Carboxy-terminal fragment of fibroblast growth factor 23 induces heart hypertrophy in sickle cell disease

International audienc

Kidney Transplantation in Patients With AA Amyloidosis: Outcomes in a French Multicenter Cohort

International audienceRationale & ObjectiveOutcomes of kidney transplantation for patients with renal AA amyloidosis are uncertain, with reports of poor survival and high rates of disease recurrence. However, data are inconclusive and mostly based on studies from the early 2000s and earlier.Study DesignRetrospective multicenter cohort study.Setting & ParticipantsWe searched the French national transplant database to identify all patients with renal AA amyloidosis who underwent kidney transplantation between 2008 and 2018.ExposuresAge, cause of amyloidosis, use of biotherapies, CRP levels.OutcomesOutcomes were all-cause mortality and allograft loss. We also reported amyloidosis allograft recurrence, occurrence of acute rejection episodes, as well as infectious, cardiovascular, and neoplastic disease events.Analytical ApproachThe Kaplan-Meier estimator for mortality and the cumulative incidence function method for allograft loss. Factors associated with patient and allograft survival were investigated using a Cox proportional hazards model and a cause-specific hazards model, respectively.ResultsEighty-six patients who received kidney transplants for AA amyloidosis at 26 French centers were included. The median age was 49.4 years (interquartile range 39.7-61.1). The main cause of amyloidosis was Familial Mediterranean Fever (37 cases, 43%). Sixteen (18.6%) patients received a biotherapy after transplantation. Patient survival was 94.0% (95% confidence interval 89.1-99.2) at 1 year and 85.5% (77.8-94.0) at 5 years post-transplantation. The cumulative incidence of allograft loss was 10.5% (4.0-17.0) at 1 year, and 13.0% (5.8-20.1) at 5 years post-transplantation. Histologically proven AA amyloidosis recurrence occurred in 5 transplants (5.8%). 55.8% of cases developed an infection requiring hospitalization and 27.9% acute allograft rejection. Multivariable analysis showed that CRP concentration at the time of transplantation was associated with patient survival (HR 1.01, 95% CI 1.00-1.02, p=0.01) and with allograft survival (HR 1.68, 95% CI 1.10-2.57, p 0.02).LimitationsThe study lacked a control group and the effect of biotherapies on transplantation outcomes could not be explored.ConclusionsThis relatively contemporary cohort of patients who received a kidney transplant for AA amyloidosis experienced favorable rates of survival and lower recurrence rates than previously reported. These data support the practice of treating these patients with kidney transplantation for end-stage kidney disease

Type 1 Diabetes in People Hospitalized for COVID-19: New Insights From the CORONADO Study

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Diagnosis and management of asymptomatic bacteriuria in kidney transplant recipients: a survey of current practice in Europe

International audienceBackgroundAsymptomatic bacteriuria is frequent in kidney transplant recipients (KTRs). However, there is no consensus on diagnosis or management. We conducted a European survey to explore current practice related to the diagnosis and management of asymptomatic bacteriuria in adult KTRs.MethodsA panel of experts from the European Renal Association–European Dialysis Transplant Association/Developing Education Science and Care for Renal Transplantation in European States working group and the European Study Group for Infections in Compromised Hosts of the European Society of Clinical Microbiology and Infectious Diseases designed this cross-sectional, questionnaire-based, self-administered survey. Invitations to participate were e-mailed to European physicians involved in the care of KTRs.ResultsTwo hundred and forty-four participants from 138 institutions in 25 countries answered the survey (response rate 30%). Most participants [72% (176/244)] said they always screen for asymptomatic bacteriuria in KTRs. Six per cent (15/240) reported never treating asymptomatic bacteriuria with antibiotics. When antimicrobial treatment was used, 24% of the participants (53/224) said they would start with empirical antibiotics. For an episode of asymptomatic bacteriuria caused by a fully susceptible microorganism and despite no contraindications, a majority of participants (121/223) said they would use a fluoroquinolone (n = 56), amoxicillin/clavulanic acid (n = 38) or oral cephalosporins (n = 27).ConclusionsScreening for and treating asymptomatic bacteriuria are common in KTRs despite uncertainties around the benefits and harms. In an era of antimicrobial resistance, further studies are needed to address the diagnosis and management of asymptomatic bacteriuria in these patients

The association between macrovascular complications and intensive care admission, invasive mechanical ventilation, and mortality in people with diabetes hospitalized for coronavirus disease-2019 (COVID-19)

International audienceAbstract Background It is not clear whether pre-existing macrovascular complications (ischemic heart disease, stroke or peripheral artery disease) are associated with health outcomes in people with diabetes mellitus hospitalized for COVID-19. Methods We conducted cohort studies of adults with pre-existing diabetes hospitalized for COVID-19 infection in the UK, France, and Spain during the early phase of the pandemic (between March 2020—October 2020). Logistic regression models adjusted for demographic factors and other comorbidities were used to determine associations between previous macrovascular disease and relevant clinical outcomes: mortality, intensive care unit (ICU) admission and use of invasive mechanical ventilation (IMV) during the hospitalization. Output from individual logistic regression models for each cohort was combined in a meta-analysis. Results Complete data were available for 4,106 (60.4%) individuals. Of these, 1,652 (40.2%) had any prior macrovascular disease of whom 28.5% of patients died. Mortality was higher for people with compared to those without previous macrovascular disease (37.7% vs 22.4%). The combined crude odds ratio (OR) for previous macrovascular disease and mortality for all four cohorts was 2.12 (95% CI 1.83–2.45 with an I 2 of 60%, reduced after adjustments for age, sex, type of diabetes, hypertension, microvascular disease, ethnicity, and BMI to adjusted OR 1.53 [95% CI 1.29–1.81]) for the three cohorts. Further analysis revealed that ischemic heart disease and cerebrovascular disease were the main contributors of adverse outcomes. However, proportions of people admitted to ICU (adjOR 0.48 [95% CI 0.31–0.75], I 2 60%) and the use of IMV during hospitalization (adjOR 0.52 [95% CI 0.40–0.68], I 2 37%) were significantly lower for people with previous macrovascular disease. Conclusions This large multinational study of people with diabetes mellitus hospitalized for COVID-19 demonstrates that previous macrovascular disease is associated with higher mortality and lower proportions admitted to ICU and treated with IMV during hospitalization suggesting selective admission criteria. Our findings highlight the importance correctly assess the prognosis and intensive monitoring in this high-risk group of patients and emphasize the need to design specific public health programs aimed to prevent SARS-CoV-2 infection in this subgroup

Effect of Tocilizumab vs Usual Care in Adults Hospitalized With COVID-19 and Moderate or Severe Pneumonia

International audienceImportance Severe pneumonia with hyperinflammation and elevated interleukin-6 is a common presentation of coronavirus disease 2019 (COVID-19).Objective To determine whether tocilizumab (TCZ) improves outcomes of patients hospitalized with moderate-to-severe COVID-19 pneumonia.Design, Setting, and Particpants This cohort-embedded, investigator-initiated, multicenter, open-label, bayesian randomized clinical trial investigating patients with COVID-19 and moderate or severe pneumonia requiring at least 3 L/min of oxygen but without ventilation or admission to the intensive care unit was conducted between March 31, 2020, to April 18, 2020, with follow-up through 28 days. Patients were recruited from 9 university hospitals in France. Analyses were performed on an intention-to-treat basis with no correction for multiplicity for secondary outcomes.Interventions Patients were randomly assigned to receive TCZ, 8 mg/kg, intravenously plus usual care on day 1 and on day 3 if clinically indicated (TCZ group) or to receive usual care alone (UC group). Usual care included antibiotic agents, antiviral agents, corticosteroids, vasopressor support, and anticoagulants.Main Outcomes and Measures Primary outcomes were scores higher than 5 on the World Health Organization 10-point Clinical Progression Scale (WHO-CPS) on day 4 and survival without need of ventilation (including noninvasive ventilation) at day 14. Secondary outcomes were clinical status assessed with the WHO-CPS scores at day 7 and day 14, overall survival, time to discharge, time to oxygen supply independency, biological factors such as C-reactive protein level, and adverse events.Results Of 131 patients, 64 patients were randomly assigned to the TCZ group and 67 to UC group; 1 patient in the TCZ group withdrew consent and was not included in the analysis. Of the 130 patients, 42 were women (32%), and median (interquartile range) age was 64 (57.1-74.3) years. In the TCZ group, 12 patients had a WHO-CPS score greater than 5 at day 4 vs 19 in the UC group (median posterior absolute risk difference [ARD] −9.0%; 90% credible interval [CrI], −21.0 to 3.1), with a posterior probability of negative ARD of 89.0% not achieving the 95% predefined efficacy threshold. At day 14, 12% (95% CI −28% to 4%) fewer patients needed noninvasive ventilation (NIV) or mechanical ventilation (MV) or died in the TCZ group than in the UC group (24% vs 36%, median posterior hazard ratio [HR] 0.58; 90% CrI, 0.33-1.00), with a posterior probability of HR less than 1 of 95.0%, achieving the predefined efficacy threshold. The HR for MV or death was 0.58 (90% CrI, 0.30 to 1.09). At day 28, 7 patients had died in the TCZ group and 8 in the UC group (adjusted HR, 0.92; 95% CI 0.33-2.53). Serious adverse events occurred in 20 (32%) patients in the TCZ group and 29 (43%) in the UC group (P = .21).Conclusions and Relevance In this randomized clinical trial of patients with COVID-19 and pneumonia requiring oxygen support but not admitted to the intensive care unit, TCZ did not reduce WHO-CPS scores lower than 5 at day 4 but might have reduced the risk of NIV, MV, or death by day 14. No difference on day 28 mortality was found. Further studies are necessary for confirming these preliminary results.Trial Registration ClinicalTrials.gov Identifier: NCT0433180

Effect of anakinra versus usual care in adults in hospital with COVID-19 and mild-to-moderate pneumonia (CORIMUNO-ANA-1): a randomised controlled trial

International audienc

Sarilumab in adults hospitalised with moderate-to-severe COVID-19 pneumonia (CORIMUNO-SARI-1): An open-label randomised controlled trial

International audienc