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Neuropathology and Applied Neurobiology Dec 2022Over the past decade, considerable efforts have been made to accelerate pathophysiological understanding of fatal neurodegenerative diseases such as amyotrophic lateral... (Review)
Review
Over the past decade, considerable efforts have been made to accelerate pathophysiological understanding of fatal neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) with brain banks at the forefront. In addition to exploratory disease mechanisms, brain banks have aided our understanding with regard to clinical diagnosis, genetics and cell biology. Across neurodegenerative disorders, the impact of brain tissue in ALS research has yet to be quantified. This review aims to outline (i) how postmortem tissues from brain banks have influenced our understanding of ALS over the last 15 years, (ii) correlate the location of dedicated brain banks with the geographical prevalence of ALS, (iii) identify the frequency of features reported from postmortem studies and (iv) propose common reporting standards for materials obtained from dedicated brain banks. A systematic review was conducted using PubMed and Web of Science databases using key words. From a total of 1439 articles, 73 articles were included in the final review, following PRISMA guidelines. Following a thematic analysis, articles were categorised into five themes; clinico-pathological (13), genetic (20), transactive response DNA binding protein 43 (TDP-43) pathology (12), non-TDP-43 neuronal pathology (nine) and extraneuronal pathology (19). Research primarily focused on the genetics of ALS, followed by protein pathology. About 63% of the brain banks were in the United States of America and United Kingdom. The location of brain banks overall aligned with the incidence of ALS worldwide with 88% of brain banks situated in Europe and North America. An overwhelming lack of consistency in reporting and replicability was observed, strengthening the need for a standardised reporting system. Overall, postmortem material from brain banks generated substantial new knowledge in areas of genetics and proteomics and supports their ongoing role as an important research tool.
Topics: Humans; Amyotrophic Lateral Sclerosis; Knowledge Discovery; Brain; Neurons; United Kingdom
PubMed: 35921237
DOI: 10.1111/nan.12845 -
Journal of Gastrointestinal Surgery :... Mar 2022Mesh implants are regularly used to help repair both hiatus hernias (HH) and diaphragmatic hernias (DH). In vivo studies are used to test not only mesh safety, but... (Review)
Review
INTRODUCTION
Mesh implants are regularly used to help repair both hiatus hernias (HH) and diaphragmatic hernias (DH). In vivo studies are used to test not only mesh safety, but increasingly comparative efficacy. Our work examines the field of in vivo mesh testing for HH and DH models to establish current practices and standards.
METHOD
This systematic review was registered with PROSPERO. Medline and Embase databases were searched for relevant in vivo studies. Forty-four articles were identified and underwent abstract review, where 22 were excluded. Four further studies were excluded after full-text review-leaving 18 to undergo data extraction.
RESULTS
Of 18 studies identified, 9 used an in vivo HH model and 9 a DH model. Five studies undertook mechanical testing on tissue samples-all uniaxial in nature. Testing strip widths ranged from 1-20 mm (median 3 mm). Testing speeds varied from 1.5-60 mm/minute. Upon histology, the most commonly assessed structural and cellular factors were neovascularisation and macrophages respectively (n = 9 each). Structural analysis was mostly qualitative, where cellular analysis was equally likely to be quantitative. Eleven studies assessed adhesion formation, of which 8 used one of four scoring systems. Eight studies measured mesh shrinkage.
DISCUSSION
In vivo studies assessing mesh for HH and DH repair are uncommon. Within this relatively young field, we encourage surgical and materials testing institutions to discuss its standardisation.
Topics: Hernia, Diaphragmatic; Hernia, Hiatal; Herniorrhaphy; Humans; Laparoscopy; Prostheses and Implants; Recurrence; Surgical Mesh
PubMed: 34935102
DOI: 10.1007/s11605-021-05227-3 -
Acta Neuropathologica Communications Sep 2019Perfusing fixatives through the cerebrovascular system is the gold standard approach in animals to prepare brain tissue for spatial biomolecular profiling, circuit... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Perfusing fixatives through the cerebrovascular system is the gold standard approach in animals to prepare brain tissue for spatial biomolecular profiling, circuit tracing, and ultrastructural studies such as connectomics. Translating these discoveries to humans requires examination of postmortem autopsy brain tissue. Yet banked brain tissue is routinely prepared using immersion fixation, which is a significant barrier to optimal preservation of tissue architecture. The challenges involved in adopting perfusion fixation in brain banks and the extent to which it improves histology quality are not well defined.
METHODOLOGY
We searched four databases to identify studies that have performed perfusion fixation in human brain tissue and screened the references of the eligible studies to identify further studies. From the included studies, we extracted data about the methods that they used, as well as any data comparing perfusion fixation to immersion fixation. The protocol was preregistered at the Open Science Framework: https://osf.io/cv3ys/ .
RESULTS
We screened 4489 abstracts, 214 full-text publications, and identified 35 studies that met our inclusion criteria, which collectively reported on the perfusion fixation of 558 human brains. We identified a wide variety of approaches to perfusion fixation, including perfusion fixation of the brain in situ and ex situ, perfusion fixation through different sets of blood vessels, and perfusion fixation with different washout solutions, fixatives, perfusion pressures, and postfixation tissue processing methods. Through a qualitative synthesis of data comparing the outcomes of perfusion and immersion fixation, we found moderate confidence evidence showing that perfusion fixation results in equal or greater subjective histology quality compared to immersion fixation of relatively large volumes of brain tissue, in an equal or shorter amount of time.
CONCLUSIONS
This manuscript serves as a resource for investigators interested in building upon the methods and results of previous research in designing their own perfusion fixation studies in human brains or other large animal brains. We also suggest several future research directions, such as comparing the in situ and ex situ approaches to perfusion fixation, studying the efficacy of different washout solutions, and elucidating the types of brain donors in which perfusion fixation is likely to result in higher fixation quality than immersion fixation.
Topics: Brain; Humans; Perfusion; Tissue Banks; Tissue Fixation
PubMed: 31488214
DOI: 10.1186/s40478-019-0799-y -
RMD Open Feb 2024In anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), histopathological assessment of affected tissue is often necessary for diagnosis and...
BACKGROUND
In anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), histopathological assessment of affected tissue is often necessary for diagnosis and assessment of disease extent. There is a requirement for validated non-invasive biomarkers to avoid the need for serial tissue biopsies.
METHODS
A systematic review of scientific databases from 2012 until present was performed to identify studies fulfilling the inclusion criteria. Studies were assessed for quality using the Strengthening the Reporting of Observational Studies in Epidemiology checklist for cohort, case-control and cross-sectional studies and the Risk of Bias Assessment tool for Non-randomised Studies, or the Cochrane Risk of Bias tool 2.0 for randomised controlled trials. A descriptive synthesis of the data for non-invasive (blood-based or urinary) biomarkers of AAV-related disease activity and organ damage was performed.
RESULTS
Twenty-two high quality studies were included. These articles reported the value of blood-based and urinary biomarkers including anti-neutrophil cytoplasmic antibodies, immune cells, complement factors, gene expression profiles, cytokines, chemokines and other proteins in the assessment of disease activity and/or organ damage in patients with AAV. Many of these biomarkers involve the alternative complement pathway, neutrophil activation and macrophage activation.
CONCLUSION
This is the first contemporary systematic review synthesising the value of non-invasive biomarkers of AAV-related disease activity and organ damage. The incorporation of individual markers in combined biomarker profiles might enhance clinical decision-making. Many unmet needs were identified; few studies involve oeosinophilic granulomatosis with polyangiitis and patients with childhood-onset AAV. Further validation of the candidate biomarkers is warranted in large prospective studies to bridge the existing knowledge gaps and apply precision health to systemic vasculitis.
Topics: Humans; Child; Granulomatosis with Polyangiitis; Prospective Studies; Cross-Sectional Studies; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Biomarkers; Antibodies, Antineutrophil Cytoplasmic; Cytokines
PubMed: 38341193
DOI: 10.1136/rmdopen-2023-003579 -
The Oncologist Feb 2024Rare cancers and other rare nonmalignant tumors comprise 25% of all cancer diagnoses and account for 25% of all cancer deaths. They are difficult to study due to many...
Rare cancers and other rare nonmalignant tumors comprise 25% of all cancer diagnoses and account for 25% of all cancer deaths. They are difficult to study due to many factors, including infrequent occurrence, lack of a universal infrastructure for data and/or tissue collection, and a paucity of disease models to test potential treatments. For each individual rare cancer, the limited number of diagnosed cases makes it difficult to recruit sufficient patients for clinical studies, and rare cancer research studies are often siloed. As a result, progress has been slow for many of these cancers. While rare cancer research efforts have increased over time, the breadth of the research landscape is not known. A recent literature search revealed a sharp increase in rare tumor, and rare cancer publications began in the early 2000s. To identify rare cancer research efforts being conducted in the US and globally, we conducted an online search of rare tumor/rare cancer research programs and identified 76 programs. To gain a deeper understanding of these programs, we composed and conducted a survey to ask programs for details about their research efforts. Of the 42 programs contacted to complete the survey, 23 programs responded. Survey results show most programs are collecting clinical data, molecular data, and biospecimens, and many are conducting molecular analyses. This landscape analysis demonstrates that multiple rare cancer research efforts are ongoing, and the rare cancer community may benefit from collaboration among stakeholders to accelerate research and improve patient outcomes.
Topics: Humans; Neoplasms; Tissue Banks; Rare Diseases; Biomedical Research
PubMed: 37878787
DOI: 10.1093/oncolo/oyad285