A Portable Magnetic Particle Spectrometer for Future Rapid and Wash-Free Bioassays.

Nowadays, there is an increasing demand for more accessible routine diagnostics for patients with respect to high accuracy, ease of use, and low cost. However, the quantitative and high accuracy bioassays in large hospitals and laboratories usually require trained technicians and equipment that is both bulky and expensive. In addition, the multistep bioassays and long turnaround time could severely affect the disease surveillance and control especially in pandemics such as influenza and COVID-19. In view of this, a portable, quantitative bioassay device will be valuable in regions with scarce medical resources and help relieve burden on local healthcare systems. Herein, we introduce the MagiCoil diagnostic device, an inexpensive, portable, quantitative, and rapid bioassay platform based on the magnetic particle spectrometer (MPS) technique. MPS detects the dynamic magnetic responses of magnetic nanoparticles (MNPs) and uses the harmonics from oscillating MNPs as metrics for sensitive and quantitative bioassays. This device does not require trained technicians to operate and employs a fully automatic, one-step, and wash-free assay with a user friendly smartphone interface. Using a streptavidin-biotin binding system as a model, we show that the detection limit of the current portable device for streptavidin is 64 nM (equal to 5.12 pmole). In addition, this MPS technique is very versatile and allows for the detection of different diseases just by changing the surface modifications on MNPs. Although MPS-based bioassays show high sensitivities as reported in many literatures, at the current stage, this portable device faces insufficient sensitivity and needs further improvements. It is foreseen that this kind of portable device can transform the multistep, laboratory-based bioassays to one-step field testing in nonclinical settings such as schools, homes, offices, etc.

Emergency valve-in-valve transcatheter aortic valve implantation for endocarditis degeneration.

The use of transcatheter aortic valve implantation (TAVI) in the emergency setting has not been widely reported, and TAVI is generally contraindicated in the context of endocarditis. Here we describe a patient developing acute cardiogenic shock due to prosthetic aortic valve degeneration with free-flow aortic regurgitation 8 months after receiving treatment for confirmed infective endocarditis. Due to his clinical status, he was deemed unfit for redo surgery, and he underwent salvage valve-in-valve (ViV)-TAVI. The patient made an excellent recovery. Postprocedure he was treated with a 6-week course of antibiotics, and at 18-months follow-up remains very well with no evidence of reinfection. This case may demonstrate that for selected patients with degenerative prosthetic aortic valve disease, despite a history of infective endocarditis, ViV-TAVI may be considered an alternative to redo surgery in the emergency setting.

COVID-19 patient with coronary thrombosis supported with ECMO and Impella 5.0 ventricular assist device: a case report.

BACKGROUND: COVID-19 can present with cardiovascular complications. CASE SUMMARY: We present a case report of a 43-year-old previously fit patient who suffered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with thrombosis of the coronary arteries causing acute myocardial infarction. These were treated with coronary stenting during which the patient suffered cardiac arrest. He was supported with automated chest compressions followed by peripheral veno-arterial extracorporeal membrane oxygenation (VA ECMO). No immediate recovery of the myocardial function was observed and, after insufficient venting of the left ventricle was diagnosed, an Impella 5 pump was implanted. The cardiovascular function recovered sufficiently and ECMO was explanted and inotropic infusions discontinued. Due to SARS-CoV-2 pulmonary infection, hypoxia became resistant to conventional mechanical ventilation and the patient was nursed prone overnight. After initial recovery of respiratory function, the patient received a tracheostomy and was allowed to wake up. Following a short period of agitation his neurological function recovered completely. During the third week of recovery, progressive multisystem dysfunction, possibly related to COVID-19, developed into multiorgan failure, and the patient died. DISCUSSION: We believe that this is the first case report of coronary thrombosis related to COVID-19. Despite the negative outcome in this patient, we suggest that complex patients may in the future benefit from advanced cardiovascular support, and may even be nursed safely in the prone position with Impella devices.

Highlights from the 2018 WIN Symposium, 25-26 June 2018, Paris: designing the future of precision oncology.

The Worldwide Innovative Networking (WIN) Symposium is the annual gathering of WIN consortium members from across the globe, representing academic institutions, pharmaceutical partners, technology companies and charitable organisations, to discuss ongoing research and the latest developments in precision oncology. The symposium held in Paris, France on 25-26 June was structured into five plenary sessions, two open forums and poster presentations. This year marked the 10th anniversary of the consortium, and the programme anchored itself with retrospectives of recent breakthroughs in personalised medicine, programme sessions reviewing the iterative design of trials in precision oncology at present, and the future of implementing personalised medicine initiatives in US and EU healthcare systems for the maximum patient benefit. This year was also marked by the absence of Dr John Mendelsohn, who has stepped down as chairman, and co-founder Professor Tomas Tursz, who passed away in April this year. The latter was given a brief memorial session at the conclusion of the symposium.

Highlights from the WIN 2017 Symposium, 26-27 June 2017, Paris, France: 'Expediting Global Innovation in Precision Cancer Medicine'.

The Worldwide Innovative Networking (WIN) symposium brings together representatives from academic institutions, pharmaceutical partners, technology companies and charitable organisations from across the globe for an annual summit, discussing ongoing research and the latest developments in precision medicine. Now, in its seventh year, the aims of the WIN consortium's annual meeting, to foster communication and collaboration between members and deliver clinical trial results that improve the care and outcomes of patients are presented in open dialogue to encourage debate and discussion. This year, the meeting was held in Paris, France from 26-27 June and consisted of six plenary sessions, two debates, and poster presentations from attendees. In keeping with the consortium's goals, presentations and posters focused on the development and integration of new therapies and updates in genome-based medicine. Among the presentations at this year's meeting, much of the focus fell on design and implementation of new designs of clinical trials, moving away from decades-long assessments of thousands of patients towards a nimble, adaptive design fitting the edicts of personalised medicine and delving into greater depths within genomic data, ranging beyond genome analysis to chart new targets in ligandomics, proteogenomics and more.

Reassessing biopsychosocial psychiatry.

Psychiatry uncomfortably spans biological and psychosocial perspectives on mental illness, an idea central to Engel's biopsychosocial paradigm. This paradigm was extremely ambitious, proposing new foundations for clinical practice as well as a non-reductive metaphysics for mental illness. Perhaps given this scope, the approach has failed to engender a clearly identifiable research programme. And yet the view remains influential. We reassess the relevance of the biopsychosocial paradigm for psychiatry, distinguishing a number of ways in which it could be (re)conceived.

Highlights from the 2016 WIN Symposium, 27-29 June 2016, Paris: personalised therapy beyond next-generation sequencing.

The Worldwide Innovative Networking (WIN) consortium is an alliance of academic institutions, pharmaceutical partners, representatives from technology companies and charitable/health payer organisations from across the globe. For the last six years, the consortium's aims have been to foster communication and collaboration between members, encourage dialogue in an open forum, and deliver clinical trial results that improve the care and outcomes of patients with cancer using the latest advances in genomic-based medicine. The annual WIN Symposium, held over two days, is a chance for its members to come together and discuss ongoing research, recent announcements, and introduce new developments in personalised medicine. This year's conference, held in Paris, France 27-29 June, consisted of six dedicated sessions, including two debates, and posters from members and participating organisations, all focusing on the latest therapeutic advances and updates in genomic analysis. Special highlights from this year included discussion of the MINDACT clinical trial, which uses a gene expression test to identify patients with breast cancer who can safely forego adjuvant chemotherapy, and the reflections on the SHIVA trial. Of particular interest to many speakers was the utilisation of liquid biopsy samples to produce near real time snapshots of tumour mutational profiles and vulnerability.

Biomarkers come of age: PD1 in the frontline and cell cycle therapy swells the ranks of personalised therapy in the European Society of Medical Oncology (ESMO) congress, Copenhagen, 7-10 October 2016.

After years of trials, Programmed Death Ligand and Receptor targeting finally debuts as a firstline therapy in combination and as a single agent regimen at the 2016 European Society of Medical Oncology (ESMO) Congress. The meeting brought together 20,522 attendees, from over 120 countries, to share updates and novel technologies from a wide swathe of oncology research. This year's theme, From Disease Treatment to Patient Care, was matched by abstract presentations starting from inception of care regimens to new standards of care in high-risk patient subgroups, to wellbeing of care providers, and finally the funding obstacles at each continental level.

Use of toxicokinetics to support chemical evaluation: Informing high dose selection and study interpretation.

Toxicokinetic (TK) information can substantially enhance the value of the data generated from toxicity testing, and is an integral part of pharmaceutical safety assessment. It is less widely used in the chemical, agrochemical and consumer products industries, but recognition of its value is growing, as reflected by increased reference to the use of TK information in new and draft OECD test guidelines. To help promote increased consideration of the important role TK can play in chemical risk assessment, we have gathered practical examples from the peer-reviewed literature, as well as in-house industry data, that highlight opportunities for the use of TK in the selection of dose levels. Use of TK can help to ensure studies are designed to be of most relevance to assessing potential risk in humans, and avoid the use of excessively high doses that could result in unnecessary suffering in experimental animals. Greater emphasis on the potential contribution of TK in guiding study design and interpretation should be incorporated in regulatory data requirements and associated guidance.

Acute cholecystits leading to ischemic ECG changes in a patient with no underlying cardiac disease.

Although chest pain with ST-segment elevation is often indicative of cardiac ischemia, it has also been described with surgical conditions such as acute cholecystitis. We report the case of a 34-year-old Caucasian female who was referred with symptoms consistent with acute cholecystitis. An electrocardiogram (ECG) showed unexpected changes with inferolateral ST-segment elevation indicative of an inferolateral myocardial infarct. Further investigations and analysis of the results along with the clinical picture meant an acute cardiac event was excluded. Gallstones were seen on ultrasound and an inflamed gallbladder, consistent with acute cholecystitis, was confirmed at laparoscopic cholecystectomy. This led to the resolution of her symptoms and a return to the isoelectric baseline of the ST segments on the ECG. Five previous cases of cholecystitis induced ECG changes have been described in the literature. This case describes the youngest patient with no previous cardiac disease. We review the literature and suggest the pathophysiological mechanism to explain these findings. When the initial diagnostic interventions for chest pain with ST-segment elevation do not yield the expected results, an alternative diagnosis such as cholecystitis should be considered.

Application of toxicokinetics to improve chemical risk assessment: implications for the use of animals.

While toxicokinetics has become an integral part of pharmaceutical safety assessment over the last two decades, its use in the chemical industry is relatively new. However, it is recognised as a potentially important tool in human health risk assessment and recent initiatives have advocated greater application of toxicokinetics as part of an improved assessment strategy for crop protection chemicals that could offer greater efficiency, use fewer animals and provide better data for risk assessment purposes. To explore the potential scientific and animal welfare benefits of increased use of toxicokinetic data across the chemical industry, an international workshop was held in 2008. Experts from a wide range of chemical industry sectors, including industrial chemicals, agrochemicals and consumer products, participated in the meeting as well as representatives from relevant regulatory authorities. Pharmaceutical industry experts were also invited, in order to share experiences from the extensive use of toxicokinetics in drug development. Given that increased generation of toxicokinetic data could potentially result in an increased number of animals undergoing testing, technologies and strategies to reduce and refine animal use for this purpose were also considered. This paper outlines and expands upon the key themes that emerged from the workshop.