Procalcitonin (PCT) is a protein that consists of 116 amino acids and is the peptide precursor of calcitonin. Calcitonin is initially biosynthesized as PCT which under normal conditions, is found in low levels in the circulation (≤ 0.1 ng/mL). 12 PCT was first described as a marker of bacterial infection in 1993 when high concentrations of calcitonin-like immunoreactivity were detected in the blood of patients with extra-thyroid diseases. 3 Using a monoclonal immunoradiometric assay for calcitonin precursors, investigators measured serum concentrations of procalcitonin in 79 children with bacterial and viral infections. They found serum PCT levels to be very high (6-53 ng/mL) in patients with severe invasive bacterial infections compared to patients with mild local bacterial infections or viral infections (0.1-1.5 ng/mL); additionally, they noticed PCT levels decreased rapidly during antibiotic therapy and that calcitonin levels were normal in all subjects irrespective of PCT levels. They concluded PCT levels are raised during bacterial septic conditions, and serum concentrations are correlated with severity of microbial invasion.A 1994 study also found PCT levels rise in response to bacterial infection, by injecting healthy volunteers with endotoxin and measuring serial PCT levels. 4 Levels were detectable

The biological activity of 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] remains controversial, but it has been suggested that it contributes to fracture healing. Cyp24a1-/- mice, synthesizing no 24R,25(OH)2D3, show suboptimal endochondral ossification during fracture repair, with smaller callus and reduced stiffness. These defects were corrected by 24R,25(OH)2D3 treatment, but not by 1,25-dihydroxyvitamin D3. Microarrays with Cyp24a1-/- callus mRNA identified FAM57B2 as a mediator of the 24R,25(OH)2D3 effect. FAM57B2 produced lactosylceramide (LacCer) upon specific binding of 24R,25(OH)2D3. Fam57b inactivation in chondrocytes (Col2-Cre Fam57bfl/fl) phenocopied the callus formation defect of Cyp24a1-/- mice. LacCer or 24R,25(OH)2D3 injections restored callus volume, stiffness, and mineralized cartilage area in Cyp24a1-null mice, but only LacCer rescued Col2-Cre Fam57bfl/fl mice. Gene expression in callus tissue suggested that the 24R,25(OH)2D3/FAM57B2 cascade affects cartilage maturation. We describe a previously unrecognized pathway influencing endochondral ossification during bone repair through LacCer production upon binding of 24R,25(OH)2D3 to FAM57B2. Our results identify potential new approaches to ameliorate fracture healing.

Study objectivesThe shock index (SI), defined as the ratio of the heart rate (HR) to the systolic blood pressure (BP), is used as a prognostic tool in trauma and in specific disease states. However, there is scarcity of data about the utility of the SI in the general emergency department (ED)population. Our goal was to use a large national database of EDs in the United States (US) to determine whether the likelihood of inpatient mortality and hospital admission was associated with initial SI at presentation.MethodsData from the National Hospital Ambulatory Medical Care Survey were retrospectively reviewed to obtain a weighted sample of all US ED visits between 2005 and 2010. All adults >18 years old who survived the ED visit were included, regardless of their chief complaint. Likelihood ratios (LR) were calculated for a range of SI values, in order to determine SI thresholds most predictive of hospital admission and inpatient mortality. +LRs >5 were considered to be clinically significant.ResultsA total of 526 455 251 adult patient encounters were included in the analysis. 56.9% were women, 73.9% were white and 53.2% were between the ages of 18 and 44 years. 88 326 638 (15.7%) unique ED visits resulted in hospital admission and 1 927 235 (2.6%) visits resulted in inpatient mortality. SI>1.3 was associated with a clinically significant increase in both the likelihood of hospital admission (+LR=6.64) and inpatient mortality (+LR=5.67). SI>0.7 and >0.9, the traditional cited cut-offs, were only associated with marginal increases (+LR= 1.13; 1.54 for SI>0.7 and +LR=1.95; 2.59 for SI>0.9 for hospital admission and inpatient mortality, respectively).ConclusionsIn this largest retrospective study to date on SI in the general ED population, we demonstrated that initial SI at presentation to the ED could potentially be useful in predicting the likelihood of hospital admission and inpatient mortality, which could help guide rapid and accurate acuity designation, resource allocation and disposition.

In our single-centre study, the initial SI recorded in the ED shows promise as a clinical metric in the general adult ED population, increasing the probability of both hospital admission and inpatient mortality, specifically at a threshold of SI >1.2.