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Sudden death is one of the leading causes of death in adults with sickle cell anemia (SCA) but its etiology remains most often unknown. Ventricular arrhythmia (VA) carries an increased risk of sudden death but its prevalence and determinants in SCA is poorly studied. The aim of this study is to identify the prevalence and predictors of VA in SCA patients. From January 2019 to March 2022, 100 SCA patients were referred to ambulatory cardiology department to specifically analyze cardiac function and were prospectively included in DREPACOEUR registry. They underwent a 24-hour ECG monitoring (24h-holter), a transthoracic echocardiography (TTE) and laboratory tests on the same day. The primary end-point was the occurrence of VA, defined as sustained or non-sustained ventricular tachycardia (VT), more than 500 premature ventricular contractions (PVCs) on 24h-holter, or recent history of VT ablation. Mean age was 46±13 years, 48% of patients were male. VA was observed in 22 (22%) patients (9 non-sustained VT [range 4-121 consecutive PVCs]), 15 with more than 500 PVCs and 1 history of VT ablation). Male sex (81 vs. 34%, p=0.02), impaired global longitudinal strain (GLS: -16±1.9% vs. -18.3±2.7%, p=0.02), and decreased platelet count (226±96G/L vs. 316±130G/L, p=0.02) were independently associated with VA occurrence. GLS correlated to PVC load/24h (r=0.39, p

Background Unexplained sudden death remains one of the leading causes of death in sickle cell disease (SCD) adults. Ventricular arrhythmia is a well-known risk factor for sudden death but its prevalence and determinants in the context of SCD remain understudied. Purpose The aim of this study was to identify echocardiographic predictors of ventricular arrhythmia in SCD. Methods From January 2019 to March 2021, consecutive adult patients with SCD referred to ambulatory cardiology department for possible cardiac involvement were prospectively included (Drepacoeur cohort). All patients that had 24-hour ECG monitoring (24h-holter) and thransthoracic echocardiography (TTE) on the same day were analysed in this study. The primary end point was the occurrence of ventricular arrhythmia, defined as sustained or non-sustained ventricular tachycardia (VT), more than 500 premature ventricular contractions (PVC) on 24h-holter, or history of VT ablation. Results Overall, 90 patients were included and 54 (60%) were analysed. Mean age was 47.6±11.6 years (range 21–69), 53% were male. Heart function was mainly preserved with a mean left ventricular ejection fraction (LVEF) of 57.9±4.9% and a mean global longitudinal strain (GLS) of −18±2.8%. Mean tricuspid regurgitation velocity was 2.6±0.4m/s. Ventricular arrhythmia was observed in 13 (24.1%) patients (4 non-sustained VT [range 4–121 consecutive PVC], 9 with more than 500 PVC [range 500–13000 PVC/24h] and 1 history of VT ablation). Regarding echocardiographic parameters, ventricular arrhythmia was associated with lower GLS (−15.8±1.8% vs. −19±2.7%, P Conclusion In SCD adults with preserved LVEF, GLS was the only independent echocardiographic predictor of ventricular arrhythmia. Funding Acknowledgement Type of funding sources: None.

Aims This study sought to link cardiac phenotypes in homozygous Sickle Cell Disease (SCD) patients with clinical profiles and outcomes using cluster analysis. Methods We analyzed data of 379 patients included in the French Etendard Cohort. A cluster analyses was performed based on echocardiographic variables, and the association between clusters, clinical profiles and outcomes was assessed. Results Three clusters were identified. Cluster 1 (n=123) patients had the lowest cardiac output, mild left cardiac cavities remodeling, mild diastolic dysfunction, and higher tricuspid regurgitation velocity (TRV). They were predominantly female and displayed the most altered functional limitation. Cluster 2 (n=102) patients had the highest cardiac output and the most remodeled cardiac cavities. Diastolic function and TRV were similar to Cluster 1. These patients had a higher blood pressure and a severe hemolytic anemia. Cluster 3 (n=154) patients had mild left cardiac cavities remodeling, normal diastolic function and lowest TRV values. They were younger with the highest hemoglobin value. Right heart catheterization was performed in 94 patients. Cluster 1 (n=33) included the majority of pre-capillary PH whilst Cluster 2 (n=34) included post-capillary PH. No PH was found in Cluster 3 (n=27). After a follow-up of 11.4±2 years, death occurred in 41 patients (11%). Cluster 2 patients had the worst prognosis with a 19% mortality rate vs. 12% in Cluster 1 and 5% in Cluster 3 (P log-rank=0,003). Conclusion Cluster analysis of echocardiography variables identified 3 hemodynamic and clinical phenotypes amongst SCD patients, each predicting a different prognosis. This article is protected by copyright. All rights reserved.

Background Severe coronavirus-induced disease 2019 (COVID-19) leads to acute respiratory distress syndrome with an increased risk of venous thrombo-embolic events. To a much lesser extent, arterial thrombo-embolic events have also been reported in this setting. Case summary Here, we describe four different cases of COVID-19 infection with ischaemic arterial events, such as a myocardial infarction with high thrombus load, ischaemic stroke on spontaneous thrombosis of the aortic valve, floating thrombus with mesenteric, splenic and renal infarction, and acute limb ischaemia. Discussion Cardiovascular risk factors such as hypertension, obesity, and diabetes are comorbidities most frequently found in patients with a severe COVID-19 infection and are associated with a higher death rate. Our goal is to provide an overview of the clinical spectrum of ischaemic arterial events that may either reveal or complicate COVID-19. Several suspected pathophysiological mechanisms could explain the association between cardiovascular events and COVID-19 (role of systemic inflammatory response syndrome, endothelial dysfunction, activation of coagulation cascade leading to a hypercoagulability state, virus-induced secondary antiphospholipid syndrome). We need additional studies of larger size, to estimate the incidence of these arterial events and to assess the efficacy of anticoagulation therapy.

Leg ulcers are a major complication of sickle cell disease (SCD) that can cause severe complications. They are particularly challenging to treat and therapeutic innovation is needed. We previously showed that SCD ulcers display a delayed wound healing due to decreased angiogenesis. During pregnancy, fetal microchimeric cells (FMC) transferred to the mothers are recruited to maternal wounds and improve angiogenesis. After delivery, FMC persist in maternal bone marrow for decades. Here, we questioned whether fetal cells could also improve SCD ulcers in the post-partum setting. We found that skin healing was similarly improved in post-partum mice and in pregnant mice, through increased proliferation and angiogenesis. In a SCD mouse model that recapitulates SCD refractory ulcers, we showed that post-partum SCD mice healed more quickly as compared to virgin ones. This was associated with the recruitment of fetal cells in maternal wounds where they harbored markers of leukocytes and endothelial cells. In a retrospective cohort of SCD patients, we demonstrated using several parameters that ever parous SCD women had a decreased burden related to leg ulcers compared to nulliparous women. Taken together, these results indicate that healing capacities of FMC are maintained long after delivery and may be targeted to promote wound healing in post-partum SCD patients.

Gadolinium is a frequently used contrast product for MRI exam. It is well known to be less immuno-reactive than iodine used in tomodensitometry but is safety is not completely exempt of secondary effect. Here we report one case of acute interstitial pulmonary toxicity due to gadolinium. After quick elimination of others possible diagnosis and broncho-alveolar lavage we establish the link between acute intra-alveolar hemorrhage and gadolinium injection. Keywords: Intra-alveolar hemorrhage, Gadolinium, Drug induced toxicity

Sickle cell disease (SCD) induces a chronic prothrombotic state. Central venous access devices (CVADs) are commonly used for chronic transfusions and iron chelation in this population. CVADs are an additional venous thromboembolism (VTE) risk factor. The role of thromboprophylaxis in this setting is uncertain. The objectives are: (1) to determine whether thromboprophylaxis reduces VTE risk in SCD patients with CVAD and (2) to explore characteristics associated with VTE risk. We identified adults with SCD and CVAD intended for chronic use (≥3 months) at two comprehensive SCD centers. Thromboprophylaxis presence; type; intensity; and patient-, catheter-, and treatment-related VTE risk factors were recorded. Among 949 patients, 49 had a CVAD (25 without and 24 with VTE prophylaxis). Thromboprophylaxis type and intensity varied widely. Patients without thromboprophylaxis had higher VTE rates (rate ratio (RR) = 4.0 (95% confidence interval: 1.2–12.6), p = 0.02). Hydroxyurea was associated with lower VTE rates (RR = 20.5 (6.4–65.3), p < 0.001). PICC lines and Vortex and Xcela Power implantable devices were associated with higher rates compared with Port-a-Cath (RR = 5.8 (1.3–25.9), p = 0.02, and RR = 58.2 (15.0–225.0), p < 0.001, respectively). Thromboprophylaxis, hydroxyurea, and CVAD subtype were independently associated with VTE. The potentially protective role of thromboprophylaxis and hydroxyurea for VTE prevention in patients with SCD and CVAD merits further exploration.

INTRODUCTION Vaso-occlusive crisis (VOC), hallmark of sickle-cell disease (SCD), is the first cause of patients' emergency room (ER) admissions and hospitalizations. Acute chest syndrome (ACS) is a life-threatening complication that can occur during VOC and prolong hospitalization and is one of the main causes of death in SCD patients. The PRESEV score, established by team members and colleagues, assesses the risk of developing ACS (Bartolucci et al., 2016). In addition, the score has been validated by an international multicenter study, involving 13 centers, distributed in five different countries (PRESEV 2 - ASH 2020). Throughout the first wave of the Covid-19 pandemic, VOC management for SCD patients was a major concern. Our sickle cell referral center set up a hotline to monitor patients suffering from VOC daily, and organized the deployment of home-care services when required. The success of this system during the first wave of the pandemic led to the establishment of DREPADOM, a home-care and hospitalization protocol for VOC management in patients who are at a low risk of developing ACS, as standard care. DESCRIPTION OF SETTING Patients eligible for DREPADOM are patients that arrive at the ER for a VOC with a low PRESEV score, meaning low risk of developing ACS; or patients that are discharged early following hospitalization for VOC. After physical examination and calculation of the PRESEV score, DREPADOM home hospitalization is systematically offered to patients arriving to the ER with a PRESEV score ≤ 5. If the patient agrees, the DREPADOM nurse coordinator then acts as a link between the pharmacist, the oxygen supplier, the homecare provider, and the DREPADOM medical platform to activate the home hospitalization protocol. This entails the delivery of oxygen supply at the patient's house, dispatch of a medical prescription of opioids and parenteral treatments, twice/thrice-daily visits from homecare nurses, and an on-call SCD expert. DREPADOM relies on a system of daily telephone calls with three levels of expertise and warning and a decision-making algorithm. This is supervised by SCD experts, who arbitrate according to the evolution of the situation (stopping the follow-up, continuing the follow-up as an outpatient, hospitalization) (Fig.1). Furthermore, nurses enter patient vitals in real-time during their daily visits on a dedicated online platform (Link4Life) that contains an integrated automatic alert system. Additionally, a daily phone update between the DREPADOM coordination and the homecare provider's coordination concerning status and evolution of the patient's global condition takes place. RESULTS Over a 6-month period, 39 patients were included in the DREPADOM home hospitalization protocol, 3 of which were included multiple times for a total of 42 inclusions. Mean age was 40 years old [±9], sex ratio was 14/25 (male/female), ER vs early discharge ratio was 21/22, and mean homecare follow-up was 3 days (±1) for both, patients arriving from the ER and early discharge patients. Throughout the third wave of the pandemic, when hospital saturation was a major concern, patients with PRESEV scores 5 ≤ 11 were also offered DREPADOM. Three patients were hospitalized (7%): one for an ACS, who was included during the 3 rd wave of the pandemic with a PRESEV score of 8; one for pyelonephritis unrelated to the VOC; and one for difficulties with venous access. No death was reported. PERSPECTIVES Preliminary satisfaction surveys show a great enthusiasm for DREPADOM, partly due to the high standard of care received, but also due to the shorter length of hospitalization. In fact, median hospital stay for VOC is 4 [3-7] days (Bartolucci, 2016) whereas median homecare follow-up was 3 [1-6] days. Figure 1 Figure 1. Disclosures Bartolucci: Hemanext: Consultancy; Jazz Pharma: Other: Lecture fees; AGIOS: Consultancy; F. Hoffmann-La Roche Ltd: Consultancy; Emmaus: Consultancy; GBT: Consultancy; INNOVHEM: Other: Co-founder; Bluebird: Consultancy, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Lecture fees, Steering committee, Research Funding; Addmedica: Consultancy, Other: Lecture fees, Research Funding; Fabre Foundation: Research Funding.

Introduction Sickle cell disease is a genetic disease with acute and chronic complications. Pediatric mortality has decreased in recent decades with the introduction of systematic antibiotic therapy, preventive management of cerebral vasculopathy and therapeutic education of families. However, in the absence of cohort follow-up at birth, life expectancy, which is a different concept from age at death, cannot be assessed. In this retrospective, monocentric study, we describe causes and circumstances of death, acute chronic complications, long-term treatments and baseline biology of these patients. It seems important to analyze the risks of morbidity and mortality in order to decide on the necessary preventive measures. Material and method: Records of patients deceased between 2000 and 2020, from the national referral center (Henri Mondor Hospital), were retrospectively reviewed. The referral center follows 3500 patients. All deaths reported to the hospital, by families, other hospitals and health professionals were retrieved from computerized records. Deaths published by the INSEE (National Institute of Statistical and Economical study) from 2000 to December 2020 were accessible and compared with our databases to identify all our deceased patients. All patients with a medical record in our center were included for the study. Patients who had never visited our center were excluded. Results: During this period 226 patients including 128 women and 138 men are recorded. Genotypes for these patients were 204(76%) SS, 41 (15%) SC, 14(5%) Sβ°thalassemia and 7 (2%) Sβ+thalassemia. The median age at death was 41 years with an IQR [32-51]. 186 (70%) patients were hospitalized, 129 (70%) of whom were admitted to intensive care. 36 (13%) patients died at home, including 15 with opioid addiction and 5 patients with psychiatric pathology, and 4 patients on dialysis. This information was not available for 44 (16%) patients. The causes of death were vaso-occlusive complications with multivisceral failure in 44 cases, 42 sepsis, among which there were 11 renal failures, 9 of which were dialyzed. 5 patients died of COVID 19. Cerebral hemorrhage and neurological accident occurred in 22 cases, 4 of which were known to have macrovasculopathy. 25 patients died of a direct complication of renal failure, of which 17 were dialysed, 8 pre-dialysed and 3 transplanted. Acute liver failure in 16 cases, 10 precapillary pulmonary hypertension, 14 DHTR, 10 end-stage heart failure were noted. Two road accidents, 2 suicides, 1 dementia are repoted. For 51 cases, there was no information on the cause or circumstance of death. The causes of death according to genotype is on Table 1. Concerning the chronic complications, 94/266 (35%) patients had significant chronic organ damage. Sixteen patients had required renal or liver transplantation in their history. End-stage organ damage was frequent, 42 had end-stage renal failure, 21 had major liver failure, of which five were transplanted and 16 were awaiting transplantation. Twenty-one patients had known heart failure, 10 of which were associated with end-stage renal disease. Ten patients were followed for significant precapillary pulmonary hypertension. Transfusion difficulties due to a history of DHTR were found for 33 patients. Fourteen patients had an opioid addiction. Nine patients were pregnant and nine had received corticosteroids. Discussion: Causes of death have changed and chronic organ failure is the leading cause of death, especially in patients with kidney, liver and heart disease. This study does not calculate life expectancy, but there was an increase in age at death of about 1/4 of the patients who were between 51 and 81 years old.The management of sickle cell disease has progressed in recent years and new therapies are being proposed. Prevention of the development of these complications is one of the new challenges, especially for renal disease, which is associated with premature mortality. DHTR and cerebral hemorrhage, Covid-19 are new entities and DHTR was probably underdiagnosed in previous publications. Pregnancy remains a period at risk, for which surveillance should be reinforced. The analysis is ongoing and correlations are currently being investigated between different parameters to find risk factors for mortality. Figure 1 Figure 1. Disclosures Habibi: Novartis: Consultancy, Honoraria; bluebird bio: Consultancy, Honoraria, Research Funding. Audard: Addmedica: Consultancy. Michel: Novartis: Consultancy; Amgen: Consultancy; Rigel: Honoraria; Alexion: Honoraria; UCB: Honoraria; Argenx: Honoraria. Galactéros: Addmedica: Membership on an entity's Board of Directors or advisory committees. Bartolucci: INNOVHEM: Other: Co-founder; Bluebird: Consultancy, Research Funding; F. Hoffmann-La Roche Ltd: Consultancy; GBT: Consultancy; Jazz Pharma: Other: Lecture fees; AGIOS: Consultancy; Hemanext: Consultancy; Emmaus: Consultancy; Fabre Foundation: Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Lecture fees, Steering committee, Research Funding; Addmedica: Consultancy, Other: Lecture fees, Research Funding.

Introduction Unexplained sudden death remains one of the leading causes of death in sickle cell disease (SCD) adults. Ventricular arrhythmia is a well-known risk factor for sudden death but its prevalence and determinants in the context of SCD remain understudied. Method From January 2019 to March 2021, consecutive adult patients with SCD referred to ambulatory cardiology department for possible cardiac involvement were prospectively included (Drepacoeur cohort). All patients that had 24-hour ECG monitoring (24h-holter) and thransthoracic echocardiography (TTE) on the same day were analysed. The primary end point was the occurrence of ventricular arrhythmia, defined as sustained or non-sustained ventricular tachycardia (VT), more than 500 premature ventricular contractions (PVC) on 24h-holter, or history of VT ablation. Results Overall, 90 patients were included and 54 (60%) were analysed. Mean age was 47.6 ± 11.6 years (range 21-69), 53% were male. Heart function was mainly preserved with a mean left ventricular ejection fraction (LVEF) of 57.9 ± 4.9% and a mean global longitudinal strain (GLS) of -18 ± 2.8%. Mean tricuspid regurgitation velocity was 2.6 ± 0.4 m/s. Ventricular arrhythmia was observed in 13 (24.1%) patients (4 non-sustained VT, 9 with more than 500 PVC and 1 history of VT ablation). Ventricular arrhythmia was associated with lower GLS (−15.8 ± 1.8% vs. −19 ± 2.7%, P Conclusion In SCD adults with preserved LVEF, GLS was the only independent echocardiographic predictor of ventricular arrhythmia.

Takayasu arteritis (TAK) is a vasculitis of the large arteries. The arterial wall, target of the immune reaction, is composed of vascular dendritic cells, endothelial cells, vascular smooth muscle cells and fibroblasts, which engage in an interaction with T cells and macrophages to, ultimately, cause luminal stenosis or aneurysmal wall damage of the vessel. A multitude of cytokines have been identified to increase in case of TAK and to be linked to disease activity. A better understanding of the physiopathological pathways and mechanisms involved, might enable a more tailored therapeutic approach in TAK.

International audience; The SARS-CoV-2 Omicron variant can escape neutralization by vaccine-elicited and convalescent antibodies. Memory B cells (MBCs) represent another layer of protection against SARS-CoV-2, as they persist after infection and vaccination and improve their affinity. Whether MBCs elicited by mRNA vaccines can recognize the Omicron variant remains unclear. We assessed the affinity and neutralization potency against the Omicron variant of several hundred naturally expressed MBC-derived monoclonal IgG antibodies from vaccinated COVID-19-recovered and -naive individuals. Compared with other variants of concern, Omicron evaded recognition by a larger proportion of MBC-derived antibodies, with only 30% retaining high affinity against the Omicron RBD, and the reduction in neutralization potency was even more pronounced. Nonetheless, neutralizing MBC clones could be found in all the analyzed individuals. Therefore, despite the strong immune escape potential of the Omicron variant, these results suggest that the MBC repertoire generated by mRNA vaccines still provides some protection against the Omicron variant in vaccinated individuals.

In addition to serum immunoglobulins, memory B cell (MBC) generation against SARS-CoV-2 represents another layer of immune protection, but the quality of MBC responses in naive and COVID-19-recovered individuals after vaccination remains ill-defined. We studied longitudinal cohorts of naive individuals and disease-recovered patients for up to 2 months after SARS-CoV-2 mRNA vaccination. We assessed the quality of the memory response by analysis of VDJ repertoires, affinity and neutralization against variants of concern (VOCs), using unbiased cultures of 2452 MBCs. Upon boosting, the MBC pool of recovered patients selectively expanded, further matured and harbored potent neutralizers against VOCs. Although naïve individuals had weaker neutralizing serum responses, half of their RBD-specific MBCs displayed high affinity towards multiple VOCs, including delta (B.1.617.2), and one-third retained neutralizing potency against beta (B.1.351). Our data suggest that an additional challenge in naive vaccinees could recall such affinity-matured MBCs and allow them to respond efficiently to VOCs., Graphical Abstract, To better understand B cell responses to SARS-CoV-2 mRNA vaccination, Sokal et al. analyzed memory B cells from COVID-19-recovered and -naive individuals. In recovered patients, vaccination amplifies a broad repertoire of matured MBCs and generates variant-neutralizing plasma cells. In naïve individuals, vaccination induces an MBC pool containing potent neutralizing clones against all current variants of concern, including beta and delta.