Rapid alkalinization factor 22 has a structural and signalling role in root hair cell wall assembly.

Pressurized cells with strong walls make up the hydrostatic skeleton of plants. Assembly and expansion of such stressed walls depend on a family of secreted RAPID ALKALINIZATION FACTOR (RALF) peptides, which bind both a membrane receptor complex and wall-localized LEUCINE-RICH REPEAT EXTENSIN (LRXs) in a mutually exclusive way. Here we show that, in root hairs, the RALF22 peptide has a dual structural and signalling role in cell expansion. Together with LRX1, it directs the compaction of charged pectin polymers at the root hair tip into periodic circumferential rings. Free RALF22 induces the formation of a complex with LORELEI-LIKE-GPI-ANCHORED PROTEIN 1 and FERONIA, triggering adaptive cellular responses. These findings show how a peptide simultaneously functions as a structural component organizing cell wall architecture and as a feedback signalling molecule that regulates this process depending on its interaction partners. This mechanism may also underlie wall assembly and expansion in other plant cell types.

Plant cell wall patterning and expansion mediated by protein-peptide-polysaccharide interaction.

Assembly of cell wall polysaccharides into specific patterns is required for plant growth. A complex of RAPID ALKALINIZATION FACTOR 4 (RALF4) and its cell wall-anchored LEUCINE-RICH REPEAT EXTENSIN 8 (LRX8)-interacting protein is crucial for cell wall integrity during pollen tube growth, but its molecular connection with the cell wall is unknown. Here, we show that LRX8-RALF4 complexes adopt a heterotetrametric configuration in vivo, displaying a dendritic distribution. The LRX8-RALF4 complex specifically interacts with demethylesterified pectins in a charge-dependent manner through RALF4's polycationic surface. The LRX8-RALF4-pectin interaction exerts a condensing effect, patterning the cell wall's polymers into a reticulated network essential for wall integrity and expansion. Our work uncovers a dual structural and signaling role for RALF4 in pollen tube growth and in the assembly of complex extracellular polymers.

Machine learning-based scoring system to predict in-hospital outcomes in patients hospitalized with COVID-19.

BACKGROUND: The evolution of patients hospitalized with coronavirus disease 2019 (COVID-19) is still hard to predict, even after several months of dealing with the pandemic. AIMS: To develop and validate a score to predict outcomes in patients hospitalized with COVID-19. METHODS: All consecutive adults hospitalized for COVID-19 from February to April 2020 were included in a nationwide observational study. Primary composite outcome was transfer to an intensive care unit from an emergency department or conventional ward, or in-hospital death. A score that estimates the risk of experiencing the primary outcome was constructed from a derivation cohort using stacked LASSO (Least Absolute Shrinkage and Selection Operator), and was tested in a validation cohort. RESULTS: Among 2873 patients analysed (57.9% men; 66.6±17.0 years), the primary outcome occurred in 838 (29.2%) patients: 551 (19.2%) were transferred to an intensive care unit; and 287 (10.0%) died in-hospital without transfer to an intensive care unit. Using stacked LASSO, we identified 11 variables independently associated with the primary outcome in multivariable analysis in the derivation cohort (n=2313), including demographics (sex), triage vitals (body temperature, dyspnoea, respiratory rate, fraction of inspired oxygen, blood oxygen saturation) and biological variables (pH, platelets, C-reactive protein, aspartate aminotransferase, estimated glomerular filtration rate). The Critical COVID-19 France (CCF) risk score was then developed, and displayed accurate calibration and discrimination in the derivation cohort, with C-statistics of 0.78 (95% confidence interval 0.75-0.80). The CCF risk score performed significantly better (i.e. higher C-statistics) than the usual critical care risk scores. CONCLUSIONS: The CCF risk score was built using data collected routinely at hospital admission to predict outcomes in patients with COVID-19. This score holds promise to improve early triage of patients and allocation of healthcare resources.

Prevalence of psychoactive drug use in patients hospitalized for acute cardiac events: Rationale and design of the ADDICT-ICCU trial, from the Emergency and Acute Cardiovascular Care Working Group and the National College of Cardiologists in Training of the French Society of Cardiology.

BACKGROUND: Psychoactive drugs, including illicit drugs, are associated with an increased rate of cardiovascular events. The prevalence and outcome of patients using these drugs at the time of admission to an intensive cardiac care unit is unknown. AIM: To assess the prevalence of psychoactive drugs detected in consecutive patients hospitalized in an intensive cardiac care unit for an acute cardiovascular event. METHODS: This is a nationwide prospective multicentre study, involving 39 centres throughout France, including all consecutive patients hospitalized in an intensive cardiac care unit within 2weeks. Psychoactive drug use will be assessed systematically by urine drug assay within 2hours of intensive cardiac care unit admission, to detect illicit (cannabinoids, cocaine, amphetamines, ecstasy, heroin and other opioids) and non-illicit (barbiturates, benzodiazepines, tricyclic antidepressants, methadone and buprenorphine) psychoactive drugs. Smoking will be investigated systematically by exhaled carbon monoxide measurement, and alcohol consumption using a standardized questionnaire. In-hospital major adverse events, including death, resuscitated cardiac arrest and cardiogenic shock, will be recorded. After discharge, all-cause death and major adverse cardiovascular events will be recorded systematically and adjudicated at 12months of follow-up. RESULTS: The primary outcome will be the prevalence of psychoactive drugs detected by systematic screening among all patients hospitalized in an intensive cardiac care unit. The in-hospital major adverse events will be analysed according to the presence or absence of detected psychoactive drugs. Subgroup analysis stratified by initial clinical presentation and type of psychoactive drug will be performed. CONCLUSIONS: This is the first prospective multicentre study to assess the prevalence of psychoactive drugs detected by systematic screening in consecutive patients hospitalized for acute cardiovascular events.

Characteristics and outcomes of patients hospitalized for COVID-19 in France: The Critical COVID-19 France (CCF) study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has led to a public health crisis. Only limited data are available on the characteristics and outcomes of patients hospitalized for COVID-19 in France. AIMS: To investigate the characteristics, cardiovascular complications and outcomes of patients hospitalized for COVID-19 in France. METHODS: The Critical COVID-19 France (CCF) study is a French nationwide study including all consecutive adults with a diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection hospitalized in 24 centres between 26 February and 20 April 2020. Patients admitted directly to intensive care were excluded. Clinical, biological and imaging parameters were systematically collected at hospital admission. The primary outcome was in-hospital death. RESULTS: Of 2878 patients included (mean±SD age 66.6±17.0 years, 57.8% men), 360 (12.5%) died in the hospital setting, of which 7 (20.7%) were transferred to intensive care before death. The majority of patients had at least one (72.6%) or two (41.6%) cardiovascular risk factors, mostly hypertension (50.8%), obesity (30.3%), dyslipidaemia (28.0%) and diabetes (23.7%). In multivariable analysis, older age (hazard ratio [HR] 1.05, 95% confidence interval [CI] 1.03-1.06; P<0.001), male sex (HR 1.69, 95% CI 1.11-2.57; P=0.01), diabetes (HR 1.72, 95% CI 1.12-2.63; P=0.01), chronic kidney failure (HR 1.57, 95% CI 1.02-2.41; P=0.04), elevated troponin (HR 1.66, 95% CI 1.11-2.49; P=0.01), elevated B-type natriuretic peptide or N-terminal pro-B-type natriuretic peptide (HR 1.69, 95% CI 1.0004-2.86; P=0.049) and quick Sequential Organ Failure Assessment score ≥2 (HR 1.71, 95% CI 1.12-2.60; P=0.01) were independently associated with in-hospital death. CONCLUSIONS: In this large nationwide cohort of patients hospitalized for COVID-19 in France, cardiovascular comorbidities and risk factors were associated with a substantial morbi-mortality burden.

History of heart failure in patients with coronavirus disease 2019: Insights from a French registry.

BACKGROUND: Although cardiovascular comorbidities seem to be strongly associated with worse outcomes in patients with coronavirus disease 2019 (COVID-19), data regarding patients with preexisting heart failure are limited. AIMS: To investigate the incidence, characteristics and clinical outcomes of patients with COVID-19 with a history of heart failure with preserved or reduced ejection fraction. METHODS: We performed an observational multicentre study including all patients hospitalized for COVID-19 across 24 centres in France from 26 February to 20 April 2020. The primary endpoint was a composite of in-hospital death or need for orotracheal intubation. RESULTS: Overall, 2809 patients (mean age 66.4±16.9years) were included. Three hundred and seventeen patients (11.2%) had a history of heart failure; among them, 49.2% had heart failure with reduced ejection fraction and 50.8% had heart failure with preserved ejection fraction. COVID-19 severity at admission, defined by a quick sequential organ failure assessment score>1, was similar in patients with versus without a history of heart failure. Before and after adjustment for age, male sex, cardiovascular comorbidities and quick sequential organ failure assessment score, history of heart failure was associated with the primary endpoint (hazard ratio [HR]: 1.41, 95% confidence interval [CI]: 1.06-1.90; P=0.02). This result seemed to be mainly driven by a history of heart failure with preserved ejection fraction (HR: 1.61, 95% CI: 1.13-2.27; P=0.01) rather than heart failure with reduced ejection fraction (HR: 1.19, 95% CI: 0.79-1.81; P=0.41). CONCLUSIONS: History of heart failure in patients with COVID-19 was associated with a higher risk of in-hospital death or orotracheal intubation. These findings suggest that patients with a history of heart failure, particularly heart failure with preserved ejection fraction, should be considered at high risk of clinical deterioration.

Life-threatening and major cardiac events during long-distance races: updates from the prospective RACE PARIS registry with a systematic review and meta-analysis.

AIMS: Limited data exist regarding the incidence and aetiology of life-threatening events such as major cardiac events or exertional heat stroke during long-distance races. We aimed to provide an updated incidence, etiology and prognosis of life-threatening events during long-distance races. METHODS: The prospective RACE PARIS registry recorded all life-threatening events/fatal events occurring during 46 marathons, half-marathons and other long-distance races in the Paris area between 2006 and 2016, comprising 1,073,722 runners. Event characteristics were determined by review of medical records and interviews with survivors. RESULTS: The incidence of life-threatening events, exertional heat stroke and major cardiac events was 3.35 per 100,000, 1.02 per 100,000 and 2.33 per 100,000, respectively, including 18 sudden cardiac arrests (1.67 per 100,000). The main aetiology of sudden cardiac arrest was myocardial ischaemia (11/18), due to acute coronary thrombosis (6/11), stable atherosclerotic coronary artery disease (2/11), coronary dissection (1/11), anomalous connection (1/11) or myocardial bridging (1/11). A third of participants with ischaemia-related major cardiac events presented with pre-race clinical symptoms. Major cardiac events were more frequent in the case of a high pollution index (6.78 per 100,000 vs. 2.07 per 100,000, odds ratio 3.27, 95% confidence interval 1.12-9.54). Case fatality was low (0.19 per 100,000). Similarly, we report in a meta-analysis of eight long-distance race registries comprising 16,223,866 runners a low incidence of long-distance race-related sudden cardiac arrest (0.82 per 100,000) and fatality (0.39 per 100,000). Death following sudden cardiac arrest was strongly associated with initial asystole or pulseless rhythm. CONCLUSION: Long-distance race-related life-threatening events remain rare although serious events. Better information for runners on the risk of pre-race clinical symptoms, outside air pollution and temperature may reduce their incidence.

Predictive factors of success at the French National Ranking Examination (NRE): a retrospective study of the student performance from a French medical school.

BACKGROUND: The national ranking examination (NRE) marks the end of the second cycle (6th university year) of French medical studies and ranks students allowing them to choose their specialty and city of residency. We studied the potential predictive factors of success at the 2015 NRE by students attending a French School of Medicine. METHODS: From March 2016 to March 2017, a retrospective study of factors associated with the 2015 NRE success was conducted and enrolled 242 students who attended their sixth year at the school of medicine of Reims. Demographic and academic data collected by a home-made survey was studied using univariate and then multivariate analysis by generalized linear regression with a threshold of p <  0.05 deemed significant. RESULTS: The factors independently associated with a better ranking at the NRE were the motivation for the preparation of the NRE (gain of 3327 ± 527 places, p <  0.0001); to have participated in the NRE white test organized by la Revue du Praticien in November 2014 (gain of 869 ± 426 places, p <  0.04), to have participated in the NRE white test organized by la conférence Hippocrate in March 2015 (+ 613 places ±297, p <  0.04). The factors independently associated with poor NRE ranking were repeating the first year (loss of 1410 places ±286, p <  0.0001), repeating a year during university course (loss of 1092 places ±385, p <  0.005), attendance of hospital internships in 6th year (loss of 706 places ±298, p <  0.02). CONCLUSIONS: The student motivation and their white tests completion were significantly associated with success at the NRE. Conversely, repeating a university year during their course and attendance of 6th year hospital internships were associated with a lower ranking.

Impact of video on the understanding and satisfaction of patients receiving informed consent before elective inpatient coronary angiography: A randomized trial.

BACKGROUND: Appropriate information about the benefits and risks of invasive procedures is crucial, but limited data is available in this field. The aim of this study was to evaluate the incremental value of a short video about coronary angiography compared with standard information, in terms of patient understanding, satisfaction and anxiety. METHODS: This prospective multicenter study included patients admitted for scheduled coronary angiography, who were randomized to receive either standard information or video information by watching a three-dimensional educational video. After information was delivered, patients were asked to complete a dedicated 16-point information questionnaire, as well as satisfaction and anxiety scales. RESULTS: From 21 September to 4 October 2015, 821 consecutive patients were randomized to receive either standard information (n=415) or standard information with an added educational video (n=406). The information score was higher in the video information group than in the standard group (11.8±2.8 vs 9.5±3.1; P<.001). This result was consistent across age and education level subgroups. Self-reported satisfaction was also higher in the video information group (8.4±1.9 vs. 7.7±2.3; P<.001), while anxiety level did not differ between groups. The variables associated with a higher information score were the use of the educational video, younger age, higher level of education, previous follow-up by a cardiologist, prior information about coronary angiography and previous coronary angiography. CONCLUSIONS: In comparison with standard information, viewing a dedicated educational video improved patients' understanding and satisfaction before scheduled coronary angiography. These results are in favor of widespread use of this incremental information tool.

[Watermelon stomach: Chronic renal failure and/or imatinib?]. / Watermelon stomach : insuffisance rénale chronique et/ou Glivec(®) ?

Watermelon stomach or gastric antral vascular ectasia (GAVE) syndrome is an uncommon cause of sometimes severe upper gastro-intestinal bleeding. Essentially based on a pathognomonic endoscopic appearance, its diagnosis may be unrecognised because mistaken with portal hypertensive gastropathy, while treatment of these two entities is different. Its etiopathogeny remains still unclear, even if it is frequently associated with different systemic illnesses as hepatic cirrhosis, autoimmune disorders and chronic renal failure. The mechanism inducing these vascular ectasia may be linked with mechanical stress on submucosal vessels due to antropyloric peristaltic motility dysfunction modulated by neurohormonal vasoactive alterations. Because medical therapies are not very satisfactory, among the endoscopic modalities, argon plasma coagulation seems to be actually the first-line treatment because the most effective and safe. However, surgical antrectomy may be sometimes necessary. Recently GAVE syndrome appeared as a new adverse reaction of imatinib mesylate, one of the tyrosine kinase inhibitors used in chronic myeloid leukemia, and we report here the observation of such a pathology in one patient treated at the same time by haemodialysis and by imatinib mesylate for chronic myeloid leukemia.