Importance of communication of CT indication for imaging yield in patients with gastrointestinal bleed.

PURPOSE: The indications for requesting a diagnostic test are important for the selection and timing of imaging protocols. We sought to evaluate the diagnostic yield and impact on patient disposition when evaluating computed tomography (CT) of the abdomen and pelvis in adult patients presenting with gastrointestinal bleeding (GIB) to the Emergency Department (ED). METHODS: This study was an observational cohort study of consecutive adult ED patients with ICD10 codes related to GIB between 5/5/2018 and 6/1/2020. CT reports were reviewed for indications, exam type and findings. Reports were classified as positive (active bleeding, recent bleeding or suspected etiology for GIB), negative or other significant findings. Methodological guidelines for reporting observational studies were followed (STROBE). RESULTS: Among 943 patients with GIB during the study period, 33% (n = 312) had an abdominopelvic CT ordered. Most CTs included contrast, 64.1% (n = 200) used a single portal venous phase and 28.9% (n = 90) were multi-phase. CT identified active bleeding in 4.2% (n = 13/312) and intraluminal blood in 2.9% (n = 9/312) patients. Patients that had GIB indications on the CT order (n = 142) were more likely to receive a multiphase study compared to those without GIB indication (n = 94) (43.0% vs. 8.5%, difference 34.5%, 95% CI 23.7% to 43.7%, p < 0.0001). Patients that received multiphase studies were more likely to have a source of GIB identified compared to single-phase (18.9% vs 1.5%, OR 15.3, 95% CI 4.4 to 53.7, p < 0.0001). In 40.3% (n = 117/290) of patients without bleeding, an intra-abdominal cause for their symptoms was identified. Those with GIB or with an identified cause were more likely to be admitted. CONCLUSIONS: One-third of patients evaluated in the ED with GIB had a CT ordered. Active GIB was detected more often when multiphase exams were performed. Multiphase exams are done more often if GIB is listed in the CT indication. When a CT is positive, patients are more likely to be admitted or observed. Accurate indications are critical to optimize exam performance.

Magnetic resonance enterography is feasible and reliable in multicenter clinical trials in patients with Crohn's disease, and may help select subjects with active inflammation.

BACKGROUND: Reliable tools for patient selection are critical for clinical drug trials. AIM: To evaluate a consensus-based, standardised magnetic resonance enterography (MRE) protocol for selecting patients for inclusion in Crohn's disease (CD) multicenter clinical trials. METHODS: This study recruited 20 patients [Crohn's Disease Activity Index (CDAI) scores: <150 (n = 8); 150-220 (n = 4); 220-450 (n = 8)], to undergo ileocolonoscopy and two MREs (with and without colonic contrast) within a 14-day period. Procedures were scored centrally using, Magnetic Resonance Index of Activity (MaRIA), and both Crohn's Disease Endoscopic Index of Severity (CDEIS) and Simplified Endoscopic Score (SES-CD). RESULTS: 37 MREs were acquired. Both MREs were evaluable in 16 patients for calculation of test-retest and inter-reader reliability scores. The MaRIA scores for the terminal ileum had excellent test-retest and inter-reader reliability, with correlations >0.9. The proximal ileum showed strong within-reader agreement (0.90-0.96), and fair between-reader agreement (0.59-0.72). MRE procedures were tolerable. MaRIA scores correlated with CDEIS and SES-CD (0.63 and 0.71), but not with CDAI (0.34). MRE identified 3 patients with intra-abdominal complications, who would otherwise have been included in clinical trials. Furthermore, both MRE and ileocolonoscopy identified active bowel wall inflammation in 2 patients with CDAI <150, and none in 1 patient with CDAI > 220. Data quality was good/excellent in 85% of scans, and fair or better in 96%. CONCLUSIONS: Magnetic resonance enterography of high-quality and reproducibility was feasible in a global multi- centre setting, with evidence for improved selectivity over CDAI and ileocolonoscopy in identifying appropriate CD patients for inclusion in therapeutic intervention trials.

Exchange bias effect in partially oxidized amorphous Fe-Ni-B based metallic glass nanostructures.

The magnetic properties of amorphous Fe-Ni-B based metallic glass nanostructures were investigated. The nanostructures underwent a spin-glass transition at temperatures below 100 K and revealed an irreversible temperature following the linear de Almeida-Thouless dependence. When the nanostructures were cooled below 25 K in a magnetic field, they exhibited an exchange bias effect with enhanced coercivity. The observed onset of exchange bias is associated with the coexistence of the spin-glass phase along with the appearance of another spin-glass phase formed by oxidation of the structurally disordered surface layer, displaying a distinct training effect and cooling field dependence. The latter showed a maximum in exchange bias field and coercivity, which is probably due to competing multiple equivalent spin configurations at the boundary between the two spin-glass phases.

Mediation analysis of the association between use of NRT for smoking reduction and attempts to stop smoking.

OBJECTIVES: Use of nicotine replacement therapy (NRT) for smoking reduction (SR) is linked to higher quit attempt rates than SR without NRT. This study aimed to assess the possible mediating roles of confidence in ability to quit, enjoyment of smoking and motivation to quit in this association. DESIGN: Cross-sectional survey. MAIN OUTCOME MEASURES: Smokers were asked if they were currently attempting SR, and if they were, whether they were using NRT. Motivation to stop, enjoyment of smoking, confidence in ability to stop, and previous quit attempts, were also assessed. RESULTS: There was no evidence that confidence in ability to quit or enjoyment of smoking mediated the association between the use of NRT for SR and attempts to quit. Only motivation to stop partially mediated between the use of NRT for SR and attempts to stop (indirect effect: odds ratio 1.08, p < 0.001). CONCLUSION: Although this study is limited by its cross-sectional design, the findings point towards the possibility that the use of NRT to aid SR may promote attempts to stop through increasing motivation to quit but not by increasing confidence or by reducing enjoyment of smoking. Longitudinal studies are required to draw firmer conclusions about the possible mediating effects of motivation to quit.

L10 FePtCu bit patterned media.

Chemically ordered 5 nm-thick L10 FePtCu films with strong perpendicular magnetic anisotropy were post-patterned by nanoimprint lithography into a dot array over a 3 mm-wide circumferential band on a 3 inch Si wafer. The dots with a diameter of 30 nm and a center-to-center pitch of 60 nm appear as single domain and reveal an enhanced switching field as compared to the continuous film. We demonstrate successful recording on a single track using shingled writing with a conventional hard disk drive write/read head.

MRx102, a triptolide derivative, has potent antileukemic activity in vitro and in a murine model of AML.

Triptolide, isolated from the herb Tripterygium wilfordii, has been shown to potently induce apoptosis in various malignant cells by inhibiting RNA synthesis and nuclear factor-κB activity. Previously, we showed that triptolide promotes apoptosis in acute myeloid leukemia (AML) cells via the mitochondria-mediated pathway, in part, by decreasing levels of the anti-apoptotic proteins XIAP and Mcl-1. MRx102 is a triptolide derivative, currently in preclinical development. Here we show that MRx102 potently promoted apoptosis in AML cell lines, with EC(50) values of 14.5±0.6 nM and 37.0±0.9 nM at 48 h for OCI-AML3 and MV4-11 cells, respectively. MRx102, at low nanomolar concentrations, also induced apoptosis in bulk, CD34(+) progenitor, and more importantly, CD34(+)CD38(-) stem/progenitor cells from AML patients, even when they were protected by coculture with bone marrow derived mesenchymal stromal cells. MRx102 decreased XIAP and Mcl-1 protein levels and inhibited RNA synthesis in OCI-AML3 cells. In vivo, MRx102 greatly decreased leukemia burden and increased survival time in non-obese diabetic/severe combined immunodeficiency mice harboring Ba/F3-ITD cells. Collectively, we demonstrated that MRx102 has potent antileukemic activity both in vitro and in vivo, has the potential to eliminate AML stem/progenitor cells and overcome microenvironmental protection of leukemic cells, and warrants clinical investigation.

Liver stiffness measurement by magnetic resonance elastography is not associated with developing hepatocellular carcinoma in subjects with compensated cirrhosis.

BACKGROUND: Liver stiffness assessed using transient elastography is described as a potential risk factor for hepatocellular carcinoma (HCC) in cirrhosis. However, the strict assessment of hepatic parenchymal areas uninvolved with HCC has not been investigated. AIM: To determine if liver stiffness of nonmalignant hepatic parenchyma using magnetic resonance elastography (MRE) is higher in patients with HCC compared with controls. METHODS: Cases were defined by compensated cirrhosis with a Child-Turcotte-Pugh score <7 and HCC by radiological criteria or histology. Control subjects with compensated cirrhosis were frequency matched with cases by gender and disease aetiology. Overt manifestations of portal hypertension and previous therapy for liver disease or HCC were exclusion criteria. Region of interest analyses were performed on hepatic parenchyma regions distant to HCC location among cases. RESULTS: Thirty patients with HCC and 60 matched controls comprised the study cohort. The mean age for cases was 64±10 years (range, 45-85) with 70% being men. Major disease aetiologies were chronic viral hepatitis (57%), non-alcoholic fatty liver disease (33%) and alcohol (10%). Twenty-eight (93%) patients had solitary HCC lesions with a mean size of 5.2 cm (range, 2-14 cm). However, patients with HCC had similar liver stiffness among uninvolved areas distant to HCC lesions, when compared with controls without HCC (mean, 6.1±2.0 vs. 6.3±2.5 kPa, P=0.7). CONCLUSION: In contrast to previous studies with transient elastography, we did not observe a systematic association between liver stiffness assessed using MRE and the presence of HCC in patients with compensated cirrhosis.

Gastric motor disturbances in patients with idiopathic rapid gastric emptying.

BACKGROUND: The mechanisms of 'idiopathic' rapid gastric emptying, which are associated with functional dyspepsia and functional diarrhea, are not understood. Our hypotheses were that increased gastric motility and reduced postprandial gastric accommodation contribute to rapid gastric emptying. METHODS: Fasting and postprandial (300kcal nutrient meal) gastric volumes were measured by magnetic resonance imaging (MRI) in 20 healthy people and 17 with functional dyspepsia; seven had normal and 10 had rapid gastric emptying. In 17 healthy people and patients, contractility was analyzed by spectral analysis of a time-series of gastric cross-sectional areas. Logistic regression models analyzed whether contractile parameters, fasting volume, and postprandial volume change could discriminate between health and patients with normal or rapid gastric emptying. KEY RESULTS: While upper gastrointestinal symptoms were comparable, patients with rapid emptying had a higher (P=0.002) body mass index than normal gastric emptying. MRI visualized propagating contractions at ∼3cpm in healthy people and patients. Compared with controls (0.32±0.04, Mean±SEM), the amplitude of gastric contractions in the entire stomach was higher (OR 4.1, 95% CI 1.2-14.0) in patients with rapid (0.48±0.06), but not normal gastric emptying (0.20±0.06). Similar differences were observed in the distal stomach. However, the propagation velocity, fasting gastric volume, and the postprandial volume change were not significantly different between patients and controls. CONCLUSIONS & INFERENCES: MRI provides a non-invasive and refined assessment of gastric volumes and contractility in humans. Increased gastric contractility may contribute to rapid gastric emptying in functional dyspepsia.

Use of nicotine replacement therapy for smoking reduction and during enforced temporary abstinence: a national survey of English smokers.

AIMS: To assess the prevalence of nicotine replacement therapy (NRT) use for smoking reduction (SR) and temporary abstinence (TA), the association between the two and the strength of the association between NRT use for SR or TA and socio-demographic characteristics, cigarette consumption and past quit attempts. DESIGN: Cross-sectional monthly surveys. SETTING: England. PARTICIPANTS: A total of 11, 414 smokers. MEASUREMENTS: Participants were asked (i) whether they were reducing the amount they smoked: if so, whether they used NRT; and (ii) whether they used NRT for TA. Demographic characteristics, daily cigarette consumption and whether a quit attempt had been made in the past 12 months were also assessed. FINDINGS: Of the participants, 56% were attempting SR, 14% were using NRT for SR and 14% were using NRT for TA. Use of NRT for SR and TA were highly correlated. The nicotine patch was the most commonly used form of NRT. The use of NRT for SR, compared with unassisted SR, was more common among older smokers, while the use of NRT for TA was more common among women. Cigarette consumption was higher in those using NRT for SR than those attempting SR without NRT. The use of NRT for SR and TA was associated positively with past quit attempts. CONCLUSIONS: Nicotine replacement therapy use for smoking reduction and temporary abstinence is common in England. The use of NRT for SR and TA does not appear to be associated with lower cigarette consumption relative to SR or TA without NRT, but is associated with a higher rate of past quit attempts.

Magnetic films on nanoperforated templates: a route towards percolated perpendicular media.

We present a study on the magnetization reversal in Co/Pt multilayer films with an out-of-plane easy axis of magnetization deposited onto substrates with densely distributed perforations with an average period as small as 34 nm. Deposition of magnetic Co/Pt multilayers onto the nanoperforated surface results in an array of magnetic nanodots surrounded by a continuous magnetic film. Following the evolution of the magnetic domain pattern in the system, we suggest that domain walls are pinned on structural inhomogeneities given by the underlying nanoperforated template. Furthermore, a series of micromagnetic simulations was performed in order to understand the modification of the pinning strength of domain walls due to the magnetic interaction between nanodots and the surrounding film. The results of the simulations show that magnetic exchange coupling between the nanodots and the surrounding film strongly influences the pinning behavior of the magnetic domain walls which can be optimized to provide maximal pinning.

Application of magnetic resonance imaging to measure fasting and postprandial volumes in humans.

Our aims were to measure the gastric volume response in excess of ingested meal volume (i.e. gastric accommodation), contribution of swallowed air to this excess, day-to-day variability of gastric volumes measured by MRI and their relationship to volumes measured by single-photon-emission computed tomography (SPECT). In 20 healthy volunteers, fasting and postprandial gastric volumes were measured after technetium(99m)-pertechnetate labeling of the gastric mucosa by SPECT and separately by MRI, using 3D gradient echo and 2D half-Fourier acquisition single-shot turbo spin echo (HASTE) sequences. Ten of these subjects had a second MRI exam to assess intra-individual variation. Thereafter, another 10 subjects had two MRI studies during which they ingested the nutrient in 30 or 150 mL aliquots. During MRI, the postprandial gastric volume change exceeded the ingested meal volume by 106 +/- 12 mL (Mean +/- SEM). The HASTE and gradient echo sequences distinguished air from fluid under fasting and postprandial conditions respectively. This postprandial excess mainly comprised air (61 +/- 5 mL), which was not significantly different when ingested as 30 or 150 mL aliquots. Fasting and postprandial gastric volumes measured by MRI were generally reproducible within subjects. During SPECT, postprandial volumes increased by 158 +/- 18 mL; gastric volumes measured by SPECT were higher than MRI. MRI measures gastric volumes with acceptable performance characteristics; the postprandial excess primarily consists of air, which is not affected by the mode of ingestion. Gastric volumes are technique specific and differ between MRI and SPECT.

CT enterography and fistulizing Crohn's disease: clinical benefit and radiographic findings.

BACKGROUND: To estimate the clinical benefit of CT enterography (CTE) in patients with fistulizing Crohn's disease and describe the appearance of fistulas at CTE. METHODS: Crohn's patients who had undergone CTE, which diagnosed an abscess or fistula, were identified. A gastroenterologist reviewed clinical notes prior to and following CTE to assess the pre-CTE clinical suspicion for fistula/abscess, and post-CTE alteration in patient management. A radiologist reassessed all fistula-positive cases, which were confirmed by a non-CT reference standard, to describe their radiologic appearance. RESULTS: Fifty-six patients had CT exams identifying 19 abscesses and 56 fistulas. There was no or remote suspicion of fistula or abscess at pre-imaging clinical assessment in 50% of patients. Thirty-four patients (61%) required a change in or initiation of medical therapy and another 10 (18%) underwent an interventional procedure based on CT enterography findings. Among 37 fistulas with reference standard confirmation, 30 (81%) were extraenteric tracts, and 32 (86%) were hyperenhancing compared to adjacent bowel loops. Most fistulas (68%) contained no internal air or fluid. CONCLUSION: CTE detects clinically occult fistulas and abscesses, resulting in changes in medical management and radiologic or surgical intervention. Most fistulas appear as hyperenhancing, extraenteric tracts, usually without internal air or fluid.

Vulnerability to smoking after trying a single cigarette can lie dormant for three years or more.

OBJECTIVE: To examine the development of smoking behaviour among adolescents who, at age 11, had tried cigarettes just once. DESIGN: A five-year prospective study. SETTING: 36 schools in South London, England. SUBJECTS: A socioeconomically and ethnically diverse sample of students completed questionnaires annually from age 11-16. A total of 5863 students took part, with an annual response rate ranging from 74-85%. 2041 (35%) provided smoking status data every year. MAIN OUTCOME MEASURES: Current smoking (smoking sometimes or more often) for the first time. Cotinine assays provided biochemical verification of smoking status. RESULTS: Students who at age 11 reported having tried smoking cigarettes just once (n = 260), but were not smoking at the time, were more likely to take-up smoking at a later age than those that had not tried smoking (n = 1719), even after a gap of up to three years of not smoking. The odds of starting to smoke at age 14 were 2.1 times greater (95% confidence interval 1.2 to 3.5) in the age 11 "one time triers" than the "non-triers", even once sex, ethnicity, deprivation, parental smoking and conduct disorder were adjusted for. CONCLUSIONS: This is the first clear demonstration of a "sleeper effect" or period of dormant vulnerability. Our findings have implications for understanding the development of cigarette use and for policies to reduce smoking in young people. Preventing children from trying even one cigarette may be important, and the design of interventions should recognise adolescents who have smoked just once, several years previously, as potentially vulnerable to later smoking uptake.

Synthesis of CoPt nanoparticles by a modified polyol method: characterization and magnetic properties.

CoPt nanoparticles with an average size of 3 nm and narrow distribution were synthesized by chemical reduction of Co(CH(3)COO)(2) and Pt(acac)(2) by polyethyleneglycol-200. The as-prepared nanoparticles have a disordered fcc structure which transformed after thermal treatment to an ordered fct structure, which results in coercivity up to 6 kOe at room temperature and 9 kOe at 5 K because of the high magnetocrystalline anisotropy of the tetragonal structure [Formula: see text].

Preoperative detection of pancreatic insulinomas on multiphasic helical CT.

OBJECTIVE: The objective was to analyze enhancement characteristics of insulinomas and to determine the ability of multiphase CT to localize these tumors. MATERIALS AND METHODS: Prospective interpretations of multiphase helical CT scans were reviewed in 30 patients who had insulinomas resected over a 5-year period. CT scans were retrospectively reviewed to determine enhancement characteristics, tumor conspicuity in each phase of enhancement, and potential causes for false-negative findings. RESULTS: Sixty-three percent (19/30) of tumors were identified on CT prospectively. An additional six tumors were visualized in retrospect, allowing characterization of 25 (83%) of 30 tumors. Most tumors were hyperdense on at least one phase (n = 19), three tumors were hypoattenuating, and three were isodense and pedunculated. Insulinomas were most conspicuous on the early phase in 15 patients and in the portal venous phase in three. All tumors that underwent pancreatic phase imaging were seen (13/13), whereas three of 18 arterial and six of 25 portal venous phase findings were inconclusive for tumor. In the six examinations with false-negative findings in which the tumor could be seen in retrospect, two tumors were isodense and pedunculated, three were in close proximity to vessels, and one had a cystic appearance. CONCLUSION: Multiphasic CT has a moderate sensitivity in the detection of insulinomas. Most tumors are more conspicuous on the earlier phases of enhancement. The pancreatic phase may be more useful than the arterial phase. Potential sources of false-negative results include tumors adjacent to vessels, pedunculated morphology, or nonhyperattenuating lesions.

Detection of flat lesions in the colon with CT colonography.

BACKGROUND: We investigated whether flat lesions of the colon could be detected on computed tomographic colonography (CTC). METHODS: CTC and conventional colonoscopy were performed on 547 consecutive patients. A subset of 22 polyps was described as flat on colonoscopy (n = 16) or CTC (n = 6) and are the basis of this report. CTC was performed with a standard technique (5-mm collimation, 3-mm reconstruction intervals). Patients were scanned in supine and prone positions. Examinations were randomly assigned and reviewed in a blinded fashion by two of three radiologists. Prospective interpretations were recorded. All patients had conventional colonoscopy, which served as the gold standard. RESULTS: Twenty-two flat lesions ranging from 0.4 to 3.5 cm were histologically classified as adenomatous (n = 8) or hyperplastic (n = 14). The sensitivities for detecting all flat lesions and flat adenomas by each reviewer were 43% and 100%, 65% and 100%, and 15% and 13%, respectively. "Double reading" resulted in detection of 68% of all lesions and 100% of adenomas. Of the seven hyperplastic polyps missed by both reviewers, four were identified retrospectively. CONCLUSION: Flat lesions of the colon represent an important source of false negative CTC examinations. Awareness of their morphology can assist radiologists in finding most of these challenging lesions.

Imaging of neuroendocrine tumors of the pancreas.

BACKGROUND: Neuroendocrine tumors of the pancreas are uncommon neoplasms of the pancreas that can occur sporadically or in association with various syndromes such as multiple endocrine neoplasia type 1 (MEN I). Patients can present with a specific clinical syndrome related to biochemically functioning tumors or with nonspecific symptoms related to mass effect or metastases. The size, function, consistency, and malignant behavior of neuroendocrine tumors are integrally related. Imaging has a major role in the preoperative localization of the primary tumor and detection of metastases. Several techniques are available including ultrasound, endoscopic ultrasound, computed tomography (CT), MR, somatostatin receptor scintigraphy, angiography, and arterial stimulation with venous sampling; each with unique advantages and limitations. The reported performance for these techniques vary widely, and as a result, recommended imaging algorithms are controversial. Recent technical advances in ultrasound, CT, and MRI have occurred that may improve the sensitivity of some of the techniques. Further improvements are likely in the future. In this chapter we will review imaging techniques used to study the pancreas as it relates to the detection of neuroendocrine tumors, imaging findings of these tumors using various imaging modalities, and the advantages, limitations and results obtained with each technique.

Prevention of graft-versus-host disease by a novel immunosuppressant, PG490-88, through inhibition of alloreactive T cell expansion.

BACKGROUND: PG490-88 is a water soluble, semisynthetic derivative of a novel compound PG490 (triptolide) purified from the Chinese herb Tripterygium Wilfordii Hook F. METHODS: PG490-88 was administrated into recipient mice in a model (B10.D2-->BALB/c) of lethal graft-versus-host disease (GVHD) to study the effects of PG490-88 on GVHD and on the various steps involved in the pathological course of GVHD. RESULTS: Injection of PG490-88 i.p. at a dose of 0.535 mg/kg/day for the first 3 weeks after transplantation protected all the recipients from developing GVHD up to 100 days after transplantation. PG490-88 inhibited in vivo both CD4+Vbeta3+ and CD8+Vbeta3+ T cell (alloreactive T cells in this model) expansion in the spleen by 64.09 and 34.02%, respectively, at the time when Vbeta3+ cell expansion was in the logarithmic phase (day 3 after transplantation). Intracellular cytokine staining without further in vitro activation demonstrated 47.42% inhibition of IL-2 production among CD4+ spleen cells in PG490-88-treated mice as compared to GVHD control on day 3 after transplantation. In contrast, CD25 (alpha chain of interleukin-2 receptor) expression did not differ. CONCLUSIONS: PG490-88 is highly effective in prevention of murine GVHD. The immunosuppressive effect of PG490-88 is mediated by inhibition of alloreactive T cell expansion through interleukin-2 production.