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.

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.

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.

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.

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.

Impact of Papillary Muscle Infarction on Ischemic Mitral Regurgitation Assessed by Magnetic Resonance Imaging.

OBJECTIVE: Ischemic mitral regurgitation is a predictor of heart failure resulting in increased mortality in patients with chronic myocardial infarction. It is uncertain whether the presence of papillary muscle (PM) infarction contributes to the development of mitral regurgitation in patients with chronic myocardial infarction (MI). The aim of the present study was to assess the correlation of PM infarction depicted by MRI with mitral regurgitation and left ventricular function. METHODS AND MATERIALS: 48 patients with chronic MI and recent MRI and echocardiography were retrospectively included. The location and extent of MI depicted by MRI were correlated with left ventricular function assessed by MRI and mitral regurgitation assessed by echocardiography. The presence, location and extent of PM infarction depicted by late gadolinium enhancement (LGE-) MRI were correlated with functional parameters and compared with patients with chronic MI but no PM involvement. RESULTS: PM infarction was found in 11 of 48 patients (23 %) using LGE-MRI. 8/11 patients (73 %) with PM infarction and 22/37 patients (59 %) without PM involvement in MI had ischemic mitral regurgitation. There was no significant difference between location, extent of MI and presence of mitral regurgitation between patients with and without PM involvement in myocardial infarction. In 4/4 patients with complete and in 4/7 patients with partial PM infarction, mitral regurgitation was present. The normalized mean left ventricular end-diastolic volume was increased in patients with ischemic mitral regurgitation. CONCLUSION: The presence of PM infarction does not correlate with ischemic mitral regurgitation. In patients with complete PM infarction and consequent discontinuity of viable tissue in the PM-chorda-mitral valve complex, the probability of developing ischemic mitral regurgitation seems to be increased. However, the severity of mitral regurgitation is not increased compared to patients with partial or no PM infarction. KEY POINTS: · No correlation between ischemic mitral regurgitation and presence of papillary muscle infarction. · Complete papillary muscle infarction results in dysfunction associated with ischemic mitral regurgitation. · Severity of mitral regurgitation not increased in patients with complete PM infarction. CITATION FORMAT: · Bretschneider C, Heinrich H, Seeger A et al. Impact of Papillary Muscle Infarction on Ischemic Mitral Regurgitation Assessed by Magnetic Resonance Imaging. Fortschr Röntgenstr 2018; 190: 42 - 50.

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).

Targeting of rifamycin SV to the colon for treatment of travelers' diarrhea: a randomized, double-blind, placebo-controlled phase 3 study.

BACKGROUND: Rifamycin SV is under development for treatment of travelers' diarrhea (TD) in a new oral formulation, Rifamycin SV MMX (RIF-MMX; Santarus Inc., San Diego, CA, USA), which targets its delivery to the colon, making it a unique rifamycin drug. METHODS: This was a randomized, double-blind, phase 3 study of adult travelers to Mexico or Guatemala experiencing acute diarrhea. A total of 264 patients received RIF-MMX (2 × 200 mg twice daily for 3 days, n = 199) or placebo (n = 65) in a 3 : 1 ratio. The primary endpoint was the length of time between the administration of first dose of study drug and passage of the last unformed stool (TLUS; after which clinical cure was declared). Other endpoints included eradication of pathogens from the stools, pathogen minimum inhibitory concentration (MIC), and adverse events (AEs). RESULTS: TLUS was significantly shorter in the RIF-MMX group (median: 46.0 hours) compared with placebo (median: 68.0 hours; p = 0.0008) and a larger percentage of RIF-MMX treated patients (81.4%) achieved clinical cure compared with placebo patients (56.9%). TLUS was significantly shorter in the subgroups of patients with enteroaggregative, enterotoxigenic, or diffusely adherent Escherichia coli infections (p = 0.0035) with nonsignificant activity against invasive bacteria (p = 0.3804). Overall pathogen eradication rates were numerically higher in the RIF-MMX group (67.0%) compared with placebo (54.8%) but the difference did not reach significance (p = 0.0836). In vitro resistance to rifamycin SV was observed in some bacteria remaining after treatment of patients with RIF-MMX but was not associated with lower efficacy in them. AEs appeared to be more frequent with placebo (38.5%) than with RIF-MMX (29.6%). CONCLUSIONS: RIF-MMX shortened the duration of TD in patients with a broad range of pathogens and was well tolerated. The unique pharmacokinetic properties of the drug offer evidence that TD pathogens work at the level of the colon.

Addition of exenatide BID to insulin glargine: a post-hoc analysis of the effect on glycemia and weight across a range of insulin titration.

BACKGROUND AND OBJECTIVE: In a 30 week, double-blind, randomized, controlled Phase 3 study in patients with type 2 diabetes mellitus, the addition of fixed-dose exenatide twice daily (BID) to titrated insulin glargine resulted in significant glycated hemoglobin (HbA(1c)) lowering and weight loss without increased hypoglycemia risk versus titrated insulin glargine alone. Because individualized insulin titration contributed to these results, this post-hoc analysis examined the results in the context of the degree of insulin titration that occurred. METHODS: Subjects on pre-existing insulin glargine (with or without oral antidiabetes agents) were randomized to placebo (n = 123) or exenatide BID (n = 138; 5 µg for 4 weeks, then 10 µg ongoing). Insulin glargine was titrated in both arms per the Treat-to-Target algorithm. Tertiles (T1, T2, T3) were based on change in insulin dose from baseline to endpoint. Change in HbA(1c), hypoglycemia risk, and weight gain were assessed per insulin dose tertile. RESULTS: The population comprised adult patients (mean age = 59 y) with type 2 diabetes and an HbA(1c) level between 7.0% and 10.5% (mean HbA(1c) = 8.4%). Insulin titration ranged from modest reductions in T1 to substantial increases in T3. Greater improvements in HbA1c were demonstrated with exenatide BID versus placebo in all tertiles (statistically significant in T2 and T3). With exenatide BID, more subjects achieved HbA(1c) <7.0% vs. placebo: T1, 44% vs. 29% (P = not significant); T2, 65% vs. 26%; T3, 54% vs. 29% (P < 0.05 for T2 and T3). Incidence of hypoglycemia was numerically lower with exenatide BID in all tertiles. Adjunctive exenatide BID was associated with statistically significantly greater weight loss (T1, T2) or mitigation of weight gain (T3) compared with placebo. Rates of nausea (42% vs. 8%), diarrhea (18% vs. 7%), and vomiting (18% vs. 4%) were higher with exenatide BID than with placebo and did not vary by tertile. CONCLUSIONS: Addition of fixed-dose exenatide BID to optimized insulin glargine, regardless of the extent of insulin titration, significantly improved glycemia without increasing hypoglycemia risk, while mitigating insulin-induced weight gain in this post-hoc analysis.

Measurement of electrical coupling between cardiac ablation catheters and tissue.

Managing cardiac arrhythmias with catheter ablation requires positioning electrodes in contact with myocardial tissue. Objective measures to assess contact and effective coupling of ablation energy are sought. An electrical coupling index (ECI) was devised using complex impedance at 20 kHz to perform in the presence of RF ablation and deliver information about electrical interactions between the tip electrode and its adjacent environment. ECI was derived and compared with clinical judgment, pacing threshold, electrogram amplitude, and ablation lesion depth and transmurality in a porcine model. ECI was also compared with force and displacement using ex vivo bovine myocardial muscle. Mean noncontact ECI was 97.2 ± 14.3 and increased to 145.2 ± 33.6 (p <; 0.001) in clinician assessed (CLIN) moderate contact. ECI significantly improved CLIN's prediction of the variance in pacing threshold from 48.7% to 56.8% ( ). ECI was indicative of contact force under conditions of smooth myocardium. Transmural lesions were associated with higher pre-RF (109 ± 17 versus 149 ± 25, ) and during-RF (82 ± 9 versus 101 ± 17, ) ECI levels. ECI is a tip specific, robust, correlate with contact and ablation efficacy, and can potentially add to clinical interpretation of electrical coupling during electrophysiology procedures.

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.

Diagnostic value of high spatial and temporal resolution time-resolved MR angiography in the workup of peripheral high-flow vascular malformations at 1.5 Tesla.

To evaluate the feasibility and diagnostic impact of time-resolved MR angiography (TR-MRA) combined with parallel imaging and low contrast dose for the assessment of peripheral high-flow vascular malformations (VM) at 1.5 Tesla (T). Twelve consecutive patients (7 female, 5 male, mean age 24.7 ± 11.1 years) with known or suspected high-flow VM underwent time-resolved MRA. Two readers individually assessed image quality, diagnostic confidence as well as hemodynamic features. Digital subtraction angiography (DSA) correlation was available in 9 patients. TR-MRA provided a comprehensive assessment of all VMs with good quality images, allowing reliable differentiation of the early and main arterial phases and of at least the early venous phase. Based on hemodynamic features VM were classified as predominantly arterial malformations in 5 cases (42%), or arteriovenous malformations in the remaining 7 cases (58%). The high-flow component of a VM was confirmed by DSA in 9/9 (100%) cases during the interventional treatment procedure. TR-MRA of peripheral VMs with temporal interpolation and stochastic spiral trajectories is feasible, allowing the assessment of dynamic inflow and vessel-specific information similar to conventional DSA. Therefore, TR-MRA represents a reasonable alternative imaging technique for the pre-treatment evaluation of high-flow VMs.

Fusion of MR coronary angiography and viability imaging: feasibility and clinical value for the assignment of myocardial infarctions.

PURPOSE: To investigate the feasibility of image fusion of MR-coronary angiography (MRCA) and delayed gadolinium enhancement imaging (LGE) and to assign areas of myocardial infarction to the corresponding supplying coronary arteries. MATERIALS AND METHODS: An interactive segmentation of the coronary arteries was performed in MRCA data sets (n=25). The LGE slices were matched onto the vessel segmentation to perform a fused analysis of coronary artery anatomy and LGE. The results were compared to the segmental model recommended by the American Heart Association (AHA). Standard of reference was the identification of the culprit lesion in the invasive coronary angiography (CA) (n=20). RESULTS: The fused analysis allowed the assignment of MI to the supplying coronary artery in 13/20 patients. The sensitivities/specificities for the assignment of MI to the three main vessels were: LAD 63%/100%, LCX 75%/100%, and RCA 56%/100%, respectively. Using the AHA segmental model the sensitivities/specificities for the correct assignment of MI to the three main vessels were: LAD 88%/58%, LCX 94%/75%, and RCA 77%/73%, respectively. CONCLUSION: Fusion images of MRCA and LGE provides added diagnostic information in the effort to determine the epicardial vessels responsible for the postischemic myocardial injury and therefore might be helpful to establish appropriate future therapeutic steps.

Association of platelet-SDF-1 with hemodynamic function and infarct size using cardiac MR in patients with AMI.

PURPOSE: Platelet-derived stromal-cell-derived factor-1 (SDF-1) plays an important role in trafficking hematopoetic progenitor cells for tissue regeneration and neovascularisation. The aim was to evaluate platelet-SDF-1 and CD34(+) progenitor cells in patients with acute myocardial infarction (AMI) compared with hemodynamic function and infarct size using late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) imaging. MATERIALS AND METHODS: We consecutively evaluated 40 patients with AMI, who received coronary angiography for primary coronary intervention. Blood was sampled for flow cytometry to determine mean fluorescence intensity (MFI) of platelet-SDF-1 and for isolation of CD34(+) progenitor cells. 48h and three months after coronary stenting, all patients underwent 1.5T CMR for volumetric assessment and LGE. RESULTS: Patients with enhanced platelet-SDF-1 expression (median≥68.5MFI) showed a significant amelioration of left ventricular ejection fraction (LVEF) (baseline vs. follow-up mean±SD: 45±6% vs. 56±6%; P=0.018) and of stroke volume (73.1±19.1mL vs. 89.9±21.3mL; P=0.032) at three-month follow-up in contrast to patients with a decreased platelet-SDF-1 expression level (LVEF: 53±8% vs. 56±10%; P=0.267; stroke volume: 85.6±23.1mL vs. 87.4±23.2mL; P=0.803). Inversely, LGE infarct size showed significantly reduced in patients with enhanced platelet-SDF-1 expression at three months (18.9±12mL vs. 6.3±5.1mL; P=0.002) compared to patients with decreased platelet-SDF-1 (12.7±12.7mL vs. 7.6±8.4mL; P=0.156). Time-dependent autocorrelation coefficients shifted for both SV (lag 1: r=-0.368; P=0.001) and the number of CD34(+) cells (lag 1: r=0.633; P=0.001) to a positive autocorrelation (SV; lag 2: r=0.295; P=0.001; CD34(+) cells; lag 2: r=0.287; P=0.001). Patients with increased number of CD34(+) cells (median≥420cells/hpf) showed a significant amelioration of stroke volume in three-month follow-up (83.9±5.3mL vs. 99.4±4.1mL; P=0.020) compared with patients with decreased number of CD34(+) cells (69.3±4.1mL vs. 76.1±3.2mL; P=0.282). CONCLUSIONS: Platelet-SDF-1 and number of CD34(+) progenitor cells are associated with CMR hemodynamic function in patients with AMI.

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.

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.

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.