Post-market surveillance of six COVID-19 point-of-care tests using pre-Omicron and Omicron SARS-CoV-2 variants.

Post-market surveillance of test performance is a critical function of public health agencies and clinical researchers that ensures tests maintaining diagnostic characteristics following their regulatory approval. Changes in product quality, manufacturing processes over time, or the evolution of new variants may impact product performance. During the COVID-19 pandemic, a plethora of point-of-care tests (POCTs) was released onto the Canadian market. This study evaluated the performance characteristics of several of the most widely distributed POCTs in Canada, including four rapid antigen tests (Abbott Panbio, BTNX Rapid Response, SD Biosensor, and Quidel QuickVue) and two molecular tests (Abbott ID NOW and Lucira Check IT). All tests were challenged with 149 SARS-CoV-2 clinical positives, including multiple variants up to and including Omicron XBB.1.5, as well as 29 clinical negatives. Results were stratified based on whether the isolate was Omicron or pre-Omicron as well as by reverse transcriptase quantitative PCR Ct value. The test performance of each POCT was consistent with the manufacturers' claims and showed no significant decline in clinical performance against any of the variants tested. These findings provide continued confidence in the results of these POCTs as they continue to be used to support decentralized COVID-19 testing. This work demonstrates the essential role of post-market surveillance in ensuring reliability in diagnostic tools.IMPORTANCEPost-market surveillance of diagnostic test performance is critical to ensure their reliability after regulatory approval. This is especially critical in the context of the COVID-19 pandemic as the use of point-of-care tests (POCTs) became widespread. Our study focused on four rapid antigen tests (Abbott Panbio, BTNX Rapid Response, SD Biosensor, and Quidel QuickVue) and two molecular tests (Abbott ID NOW and Lucira Check IT) that were widely distributed across Canada, assessing their performance using many SARS-CoV-2 variants, including up to Omicron subvariant XBB.1.5. Overall, we found no significant difference in performance against any variant, reinforcing confidence in their use. As concerns in test efficacy have been raised by news outlets, particularly regarding the BTNX Rapid Response, this work is even more timely and crucial. Our research offers insights into the performance of widely used COVID-19 POCTs but also highlights the necessity for post-market surveillance.

Decompressive craniectomy plus best medical treatment versus best medical treatment alone for spontaneous severe deep supratentorial intracerebral haemorrhage: a randomised controlled clinical trial.

BACKGROUND: It is unknown whether decompressive craniectomy improves clinical outcome for people with spontaneous severe deep intracerebral haemorrhage. The SWITCH trial aimed to assess whether decompressive craniectomy plus best medical treatment in these patients improves outcome at 6 months compared to best medical treatment alone. METHODS: In this multicentre, randomised, open-label, assessor-blinded trial conducted in 42 stroke centres in Austria, Belgium, Finland, France, Germany, the Netherlands, Spain, Sweden, and Switzerland, adults (18-75 years) with a severe intracerebral haemorrhage involving the basal ganglia or thalamus were randomly assigned to receive either decompressive craniectomy plus best medical treatment or best medical treatment alone. The primary outcome was a score of 5-6 on the modified Rankin Scale (mRS) at 180 days, analysed in the intention-to-treat population. This trial is registered with ClincalTrials.gov, NCT02258919, and is completed. FINDINGS: SWITCH had to be stopped early due to lack of funding. Between Oct 6, 2014, and April 4, 2023, 201 individuals were randomly assigned and 197 gave delayed informed consent (96 decompressive craniectomy plus best medical treatment, 101 best medical treatment). 63 (32%) were women and 134 (68%) men, the median age was 61 years (IQR 51-68), and the median haematoma volume 57 mL (IQR 44-74). 42 (44%) of 95 participants assigned to decompressive craniectomy plus best medical treatment and 55 (58%) assigned to best medical treatment alone had an mRS of 5-6 at 180 days (adjusted risk ratio [aRR] 0·77, 95% CI 0·59 to 1·01, adjusted risk difference [aRD] -13%, 95% CI -26 to 0, p=0·057). In the per-protocol analysis, 36 (47%) of 77 participants in the decompressive craniectomy plus best medical treatment group and 44 (60%) of 73 in the best medical treatment alone group had an mRS of 5-6 (aRR 0·76, 95% CI 0·58 to 1·00, aRD -15%, 95% CI -28 to 0). Severe adverse events occurred in 42 (41%) of 103 participants receiving decompressive craniectomy plus best medical treatment and 41 (44%) of 94 receiving best medical treatment. INTERPRETATION: SWITCH provides weak evidence that decompressive craniectomy plus best medical treatment might be superior to best medical treatment alone in people with severe deep intracerebral haemorrhage. The results do not apply to intracerebral haemorrhage in other locations, and survival is associated with severe disability in both groups. FUNDING: Swiss National Science Foundation, Swiss Heart Foundation, Inselspital Stiftung, and Boehringer Ingelheim.

Swiss trial of decompressive craniectomy versus best medical treatment of spontaneous supratentorial intracerebral haemorrhage (SWITCH): an international, multicentre, randomised-controlled, two-arm, assessor-blinded trial.

RATIONALE: Decompressive craniectomy (DC) is beneficial in people with malignant middle cerebral artery infarction. Whether DC improves outcome in spontaneous intracerebral haemorrhage (ICH) is unknown. AIM: To determine whether DC without haematoma evacuation plus best medical treatment (BMT) in people with ICH decreases the risk of death or dependence at 6 months compared to BMT alone. METHODS AND DESIGN: SWITCH is an international, multicentre, randomised (1:1), two-arm, open-label, assessor-blinded trial. Key inclusion criteria are age ⩽75 years, stroke due to basal ganglia or thalamic ICH that may extend into cerebral lobes, ventricles or subarachnoid space, Glasgow coma scale of 8-13, NIHSS score of 10-30 and ICH volume of 30-100 mL. Randomisation must be performed <66 h after onset and DC <6 h after randomisation. Both groups will receive BMT. Participants randomised to the treatment group will receive DC of at least 12 cm in diameter according to institutional standards. SAMPLE SIZE: A sample of 300 participants randomised 1:1 to DC plus BMT versus BMT alone provides over 85% power at a two-sided alpha-level of 0.05 to detect a relative risk reduction of 33% using a chi-squared test. OUTCOMES: The primary outcome is the composite of death or dependence, defined as modified Rankin scale score 5-6 at 6 months. Secondary outcomes include death, functional status, quality of life and complications at 180 days and 12 months. DISCUSSION: SWITCH will inform physicians about the outcomes of DC plus BMT in people with spontaneous deep ICH, compared to BMT alone. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02258919.

Acute care bundles should be used for patients with intracerebral haemorrhage: An expert consensus statement.

PURPOSE: Intracerebral haemorrhage (ICH) is the most devastating form of stroke and a major cause of disability. Clinical trials of individual therapies have failed to definitively establish a specific beneficial treatment. However, clinical trials of introducing care bundles, with multiple therapies provided in parallel, appear to clearly reduce morbidity and mortality. Currently, not enough patients receive these interventions in the acute phase. METHODS: We convened an expert group to discuss best practices in ICH and to develop recommendations for bundled care that can be delivered in all settings that treat acute ICH, with a focus on European healthcare systems. FINDINGS: In this consensus paper, we argue for widespread implementation of formalised care bundles in ICH, including specific metrics for time to treatment and criteria for the consideration of neurosurgical therapy. DISCUSSION: There is an extraordinary opportunity to improve clinical care and clinical outcomes in this devastating disease. Substantial evidence already exists for a range of therapies that can and should be implemented now.

Cutting Edge: PDGF-DD Binding to NKp44 Costimulates TLR9 Signaling and Proinflammatory Cytokine Secretion in Human Plasmacytoid Dendritic Cells.

NKp44 is a human receptor originally found on activated NK cells, group 1 and group 3 innate lymphoid cells that binds dimers of platelet-derived growth factor D (PDGF-DD). NKp44 is also expressed on tissue plasmacytoid dendritic cells (PDCs), but NKp44-PDGF-DD interaction on PDCs remains unstudied. Engagement of NKp44 with PDGF-DD in vitro enhanced PDC secretion of IFN-α, TNF, and IL-6 in response to the TLR9 ligand CpG-ODN, but not TLR7/8 ligands. In tissues, PDCs were found in close contact with PDGF-DD-expressing cells in the high endothelial venules and epithelium of tonsils, melanomas, and skin lesions infected with Molluscum contagiosum. Recombinant PDGF-DD enhanced the serum IFN-α response to systemic HSV-1 infection in a humanized mouse model. We conclude that NKp44 integrates with TLR9 signaling to enhance PDC cytokine production. These findings may have bearings for immune responses to TLR9-based adjuvants, therapy for tumors expressing PDGF-DD, and infections with DNA viruses that induce PDGF-DD expression to enhance viral spread.

AhR and CYP1B1 Control Oxygen Effects on Bone Marrow Progenitor Cells: The Enrichment of Multiple Olfactory Receptors as Potential Microbiome Sensors.

Polycyclic aromatic hydrocarbon (PAH) pollutants and microbiome products converge on the aryl hydrocarbon receptor (AhR) to redirect selective rapid adherence of isolated bone marrow (BM) cells. In young adult mice, Cyp1b1-deficiency and AhR activation by PAH, particularly when prolonged by Cyp1a1 deletion, produce matching gene stimulations in these BM cells. Vascular expression of Cyp1b1 lowers reactive oxygen species (ROS), suppressing NF-κB/RelA signaling. PAH and allelic selectivity support a non-canonical AhR participation, possibly through RelA. Genes stimulated by Cyp1b1 deficiency were further resolved according to the effects of Cyp1b1 and Cyp1a1 dual deletions (DKO). The adherent BM cells show a cluster of novel stimulations, including select developmental markers; multiple re-purposed olfactory receptors (OLFR); and α-Defensin, a microbial disruptor. Each one connects to an enhanced specific expression of the catalytic RNA Pol2 A subunit, among 12 different subunits. Mesenchymal progenitor BMS2 cells retain these features. Cyp1b1-deficiency removes lymphocytes from adherent assemblies as BM-derived mesenchymal stromal cells (BM-MSC) expand. Cyp1b1 effects were cell-type specific. In vivo, BM-MSC Cyp1b1 expression mediated PAH suppression of lymphocyte progenitors. In vitro, OP9-MSC sustained these progenitors, while Csf1 induced monocyte progenitor expansion to macrophages. Targeted Cyp1b1 deletion (Cdh5-Cre; Cyp1b1fl/fl) established endothelium control of ROS that directs AhR-mediated suppression of B cell progenitors. Monocyte Cyp1b1 deletion (Lyz2-Cre; Cyp1b1fl/fl) selectively attenuated M1 polarization of expanded macrophages, but did not enhance effects on basal M2 polarization. Thus, specific sources of Cyp1b1 link to AhR and to an OLFR network to provide BM inflammatory modulation via diverse microbiome products.

Comparison of Tiling Artifact Removal Methods in Secondary Ion Mass Spectrometry Images.

Time-of-flight secondary ion mass spectrometry (ToF-SIMS) imaging is used across many fields for the atomic and molecular characterization of surfaces, with both high sensitivity and high spatial resolution. When large analysis areas are required, standard ToF-SIMS instruments allow for the acquisition of adjoining tiles, which are acquired by rastering the primary ion beam. For such large area scans, tiling artifacts are a ubiquitous challenge, manifesting as intensity gradients across each tile and/or sudden changes in intensity between tiles. Such artifacts are thought to be related to a combination of sample charging, local detector sensitivity issues, and misalignment of the primary ion gun, among other instrumental factors. In this work, we investigated six different computational tiling artifact removal methods: tensor decomposition, multiplicative linear correction, linear discriminant analysis, seamless stitching, simple averaging, and simple interpolating. To ensure robustness in the study, we applied these methods to three hyperspectral ToF-SIMS data sets and one OrbiTrapSIMS data set. Our study includes a carefully designed statistical analysis and a quantitative survey that subjectively assessed the quality of the various methods employed. Our results demonstrate that while certain methods are useful and preferred more often, no one particular approach can be considered universally acceptable and that the effectiveness of the artifact removal method is strongly dependent on the particulars of the data set analyzed. As examples, the multiplicative linear correction and seamless stitching methods tended to score more highly on the subjective survey; however, for some data sets, this led to the introduction of new artifacts. In contrast, simple averaging and interpolation methods scored subjectively poorly on the biological data set, but more highly on the microarray data sets. We discuss and explore these findings in depth and present general recommendations given our findings to conclude the work.

Fully automated point spread function analysis using PyCalibrate.

Reproducibility is severely limited if instrument performance is assumed rather than measured. Within optical microscopy, instrument performance is typically measured using sub-resolution fluorescent beads. However, the process is performed infrequently as it is requires time and suitably trained staff to acquire and then process the bead images. Analysis software still requires the manual entry of imaging parameters. Human error from repeatedly typing these parameters can significantly affect the outcome of the analysis, rendering the results less reproducible. To avoid this issue, PyCalibrate has been developed to fully automate the analysis of bead images. PyCalibrate can be accessed either by executing the Python code locally or via a user-friendly web portal to further improve accessibility when moving between locations and machines. PyCalibrate interfaces with the BioFormats library to make it compatible with a wide range of proprietary image formats. In this study, PyCalibrate analysis performance is directly compared with alternative free-access analysis software PSFj, MetroloJ QC and DayBook 3 and is demonstrated to have equivalent performance but without the need for user supervision.

Training-induced circuit-specific excitatory synaptogenesis in mice is required for effort control.

Synaptogenesis is essential for circuit development; however, it is unknown whether it is critical for the establishment and performance of goal-directed voluntary behaviors. Here, we show that operant conditioning via lever-press for food reward training in mice induces excitatory synapse formation onto a subset of anterior cingulate cortex neurons projecting to the dorsomedial striatum (ACC→DMS). Training-induced synaptogenesis is controlled by the Gabapentin/Thrombospondin receptor α2δ-1, which is an essential neuronal protein for proper intracortical excitatory synaptogenesis. Using germline and conditional knockout mice, we found that deletion of α2δ-1 in the adult ACC→DMS circuit diminishes training-induced excitatory synaptogenesis. Surprisingly, this manipulation does not impact learning but results in a significant increase in effort exertion without affecting sensitivity to reward value or changing contingencies. Bidirectional optogenetic manipulation of ACC→DMS neurons rescues or phenocopies the behaviors of the α2δ-1 cKO mice, highlighting the importance of synaptogenesis within this cortico-striatal circuit in regulating effort exertion.

Absorption, Distribution, Metabolism, and Excretion of [14C]iptacopan in Healthy Male Volunteers and in In Vivo and In Vitro Studies.

Iptacopan (LNP023) is an oral, small-molecule, first-in-class, highly potent proximal complement inhibitor that specifically binds factor B and inhibits the alternative complement pathway. Iptacopan is currently in development as a targeted treatment of paroxysmal nocturnal hemoglobinuria and multiple other complement-mediated diseases. In this study, the absorption, distribution, metabolism, and excretion (ADME) of iptacopan was characterized in six healthy volunteers after a single 100 mg oral dose of [14C]iptacopan. This was supplemented with an in vivo rat ADME study and metabolite exposure comparisons between human, rat, and dog, in addition to in vitro assays, to better understand the clearance pathways and enzymes involved in the metabolism of iptacopan. The fraction of [14C]iptacopan absorbed was estimated to be about 71%, with a time to maximum concentration of 1.5 hours and elimination half-life from plasma of 12.3 hours. Following a single dose of [14C]iptacopan, 71.5% of the radioactivity was recovered in feces and 24.8% in urine. [14C]iptacopan was primarily eliminated by hepatic metabolism. The main biotransformation pathways were oxidative metabolism via CYP2C8, with M2 being the major oxidative metabolite, and acyl glucuronidation via UGT1A1. The two acyl glucuronide metabolites in human plasma, M8 and M9, each accounted for ≤ 10% of the total circulating drug-related material; systemic exposure was also observed in toxicology studies in rat and dog, suggesting a low risk associated with these metabolites. Binding of iptacopan to its target, factor B, in the bloodstream led to a concentration-dependent blood:plasma distribution and plasma protein binding of [14C]iptacopan. SIGNIFICANCE STATEMENT: We characterized the pharmacokinetics, excretion, metabolism and elimination of [14C]iptacopan (an oral, selective small-molecule inhibitor of factor B) in healthy human subjects. [14C]iptacopan was primarily eliminated by metabolism. The primary biotransformation pathways were oxidative metabolism via CYP2C8 and acyl glucuronidation via UGT1A1. Direct secretion of iptacopan into urine and potentially bile represented additional elimination mechanisms. Binding of iptacopan to its target, factor B, in the bloodstream led to a concentration-dependent blood:plasma distribution and plasma protein binding of [14C]iptacopan.

Achieving high union rates after first metatarsophalangeal joint arthrodesis: Radiographic outcomes and technical pitfalls.

BACKGROUND: Fusion of the first metatarsophalangeal (MTP1) joint is a common surgery performed to correct hallux rigidus, hallux rigidus et valgus and other painful degenerative diseases of the MTP1. AIM: To assess outcomes of our surgical technique including non-union rates, accuracy and aims of correction. METHODS: Between September 2011 and November 2020 a total 72 of MTP1 fusions were performed using a low profile, pre-contoured dorsal locking plate and a plantar compression screw. Union and revision rates were analyzed with a minimum clinical and radiological follow up of at least 3 mo (range 3-18 mo). The following parameters were evaluated on pre- and postoperative conventional radiographs: Intermetatarsal angle, Hallux-valgus angle, dorsal extension of the proximal phalanx (P1) in relation to the floor and the angle between the Metatarsal 1 and the P1 (MT1-P1 angle). Descriptive statistical analysis was performed. Pearson analysis was used to assess for correlations between radiographic parameters and achievement of fusion. RESULTS: An overall union rate of 98.6% (71/72) was achieved. Two out of 72 patients did not primarily fuse with one patient suffering from a non-union, whilst the other demonstrating a radiological delayed union without clinical symptoms, with eventually complete fusion after 18 mo. There was no correlation between the measured radiographic parameters and the achievement of fusion. We believe the reason for the non-union was mainly attributed to the patient's incompliance without wearing the therapeutic shoe leading to a fracture of the P1. Furthermore, we didn`t find any correlation between fusion and the degree of correction. CONCLUSION: With our surgical technique, high union rates (98%) can be achieved using a compression screw and a dorsal variable-angle locking plate to treat degenerative diseases of the MTP1.

Emergence of Inducible Macrolide Resistance in Mycobacterium chelonae Due to Broad-Host-Range Plasmid and Chromosomal Variants of the Novel 23S rRNA Methylase Gene, erm(55).

Macrolides are a mainstay of therapy for infections due to nontuberculous mycobacteria (NTM). Among rapidly growing mycobacteria (RGM), inducible macrolide resistance is associated with four chromosomal 23S rRNA methylase (erm) genes. Beginning in 2018, we detected high-level inducible clarithromycin resistance (MICs of ≥16µg/mL) in clinical isolates of Mycobacterium chelonae, an RGM species not previously known to contain erm genes. Using whole-genome sequencing, we identified a novel plasmid-mediated erm gene. This gene, designated erm(55)P, exhibits <65% amino acid identity to previously described RGM erm genes. Two additional chromosomal erm(55) alleles, with sequence identities of 81% to 86% to erm(55)P, were also identified and designated erm(55)C and erm(55)T. The erm(55)T is part of a transposon. The erm(55)P allele variant is located on a putative 137-kb conjugative plasmid, pMchErm55. Evaluation of 133 consecutive isolates from 2020 to 2022 revealed 5 (3.8%) with erm(55). The erm(55)P gene was also identified in public data sets of two emerging pathogenic pigmented RGM species: Mycobacterium iranicum and Mycobacterium obuense, dating back to 2008. In both species, the gene appeared to be present on plasmids homologous to pMchErm55. Plasmid-mediated macrolide resistance, not described previously for any NTM species, appears to have spread to multiple RGM species. This has important implications for antimicrobial susceptibility guidelines and treatment of RGM infections. Further spread could present serious consequences for treatment of other macrolide-susceptible RGM. Additional studies are needed to determine the transmissibility of pMchErm55 and the distribution of erm(55) among other RGM species.

IL17RB and IL17REL Expression Are Associated with Improved Prognosis in HPV-Infected Head and Neck Squamous Cell Carcinomas.

Changes in the cellular secretome are implicated in virus infection, malignancy, and anti-tumor immunity. We analyzed the association between transcriptional signatures (TS) from 24 different immune and stromal cell types on the prognosis of HPV-infected and HPV-free head and neck squamous carcinoma (HNSCC) patients from The Cancer Genome Atlas (TCGA) cohort. We found that HPV-positive HNSCC patients have tumors with elevated immune cell TS and improved prognosis, which was specifically associated with an increased tumor abundance of memory B and activated natural killer (NK) cell TS, compared to HPV-free HNSCC patients. HPV-infected patients upregulated many transcripts encoding secreted factors, such as growth factors, hormones, chemokines and cytokines, and their cognate receptors. Analysis of secretome transcripts and cognate receptors revealed that tumor expression of IL17RB and IL17REL are associated with a higher viral load and memory B and activated NK cell TS, as well as improved prognosis in HPV-infected HNSCC patients. The transcriptional parameters that we describe may be optimized to improve prognosis and risk stratification in the clinic and provide insights into gene and cellular targets that may potentially enhance anti-tumor immunity mediated by NK cells and memory B cells in HPV-infected HNSCC patients.

The DataHarmonizer: a tool for faster data harmonization, validation, aggregation and analysis of pathogen genomics contextual information.

Pathogen genomics is a critical tool for public health surveillance, infection control, outbreak investigations as well as research. In order to make use of pathogen genomics data, they must be interpreted using contextual data (metadata). Contextual data include sample metadata, laboratory methods, patient demographics, clinical outcomes and epidemiological information. However, the variability in how contextual information is captured by different authorities and how it is encoded in different databases poses challenges for data interpretation, integration and their use/re-use. The DataHarmonizer is a template-driven spreadsheet application for harmonizing, validating and transforming genomics contextual data into submission-ready formats for public or private repositories. The tool's web browser-based JavaScript environment enables validation and its offline functionality and local installation increases data security. The DataHarmonizer was developed to address the data sharing needs that arose during the COVID-19 pandemic, and was used by members of the Canadian COVID Genomics Network (CanCOGeN) to harmonize SARS-CoV-2 contextual data for national surveillance and for public repository submission. In order to support coordination of international surveillance efforts, we have partnered with the Public Health Alliance for Genomic Epidemiology to also provide a template conforming to its SARS-CoV-2 contextual data specification for use worldwide. Templates are also being developed for One Health and foodborne pathogens. Overall, the DataHarmonizer tool improves the effectiveness and fidelity of contextual data capture as well as its subsequent usability. Harmonization of contextual information across authorities, platforms and systems globally improves interoperability and reusability of data for concerted public health and research initiatives to fight the current pandemic and future public health emergencies. While initially developed for the COVID-19 pandemic, its expansion to other data management applications and pathogens is already underway.

Unsupervised discovery of ancestry-informative markers and genetic admixture proportions in biobank-scale datasets.

Admixture estimation plays a crucial role in ancestry inference and genome-wide association studies (GWASs). Computer programs such as ADMIXTURE and STRUCTURE are commonly employed to estimate the admixture proportions of sample individuals. However, these programs can be overwhelmed by the computational burdens imposed by the 105 to 106 samples and millions of markers commonly found in modern biobanks. An attractive strategy is to run these programs on a set of ancestry-informative SNP markers (AIMs) that exhibit substantially different frequencies across populations. Unfortunately, existing methods for identifying AIMs require knowing ancestry labels for a subset of the sample. This supervised learning approach creates a chicken and the egg scenario. In this paper, we present an unsupervised, scalable framework that seamlessly carries out AIM selection and likelihood-based estimation of admixture proportions. Our simulated and real data examples show that this approach is scalable to modern biobank datasets. OpenADMIXTURE, our Julia implementation of the method, is open source and available for free.

Routine cerebral embolic protection in transcatheter aortic valve implantation: rationale and design of the randomised British Heart Foundation PROTECT-TAVI trial.

Transcatheter aortic valve implantation (TAVI) is an established treatment for aortic stenosis. Cerebral embolic protection (CEP) devices may impact periprocedural stroke by capturing debris destined for the brain. However, there is a lack of high-quality randomised trial evidence supporting the use of CEP during TAVI. The British Heart Foundation (BHF) PROTECT-TAVI trial will address whether the routine use of CEP reduces the incidence of stroke in patients undergoing TAVI. BHF PROTECT-TAVI is a prospective, open-label, outcome-adjudicated, multicentre randomised controlled trial. The trial is open to all adult patients scheduled for TAVI at participating specialist cardiac centres across the United Kingdom who are able to receive the CEP device. The trial will recruit 7,730 participants. Participants will be randomised in a 1:1 ratio to undergo TAVI with CEP or TAVI without CEP (standard of care). The primary outcome is the incidence of stroke at 72 hours post-TAVI. Key secondary outcomes include the incidence of stroke and all-cause mortality up to 12 months post-TAVI, disability and cognitive outcomes, stroke severity, access site complications and a health economics analysis. The sample size of 7,730 participants has 80% power to detect a 33% relative risk reduction from a 3% incidence of the primary outcome in the controls. Trial recruitment commenced in October 2020. As of October 2022, 3,068 patients have been enrolled. BHF PROTECT-TAVI is designed to provide definitive evidence on the clinical efficacy and cost-effectiveness of using routine CEP with the SENTINEL device to reduce stroke in TAVI.

A Complete Whole-Genome Sequence of Ignavigranum ruoffiae Strain CPL 242382-20, an Opportunistic Human Pathogen Recovered from a Breast Cyst.

Ignavigranum ruoffiae is a rare human pathogen. Strain CPL 242382-20 was isolated in Manitoba, Canada, from a breast cyst. Whole-genome sequencing was performed with the Oxford Nanopore Technologies MinION and Illumina MiSeq platforms. The circular chromosome is 1,949,382 bp with 39.68% G+C content and 1,765 protein-coding genes.