Genetic and Phenotypic Characterization of the Fungal Pathogen Cytospora plurivora from Western Colorado Peach Orchards and the Development of a ddPCR Assay for Detection and Quantification.

Cytospora canker is one of the most important diseases affecting peach production in Colorado, yet previous efforts to characterize Cytospora species diversity in Colorado have relied exclusively on morphological traits. Recently, several new Cytospora species were described from peach orchards within the United States using molecular and morphological data, prompting the need to reexamine Cytospora spp. present on peach trees in Colorado. A total of 137 isolates of Cytospora spp. were collected from eight orchards in western Colorado. Isolates were sequenced at the internal transcribed spacer region and elongation factor 1-α and assessed with reference sequences in phylogenetic analyses. All isolates from western Colorado peach trees resolved with the newly described Cytospora plurivora. In addition to molecular characterization, temperature growth and virulence assays were conducted to assess phenotypic variation among the isolates from western Colorado. Variation across isolates was found both in growth at different temperatures and in virulence. Ancestral state reconstruction analyses resolved the most virulent (and most often collected) haplotypes together in a well-supported clade from which a single monophyletic origin of high virulence can be inferred. Finally, a droplet digital PCR assay was developed for use in ongoing and future studies to detect and quantify C. plurivora from field and laboratory samples.

Is there coronary artery disease in the cancer patient who manifests with chest pain, shortness of breath and/or tachycardia? A retrospective observational cohort.

OBJECTIVE: Cancer therapies lead to chest pain (CP), shortness of breath (SOB), and/or tachydysrhythmias (TACH Y) requiring cardiac risk stratification including coronary computed tomographic angiography (CCTA). We posit that cancer patients with CP, SOB and/or TACH Y have greater odds of having coronary artery disease (CAD) identified by CCTA than those that do not. METHODS: Eligibility for this IRB-approved retrospective observational cohort included those with cancer that had CCTA performed. Groups were stratified with and without CP, SOB, and/or TACH Y. Electronic medical records were mined for appropriate CPT codes from 01012010 to 08312013. Demographics, cancer type, and clinical outcomes were obtained. Standard t tests, odds ratios, and frequencies were used. RESULTS: Of 176 participants identified; 84 were male (48 %) and 118 were Caucasian (67 %). Of those, 100/176 (57 %) had CP, SOB, and/or TACH Y; 72/100 (72 %) had CP; 10/100 (10 %) had TACH Y; and 18/100 (18 %) had SOB. Of the 72 with CP, 40 (56 %) had CAD; of the 10 with TACH Y, 6 (60 %) had CAD; of the 18 with SOB, and 10 (56 %) had CAD. Thus, a 2.6-fold increased odds of having CAD (56/100 = 56 %) compared to 25/76 (33 %) in the group with cancer without CP, SOB, and/or TACH Y (95 % CI = 1.40 to 4.83; p = 0.003). CONCLUSION: Cancer patients with CP, SOB, and/or TACH Y have a 2.6-fold increased odds of having CAD compared to cancer patients without CP, SOB, and/or TACH Y (95 % CI = 1.40 to 4.83; p = 0.003).

Preoperative assessment of peritoneal carcinomatosis: intraindividual comparison of 18F-FDG PET/CT and MRI.

OBJECTIVE: Exact determination of localization and extent of peritoneal carcinomatosis (PC) before peritonectomy and hyperthermic intraperitoneal chemotherapy (HIPEC) is crucial for the clinical outcome. Our study compares dynamic contrast enhanced 3D MRI (T1wDCE) and 18F-FDG PET/CT regarding diagnostic accuracy in correlation with surgical exploration (SE) and histological (HI) results. MATERIALS AND METHODS: 15 patients with PC were examined on a 1.5T MRI and 16 slice PET/CT. MRI: coronal T1wDCE covering the complete abdomen (0.15 mmol Gd-chelate/kg BW, 2000 mL mannitol solution p.o., 40 mg buscopan i.v.). PET-CT: contrast enhanced 16slice CT (120 mL ultravist 370 i.v., 1000 mL mannitol solution p.o., 40 mg buscopan i.v.), PET: 350 MBq 18-FDG i.v., 3 min acquisition time/bed, 60 min after tracer injektion). Assessment by two independent, experienced observers in correlation with results of SE and HI for each abdominal segment based on the peritoneal cancer index (PCI) proposed by Sugarbaker and co-authors. RESULTS: MRI and PET/CT provided reliable detection of PC. One patient had to be excluded from statistical analysis. In summary, 182 segments were assessed (13/patient, 14 patients, one patient excluded from statistical analysis). PC was found in 118 by MRI, 124 by PET/CT. 4 segments were classified false positive for MRI, 2 for PET/CT. False negative segments (MRI: 17, PET/CT: 9) did not result in irresectability. Positive predictive value for PC/segment was 97/98%, negative predictive value 73/84%, sensitivity 87/93%, specificity 92/96%, and diagnostic accuracy 88/94% (MRI/PET/CT). CONCLUSION: With high diagnostic accuracy for PC of both, MRI and PET/CT, PET/CT provides better diagnostic accuracy and especially better NPV.

The role of stress factors in severity of Cytospora plurivora in greenhouse and field plantings of 13 peach (Prunus persica) cultivars.

Understanding the host-pathogen-environmental interactions in a pathosystem is essential for management of diseases and diminished crop yields. Abiotic stressors such as cold damage, water deficit, and high pH soils can be major limiting factors to tree fruit production. Along with decreased yields, these abiotic factors can have direct implications for disease severity within orchards. Cytospora plurivora is a ubiquitous fungal canker pathogen in western Colorado, USA and is a major focus in integrated pest management strategies. This research evaluated the influence of biotic and abiotic stress factors on peach tree health. Thirteen peach cultivars were placed under abiotic stress and inoculated with C. plurivora in greenhouse and field conditions. Under deficit irrigation, C. plurivora infections were significantly larger and more severe in both the greenhouse and field trials when compared with those under the full-irrigation controls. In controlled greenhouse conditions, a positive correlation between lesion size and water potential was evident, but no trend of cultivar tolerance was observed. Furthermore, increase in irrigation water pH, through additions of sodium carbonate and bicarbonate, in the greenhouse trials resulted in decreased leaf water potentials and increased pathogen necrotic tissue volumes (mm3). In field trials, there was no positive relationship between lesion size and water potential; trees with the most negative water potentials had the smallest lesions sizes that did not correspond to cultivar, suggesting that other abiotic or biotic factors may be shielding water stressed trees from increased pathogen aggression. This research highlights the importance of proper irrigation and soil pH management as tools for the management of Cytospora canker in peach orchards.

Peritoneal carcinomatosis: comparison of dynamic contrast-enhanced magnetic resonance imaging with surgical and histopathologic findings.

OBJECTIVE: In patients with peritoneal carcinomatosis (PC) accurate preoperative assessment is essential to determine indication and surgical procedure to ensure optimal outcome. Purpose of our study was to assess the diagnostic accuracy (DA) of multiphasic dynamic contrast-enhanced MRI to determine the extent of PC in correlation with surgical and histopathological findings. MATERIALS AND METHODS: 14 Patients with proven PC were examined on a 1.5T system before peritonectomy and hyperthermic intraperitoneal chemotherapy. Patient preparation included oral application of 2000 mL mannitol solution and 40 mg butylscopolaminiumbromid i.v. Coronal contrast-enhanced multiphasic dynamic T1w 3D gre sequences (T1W DCE) (0.15 mmol Gd-chelate/kg bw) covering the whole abdomen were acquired (TR 2.9 ms, TE 1.1 ms, resolution 2.0 × 2.0 × 1.8 mm, FOV 400 × 400 mm). MRI was assessed by two radiologists and correlated with surgical exploration (SE) and histopathology for each segment based on the peritoneal cancer index proposed by Sugarbaker et al. RESULTS: In total, 182 segments were evaluated. PC was found in 118/121 of 182 segments (reader 1/2) by MRI and in 131 segments by SE. In 4/7 segments MRI was false positive. False negative segments 17/17 in MRI did not result in irresectability. The positive predictive value for PC per segment of MRI was 97%/94%, the negative predictive value 73%/72%, the sensitivity 87%/87% and the specificity 92%/86%. The DA was 88%/87%. CONCLUSION: T1W DCE is an accurate and clinical valuable tool for the preoperative assessment of peritoneal tumor spread.

The CALCIPHYX study: a randomized, double-blind, placebo-controlled, Phase 3 clinical trial of SNF472 for the treatment of calciphylaxis.

BACKGROUND: Calcific uraemic arteriolopathy (CUA; calciphylaxis) is a rare disease seen predominantly in patients receiving dialysis. Calciphylaxis is characterized by poorly healing or non-healing wounds, and is associated with mortality, substantial morbidity related to infection and typically severe pain. In an open-label Phase 2 clinical trial, SNF472, a selective inhibitor of vascular calcification, was well-tolerated and associated with improvement in wound healing, reduction of wound-related pain and improvement in wound-related quality of life (QoL). Those results informed the design of the CALCIPHYX trial, an ongoing, randomized, placebo-controlled, Phase 3 trial of SNF472 for treatment of calciphylaxis. METHODS: In CALCIPHYX, 66 patients receiving haemodialysis who have an ulcerated calciphylaxis lesion will be randomized 1:1 to double-blind SNF472 (7 mg/kg intravenously) or placebo three times weekly for 12 weeks (Part 1), then receive open-label SNF472 for 12 weeks (Part 2). All patients will receive stable background care, which may include pain medications and sodium thiosulphate, in accordance with the clinical practices of each site. A statistically significant difference between the SNF472 and placebo groups for improvement of either primary endpoint at Week 12 will demonstrate efficacy of SNF472: change in Bates-Jensen Wound Assessment Tool-CUA (a quantitative wound assessment tool for evaluating calciphylaxis lesions) or change in pain visual analogue scale score. Additional endpoints will address wound-related QoL, qualitative changes in wounds, wound size, analgesic use and safety. CONCLUSIONS: This randomized, placebo-controlled Phase 3 clinical trial will examine the efficacy and safety of SNF472 in patients who have ulcerated calciphylaxis lesions. Patient recruitment is ongoing.

Pretreatment evaluation of peripheral vascular malformations using low-dose contrast-enhanced time-resolved 3D MR angiography: initial results in 22 patients.

OBJECTIVE: The objective of our study was to assess the feasibility and diagnostic performance of time-resolved MR angiography (MRA) in the pretreatment evaluation of peripheral vascular malformations at 1.5 T. SUBJECTS AND METHODS: Twenty-two consecutive patients (15 women and seven men; mean age, 22.1 ± 12.1 years) who were known or suspected to have vascular malformations were studied using time-resolved MRA with interleaved stochastic trajectories and parallel acquisition followed by conventional MRA (n = 12). All studies were performed on a 1.5-T whole-body MR system. Image sets of time-resolved and conventional MRA were independently reviewed by two observers for image quality, level of confidence and presence, location, and classification of vascular malformations. The interobserver agreement was calculated using conventional MRA as the standard of reference. RESULTS: On the basis of time-resolved MRA, nine of the lesions were categorized as high-flow arteriovenous malformations (AVMs), the remaining 13 lesions were categorized as low-flow vascular malformations or hemangiomas. There was no significant difference in the image quality grading scores between the two observers for time-resolved MRA (p = 0.61) and conventional MRA (p = 0.54). The kappa coefficient revealed good agreement (κ = 0.76) between time-resolved MRA and conventional MRA. Both observers visualized fine vascular details with higher confidence in two patients on conventional MRA. The additional functional information regarding feeding artery and flow patterns provided by time-resolved MRA was confirmed by digital subtraction in all nine cases. CONCLUSION: Time-resolved MRA provided the temporal information needed for the appropriate classification of vascular malformations, enabling visualization of both the arterial feeders and draining veins. Furthermore, time-resolved MRA has the potential to be used as an initial and screening diagnostic tool obviating conventional MRA to categorize these lesions and determine their extent to correctly guide treatment.

Multiple actions of systemic artemin in experimental neuropathy.

The clinical management of neuropathic pain is particularly challenging. Current therapies for neuropathic pain modulate nerve impulse propagation or synaptic transmission; these therapies are of limited benefit and have undesirable side effects. Injuries to peripheral nerves result in a host of pathophysiological changes associated with the sustained expression of abnormal pain. Here we show that systemic, intermittent administration of artemin produces dose- and time-related reversal of nerve injury-induced pain behavior, together with partial to complete normalization of multiple morphological and neurochemical features of the injury state. These effects of artemin were sustained for at least 28 days. Higher doses of artemin than those completely reversing experimental neuropathic pain did not elicit sensory or motor abnormalities. Our results indicate that the behavioral symptoms of neuropathic pain states can be treated successfully, and that partial to complete reversal of associated morphological and neurochemical changes is achievable with artemin.

Multicenter, double-blind, randomized, intraindividual crossover comparison of gadobenate dimeglumine and gadopentetate dimeglumine for MR angiography of peripheral arteries.

PURPOSE: To prospectively compare the image quality and diagnostic performance achieved with doses of gadobenate dimeglumine and gadopentetate dimeglumine of 0.1 mmol per kilogram of body weight in patients undergoing contrast material-enhanced magnetic resonance (MR) angiography of the pelvis, thigh, and lower-leg (excluding foot) for suspected or known peripheral arterial occlusive disease. MATERIALS AND METHODS: Institutional review board approval was granted from each center and informed written consent was obtained from all patients. Between November 2006 and January 2008, 96 patients (62 men, 34 women; mean age, 63.7 years +/- 10.4 [standard deviation]; range, 39-86 years) underwent two identical examinations at 1.5 T by using three-dimensional spoiled gradient-echo sequences and randomized 0.1-mmol/kg doses of each agent. Images were evaluated on-site for technical adequacy and quality of vessel visualization and offsite by three independent blinded readers for anatomic delineation and detection/exclusion of pathologic features. Comparative diagnostic performance was determined in 31 patients who underwent digital subtraction angiography. Data were analyzed by using the Wilcoxon signed-rank, McNemar, and Wald tests. Interreader agreement was determined by using generalized kappa statistics. Differences in quantitative contrast enhancement were assessed and a safety evaluation was performed. RESULTS: Ninety-two patients received both agents. Significantly better performance (P < .0001; all evaluations) with gadobenate dimeglumine was noted on-site for technical adequacy and vessel visualization quality and offsite for anatomic delineation and detection/exclusion of pathologic features. Contrast enhancement (P < or = .0001) and detection of clinically relevant disease (P < or = .0028) were significantly improved with gadobenate dimeglumine. Interreader agreement for stenosis detection and grading was good to excellent (kappa = 0.749 and 0.805, respectively). Mild adverse events were reported for four (six events) and five (eight events) patients after gadobenate dimeglumine and gadopentetate dimeglumine, respectively. CONCLUSION: Higher-quality vessel visualization, greater contrast enhancement, fewer technical failures, and improved diagnostic performance are obtained with gadobenate dimeglumine, relative to gadopentetate dimeglumine, when compared intraindividually at 0.1-mmol/kg doses in patients undergoing contrast-enhanced MR angiography for suspected peripheral arterial occlusive disease.

Comparison of contrast-enhanced MR angiography to intraarterial digital subtraction angiography for evaluation of peripheral arterial occlusive disease: results of a phase III multicenter trial.

PURPOSE: To evaluate the efficacy and safety of 0.1 mmol/kg gadodiamide administration for contrast-enhanced magnetic resonance angiography (CE-MRA) in detecting hemodynamically relevant main stenosis (ie, > or = 50% or occlusion) of aortoiliac arteries. MATERIALS AND METHODS: In a multicenter, phase 3, controlled study, patients with suspected or proven peripheral arterial occlusive disease (PAOD) underwent CE-MRA with administration of gadodiamide. Intraarterial digital subtraction angiography (IA-DSA) was used as the reference. The study was approved by all Institutional Review Boards or Institutional Ethic Committees prior to commencement of patient recruitment and written informed consent was obtained from all patients. RESULTS: Independent readers rated 25%-45% of CE-MRA images as excellent compared with 0.3%-6% of noncontrast MRA images. Mean imaging acquisition time for CE-MRA was <1 minute (0.7 +/- 1.9 minutes) versus 10 minutes (10.8 +/- 3.0) for noncontrast MRA. Sensitivity, specificity, and accuracy of CE-MRA were superior compared with those of noncontrast MRA in detecting significant arterial stenoses. Compared with IA-DSA, the sensitivity of CE-MRA ranged from 80%-88% and the specificity from 73% to 92% for the three blinded readers, at the patient level. CONCLUSION: Diagnostic results with CE-MRA were superior and more consistent compared with noncontrast MRA for detecting hemodynamically relevant main stenoses in patients with suspected or proven PAOD and compared favorably with IA-DSA as a reference standard.

Endotoxin exposure during late pregnancy alters ovine offspring febrile and hypothalamic-pituitary-adrenal axis responsiveness later in life.

A growing number of studies indicate that maternal infection during pregnancy is associated with adverse fetal development and neonatal health. In this study, late gestating sheep (day 135) were challenged systemically with saline (0.9%) or Escherichia coli lipopolysaccharide endotoxin (400 ng/kg x 3 consecutive days, or 1.2 microg/kg x 1 day) in order to assess the impact of maternal endotoxemia on the developing fetal neuroendocrine-immune system. During adulthood, cortisol secretion and febrile responses of female offspring and the cortisol response of the male offspring to endotoxin (400 ng/kg), as well as the female cortisol response to adrenocorticotropic hormone (ACTH) challenge, were measured to assess neuroendocrine-immune function. These studies revealed that maternal endotoxin treatment during late gestation altered the female febrile and male and female cortisol response to endotoxin exposure later in life; however, the response was dependent on the endotoxin treatment regime that the pregnant sheep received. The follow-up ACTH challenge suggests that programing of the adrenal gland may be altered in the female fetus during maternal endotoxemia. The long-term health implications of these changes warrant further investigation.

Towards risk stratification in systemic atherosclerosis: value of myocardial function and viability imaging as an adjunct to MR angiography.

OBJECTIVES: To longitudinally assess the value of cardiac functional and viability imaging as a supplement to MR angiography in patients with atherosclerotic disease. METHODS: Cardiac MRI was performed in 195 consecutive patients with symptomatic peripheral arterial disease. Of these, 186 patients were followed for 22 +/- 5 months for the presence of cardiac events (cardiac death, acute coronary syndrome and hospitalisation as a result of congestive heart failure). RESULTS: Myocardial viability imaging showed a high prevalence of known (n = 31) and occult myocardial infarctions (MI) (n = 26). Cardiac events occurred more often in patients with reduced ventricular function (ejection fraction (EF) less than 40%, cardiac event in 4/8 patients; EF 40-55%, cardiac event in 10/40 patients; EF greater than 55%, cardiac event in 15/138 patients) as well as in patients with occult MI (8/25 patients) and known MI (11/30 patients). In patients with normal function, the detection of a previous MI was of high relevance to prognosis. CONCLUSIONS: Both reduced EF and the presence of MI influence patients' prognoses. Performing cardiac MRI in this patient population may influence further patient management including intensified risk factor intervention.

High resolution myocardial magnetic resonance stress perfusion imaging at 3 T using a 1 M contrast agent.

OBJECTIVE: Stress perfusion magnetic resonance imaging (MSPMRI) is an established technique for the assessment of myocardial perfusion. Shortcomings at 1.5 T are low signal to noise ratio (SNR) and contrast to noise ratio (CNR). One approach to overcome these shortcomings is to increase field strength and contrast concentration. The aim of our study was to investigate the diagnostic capability of high resolution MSPMRI at 3-T field strength using a 1 M contrast agent. MATERIAL AND METHODS: Fifty-seven patients (62.3 +/- 11.0 years) with symptoms of coronary artery disease (CAD) were examined at 3 T. MMRSPI was assessed using a 2D saturation recovery gradient echo (SR GRE) sequence in short axis orientation (TR 1.9 ms, TE 1.0 ms, flip 12 degrees , 0.1 mmol gadobutrol/kg body weight (bw), 140 microg adenosine/kg bw/min). Perfusion images were assessed visually and semiquantitatively (upslope, peak signal intensity (SI), and myocardial perfusion reserve index (MPRI)). Standard of reference was invasive coronary angiography. RESULTS: Stress-induced hypoperfusion was found in 43 patients. Sensitivity for hemodynamically relevant CAD (stenoses greater than 70%) was 95%/98%, specificity 80%/87%, diagnostic accuracy 91%/95% (reader 1/reader 2). The MPRI was significantly lower in hypoperfused myocardium (1.3 +/- 0.2) compared with normal myocardium (2.6 +/- 0.7). CONCLUSION: High resolution MMRSPI at 3 T using 1 M contrast agent under daily routine conditions provides reliable detection of stress-induced myocardial hypoperfusion with higher diagnostic accuracy than 1.5-T conditions.

A novel assay to measure calcification propensity: from laboratory to humans.

Cardiovascular calcification (CVC) contributes to morbidity and mortality in patients undergoing dialysis. We examined the pharmacodynamic effects of SNF472, a calcification inhibitor, on plasma calcium phosphate crystallization using spectrometric measurements, and its correlations with effects on CVC in rats or humans. Rats (N = 38) injected with vitamin D (days 1-3) to induce CVC were infused with saline or SNF472 (days 1-12). Inhibition of CVC was 50-65% with SNF472 3 mg/kg and ~ 80% with SNF472 10 or 30 mg/kg. SNF472 dose-dependently inhibited calcium phosphate crystallization, which correlated with inhibition of CVC (r = 0.628, P = 0.005). In patients with calciphylaxis (N = 14), infusion of SNF472 (~ 7 mg/kg) during hemodialysis for 12 weeks inhibited calcium phosphate crystallization by nearly 70%. In patients with CVC (N = 274), infusion of SNF472 during hemodialysis for 52 weeks inhibited calcium phosphate crystallization (placebo: 15%; 300 mg: 61%; 600 mg: 75%), which correlated with inhibition of CVC (r = 0.401, P = 0.003). These findings show a direct correlation between inhibition of calcium phosphate crystallization in plasma and inhibition of CVC both in a rat model and in humans, supporting the use of the pharmacodynamic assay in clinical trials as a potentially predictive tool to evaluate the activity of calcification inhibitors.

Ultrafast whole-body MR angiography with two-dimensional parallel imaging at 3.0 T: feasibility study.

The study was approved by the local ethics committee, and informed consent was provided by all participants prior to the examination. The aim of the study was to assess the feasibility of whole-body three-dimensional (3D) contrast material-enhanced magnetic resonance (MR) angiography with parallel imaging in the phase- and section-encoding directions (ie, integrated parallel acquisition technique [iPAT(2); Siemens, Erlangen, Germany]) for all anatomic imaging stations in combination with a single injection of contrast material. Whole-body contrast-enhanced MR angiography was performed in 23 patients at 3.0 T. Images were evaluated by two independent observers for quality on a four-point scale (where a score of 1 indicated poor image quality and a score of 4, excellent image quality); signal-to-noise ratios (SNRs) and contrast-to-noise ratios (CNRs) were calculated for representative vessel regions in each station. Mean image quality scores were 3.13 +/- 1.15 (standard deviation) and 3.17 +/- 1.14 for observers 1 and 2, respectively (kappa = 0.81). Signal intensity measurements revealed mean SNR values between 36.2 +/- 8.0 and 56.2 +/- 17.7 and mean CNR values between 29.0 +/- 7.4 and 48.2 +/- 15.7. The data suggest that contrast-enhanced MR angiography with iPAT(2) is feasible for whole-body applications and allows acquisition of 3D data sets with adequate spatial resolution within short measurement times, facilitating a single injection of contrast material.

First in human validation of impedance-based catheter tip-to-tissue contact assessment in the left atrium.

BACKGROUND: In this study, a new method of contact assessment based on the measurement of the local electrical properties at the catheter tip-to-tissue interface was validated in a blinded fashion in vivo in the human left atrium. METHODS: Using a 3-terminal circuit model, local resistance and reactance between catheter tip and tissue surface were measured and combined in an electrical coupling index (ECI). Twelve patients undergoing atrial fibrillation (AF) catheter ablation were included in this study. The catheter was placed in the left atrium at various levels of contact. Blinded to the physician, measurements of electrogram amplitudes, pacing thresholds, and impedances at the catheter tip-to-tissue interface were performed. RESULTS: As the catheter went from noncontact to contact, ECI increased from 118 +/- 15 to 145 +/- 24 (P < 0.0001), electrogram amplitudes increased from 0.14 +/- 0.16 to 2.0 +/- 1.9 mV (P < 0.0001), and pacing thresholds decreased from 13.9 +/- 3.1 to 3.1 +/- 2.0 mA (P < 0.0001). ECI was significantly higher in vascular tissue as compared with trabeculated and smooth myocardium. Patch orientation, operator, body mass index, or clinical type of AF had no influence on ECI values. On a patient-by-patient analysis, true contact/noncontact locations showed a mean ECI difference of 32.7 +/- 11.6 units (95% CI 25.8-39.6). A cut-off value of 5 ECI units was able to separate contact from noncontact with 97% sensitivity and 95% specificity. CONCLUSION: Measurement of local impedances between catheter tip and tissue is feasible to reproducibly describe electrical catheter contact within the left atrium in a clinical setting of AF catheter ablation.

Intraindividual comparison of myocardial delayed enhancement MR imaging using gadobenate dimeglumine at 1.5 T and 3 T.

For contrast-enhanced imaging techniques relying on strong T1 weighting, 3 T provides increased contrast compared with 1.5 T. The aim of our study was the intraindividual comparison of delayed enhancement MR imaging at 1.5 T and at 3 T. Twenty patients with myocardial infarction were examined at 1.5 T and 3 T. Fifteen minutes after injection of contrast agent (0.1 mmol gadobenate dimeglumine per kg body weight), inversion recovery gradient recalled echo (IR-GRE) sequences were acquired (1.5 T/3 T: TR 11.0/9.9 ms, TE 4.4/4.9 ms, flip 30 degrees /30 degrees , slice thickness 6/6 mm) to assess myocardial viability. Two observers rated image quality (Wilcoxon signed rank test). Quantification of hyperenhanced myocardium and standardized SNR/CNR measurements were performed (Student's t test). There was no significant difference with respect to image quality (1.5 T/3 T: 3.5/3.3, p = 0.34, reader 1; 2.4/2.7, p = 0.12, reader 2) and infarction size (760 +/- 566/828 +/- 677 mm(2) at 1.5 T, 808 +/- 639/826 +/- 726 mm(2) at 3 T, reader 1/reader 2, p > 0.05). Mean SNR in hyperenhanced/normal myocardium was 19.2/6.2 at 1.5 T and 29.5/8.8 at 3 T (p < 0.05). Mean CNR was 14.3 at 1.5 T and 26.0 at 3 T (p < 0.05). Delayed enhancement MR imaging at 3 T is a robust procedure yielding superior tissue contrast at 3 T compared with 1.5 T which is, however, not reflected by increased image quality.

Three-dimensional cine MRI in free-breathing infants and children with congenital heart disease.

BACKGROUND: Patients with congenital heart disease frequently have complex cardiac and vascular malformations requiring detailed non-invasive diagnostic evaluation including functional parameters. OBJECTIVE: To evaluate the morphological and functional information provided by a novel 3-D cine steady-state free-precession (SSFP) sequence. MATERIALS AND METHODS: Twenty consecutive children (mean age 2.2 years, nine boys) were examined using a 1.5-T MR system including 2-D cine gradient-recalled-echo sequences, static 3-D SSFP and 3-D cine SSFP sequences. RESULTS: Measurement of ventricular structures and volumes showed close agreement between the 3-D cine SSFP sequence and the 2-D cine gradient-recalled-echo and static 3-D SSFP sequences (left ventricular volumes mean difference 1.0-1.9 ml and 8.8-11.4%, respectively; right ventricular volumes 1.7-2.1 ml and 9.9-16.9%, respectively). No systematic bias was observed. CONCLUSION: 3-D cine MRI provides anatomic as well as functional information with sufficient spatial and temporal resolution in free-breathing infants with congenital heart disease.

Improvement in wound healing, pain, and quality of life after 12 weeks of SNF472 treatment: a phase 2 open-label study of patients with calciphylaxis.

BACKGROUND: Calciphylaxis in end-stage renal disease is characterized by painful necrotic skin ulcers and high mortality. There are no approved therapies. SNF472, an intravenous formulation of myo-inositol hexaphosphate, inhibits the formation and growth of hydroxyapatite crystals, the final common pathway in the pathogenesis of vascular calcification. METHODS: In this open-label, single-arm study, calciphylaxis patients on thrice-weekly hemodialysis and standard care, received intravenous SNF472 3 times per week for 12 weeks. The primary endpoint was wound healing assessed using the quantitative Bates-Jensen Wound Assessment Tool (BWAT). Pain visual analog scale (VAS), quality of life (wound-QoL), and qualitative wound image review were secondary endpoints. Quantitative changes from baseline were analyzed by paired t-tests using multiple imputation to account for missing observations. RESULTS: Fourteen patients received SNF472. Improvements from baseline to week 12 were observed for mean BWAT score (- 8.1; P < 0.001), pain VAS (- 23.6 mm; P = 0.015) and wound-QoL global score (- 0.90; P = 0.003). Of the 9 patients with ulcerated lesions at baseline who completed treatment, wound image review showed improvement for 7. SNF472 was well tolerated with no serious treatment-related adverse events. The most common adverse events were infections which occur frequently in patients on hemodialysis. None of these were considered as treatment-related. CONCLUSIONS: SNF472 was well-tolerated and improvements from baseline to week 12 in wound healing, pain, and quality of life were observed. A randomized, double-blind, placebo-controlled trial is planned to evaluate SNF472 in patients with calciphylaxis.