Cardiomyopathies dilatées d’origine toxique

Dilated cardiomyopathy is defined by the presence of left ventricular dilatation and contractile dysfunction in the absence of abnormal loading conditions and severe coronary artery disease. Once dilated cardiomyopathy is discovered, a careful and detailed history with laboratory tests may reveal a potential toxic cause. In this article, we present the case of a patient with suspected toxic dilated cardiomyopathy, and then discuss the common causes and treatment of toxic dilated cardiomyopathy.La cardiomyopathie dilatée est définie par la présence d’une dilatation ventriculaire gauche et d’un dysfonctionnement contractile en l’absence de conditions de charge anormales et de coronaropathie sévère. Une fois qu’une cardiomyopathie dilatée est découverte, une anamnèse minutieuse et détaillée associée à des tests de laboratoire exhaustifs peut révéler une cause toxique potentielle. Dans cet article, nous présentons le cas d’une patiente avec suspicion de cardiomyopathie dilatée d’origine toxique, puis discutons des causes fréquentes et du traitement de la cardiomyopathie dilatée d’origine toxique

A Cellular Assay for Spike/ACE2 Fusion: Quantification of Fusion-Inhibitory Antibodies after COVID-19 and Vaccination

Not all antibodies against SARS-CoV-2 inhibit viral entry, and hence, infection. Neutralizing antibodies are more likely to reflect real immunity; however, certain tests investigate protein/protein interaction rather than the fusion event. Viral and pseudoviral entry assays detect functionally active antibodies but are limited by biosafety and standardization issues. We have developed a Spike/ACE2-dependent fusion assay, based on a split luciferase. Hela cells stably transduced with Spike and a large fragment of luciferase were co-cultured with Hela cells transduced with ACE2 and the complementary small fragment of luciferase. Cell fusion occurred rapidly allowing the measurement of luminescence. Light emission was abolished in the absence of Spike and reduced in the presence of proteases. Sera from COVID-19-negative, non-vaccinated individuals or from patients at the moment of first symptoms did not lead to a significant reduction of fusion. Sera from COVID-19-positive patients as well as from vaccinated individuals reduced the fusion. This assay was more correlated to pseudotyped-based entry assay rather than serology or competitive ELISA. In conclusion, we report a new method measuring fusion-inhibitory antibodies in serum, combining the advantage of a complete Spike/ACE2 interaction active on entry with a high degree of standardization, easily allowing automation in a standard bio-safety environment

Role of Clinical Characteristics and Biomarkers at Admission to Predict One-Year Mortality in Elderly Patients with Pneumonia

Background: A hospitalization for community-acquired pneumonia results in a decrease in long-term survival in elderly patients. We assessed biomarkers at admission to predict one-year mortality in a cohort of elderly patients with pneumonia.Methods: A prospective observational study included patients >65 years hospitalized with pneumonia. Assessment of PSI, CURB-65, and biomarkers (C-reactive protein (CRP), procalcitonin (PCT), NT-pro-B-type natriuretic peptide (NT-proBNP), interleukin (IL)-6 and -8, tumor necrosis factor alpha (TNF-α), serum amyloid A (SAA), neopterin (NP), myeloperoxidase (MPO), anti-apolipoprotein A-1 IgG (anti-apoA-1), and anti-phosphorylcholine IgM (anti-PC IgM)) was used to calculate prognostic values for one-year mortality using ROC curve analyses. Post hoc optimal cutoffs with corresponding sensitivity (SE) and specificity (SP) were determined using the Youden index.Results: A total of 133 patients were included (median age 83 years [IQR: 78-89]). Age, dementia, BMI, NT-proBNP (AUROC 0.65 (95% CI: 0.55-0.77)), and IL-8 (AUROC 0.66 (95% CI: 0.56-0.75)) were significantly associated with mortality, with NT-proBNP (HR 1.01 (95% CI 1.00-1.02) and BMI (HR 0.92 (95% CI 0.85-1.000) being independent of age, gender, comorbidities, and PSI with Cox regression. At the cutoff value of 2200 ng/L, NT-proBNP had 67% sensitivity and 70% specificity. PSI and CURB-65 were not associated with mortality.Conclusions: NT-proBNP levels upon admission and BMI displayed the highest prognostic accuracy for one-year mortality and may help clinicians to identify patients with poor long-term prognosis.</p

Kinetics of inflammatory biomarkers to predict one-year mortality in older patients hospitalized for pneumonia: a multivariable analysis

Objectives: Long-term mortality is increased in older patients with pneumonia. We aimed to test whether residual inflammation is predictive of one-year mortality after pneumonia. Methods: Inflammation biomarkers (C-reactive protein [CRP], interleukin [IL]-6 and IL-8, tumor necrosis factor-α, serum amyloid A, neopterin, myeloperoxidase, anti-apolipoprotein A-1, and anti-phosphorylcholine IgM) were measured at admission and discharge in older patients hospitalized for pneumonia in a prospective study. Univariate and multivariate analyses were conducted using absolute level at discharge and relative and absolute differences between admission and discharge for all biomarkers, along with usual prognostic factors. Results: In the 133 included patients (median age, 83 years [interquartile range: 78-89]), one-year mortality was 26%. In univariate analysis, the relative difference of CRP levels had the highest area under the receiver operating characteristic curve (0.70; 95% confidence interval [CI] 0.60-0.80). A decrease of CRP levels of more than 67% between admission and discharge had 68% sensitivity and 68% specificity to predict survival. In multivariate analysis, lower body mass index (hazard ratio=0.87 [CI 95% 0.79-0.96], P-value=0.01), higher IL-8 (hazard ratio=1.02 [CI 95% 1.00-1.04], P-value=0.02), and higher CRP (1.01 [95% CI 1.00-1.02], P=0.01) at discharge were independently associated with mortality. Conclusion: Higher IL-8 and CRP levels at discharge were independently associated with one-year mortality. The relative CRP difference during hospitalization was the best individual biomarker for predicting one-year mortality.</p

Decreased Levels of SARS-CoV-2 Fusion-Inhibitory Antibodies in the Serum of Aged COVID-19 Patients

Background: The SARS-CoV-2 pandemic was particularly devastating for elderly people, and the underlying mechanisms of the disease are still poorly understood. In this study, we investigated fusion inhibitory antibodies (fiAbs) in elderly and younger COVID-19 patients and analyzed predictive factors for their occurrence. Methods: Data and samples were collected in two cohorts of hospitalized patients. A fusion assay of SARS-CoV-2 spike-expressing cells with ACE2-expressing cells was used to quantify fiAbs in the serum of patients. Results: A total of 108 patients (52 elderly (mean age 85 ± 7 years); 56 young (mean age 52 ± 10 years)) were studied. The concentrations of fiAbs were lower in geriatric patients, as evidenced at high serum dilutions (1/512). The association between fiAbs and anti-Spike Ig levels was weak (correlation coefficient &amp;lt; 0.3), but statistically significant. Variables associated with fusion were the delay between the onset of symptoms and testing (HR = -2.69;p&amp;lt; 0.001), clinical frailty scale (HR = 4.71;p= 0.035), and WHO severity score (HR = -6.01,p= 0.048). Conclusions: Elderly patients had lower fiAbs levels after COVID-19 infection. The decreased fiAbs levels were associated with frailty.</p

Undetected causes of death in hospitalized elderly with COVID-19: lessons from autopsy

Mechanisms and causes of death in older patients with SARS-CoV-2 infection are still poorly understood