A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock

Factors associated with delay in transfer of patients with ST-segment elevation myocardial infarction from first medical contact to catheterization laboratory: Lessons from CRAC, a French prospective multicentre registry

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Is coronary multivessel disease in acute myocardial infarction patients still associated with worse clinical outcomes at 1-year?

International audienceBackgroundST‐elevation myocardial infarction (STEMI) patients with multivessel disease (MVD) are associated with a worse prognosis. However, few comparisons are available according to coronary status in the era of modern reperfusion and optimized secondary prevention.HypothesisWe hypothesized that the difference in prognosis according to number of vessel disease in STEMI patients has reduced.MethodsAll consecutive STEMI patients undergoing primary percutaneous coronary intervention (PCI) within 24 h of symptoms onset between January 1, 2014 and June 30, 2016 enrolled in the CRAC (Club Régional des Angioplasticiens de la région Centre) France PCI registry were analyzed. Baseline characteristics, management, and outcomes at 1‐year were analyzed according to coronary status (one‐, two‐, and three‐VD).ResultsA total of 1886 patients (mean age 62.2 ± 14.0 year; 74% of male) were included. Patients with MVD (two or three‐VD) represented 53.7%. They were older with higher cardiovascular risk factor profile. At 1 year, the rate of major adverse cardiovascular events (MACE, defined as all‐cause death, stroke or re‐MI) was 10%, 12%, and 12% in one‐, two, and three‐VD respectively (p = .28). In multivariable adjusted Cox proportional hazard regression model, two‐ and three‐VD were not associated with higher rate of MACE compared to patients with single VD (HR, 1.09; 95%CI 0.76–1.56 for two‐VD; HR, 0.74; 95%CI 0.48–1.14 for three‐VD).ConclusionsMVD still represents an important proportion of STEMI patients but their prognoses were not associated with worse clinical outcomes at 1‐year compared with one‐VD patients in a modern reperfusion area and secondary medication prevention

Economic evaluation of fractional flow reserve-guided versus angiography-guided multivessel revascularisation in ST-segment elevation myocardial infarction patients in the FLOWER-MI randomised trial

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Impact of coronary artery disease in patients undergoing transcatheter aortic valve replacement: Insights from the FRANCE-2 registry

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The lmo0501 gene coding for a putative transcription activator protein in Listeria monocytogenes promotes growth under cold, osmotic and acid stress conditions

In Listeria monocytogenes EGDe, the lmo0501 gene locus encodes a protein similar to the mannitol transcription regulator (MltR) protein in Bacillus subtilis and Bacillus stearothermophilus. In this study we investigated its functional role in L. monocytogenes EGDe cells in view of growth under different stress conditions. Increased lmo0501 gene expression at mRNA level was detected in response to cold, osmotic and organic acid stress exposure. An EGDe Δlmo0501 mutant strain was diminished in growth compared to the wild type strain in minimal defined medium containing either glucose or fructose, as carbon sources. Growth of the lmo0501 null mutant was retarded growth under cold (4 °C), salt (NaCl) and organic acid stress conditions relative to the parental wild type strain. Our results confirm the role of the lmo0501 gene in adaptation of L. monocytogenes cells to food preservation stress conditions as well as to the efficient utilization of glucose and fructose as carbon sources

The France PCI registry: Design, methodology and key findings

International audienceBackground: Obstructive coronary artery disease is the main cause of death worldwide. By tracking events and gaining feedback on patient management, the most relevant information is provided to public health services to further improve prognosis.Aims: To create an inclusive and accurate registry of all percutaneous coronary intervention (PCI) proce-dures performed in France, to assess and improve the quality of care and create research incentives. Also, to describe the methodology of this French national registry of interventional cardiology, and present early key findings. Methods: The France PCI registry is a multicentre observational registry that includes consecutive patients undergoing coronary angiography and/or PCI. The registry was set up to provide online data analysis and structured reports of PCI activity, including process of care measures and assessment of risk-adjusted outcomes in all French PCI centres that are willing to participate. More than 150 baseline data items, describing demographic status, PCI indications and techniques, and in-hospital and 1-year outcomes, are captured into local reporting software by medical doctors and local research technicians, with subsequent encryption and internet transfer to central data servers. Annual activity reports and scoring tools available on the France PCI website enable users to benchmark and improve clinical practices. External validation and consistency assessments are performed, with feedback of data completeness to centres.Results: Between 01 January 2014 and 31 December 2022, participating centres increased from six to 47, and collected 364,770 invasive coronary angiograms and 176,030 PCIs, including 54,049 non-ST -segment elevation myocardial infarction cases and 31,631 ST-segment elevation myocardial infarction cases. Fifteen studies stemming from the France PCI registry have already been published. Conclusions: This fully electronic, daily updated, high-quality, low-cost, national registry is sustainable, and is now expanding. Merging with medicoeconomic databases and nested randomized scientific studies are ongoing steps to expand its scientific potential

Seasonal variations of patients presenting dyspnea to emergency departments in Europe: Results from the EURODEM Study

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