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Aims Recent insights have emphasized the importance of myocardial and systemic inflammation in Takotsubo syndrome (TTS). In a large registry of unselected patients, we sought to evaluate whether residual high inflammatory response (RHIR) could impact cardiovascular outcome after TTS. Methods and results Patients with TTS were retrospectively included between 2008 and 2018 in three general hospitals. Three hundred eighty‐five patients with TTS were split into three subgroups, according to tertiles of C‐reactive protein (CRP) levels at discharge (CRP 19 mg/L). The primary endpoint was the impact of RHIR, defined as CRP >19 mg/L at discharge, on cardiac death or hospitalization for heart failure. Follow up was obtained in 382 patients (99%) after a median of 747 days. RHIR patients were more likely to have a history of cancer or a physical trigger. Left ventricular ejection fraction (LVEF) at admission and at discharge were comparable between groups. By contrast, RHIR was associated with lower LVEF at follow up (61.7% vs. 60.7% vs. 57.9%; P = 0.004) and increased cardiac late mortality (0% vs. 0% vs. 10%; P = 0.001). By multivariate Cox regression analysis, RHIR was an independent predictor of cardiac death or hospitalization for heart failure (hazard ratio: 1.87; 95% confidence interval: 1.08 to 3.25; P = 0.025). Conclusions Residual high inflammatory response was associated with impaired LVEF at follow up and was evidenced as an independent factor of cardiovascular events. All together, these findings underline RHIR patients as a high‐risk subgroup, to target in future clinical trials with specific therapies to attenuate RHIR.

PURPOSE OF THE STUDY Evaluation of the success rate of revision ACL reconstruction using the cadaverous BTB allogeneic graft and comparison of the outcomes achieved with the data of patients after the primary ACL reconstruction using the autologous BTB graft with filtering out the potential effect of diversity of the groups of patients as concerns sex and age. MATERIAL AND METHODS The evaluated outcomes of 34 patients operated in the period 2004-2017, i.e. with the minimum follow-up period of three years, were compared with the outcomes of 34 patients selected individually so that in pairs the age and sex are identical - 10 women and 24 men in the range of age from 20 to 44 years, with the median of 29 years at the time of surgery. The assessment and comparison of the outcomes achieved are done according to the Lysholm and Tegner scores. RESULTS The mean Lysholm score of the patients after the revision ACL reconstruction using the cadaverous BTB allograft achieved 54.7 points preoperatively, 72.3 points at the 1-year follow-up and 77.4 points at the 3-year follow-up. The Tegner score at the time of full performance before the injury was 7.7 points, whereas it was 5.8 points after the injury and 6.5 points three years after the surgery. In the group of patients after the primary ACL reconstruction using the autologous BTB graft, the Lysholm score was 64.4 points preoperatively, 85.1 points one year postoperatively and 88.2 points three years postoperatively. The results according to the Tegner score achieved by the primary control group at respective follow-up periods were 6.7 points, 5.1 points and 6.2 points respectively. DISCUSSION The increase in the number of performed ACL reconstructions leads also to an increase in the number of revision surgeries. This trend is also fuelled by the change in the lifestyle, the shift in age-related indication criteria for surgery, and other factors. The realistic expectations regarding the outcome of the revision ACL reconstruction shall take into account the effect of multiple insults that the knee must withstand. Even though subjective improvement of the knee condition is usually experienced postoperatively, the achieved outcomes tend to be less positive than in primary reconstructions. The return to the original pre-injury level of sports activities is achieved less frequently after revision surgeries. CONCLUSIONS The revision surgery of ACL rupture using the cadaverous BTB graft is a safe and reliable technique. It has a potential to improve the subjective satisfaction of the patient, nonetheless the mean postoperative Lysholm score is not so high as that achieved in patients after primary ACL reconstruction. Key words: anterior cruciate ligament, revision ACL reconstruction, cadaverous BTB graft, ACL graft rerupture.

Introduction Patients with atrial fibrillation (AF) are likely to have multiple co-morbidities and receive anticoagulants after TAVR, which lead to a poor prognosis including bleeding events. Closure time adenosine diphosphate (CT-ADP) is a primary hemostasis point-of-care test used as a surrogate marker of high molecular weight (HMW) multimers defect of Von Willebrand factor (VWF). Our prior studies suggest that prolongation of CT-ADP (>180 seconds) after TAVR is a major determinant of early and late major/life-threatening bleeding complications (MLBCs). Purpose To evaluate the impact of post-procedural CT-ADP >180sec on bleeding events in AF patients. Methods We included 878 patients from our prospective TAVR registry between 2010 and 2019. Bleeding complications were assessed according to the VARC-2 (Valve Academic Research Consortium-2) criteria. Major adverse cardiac and cerebrovascular events (MACCE) was defined as a composite of all-cause death, myocardial infarction, stroke, and heart failure hospitalization within 1-year after TAVR. Ongoing primary haemostasis disorder was defined by post-procedure CT-ADP >180sec. Primary endpoint was the occurrence of MLBCs during the first year and the second endpoint was 1-year MACCE. Results Patients with AF had a higher incidence of all-cause mortality (15% vs. 8%, p=0.002), MACCE (29% vs. 20%, p=0.002), and MLBCs (20% vs. 12%, p=0.001) within 1-year compared to non-AF patients. When the cohort was split into 4 subgroups according to AF and CT-ADP >180sec, patients with AF and CT-ADP >180sec had the highest risk of MLBCs (log-rank test; p180sec had 4.6-fold higher risk of MLBCs within 1 year compared to non-AF patients with CT-ADP ≤180sec (hazard ratio: 4.60; 95% confidence interval: 2.18 - 9.68; p Conclusion Among TAVR patients, AF with post-procedural CT-ADP >180 sec was identified as a strong independent predictor of MLBCs at 1-year follow-up. Our study suggest that persistent primary haemostasis disorders contribute to a higher risk of bleeding events particularly in AF patients and may be considered for a tailored and risk-adjusted antithrombotic therapy after TAVR. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Dr Matsushita received a grant from Edwards Lifesciences.

BACKGROUND Although there is an apparent rapid and spontaneous recovery of left ventricular ejection fraction (LVEF) in patients with Takotsubo syndrome (TTS), recent studies have demonstrated a long-lasting functional impairment in those patients. The present study sought to evaluate the predictors of incomplete recovery following TTS and its impact on cardiovascular mortality.Methods and Results:Patients with TTS between 2008 and 2018 were retrospectively enrolled at 3 different institutions. After exclusion of in-hospital deaths, 407 patients were split into 2 subgroups according to whether their LVEF was >50% (recovery group; n=341), or ≤50% (incomplete recovery group; n=66) at the chronic phase. Multivariate logistic regression analysis found that LVEF (odds ratio [OR]: 0.94; 95% confidence interval [CI]: 0.91-0.98; P

The Pacific coastal temperate rainforest (PCTR) is a global hot-spot for carbon cycling and export. Yet the influence of microorganisms on carbon cycling processes in PCTR soil is poorly characterized. We developed and tested a conceptual model of seasonal microbial carbon cycling in PCTR soil through integration of geochemistry, micro-meteorology, and eukaryotic and prokaryotic ribosomal amplicon (rRNA) sequencing from 216 soil DNA and RNA libraries. Soil moisture and pH increased during the wet season, with significant correlation to net CO2 flux in peat bog and net CH4 flux in bog forest soil. Fungal succession in these sites was characterized by the apparent turnover of Archaeorhizomycetes phylotypes accounting for 41% of ITS libraries. Anaerobic prokaryotes, including Syntrophobacteraceae and Methanomicrobia increased in rRNA libraries during the wet season. Putatively active populations of these phylotypes and their biogeochemical marker genes for sulfate and CH4 cycling, respectively, were positively correlated following rRNA and metatranscriptomic network analysis. The latter phylotype was positively correlated to CH4 fluxes (r = 0.46, p

Background Electrocardiographic strain pattern (ESP) has recently been associated with increased adverse outcome in aortic stenosis and after surgical aortic valve replacement. Our study sought to determine the impact and incremental value of ESP pattern in predicting adverse outcome after transcatheter aortic valve replacement. Methods and Results A total of 585 patients with severe aortic stenosis (mean age, 83±7 years; men, 39.8%) were enrolled for transcatheter aortic valve replacement from November 2012 to May 2018. ESP was defined as ≥1‐mm concave down‐sloping ST‐segment depression and asymmetrical T‐wave inversion in the lateral leads. The primary end points of the study were all‐cause mortality, rehospitalization for heart failure, myocardial infarction, and stroke. A total of 178 (30.4%) patients were excluded because of left bundle‐branch block (n=103) or right bundle‐branch block (n=75). Among the 407 remaining patients, 106 had ESP (26.04%). At a median follow‐up of 20.00 months (11.70–29.42 months), no impact of electric strain on overall and cardiac death could be established. By contrast, incidence of rehospitalization for heart failure was significantly higher (33/106 [31.1%] versus 33/301 [11%]; P P Conclusions In patients with aortic stenosis who were eligible for transcatheter aortic valve replacement, ESP is frequent and associated with an increased risk of postinterventional heart failure regardless of preoperative left ventricular hypertrophy. ESP represents an easy, objective, reliable, and low‐cost tool to identify patients who may benefit from intensified postinterventional follow‐up.

Background Coronary artery disease (CAD) has been recognized as a major determinant of Covid-19 vulnerability and severity. We sought to compare demographic characteristics, clinical presentation, and outcomes for Covid-19 in a large cohort of chronic CAD patients living in Strasbourg's cluster region ( Fig. 1 ). Methods Follow-up was conducted by telephone interviews performed by cardiologists one month after the start of the French lockdown. The primary outcome was the composite of death or hospitalization related to Covid-19 infection. Secondary endpoints included Covid-19 related death, Covid-19 related hospitalization, intensive care unit (ICU) admission, allcause mortality, cardiovascular (CV) mortality and healthcare compliance. Results Out of 891 patients included, twenty CAD patients (2.2%) had RT-PCR confirmed Covid-19 infection. Confirmed or suspect cases were evidenced in 48 patients (5.4%). Covid-19 patients showed lower left ventricular ejection fraction, were more frequently obese, less likely to smoke or follow lipid lowering therapy. The composite of death or hospitalization related to Covid-19 was 90%. Mortality rate was 30% among confirmed Covid-19 patients. Drugs’ discontinuation rate was low (1.1%) during the confinement. Reticence to consult a healthcare professional occurred in 6.4%. Postponement or cancellation of non-essential medical visits occurred in 15,7% ( Table 1 ). Conclusions Coronary patients from a large French cluster of COVID-19 showed a high risk of Covid-19 infection and worse in-hospital outcomes.

Background Acute kidney injury (AKI) is associated with a dismal prognosis in Transcatheter Aortic Valve replacement (TAVR). Acute kidney recovery (AKR), a phenomenon reverse to AKI has recently been associated with better outcomes. Methods Between November 2012 to May 2018, we explored consecutive patients referred to our Heart Valve Center for TAVR. AKI was defined according to the VARC-2 definition. Mirroring the VARC-2 definition of AKI, AKR was defined as a decrease in serum creatinine (≥50%) or ≥25% improvement in GFR up to 72 hours after TAVR. Results AKI and AKR were respectively observed in 8.3 and 15.7% of the 574 patients included. AKI and AKR patients were associated to more advanced kidney disease at baseline. At a median follow-up of 608 days (range 355–893), AKI and AKR patients experienced an increased cardiovascular mortality compared to unchanged renal function patients (14.6% and 17.8% respectively, vs. 8.1%, CI 95%, pp < 0.001) was the strongest independent factor associated with AKI similarly to baseline creatinine level (HR: 1; 95% CI 1 to 1.1 p < 0.001) for AKR. 72-hours post procedural AKR (HR: 2.26; 95% CI 1.14 to 4.88; p = 0.021) was the strongest independent predictor of CV mortality. Conclusions Both AKR and AKI negatively impact long term clinical outcomes of patients undergoing TAVR.

Introduction Although there is an apparent rapid and spontaneous recovery of left ventricular ejection fraction (LVEF) in patients with takotsubo cardiomyopathy, recent studies have demonstrated the long-lasting functional impairment in those patients. Purpose We sought to evaluate the predictors of incomplete recovery in chronic phase and its impact on cardiovascular mortality after takotsubo cardiomyopathy. Methods Patients with takotsubo cardiomyopathy between 2008 and 2018 were retrospectively enrolled in three different institutions. Takotsubo cardiomyopathy was diagnosed according to the European Society of Cardiology Heart Failure Association criteria. After exclusion of in-hospital deaths, 407 patients were split into 2 subgroups according whether their LVEF were >50% (recovery group; n=333), or ≤50% (incomplete recovery group; n=74) at follow-up. The primary endpoint was the impact of incomplete recovery on cardiovascular mortality. Results Patients with incomplete recovery were more likely to be male, to have dementia, pacemaker, and supraventricular arrhythmia. C-reactive protein (CRP) levels on admission, at peak, and at discharge were significantly higher in patients with incomplete recovery. By multivariate logistic regression analysis, lower EF at discharge (odds ratio [OR]: 0.91; 95% confidence interval [CI]: 0.88 to 0.95; p Conclusions We demonstrate that incomplete recovery after takotsubo cardiomyopathy is characterized by a residual systemic inflammation and an increased cardiac mortality at follow-up. Altogether, our findings underline patients with persistent inflammation as a high-risk subgroup, to target in future clinical trials with specific therapies to attenuate inflammation. Funding Acknowledgement Type of funding source: None

Introduction Current recommendations support short-term dual antiplatelet therapy (DAPT) for patients undergoing transcatheter aortic valve replacement (TAVR) despite no relevant study exploring the extent of platelet inhibition by clopidogrel. Purpose To assess whether P2Y12 inhibition by clopidogrel as evaluated by vasodilator-stimulated phosphoprotein flow cytometry test (VASP-FCT) impacts 1-year clinical outcomes in patients undergoing TAVR. Methods Patients were included in a prospective registry between February 2010 and May 2019. VASP-FCT was assessed 24h after the procedure. Responder to clopidogrel was defined by a platelet reactivity index ≤50%. Results Of 640 patients who underwent TAVR with preprocedural clopidogrel therapy, we enrolled 491 patients for whom VASP data were available. Responders were identified in 22% (n=110) of patients and low responders were 78% (n=381) of patients. Low body mass index, active cancer, and clopidogrel on admission were found to be independent predictors of responder. Mean transaortic pressure gradient was lower in the responder group at 1-month post-TAVR (9.9±4.4 mmHg vs. 11.2±5.8 mmHg, p=0.03) but was similar at 1-year (11.5±6.2 mmHg vs. 11.9±7.4 mmHg, p=0.74). By multivariate Cox regression analysis, patients responding to clopidogrel (hazard ratio [HR]: 2.19; 95% confidence interval [CI]: 1.04 to 3.64; p=0.04), prior PCI (HR: 2.12; 95% CI: 1.07 to 4.37; p=0.03), and mean transaortic pressure gradient at baseline (HR: 0.07; 95% CI: 0.01 to 0.70; p=0.02) were identified as independent predictors of 1-year adverse clinical outcomes, including all-cause death, myocardial infarction, stroke, and heart failure hospitalization. Conclusions Appropriate P2Y12 inhibition by clopidogrel is a major determinant of adverse clinical events after TAVR. In sum, the present data challenges the need of DAPT as a standard therapy during TAVR. Figure 1 Funding Acknowledgement Type of funding source: None

Introduction Paravalvular leakage (PVL) following transcatheter aortic valve replacement (TAVR) is associated with greater mortality. In clinical practice, determining PVL severity after TAVR remains challenging and often requires multiparametric assessment. Purpose This study sought to evaluate the respective value of various modalities of PVL assessments, including transthoracic echocardiography (TTE), cine-angiography, aortic regurgitation index (ARI), and closure time with adenosine diphosphate (CT-ADP), in the prediction of adverse clinical outcomes. Methods We included 1044 patients from our prospective TAVR registry between February 2010 and May 2019. Major adverse cardiac and cerebrovascular events (MACCE) was defined as a composite of all-cause death, myocardial infarction, stroke, and heart failure hospitalization within 1-year. Established cutoff values of ARI (180 sec) were used to assess the presence of PVL after TAVR. Results Moderate to severe PVL occurred in 14.2% and 5.2% of patients as measured by TTE and angiography. The rate of patients with ARI 180 sec were 36.5% and 24.9%, respectively. Among the four modalities, PVL evaluated by angiography predicted poorer clinical outcomes (Log rank test; p=0.001), whereas TTE, ARI 180 sec were not associated with 1-year MACCE. By multivariate Cox regression analysis, moderate to severe PVL by angiography was an independent predictor of 1-year MACCE (hazard ratio: 1.96; 95% confidence interval: 1.22–3.00; p=0.007). Conclusions Paravalvular leakage measured by angiography was evidenced as the most meaningful modality in the prediction of adverse clinical outcomes. Future multicenter studies are warranted to ensure these findings in the current TAVR era. Figure 1 Funding Acknowledgement Type of funding source: None

AIMS: Cardiovascular disease has been recognized as a major determinant of coronavirus disease 2019 (COVID-19) vulnerability and severity. Angiotensin-converting enzyme (ACE) 2 is a functional receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is up-regulated in patients with heart failure. We sought to examine the potential association between reduced left ventricular ejection fraction (LVEF) and the susceptibility to SARS-CoV-2 infection. METHODS AND RESULTS: Of the 1162 patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention between February 2014 and October 2018, we enrolled 889 patients with available clinical follow-up data. Follow-up was conducted by telephone interviews 1 month after the start of the French lockdown which began on 17 March 2020. Patients were divided into two groups according to LVEF 60;40% (reduced LVEF) (n = 91) or ≥40% (moderately reduced + preserved LVEF) (n = 798). The incidence of COVID-19-related hospitalization or death was significantly higher in the reduced LVEF group as compared with the moderately reduced + preserved LVEF group (9% vs. 1%, P 60; 0.001). No association was found between discontinuation of ACE-inhibitor or angiotensin-receptor blockers and COVID-19 test positivity. By multivariate logistic regression analysis, reduced LVEF was an independent predictor of COVID-19 hospitalization or death (odds ratio: 6.91, 95% confidence interval: 2.60 to 18.35, P 60; 0.001). CONCLUSIONS: In a large cohort of patients with previous ACS, reduced LVEF was associated with increased susceptibility to COVID-19. Aggressive COVID-19 testing and therapeutic strategies may be considered for patient with impaired heart function.

15 pages, 5 figures, supplementary material https://doi.org/10.3389/fmicb.2019.02373.-- The datasets generated for this study can be found in NCBI Sequence Read Archive, PRJNA521526 and PRJNA396681. The reference database generated in this study and provided in Supplementary Table S1 has also been deposited in PR2 (Guillou et al., 2013) and it is available at https://github.com/pr2database/pr2database. PR2 will also host future updates of this reference database.-- Corrigendum: Assessing the Diversity and Distribution of Apicomplexans in Host and Free-Living Environments Using High-Throughput Amplicon Data and a Phylogenetically Informed Reference, del Campo J, Heger TJ, Rodríguez-Martínez R, Worden AZ, Richards TA, Massana R and Keeling PJ, Frontiers in Microbiology 11:576322. doi: 10.3389/fmicb.2020.576322, Apicomplexans are a group of microbial eukaryotes that contain some of the most well-studied parasites, including the causing agents of toxoplasmosis and malaria, and emergent diseases like cryptosporidiosis or babesiosis. Decades of research have illuminated the pathogenic mechanisms, molecular biology, and genomics of model apicomplexans, but we know little about their diversity and distribution in natural environments. In this study we analyze the distribution of apicomplexans across a range of both host-associated and free-living environments. Using publicly available small subunit (SSU) rRNA gene databases, high-throughput environmental sequencing (HTES) surveys, and our own generated HTES data, we developed an apicomplexan reference database, which includes the largest apicomplexan SSU rRNA tree available to date and encompasses comprehensive sampling of this group and their closest relatives. This tree allowed us to identify and correct incongruences in the molecular identification of apicomplexan sequences. Analyzing the diversity and distribution of apicomplexans in HTES studies with this curated reference database also showed a widespread, and quantitatively important, presence of apicomplexans across a variety of free-living environments. These data allow us to describe a remarkable molecular diversity of this group compared with our current knowledge, especially when compared with that identified from described apicomplexan species. This is most striking in marine environments, where potentially the most diverse apicomplexans apparently exist, but have not yet been formally recognized. The new database will be useful for microbial ecology and epidemiological studies, and provide valuable reference for medical and veterinary diagnosis especially in cases of emerging, zoonotic, and cryptic infections, This work was funded by a grant from the Canadian Institutes of Health Research (MOP-42517). JC was supported by a grant from the Tula Foundation to the Centre for Microbial Biodiversity and Evolution and the Marie Curie International Outgoing Fellowship FP7-PEOPLE-2012-IOF-331450 CAARL. TH was supported by the Swiss National Science Foundation (SNSF) grant (PA00P3 145374)

Background New-onset conduction abnormalities (CAs) following transcatheter aortic valve replacement (TAVR) are associated with hospital rehospitalization and long-term mortality, but available predictors are sparse. This study sought to determine clinical predictors of new-onset left bundle branch block (LBBB) and new permanent pacemaker (PPM) implantation in patients undergoing TAVR.Methods and Results:We enrolled 290 patients who received SAPIEN 3 (Edwards Lifesciences, Irvine, CA, USA; n=217) or Evolut R (Medtronic, Minneapolis, MN, USA; n=73) from a prospective registry at Nouvel Hopital Civil, Strasbourg, France between September 2014 and February 2018. Of 242 patients without pre-existing LBBB, 114 (47%) experienced new-onset LBBB and/or new PPM implantation. A difference between membranous septal length and implantation depth (∆MSID) was the only predictor of CAs for both types of valves. In the multivariate analysis, PR interval and ∆MSID remained as sole predictors of CAs. The risk for adverse clinical events, including all-cause death, myocardial infarction, stroke, and heart failure hospitalization, was higher for patients with CAs as compared with patients without CAs (hazard ratio: 2.10; 95% confidence interval: 1.26 to 3.57; P=0.004). Conclusions Computed tomography assessment of membranous septal anatomy and implantation depth predicted CAs after TAVR with new-generation valves. Future studies are required to identify whether adjustment of the implantation depth can reduce the risk of CAs and adverse clinical outcomes.

Background Stroke is a major cause of disability after transcatheter aortic valve replacement (TAVR) and stroke prediction models and data are crucially needed. Following TAVR, high molecular weight (HMW) multimers defect of von Willebrand factor (VWF) as assessed by closure time of adenosine diphosphate (CT-ADP) value > 180 seconds is an independent predictor of bleeding events. This study sought to identify predictors of ischemic neurological events in patients who underwent TAVR and the specific impact of HMW multimers defect of VWF. Methods Patients were prospectively enrolled between November 2012 and May 2018 at our institution. The CT-ADP, a point-of-care measure of hemostasis, was assessed the day before and 24 hours after the procedures. The rate of ischemic stroke and transient ischemic attack (TIA) was recorded up to 30 days after the procedures. Results Of 565 TAVR patients, ischemic stroke/TIA was observed in 21 (3.7%) patients within 30 days. Ischemic stroke/TIA was associated with major/life-threatening bleeding complications (MLBCs) (9 [43%] vs. 88 [16%], p = 0.002) and postprocedure CT-ADP > 180 seconds (10 [48%] vs. 116 [21%], p = 0.01). By multivariate analysis, MLBCs (odds ratio [OR]: 3.58; 95% confidence interval [CI]: 1.45–8.84; p = 0.006) and postprocedure CT-ADP > 180 seconds (OR: 3.38; 95% CI: 1.38–8.25; p = 0.008) were evidenced as independent predictors of ischemic stroke/TIA. Conclusion MLBCs and CT-ADP > 180 seconds were identified as predictors for ischemic stroke or TIA. The present study suggests that the defects of HMW multimers of the VWFs may contribute not only to bleeding events but also to thrombotic events.

Background: The impact of coronary artery disease (CAD) and revascularization by percutaneous coronary intervention (PCI) on prognosis in patients undergoing transcatheter aortic valve replacement (TAVR) remain debated. A dismal prognosis in patients undergoing PCI has been associated with elevated baseline SYNTAX score (bSS) and residual SYNTAX score (rSS). The objective was to investigate whether the degree of bSS and rSS impacted ischemic and bleeding events after TAVR. Methods: bSS and rSS were calculated in 311 patients admitted for TAVR. The primary outcome was the occurrence of major adverse cardiac events (MACE), a composite endpoint of myocardial infarction, stroke, cardiovascular death, or rehospitalization for heart failure. The occurrence of late major/life-threatening bleeding complications (MLBCs) and each primary endpoint individually were the secondary endpoints. Results: bSS &gt, 22 was associated with higher occurrence of MACE (p = 0.013). rSS &gt, 8 and bSS &gt, 22 had no impact on overall cardiovascular mortality. rSS &gt, 22 were associated with higher rates of myocardial infarction (p = 0.001 and p = 0.004) and late occurrence of MLBCs. Multivariate analysis showed that bSS &gt, 22 (sHR 2.48) and rSS &gt, 8 (sHR 2.35) remained predictors of MLBCs but not of myocardial infarction. Conclusion: Incomplete coronary revascularization and CAD burden did not impact overall and cardiac mortality but constitute predictors of late MLBCs in TAVR patients.

Environmental sequencing surveys of soils and freshwaters revealed high abundance and diversity of the Rhogostomidae, a group of omnivorous thecate amoebae. This is puzzling since only a few Rhogostomidae species have yet been described and only a handful of reports mention them in field surveys. We investigated the putative cryptic diversity of the Rhogostomidae by a critical re-evaluation of published environmental sequencing data and in-depth ecological and morphological trait analyses. The Rhogostomidae exhibit an amazing diversity of genetically distinct clades that occur in a variety of different environments. We further broadly sampled for Rhogostomidae species, based on these isolates, we describe eleven new species and highlight important morphological traits for species delimitation. The most important environmental drivers that shape the Rhogostomidae community were soil moisture, soil pH, and total plant biomass. The length/width ratio of the theca was a morphological trait related to the colonized habitats, but not the shape and size of the aperture that is often linked to moisture adaption in testate and thecate amoebae.

Acute kidney injury (AKI) following transcatheter aortic valve replacement (TAVR) is associated with a dismal prognosis. Elevated renal resistive index (RRI), through renal Doppler ultrasound (RDU) evaluation, has been associated with AKI development and increased systemic arterial stiffness. Our pilot study aimed to investigate the performance of Doppler based RRI to predict AKI and outcomes in TAVR patients. From May 2018 to May 2019, 100 patients with severe aortic stenosis were prospectively enrolled for TAVR and concomitant RDU evaluation at our institution (Nouvel H&ocirc, pital Civil, Strasbourg University, France). AKI by serum Creatinine (sCr-AKI) was defined according to the VARC-2 definition and AKI by serum Cystatin C (sCyC-AKI) was defined as an sCyC increase of greater than 15% with baseline value. Concomitant RRI measurements as well as renal and systemic hemodynamic parameters were recorded before, one day, and three days after TAVR. It was found that 10% of patients presented with AKIsCr and AKIsCyC. The whole cohort showed higher baseline RRI values (0.76 &plusmn, 0.7) compared to normal known and accepted values. AKIsCyC had significant higher post-procedural RRI one day (Day 1) after TAVR (0.83 &plusmn, 0.1 vs. 0.77 &plusmn, 0.6, CI 95%, p = 0.005). AUC for AKIsCyC was 0.766 and a RRI cut-off value of &ge, 0.795 had the most optimal sensitivity/specificity (80/62%) combination. By univariate Cox analysis, Mehran Risk Score, higher baseline right atrial pressure at baseline &gt, 0.8 RRI values one day after TAVR (HR 6.5 (95% CI 1.3&ndash, 32.9, p = 0.021) but not RRI at baseline were significant predictors of AKIsCyC. Importantly, no significant impact of baseline biological parameters, renal or systemic parameters could be demonstrated. Doppler-based RRI can be helpful for the non-invasive assessment of AKI development after TAVR.

Beta diversity is a key component of biodiversity with implications ranging from species dynamics to ecosystem functioning. However, β-diversity and its drivers have received little attention, especially for micro-eukaryotes which play key roles in soil functioning. We studied the diversity of soil micro-eukaryotes in a Swiss lowland floodplain using high-throughput Illumina sequencing of soil DNA. We determined the temporal vs. spatial patterns of soil micro-eukaryotic α- and β-diversity in six contrasted habitats sampled over one year. We identified the drivers of these patterns among soil conditions and functions and identified indicator taxa of habitats in each season. We found higher spatial than temporal variability and a strong space-time interaction in soil micro-eukaryotic diversity patterns as well as in their edaphic drivers, which contrasts with previous observation of bacterial diversity patterns. Our results show that, although soil micro-eukaryotic diversity indeed varies seasonally, it is correlated most strongly with edaphic variables and vegetation but the strength of correlations with individual drivers varied seasonally. Microbial diversity patterns and their drivers can thus differ quite substantially among seasons and taxa. Despite the dominance of spatial patterns, the temporal component of microbial diversity should not be ignored to accurately estimate the diversity and the complexity of soil microbial community assembly processes. Given the importance of soil microbial diversity for ecosystem functioning such knowledge is relevant for land management.

International audience; The use of synthetic pesticides in agriculture is increasingly debated. However, few studies have compared the impact of synthetic pesticides and alternative biopesticides on non-target soil microorganisms playing a central role in soil functioning.We conducted a mesocosm experiment and used high-throughput amplicon sequencing to test the impact of a fungal biopesticide and a synthetic fungicide on the diversity, the taxonomic and functional compositions, and co-occurrence patterns of soil bacterial, fungal and protist communities.Neither the synthetic pesticide nor the biopesticide had a significant effect on microbial α-diversity. However, both types of pesticides decreased the complexity of the soil microbial network. The two pesticides had contrasting impacts on the composition of microbial communities and the identity of key taxa as revealed by microbial network analyses. The biopesticide impacted keystone taxa that structured the soil microbial network. The synthetic pesticide modified biotic interactions favouring taxa that are less efficient at degrading organic compounds. This suggests that the biopesticides and the synthetic pesticide have different impact on soil functioning.Altogether, our study shows that pest management products may have functionally significant impacts on the soil microbiome even if microbial α-diversity is unaffected. It also illustrates the potential of high-throughput sequencing analyses to improve the ecotoxicological risk assessment of pesticides on non-target soil microorganisms.

Background Electrocardiographic (ECG) strain pattern has recently been associated with increased adverse outcome in aortic stenosis (AS) and after surgical aortic valve replacement (AVR). However, the relation linking ECG strain and cardiovascular MACE in patients with transcatheter aortic valve replacement (TAVR) has not been yet described. Objectives The aim of our study was to determine the impact and incremental value of ECG Strain pattern in predicting adverse outcome after TAVR. Methods 585 patients with severe AS (mean age: 83±7 male 39.8%) were enrolled from November 2012 to May 2018. ECG strain pattern was defined as ≥1 mm concave down-sloping ST-segment depression and asymmetrical T-wave inversion in the lateral leads. Patients with baseline left bundle branch block (LBBB), right bundle branch block (RBBB) or ventricular paced rhythm were excluded. All patients underwent transthoracic echocardiography (TTE) before TAVR and at 30 days follow up. The primary endpoints of the study were the overall all-cause mortality after TAVR, rehospitalization for Hearth failure (HF), myocardial infarction and stroke. Results 178 (30.4%) patients were excluded from analyses owing to the presence of either LBBB (n=103) or RBBB (n=75). Among the 407 remaining patients, 106 had ECG strain pattern (26.04%). Patients with ECG strain were significantly younger (81.6±8 years vs 83.5±6.8 years; p=0.022), had lower BMI (23±4.5 kg.m2 vs 27.9±6.8 kg.m2; p=0.02) more severe AS (mean gradient 52.3±15.2 mmHg vs 47.9±11.8 mmHg; p=0.003), significant lower LVEF (51.8±15% vs 58.4±10.7%; p Conclusion In patients with AS eligible for TAVR, ECG Strain Pattern is frequent and associated with an increased risk of post interventional heart failure regardless of preoperative LVH. ECG Strain pattern represents an easy, objective, reliable and low-cost tool to identify patients who may benefit from an extend and intensified post-interventional follow-up.

Although previous studies, mostly based on microscopy analyses of a few groups of protists, have suggested that protists are abundant and diverse in litter and moss habitats, the overall diversity of moss and litter associated protists remains elusive. Here, high-throughput environmental sequencing was used to characterize the diversity and community structure of litter- and moss-associated protists along a gradient of soil drainage and forest primary productivity in a temperate rainforest in British Columbia. We identified 3262 distinct protist OTUs from 36 sites. Protists were strongly structured along the landscape gradient, with a significant increase in alpha diversity from the blanket bog ecosystem to the zonal forest ecosystem. Among all investigated environmental variables, calcium content was the most strongly associated with the community composition of protists, but substrate composition, plant cover and other edaphic factors were also significantly correlated with these communities. Furthermore, a detailed phylogenetic analysis of unicellular opisthokonts identified OTUs covering most lineages, including novel OTUs branching with Discicristoidea, the sister group of Fungi, and with Filasterea, one of the closest unicellular relatives to animals. Altogether, this study provides unprecedented insight into the community composition of moss- and litter-associated protists.

Photosynthetic picoeukaryotes contribute a significant fraction of primary production in the upper ocean. Micromonas pusilla is an ecologically relevant photosynthetic picoeukaryote, abundantly and widely distributed in marine waters. Grazing by protists may control the abundance of picoeukaryotes such as M. pusilla, but the diversity of the responsible grazers is poorly understood. To identify protists consuming photosynthetic picoeukaryotes in a productive North Pacific Ocean region, we amended seawater with living 15 N, 13 C-labelled M. pusilla cells in a 24-h replicated bottle experiment. DNA stable isotope probing, combined with high-throughput sequencing of V4 hypervariable regions from 18S rRNA gene amplicons (Tag-SIP), identified 19 operational taxonomic units (OTUs) of microbial eukaryotes that consumed M. pusilla. These OTUs were distantly related to cultured taxa within the dinoflagellates, ciliates, stramenopiles (MAST-1C and MAST-3 clades) and Telonema flagellates, thus, far known only from their environmental 18S rRNA gene sequences. Our discovery of eukaryotic prey consumption by MAST cells confirms that their trophic role in marine microbial food webs includes grazing upon picoeukaryotes. Our study provides new experimental evidence directly linking the genetic identity of diverse uncultivated microbial eukaryotes to the consumption of picoeukaryotic phytoplankton in the upper ocean.

Background Dual antiplatelet therapy (DAPT) has been proposed to explain the increased occurrence of major bleeding events after transcatheter aortic valve replacement (TAVR) despite no relevant study exploring the extent of platelet inhibition by clopidogrel. Purpose To assess whether P2Y12 inhibition by clopidogrel as evaluated by vasodilator-stimulated phosphoprotein (VASP) flow cytometry test impacts clinical outcomes in patients undergoing TAVR. Methods Patients were enrolled in a prospective registry at Nouvel Hopital Civil, Strasbourg, France between February 2010 and May 2019. VASP flow cytometry test was assessed 24 h after the procedure. Responder to clopidogrel was defined by a platelet reactivity index ≤ 50%. The primary endpoint was 90-day major adverse cardiac and cerebrovascular events (MACCE), including all-cause death, myocardial infarction, stroke, and heart failure hospitalization. The secondary endpoint was 1-year MACCE. Results Of the 828 patients with available VASP monitoring, we enrolled 491 TAVR patients with preprocedural clopidogrel therapy. Responders were identified in 22% (n = 110) and low responders in 78% (n = 381) of patients. By multivariate Cox regression analysis, patients responding to clopidogrel (hazard ratio [HR]: 2.16; 95% confidence interval [CI]: 1.16 to 3.91: P = 0.02) and previous PCI (HR: 2.24; 95% CI: 1.07 to 4.81; P = 0.03) were identified as independent predictors of 90-day MACCE. The cumulative event-free survival rate at 90-day and 1-year was significantly lower in the responder group ( Fig. 1 ). Conclusions Appropriate P2Y12 inhibition by clopidogrel is a major determinant of 90-day and 1-year post-TAVR adverse clinical events. In sum, the present data challenge DAPT as a standard therapy during TAVR.

Denis,It’s ironic that when facing a problem like this – being asked to write a piece about the way you affected us in the labs we share – our first instinct would be to come and talk to you, to ge...

Background The respective influences of coronary artery disease (CAD) and revascularization by percutaneous coronary intervention (PCI) on prognosis in patients undergoing Transcatheter aortic-valve replacement (TAVR) remain highly controversial. The residual SYNTAX Score (rSS) has been developed to assess the impact of residual CAD after PCI. Both baseline SYNTAX Score (bSS) and rSS have been associated with dismal prognosis in patients undergoing PCI. Objectives To assess whether the degree of bSS and rSS impact ischemic and bleeding events after TAVR. Method Three hundred and eleven patients were admitted for TAVR. Severe CAD was defined by bSS > 22. Incomplete revascularization was defined by rSS > 8. The primary outcome was the occurrence of a composite endpoint of either cardiovascular death, myocardial infarction, stroke or rehospitalization for heart failure (MACE). Secondary endpoints included each primary endpoint individually and the occurrence of late major/life threatening bleeding complications (MLBCs). Results After a median follow-up of 830 days, bSS > 22 was associated with higher occurrence of MACE (P = 0.013). However, bSS > 22 and rSS > 8 had no impact on overall cardiovascular mortality. By contrast, they were associated with higher rates of periprocedural major bleeding (P = 0.002), myocardial infarction (P = 0.001) and late occurrence of MLBCs and transfusion rate (P = 0.005). Results of multivariate analysis showed that bSS > 22 (HR 2.43 95% CI (1.01–5.85); P = 0.048) and rSS > 8 (HR 2.39 95% CI (1.2–4.7); P = 0.013) remained predictors of MLBCs but not of myocardial infarction ( Table 1 , Fig. 1 ). Conclusion In unselected TAVR patients, initial CAD burden and incomplete coronary revascularization did not impact overall and cardiac mortality but constitute reliable predictors of late MLBCs.

Background The impact of antithrombotic regimen and platelet inhibition extent on subclinical leaflet thrombosis (SLT) detected by cardiac multidetector computed tomography (MDCT) after transcatheter aortic-valve replacement (TAVR) is not well established. Hypoattenuation affecting motion (HAM) has been proposed as a surrogate marker of SLT and is characterized by hypoattenuated leaflet thickening (HALT) and concomitant reduction in leaflet motion (RELM). Purpose We sought to investigate (i) the prevalence of HAM and HALT, (ii) the predictors of SLT, (iii) the impact of oral anticoagulant (OAC), platelet inhibition extent and primary haemostasis disorders on SLT. Methods Of 187 consecutive patients who underwent TAVR from August 1st 2017 to March 31th 2018, 90 of them had cardiac CT at relevant follow-up. Clinical, biological, echocardiographic, procedural characteristics and treatments were collected before, at discharge and 1 year after TAVR. P2Y12 platelet inhibition extent and primary haemostasis disorders were investigated using platelet PRI-VASP and CT-ADP point of care assays. Results Eighty five post-TAVR CTs out of 90 were ranked for clarity. HAM was evidenced in 13 patients (15%) and HALT in 30 patients (35%). No impact of P2Y12 inhibition nor primary haemostasis disorders on SLT could be evidenced. No impact of SLT on valve deterioration evaluated by transthorac echocardiography (TTE) and clinical events could be established at 12 months follow-up. By multivariate analysis, lack of oral anticoagulant therapy at discharge (HR 12.130 CI 95% [1.394–150.582]; P = 0.028) and higher haemoglobin levels were evidenced as independent predictors of SLT. In 4 patients with HAM, MDCT follow-up after initiation of OAC therapy showed a complete regression of HAM ( Fig. 1 ). Conclusion SLT was evidenced in a sizeable proportion of patients after TAVR and was mainly determined by the lack of oral anticoagulant therapy. No impact of platelet inhibition extent on SLT could be evidenced.

Background Cardiovascular diseases and cancer are the two leading causes of mortality in the world and their association is a therapeutic challenge. Current data showed that patients with active cancer and severe aortic stenosis have better survival after aortic-valve replacement in comparison with those have medical treatment. Presence of active cancer is frequently a reason to decline surgery due to the fear of periprocedural complications in this frail population and transcatheter aortic-valve replacement (TAVR) appears like the treatment of choice in this situation. However, data concerning outcomes in this case are limited and contradictory. Purpose This study aims to constitute the first French cohort of patients with active cancer undergoing TAVR in order to determine their prevalence, characteristics, perioperative outcomes and mortality. Methods We prospectively included all consecutive patients who underwent TAVR in our institution (Nouvel Hopital Civil, Strasbourg, France). Active cancer status at the time of the procedure was determined by a specialist physician with an anatomopathological diagnosis in all cases where it was possible. Primary endpoint was all-cause mortality during follow-up. Results Among 585 patients who underwent TAVR, 62 had an active cancer. All-cause mortality was significantly higher in patients with active cancer in comparison with those without cancer (38.7% vs. 20.1% respectively; P = 0.001). This excess of mortality is mainly driven by non-cardiovascular causes of death. Other periprocedural complications (major adverse cardiovascular events, bleeding, rehospitalization for heart failure, acute kidney injury) did not differ between the two groups ( Fig. 1 ). Conclusion In patients who underwent TAVR, active cancer is a non-negligible comorbidity. All-cause mortality is higher in this population, mainly driven by non-cardiovascular mortality. However, periprocedural complications are not increased in this specific population.

Dietary amino acids are used for the synthesis of body protein, animal products, and many other nitrogen-or sulfur-containing compounds with important physiological functions. The utilization of dietary amino acids in the course of digestion, absorption, and intermediary metabolism is affected by many internal and external factors, the knowledge of which may be of vital importance for the estimation of amino acid requirements and the formulation of well-balanced diet. The effect of dietary level of amino acids on their utilization is well known. The dominant factor affecting the efficiency of utilization of an amino acid is its proportion in the diet relative to the requirement. The efficiency of utilization of amino acids for growth and maintenance was calculated from the retained amount increased by the maintenance requirements. Studies on amino acid retention and oxidation have shown that the efficiency of utilization is inherent to individual amino acids and may differ even under comparable dietary conditions.

Apicomplexans are a group of microbial eukaryotes that contain some of the most well-studied parasites, including widespread intracellular pathogens of mammals such as Toxoplasma and Plasmodium (the agent of malaria), and emergent pathogens like Cryptosporidium and Babesia. Decades of research have illuminated the pathogenic mechanisms, molecular biology, and genomics of model apicomplexans, but we know surprisingly little about their diversity and distribution in natural environments. In this study we analyze the distribution of apicomplexans across a range of both host-associated and free-living environments, covering animal hosts from cnidarians to mammals, and ecosystems from soils to fresh and marine waters. Using publicly available small subunit (SSU) rRNA gene databases, high-throughput environmental sequencing (HTES) surveys such as Tara Oceans and VAMPS, as well as our own generated HTES data, we developed an apicomplexan reference database, which includes the largest apicomplexan SSU rRNA tree available to date and encompasses comprehensive sampling of this group and their closest relatives. This tree allowed us to identify and correct incongruences in the molecular identification of sequences, particularly within the hematozoans and the gregarines. Analyzing the diversity and distribution of apicomplexans in HTES studies with this curated reference database also showed a widespread, and quantitatively important, presence of apicomplexans across a variety of free-living environments. These data allow us to describe a remarkable molecular diversity of this group compared with our current knowledge, especially when compared with that identified from described apicomplexan species. This revision is most striking in marine environments, where potentially the most diverse apicomplexans apparently exist, but have not yet been formally recognized. The new database will be useful for both microbial ecology and epidemiological studies, and provide valuable reference for medical and veterinary diagnosis especially in cases of emerging, zoonotic, and cryptic infections.

Background and purpose Acute kidney injury (AKI) remains associated with a dismal prognosis in TAVR. Acute kidney recovery (AKR), a phenomenon reverse to AKI has recently been associated with better outcomes. Methods Between November 2012 to May 2018, we explored consecutive patients referred to our Heart Valve Center for TAVR. AKI was defined according to the VARC-2 definition. Mirroring the VARC-2 definition of AKI, AKR was defined as a decrease in serum creatinine (≥ 50%) or ≥ 25% improvement in GFR up to 72 hours after TAVR. Results AKI and AKR were respectively observed in 8.3 and 15.7% of the 574 patients included. AKI and AKR patients were associated to more advanced kidney disease at baseline. At a median follow-up of 608 days (range 355–893), AKI and AKR patients experienced an increased cardiovascular mortality compared to unchanged renal function patients (14.6% and 17.8% respectively, vs. 8.1%, CI 95%, P Fig. 1 ). Conclusions 72-hours post procedural AKR patients are a subgroup of patients at high risk of post TAVR cardiovascular complications

Background Electrocardiographic (ECG) strain pattern (ESP) has recently been associated with increased adverse outcome in aortic stenosis (AS) and after surgical aortic-valve replacement (AVR). However, the relation linking ESP and cardiovascular MACE in patients with transcatheter aortic-valve replacement (TAVR) has not been yet described. Objectives Our study sought to determine the impact and incremental value of ESP pattern in predicting adverse outcome after TAVR. Methods A total of 585 patients with severe AS (mean age: 83 ± 7 years; male 39.8%) were enrolled for TAVR from November 2012 to May 2018. ESP was defined as ≥ 1 mm concave down-sloping ST-segment depression and asymmetrical T-wave inversion in the lateral leads. Patients with baseline left bundle branch block (LBBB), right bundle branch block (RBBB) or ventricular paced rhythm were excluded. The primary endpoints of the study were the overall all-cause mortality after TAVR, rehospitalization for hearth failure (HF), myocardial infarction and stroke. Results 178 (30.4%) patients were excluded owing to LBBB (n = 103) or RBBB (n = 75). Among the 407 remaining patients, 106 had ESP (26.04%). Patients with ESP were younger, had lower BMI and more severe AS and significant lower LVEF. At a median follow-up of 608 days (356–895), no impact of electric strain on overall and cardiac death could be established. By contrast, incidence of rehospitalization for HF was significantly higher (33 (31.1%) vs. 33 (11%); P Conclusion In patients with AS eligible for TAVR, ESP is frequent and associated with an increased risk of post interventional heart failure regardless of preoperative LVH. ESP represents an easy, objective, reliable and low-cost tool to identify patients who may benefit from intensified post-interventional follow-up.

PURPOSE OF THE STUDY Neuromuscular deformities of the spine represent surgically uneasy to solve problems as well as serious handicaps causing sitting instability, pressure ulcers as well as pain. The aim of our study is to conduct a retrospective clinical analysis of the results of surgical correction of these deformities. This paper presents the use of a recent technique of sacral-alar-iliac (S2AI) screws and its comparison with other techniques of pelvic stabilisation. MATERIAL AND METHODS The group of 41 patients treated surgically with S2AI screws technique and transpedicular or hybrid instrumentation of the spine consisted of patients with the primary diagnosis of muscular dysthrophy, spinal muscular atrophy, cerebral palsy and some other neuromuscular diseases. The results of pelvic obliquity correction and scoliotic correction in combined neuromuscular deformities of the spine and pelvis were analysed. The technique of S2AI screws implantation and the possibility of their free-hand technique implementation were presented. RESULTS In the followed-up group of patients an average correction of pelvic obliquity by 81% (from 29.1 degrees before the operation to 5.6 degrees after the operation) was reported. On average, 74% correction of scoliotic spine deformity was achieved (from 83.3 degrees before the operation to 22.5 degrees after the operation). In both the cases neither a significant loss of correction at the minimum one-year follow-up nor any serious complications associated with grappling of pelvic fixation were observed. DISCUSSION The S2AI screws offer at least the same stability and ability of correction as iliac screws and at the same time they provide significantly better results compared with the older methods of pelvic fixation such as the Galvestone technique. With a good knowledge of the surgical technique and anatomical aspects this technique can be applied in the form of a free-hand technique. Navigation as well as robotic techniques can help with the accurate positioning of the S2AI screw. Transfixation of sacroiliacal syndesmosis in patients with a neuromuscular handicap does not lead to deterioration of their mobility. CONCLUSIONS Simultaneous stabilisation of spine and pelvis makes it possible to achieve a good quality correction of the deformity and good clinical results over a long period of time. It allows for stability of the sitting position of the patients and improves the quality of their lives. Nowadays, the S2AI screws are considered to be biomechanically the best quality pelvic fixation, eliminating subcutaneous prominence of the instrumentation and reducing the risk of skin decubitus. Key words:neuromuscular deformity, sacral-alar-iliac screw, pelvic obliquity, stabilization, scoliosis.