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Background: Early sepsis diagnosis has emerged as one of the main challenges in the emergency room. Measurement of sepsis biomarkers is largely used in current practice to improve the diagnosis accuracy. Monocyte distribution width (MDW) is a recent new sepsis biomarker, available as part of the complete blood count with differential. The objective was to evaluate the performance of MDW for the detection of sepsis in the emergency department (ED) and to compare to procalcitonin (PCT) and C-reactive protein (CRP). Methods: Subjects whose initial evaluation included a complete blood count were enrolled consecutively in 2 EDs in France and Spain and categorized per Sepsis-2 and Sepsis-3 criteria. The performance of MDW for sepsis detection was compared to that of procalcitonin (PCT) and C-reactive protein (CRP). Results: A total of 1,517 patients were analyzed: 837 men and 680 women, mean age 61 ± 19 years, 260 (17.1%) categorized as Sepsis-2 and 144 patients (9.5%) as Sepsis-3. The AUCs [95% confidence interval] for the diagnosis of Sepsis-2 were 0.81 [0.78–0.84] and 0.86 [0.84–0.88] for MDW and MDW combined with WBC, respectively. For Sepsis-3, MDW performance was 0.82 [0.79–0.85]. The performance of MDW combined with WBC for Sepsis-2 in a subgroup of patients with low sepsis pretest probability was 0.90 [0.84–0.95]. The AUC for sepsis detection using MDW combined with WBC was similar to CRP alone (0.85 [0.83–0.87]) and exceeded that of PCT. Combining the biomarkers did not improve the AUC. Compared to normal MDW, abnormal MDW increased the odds of Sepsis-2 by factor of 5.5 [4.2–7.1, 95% CI] and Sepsis-3 by 7.6 [5.1–11.3, 95% CI]. Conclusions: MDW in combination with WBC has the diagnostic accuracy to detect sepsis, particularly when assessed in patients with lower pretest sepsis probability. We suggest the use of MDW as a systematic screening test, used together with qSOFA score to improve the accuracy of sepsis diagnosis in the emergency department. Trial Registration ClinicalTrials.gov (NCT03588325). [ABSTRACT FROM AUTHOR]

An abstract of the paper "The Formation of a Ca2+ -dependent Complex of C-reactive Protein and Very Low Density Lipoprotein Causes the Biphasic Transmittance Waveform," by Michael Nesheim, John Samis and colleagues is presented.

The 'biphasic transmittance waveform' (BTW) refers to a decrease in light transmittance that often occurs prior to clotting in coagulation assays of critically ill patient plasmas. It correlates with disseminated intravascular coagulation and mortality. The present work shows that the BTW is due to the rapid formation of a precipitate and a coincident change in turbidity in re-calcified plasma. The precipitate was isolated from patient plasma and contained lipids typical of very low density lipoprotein (VLDL), plus the proteins apolipoprotein B-100 and C-reactive protein (CRP). Precipitation also occurred in normal plasma supplemented with CRP. In addition, CRP precipitated with VLDL and intermediate density lipoprotein, but not low density lipoprotein or high density lipoprotein. The Kd value for the CRP/VLDL interaction is 340 nM. The IC50 value of Ca2+ for complex formation is 5.0 mM, and epsilon-aminocaproic acid inhibits the process. In 15 plasmas with the BTW from critically ill patients, CRP was highly elevated (77-398 microg/mL) and VLDL cholesterol ranged from 0.082 to 1.32 mM. The magnitude of the turbidity change on re-calcification correlated well with the calculated level of the CRP/VLDL complex. Thus, the Ca2+-dependent formation of a complex between CRP and VLDL accounts for the BTW.

A decrease in light transmittance before clot formation, manifesting as a biphasic waveform (BPW) pattern in coagulation assays, was previously correlated with the onset of disseminated intravascular coagulation (DIC). In this study of 1187 consecutive admissions to the intensive care unit, the degree of this change on admission predicts DIC better than D-dimer measurements. Additionally, the BPW preceded the time of DIC diagnosis by 18 hours, on average, in 56% (203 of 362) of DIC patients. The BPW is due to the rapid formation of a precipitate and coincident turbidity change on recalcification of plasma. The isolated precipitate contains very-low-density lipoprotein (VLDL) and C-reactive protein (CRP). The addition of CRP and Ca(++) to normal plasma also causes the precipitation of VLDL and IDL, but not LDL or HDL. The K(d) of the CRP/VLDL interaction is 340 nM, and the IC(50) for Ca(++) is 5.0 mM. In 15 plasmas with the BPW, CRP was highly elevated (77-398 microg/mL), and the concentration of isolated VLDL ranged from 0.082 to 1.32 mM (cholesterol). The turbidity change on recalcification correlates well with the calculated level of the CRP-VLDL complex. Clinically, the BPW better predicts for DIC than either CRP or triglyceride alone. The complex may have pathophysiological implications because CRP can be detected in the VLDL fraction from sera of patients with the BPW, and the VLDL fraction has enhanced prothrombinase surface activity. The complex has been designated lipoprotein complexed C-reactive protein.