What is a safe waiting time for coronary artery bypass surgery?

To determine the factors that influenced doctors' prioritization and decisions on safe waiting time for coronary artery bypass surgery, 50 'paper patients', based on a random sample of cases who actually had surgery, were assessed by 33 clinicians. We used linear regression models to reflect the impact of clinical and non-clinical 'cues' on safe waiting time and priority decisions. The benefits of surgery tended to be over-estimated. For example, the average perceived gain in life expectancy for patients with left main-stem disease was 6.74 years. However, models incorporating only the perceptions of benefit as independent variables (i.e. the anticipated symptom reduction, MI risk reduction and life expectancy extension), had only modest explanatory power (mean R2 was 0.55 for safe waiting time, and 0.56 for priority decisions). Models which incorporated perceptions of benefit and the cases' clinical and non-clinical characteristics had generally much higher explanatory power (mean R2, 0.83 and 0.86, respectively). Lifestyle and demographic variables had much less impact on the doctors' judgements than the major clinical cues of angina severity and left main-stem stenosis. Demographic and lifestyle cues had different impacts on safe waiting time and priority for about 25% of doctors.      

Thrombosis in inflammatory bowel disease: clinical setting, procoagulant profile and factor V Leiden

Patients with inflammatory bowel disease have an increased frequency of thromboembolism, and microvascular thrombosis has been proposed as a contributory pathogenic factor. The mechanism of enhanced procoagulant activity is not understood. We examined the clinical setting of thromboembolic events in 52 patients with Crohn's disease or ulcerative colitis, and assessed the procoagulant laboratory profile, including Factor V Leiden, in a subset of 20 patients to identify procoagulant risk factors. Patients who developed thrombosis tended to be young; 60% of thrombotic events occurred in patients under 50 years. Multiple thromboembolic episodes occurred in 13% and unusual sites of thrombosis (e.g. intracardiac, cerebral, inominate veins) in 11%. No risk factor was identifiable in 52% of cases and two-thirds of thromboses occurred in an out-patient setting. The mortality rate was 8%. Evidence for inflammatory disease activity was found in only 45% of patients with ulcerative colitis at the time of the thromboembolic event, in contrast to 89% of those with Crohn's disease. Assays for specific coagulation defects were negative in all cases tested (protein S, C were normal in 17/17; anti-thrombin III, anti-phospholipid antibodies and activated protein C resistance were negative in 20/20, and only 1/20 patients was found to be heterozygous for Factor V leiden. Thrombosis in inflammatory bowel disease is important because it occurs in a young population, often in unusual sites, and has a high mortality. The development of thrombosis is related to active inflammatory disease in most patients with Crohn's disease but apparently not in those with ulcerative colitis. Since approximately half of the patients had no other identifiable risk factor, there remains a substantial group of patients with IBD who develop thrombosis for unknown reasons.      

Effect of freezing on the in vivo recovery of irradiated red cells

BACKGROUND: Transfusion-associated graft-versus-host disease can be prevented by gamma radiation of blood components. The increased use of blood components donated for patients by their family members has resulted in an increased demand for the storage and handling of irradiated units, and the ability to freeze the cells would allow storage beyond their current expiration date. STUDY DESIGN AND METHODS: To assess the effect of freezing and deglycerolization on irradiated red cells, studies of autologous radiolabeled red cell recovery were performed using normal volunteers. Each unit of CPDA-1 red cells was immediately divided into two equal volumes. Further handling of each half was identical except that one was irradiated (3500 cGy). The units were grouped under three protocols: I, irradiated on Day 0 and frozen on Day 5 (n = 4); II, irradiated on Day 7, rejuvenated, and frozen on Day 14 (n = 5); and III, irradiated on Day 14, rejuvenated, and frozen on Day 18 (n = 3). All cells were frozen for 3 to 10 months at -80 degrees C. RESULTS: Irradiated and control units showed no significant differences in supernatant potassium or hemoglobin. Autologous 24-hour posttransfusion recoveries (mean +/− SD) for the three groups were: I, 89.7 +/− 5.6 percent (control, 90.6 +/− 3.2%); II, 85.3 +/− 5.7 percent (control, 83.7 +/− 3.0%); and III, 79.5 +/− 1.4 percent (control, 82.6 +/− 5.2%). CONCLUSION: Irradiated red cells can be frozen after being stored under various conditions and can still meet established guidelines requiring 75-percent recovery 24 hours after transfusion.     

The stated and tacit impact of demographic and lifestyle factors on prioritization decisions for cardiac surgery

In a clinical judgement analysis, we used linear regression models to reflect the impact of clinical and non-clinical cues on priority decisions, by comparing the stated prioritization policies of 30 clinicians with their actual policies as revealed by an appraisal of 50 'paper patients'. Correspondence was modest for some cues, e.g. 25 doctors said they accounted for age, but age only had a significant bearing in the derived decision models of two doctors. Correspondence between the derived and expressed weights was greatest for clinical angina grade and the presence of left main stem stenosis. Correlation between the rank order of importance between the two models was poor for most of the cues, and statistically significant only for smoking. However, stated policies made it appear that lifestyle factors such as smoking habit would influence prioritization decisions for most clinicians but policies derived from actual prioritization decisions seldom related to lifestyle or demographic variables. There were significant differences in the degree of correlation between the two models according to the experience of the clinician. However, correspondence was not significantly better for doctors with cardiological training than those without. The overall contribution of demographic and lifestyle factors to decision making appears to be small, suggesting that they should be omitted from prioritization guidelines.      

Assembly of Weibel-Palade body-like tubules from N-terminal domains of von Willebrand factor

Endothelial cells assemble von Willebrand factor (VWF) multimers into ordered tubules within storage organelles called Weibel-Palade bodies, and tubular packing is necessary for the secretion of VWF filaments that can bind connective tissue and recruit platelets to sites of vascular injury. We now have recreated VWF tubule assembly in vitro, starting with only pure VWF propeptide (domains D1D2) and disulfide-linked dimers of adjacent N-terminal D'D3 domains. Assembly requires low pH and calcium ions and is reversed at neutral pH. Quick-freeze deep-etch electron microscopy and three-dimensional reconstruction of negatively stained images show that tubules contain a repeating unit of one D'D3 dimer and two propeptides arranged in a right-handed helix with 4.2 units per turn. The symmetry and location of interdomain contacts suggest that decreasing pH along the secretory pathway coordinates the disulfide-linked assembly of VWF multimers with their tubular packaging.     

Reduced amygdala volume in newly admitted psychiatric in-patients with unipolar major depression

Structural neuroimaging studies investigating amygdala volumes in patients suffering from major depression have yielded variable results. Discrepant findings across studies may be attributable in part to heterogeneity with respect to antidepressant medication and to lack of adequate control for the effects of total brain volume and age. Here, 24 unipolar depressed in-patients newly admitted to a psychiatric unit and 14 healthy control participants matched for age, gender, and years of education underwent quantitative magnetic resonance imaging (MRI) toward the end of a one-week washout period. Saliva cortisol was measured at 08.00 and at 16.00 h in patients during washout. Absolute amygdala volumes were significantly reduced in the patient group (by 13% in left amygdala and 12% in right amygdala). The effect of reduced amygdala volumes in patients remained significant after correction for brain volume (BV) and age. Furthermore, amygdala volume measurements in the patient sample showed a significant inverse relationship to the number of preceding depressive episodes. In patients, severity of disease (baseline HAMD scores) and baseline cortisol levels were not related to amygdala volume. This study of a sample of unmedicated depressed in-patients adds to the small, yet growing, body of evidence linking untreated major depression to reduced amygdala volume.     

Hippocampal volume reduction and HPA-system activity in major depression

Structural imaging studies investigating hippocampal volumes in patients suffering from major depression have yielded mixed results. Here, 24 unipolar depressed in-patients and 14 healthy controls carefully matched for age, gender, and years of education underwent quantitative magnetic resonance imaging (MRI). Saliva cortisol was measured at 0800 and 1600 h in patients during a one-week wash-out and the following 4 weeks. Hippocampal volumes were significantly reduced in the patient group even after adjusting for intracranial brain volume (ICV) and age. Across groups, age was significantly negatively correlated with uncorrected hippocampal volumes. In patients, severity of disease (baseline HAMD scores) and baseline cortisol levels were not related to hippocampal volumes. However, there was a negative association between duration of the index episode before hospitalization and hippocampal volumes. Additionally, hippocampal volumes were significantly negatively correlated with duration of illness. Finally, we observed a trend for higher hippocampal volumes in those patients who showed a subsequent decrease in cortisol levels under pharmacotherapy.     

Systemic nanoparticle paclitaxel (nab-paclitaxel) for in-stent restenosis I (SNAPIST-I): a first-in-human safety and dose-finding study

BACKGROUND: Paclitaxel-eluting stents inhibit restenosis; however, this technology has drawbacks (e.g., stent thrombosis, requirement for long-term antiplatelet therapy, and cost--particularly for patients with multivessel disease). Systemic treatment with a novel 130-nm, albumin-bound particle form of paclitaxel (nab-paclitaxel) has been shown to reduce restenosis in animals. HYPOTHESIS: This study was designed to establish the safety and optimal dose of systemic nab-paclitaxel for reducing in-stent restenosis in humans. If well tolerated, systemic nab-paclitaxel may be used with any available bare-metal stent and at potentially lower cost than drug-eluting stents. METHODS: Patients received nab-paclitaxel 10, 30, 70, or 100 mg/m(2) intravenously after stenting of a single de novo lesion >or= 3 mm in diameter. Study endpoints included safety and major adverse cardiac events (MACE) at 2 and 6 months. RESULTS: Data were obtained for all 23 enrolled patients (mean age 66 +/- 10 years, 74% men, 26% with diabetes). No significant adverse events (AE) were attributable to nab-paclitaxel at 10 or 30 mg/m(2). Moderate neutropenia, moderate sensory neuropathy, and mild to moderate, reversible alopecia occurred only at doses of 70 and 100 mg/m(2); therefore, doses of 70 mg/m(2) or higher were considered unacceptable in this patient population. No MACE were reported at 2 months. At 6 months, 4 target lesion revascularizations (TLR) for restenoses were reported (2 each in the 10- and 100-mg/m(2)-dose groups). CONCLUSIONS: Systemic nab-paclitaxel was well tolerated at doses below 70 mg/m(2) in this group of patients; no unexpected AE were noted. Additional studies are under way to explore intravenous and intracoronary administration of nab-paclitaxel.     

Flat panel detector-based volumetric computed tomography (fpVCT): performance evaluation of volumetric methods by using different phantoms in comparison to 64-multislice computed tomography

OBJECTIVES: Evaluation of a silicon-based flat panel volumetric computed tomography (fpVCT) and multislice CT in terms of volumetry of phantoms with different algorithms. Furthermore, to compare the different volumetric analysis methods themselves. MATERIALS AND METHODS: Four phantoms of different materials have been scanned with fpVCT (GE prototype with circular gantry with 2 aSi/CsI flat panel detector) and a 64-slice spiral CT (MSCT: LightSpeed VCT). Three spherical phantoms of different materials and 1 phantom with an irregular shape were evaluated. True volumes were calculated in dependence from the diameter or by water displacement method. Imaging parameters (80 kVp, 100 mA) and the position of the phantoms were identical in both techniques. After reconstruction of the images different algorithms have been used 4 times for each phantom. These analysis methods have been performed: Region growing, threshold method, planimetry, 3-dimensional volumetry measurement by using the equation of an ellipsoid (ellipse) and an advanced lung analysis modus [single advanced lung analysis (ALA)]. The mean values and the standard deviations have been evaluated and compared with the true volumes. RESULTS: In all phantoms fpVCT showed better results with lower deviations from the true values than in MSCT, especially for small volumes of the phantoms. However, the results of the ALA single method demonstrated no significant difference between the fpVCT and MSCT. The comparison of the different analysis methods revealed that 3-dimensional measurement with the ellipse method was the worst method for volume estimation, especially for the irregularly formed phantom. CONCLUSION: fpVCT was superior to MSCT in the volumetry of small objects. The ellipse method has been shown to be the worst for volumetry with the highest relative deviations from the true volume value. The single ALA method shows the lowest standard deviation thereby revealing a reproducible volumetric method for small nodules. However, further future developments of volumetric analysis methods are necessary to use them accurately in daily routine. Due to the truly isotropic volume data set with high spatial resolution fpVCT is a powerful tool for the volumetry of small nodules.