate the risks. Our study allowed to establish critical points and steps necessary to implement a new process for safe stromal lenticule preparation by the eye banks to be used in additive keratoplasty. Moreover, it shows that the EuroGTP II tool is useful to assess and identify risk reduction strategies for introduction of new Tissue and Cellular Therapies and Products into the clinical practice.

Geospatial Mapping as a Guide for Resource Allocation Among Burn Centers in India.

Timely treatment is essential for optimal outcomes after burn injury, but the method of resource distribution to ensure access to proper care in developing countries remains unclear. We therefore sought to examine access to burn care and the presence/absence of resources for burn care in India. We surveyed all eligible burn centers (n = 67) in India to evaluate burn care resources at each facility. We then performed a cross-sectional geospatial analysis using geocoding software (ArcGIS 10.3) and publicly available hospital-level data (WorldStreetMap, WorldPop database) to predict the time required to access care at the nearest burn center. Our primary outcome was the time required to reach a burn facility within India. Descriptive statistics were used to present our results. Of the 67 burn centers that completed the survey, 45% were government funded. More than 1 billion (75.1%) Indian citizens live within 2 hours of a burn center, but only 221.9 million (15.9%) live within 2 hours of a burn center with both an intensive care unit (ICU) and a skin bank. Burn units are staffed primarily by plastic surgeons (n = 62, 93%) with an average of 5.8 physicians per unit. Most burn units (n = 53, 79%) have access to hemodialysis. While many Indian citizens live within 2 hours of a burn center, most centers do not offer ICU and skin bank services that are essential for modern burn care. Reallocation of resources to improve transportation and availability of ICU and skin bank services is necessary to improve burn care in India.

Situacion actual de los bancos de tejidos en colombia: tejido osteomuscular / Current situation of tissue banks in colombia: musculoskeletal tissue

Introducción El tejido óseo es el segundo tejido más trasplantado en el ser humano. Los Ortopedistas y Odontólogos son los principales profesionales que lo utilizan en sus procedimientos. El objetivo de este trabajo fué caracterizar la actividad de los Bancos certificados del país para Tejido Osteomuscular. Materiales y Métodos Mediante encuesta realizada vía teleconferencia a cada Banco de tejidos, se evalúan ítems de donación, extracción, procesamiento, almacenamiento, distribución y capacidad de producción de los tejidos Osteomusculares. La información es complementada con actas de certificación de Buenas Prácticas del Invima (Instituto Nacional para la Vigilancia de Medicamentos y Alimentos) e información suministrada por el INS (Instituto Nacional de Salud) de las estadísticas reportadas por los bancos mensualmente. Resultados El tejido procesado procede de donantes de medicina legal 77%, IPS (Instituciones Prestadoras de Servicios de Salud) 5% y donantes vivos 17%. La edad de donación es de 45 a 70 años dependiendo de si es tejido estructural, género y condición del donante vivo/muerto. Las tecnologías para el control microbiológico son variadas, encontrando condiciones asépticas de procesamiento, antibióticos y radiación Gamma. Los productos finales ofrecidos son tejido fresco, liofilizado, pulverizado, decalcificado y matriz ósea desmineralizada. El periodo de almacenamiento máximo encontrado es de 5 años. Se estima que por donante real se obtendrían 67 unidades de implantes en Colombia. Discusión El desarrollo Tecnológico de los Bancos Colombianos de tejido Osteomuscular alcanza altos estándares internacionales, pudiéndose cubrir la variada demanda de productos internos necesarios para todas las especialidades, sin embargo se encuentra un rezago en los procesos de aprovechamiento suficiente de los tejidos procedente de los donantes y de la distribución de los mismos. Nivel de Evidencia: IV.

Background The bone is the second most transplanted tissue in humans. Orthopaedists and Dentists are the main professionals that use it in their procedures. The aim of this study was to describe the activity of the certified musculoskeletal tissue banks in Colombia. Methodology The extraction, processing, storage, distribution, and production capacity of musculoskeletal tissues donated to each Tissue Bank were evaluated using a questionnaire completed via teleconference. The information was supplemented with records of management certification of Good Practices, Invima registers, and information provided by the NHI (Colombian National Health Institute) statistics reported by tissue banks each month. Results The processed tissue comes from forensic donors (77%), IPS health care institutions (5%), and 17% from living donors. Donor age was 45 to 70 years, depending on whether it was structural tissue, gender, and condition of live / dead donor. Technologies for microbiological control varied, with aseptic processing, antibiotics, and gamma radiation being found. The final products offered are fresh tissue, lyophilised, pulverised, decalcified, and demineralized bone matrix. The maximum storage period found was 5 years. It is estimated that 67 tissue units could be obtained from each donor in Colombia. Discussion Technological development of Colombian musculoskeletal Tissue Banks is of the highest international standards, being able to meet the varied demand for domestic products necessary for all related medical fields. However, it was identified that there was a lag in the distribution process, as well as in usability and taking advantage of the availability, and use of tissues from donors. Evidence Level: IV

Addressing Challenges in Converting Grant-Funded Infrastructures to Broadly Used Research Resources.

The NCI invests heavily in research resources to serve the research community, including datasets, biospecimen banks, and networks of institutions in which clinical trials and other human subjects research are conducted. These resources often begin as grant-funded infrastructure initiated by scientists based on their own scientific interests, with a subsequent recognition of additional scientific uses. Although converting existing project-specific research activities into research resources may appear efficient in terms of time and financial investment, challenges can arise that undermine this efficiency and jeopardize future use. Here, we describe three challenges in the conversion process: (i) project-based infrastructure versus a research resource for a broader research community; (ii) complexity versus ease of use; and (iii) individual professional goals versus research resource priorities. We use our experience with the NCI-funded Cancer Research Network, particularly the Virtual Data Warehouse, to illustrate each challenge, concluding with strategies to mitigate each one. As studies grow in size and complexity, an ever-increasing volume of data, biospecimens, and human subjects research networks will be available for conversion to resources for scientific questions beyond those originally proposed. Addressing likely challenges thoughtfully can result in a more efficient conversion process and ultimately greater scientific impact.

Assessment of Striatal Dopamine Transporter Binding in Individuals With Major Depressive Disorder: In Vivo Positron Emission Tomography and Postmortem Evidence.

Importance: Major depressive disorder (MDD) might involve dopamine (DA) reductions. The DA transporter (DAT) regulates DA clearance and neurotransmission and is sensitive to DA levels, with preclinical studies (including those involving inescapable stressors) showing that DAT density decreases when DA signaling is reduced. Despite preclinical data, evidence of reduced DAT in MDD is inconclusive. Objective: Using a highly selective DAT positron emission tomography (PET) tracer ([11C] altropane), DAT availability was probed in individuals with MDD who were not taking medication. Levels of DAT expression were also evaluated in postmortem tissues from donors with MDD who died by suicide. Design, Setting, and Participants: This cross-sectional PET study was conducted at McLean Hospital (Belmont, Massachusetts) and Massachusetts General Hospital (Boston) and enrolled consecutive individuals with MDD who were not taking medication and demographically matched healthy controls between January 2012 and March 2014. Brain tissues were obtained from the Douglas-Bell Canada Brain Bank. For the PET component, 25 individuals with current MDD who were not taking medication and 23 healthy controls recruited from McLean Hospital were included (all provided usable data). For the postmortem component, 15 individuals with depression and 14 healthy controls were considered. Intervention: PET scan. Main Outcomes and Measures: Striatal and midbrain DAT binding potential was assessed. For the postmortem component, tyrosine hydroxylase and DAT levels were evaluated using Western blots. Results: Compared with 23 healthy controls (13 women [56.5%]; mean [SD] age, 26.49 [7.26] years), 25 individuals with MDD (19 women [76.0%]; mean [SD] age, 26.52 [5.92] years) showed significantly lower in vivo DAT availability in the bilateral putamen and ventral tegmental area (Cohen d range, -0.62 to -0.71), and both reductions were exacerbated with increasing numbers of depressive episodes. Unlike healthy controls, the MDD group failed to show an age-associated reduction in striatal DAT availability, with young individuals with MDD being indistinguishable from older healthy controls. Moreover, DAT availability in the ventral tegmental area was lowest in individuals with MDD who reported feeling trapped in stressful circumstances. Lower DAT levels (and tyrosine hydroxylase) in the putamen of MDD compared with healthy controls were replicated in postmortem analyses (Cohen d range, -0.92 to -1.15). Conclusions and Relevance: Major depressive disorder, particularly with recurring episodes, is characterized by decreased striatal DAT expression, which might reflect a compensatory downregulation due to low DA signaling within mesolimbic pathways.

Precision Radiotherapy and Radiation Risk Assessment: How Do We Overcome Radiogenomic Diversity?

Precision medicine is a rapidly developing area that aims to deliver targeted therapies based on individual patient characteristics. However, current radiation treatment is not yet personalized; consequently, there is a critical need for specific patient characteristics of both tumor and normal tissues to be fully incorporated into dose prescription. Furthermore, current risk assessment following environmental, occupational, or accidental exposures to radiation is based on population effects, and does not account for individual diversity underpinning radiosensitivity. The lack of personalized approaches in both radiotherapy and radiation risk assessment resulted in the current situation where a population-based model, effective dose, is being used. In this review article, to stimulate scientific discussion for precision medicine in both radiotherapy and radiation risk assessment, we propose a novel radiological concept and metric - the personalized dose and the personalized risk index - that incorporate individual physiological, lifestyle-related and genomic variations and radiosensitivity, outlining the potential clinical application for precision medicine. We also review on recent progress in both genomics and biobanking research, which is promising for providing novel insights into individual radiosensitivity, and for creating a novel conceptual framework of precision radiotherapy and radiation risk assessment.

Quality assessment on the long-term cryopreservation and nucleic acids extraction processes implemented in the andalusian public biobank.

Human samples are commonly collected and long-term stored in biobanks for current and future analyses. Even though techniques for freezing human blood are well established, the storage time can compromise the cell viability as well as the yield and quality of nucleic acids (RNA and DNA) extracted from them. In this study, a protocol to obtain peripheral blood mononuclear cells (PBMCs) from 70 subjects, which were stored at - 196 °C from EDTA tubes for a long-term, was assessed. In parallel; a protocol to obtain DNA from the same subjects, which were stored at - 80 °C from citrate tubes, was also studied. Samples stored from 2008 to 2012 were studied and the results obtained showed that there were no statistically significant differences in the RNA or DNA extracted in terms of purity, integrity and functionality The freezing protocol used by the Málaga Biobank shows that viable PBMCs and DNA could be kept for a period of, at least, 10 years, with a high quality and performance. Furthermore, RNA extracted from these PBMCs presents also a good quality and performance. Therefore, the samples frozen according to the conditions of the protocols assessed in this study could be optimal for biomedical research.

Comprehensive assessment of cryogenic storage risk and quality management concerns: best practice guidelines for ART labs.

Recent publicized events of cryogenic storage tank failures have created nationwide concern among infertility patients and patients storing embryos and gametes for future use. To assure patient confidence, quality management (QM) plans applied by in vitro fertilization (IVF) laboratories need to include a more comprehensive focus on the cryostorage of reproductive specimens. The purpose of this review is to provide best practice guidelines for the cryogenic storage of sperm, oocytes, embryos, and other reproductive tissues (e.g., testicular and ovarian tissue, cord blood cells, and stem cells) and recommend a strategy of thorough and appropriate quality and risk management procedures aimed to alleviate or minimize the consequences from catastrophic events.

Centralised versus decentralised manufacturing and the delivery of healthcare products: A United Kingdom exemplar.

BACKGROUND: The cell and gene therapy (CGT) field is at a critical juncture. Clinical successes have underpinned the requirement for developing manufacturing capacity suited to patient-specific therapies that can satisfy the eventual demand post-launch. Decentralised or 'redistributed' manufacturing divides manufacturing capacity across geographic regions, promising local, responsive manufacturing, customised to the end user, and is an attractive solution to overcome challenges facing the CGT manufacturing chain. METHODS: A study was undertaken building on previous, so far unpublished, semi-structured interviews with key opinion leaders in advanced therapy research, manufacturing and clinical practice. The qualitative findings were applied to construct a cost of goods model that permitted the cost impact of regional siting to be combined with variable and fixed costs of manufacture of a mesenchymal stromal cell product. RESULTS: Using the United Kingdom as an exemplar, cost disparities between regions were examined. Per patient dose costs of ~£1,800 per 75,000,000 cells were observed. Financial savings from situating the facility outside of London allow 25-41 additional staff or 24-35 extra manufacturing vessels to be employed. Decentralised quality control to mitigate site-to-site variation was examined. Partial decentralisation of quality control was observed to be financially possible and an attractive option for facilitating release 'at risk'. DISCUSSION: There are important challenges that obstruct the easy adoption of decentralised manufacturing that have the potential to undermine the market success of otherwise promising products. By using the United Kingdom as an exemplar, the modelled data provide a framework to inform similar regional policy considerations across other global territories.

Information technology for brain banking.

Implementing and maintaining the information technology (IT) infrastructure of a brain bank can be a daunting task for any brain bank coordinator, particularly when access to both funds and IT professionals is limited. Many questions arise when attempting to determine which IT products are most suitable for a brain bank. The requirements of each brain bank must be assessed carefully to ensure that the chosen IT infrastructure will be able to meet those requirements successfully and will be able to expand and adapt as the size of the brain bank increases. This chapter provides some valuable insights to be considered when implementing the IT infrastructure for a brain bank and discusses the pros and cons of various approaches and products.

A new viewpoint: running a nonprofit brain bank as a business.

It has become clear over the past decades that studying postmortem human brain tissue is one of the most effective ways to increase our knowledge of the pathogenesis and etiology of neuropathologic and psychiatric diseases. Many breakthroughs in neuroscience have depended on the availability of human brain tissue. However, the process of brain banking presents many different challenges, including the high cost that is associated with collecting the samples and with providing the diagnostics, storage, and distribution. Funding is generally from research and facility grants and donations but all are irregular, uncertain, and only cover the costs for a determined period of time. For professional brain banks with extensive prospective donor programs and that are open-access it can be very beneficial to draft a business plan to achieve long-term sustainability. Such a business plan should identify the interests of the stakeholders and address the implementation of cost efficiency and cost recovery systems.

Scaling Safe Access to Fecal Microbiota Transplantation: Past, Present, and Future.

PURPOSE OF REVIEW: Universal stool banks (USBs) have emerged as a potential model for scaling access to fecal microbiota transplantation (FMT) for Clostridium difficile infection (CDI). In this review, we outline the historical barriers constraining access to FMT, the evidence on methods and outcomes of USBs, and potential future directions for expanding access. RECENT FINDINGS: Key historical barriers to FMT access include regulatory uncertainty, operational complexity of sourcing screened donor material, and logistical challenges of delivering fresh treatment preparations. USBs have demonstrated that FMT can be delivered safely at scale by centralizing donor selection, material processing, and safety monitoring. More evidence is needed to optimize USB methods, including for donor screening, material processing, and novel delivery modalities. USBs have catalyzed broad access to FMT in North America and Europe. Future directions include developing evidence regarding oral preparations, harmonizing guidelines, disseminating best practice protocols, establishing long-term safety profiles, and expanding access to geographic areas of unmet need.

Experimental procedures for decontamination and microbiological testing in cardiovascular tissue banks.

IMPACT STATEMENT: Sterility testing is a critical issue in the recovery, processing, and release of tissue allografts. Contaminated allografts are often discarded, increasing costs, and reducing tissue stocks. Given these concerns, it is important to determine the most effective methodology for sterility testing. This work provides an overview of microbiological methods for sampling and culturing donor grafts for cardiovascular tissue banking.