QuantiFERON-TB Gold assay for the diagnosis of latent tuberculosis infection.

Tuberculin skin test (TST) has been used for 100 years for the diagnosis of latent tuberculosis (TB) infection (LTBI). In recent years, increasing interest in the diagnosis of TB has led to the development of new assays. QuantiFERON-TB Gold (QFT-G) is an IFN-gamma-release assay that measures the release of interferon after stimulation in vitro by Mycobacterium tuberculosis antigens. The main advantage of this assay with respect to TST is the lack of crossreaction with bacillus Calmette-Guérin and most nontuberculous mycobacteria. QFT-G also eliminates the need for the patient to return for test reading in 48-72 h. In the immunocompromised host and in pediatric populations, studies suggest that the QFT-G better correlates with the risk of TB than the TST, but data remain inconclusive. In contrast to TST, there are no prospective studies regarding the association of the QFT-G result and the risk for development of TB. Given its advantages, the QFT-G may become the standard test for the diagnosis of LTBI.

Effect of transnasal insufflation on sleep disordered breathing in acute stroke: a preliminary study.

BACKGROUND AND PURPOSE: Sleep disordered breathing (SDB) is frequent in acute stroke patients and is associated with early neurologic worsening and poor outcome. Although continuous positive airway pressure (CPAP) effectively treats SDB, compliance is low. The objective of the present study was to assess the tolerance and the efficacy of a continuous high-flow-rate air administered through an open nasal cannula (transnasal insufflation, TNI), a less-intrusive method, to treat SDB in acute stroke patients. METHODS: Ten patients (age, 56.8 ± 10.7 years), with SDB ranging from moderate to severe (apnea-hypopnea index, AHI, >15/h of sleep) and on a standard sleep study at a mean of 4.8 ± 3.7 days after ischemic stroke (range, 1-15 days), were selected. The night after, they underwent a second sleep study while receiving TNI (18 L/min). RESULTS: TNI was well tolerated by all patients. For the entire group, TNI decreased the AHI from 40.4 ± 25.7 to 30.8 ± 25.7/h (p = 0.001) and the oxygen desaturation index >3% from 40.7 ± 28.4 to 31 ± 22.5/h (p = 0.02). All participants except one showed a decrease in AHI. The percentage of slow-wave sleep significantly increased with TNI from 16.7 ± 8.2% to 22.3 ± 7.4% (p = 0.01). There was also a trend toward a reduction in markers of sleep disruption (number of awakenings, arousal index). CONCLUSIONS: TNI improves SDB indices, and possibly sleep parameters, in stroke patients. Although these changes are modest, our findings suggest that TNI is a viable treatment alternative to CPAP in patients with SDB in the acute phase of ischemic stroke.

Role of dendritic cells in the lung: in vitro models, animal models and human studies

Dendritic cells (DCs) are the most potent antigen-presenting cells in the human lung and are now recognized as crucial initiators of immune responses in general. They are arranged as sentinels in a dense surveillance network inside and below the epithelium of the airways and alveoli, where thet are ideally situated to sample inhaled antigen. DCs are known to play a pivotal role in maintaining the balance between tolerance and active immune response in the respiratory system. It is no surprise that the lungs became a main focus of DC-related investigations as this organ provides a large interface for interactions of inhaled antigens with the human body. During recent years there has been a constantly growing body of lung DC-related publications that draw their data from in vitro models, animal models and human studies. This review focuses on the biology and functions of different DC populations in the lung and highlights the advantages and drawbacks of different models with which to study the role of lung DCs. Furthermore, we present a number of up-to-date visualization techniques to characterize DC-related cell interactions in vitro and/or in vivo.

Seal properties of TachoSil: in vitro hemodynamic measurements.

Fibrin glue products and collagen patches are frequently used as a sealing product, preventing surgical side bleedings. This is especially true in the field of cardiovascular surgery, where increasing numbers of patients are being operated with antiplatelet and anticoagulation therapy. The aim of this report was, in an in vitro hemodynamic setting, to examine the sealant properties of the TachoSil (Nycomed Pharma, Linz, Austria) patch. Burst pressure and normal force of 15 TachoSil sealed defects were measured. This was determined in a closed hydraulic system. Mean burst pressure load for a 5-mm defect was 69+/-11.4 mmHg; for a 7-mm defect was 63+/-16 mmHg; and, 62+/-16 mmHg for the defect with a diameter of 10 mm (P>0.05). The mean calculated normal force was as follows: 0.91+/-0.15 N for the 5 mm defect, 6.5+/-1.6 N for the 7 mm, and 8.1+/-0.75 N for the 10 mm defect. The TachoSil patch has the capability to seal small defects. However, at the larger defects the seal character was significantly reduced. These results suggest that the device may be a good alternative for hemostasis for small defects. The capacity to curtail or stop hemorrhage at the larger defects is unlikely.

Effect of transnasal insufflation on sleep disordered breathing in acute stroke: a preliminary study.

BACKGROUND AND PURPOSE: Sleep disordered breathing (SDB) is frequent in acute stroke patients and is associated with early neurologic worsening and poor outcome. Although continuous positive airway pressure (CPAP) effectively treats SDB, compliance is low. The objective of the present study was to assess the tolerance and the efficacy of a continuous high-flow-rate air administered through an open nasal cannula (transnasal insufflation, TNI), a less-intrusive method, to treat SDB in acute stroke patients. METHODS: Ten patients (age, 56.8 ± 10.7 years), with SDB ranging from moderate to severe (apnea-hypopnea index, AHI, >15/h of sleep) and on a standard sleep study at a mean of 4.8 ± 3.7 days after ischemic stroke (range, 1-15 days), were selected. The night after, they underwent a second sleep study while receiving TNI (18 L/min). RESULTS: TNI was well tolerated by all patients. For the entire group, TNI decreased the AHI from 40.4 ± 25.7 to 30.8 ± 25.7/h (p = 0.001) and the oxygen desaturation index >3% from 40.7 ± 28.4 to 31 ± 22.5/h (p = 0.02). All participants except one showed a decrease in AHI. The percentage of slow-wave sleep significantly increased with TNI from 16.7 ± 8.2% to 22.3 ± 7.4% (p = 0.01). There was also a trend toward a reduction in markers of sleep disruption (number of awakenings, arousal index). CONCLUSIONS: TNI improves SDB indices, and possibly sleep parameters, in stroke patients. Although these changes are modest, our findings suggest that TNI is a viable treatment alternative to CPAP in patients with SDB in the acute phase of ischemic stroke.

Subgroup And Quality Of Life Analyses Of The Phase Iii Clinical Trial Of Novottf-100a Versus Best Standard Chemotherapy For Recurrent Glioblastoma

BACKGROUND: NovoTTF is a portable device delivering low-intensity, intermediate-frequency, electric fields using noninvasive, disposable scalp electrodes. These fields physically interfere with cell division. Preliminary studies in recurrent and newly diagnosed glioblastoma (GBM) have shown promising results. A phase III study in recurrent GBM has recently been concluded. METHODS: Adults (KPS ≥ 70%) with recurrent GBM (any recurrence) were randomized (stratified by surgery and center) to either NovoTTF administered continuously (20-24 hours/day, 7 days/week) or the best available chemotherapy (best physician choice [BPC]). Primary endpoint was overall survival (OS); 6-month progression-free survival (PFS6), 1-year survival, and QOL were secondary endpoints. RESULTS: Two hundred thirty-seven patients were randomized (28 centers in the United States and Europe) to either NovoTTF alone (120 patients) or BPC (117 patients). Patient characteristics were balanced, median age was 54 years (range, 23-80 years), median KPS was 80% (range, 50-100). One quarter had surgery for recurrence, and over half were at their second or more recurrence. A survival advantage for the device group was seen in patients treated according to protocol (median OS, 7.8 months vs. 6.1 months; n = 185; p = 0.01). Moreover, subgroup analysis in patients with better prognostic baseline characteristics (KPS ≥ 80%; age ≤ 60; 1st-3rd recurrence) demonstrated a robust survival benefit for NovoTTF patients compared to matched BPC patients (median OS, 8.8 months vs. 6.6 months; n = 110; p < 0.01). In this group, 1-year survival was 35% vs. 20% and PFS6 was 25.6% vs. 7.7%. Interestingly, in patients who failed bevacizumab prior to the trial, OS was also significantly extended by NovoTTF (4.4 months vs. 3.1 months; n = 23 vs. n = 21; p < 0.02). Quality of life was equivalent or superior in NovoTTF patients. CONCLUSIONS: NovoTTF, a noninvasive, novel cancer treatment modality shows significant therapeutic efficacy with improved quality of life. The impact of NovoTTF was more pronounced when patients with better baseline prognostic factors were treated. A large scale phase III clinical trial in newly diagnosed GBM is currently being conducted.

Clinical management and burden of bipolar disorder: a multinational longitudinal study (WAVE-bd Study)

BACKGROUND: Studies in bipolar disorder (BD) to date are limited in their ability to provide a whole-disease perspective--their scope has generally been confined to a single disease phase and/or a specific treatment. Moreover, most clinical trials have focused on the manic phase of disease, and not on depression, which is associated with the greatest disease burden. There are few longitudinal studies covering both types of patients with BD (I and II) and the whole course of the disease, regardless of patients' symptomatology. Therefore, the Wide AmbispectiVE study of the clinical management and burden of Bipolar Disorder (WAVE-bd) (NCT01062607) aims to provide reliable information on the management of patients with BD in daily clinical practice. It also seeks to determine factors influencing clinical outcomes and resource use in relation to the management of BD. METHODS: WAVE-bd is a multinational, multicentre, non-interventional, longitudinal study. Approximately 3000 patients diagnosed with BD type I or II with at least one mood event in the preceding 12 months were recruited at centres in Austria, Belgium, Brazil, France, Germany, Portugal, Romania, Turkey, Ukraine and Venezuela. Site selection methodology aimed to provide a balanced cross-section of patients cared for by different types of providers of medical aid (e.g. academic hospitals, private practices) in each country. Target recruitment percentages were derived either from scientific publications or from expert panels in each participating country. The minimum follow-up period will be 12 months, with a maximum of 27 months, taking into account the retrospective and the prospective parts of the study. Data on demographics, diagnosis, medical history, clinical management, clinical and functional outcomes (CGI-BP and FAST scales), adherence to treatment (DAI-10 scale and Medication Possession Ratio), quality of life (EQ-5D scale), healthcare resources, and caregiver burden (BAS scale) will be collected. Descriptive analysis with common statistics will be performed. DISCUSSION: This study will provide detailed descriptions of the management of BD in different countries, particularly in terms of clinical outcomes and resources used. Thus, it should provide psychiatrists with reliable and up-to-date information about those factors associated with different management patterns of BD. TRIAL REGISTRATION NO: ClinicalTrials.gov: NCT01062607.

The role of embolic protection devices during carotid stenting prior to cardiac surgery in asymptomatic patients: Empty filters?

Objectives: The purpose of this study was to analyze the debris captured in the distal protection filters used during carotid artery stenting (CAS). Background: CAS is an option available to high-risk patients requiring revascularization. Filters are suggested for optimal stroke prevention during CAS. Methods: From May 2005 to June 2007, filters from 59 asymptomatic patients who underwent CAS were collected and sent to a specialized laboratory for light-microscope and histological analysis. Peri- and postprocedural outcomes were assessed during 1-year follow-up. Results: On the basis of biomedical imaging of the filter debris, the captured material could not be identified as embolized particles from the carotid plaque. On histological analysis the debris consisted mainly of red blood cell aggregates and/ or platelets, occasionally accompanied by granulocytes. We found no consistent histological evidence of embolized particles originating from atherosclerotic plaques. Post-procedure, three neurological events were reported: two (3.4%) transient ischemic attacks (TIA) and one (1.7%) ipsilateral minor stroke. Conclusion: The filters used during CAS in asymptomatic patients planned for cardiac surgery often remained empty. These findings may be explained by assuming that asymptomatic patients feature a different atherosclerotic plaque composition or stabilization through antiplatelet medication. Larger, randomized trials are clearly warranted, especially in the asymptomatic population. © 2012 Wiley Periodicals, Inc.

Special investigation of the City of Defiance for the period March 12, 2013 through April 30, 2015

Special investigation of the City of Defiance for the period March 12, 2013 through April 30, 2015

Audit report on the City of Minburn, Iowa for the year ended June 30, 2015

Audit report on the City of Minburn, Iowa for the year ended June 30, 2015

Agreed-upon procedures report on the City of Pleasanton, Iowa for the period July 1, 2014 through June 30, 2015

Agreed-upon procedures report on the City of Pleasanton, Iowa for the period July 1, 2014 through June 30, 2015

Improving T2 -weighted imaging at high field through the use of kT -points.

PURPOSE: At high magnetic field strengths (B0 ≥ 3 T), the shorter radiofrequency wavelength produces an inhomogeneous distribution of the transmit magnetic field. This can lead to variable contrast across the brain which is particularly pronounced in T2 -weighted imaging that requires multiple radiofrequency pulses. To obtain T2 -weighted images with uniform contrast throughout the whole brain at 7 T, short (2-3 ms) 3D tailored radiofrequency pulses (kT -points) were integrated into a 3D variable flip angle turbo spin echo sequence. METHODS: The excitation and refocusing "hard" pulses of a variable flip angle turbo spin echo sequence were replaced with kT -point pulses. Spatially resolved extended phase graph simulations and in vivo acquisitions at 7 T, utilizing both single channel and parallel-transmit systems, were used to test different kT -point configurations. RESULTS: Simulations indicated that an extended optimized k-space trajectory ensured a more homogeneous signal throughout images. In vivo experiments showed that high quality T2 -weighted brain images with uniform signal and contrast were obtained at 7 T by using the proposed methodology. CONCLUSION: This work demonstrates that T2 -weighted images devoid of artifacts resulting from B1 (+) inhomogeneity can be obtained at high field through the optimization of extended kT -point pulses. Magn Reson Med 71:1478-1488, 2014. © 2013 Wiley Periodicals, Inc.

Cardiac hypertrophy, low blood pressure, and low aldosterone levels in mice devoid of the three circadian PAR bZip transcription factors DBP, HLF, and TEF.

The cardiovascular system is under the control of the circadian clock, and disturbed circadian rhythms can induce cardiovascular pathologies. This cyclic regulation is probably brought about by the circadian expression of genes encoding enzymes and regulators involved in cardiovascular functions. We have previously shown that the rhythmic transcription of output genes is, in part, regulated by the clock-controlled PAR bZip transcription factors DBP (albumin D-element Binding Protein), HLF (Hepatic Leukemia Factor), and TEF (Thyrotroph Embryonic Factor). The simultaneous deletion of all three PAR bZip transcription factors leads to increased morbidity and shortened life span. Here, we demonstrate that Dbp/Tef/Hlf triple knockout mice develop cardiac hypertrophy and left ventricular dysfunction associated with a low blood pressure. These dysfunctions are exacerbated by an abnormal response to this low blood pressure characterized by low aldosterone levels. The phenotype of PAR bZip knockout mice highlights the importance of circadian regulators in the modulation of cardiovascular functions.