A review of the usefulness of D-Dimer in the diagnosis of pulmonary embolism

Pulmonary embolism is a potentially fatal condition that is extremely difficult to accurately diagnose clinically, usually relying on radiological investigations to make the diagnosis. These confirmatory tests are expensive, time consuming and may be associated with considerable morbidity. Thus, the utility of a blood test that reliably makes or refutes the diagnosis is apparent. Most blood tests involve the later stages of thrombolysis. Of these, the D-Dimer tests are the most sensitive, and when combined with monoclonal antibody technology, are of clinical value. Enzyme-linked immunosorbent assay D-Dimer tests have good sensitivity (95%) and moderate specificity (30–45%), but technical considerations prevent their routine use. Latex agglutination tests overcome these technical problems, but their sensitivity is variable (46–100%). Two recently introduced tests show promise. The NYCO-CARD D-Dimer test is a semiquantitative modified enzyme-linked immunosorbent assay test. Relatively few clinical studies have been performed and further validation studies are required. The SimpliRED D-Dimer test uses a new bispecific antibody technique, allows bed-side testing, and has good sensitivity (84–100%) and negative predictive values (92–99%). These tests could be used to screen low risk patients, thus avoiding ventilation-perfusion scans, or in combination with ventilation-perfusion scans and lower limb studies to avoid angiograms in intermediate probability pulmonary embolism patients. Future research will define where these tests show greatest utility, particularly in which patient subgroups, or symptom time intervals.     

The chances that an emergency physician will demonstrate three abdominal aortic aneurysms by ultrasound in the emergency department for credentialing: A statistician's view

The Australasian College for Emergency Medicine requires 15 proctored examinations of the aorta for credentialing in ultrasonography for abdominal aortic aneurysm (AAA). Furthermore, at least three examinations need to be positive for an aneurysm. In the ED where AAA presentations are sporadic, what are the chances that an emergency physician (EP) will have the opportunity to demonstrate three AAAs in the next 12 months? The probability of an event occurring within a given time‐frame can be modelled by the Poisson distribution. Central to the Poisson distribution is the infrequency of the event such as encountering an AAA in the ED. An EP working 30 clinical hours/week in our tertiary‐referral hospital ED can be expected to encounter 15.6 (3.6 symptomatic + 12 asymptomatic) AAA in the next 12 months. The probability of seeing three or more cases during this time is 99.9%. Assuming a proctor can be found for half the cases, the probability of an EP performing proctored ultrasound examinations in at least three AAAs is 98%. This probability drops to 89% if a proctor can be found for only one‐third of cases. For an EP to be almost 100% certain of meeting the credentialing requirements, he/she would need almost 10 proctored ultrasound cases of AAA to be available within his/her shifts during the year. The Poisson distribution has enabled us to model the probability of encountering a given number of AAA in the ED. Analysis such as this may help rationalise the numbers needed for credentialing.     

Infliximab dependency in pediatric Crohn's disease: long-term follow-up of an unselected cohort

BACKGROUND: Infliximab is effective for induction and maintenance of remission in Crohn's disease. It is unknown how long patients should be kept on infliximab therapy. The primary aim of this study was to assess duration of effective maintenance therapy and infliximab dependency in pediatric CD patients initially responding to infliximab therapy. METHODS: All pediatric patients treated with infliximab by pediatric gastroenterologists in the Netherlands because of severe luminal or fistulizing CD with initial response to infliximab therapy were reviewed. Duration of therapy, clinical response and adverse events were recorded. RESULTS: Sixty-six CD patients (37 boys) in 10 hospitals were initially responding to infliximab therapy. Mean age at the start of infliximab therapy was 14.5 years (range, 8.1-18.5 years). Mean follow-up since infliximab was started was 41.3 months (range 12-165). In total, 991 infusions were administered. Analysis demonstrates that 15.2% of patients had prolonged response, while 56.1% were infliximab dependent and 28.8% lost response. In total, 10 patients (15.2%) developed an infection during infliximab therapy and 8 (12.1%) had an immediate allergic reaction. CONCLUSIONS: Good clinical response to maintenance infliximab therapy was seen in 70% of patients. Infliximab maintenance therapy seems very effective and safe in pediatric CD. However, more than half of the patients in this cohort is dependent on repeated infliximab infusions. The number of infliximab infusions received when patients lost response to infliximab was diverse. There was no statistical difference regarding response to infliximab therapy when started early as compared to later in the course of Crohn's disease.     

Extended long-term culture reveals a highly quiescent and primitive human hematopoietic progenitor population

Long-term culture-initiating cells (LTC-IC) are hematopoietic progenitors able to generate colony-forming unit-cells (CFU) after 5 to 8 weeks (35 to 60 days) of culture on bone marrow (BM) stroma and represent the most primitive progenitors currently detectable in vitro. We have recently reported that long-term cultures initiated with CD34+CD38- cells from BM or cord blood are able to continue generating CFU for at least 100 days, ie, beyond the standard LTC-IC period. In this report, single-cell cultures from cord blood and retroviral marking of cord blood and BM were used to study whether the subpopulation of CD34+CD38- cells able to generate CFU beyond 60 days ("extended long-term culture-initiating cells" or ELTC-IC) are functionally distinct from LTC-IC in terms of timing of initial clonal proliferation and generative capacity. All cord blood LTC-IC formed clones of greater than 50 cells by day 30. In contrast, cord blood ELTC- IC proliferated later in culture, 50% forming clones after day 30. Although efficient retroviral marking of LTC-IC was seen (25% to 45%), marking of ELTC-IC was inefficient (< 1%), consistent with a more quiescent progenitor population. There was a positive correlation between time of clonal proliferation and generative capacity. ELTC-IC generated threefold to fourfold more progeny than did LTC-IC (P < .002). These studies show that there is a functional hierarchy of progenitors in long-term culture which correlates with their level of quiescence. By extending the LTC-IC assay, a more primitive progenitor may be studied that may be functionally closer to the human long-term repopulation stem cell in vivo.