Proteins of the mitotic checkpoint and spindle are related to chromosomal instability and unfavourable prognosis in patients with myelodysplastic syndrome.

AIMS: To study the immunoexpression of proteins related to the mitotic checkpoint (cell division cycle 20 (CDC20), mitotic arrest deficient 2 (MAD2)) and the mitotic spindle (Aurora-B) in patients with myelodysplastic syndrome (MDS). METHODS: Protein expression was analysed in bone marrow tissue samples from 40 patients with MDS using immunohistochemistry. Prognostic markers (transfusion dependency, depth of cytopenias, chromosomal abnormalities and survival) were also studied. RESULTS: Higher MAD2 expression was observed among patients with platelets <50×10(9)/L than among patients with platelets ≥50×10(9)/L (42.6±22.8% vs 22.7±19.1%, respectively). Higher CDC20 expression was identified among patients with three dysplasias compared with patients who presented with one or two dysplasias (33.9±24.1% vs 10.5±5.7% vs 12.8±7.8%, respectively), among patients who exhibited a complex versus non-complex karyotype (50.0±30.2% vs 18.4±14%, respectively) and among patients with platelets <50×10(9)/L vs platelets ≥50×10(9)/L (38.2±26.2% vs 16.1±12.4%, respectively). Higher Aurora-B expression was found in patients with an abnormal versus normal karyotype (21.2±13.2% vs 7.5±5.0%, respectively). High expression of MAD2 and CDC20 (≥50%) was associated with severe thrombocytopenia. We also found statistically significant differences in the overall survival rate when comparing different degrees of CDC20, MAD2 and Aurora-B protein expression. CONCLUSIONS: To the best of our knowledge, this is the first report to demonstrate that these proteins are associated with chromosomal abnormalities and poor prognosis in patients with MDS.

Acute and short-term effect of an extra dose of formoterol in COPD patients.

RATIONALE: Formoterol action may decrease progressively after its inhalation. It is unknown if this decrease of bronchodilation following formoterol use could be associated with worsening hyperinflation. OBJECTIVES: To investigate whether the use of an extra daily dose of formoterol could promote a greater reduction in lung hyperinflation and a greater improvement in inspiratory capacity (IC) compared to usual doses. METHODS: 56 hyperinflated COPD patients were divided into two groups: F2 and F3. Basal evaluation was carried out after 5 days of formoterol washout. In order to evaluate the acute effect, spirometry and body plethysmography were performed 8 h after the first formoterol dose in both groups and repeated 1 h after an additional formoterol dose (F3) or placebo (F2). The short-term effect was evaluated by measuring the resting lung function after a 14-day period of formoterol t.i.d. (F3) or formoterol b.i.d. + placebo (F2). MEASUREMENTS AND MAIN RESULTS: A second formoterol dose inhaled 8 h after the previous dose promoted additional improvements in lung function, as demonstrated by higher IC (118 ± 140 mL, p < 0.001) and lower functional residual capacity (FRC) (-383 ± 367 mL, p < 0.001). On day 15, the mean differences from baseline regarding all lung function variables were similar between the groups. CONCLUSION: An extra daily dose of formoterol inhaled 8 h after a previous dose could result in an acute additional peak of bronchodilation. However, short-term formoterol t.i.d. showed no advantages over formoterol b.i.d. concerning reduction of hyperinflation in resting lung function.

Epidemiology of and factors associated with end-of-life decisions in a surgical intensive care unit.

OBJECTIVE: To investigate the epidemiology of and possible factors associated with end-of-life decisions in a surgical intensive care unit. DESIGN: Analysis of prospectively collected data. SETTING: University hospital surgical intensive care unit. PATIENTS: All patients admitted to the surgical intensive care unit between September 2002 and July 2006. MEASUREMENTS AND MAIN RESULTS: During the study period, 14,720 patients were admitted to the surgical intensive care unit (61.8 male; mean age, 62 yrs). The prevalence of end-of-life decisions was 2.7% (n = 398); 230 patients (1.6%) had a do-not-resuscitate order, 90 (0.6%) had a decision to withhold therapy, and 78 (0.5%) had a decision to withdraw life-supportive therapy. Patients with end-of-life decisions had higher severity scores on the day of intensive care unit admission, were mostly unplanned admissions, were older, and were more commonly referred from the emergency room or other hospitals compared to those who did not have an end-of-life decision. The prevalence of end-of-life decisions increased significantly with the severity of sepsis. An end-of-life decision was made for 29% of the patients who died in the intensive care unit. Intensive care unit and hospital mortality rates were 6.1% and 10.3%, respectively, overall, and 65.1% and 82.2%, respectively, in patients with an end-of-life decision. In multivariate analysis, older age, admission from another hospital, cirrhosis, sepsis syndromes, simplified acute physiology score II, and sequential organ failure assessment scores were independently associated with end-of-life decisions. CONCLUSIONS: Twenty-nine percent of patients who die in the surgical intensive care unit have an end-of-life decision. Severe sepsis/septic shock was associated with a 16-fold increased likelihood of having an end-of-life decision.