Has the biobank bubble burst? Withstanding the challenges for sustainable biobanking in the digital era

Biobanks have been heralded as essential tools for translating biomedical research into practice, driving precision medicine to improve pathways for global healthcare treatment and services. Many nations have established specific governance systems to facilitate research and to address the complex ethical, legal and social challenges that they present, but this has not lead to uniformity across the world. Despite significant progress in responding to the ethical, legal and social implications of biobanking, operational, sustainability and funding challenges continue to emerge. No coherent strategy has yet been identified for addressing them. This has brought into question the overall viability and usefulness of biobanks in light of the significant resources required to keep them running. This review sets out the challenges that the biobanking community has had to overcome since their inception in the early 2000s. The first section provides a brief outline of the diversity in biobank and regulatory architecture in seven countries: Australia, Germany, Japan, Singapore, Taiwan, the UK, and the USA. The article then discusses four waves of responses to biobanking challenges. This article had its genesis in a discussion on biobanks during the Centre for Health, Law and Emerging Technologies (HeLEX) conference in Oxford UK, co-sponsored by the Centre for Law and Genetics (University of Tasmania). This article aims to provide a review of the issues associated with biobank practices and governance, with a view to informing the future course of both large-scale and smaller scale biobanks

Doxycycline versus prednisolone as an initial treatment strategy for bullous pemphigoid: a pragmatic non-inferiority randomised controlled trial

Background: Bullous pemphigoid (BP) is a blistering skin disorder with increased mortality. We tested whether a strategy of starting treatment with doxycycline conveys acceptable short-term blister control whilst conferring long-term safety advantages over starting treatment with oral corticosteroids. Methods: Pragmatic multi-centre parallel-group randomised controlled trial of adults with BP (≥3 blisters ≥2 sites and linear basement membrane IgG/C3) plus economic evaluation. Participants were randomised to doxycycline (200 mg/day) or prednisolone (0·5 mg/kg/day). Localised adjuvant potent topical corticosteroids (<30 g/week) was permitted weeks 1-3. The non-inferiority primary effectiveness outcome was the proportion of participants with ≤3 blisters at 6 weeks. We assumed that doxycycline would be 25% less effective than corticosteroids with a 37% acceptable margin of noninferiority. The primary safety outcome was the proportion with severe, life-threatening or fatal treatment-related adverse events by 52 weeks. Analysis used a regression model adjusting for baseline disease severity, age and Karnofsky score, with missing data imputed. Results: 132 patients were randomised to doxycycline and 121 to prednisolone from 54 UK and 7 German dermatology centres. Mean age was 77·7 years and 68.4% had moderate to severe baseline disease. For those starting doxycycline, 83/112 (74·1%) had ≤3 blisters at 6 weeks compared with 92/101 (91·1%) for prednisolone, a difference of 18·6% favouring prednisolone (upper limit of 90% CI, 26·1%, within the predefined 37% margin). Related severe, life-threatening and fatal events at 52 weeks were 18·5% for those starting doxycycline and 36·6% for prednisolone (mITT analysis), an adjusted difference of 19·0% (95% CI, 7·9%, 30·1%, p=0·001). Conclusions: A strategy of starting BP patients on doxycycline is non-inferior to standard treatment with oral prednisolone for short-term blister control and significantly safer long-term

Key challenges in bringing CRISPR-mediated somatic cell therapy into the clinic.

Genome editing using clustered regularly interspersed short palindromic repeats (CRISPR) and CRISPR-associated proteins offers the potential to facilitate safe and effective treatment of genetic diseases refractory to other types of intervention. Here, we identify some of the major challenges for clinicians, regulators, and human research ethics committees in the clinical translation of CRISPR-mediated somatic cell therapy

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin with gemtuzumab ozogamicin improves event-free survival in younger patients with newly diagnosed aml and overall survival in patients with npm1 and flt3 mutations

Purpose To determine the optimal induction chemotherapy regimen for younger adults with newly diagnosed AML without known adverse risk cytogenetics. Patients and Methods One thousand thirty-three patients were randomly assigned to intensified (fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin [FLAG-Ida]) or standard (daunorubicin and Ara-C [DA]) induction chemotherapy, with one or two doses of gemtuzumab ozogamicin (GO). The primary end point was overall survival (OS). Results There was no difference in remission rate after two courses between FLAG-Ida + GO and DA + GO (complete remission [CR] + CR with incomplete hematologic recovery 93% v 91%) or in day 60 mortality (4.3% v 4.6%). There was no difference in OS (66% v 63%; P = .41); however, the risk of relapse was lower with FLAG-Ida + GO (24% v 41%; P < .001) and 3-year event-free survival was higher (57% v 45%; P < .001). In patients with an NPM1 mutation (30%), 3-year OS was significantly higher with FLAG-Ida + GO (82% v 64%; P = .005). NPM1 measurable residual disease (MRD) clearance was also greater, with 88% versus 77% becoming MRD-negative in peripheral blood after cycle 2 (P = .02). Three-year OS was also higher in patients with a FLT3 mutation (64% v 54%; P = .047). Fewer transplants were performed in patients receiving FLAG-Ida + GO (238 v 278; P = .02). There was no difference in outcome according to the number of GO doses, although NPM1 MRD clearance was higher with two doses in the DA arm. Patients with core binding factor AML treated with DA and one dose of GO had a 3-year OS of 96% with no survival benefit from FLAG-Ida + GO. Conclusion Overall, FLAG-Ida + GO significantly reduced relapse without improving OS. However, exploratory analyses show that patients with NPM1 and FLT3 mutations had substantial improvements in OS. By contrast, in patients with core binding factor AML, outcomes were excellent with DA + GO with no FLAG-Ida benefit

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p&lt;0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p&lt;0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p&lt;0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP &gt;5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification