Culture-negative bivalvular endocarditis with myocardial destruction in a patient with systemic lupus erythematosus: a case report

Culture-negative endocarditis has long been associated with systemic lupus erythematosus, but is usually asymptomatic or involves a single valve. We present a patient with destructive culture-negative endocarditis that remains without a microbial etiology despite an exhaustive workup using advanced diagnostic techniques in a patient with systemic lupus erythematosus

Comparison of Serum Beta 2-Microglobulin and 24 hour Urinary Creatinine Clearance as a Prognostic Factor in Multiple Myeloma

A new staging system for multiple myeloma (MM) has utilized serum concentrations of beta 2-microglobulin (Sβ2M) and albumin as important prognostic factors for survival. Since Sβ2M is an indicator of glomerular filtration rate, we compared the prognostic values of Sβ2M and 24-hr urinary creatinine clearance (Ccr) in patients with MM. We retrospectively reviewed the records of 170 MM patients from January 1996 to November 2003 whose 24-hr urinary Ccr was available at the time of diagnosis. We found that pretreatment Sβ2M was inversely related to Ccr (Spearman's correlation coefficient=-0.787). In univariate analysis, the hazard ratio (HR) of death was 1.043 (p<0.001) for Sβ2M and 0.985 (p<0.001) for Ccr. Multivariate analysis showed that Sβ2M (HR 1.030, p=0.010) and Ccr (HR 0.993, p=0.059) were significant prognostic factors in patients' survival. In conclusion, 24-hr urinary Ccr may be utilized for staging of patients with MM

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Rule-out of non-ST elevation myocardial infarction by five point of care cardiac troponin assays according to the 0 h/3 h algorithm of the European Society of Cardiology

BACKGROUND Point of care (POC) assays for cardiac troponins I or T (cTnI or cTnT) may accelerate the diagnosis of patients with suspected acute coronary syndrome (ACS). However, their clinical utility according to the 0 h/3 h algorithm recommended by the European Society of Cardiology (ESC) for non-ST elevation myocardial infarction (NSTEMI) is unknown. METHODS Blood samples from 90 patients with suspected ACS were obtained at hospital admission and 3 h later. Concentrations of cTn were determined using five POC assays (AQT90 FLEX cTnI and cTnT; PATHFAST™ cTnI; Stratus CS 200 cTnI; and Triage MeterPro cTnI) and two guideline-acceptable high-sensitivity (hs) immunoassays. RESULTS For the diagnosis of NSTEMI (n=15), AUCs for Abbott hs-cTnI and Roche hs-cTnT were 0.86 [95% confidence interval (CI), 0.75-0.96] and 0.88 (95% CI, 0.80-0.95), respectively, at admission, and 0.96 and 0.94, respectively, 3 h later. With the 99th percentile cutoff, their sensitivities were 62% and 92%, respectively, at admission, and 77% and 100%, respectively, 3 h later. The PATHFAST™ cTnI assay showed AUCs of 0.90 (95% CI, 0.82-0.97) and 0.94 (95% CI, 0.89-1.00), respectively, and sensitivities of 67% and 75% at admission and 3 h later, respectively. The other cTn POC assays had AUCs of 0.71 (95% CI, 0.53-0.89) to 0.84 (95% CI, 0.71-0.96) and 0.86 (95% CI, 0.72-0.99) to 0.87 (95% CI, 0.75-0.99) and sensitivities of 39%-50% and 62%-77% at admission and 3 h later, respectively. CONCLUSIONS PATHFAST™ cTnI assay proved itself as comparable to ESC-guideline acceptable hs-cTn assays. The lower sensitivity of the other POC assays limits their clinical utility and would require longer follow-up monitoring of patients for the safe NSTEMI rule-out

Clinical features and survival outcomes in IgD myeloma: a study by Asia Myeloma Network (AMN)

10.1038/s41375-020-01060-wLEUKEMIA3561797-180