An international multidisciplinary consensus statement on fasting before procedural sedation in adults and children.

The multidisciplinary International Committee for the Advancement of Procedural Sedation presents the first fasting and aspiration prevention recommendations specific to procedural sedation, based on an extensive review of the literature. These were developed using Delphi methodology and assessment of the robustness of the available evidence. The literature evidence is clear that fasting, as currently practiced, often substantially exceeds recommended time thresholds and has known adverse consequences, for example, irritability, dehydration and hypoglycaemia. Fasting does not guarantee an empty stomach, and there is no observed association between aspiration and compliance with common fasting guidelines. The probability of clinically important aspiration during procedural sedation is negligible. In the post-1984 literature there are no published reports of aspiration-associated mortality in children, no reports of death in healthy adults (ASA physical status 1 or 2) and just nine reported deaths in adults of ASA physical status 3 or above. Current concerns about aspiration are out of proportion to the actual risk. Given the lower observed frequency of aspiration and mortality than during general anaesthesia, and the theoretical basis for assuming a lesser risk, fasting strategies in procedural sedation can reasonably be less restrictive. We present a consensus-derived algorithm in which each patient is first risk-stratified during their pre-sedation assessment, using evidence-based factors relating to patient characteristics, comorbidities, the nature of the procedure and the nature of the anticipated sedation technique. Graded fasting precautions for liquids and solids are then recommended for elective procedures based upon this categorisation of negligible, mild or moderate aspiration risk. This consensus statement can serve as a resource to practitioners and policymakers who perform and oversee procedural sedation in patients of all ages, worldwide.

Pulmonary aspiration during procedural sedation: a comprehensive systematic review.

Background: Although pulmonary aspiration complicating operative general anaesthesia has been extensively studied, little is known regarding aspiration during procedural sedation. Methods: We performed a comprehensive, systematic review to identify and catalogue published instances of aspiration involving procedural sedation in patients of all ages. We sought to report descriptively the circumstances, nature, and outcomes of these events. Results: Of 1249 records identified by our search, we found 35 articles describing one or more occurrences of pulmonary aspiration during procedural sedation. Of the 292 occurrences during gastrointestinal endoscopy, there were eight deaths. Of the 34 unique occurrences for procedures other than endoscopy, there was a single death in a moribund patient, full recovery in 31, and unknown recovery status in two. We found no occurrences of aspiration in non-fasted patients receiving procedures other than endoscopy. Conclusions: This first systematic review of pulmonary aspiration during procedural sedation identified few occurrences outside of gastrointestinal endoscopy, with full recovery typical. Although diligent caution remains warranted, our data indicate that aspiration during procedural sedation appears rare, idiosyncratic, and typically benign.

Effect of dose reduction on image registration and image quality for cone-beam CT in radiotherapy.

INTRODUCTION: The additional radiation exposure applied to patients undergoing cone-beam computed tomography (CBCT) for image registration in radiation therapy is of great concern. Since a decrease in CBCT dose is linked to a degradation of image quality, the consequences of dose reduction on the registration process have to be investigated. MATERIAL AND METHODS: This paper examines image quality and registration of low-contrast structures on an Elekta XVI for the two treatment areas prostate and chest while gradually decreasing the mAs per frame and the number of projections per CBCT to achieve dose reduction. RESULTS: Ideal results for image quality were obtained for 1.6 mAs/frame and 377 projections in prostate scans and 0.63 mAs/frame and 440 projections in chest images. Lower as well as higher total mAs lead to a decrease in image quality. In spite of poor image quality, registration can be successfully performed even for lowest possible settings. CONCLUSION: The results for registration allow an extensive dose reduction in both treatment areas. Very low mAs, however, do not qualify for clinical use because subjective judgment of the registration process is impossible. Compared to default presets the use of settings for acceptable image quality already permit a decrease in exposure of about 40 % (29.0 to 16.7 mGy) in prostate scans and 60 % (18.3 to 7.7 mGy) in chest scans.

Dual-energy computed tomography after endovascular aortic aneurysm repair: the role of hard plaque imaging for endoleak detection.

OBJECTIVES: To assess the diagnostic accuracy of dual-energy computed tomography (DECT) for detection of endoleaks and aneurysm sac calcifications after endovascular aneurysm repair (EVAR) using hard plaque imaging algorithms. MATERIALS AND METHODS: One hundred five patients received 108 triple-phase contrast-enhanced CT (non-contrast, arterial and delayed phase) after EVAR. The delayed phase was acquired in dual-energy and post-processed using the standard (HPI-S) and a modified (HPI-M) hard plaque imaging algorithm. The reference standard was determined using the triple-phase CT and contrast-enhanced ultrasound. All images were analysed separately for the presence of endoleaks and calcifications by two independent readers; sensitivity, specificity and interobserver agreement were calculated. RESULTS: Endoleaks and calcifications were present in 25.9 % (28/108) and 20.4 % (22/108) of images. The HPI-S images had a sensitivity/specificity of 54 %/100 % (reader 1) and 57 %/99 % (reader 2), the HPI-M images of 93 %/92 % (reader 1) and 96 %/92 % (reader 2) for detection of endoleaks. For detection of calcifications HPI-S had a sensitivity/specificity of 91 %/99 % (reader 1) and 95 %/97 % (reader 2), the HPI-M images of 91 %/99 % (reader 1) and 91 %/99 % (reader 2), respectively. CONCLUSION: Using HPI-M, DECT enables an accurate diagnosis of endoleaks after EVAR and allows distinguishing between endoleaks and calcifications with high diagnostic accuracy. KEY POINTS: • Dual-energy computed tomography allows the diagnosis of aortic pathologies after EVAR. • Hard plaque imaging algorithms can distinguish between endoleaks and aneurysm sac calcifications. • The modified hard plaque imaging algorithm detects endoleaks with high diagnostic accuracy.

High-pitch dual-source CT angiography of supra-aortic arteries: assessment of image quality and radiation dose.

INTRODUCTION: High-pitch CT angiography (CTA) is a recent innovation that allows significant shortening of scan time with volume coverage of 43 mm per second. The aim of our study was to assess this technique in CTA of the head and neck. METHODS: CTA of supra-aortic arteries was performed in 50 patients using two acquisition protocols: conventional single-source 64-slice (pitch 1.2) and high-pitch dual-source 128-slice CT (pitch 3.2). Subjective and objective image quality of supra-aortic vessel ostia as well as intra- and extra-cranial segments was retrospectively assessed by blinded readers and radiation dose compared between the two protocols. RESULTS: Conventional and high-pitch CTA achieved comparable signal-to-noise ratios in arterial (54.3 ± 16.5 versus 57.3 ± 14.8; p = 0.50) and venous segments (15.8 ± 6.7 versus 18.9 ± 8.9; p = 0.21). High-pitch scanning was, however, associated with sharper delineation of vessel contours and image quality significantly improved at the level of supra-aortic vessel ostia (p < 0.0001) as well as along the brachiocephalic trunk (p < 0.0001), the subclavian arteries (p < 0.0001), proximal common carotid arteries (p = 0.01), and vertebral V1 segments (p < 0.0001). Using the high-pitch mode, the dose-length product was reduced by about 35% (218.2 ± 30 versus 141.8 ± 20 mGy × cm). CONCLUSIONS: Due to elimination of transmitted cardiac motion, high-pitch CTA of the neck improves image quality in the proximity of the aortic arch while significantly lowering radiation dose. The technique thus qualifies as a promising alternative to conventional spiral CTA and may be particularly useful for identification of ostial stenosis.

The immunosuppressive fungal metabolite gliotoxin specifically inhibits transcription factor NF-kappaB.

Opportunistic infections, such as aspergillosis, are among the most serious complications suffered by immunocompromised patients. Aspergillus fumigatus and other pathogenic fungi synthesize a toxic epipolythiodioxopiperazine metabolite called gliotoxin. Gliotoxin exhibits profound immunosuppressive activity in vivo. It induces apoptosis in thymocytes, splenocytes, and mesenteric lymph node cells and can selectively deplete bone marrow of mature lymphocytes. The molecular mechanism by which gliotoxin exerts these effects remains unknown. Here, we report that nanomolar concentrations of gliotoxin inhibited the activation of transcription factor NF-kappaB in response to a variety of stimuli in T and B cells. The effect of gliotoxin was specific because, at the same concentrations, the toxin did not affect activation of the transcription factor NF-AT or of interferon-responsive signal transducers and activators of transcription. Likewise, the activity of the constitutively DNA-binding transcription factors Oct-1 and cyclic AMP response element binding protein (CREB), as well as the activation of protein tyrosine kinases p56lck and p59fyn, was not altered by gliotoxin. Very high concentrations of gliotoxin prevented NF-kappaB DNA binding in vitro. However, in intact cells, inhibition of NF-kappaB did not occur at the level of DNA binding; rather, the toxin appeared to prevent degradation of IkappaB-alpha, NF-kappaB's inhibitory subunit. Our data raise the possibility that the immunosuppression observed during aspergillosis results in part from gliotoxin-mediated NF-kappaB inhibition.

Suppression of heart rate variability after supramaximal exertion.

Wingate test is short anaerobic exercise, performed with maximal power, whereas aerobic exercise at 85% maximal heart rate (HR(max)) may be performed for long period. Sustained HR elevations and changes in autonomic activity indices have been observed after latter kind of exercise. Several studies reported reduction in mean interval between consecutive R peaks in ECG (RRI) 1 h after Wingate test; however, underlying changes in autonomic activity remain elusive. In eight young males, RRI and heart rate variability (HRV) were measured daily over two 5-day trials. Subjects exercised on third day of each trial, measurements were taken 1 h after (i) two consecutive 30-s bouts of Wingate tests or (ii) after a 30-min exercise at 85% HR(max), with subjects in supine rest and breathing either spontaneously or at controlled rates of 6 and 15 breaths / min. RRI was significantly shorter after Wingate and submaximal exercise, reduction of high- and low-frequency components of HRV attained reliability only after Wingate tests. This pattern remained preserved for three modes of breathing: spontaneous, 6 and 15 breaths /min. After 24 and 48 h, no exercise effects were traceable. We hypothesize that (i) anaerobic exertion is followed by sustained inhibition of vagal activity, (ii) parasympathetic system plays dominant role in mediating suppression of high- and low-HRV frequency components during postexercise recovery, (iii) degree of alteration of autonomic activity caused by anaerobic and strenuous aerobic exercise may be similar and (iv) normalization of vagal activity precedes normalization of sympathetic cardiac nerves activity during final stage of postexercise recovery.

Dual Energy CT Kidney Stone Differentiation in Photon Counting Computed Tomography.

This study evaluates the capabilities of a whole-body photon counting CT system to differentiate between four common kidney stone materials, namely uric acid (UA), calcium oxalate monohydrate (COM), cystine (CYS),and apatite (APA) ex vivo. Two different x-ray spectra (120 kV and 140 kV) were applied and two acquisition modes were investigated; The macro-mode generates two energy threshold based image-volumes and two energy bin based image-volumes. In the chesspattern-mode, however, four energy thresholds are applied. A virtual low energy image, as well as a virtual high energy image are derived from initial threshold-based images, while considering their statistically correlated nature. The energy bin based images of the macro-mode, as well as the virtual low and high energy image of the chesspattern-mode serve as input for our dual energy evaluation. The dual energy ratio of the individually segmented kidney stones were utilized to quantify the discriminability of the different materials. The dual energy ratios of the two acquisition modes showed high correlation for both applied spectra. Wilcoxon-rank sum tests and the evaluation of the area under the receiver operating characteristics curves suggest that the UA kidney stones are best differentiable from all other materials (AUC = 1.0), followed by CYS (AUC ≈ 0.9 compared against COM and APA). COM and APA, however, are hardly distinguishable (AUC between 0.63 and 0.76). The results hold true for the measurements of both spectra and both acquisition modes.

Image movement of the Elekta EPID during gantry rotation: Effects on the verification of dose distributions.

PURPOSE: The use of Electronic Portal Imaging Devices (EPIDs) to acquire dosimetric information, especially for 3D-back-projection, has been increasingly extended. For a precise back-projection, the accurate knowledge of the movement characteristics of the EPID during gantry rotation is an essential requirement. METHODS AND MATERIAL: Measurements were conducted with different alignments of steel balls, which were mounted on the treatment table to avoid secondary effects such as the mechanical sag of gantry or jaws. The image movement of the EPID was determined by comparing the predicted projections of the phantoms with the EPID acquired image. Effects on dosimetric verifications were evaluated by γ-evaluation. RESULTS: The measurement results showed that the shift of the EPID image is larger in Y direction than in X direction. A maximum rotation of 0.3° and nodding of 2.4° of the detector was calculated. Changes in SDD were found up to 10mm. The angles of nodding are overall higher at discrete gantry angles in comparison to images detected for continuous rotation. Using these results we were able to correct the EPID images used for verification measurements. γ-evaluation revealed a significantly improved agreement between planned and measured EPID signal values. CONCLUSION: The measurement methods and algorithms introduced in this study are simple and comprehensive. Using these methods and algorithms we were able to quantify the major effects on geometrical and dosimetric characteristics. This allows the correction of EPID signal measurements for these effects related to the gantry angle, leading to an improved γ-evaluation for treatment plans.

Electromagnetic versus fluoroscopic mapping of the inferior isthmus for ablation of typical atrial flutter: A prospective randomized study.

BACKGROUND: Radiofrequency catheter ablation within the tricuspid annulus-inferior caval vein isthmus can cure typical atrial flutter. The target for ablation, nonetheless, is relatively wide, and standard ablation procedures may require significant exposure to radiation. METHODS AND RESULTS: A total of 50 patients (mean age, 58+/-11 years) with typical atrial flutter were prospectively randomized to receive isthmus ablation using conventional fluoroscopy for catheter navigation (group I, n=24) or electromagnetic mapping (group II, n=26). Complete bidirectional isthmus block was verified with double potential mapping. If complete isthmus block could not be achieved after 20 radiofrequency pulses or 25 minutes of fluoroscopy, the patients were switched to the other group. Eight patients from group I (33%) but only 1 patient from group II (4%) were switched. Overall, complete isthmus block was achieved in 47 of 50 patients (94%). The overall fluoroscopy time, including the placement of the diagnostic catheters, was 22.0+/-6.3 minutes in group I and 3.9+/-1.5 minutes in group II (P:<0.0001). The fluoroscopy time needed for isthmus mapping was 17.7+/-6.5 minutes in group I and 0.2+/-0.3 minutes in group II (P:<0.0001). CONCLUSIONS: Electromagnetic mapping during the induction of linear lesions for the ablation of atrial flutter permitted a highly significant reduction in exposure to fluoroscopy while maintaining high efficacy, and it allowed the time required for fluoroscopy to be reduced to levels anticipated for diagnostic electrophysiological studies.

Gene structures and properties of enzymes of the plasmid-encoded nicotine catabolism of Arthrobacter nicotinovorans.

Arthrobacter nicotinovorans is a Gram-positive aerobic soil bacterium able to grow on nicotine as its sole source of carbon and nitrogen. The initial steps of nicotine catabolism are catalyzed by nicotine dehydrogenase, the l- and d-specific 6-hydroxynicotine oxidases, and ketone dehydrogenase. The genes encoding these enzymes reside on a 160 kb plasmid, pAO1. The cccDNA of this plasmid was isolated in high purity and reasonable yield. It served as template material for the construction of a lambda-phage DNA library of the plasmid. The genes coding for 6-hydroxy-l-nicotine oxidase and for the subunits of the heterotrimeric ketone dehydrogenase were identified, subcloned and sequenced. The 6-hlno gene was identified as a 1278 bp open reading frame; its regulatory elements were also recognized. The derived primary structure of the monomer of apo-6-hydroxy-l-nicotine oxidase (46,264.5 Da) agrees with the data obtained by partial amino acid sequencing. 6-Hydroxy-l-nicotine oxidase and 6-hydroxy-d-nicotine oxidase were expressed in Escherichia coli and obtained in a state of high purity and crystallized. Ketone dehydrogenase (KDH) was found to be a heterotrimer with subunits of molecular mass 89,021.71, 26,778.65 and 17,638.88. The genes of KDH-A and KDH-B are juxtaposed; the A of the stop codon of KDH-A is used in the start codon of KDH-B, eliciting a frame shift. KDH-C is separated from KDH-A by 281 bp.

Performance differences between addicts and non-addicts.

Methadone addicts and non-addict controls were tested before and after receiving up to 10 mg of methadone on simple visual reaction time tests and on a vigilance type visual attention test. Addicts were faster than controls on pre-drug testing, although there were no pre-drug differences between groups on the attention task. Addicts maintained faster reaction times than controls even when money was offered as an incentive for speed. Additional methadone did not affect addict performance on any of the tasks. Methadone slowed control reaction times in a dose-related fashion. No significant attention decrements were seen after methadone in controls. Visual reaction time differences between addicts and controls cannot be attributed to group differences in motivation or ability to attend. Slowing of reaction time with acute dose of methadone in controls cannot be attributed to the effect of the drug on attention. An hypothesized drug-induced decrease in visual sensitivity with acute dose in controls and a drug-induced increase in visual sensitivity with chronic dose in addicts can account for the presented data.

Combined stentless mitral valve implantation and radiofrequency ablation.

BACKGROUND: The aim of this study was to evaluate the results of combined stentless mitral valve (SMV) replacement and intraoperative radiofrequency ablation for chronic atrial fibrillation (IRAAF) to restore physiologic hemodynamic function. METHODS: Since July 1998 12 patients (72+/-4 years, 10 women, mitral stenosis/mitral incompetence 8/4, NYHA 3.3+/-0.4, CI 1.8+/-0.5) had SMV implantation and received additional IRAAF by inducing continuous left atrial lesion lines from the MV annulus to all four pulmonary veins and to the atriotomy. RESULTS: The flexible SMV was implanted at the papillary muscles and at the annulus using a conventional (n = 6) or a minimally invasive approach (n = 6). Sinus rhythm was successfully restored in 10 of 12 patients with 6- and 12-months' follow-up; 2 required DDD-pacemaker implantation. However, in the early postoperative period several interventions including medical treatment (sotalol or amiodarone) in 9 and electrical cardioversion in 7 patients was required. Two patients required reinterventions: 1 cardioversion and 1 amiodarone medication after 3 and 6 months, respectively. At echocardiography the SMV demonstrated good hemodynamic function and atrial contraction. CONCLUSIONS: Restoration of physiologic cardiac function by SMV implantation and IRAAF is advantageous and no further anticoagulation is required.

Imaging the pain of low back pain: functional magnetic resonance imaging in combination with monitoring subjective pain perception allows the study of clinical pain states.

Most brain imaging studies of pain are done using a two-state subtraction design (state-related design). More recently event-related functional magnetic reasonance imaging (fMRI) has also been used for studying pain. Both designs severely limit the application of the technology to clinical pain states. Recently we demonstrated that monitoring time fluctuations of perceived pain could be used with fMRI to identify brain regions involved in conscious, subjective perception of pain. Here we extend the methodology to demonstrate that the same approach can be used to study clinical pain states. Subjects are equipped with a finger-spanning device to continuously rate and log their perceived pain during fMRI data collection. These ratings are convolved with a canonical hemodynamic response function to generate predictor waveforms with which related brain activity can be identified. Chronic low back pain patients and a normal volunteer were used. In one series of fMRI scans the patient simply lies in the scanner and indicates spontaneous fluctuations of the subjective pain. In other fMRI scans, a straight-leg raising procedure is performed to exacerbate the back pain. In the normal volunteer, fMRI scans were done during painful and non-painful straight-leg raisings. The results indicate the feasibility of differentiating between different pain states. We argue that the approach can be generalized to identify brain circuitry underlying diverse clinical pain conditions.

Prefrontal cortical hyperactivity in patients with sympathetically mediated chronic pain.

Chronic pain continues to impose a large burden of suffering, yet its neural correlates remain poorly understood. In sympathetically mediated chronic pain (SMP), peripheral sympathetic blockade temporarily relieves this pain, so that related neural activity can be studied without perturbing sensory inputs. We used functional magnetic resonance imaging and thermal painful stimuli applied to the chronically painful body site, before and after sympathetic blockade, to examine the cortical network of chronic pain. The chronic SMP state was associated with a widely spread prefrontal hyperactivity, increased anterior cingulate activity and decreased activity in the thalamus contralateral to the body side suffering from SMP, but was unrelated to sensorimotor activity. Ineffective sympathetic blocks, i.e. blocks that did not diminish the SMP pain, did not change the cortical responses to the painful thermal stimulus; while effective placebo resulted in similar responses to those of effective blocks. These findings provide evidence for abnormal brain responses to pain in patients with chronic SMP, which engages prefrontal/limbic networks more extensively than in acute pain-states.

Factors associated with urban gay men's treatment initiation decisions for HIV infection.

While a public health emphasis on primary prevention of human immunodeficiency virus (HIV) infection continues, it is recognized that large numbers of individuals are already infected. Efforts at secondary prevention focus on early medical intervention and may be effective in slowing progression to a diagnosis of AIDS. Understanding the factors that promote or impede seropositive individuals from receiving prompt medical treatment and complying with treatment regimens is essential to prolonging survival. During unstructured interviews in an ongoing study of sexual decision-making, 55 urban, gay, seropositive men spontaneously offered information about their treatment choices for their HIV infection. Findings regarding their considerations in initiating, delaying, or rejecting medical treatment are presented.

New mutations affecting induced mutagenesis in yeast.

Previously isolated mutations in baker's yeast, Saccharomyces cerevisiae, that impair induced mutagenesis were all identified with the aid of tests that either exclusively or predominantly detect base-pair substitutions. To avoid this bias, we have screened 11 366 potentially mutant clones for UV-induced reversion of the frameshift allele, his4-38, and have identified 10 mutants that give much reduced yields of revertants. Complementation and recombination tests show that 6 of these carry mutations at the previously known REV1, REV1 and REV3 loci, while the remaining 4 define 3 new genes, REV4 (2 mutations), REV5 and REV6. The rev4 mutations are readily suppressed in many genetic backgrounds and, like the rev5 mutation, impart only a limited deficiency for induced mutagenesis: it is likely, therefore that the REV4+ and REV5+ gene functions are only remotely concerned with this process. The rev6 mutants have a more general deficiency, however, as well as marked sensitivity to UV and an increased spontaneous mutation rate, properties that suggest the REV6 gene is directly involved in mutation induction. The REV5 gene is located about 1 cM proximal to CYC1 on chromosome X.

[Clinical use of gradient echo sequences of longer repetition times]. / Klinische Anwendung von Gradientenecho-Sequenzen mit längeren Repetitionszeiten.

Studies designed to optimise image contrasts of gradient echo sequences showed, that especially repetition times between 250 and 500 ms in combination with adequate echo times and flip angles provide new image contrasts. The clinical purpose of gradient echo sequences with longer TR was systematically evaluated in 450 patients. A major advantage of GE sequences was the low signal intensity of fat and bone tissue. On the other hand different pathologic changes showed a high signal intensity in comparison to T2 weighted spin echo sequences as well. With the possibility of multiple slices GE sequences were of outstanding diagnostic value especially in MR of soft tissue and of the musculoskeletal system. T2 weighted SE sequences provided no additional informations and could therefore be omitted in a great number of examinations.

[Comparison of mammography and automated sonography in 700 patients]. / Vergleich von Mammographie und automatisierter Sonographie an 700 Patienten.

700 patients underwent routinely x-ray mammography and breast ultrasound with an automated grey-scale breast scanner. The parenchymal pattern of the ultrasound B-scan was morphological identical to the x-ray film. The echogram gave further informations about the topographic localisation of pathologic lesions to the chest wall including the pectoral muscles. The sonogram was of no value in 10 percent due to diffuse reflection of the breast. In cystic disease the diagnostic accuracy of the ultrasound was with about 100 percent superior to that of x-ray mammography. On the contrary the accuracy of the x-ray mammography was higher than that of ultrasound in the diagnosis of benign or malignant solids. Benign adenoma smaller than 1 cm could not be definetively recognised as carcinoma of this size. The diagnostic accuracy of the sonogram was 70 percent by 40 histologically proved carcinomas. The only use of the automated scanner in the diagnostics of the breast seams to be not justified, even not as a screening method, especially because small tumors with good prognosis are not recognized, however, the ultrasound gives additional important informations in the differential diagnosis of benign and malignant lesions of the female breast.