A retrospective review of vital signs and clinical outcomes of febrile infants younger than 3 months old presenting to the emergency department.

OBJECTIVES: Febrile infants younger than 3 months old present a diagnostic dilemma to the emergency physician. We aim to describe a large population of febrile infants less than 3 months old presenting to a pediatric emergency department (ED) and to assess the performance of current heart rate guidelines in the prediction of serious infections (SI). MATERIALS AND METHODS: We performed a retrospective review of febrile infants younger than 3 months old, between March 2015 and Feb 2016, in a large tertiary pediatric ED. We documented the primary outcome of SI for each infant, as well as the clinical findings, vital signs, and Severity Index Score (SIS). We assessed the performance of the Paediatric Canadian Triage and Acuity Scale (PaedCTAS), Advanced Pediatric Life Support (APLS) guidelines and Fleming normal reference values, using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under receiver operating characteristics curve (AUC). RESULTS: 1057 infants were analyzed, with 326 (30.6%) infants diagnosed with SI. High temperature, tachycardia, and low SIS score were significantly associated with SI. Item analysis showed that the SIS performance was driven by the presence of mottling (p = 0.003) and high temperature (p<0.001). The APLS guideline had the highest sensitivity (66.0%, 95% CI 60.5-71.1%), NPV (73.3%, 95% CI 69.7-76.5%) and AUC (0.538), while the PaedCTAS (2 standard deviation from normal) had the highest specificity (98.5%, 95% CI 97.3-99.3%) and PPV (55.2%, 95% CI 32.7-71.0%). CONCLUSIONS: Current guidelines on infantile heart rates have a variable performance. In our study, the APLS heart rate guidelines performed with the highest sensitivity, but no individual guideline predicted for SIs satisfactorily.

Leeches run cold, then hot.

Food processing is costly, potentially limiting the energy and time devoted to other essential functions such as locomotion or reproduction. In ectotherms, post-prandial thermophily, the selection of a warm environmental temperature after feeding, may be advantageous in minimizing the duration of this elevated cost. Although present in many vertebrate taxa, this behaviour had not previously been observed in invertebrates. Sanguivorous leeches ingest large blood meals that are costly to process and limit mobility until excess fluid can actively be expelled to reduce body volume. When presented with a temperature gradient from 10°C to 30°C, leeches select a temperature that is significantly warmer (24.3 ± 0.9°C, n = 6) than their acclimation temperature (T(a), 21°C). Unfed leeches preferred temperatures that were significantly cooler than ambient (12.8 ± 0.9°C, n = 6). This behavioural strategy is consistent with minimizing the time course of elevated post-feeding energy costs and reducing energy expenditure during fasting. Our observations raise the possibility that thermoregulatory behaviour of this type is an unrecognized feature of other invertebrate taxa.

Use of mass spectrometry to identify protein biomarkers of disease severity in the synovial fluid and serum of patients with rheumatoid arthritis.

OBJECTIVE: To identify a panel of candidate protein biomarkers of rheumatoid arthritis (RA) that can predict which patients will develop erosive, disabling disease. METHODS: A 2-step proteomic approach was used for biomarker discovery and verification. In the first step, 2-dimensional liquid chromatography-coupled tandem mass spectrometry was used to generate protein profiles of synovial fluid (SF) from patients with either erosive RA (n = 5) or nonerosive RA (n = 5). In the second step, the selected candidate markers were verified using quantitative multiple reaction monitoring mass spectrometry in sera of patients with erosive RA (n = 15) or nonerosive RA (n = 15) and of healthy controls (n = 15). RESULTS: Through differential profiling of proteins in the <40-kd portion of the SF proteome, we selected 33 prospective candidate biomarkers from a total of 418 identified proteins. Among the proteins that were elevated in the SF of patients with erosive RA were C-reactive protein (CRP) and 6 members of the S100 protein family of calcium-binding proteins. Significantly, levels of CRP, S100A8 (calgranulin A), S100A9 (calgranulin B), and S100A12 (calgranulin C) proteins were also elevated in the serum of patients with erosive disease compared with patients with nonerosive RA or healthy individuals. CONCLUSION: Several potential protein marker candidates have been identified for prognosis of the erosive form of RA. This study demonstrates the facility of using protein mass spectrometry in SF and serum for global discovery and verification of clinically relevant sets of disease biomarkers.

Identification of two novel loci for dominantly inherited familial amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive, adult-onset motor neuron disease that arises as a dominantly inherited trait in approximately 10% of ALS cases. Mutations in one gene, cytosolic Cu/Zn superoxide dismutase (SOD1), account for approximately 25% of familial ALS (FALS) cases. We have performed a genetic linkage screen in 16 pedigrees with FALS with no evidence for mutations in the SOD1 gene and have identified novel ALS loci on chromosomes 16 and 20. The analysis of these genes will delineate pathways implicated as determinants of motor-neuron viability and provide insights into possible therapies for ALS.