Publications by authors named "Thierry Lefevre"

401 Publications

Detection of Plasmodium falciparum in laboratory-reared and naturally infected wild mosquitoes using near-infrared spectroscopy.

Sci Rep 2021 May 13;11(1):10289. Epub 2021 May 13.

MRC Centre for Global Infectious Disease Analysis, Infectious Disease Epidemiology, Imperial College London, London, W2 1PG, UK.

There is an urgent need for high throughput, affordable methods of detecting pathogens inside insect vectors to facilitate surveillance. Near-infrared spectroscopy (NIRS) has shown promise to detect arbovirus and malaria in the laboratory but has not been evaluated in field conditions. Here we investigate the ability of NIRS to identify Plasmodium falciparum in Anopheles coluzzii mosquitoes. NIRS models trained on laboratory-reared mosquitoes infected with wild malaria parasites can detect the parasite in comparable mosquitoes with moderate accuracy though fails to detect oocysts or sporozoites in naturally infected field caught mosquitoes. Models trained on field mosquitoes were unable to predict the infection status of other field mosquitoes. Restricting analyses to mosquitoes of uninfectious and highly-infectious status did improve predictions suggesting sensitivity and specificity may be better in mosquitoes with higher numbers of parasites. Detection of infection appears restricted to homogenous groups of mosquitoes diminishing NIRS utility for detecting malaria within mosquitoes.
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http://dx.doi.org/10.1038/s41598-021-89715-1DOI Listing
May 2021

A non-destructive sugar-feeding assay for parasite detection and estimating the extrinsic incubation period of Plasmodium falciparum in individual mosquito vectors.

Sci Rep 2021 Apr 29;11(1):9344. Epub 2021 Apr 29.

Institut de Recherche en Sciences de la Santé, Bobo-Dioulasso, Burkina Faso.

Despite its epidemiological importance, the time Plasmodium parasites take to achieve development in the vector mosquito (the extrinsic incubation period, EIP) remains poorly characterized. A novel non-destructive assay designed to estimate EIP in single mosquitoes, and more broadly to study Plasmodium-Anopheles vectors interactions, is presented. The assay uses small pieces of cotton wool soaked in sugar solution to collect malaria sporozoites from individual mosquitoes during sugar feeding to monitor infection status over time. This technique has been tested across four natural malaria mosquito species of Africa and Asia, infected with Plasmodium falciparum (six field isolates from gametocyte-infected patients in Burkina Faso and the NF54 strain) and across a range of temperatures relevant to malaria transmission in field conditions. Monitoring individual infectious mosquitoes was feasible. The estimated median EIP of P. falciparum at 27 °C was 11 to 14 days depending on mosquito species and parasite isolate. Long-term individual tracking revealed that sporozoites transfer onto cotton wool can occur at least until day 40 post-infection. Short individual EIP were associated with short mosquito lifespan. Correlations between mosquito/parasite traits often reveal trade-offs and constraints and have important implications for understanding the evolution of parasite transmission strategies.
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http://dx.doi.org/10.1038/s41598-021-88659-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085177PMC
April 2021

Incidence, predictors, and outcomes associated with acute kidney injury in patients undergoing transcatheter aortic valve replacement: from the BRAVO-3 randomized trial.

Clin Res Cardiol 2021 May 11;110(5):649-657. Epub 2021 Apr 11.

The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, USA.

Background: Acute kidney injury (AKI) is not uncommon in patients undergoing transcatheter aortic valve replacement (TAVR).

Objective: We examined the incidence, predictors, and outcomes of AKI from the BRAVO 3 randomized trial.

Methods: The BRAVO-3 trial included 802 patients undergoing transfemoral TAVR randomized to bivalirudin vs. unfractionated heparin (UFH). The primary endpoint of the trial was Bleeding Academic Research Consortium (BARC) type ≥ 3b bleeding at 48 h. Total follow-up was to 30 days. AKI was adjudicated using the modified RIFLE (Valve Academic Research Consortium, VARC 1) criteria through 30-day follow-up, and in a sensitivity analysis AKI was assessed at 7 days (modified VARC-2 criteria). We examined the incidence, predictors, and 30-day outcomes associated with diagnosis of AKI. We also examined the effect of procedural anticoagulant (bivalirudin or unfractionated heparin, UFH) on AKI within 48 h after TAVR.

Results: The trial population had a mean age of 82.3 ± 6.5 years including 48.8% women with mean EuroScore I 17.05 ± 10.3%. AKI occurred in 17.0% during 30-day follow-up and was associated with greater adjusted risk of 30-day death (13.0% vs. 3.5%, OR 5.84, 95% CI 2.62-12.99) and a trend for more BARC ≥ 3b bleeding (15.1% vs. 8.6%, OR 1.80, 95% CI 0.99-3.25). Predictors of 30-day AKI were baseline hemoglobin, body weight, and pre-existing coronary disease. AKI occurred in 10.7% at 7 days and was associated with significantly greater risk of 30-day death (OR 6.99, 95% CI 2.85-17.15). Independent predictors of AKI within 7 days included pre-existing coronary or cerebrovascular disease, chronic kidney disease (CKD), and transfusion which increased risk, whereas post-dilation was protective. The incidence of 48-h AKI was higher with bivalirudin compared to UFH in the intention to treat cohort (10.9% vs. 6.5%, p = 0.03), but not in the per-protocol assessment (10.7% vs. 7.1%, p = 0.08).

Conclusion: In the BRAVO 3 trial, AKI occurred in 17% at 30 days and in 10.7% at 7 days. AKI was associated with a significantly greater adjusted risk for 30-day death. Multivariate predictors of AKI at 30 days included baseline hemoglobin, body weight, and prior coronary artery disease, and predictors at 7 days included pre-existing vascular disease, CKD, transfusion, and valve post-dilation. Bivalirudin was associated with greater AKI within 48 h in the intention to treat but not in the per-protocol analysis.
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http://dx.doi.org/10.1007/s00392-020-01787-7DOI Listing
May 2021

Proximal Optimisation Technique Versus Final Kissing Balloon Inflation in Coronary Bifurcation Lesions: the Randomised, Multicenter PROPOT Trial.

EuroIntervention 2021 Mar 30. Epub 2021 Mar 30.

Department of Medicine, Division of Cardiology, Teikyo University School of Medicine, Tokyo, Japan.

Background: Clinical implications of proximal optimisation technique (POT) for bifurcation lesions have not been investigated in a randomised controlled trial.

Aims: This study aimed to investigate whether proximal optimisation technique (POT) is superior in terms of stent apposition compared with the conventional kissing balloon technique (KBT) in real-life bifurcation lesions using optical coherence tomography (OCT).

Methods: A total of 120 patients from 15 centres were randomised into two groups: POT followed by side branch dilation or KBT. Finally, 57 and 58 patients in the POT and KBT groups, respectively, were analysed. OCT was performed at baseline, immediately after wire recrossing to the side branch, and at the final procedure.

Results: The primary endpoint was the rate of malapposed struts assessed by the final OCT. The rate of malapposed struts did not differ between the POT and KBT groups (in-stent proximal site: 10.4% vs. 7.7%, p=0.33; bifurcation core: 1.4% vs. 1.1%, p=0.67; core's distal edge: 6.2% vs. 5.3%, p=0.59). More additional treatments were required among the POT group (40.4% vs. 6.9%, p<0.01). At 1-year follow-up, only one patient in each group underwent target lesion revascularisation (2.0% vs. 1.9%).

Conclusions: POT followed by side branch dilation did not show any advantages over conventional KBT in terms of stent apposition, however, the excellent mid-term clinical outcomes were observed in both strategies.
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http://dx.doi.org/10.4244/EIJ-D-20-01386DOI Listing
March 2021

Prognostic significance of vascular and valvular calcifications in low- and high-gradient aortic stenosis.

Eur Heart J Cardiovasc Imaging 2021 Mar 8. Epub 2021 Mar 8.

University of Lyon, CREATIS UMR5220, INSERM U1044, INSA-15, 7 avenue Jean Capelle 69621 Villeurbanne Cedex, Lyon, France.

Aims: In low-gradient aortic stenosis (LGAS), the high valvulo-arterial impedance observed despite low valvular gradient suggests a high vascular load. Thoracic aortic calcifications (TACs) and valvular aortic calcifications (VACs) are, respectively, surrogates of aortic load and aortic valvular gradient. The aim of this study was to compare the respective contributions of TAC and VAC on 3-year cardiovascular (CV) mortality following TAVI in LGAS vs. high-gradient aortic stenosis (HGAS) patients.

Methods And Results: A total of 1396 consecutive patients were included. TAC and VAC were measured on the pre-TAVI CT-scan. About 435 (31.2%) patients had LGAS and 961 (68.8%) HGAS. LGAS patients were more prone to have diabetes, coronary artery disease (CAD), atrial fibrillation (AF), and lower left ventricular ejection fraction (LVEF), P<0.05 for all. During the 3 years after TAVI, 245(17.8%) patients experienced CV mortality, 92(21.6%) in LGAS and 153(16.2%) in HGAS patients, P=0.018. Multivariate analysis adjusted for age, gender, diabetes, AF, CAD, LVEF, renal function, vascular access, and aortic regurgitation showed that TAC but not VAC was associated with CV mortality in LGAS, hazard ratio (HR) 1.085 confidence interval (CI) (1.019-1.156), P=0.011, and HR 0.713 CI (0.439-1.8), P=0.235; the opposite was observed in HGAS patients with VAC but not TAC being associated with CV mortality, HR 1.342 CI (1.034-1.742), P=0.027, and HR 1.015 CI (0.955-1.079), P=0.626.

Conclusion : TAC plays a major prognostic role in LGAS while VAC remains the key in HGAS patients. This confirms that LGAS is a complex vascular and valvular disease.
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http://dx.doi.org/10.1093/ehjci/jeab039DOI Listing
March 2021

Predicting the public health impact of a malaria transmission-blocking vaccine.

Nat Commun 2021 03 8;12(1):1494. Epub 2021 Mar 8.

Medical Research Council Centre for Global Infections Disease Analysis, Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.

Transmission-blocking vaccines that interrupt malaria transmission from humans to mosquitoes are being tested in early clinical trials. The activity of such a vaccine is commonly evaluated using membrane-feeding assays. Understanding the field efficacy of such a vaccine requires knowledge of how heavily infected wild, naturally blood-fed mosquitoes are, as this indicates how difficult it will be to block transmission. Here we use data on naturally infected mosquitoes collected in Burkina Faso to translate the laboratory-estimated activity into an estimated activity in the field. A transmission dynamics model is then utilised to predict a transmission-blocking vaccine's public health impact alongside existing interventions. The model suggests that school-aged children are an attractive population to target for vaccination. Benefits of vaccination are distributed across the population, averting the greatest number of cases in younger children. Utilising a transmission-blocking vaccine alongside existing interventions could have a substantial impact against malaria.
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http://dx.doi.org/10.1038/s41467-021-21775-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940395PMC
March 2021

Biodegradable polymer sirolimus-eluting stents vs durable polymer everolimus-eluting stents in patients undergoing percutaneous coronary intervention: A meta-analysis of individual patient data from 5 randomized trials.

Am Heart J 2021 May 17;235:140-148. Epub 2021 Feb 17.

Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

Background: Newest generation drug-eluting stents combine biodegradable polymers with ultrathin stent platforms in order to minimize vessel injury and inflammatory response. Evidence from randomized controlled trials suggested that differences in stent design translate into differences in clinical outcome. The aim of the present study was to evaluate the safety and efficacy of ultrathin strut, biodegradable polymer sirolimus eluting stents (BP SES) compared with thin strut, durable polymer everolimus-eluting stents (DP EES) among patients undergoing percutaneous coronary intervention (PCI).

Methods: We pooled individual participant data from 5 randomized trials (NCT01356888, NCT01939249, NCT02389946, NCT01443104, NCT02579031) including a total of 5,780 patients, and performed a one-stage meta-analysis using a mixed effects Cox regression model.

Results: At a median duration of follow-up of 739 days (interquartile range 365-1,806 days), target-lesion failure occurred in 337 (10.3%) and 304 (12.2%) patients treated with BP SES and DP EES (HR 0.86, 95%CI 0.71-1.06, P = .16). There were no significant differences between BP SES and DP EES with regards to cardiac death (111 (3.4%) vs 102 (4.1%); HR 1.05, 95%CI 0.80-1.37, P = .73), target-vessel myocardial infarction (136 (4.1%) vs 126 (5.0%), HR 0.79, 95%CI 0.62-1.01, P = .061), and clinically-driven target-lesion revascularization (163 (5.0%) vs 147 (5.9%); HR 0.94, 95%CI 0.75-1.18, P = .61). The effect was consistent across major subgroups. In a landmark analysis, there was no significant interaction between treatment effect and timing of events.

Conclusions: In this patient-level meta-analysis of 5 randomized controlled trials, BP SES were associated with a similar risk of target-lesion failure compared with DP EES among patients undergoing PCI.

Study Registration: PROSPERO registry (CRD42018109098).
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http://dx.doi.org/10.1016/j.ahj.2021.02.009DOI Listing
May 2021

The effect of transcatheter aortic valve implantation approaches on mortality.

Catheter Cardiovasc Interv 2021 Jan 14. Epub 2021 Jan 14.

Department of Cardiology, St. Antonius Hospital, Nieuwegein, The Netherlands.

Objectives: We aimed to evaluate the effect of transcatheter aortic valve implantation (TAVI) approaches on mortality and identify effect modifiers and predictors for mortality.

Background: Alternative access routes to transfemoral (TF) TAVI include the surgical intra-thoracic direct-aortic (DA) and transapical (TA) approach. TA TAVI has been associated with a higher mortality rate. We hypothesized that this is related to effect modifiers, in particular the left ventricular ejection fraction (LVEF).

Methods: This multicentre study derived its data from prospective registries. To adjust for confounders, we used propensity-score based, stabilized inverse probability weighted Cox regression models.

Results: In total, 5,910 patients underwent TAVI via TF (N = 4,072), DA (N = 524), and TA (N = 1,314) access. Compared to TF, 30-day mortality was increased among DA (HR 1.87, 95%CI 1.26-2.78, p = .002) and TA (HR 3.34, 95%CI 2.28-4.89, p < .001) cases. Compared to TF, 5-year mortality was increased among TA cases (HR 1.50, 95%CI 1.24-1.83, p < .001). None of the variables showed a significant interaction between the approaches and mortality. An impaired LVEF (≤35%) increased mortality in all approaches.

Conclusions: The surgical intra-thoracic TA and DA TAVI are both associated with a higher 30-day mortality than TF TAVI. TA TAVI is associated with a higher 5-year mortality than TF TAVI. The DA approach may therefore have some advantages over the TA approach when TF access is not feasible.
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http://dx.doi.org/10.1002/ccd.29456DOI Listing
January 2021

Plasmodium falciparum gametocyte carriage in symptomatic patients shows significant association with genetically diverse infections, anaemia, and asexual stage density.

Malar J 2021 Jan 7;20(1):31. Epub 2021 Jan 7.

Institut de Recherche en Sciences de La Santé/ Clinical Research Unit of Nanoro (IRSS-URCN), Nanoro, Burkina Faso.

Background: Multi-genotype malaria infections are frequent in endemic area, and people commonly harbour several genetically distinct Plasmodium falciparum variants. The influence of genetic multiplicity and whether some specific genetic variants are more or less likely to invest into gametocyte production is not clearly understood. This study explored host and parasite-related risk factors for gametocyte carriage, and the extent to which some specific P. falciparum genetic variants are associated with gametocyte carriage.

Methods: Gametocytes and asexual forms were detected by light microscopy on thick smears collected between 2010 and 2012 in Nanoro, Burkina Faso. Merozoite surface protein 1 and 2 were genotyped by nested PCR on clinical samples. Associations between gametocyte carriage and factors, including multiplicity of infection, parasite density, patient age, gender, haemoglobin (Hb) level, and body temperature were assessed. The relationship between the presence of a particular msp1 and msp2 genetic variants and gametocyte carriage was also explored.

Results: Of the 724 samples positive to P. falciparum and successfully genotyped, gametocytes were found in 48 samples (6.63%). There was no effect of patient gender, age and body temperature on gametocyte carriage. However, the probability of gametocyte carriage significantly increased with increasing values of multiplicity of infection (MOI). Furthermore, there was a negative association between parasite density and gametocyte carriage. MOI decreased with parasite density in gametocyte-negative patients, but increased in gametocyte carriers. The probability of gametocyte carriage decreased with Hb level. Finally, the genetic composition of the infection influenced gametocyte carriage. In particular, the presence of RO33 increased the odds of developing gametocytes by 2 while the other allelic families K1, MAD20, FC27, and 3D7 had no significant impact on the occurrence of gametocytes in infected patients.

Conclusion: This study provides insight into potential factors influencing gametocyte production in symptomatic patients. The findings contribute to enhance understanding of risk factors associated with gametocyte carriage in humans. Trial registration NCT01232530.
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http://dx.doi.org/10.1186/s12936-020-03559-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791700PMC
January 2021

Patient with heart failure: importance to treat valvular diseases.

Eur Heart J Suppl 2020 Dec 23;22(Suppl Pt t):P38-P41. Epub 2020 Dec 23.

Department of Cardiology, University Hospital of Poitiers, Poitiers, France.

COVID-19 pandemic is causing an unprecedented burden on healthcare resources and this includes treatment of heart failure and valvular heart diseases (VHD). Percutaneous procedures have broadened the number of patients with VHD who could be treated. However, COVID-19 pandemic has challenged their implementation. The risk of in-hospital infection, resources reallocation, reduced access to hospital caused a substantial delay of VHD treatment with an increased risk of clinical worsening and mortality. Now, the pandemic is not ended and subsequent waves are likely. Reorganization of our healthcare resources is needed, including a proper algorithm for patients' prioritization, based on the severity of their valve disease, their life expectancy, complexity of the intervention, and the resources available. A wider use of telemedicine for patients' selection and follow-up and any measurement that can shorten the duration of the hospital stay must be adopted. Patients' and healthcare staff screening for COVID-19 and all needed procedures to prevent infection will continue to be mandatory. Percutaneous procedures, compared to surgery, are associated with a lower risk of infection and a lower need for in-hospital resources, including a shorter duration of hospital stay. This may favour their adoption when the risk of viral infection is high.
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http://dx.doi.org/10.1093/eurheartj/suaa184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757709PMC
December 2020

A mating-induced reproductive gene promotes Anopheles tolerance to Plasmodium falciparum infection.

PLoS Pathog 2020 12 21;16(12):e1008908. Epub 2020 Dec 21.

Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States of America.

Anopheles mosquitoes have transmitted Plasmodium parasites for millions of years, yet it remains unclear whether they suffer fitness costs to infection. Here we report that the fecundity of virgin and mated females of two important vectors-Anopheles gambiae and Anopheles stephensi-is not affected by infection with Plasmodium falciparum, demonstrating that these human malaria parasites do not inflict this reproductive cost on their natural mosquito hosts. Additionally, parasite development is not impacted by mating status. However, in field studies using different P. falciparum isolates in Anopheles coluzzii, we find that Mating-Induced Stimulator of Oogenesis (MISO), a female reproductive gene strongly induced after mating by the sexual transfer of the steroid hormone 20-hydroxyecdysone (20E), protects females from incurring fecundity costs to infection. MISO-silenced females produce fewer eggs as they become increasingly infected with P. falciparum, while parasite development is not impacted by this gene silencing. Interestingly, previous work had shown that sexual transfer of 20E has specifically evolved in Cellia species of the Anopheles genus, driving the co-adaptation of MISO. Our data therefore suggest that evolution of male-female sexual interactions may have promoted Anopheles tolerance to P. falciparum infection in the Cellia subgenus, which comprises the most important malaria vectors.
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http://dx.doi.org/10.1371/journal.ppat.1008908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785212PMC
December 2020

Optical Coherence Tomography to Guide Percutaneous Coronary Intervention of the Left Main Coronary Artery: the LEMON study.

EuroIntervention 2020 Nov 24. Epub 2020 Nov 24.

Department of Cardiology, Institut Mutualiste Montsouris, Paris, France.

Aims: IVUS is currently recommended by international guidelines to guide left main stem (LMS) PCI. Although OCT resolution outmatches IVUS, this tool is not yet recommended in LMS angioplasty due to the absence of data. This pilot study aimed to analyze the feasibility, safety and impact of OCT-guided LMS PCI.

Methods And Results: This prospective, multicenter trial investigated whether patients might benefit from OCT-guided PCI for mid/distal LMS according to a pre-specified protocol. The primary endpoint was procedural success defined as follows: residual angiographic stenosis <50% + TIMI 3 flow in all branches + adequate OCT stent expansion (LEMON criteria). Seventy patients were included in the final analysis (median age: 72 (64-81) y, 73% male). The OCT pre-specified protocol was applied in all patients. The primary endpoint was achieved in 86 % of subjects. Adequate stent expansion was observed in 86%, significant edge dissection in 30% and residual significant struts malapposition in 24% of the cases. OCT guidance modified operators' strategy in 26% of the patients. The one-year survival free from major clinical adverse events was 98.6 (97.2-100) %.

Conclusions: This study is the first to report the feasibility and performance of OCT-guided LMS PCI according to a pre-specified protocol.
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http://dx.doi.org/10.4244/EIJ-D-20-01121DOI Listing
November 2020

Aortic valve replacement: validation of the Toronto Aortic Stenosis Quality of Life Questionnaire.

ESC Heart Fail 2021 Feb 18;8(1):270-279. Epub 2020 Nov 18.

Department of Psychiatry, University Health Network, Toronto, Canada.

Aims: There is no quality of life tool specifically developed for patients with severe aortic stenosis (AS) to assess how this chronic condition and its treatment affect patients. The Toronto Aortic Stenosis Quality of Life Questionnaire (TASQ) has been developed to overcome this gap. The results of the validation of the TASQ in patients undergoing treatment for severe AS are presented.

Methods And Results: Prospective study at 10 centres in Europe and Canada, which enrolled 274 patients with severe symptomatic AS undergoing surgical or transcatheter aortic valve replacement. Mean TASQ score at baseline was 71.2 points and increased to 88.9 three months after aortic valve implantation (P < 0.001). Increases were seen for the emotional impact (32.0 to 39.0; P < 0.001), physical limitations (14.8 to 22.0; P < 0.001), and physical symptoms (8.5 vs. 11.0; P < 0.001) domains. Internal consistency was good/excellent for overall TASQ score (α = 0.891) and for the physical limitation, emotional impact, and social limitation domains (α = 0.815-0.950). Test-retest reliability was excellent or strong for the overall TASQ (intraclass correlation coefficient of 0.883) and for the physical symptoms, physical limitation, emotional impact, and social limitation domains (intraclass correlation coefficient of 0.791-0.895). Responsiveness was medium overall (Cohen's d = 0.637) and medium/large for physical symptoms, emotional impact, and physical limitations (0.661-0.812). Sensitivity to change was significant for physical symptoms, physical limitations (both P < 0.001), emotional impact (P = 0.003), and social limitations (P = 0.038).

Conclusions: The TASQ is a new, brief, self-administered, and clinically relevant health-specific tool to measure changes in quality of life in patients with AS undergoing an intervention.
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http://dx.doi.org/10.1002/ehf2.12961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835556PMC
February 2021

Percutaneous coronary intervention for bifurcation coronary lesions: the 15 consensus document from the European Bifurcation Club.

EuroIntervention 2021 Mar;16(16):1307-1317

Insitute of Cardiology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.

The 15th European Bifurcation Club (EBC) meeting was held in Barcelona in October 2019. It facilitated a renewed consensus on coronary bifurcation lesions (CBL) and unprotected left main (LM) percutaneous interventions. Bifurcation stenting techniques continue to be refined, developed and tested. It remains evident that a provisional approach with optional side branch treatment utilising T, T and small protrusion (TAP) or culotte continues to provide flexible options for the majority of CBL patients. Debate persists regarding the optimal treatment of side branches, including assessment of clinical significance and thresholds for bail-out treatment. In more complex CBL, especially those involving the LM, adoption of dedicated two-stent techniques should be considered. Operators using such techniques have to be fully familiar with their procedural steps and should acknowledge associated limitations and challenges. When using two-stent techniques, failure to perform a final kissing inflation is regarded as a technical failure, since it may jeopardise clinical outcome. The development of novel technical tools and drug regimens deserves attention. In particular, intracoronary imaging, bifurcation simulation, drug-eluting balloon technology and tailored antiplatelet therapy have been identified as promising tools to enhance clinical outcomes. In conclusion, the evolution of a broad spectrum of bifurcation PCI components has resulted from studies extending from bench testing to randomised controlled trials. However, further advances are still needed to achieve the ambitious goal of optimising the clinical outcomes for every patient undergoing PCI on a CBL. Visual summary. 15th consensus document from the European Bifurcation Club.
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http://dx.doi.org/10.4244/EIJ-D-20-00169DOI Listing
March 2021

Preprocedural anemia in females undergoing transcatheter aortic valve implantation: Insights from the WIN-TAVI registry.

Catheter Cardiovasc Interv 2021 Apr 1;97(5):E704-E715. Epub 2020 Oct 1.

Institut Hospitalier Jacques Cartier, Ramsay Générale de Santé, Massy, France.

Objectives: To assess the impact of anemia on clinical outcomes in female patients enrolled in the Women's InterNational transcatheter aortic valve implantation (WIN-TAVI) registry.

Background: Anemia is highly prevalent among females who constitute half of TAVI candidates, yet, its clinical significance remains poorly investigated.

Methods: Patients were divided into three groups according to preprocedural hemoglobin (Hb) level: (1) no anemia (Hb ≥12 g/dl), (2) mild-to-moderate anemia (10 ≤ Hb <12 g/dl), and (3) severe anemia (Hb <10 g/dl). The primary outcome was the occurrence of Valve Academic Research Consortium (VARC)-2 efficacy endpoint, a composite of mortality, stroke, myocardial infarction (MI), hospitalization for valve-related symptoms or heart failure or valve-related dysfunction at 1-year follow-up.

Results: Hemoglobin level was available in 877 (86.1%) patients: 412 (47.0%) had no anemia, 363 (41.4%) had mild-to-moderate anemia, and 102 (11.6%) had severe anemia. The latter group had a higher prevalence of cardiovascular risk factors. Compared with patients without anemia, severe anemia was associated with a greater risk of VARC-2 efficacy endpoint ( HR 1.71, 95% CI: 1.02-2.87, p = .04), all-cause death ( HR 2.36, 95% CI: 1.31-4.26, p = .004) and a composite of death, MI or stroke ( HR 1.88, 95% CI: 1.10-3.22, p = .02) at 1 year. Moreover, an increased risk of late mortality ( HR 1.15, 95% CI: 1.02-1.30, p = .03) was observed with every 1 g/dl decrease in hemoglobin level.

Conclusion: Severe anemia in females undergoing TAVI was independently associated with increased rates of VARC-2 efficacy endpoint and mortality at 1 year.
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http://dx.doi.org/10.1002/ccd.29276DOI Listing
April 2021

Drug coated balloons and their role in bifurcation coronary angioplasty: appraisal of the current evidence and future directions.

Expert Rev Med Devices 2020 Oct 14;17(10):1021-1033. Epub 2020 Oct 14.

Department of Cardiology, Clinical Center of Serbia, and Medical Faculty, University of Belgrade , Belgrade, Serbia.

Introduction: Coronary Bifurcation lesions are technically more challenging and Bifurcation percutaneous coronary intervention (PCI) remains a challenge with unpredictable and sub-optimal clinical and angiographic results. Drug-Coated Balloons (DCB) are emerging devices in the field of coronary intervention with promising results that may overcome some of drug eluting stents limitations and may have potential advantages in complex bifurcation PCI.

Areas Covered: We have performed a re-appraisal about the issues with current bifurcation PCI techniques and the use of DCB in the treatment of Bifurcation lesions. Several studies performed utilizing DCB are described and critically appraised. Over the recent years, there have been tremendous developments in the DCB technology, lesion preparation, clinical experience, and clinical data during bifurcation PCI. The current review describes the advances in the DCB technology, pharmacokinetics, role of excipients, and optimization of the technique. Special emphasis in lesion preparation and potential pathway of using DCB in bifurcation PCI is proposed.

Expert Opinion: Although different proof of concept and pilot studies have shown promising results in treatment of bifurcation lesions with DCB, larger randomized trials and/or international consensus papers are required to enable worldwide translation of this idea to clinical practice.
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http://dx.doi.org/10.1080/17434440.2020.1831385DOI Listing
October 2020

Left Atrial Appendage Closure in Patients With Atrial Fibrillation at Very High Bleeding Risk Without Postimplantation Antithrombotic Therapy.

J Invasive Cardiol 2020 Oct;32(10):385-391

Institut Cardiovasculaire Paris Sud, 6 Avenue du Noyer Lambert, 91300 Massy, France.

Objectives: We assess the proportion, baseline characteristics, and outcomes of a cohort of very high bleeding risk (HBR) patients discharged with no antithrombotic therapy after left atrial appendage closure (LAAC).

Background: The optimal antithrombotic therapy after LAAC remains controversial. However, a substantial proportion of patients have HBR and are contraindicated to any antithrombotic therapy. Data regarding the feasibility and safety of such a strategy are scarce.

Methods: All patients who underwent LAAC at our institution between October 2013 and December 2018 were included. Clinical, procedural, and imaging data were collected prospectively, and patients receiving no antithrombotic therapy were compared with those receiving at least 1 agent.

Results: A total of 152 patients were included. At discharge, 72 (47.3%) received single-antiplatelet therapy (SAPT), 57 (37.5%) received dual-antiplatelet therapy (DAPT), and 22 (14.5%) received no antithrombotic therapy (NATT). One patient received a combination of aspirin and vitamin K antagonist. There were no differences regarding baseline characteristics between NATT patients and the others. At a median follow-up of 16 months, 25 patients died. There were no differences between NATT patients and others regarding all-cause mortality (9.1% vs 18.8%, respectively; P=.07) or ischemic stroke (0.0% vs 4.2%, respectively; P=.20). There were 4 episodes of major bleeding, but none occurred in the NATT group, and no device-related thrombosis was seen on computed tomography scan performed within 12 weeks after LAAC.

Conclusions: In highly selected patients at very HBR, discontinuation of any antithrombotic therapy after LAAC appears safe and feasible.
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October 2020

Impact of Mitral Regurgitation Severity and Left Ventricular Remodeling on Outcome After MitraClip Implantation: Results From the Mitra-FR Trial.

JACC Cardiovasc Imaging 2021 Apr 16;14(4):742-752. Epub 2020 Sep 16.

Hopital Cardiovasculaire Louis Pradel, Chirurgie Cardio-Vasculaire et Transplantation Cardiaque, Hospices Civils de Lyon and Claude Bernard University, Lyon, France. Electronic address:

Objectives: This study aimed to identify a subset of patients based on echocardiographic parameters who might have benefited from transcatheter correction using the MitraClip system in the MITRA-FR (Percutaneous Repair with the MitraClip Device for Severe Functional/Secondary Mitral Regurgitation) trial.

Background: It has been suggested that differences in the degree of mitral regurgitation (MR) and left ventricular (LV) remodeling may explain the conflicting results between the MITRA-FR and the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trials.

Methods: In a post hoc analysis, we evaluated the interaction between the intervention and subsets of patients defined based on MR severity (effective regurgitant orifice [ERO], regurgitant volume [RVOL] and regurgitant fraction [RF]), LV remodeling (end-diastolic and end-systolic diameters and volumes) and combination of these parameters with respect to the composite of death from any cause or unplanned hospitalization for heart failure at 24 months.

Results: We observed a neutral impact of the intervention in subsets with the highest MR degree (ERO ≥30 mm, RVOL ≥45 ml or RF ≥50%) as in patients with milder MR degree. The same was seen in subsets with the milder LV remodeling using either diastolic or systolic diameters or volumes. When parameters of MR severity and LV remodeling were combined, there was still no benefit of the intervention including in the subset of patients with an ERO/end-diastolic volume ratio ≥ 0.15 despite similar ERO and LV end-diastolic volume compared with COAPT patients.

Conclusions: In the MITRA-FR trial, we could not identify a subset of patients defined based on the degree of the regurgitation, LV remodeling or on their combination, including those deemed as having disproportionate MR, that might have benefited from transcatheter correction using the MitraClip system. (Multicentre Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients With Severe Secondary Mitral Regurgitation [MITRA-FR]; NCT01920698).
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http://dx.doi.org/10.1016/j.jcmg.2020.07.021DOI Listing
April 2021

Individual patient data analysis of the BIOFLOW study program comparing safety and efficacy of a bioresorbable polymer sirolimus eluting stent to a durable polymer everolimus eluting stent.

Catheter Cardiovasc Interv 2020 Sep 5. Epub 2020 Sep 5.

Herzzentrum, Segeberger Kliniken GmbH, Bad Segeberg, Germany.

Objectives: This analysis of pooled individual patient data (IPD) aimed to evaluate the safety and efficacy of a bioresorbable polymer sirolimus eluting stent system (BP-SES; Orsiro) compared to a durable polymer everolimus eluting stent system (DP-EES; Xience) in the pooled population as well as in subgroups.

Methods: IPD with up to 12 months follow-up of the randomized controlled trials BIOFLOW-II (NCT01356888), -IV (NCT01939249), and -V (NCT02389946) as well as the all comers registry BIOFLOW-III (NCT01553526) were pooled. A total of 3,717 subjects (2,923 in BP-SES and 794 in DP-EES) with 5,328 lesions (4,225 lesions in BP-SES and 1,103 in DP-EES) were included in the IPD. The primary endpoint was target lesion failure (TLF) at 12 months follow-up. Subgroups analyzed included diabetes, age (≥65 years), gender, complex lesions (B2/C), small vessels (reference vessel diameter ≤2.75 mm), multivessel treatment, renal disease, and patients with acute coronary syndrome.

Results: Overall, TLF at 12 months was significantly lower with 5.2%in the BP-SES group versus 7.6% in the DP-EES group (p = .0098). Similarly, target vessel myocardial infarction (TV-MI) was 3.1 versus 5.7% (p = .0005). The rate of stent thrombosis was similar in both groups (0.004%). By regression analysis, an independent stent effect in favor of BP-SES was observed for TLF (p = .0043) and TV-MI (p = .0364) in small vessels.

Conclusion: Results of this IPD analysis suggest that the BP-SES with ultrathin struts is as safe as and more efficacious than DP-EES in the overall cohort and especially in small vessels.
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http://dx.doi.org/10.1002/ccd.29254DOI Listing
September 2020

Determinants of Plasmodium falciparum multiplicity of infection and genetic diversity in Burkina Faso.

Parasit Vectors 2020 Aug 20;13(1):427. Epub 2020 Aug 20.

Institut de Recherche en Sciences de la Santé/Clinical Research Unit of Nanoro (IRSS-URCN), Nanoro, Burkina Faso.

Background: Investigating malaria transmission dynamics is essential to inform policy decision making. Whether multiplicity of infection (MOI) dynamic from individual infections could be a reliable malaria metric in high transmission settings with marked variation in seasons of malaria transmission has been poorly assessed. This study aimed at investigating factors driving Plasmodium falciparum MOI and genetic diversity in a hyperendemic area of Burkina Faso.

Methods: Blood samples collected from a pharmacovigilance trial were used for polymerase chain reaction genotyping of the merozoite surface proteins 1 and 2. MOI was defined as the number of distinct parasite genotypes co-existing within a particular infection. Monthly rainfall data were obtained from satellite data of the Global Precipitation Measurement Database while monthly malaria incidence aggregated data were extracted from District Health Information Software 2 medical data of the Center-West health regional direction.

Results: In the study area, infected people harboured an average of 2.732 (± 0.056) different parasite genotypes. A significant correlation between the monthly MOI and the monthly malaria incidence was observed, suggesting that MOI could be a good predictor of transmission intensity. A strong effect of season on MOI was observed, with infected patients harbouring higher number of parasite genotypes during the rainy season as compared to the dry season. There was a negative relationship between MOI and host age. In addition, MOI decreased with increasing parasite densities, suggesting that there was a within-host competition among co-infecting genetically distinct P. falciparum variants. Each allelic family of the msp1 and msp2 genes was present all year round with no significant monthly fluctuation.

Conclusions: In high malaria endemic settings with marked variation in seasons of malaria transmission, MOI represents an appropriate malaria metric which provides useful information about the longitudinal changes in malaria transmission in a given area. Besides transmission season, patient age and parasite density are important factors to consider for better understanding of variations in MOI. All allelic families of msp1 and msp2 genes were found in both dry and rainy season. The approach offers the opportunity of translating genotyping data into relevant epidemiological information for malaria control.
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http://dx.doi.org/10.1186/s13071-020-04302-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7441709PMC
August 2020

Impact of diabetes mellitus on female subjects undergoing transcatheter aortic valve implantation: Insights from the WIN-TAVI international registry.

Int J Cardiol 2021 Jan 16;322:65-69. Epub 2020 Aug 16.

San Raffaele Scientific Institute, Milan, Italy.

Background: Female subjects constitute half of all transcatheter aortic valve implantation (TAVI) candidates, but the association between important comorbidities such as diabetes mellitus (DM) and clinical outcomes after TAVI remains unclear in this group.

Method: WIN-TAVI is a real-world international registry of exclusively female subjects undergoing TAVI. The study population was stratified into those with (DM) and those without DM (NDM). Valve Academic Research Consortium (VARC)-2 efficacy (composite of all-cause death, stroke, myocardial infarction, hospitalization for valve-related symptoms or worsening congestive heart failure, or valve-related dysfunction) was the primary endpoint for this analysis.

Results: Of the 1012 subjects included in this study, 264 (26.1%) had DM at baseline. DM patients were younger but had a higher burden of comorbidities. There were no differences in VARC-2 efficacy events between DM and NDM patients at 30 days or 1 year. Conversely, patients with DM had a lower risk of VARC-2 life threatening bleeding at 30 days and 1 year after TAVI compared to NDM patients, which remained significant even after multivariable adjustment (HR, 0.34, 95% CI, 0.12-0.99; p = .047). In the subgroup analysis, insulin-dependent DM was not associated with an increased risk of adverse outcomes.

Conclusions: Among female patients undergoing TAVI, more than one-fourth of the subjects presented with DM. At 1-year follow-up, DM was associated with lower bleeding complications and no increase in the risk of other adverse events, including mortality, after TAVI.
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http://dx.doi.org/10.1016/j.ijcard.2020.08.035DOI Listing
January 2021

Cancer and mosquitoes - An unsuspected close connection.

Sci Total Environ 2020 Nov 30;743:140631. Epub 2020 Jun 30.

MIVEGEC, Univ. Montpellier, CNRS, IRD, Montpellier, France; Centre for Ecological and Evolutionary Research on Cancer (CREEC), Montpellier, France; Centre de Recherche en Écologie et Évolution de la Santé (CREES), Montpellier, France.

Cancer is a major public health issue and represents a significant burden in countries with different levels of economic wealth. In parallel, mosquito-borne infectious diseases represent a growing problem causing significant morbidity and mortality worldwide. Acknowledging that these two concerns are both globally distributed, it is essential to investigate whether they have a reciprocal connection that can fuel their respective burdens. Unfortunately, very few studies have examined the link between these two threats. This review provides an overview of the possible links between mosquitoes, mosquito-borne infectious diseases and cancer. We first focus on the impact of mosquitoes on carcinogenesis in humans including the transmission of oncogenic pathogens through mosquitoes, the immune reactions following mosquito bites, the presence of non-oncogenic mosquito-borne pathogens, and the direct transmission of cancer cells. The second part of this review deals with the direct or indirect consequences of cancer in humans on mosquito behaviour. Thirdly, we discuss the potential impacts that natural cancers in mosquitoes can have on their life history traits and therefore on their vector capacity. Finally, we discuss the most promising research avenues on this topic and the integrative public health strategies that could be envisioned in this context.
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http://dx.doi.org/10.1016/j.scitotenv.2020.140631DOI Listing
November 2020

General Anesthesia or Conscious Sedation for Transfemoral Aortic Valve Replacement with the SAPIEN 3 Transcatheter Heart Valve.

Int Heart J 2020 Jul 18;61(4):713-719. Epub 2020 Jul 18.

University Heart Center.

Differences in the benefits of conscious sedation (CS) and general anesthesia (GA) during transfemoral aortic valve implantation (TAVI) are unclear.We aimed to assess differences in procedural and clinical outcomes based on the type of anesthesia received during TAVI.We analyzed SOURCE 3 Registry data for patients who received the SAPIEN 3 valve by type of anesthesia used during TAVI.Of the 1694 TAVI patients, 1027 received CS and 667 received GA. Patients were similar at baseline (81.5 years; Society of Thoracic Surgeons risk score 7.0). Compared with the GA group, the CS group had fewer intra-procedural transesophageal echocardiography (TEE) and post implantation dilatations performed, and less contrast medium was used. The CS group had significantly less kidney injury at 7 days post-procedure than the GA group (0.4% versus 1.5%, P = 0.014). Moderate paravalvular leaks (PVL) occurred more frequently in the CS group versus the GA group (2.2% versus 0.8%; P = 0.041). No severe PVL were reported. Median total hospital length of stay (LOS) after TAVI was 10 days in the CS group and 11 days in the GS group. At 30 days, all-cause death was 2.1% in CS and 1.7% in GS (P = 0.47), and myocardial infarction was 0.2% in CS and 0.1% in GS (P = 0.83).Our analyses found no significant major outcome differences between CS and GA during TAVI.
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http://dx.doi.org/10.1536/ihj.19-567DOI Listing
July 2020

High Plasmodium infection intensity in naturally infected malaria vectors in Africa.

Int J Parasitol 2020 10 15;50(12):985-996. Epub 2020 Jul 15.

Unité MIVEGEC, IRD 224-CNRS 5290-Université Montpellier, Montpellier, France.

The population dynamics of human to mosquito malaria transmission in the field has important implications for the genetics, epidemiology and control of malaria. The number of oocysts in oocyst-positive mosquitoes developing from a single, naturally acquired infectious blood meal (herein referred to as a single-feed infection load) greatly influences the efficacy of transmission blocking interventions but still remains poorly documented. During a year-long analysis of malaria parasite transmission in Burkina Faso we caught and dissected wild malaria vectors to assess Plasmodium oocyst prevalence and load (the number of oocysts counted in mosquitoes with detectable oocysts) and the prevalence of salivary gland sporozoites. This was compared with malaria endemicity in the human population, assessed in cross-sectional surveys. Data were analysed using a novel transmission mathematical model to estimate the per bite transmission probability and the average single-feed infection load for each location. The observed oocyst load and the estimated single-feed infection load in naturally infected mosquitoes were substantially higher than previous estimates (means ranging from 3.2 to 24.5 according to seasons and locations) and indicate a strong positive association between the single-feed infection load and parasite prevalence in humans. This work suggests that highly infected mosquitoes are not rare in the field and might have a greater influence on the epidemiology and genetics of the parasite, and on the efficacy of novel transmission blocking interventions.
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http://dx.doi.org/10.1016/j.ijpara.2020.05.012DOI Listing
October 2020

European Bifurcation Club white paper on stenting techniques for patients with bifurcated coronary artery lesions.

Catheter Cardiovasc Interv 2020 11 24;96(5):1067-1079. Epub 2020 Jun 24.

Medical Faculty, Department of Cardiology, Clinical Center of Serbia, University of Belgrade, Belgrade, Serbia.

Background: Defining the optimal conduction of percutaneous-coronary-intervention (PCI) to treat bifurcation lesions has been the subject of many clinical studies showing that the applied stenting technique may influence clinical outcome. Accordingly, bifurcation stenting classifications and technical sequences should be standardized to allow proper reporting and comparison.

Methods: The European Bifurcation Club (EBC) is a multidisciplinary group dedicated to optimize the treatment of bifurcations and previously created a classification of bifurcation stenting techniques that is based on the first stent implantation site. Since some techniques have been abandoned, others have been refined and dedicated devices became available, EBC promoted an international task force aimed at updating the classification of bifurcation stenting techniques as well as at highlighting the best practices for most popular techniques. Original descriptive images obtained by drawings, bench tests and micro-computed-tomographic reconstructions have been created in order to serve as tutorials in both procedure reporting and clinical practice.

Results: An updated Main-Across-Distal-Side (MADS)-2, classification of bifurcation stenting techniques has been realized and is reported in the present article allowing standardized procedure reporting in both clinical practice and scientific studies. The EBC-promoted task force deeply discussed, agreed on and described (using original drawings and bench tests) the optimal steps for the following major bifurcation stenting techniques: (a) 1-stent techniques ("provisional" and "inverted provisional") and (b) 2-stent techniques ("T/TAP," "culotte," and "DK-crush").

Conclusions: The present EBC-promoted paper is intended to facilitate technique selection, reporting and performance for PCI on bifurcated lesions during daily clinical practice.
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http://dx.doi.org/10.1002/ccd.29071DOI Listing
November 2020

Different distribution of malaria parasite in left and right extremities of vertebrate hosts translates into differences in parasite transmission.

Sci Rep 2020 06 23;10(1):10183. Epub 2020 Jun 23.

Department of Ecology and Evolution, CH-1015, Lausanne, Switzerland.

Malaria, a vector-borne disease caused by Plasmodium spp., remains a major global cause of mortality. Optimization of disease control strategies requires a thorough understanding of the processes underlying parasite transmission. While the number of transmissible stages (gametocytes) of Plasmodium in blood is frequently used as an indicator of host-to-mosquito transmission potential, this relationship is not always clear. Significant effort has been made in developing molecular tools that improve gametocyte density estimation and therefore prediction of mosquito infection rates. However a significant level of uncertainty around estimates remains. The weakness in the relationship between gametocyte burden, measured from a blood sample, and the mosquito infection rate could be explained by a non-homogeneous distribution of gametocytes in the bloodstream. The estimated gametocyte density would then only be a single snapshot that does not reflect the host infectivity. This aspect of Plasmodium infection, however, remains largely neglected. In both humans and birds, we found here that the gametocyte densities differed depending on which side of the body the sample was taken, suggesting that gametocytes are not homogeneously distributed within the vertebrate host. We observed a fluctuating asymmetry, in other words, the extremity of the body with the highest density of parasites is not always the same from one individual to another. An estimation of gametocyte density from only one blood sample, as is commonly measured, could, therefore, over- or underestimated the infectivity of gametocyte carriers. This might have important consequences on the epidemiology of the disease since we show that this variation influences host-to-mosquito transmission. Vectors fed on the least infected body part had a lower parasite burden than those fed on the most infected part. The heterogeneous distribution of gametocytes in bloodstream should be considered to improve diagnosis and test new malaria control strategies.
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http://dx.doi.org/10.1038/s41598-020-67180-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311528PMC
June 2020

Effect of irradiation on the survival and susceptibility of female Anopheles arabiensis to natural isolates of Plasmodium falciparum.

Parasit Vectors 2020 May 20;13(1):266. Epub 2020 May 20.

Institut de Recherche en Sciences de la Santé, Bobo-Dioulasso, Burkina Faso.

Background: The sterile insect technique (SIT) is a vector control strategy relying on the mass release of sterile males into wild vector populations. Current sex separation techniques are not fully efficient and could lead to the release of a small proportion of females. It is therefore important to evaluate the effect of irradiation on the ability of released females to transmit pathogens. This study aimed to assess the effect of irradiation on the survival and competence of Anopheles arabiensis females for Plasmodium falciparum in laboratory conditions.

Methods: Pupae were irradiated at 95 Gy of gamma-rays, and emerging females were challenged with one of 14 natural isolates of P. falciparum. Seven days post-blood meal (dpbm), irradiated and unirradiated-control females were dissected to assess the presence of oocysts, using 8 parasite isolates. On 14 dpbm, sporozoite dissemination in the head/thorax was also examined, using 10 parasites isolates including 4 in common with the 7 dpbm dissection (oocyst data). The survivorship of irradiated and unirradiated-control mosquitoes was monitored.

Results: Overall, irradiation reduced the proportion of mosquitoes infected with the oocyst stages by 17% but this effect was highly inconsistent among parasite isolates. Secondly, there was no significant effect of irradiation on the number of developing oocysts. Thirdly, there was no significant difference in both the sporozoite infection rate and load between the irradiated and unirradiated-control mosquitoes. Fourthly, irradiation had varying effects on female survival with either a negative effect or no effect.

Conclusions: The effect of irradiation on mosquito competence strongly varied among parasite isolates. Because of such isolate variability and, the fact that different parasite isolates were used to collect oocyst and sporozoite data, the irradiation-mediated reduction of oocyst prevalence was not confirmed for the sporozoite stages. Our data indicate that irradiated female An. arabiensis could contribute to malaria transmission, and highlight the need for perfect sexing tools, which would prevent the release of females as part of SIT programmes.
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http://dx.doi.org/10.1186/s13071-020-04135-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238563PMC
May 2020

Evaluation of length of stay after transfemoral transcatheter aortic valve implantation with SAPIEN 3 prosthesis: A French multicentre prospective observational trial.

Arch Cardiovasc Dis 2020 Jun - Jul;113(6-7):391-400. Epub 2020 May 14.

Normandie University, UNIROUEN, INSERM U1096, Department of Cardiology, Rouen University Hospital, FHU REMOD-VHF, 76000 Rouen, France.

Background: Complications decrease after transfemoral transcatheter aortic valve implantation (TAVI), and early discharge is feasible and safe in selected populations.

Aims: To evaluate length of stay (LOS) and reasons for prolonged hospitalisation after transfemoral TAVI in unselected patients.

Methods: Patients with severe aortic stenosis, who had transfemoral TAVI with the SAPIEN 3 prosthesis using exclusively local anaesthesia, were prospectively and consecutively included at five French high-volume centres. LOS was calculated from TAVI procedure to discharge. Reasons for prolonged hospitalisation (i.e.>3 days) were evaluated.

Results: Between 2017 and 2018, 293 patients were included, with a mean age of 82.4±6.5 years and a mean logistic EuroSCORE of 13.7±9.0%. The in-hospital mortality rate was 1.4%. The median LOS was 5 (3-7) days, and varied considerably between centres (from 2 to 7 days). Sixty-four (21.8%) patients were discharged within 3 days after transfemoral TAVI. Reported reasons for prolonged hospitalisation were complications in 62.2%, loss of autonomy in 3.1%, discharge refusal in 2.2% and logistical reasons in 0.9%. In 31.6% of cases, the investigators reported no apparent reasons.

Conclusions: The results of our study suggest that LOS after transfemoral TAVI, using the SAPIEN 3 prosthesis and a minimalist approach, varies considerably between centres. In almost a third of cases, hospitalisation was prolonged without any apparent reason. Efforts should be made to educate centres to reduce LOS.
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http://dx.doi.org/10.1016/j.acvd.2019.11.010DOI Listing
September 2020

Frailty and Bleeding in Older Adults Undergoing TAVR or SAVR: Insights From the FRAILTY-AVR Study.

JACC Cardiovasc Interv 2020 05;13(9):1058-1068

Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada; Centre for Clinical Epidemiology, Jewish General Hospital, Lady Davis Institute for Medical Research, Montreal, Quebec, Canada; Division of Cardiology, Jewish General Hospital, McGill University, Montreal, Quebec, Canada. Electronic address:

Objectives: The aim of this study was to examine the value of frailty to predict in-hospital major bleeding and determine its impact on mid-term mortality following transcatheter (TAVR) or surgical (SAVR) aortic valve replacement.

Background: Bleeding complications are harbingers of mortality and major morbidity in patients undergoing TAVR or SAVR. Despite the high prevalence of frailty in this population, little is known about its effects on bleeding risk.

Methods: A post hoc analysis was performed of the multinational FRAILTY-AVR (Frailty Aortic Valve Replacement) cohort study, which prospectively enrolled older adults ≥70 years of age undergoing TAVR or SAVR. Trained researchers assessed frailty using a questionnaire and physical performance battery pre-procedure and ascertained clinical data from the electronic health record. The primary endpoint was major or life-threatening bleeding during the index hospitalization, and the secondary endpoint was units of packed red blood cells transfused.

Results: The cohort consisted of 1,195 patients with a mean age of 81.3 ± 6.0 years. The incidence of life-threatening bleeding, major bleeding with a clinically apparent source, and major bleeding without a clinically apparent source was, respectively, 3%, 6%, and 9% in the TAVR group and 8%, 10%, and 31% in the SAVR group. Frailty measured using the Essential Frailty Toolset was an independent predictor of major bleeding and packed red blood cell transfusions in both groups. Major bleeding was associated with a 3-fold increase in 1-year mortality following TAVR (odds ratio: 3.40; 95% confidence interval: 2.22 to 5.21) and SAVR (odds ratio: 2.79; 95% confidence interval: 1.25 to 6.21).

Conclusions: Frailty is associated with post-procedural major bleeding in older adults undergoing TAVR and SAVR, which is in turn associated with a higher risk for mid-term mortality.
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http://dx.doi.org/10.1016/j.jcin.2020.01.238DOI Listing
May 2020

Analysis of length of stay after transfemoral transcatheter aortic valve replacement: results from the FRANCE TAVI registry.

Clin Res Cardiol 2021 Jan 25;110(1):40-49. Epub 2020 Apr 25.

Department of Cardiology, Rouen University Hospital, Normandie Univ, UNIROUEN, INSERM U1096, FHU REMOD-VHF, 76000, Rouen, France.

Background: Currently, there are no recommendations regarding the minimum duration of in-hospital monitoring after transfemoral (TF) transcatheter aortic valve replacement (TAVR) and practices are extremely heterogeneous. We, therefore, aimed to evaluate length of stay (LOS) and predictive factors for late discharge after TF TAVR using data from the FRANCE TAVI registry.

Methods: TAVR was performed in 12,804 patients in 48 French centers between 2013 and 2015. LOS was evaluated in 5857 TF patients discharged home. LOS was calculated from TAVR procedure (day 0) to discharge. The study population was divided into three groups based on LOS values. Patients discharged within 3 days constituted the "very early" discharge group, patients with a LOS between 3 and 6 days constituted the "early" discharge group, and patients with a length of stay > 6 days constituted the "late" discharge group.

Results: The median LOS was 7 (5-9) days and was extremely variable among centers. The proportion of patients discharged very early, early, and late was 4.4% (n = 256), 33.7% (n = 1997), and 61.9% (n = 3624) respectively. Variables associated with late discharge were female sex, co-morbidities, major complications, self-expandable valve, general anesthesia, and a significant center effect. In contrast, history of previous pacemaker was a protective factor. The composite of death and re-admission in the very early and early versus late discharge groups was similar at 30 days (3.3% vs. 3.5%, p = 0.66).

Conclusions: LOS is extremely variable after TF TAVR in France. Co-morbidities and complications were predictive factors of late discharge after TAVI. Interestingly, the use of self-expandable prosthesis and general anesthesia may also contribute to late discharge. Our results confirm that early discharge is safe.
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http://dx.doi.org/10.1007/s00392-020-01647-4DOI Listing
January 2021