Reliability of an fMRI paradigm for emotional processing in a multisite longitudinal study

Multisite neuroimaging studies can facilitate the investigation of brain‐related changes in many contexts, including patient groups that are relatively rare in the general population. Though multisite studies have characterized the reliability of brain activation during working memory and motor functional magnetic resonance imaging tasks, emotion processing tasks, pertinent to many clinical populations, remain less explored. A traveling participants study was conducted with eight healthy volunteers scanned twice on consecutive days at each of the eight North American Longitudinal Prodrome Study sites. Tests derived from generalizability theory showed excellent reliability in the amygdala ( = 0.82), inferior frontal gyrus (IFG; = 0.83), anterior cingulate cortex (ACC; = 0.76), insula ( = 0.85), and fusiform gyrus ( = 0.91) for maximum activation and fair to excellent reliability in the amygdala ( = 0.44), IFG ( = 0.48), ACC ( = 0.55), insula ( = 0.42), and fusiform gyrus ( = 0.83) for mean activation across sites and test days. For the amygdala, habituation ( = 0.71) was more stable than mean activation. In a second investigation, data from 111 healthy individuals across sites were aggregated in a voxelwise, quantitative meta‐analysis. When compared with a mixed effects model controlling for site, both approaches identified robust activation in regions consistent with expected results based on prior single‐site research. Overall, regions central to emotion processing showed strong reliability in the traveling participants study and robust activation in the aggregation study. These results support the reliability of blood oxygen level‐dependent signal in emotion processing areas across different sites and scanners and may inform future efforts to increase efficiency and enhance knowledge of rare conditions in the population through multisite neuroimaging paradigms. Hum Brain Mapp 36:2558–2579, 2015. © 2015 Wiley Periodicals, Inc .     

Similar Neutrophil-Driven Inflammatory and Antibacterial Responses in Elderly Patients with Symptomatic and Asymptomatic Bacteriuria

Differential diagnosis of asymptomatic bacteriuria (ASB) and urinary tract infection (UTI) is based on the presence of diverse symptoms, including fever (≥38.5°C), rigors, malaise, lethargy, flank pain, hematuria, suprapubic discomfort, dysuria, and urgent or frequent urination. There is consensus in the medical community that ASB warrants antibiotic treatment only for patients undergoing urological procedures that lead to mucosal bleeding, catheterized individuals whose ASB persists for more than 48 h after catheter removal, and pregnant women. Pyuria is associated with UTI and implicates host immune responses via release of antibacterial effectors and phagocytosis of pathogens by neutrophils. Such responses are not sufficiently described for ASB. Metaproteomic methods were used here to identify the pathogens and evaluate molecular evidence of distinct immune responses in cases of ASB compared to UTI in elderly patients who were hospitalized upon injury. Neutrophil-driven inflammatory responses to invading bacteria were not discernible in most patients diagnosed with ASB compared to those with UTI. In contrast, proteomic urine analysis for trauma patients with no evidence of bacteriuria, including those who suffered mucosal injuries via urethral catheterization, rarely showed evidence of neutrophil infiltration. The same enzymes contributing to the synthesis of leukotrienes LTB₄ and LTC₄, mediators of inflammation and pain, were found in the UTI and ASB cohorts. These data support the notion that the pathways mediating inflammation and pain in most elderly patients with ASB are not quantitatively different from those seen in most elderly patients with UTI and warrant larger clinical studies to assess whether a common antibiotic treatment strategy for elderly ASB and UTI patients is justified.     

Dengue in an area of the Colombian Caribbean

Background:

In Colombia, dengue is an endemic disease and the four serotypes have been reported.

Objective:

To describe the frequency and severity of dengue in an area of the Colombian Caribbean (Department of Cordoba)

Methods:

A retrospective study was conducted. Two data sources were analysed: The database from the Direction of Health in Córdoba, and clinical registers of patients diagnosed with haemorrhagic fevers and fevers of unknown origin in reference hospitals.

Results:

The mean incidence of dengue between 2003-2010 was 36.5 cases/10⁵ inhabitants (CI95%: 34.3-37.5) and adjusted for sub-reporting, could be between 178.5 and 521.6. The mean incidence of severe dengue was 4.7 cases/10⁵ inhabitants (CI95%: 4.3-5.0). Mean mortality rate due to dengue was 0.3 cases/10⁵ inhabitants. The fatality rate was below 1%. The mean total leukocyte count in patients with dengue was 6,181 mm³ (CI95%: 5,973-6,389) and with severe Dengue was 4,729 mm³ (CI95%: 4,220-5,238). The average platelet count in patients with Dengue was 118,793/mm³ (CI95%: 107,255-130,331) and in patients with Severe Dengue 77,655 (CI95%: 59,640-95,670). Both differences were statistically significant (p <0.05). The frequency of laboratories test per patient in patients with Dengue and severe Dengue were different.

Conclusion:

The department of Cordoba is a highly endemic zone of Dengue and severe Dengue in the Colombian Caribbean. Moreover, the results show significant differences between dengue and severe dengue so much in tests as in frequency of use of healthcare services.     

Angiopoietin-2 and angiopoietin-like 4 protein provide prognostic information in patients with suspected acute coronary syndrome

Background

Plasma levels of angiopoietin-2 (ANGPT2) and angiopoietin-like 4 protein (ANGPTL4) reflect different pathophysiological aspects of cardiovascular disease. We evaluated their association with outcome in a hospitalized Norwegian patient cohort (n = 871) with suspected acute coronary syndrome (ACS) and validated our results in a similar Argentinean cohort (n = 982).

Methods

A cox regression model, adjusting for traditional cardiovascular risk factors, was fitted for ANGPT2 and ANGPTL4, respectively, with all-cause mortality and cardiac death within 24 months and all-cause mortality within 60 months as the dependent variables.

Results

At 24 months follow-up, 138 (15.8%) of the Norwegian and 119 (12.1%) of the Argentinian cohort had died, of which 86 and 66 deaths, respectively, were classified as cardiac. At 60 months, a total of 259 (29.7%) and 173 (17.6%) patients, respectively, had died. ANGPT2 was independently associated with all-cause mortality in both cohorts at 24 months [hazard ratio (HR) 1.27 (95% confidence interval (CI), 1.08–1.50) for Norway, and HR 1.57 (95% CI, 1.27–1.95) for Argentina], with similar results at 60 months [HR 1.19 (95% CI, 1.05–1.35) (Norway), and HR 1.56 (95% CI, 1.30–1.88) (Argentina)], and was also significantly associated with cardiac death [HR 1.51 (95% CI, 1.14–2.00)], in the Argentinean population. ANGPTL4 was significantly associated with all-cause mortality in the Argentinean cohort at 24 months [HR 1.39 (95% CI, 1.15–1.68)] and at 60 months [HR 1.43 (95% CI, 1.23–1.67)], enforcing trends in the Norwegian population.

Conclusions

ANGPT2 and ANGPTL4 were significantly associated with outcome in similar ACS patient cohorts recruited on two continents.

Clinical Trial Registration

ClinicalTrials.gov Identifier: NCT00521976. ClinicalTrials.gov Identifier: NCT01377402.

     

Human endothelial cells derived from circulating progenitors display specific functional properties compared with mature vessel wall endothelial cells

Endothelial progenitor cells (EPCs) were shown to be present in systemic circulation and cord blood. We investigated whether EPCs display specific properties compared with mature endothelial cells. Human cord blood CD34+ cells were isolated and adherent cells were amplified under endothelial conditions. Expression of specific markers identified them as endothelial cells, also called endothelial progenitor-derived cells (EPDCs). When compared to mature endothelial cells, human umbilical vein endothelial cells (HUVECs) and human bone marrow endothelial cells (HBMECs), endothelial markers, were expressed to the same extent except for KDR, which is expressed more in EPDCs. They display a higher proliferation potential. Functional studies demonstrated that EPDCs were more sensitive to angiogenic factors, which afford these cells greater protection against cell death compared with HUVECs. Moreover, EPDCs exhibit more hematopoietic supportive activity than HUVECs. Finally, studies in nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice demonstrated that human circulating EPCs are able to colonize a Matrigel plug. EPDCs display the morphology and phenotype of endothelial cells. Their functional features indicate, however, that although these cells have undergone some differentiation steps, they still have the properties of immature cells, suggesting greater tissue repair capabilities. Future use of in vitro amplified peripheral blood EPDCs may constitute a challenging strategy for cell therapy.     

Dexmedetomidine versus standard care sedation with propofol or midazolam in intensive care: an economic evaluation

IntroductionDexmedetomidine was shown in two European randomized double-blind double-dummy trials (PRODEX and MIDEX) to be non-inferior to propofol and midazolam in maintaining target sedation levels in mechanically ventilated intensive care unit (ICU) patients. Additionally, dexmedetomidine shortened the time to extubation versus both standard sedatives, suggesting that it may reduce ICU resource needs and thus lower ICU costs. Considering resource utilization data from these two trials, we performed a secondary, cost-minimization analysis assessing the economics of dexmedetomidine versus standard care sedation.MethodsThe total ICU costs associated with each study sedative were calculated on the basis of total study sedative consumption and the number of days patients remained intubated, required non-invasive ventilation, or required ICU care without mechanical ventilation. The daily unit costs for these three consecutive ICU periods were set to decline toward discharge, reflecting the observed reduction in mean daily Therapeutic Intervention Scoring System (TISS) points between the periods. A number of additional sensitivity analyses were performed, including one in which the total ICU costs were based on the cumulative sum of daily TISS points over the ICU period, and two further scenarios, with declining direct variable daily costs only.ResultsBased on pooled data from both trials, sedation with dexmedetomidine resulted in lower total ICU costs than using the standard sedatives, with a difference of €2,656 in the median (interquartile range) total ICU costs—€11,864 (€7,070 to €23,457) versus €14,520 (€7,871 to €26,254)—and €1,649 in the mean total ICU costs. The median (mean) total ICU costs with dexmedetomidine compared with those of propofol or midazolam were €1,292 (€747) and €3,573 (€2,536) lower, respectively. The result was robust, indicating lower costs with dexmedetomidine in all sensitivity analyses, including those in which only direct variable ICU costs were considered. The likelihood of dexmedetomidine resulting in lower total ICU costs compared with pooled standard care was 91.0% (72.4% versus propofol and 98.0% versus midazolam).ConclusionsFrom an economic point of view, dexmedetomidine appears to be a preferable option compared with standard sedatives for providing light to moderate ICU sedation exceeding 24 hours. The savings potential results primarily from shorter time to extubation.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00479661","term_id":"NCT00479661"}}NCT00479661 (PRODEX), {"type":"clinical-trial","attrs":{"text":"NCT00481312","term_id":"NCT00481312"}}NCT00481312 (MIDEX).

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-015-0787-y) contains supplementary material, which is available to authorized users.     

A prospective randomized trial of tocainide in patients following myocardial infarction

One hundred forty-six patients with recent acute myocardial infarction were grouped at random into those treated with tocainide, an oral analogue of lignocaine, or placebo and followed up for 6 months. In addition to standard investigations, a 24-hour ambulatory taped ECG recording was obtained prior to randomization and thereafter at 2, 8, 16, and 24 hours after discharge. The ECGs were analyzed by means of an automated, computerized reporting system. Forty-two patients had significant ventricular arrhythmias, 10 of whom had effective plasma levels of tocainide compared with 27 patients on placebo (P < 0.005). In the placebo patients with increasing mobilization there was a consistent rise in the number of ventricular ectopic beats per day. There was no such increase in the tocainide patients (p < 0.01). Side effects were few and the incidence of central nervous system side effects was similar in both the tocainide and placebo groups. There was no conclusive evidence of myocardial depression, heart rate and blood pressure being unchanged over the 6-month period. Although ventricular arrhythmias were suppressed, the number of patients in the study was too small to draw conclusions regarding the mortality rate.     

Pneumopericardium due to transdiaphragmatic perforation of a gastric ulcer

Summary A 65-year-old man presented with cardiogenic shock and massive pneumopericardium. A gastropericardial fistula due to transdiaphragmatic penetration of a large fundal ulcer was documented radiographically and confirmed at autopsy. Previously recorded cases of pneumopericardium complicating gastric ulcers or other diseases of the digestive tract are briefly reviewed.