scholarly journals Insights into therapeutic products, preclinical research models, and clinical trials in cardiac regenerative and reparative medicine: where are we now and the way ahead. Current opinion paper of the ESC Working Group on Cardiovascular Regenerative and Reparative Medicine

2020 ◽  
Author(s):  
Lilian Grigorian-Shamagian ◽  
Ricardo Sanz-Ruiz ◽  
Andreu Climent ◽  
Lina Badimon ◽  
Lucio Barile ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Working Group ◽  
Clinical Success ◽  
Lessons Learned ◽  
Preclinical Research ◽  
Great Expectations ◽  
The Past ◽  
Active Research ◽  
Main Ideas ◽  
Clinical Potential

Abstract Great expectations have been set around the clinical potential of regenerative and reparative medicine in the treatment of cardiovascular diseases [i.e. in particular, heart failure (HF)]. Initial excitement, spurred by encouraging preclinical data, resulted in a rapid translation into clinical research. The sobering outcome of the resulting clinical trials suggests that preclinical testing may have been insufficient to predict clinical outcome. A number of barriers for clinical translation include the inherent variability of the biological products and difficulties to develop potency and quality assays, insufficient rigour of the preclinical research and reproducibility of the results, manufacturing challenges, and scientific irregularities reported in the last years. The failure to achieve clinical success led to an increased scrutiny and scepticism as to the clinical readiness of stem cells and gene therapy products among clinicians, industry stakeholders, and funding bodies. The present impasse has attracted the attention of some of the most active research groups in the field, which were then summoned to analyse the position of the field and tasked to develop a strategy, to re-visit the undoubtedly promising future of cardiovascular regenerative and reparative medicine, based on lessons learned over the past two decades. During the scientific retreat of the ESC Working Group on Cardiovascular Regenerative and Reparative Medicine (CARE) in November 2018, the most relevant and timely research aspects in regenerative and/or reparative medicine were presented and critically discussed, with the aim to lay out a strategy for the future development of the field. We report herein the main ideas and conclusions of that meeting.

scholarly journals A new era in idiopathic pulmonary fibrosis: considerations for future clinical trials

2015 ◽  
Vol 46 (1) ◽  
pp. 243-249 ◽  
Author(s):  
Harold R. Collard ◽  
Williamson Z. Bradford ◽  
Vincent Cottin ◽  
Kevin R. Flaherty ◽  
Talmadge E. King ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Rapid Development ◽  
Late Phase ◽  
Lessons Learned ◽  
New Era ◽  
The Past ◽  
Substantial Progress ◽  
Important Time

The past decade has seen substantial progress in understanding the pathobiology, natural history, and clinical significance of idiopathic pulmonary fibrosis (IPF), culminating in the establishment of two effective medical therapies. Now seems an important time to reconsider the design and conduct of future IPF clinical trials. Building on lessons learned over the past decade, we use this perspective to lay out four key considerations for moving forward effectively and efficiently with the next generation of clinical trials in IPF. These are: development of a coordinated IPF clinical trials network; establishment of expectations for early phase proof of concept studies; adaptation of late-phase efficacy trial designs to the emergence of approved therapies, and; agreement on primary end-points for late phase clinical trials. Continued progress in the field of IPF will require creativity and collaboration on the part of all stakeholders. We believe that addressing these four considerations will encourage and enable investment in this new era of drug development in IPF, and will lead to more rapid development of effective therapies.

Lessons Learned from Major Clinical Trials Conducted Over the Past Decades

2014 ◽  
pp. 77-97 ◽  
Author(s):  
Peter Schüler ◽  
Klaudius Siegfried ◽  
Michael Hüll
Keyword(s):  
Clinical Trials ◽  
Lessons Learned ◽  
The Past

Protective effects of activated protein C in sepsis

2008 ◽  
Vol 100 (10) ◽  
pp. 582-592 ◽  
Author(s):  
Lisa J. Toltl ◽  
Laura L. Swystun ◽  
Laura Pepler ◽  
Patricia C. Liaw
Keyword(s):  
Host Response ◽  
Protein C ◽  
Clinical Success ◽  
Activated Protein C ◽  
Endothelial Permeability ◽  
Protective Effects ◽  
Preclinical Research ◽  
The Past ◽  
A Cell ◽  
Barrier Breakdown

SummarySepsis remains a complex syndrome associated with significant morbidity and mortality. It is now widely accepted that the pathways of inflammation, coagulation, apoptosis, and endothelial permeability are intimately linked in sepsis pathophysiology. The clinical success of activated protein C (APC), a natural anticoagulant, in reducing mortality in patients with severe sepsis has fuelled basic and preclinical research on the protective effects of this molecule. Over the past 15 years, impressive research advances have provided novel insights into the multifunctional activities of APC. APC is now viewed not only as an anticoagulant, but also as a cell signaling molecule that dampens the excessive or insufficiently controlled host response during sepsis. This review attempts to summarize the pleiotropic activities of APC with focus on its ability to inhibit coagulation, inflammation, apoptosis, and endothelial barrier breakdown. A comprehensive PUBMED literature review up to May 2008 was conducted.

Pursuit of the Abscopal Effect

2020 ◽  
Vol 04 (04) ◽  
pp. 369-372
Author(s):  
Paul B. Romesser ◽  
Christopher H. Crane
Keyword(s):  
Tumor Immunology ◽  
Antitumor Immunity ◽  
Clinical Success ◽  
Immune Recognition ◽  
Immune Modulators ◽  
Cancer Subtypes ◽  
The Past ◽  
Tumor Irradiation ◽  
Wide Range ◽  
Tumor Recognition

AbstractEvasion of immune recognition is a hallmark of cancer that facilitates tumorigenesis, maintenance, and progression. Systemic immune activation can incite tumor recognition and stimulate potent antitumor responses. While the concept of antitumor immunity is not new, there is renewed interest in tumor immunology given the clinical success of immune modulators in a wide range of cancer subtypes over the past decade. One particularly interesting, yet exceedingly rare phenomenon, is the abscopal response, characterized by a potent systemic antitumor response following localized tumor irradiation presumably attributed to reactivation of antitumor immunity.

Great Expectations

2008 ◽  
Author(s):  
Charles Dickens ◽  
Robert Douglas-Fairhurst
Keyword(s):  
Great Expectations ◽  
The Past ◽  
Theatrical Adaptation

‘You are to understand, Mr. Pip, that the name of the person who is your liberal benefactor remains a profound secret.’ Young Pip lives with his sister and her husband the blacksmith, with few prospects for advancement until a mysterious benefaction takes him from the Kent marshes to London. Pip is haunted by figures from his past - the escaped convict Magwitch, the time-withered Miss Havisham and her proud and beautiful ward, Estella - and in time uncovers not just the origins of his great expectations but the mystery of his own heart. A powerful and moving novel, Great Expectations is suffused with Dickens’s memories of the past and its grip on the present, and it raises disturbing questions about the extent to which individuals affect each other’s lives. This edition includes a lively introduction, Dickens’s working notes, the novel’s original ending, and an extract from an early theatrical adaptation. It reprints the definitive Clarendon text.

scholarly journals ANCA Status or Clinical Phenotype — What Counts More?

2021 ◽  
Vol 23 (6) ◽  
Author(s):  
Martin Windpessl ◽  
Erica L. Bettac ◽  
Philipp Gauckler ◽  
Jae Il Shin ◽  
Duvuru Geetha ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Granulomatosis With Polyangiitis ◽  
Clinical Phenotype ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Cardiovascular Death ◽  
Genetic Associations ◽  
Ongoing Debate ◽  
The Past ◽  
Anca Associated Vasculitis

Abstract Purpose of Review There is ongoing debate concerning the classification of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. That is, whether classification should be based on the serotype (proteinase 3 (PR3)- or myeloperoxidase (MPO)-ANCA) or on the clinical phenotype (granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA)). To add clarity, this review focused on integration of the most recent literature. Recent Findings Large clinical trials have provided evidence that a serology-based risk assessment for relapses is more predictive than distinction based on the phenotype. Research conducted in the past decade indicated that a serology-based approach more closely resembles the genetic associations, the clinical presentation (i.e., lung involvement), biomarker biology, treatment response, and is also predicting comorbidities (such as cardiovascular death). Summary Our review highlights that a serology-based approach could replace a phenotype-based approach to classify ANCA-associated vasculitides. In future, clinical trials and observational studies will presumably focus on this distinction and, as such, translate into a “personalized medicine.”

scholarly journals In silico imaging clinical trials: cheaper, faster, better, safer, and more scalable

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Aldo Badano
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Medical Devices ◽  
In Silico ◽  
Lessons Learned ◽  
Patient Access ◽  
High Quality ◽  
Virtual Imaging ◽  
Regulatory Evaluation

AbstractImaging clinical trials can be burdensome and often delay patient access to novel, high-quality medical devices. Tools for in silico imaging trials have significantly improved in sophistication and availability. Here, I describe some of the principal advantages of in silico imaging trials and enumerate five lessons learned during the design and execution of the first all-in silico virtual imaging clinical trial for regulatory evaluation (the VICTRE study).

scholarly journals Whither Magnetic Hyperthermia? A Tentative Roadmap

Materials ◽  
2021 ◽  
Vol 14 (4) ◽  
pp. 706
Author(s):  
Irene Rubia-Rodríguez ◽  
Antonio Santana-Otero ◽  
Simo Spassov ◽  
Etelka Tombácz ◽  
Christer Johansson ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Nanoparticle Synthesis ◽  
Careful Analysis ◽  
Magnetic Hyperthermia ◽  
Lessons Learned ◽  
In Vivo Testing ◽  
Evolution Of Science ◽  
Made In ◽  
Critical Aspects

The scientific community has made great efforts in advancing magnetic hyperthermia for the last two decades after going through a sizeable research lapse from its establishment. All the progress made in various topics ranging from nanoparticle synthesis to biocompatibilization and in vivo testing have been seeking to push the forefront towards some new clinical trials. As many, they did not go at the expected pace. Today, fruitful international cooperation and the wisdom gain after a careful analysis of the lessons learned from seminal clinical trials allow us to have a future with better guarantees for a more definitive takeoff of this genuine nanotherapy against cancer. Deliberately giving prominence to a number of critical aspects, this opinion review offers a blend of state-of-the-art hints and glimpses into the future of the therapy, considering the expected evolution of science and technology behind magnetic hyperthermia.

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