Feasibility and diagnostic reliability of quantitative flow ratio in the assessment of non-culprit lesions in acute coronary syndrome

Several studies have demonstrated the feasibility and safety of hemodynamic assessment of non-culprit coronary arteries in setting of acute coronary syndromes (ACS) using fractional flow reserve (FFR) measurements. Quantitative flow ratio (QFR), recently introduced as angiography-based fast FFR computation, has been validated with good agreement and diagnostic performance with FFR in chronic coronary syndromes. The aim of this study was to assess the feasibility and diagnostic reliability of QFR assessment during primary PCI. A total of 321 patients with ACS and multivessel disease, who underwent primary PCI and were planned for staged PCI of at least one non-culprit lesion were enrolled in the analysis. Within this patient cohort, serial post-hoc QFR analyses of 513 non-culprit vessels were performed. The median time interval between primary and staged PCI was 49 [42-58] days. QFR in non-culprit coronary arteries did not change between acute and staged measurements (0.86 vs 0.87, p = 0.114), with strong correlation (r = 0.94, p ≤ 0.001) and good agreement (mean difference -0.008, 95%CI -0.013-0.003) between measurements. Importantly, QFR as assessed at index procedure had sensitivity of 95.02%, specificity of 93.59% and diagnostic accuracy of 94.15% in prediction of QFR ≤ 0.80 at the time of staged PCI. The present study for the first time confirmed the feasibility and diagnostic accuracy of non-culprit coronary artery QFR during index procedure for ACS. These results support QFR as valuable tool in patients with ACS to detect further hemodynamic relevant lesions with excellent diagnostic performance and therefore to guide further revascularisation therapy

Prognostic impact of fractional flow reserve measurements in patients with acute coronary syndromes: a subanalysis of the FLORIDA study

Randomized trials suggest benefits for fractional flow reserve (FFR)-guided vs. angiography-guided treatment strategies in well-defined and selected patient cohorts with acute coronary syndromes (ACS). The long-term prognostic value of FFR measurement in unselected all-comer ACS patients, however, remains unknown. This subanalysis of the Fractional FLOw Reserve In cardiovascular DiseAses (FLORIDA) study sought to investigate the long-term effects of FFR in the management of lesions in patients with acute coronary syndrome (ACS). FLORIDA was an observational all-comer cohort study performed in Germany, that was population-based and unselected. Patients enrolled into the anonymized InGef Research Database presenting with ACS and undergoing coronary angiography between January 2014 and December 2015 were included in the analysis. Patients were stratified into either the FFR-guided or the angiography-guided treatment arm, based on the treatment received. A matched cohort study design was used. The primary endpoint was all-cause mortality. The secondary endpoint was major adverse cardiovascular events (MACE), a composite of death, non-fatal myocardial infarction (MI), and repeat revascularization. Follow-up time was 3 years. Rates of 3-year mortality were 10.2 and 14.0% in the FFR-guided and the angiography-guided treatment arms (p = 0.04), corresponding to a 27% relative risk reduction for FFR in ACS patients. Rates of MACE were similar in both arms (47.7 vs. 51.5%, p = 0.14), including similar rates of non-fatal MI (27.7 vs. 25.4%, p = 0.47) and revascularization (9.9 vs. 12.1%, p = 0.17). In this large, all-comer observational study of ACS patients, FFR-guided revascularization was associated with a lower mortality at 3 years. This finding encourages the routine use of FFR to guide lesion revascularization in patients presenting with ACS

Proteasome subunit variants cause neurosensory syndrome combining deafness and cataract due to proteotoxic stress

The ubiquitin–proteasome system degrades ubiquitin‐modified proteins to maintain protein homeostasis and to control signalling. Whole‐genome sequencing of patients with severe deafness and early‐onset cataracts as part of a neurological, sensorial and cutaneous novel syndrome identified a unique deep intronic homozygous variant in the PSMC3 gene, encoding the proteasome ATPase subunit Rpt5, which lead to the transcription of a cryptic exon. The proteasome content and activity in patient\u27s fibroblasts was however unaffected. Nevertheless, patient\u27s cells exhibited impaired protein homeostasis characterized by accumulation of ubiquitinated proteins suggesting severe proteotoxic stress. Indeed, the TCF11/Nrf1 transcriptional pathway allowing proteasome recovery after proteasome inhibition is permanently activated in the patient\u27s fibroblasts. Upon chemical proteasome inhibition, this pathway was however impaired in patient\u27s cells, which were unable to compensate for proteotoxic stress although a higher proteasome content and activity. Zebrafish modelling for knockout in PSMC3 remarkably reproduced the human phenotype with inner ear development anomalies as well as cataracts, suggesting that Rpt5 plays a major role in inner ear, lens and central nervous system development

Knowledge Base on Species Life Traits : A Spanish/French Plinian Core implementation use case

International audienceThe French “Traits” working group was created in 2021 to support the development of the national knowledge base on species life traits managed by the PatriNat department*1, to identify and implement a suitable standard for managing and sharing species life traits (including interactions) at the national, then international, level. Its core members are part of several PatriNat teams (Species Knowledge, Dissemination & Mediation, Coordination of Information Systems), as well as other French research units*2 working on the topic of traits and ontologies. The Plinian Core (Plinian Core Task Group 2021) was first discussed in 2004 and its development began in 2005–2006 when the first version was deployed as a collaboration between InBIO*3 (Costa Rica) and GBIF Spain*4. It reuses and extends the Darwin Core vocabulary (Wieczorek et al. 2012, Darwin Core Maintenance Interest Group 2014) to describe different aspects of biological species information, that is, all kinds of properties or traits related to taxa, including biological and non-biological species traits. The Plinian Core was discussed with Dr Pando (convener of the TDWG Plinian Core Task Group*5) during one of the Traits working group meetings, and was found to be relevant to the French species life traits database (currently in development). The Traits working group future works will be following the example of the Plinian Core-based EIDOS database*6 (Spanish Ministry for the Ecological Transition), which allows for detailed species pages with distinct information sections (e.g., interactions, taxonomy, legal status, conservation). This collaboration resulted in a Capacity Enhancement Support Programme project submission (GBIF 2023) between French and Spanish partners, allowing for the consolidation of both the infrastructure and the sharing process of species life traits for taxa found on all French territories, as well as European Union territories. Additionally, this is an opportunity to provide information to GBIF (Global Biodiversity Information Facility) through a new update of the TAXREF (Gargominy 2022) national checklist, one of the core constituents of the GBIF Backbone Taxonomy (GBIF 2022). Species life traits and interactions will be added thanks to the new Plinian Core extension implemented on the GBIF Integrated Publishing Toolkit (IPT),*7 and an Atlas of Living Australia’s architecture BIE (Biodiversity Information Explorer) module*8 developed by Costa Rica in the context of a Capacity Enhancement Support Programme (CESP) project carried out with SIBBR*9 (GBIF Brasil)

Prognostic Impact of Pancoronary Quantitative Flow Ratio Assessment in Patients Undergoing Percutaneous Coronary Intervention for Acute Coronary Syndromes

BACKGROUND Quantitative flow ratio (QFR) has been introduced as a novel angiography-based modality for fast hemodynamic assessment of coronary artery lesions and validated against fractional flow reserve. This study sought to define the prognostic role of pancoronary QFR assessment in patients with acute coronary syndrome (ACS) including postinterventional culprit and nonculprit vessels. METHODS In a total of 792 patients with ACS (48.6% ST-segment-elevation ACS and 51.4% non-ST-segment-elevation ACS), QFR analyses of postinterventional culprit (n=792 vessels) and nonculprit vessels (n=1231 vessels) were post hoc performed by investigators blinded to clinical outcomes. The follow-up comprised of major adverse cardiovascular events, including all-cause mortality, nonfatal myocardial infarction, and ischemia-driven coronary revascularization within 2 years after the index ACS event. RESULTS Major adverse cardiovascular events as composite end point occurred in 99 patients (12.5%). QFR with an optimal cutoff value of 0.89 for postinterventional culprit vessels and 0.85 for nonculprit vessels emerged as independent predictor of major adverse cardiovascular events after ACS (nonculprit arteries: adjusted odds ratio, 3.78 [95% CI, 2.21-6.45], P<0.001 and postpercutaneous coronary intervention culprit arteries: adjusted odds ratio, 3.60 [95% CI, 2.09-6.20], P<0.001). CONCLUSIONS The present study for the first time demonstrates the prognostic implications of a pancoronary angiography-based functional lesion assessment in patients with ACS. Hence, QFR offers a novel tool to advance risk stratification and guide therapeutic management after ACS

Interaction of a Densovirus with Glycans of the Peritrophic Matrix Mediates Oral Infection of the Lepidopteran Pest Spodoptera frugiperda

The success of oral infection by viruses depends on their capacity to overcome the gut epithelial barrier of their host to crossing over apical, mucous extracellular matrices. As orally transmitted viruses, densoviruses, are also challenged by the complexity of the insect gut barriers, more specifically by the chitinous peritrophic matrix, that lines and protects the midgut epithelium; how capsids stick to and cross these barriers to reach their final cell destination where replication goes has been poorly studied in insects. Here, we analyzed the early interaction of the Junonia coenia densovirus (JcDV) with the midgut barriers of caterpillars from the pest Spodoptera frugiperda. Using combination of imaging, biochemical, proteomic and transcriptomic analyses, we examined in vitro, ex vivo and in vivo the early interaction of the capsids with the peritrophic matrix and the consequence of early oral infection on the overall gut function. We show that the JcDV particle rapidly adheres to the peritrophic matrix through interaction with different glycans including chitin and glycoproteins, and that these interactions are necessary for oral infection. Proteomic analyses of JcDV binding proteins of the peritrophic matrix revealed mucins and non-mucins proteins including enzymes already known to act as receptors for several insect pathogens. In addition, we show that JcDV early infection results in an arrest of N-Acetylglucosamine secretion and a disruption in the integrity of the peritrophic matrix, which may help viral particles to pass through. Finally, JcDV early infection induces changes in midgut genes expression favoring an increased metabolism including an increased translational activity. These dysregulations probably participate to the overall dysfunction of the gut barrier in the early steps of viral pathogenesis. A better understanding of early steps of densovirus infection process is crucial to build biocontrol strategies against major insect pests

Table2_Fractional flow reserve measurements and long-term mortality—results from the FLORIDA study.docx

BackgroundRandomized evidence suggested improved outcomes in fractional flow reserve (FFR) guidance of coronary revascularization compared to medical therapy in well-defined patient cohorts. However, the impact of FFR-guided revascularization on long-term outcomes of unselected patients with chronic or acute coronary syndromes (ACS) is unknown.AimsThe FLORIDA (Fractional FLOw Reserve In cardiovascular DiseAses) study sought to investigate outcomes of FFR-guided vs. angiography-guided treatment strategies in a large, real-world cohort.MethodsThis study included patients enrolled into the German InGef Research Database. Patients undergoing coronary angiography between January 2014 and December 2015 were included in the analysis. Eligible patients had at least one inpatient coronary angiogram for suspected coronary artery disease between January 2014 and December 2015. Patients were stratified into FFR arm if a coronary angiography with adjunctive FFR measurement was performed, otherwise into the angiography-only arm. Matching was applied to ensure a balanced distribution of baseline characteristics in the study cohort. Patients were followed for 3 years after index date and primary endpoint was all-cause mortality.ResultsIn the matched population, mortality at 3 years was 9.6% in the FFR-assessed group and 12.6% in the angiography-only group (p = 0.002), corresponding to a 24% relative risk reduction with use of FFR. This effect was most pronounced in patients in whom revascularization was deferred based on FFR (8.7% vs. 12.3%, p = 0.04) and in high-risk subgroups including patients aged ≥75 years (14.9% vs. 20.1%, p ConclusionsFFR-based revascularization strategy was associated with reduced mortality at 3 years. These findings further support the use of FFR in everyday clinical practice.</p

Table1_Fractional flow reserve measurements and long-term mortality—results from the FLORIDA study.docx

BackgroundRandomized evidence suggested improved outcomes in fractional flow reserve (FFR) guidance of coronary revascularization compared to medical therapy in well-defined patient cohorts. However, the impact of FFR-guided revascularization on long-term outcomes of unselected patients with chronic or acute coronary syndromes (ACS) is unknown.AimsThe FLORIDA (Fractional FLOw Reserve In cardiovascular DiseAses) study sought to investigate outcomes of FFR-guided vs. angiography-guided treatment strategies in a large, real-world cohort.MethodsThis study included patients enrolled into the German InGef Research Database. Patients undergoing coronary angiography between January 2014 and December 2015 were included in the analysis. Eligible patients had at least one inpatient coronary angiogram for suspected coronary artery disease between January 2014 and December 2015. Patients were stratified into FFR arm if a coronary angiography with adjunctive FFR measurement was performed, otherwise into the angiography-only arm. Matching was applied to ensure a balanced distribution of baseline characteristics in the study cohort. Patients were followed for 3 years after index date and primary endpoint was all-cause mortality.ResultsIn the matched population, mortality at 3 years was 9.6% in the FFR-assessed group and 12.6% in the angiography-only group (p = 0.002), corresponding to a 24% relative risk reduction with use of FFR. This effect was most pronounced in patients in whom revascularization was deferred based on FFR (8.7% vs. 12.3%, p = 0.04) and in high-risk subgroups including patients aged ≥75 years (14.9% vs. 20.1%, p ConclusionsFFR-based revascularization strategy was associated with reduced mortality at 3 years. These findings further support the use of FFR in everyday clinical practice.</p

Proteasome subunit PSMC3 variants cause neurosensory syndrome combining deafness and cataract due to proteotoxic stress

International audienceThe ubiquitin-proteasome system degrades ubiquitin-modified proteins to maintain protein homeostasis and to control signalling. Whole-genome sequencing of patients with severe deafness and early-onset cataracts as part of a neurological, sensorial and cuta-neous novel syndrome identified a unique deep intronic homozygous variant in the PSMC3 gene, encoding the proteasome ATPase subunit Rpt5, which lead to the transcription of a cryptic exon. The protea-some content and activity in patient's fibroblasts was however unaffected. Nevertheless, patient's cells exhibited impaired protein homeostasis characterized by accumulation of ubiquitinated proteins suggesting severe proteotoxic stress. Indeed, the TCF11/Nrf1 tran-scriptional pathway allowing proteasome recovery after proteasome inhibition is permanently activated in the patient's fibroblasts. Upon chemical proteasome inhibition, this pathway was however impaired in patient's cells, which were unable to compensate for proteotoxic stress although a higher proteasome content and activity. Zebrafish modelling for knockout in PSMC3 remarkably reproduced the human phenotype with inner ear development anomalies as well as cataracts , suggesting that Rpt5 plays a major role in inner ear, lens and central nervous system development