Are liver contour and bone fusion comparable to fiducials for IGRT in liver SBRT?

Introduction: Liver stereotactic body radiotherapy (SBRT) is increasingly being used to treat tumours. The purpose of this study was to compare the differences in patient positioning when using implanted fiducials as surrogates compared to alternative methods based on liver contour or bone registration. Material and methods: Eighteen patients treated with SBRT who underwent a fiducial placement procedure were included. Fiducial guidance was our gold standard to guide treatment in this study. After recording the displacements, when fusing the planning CT and CBCT performed in the treatment unit using fiducials, liver contour and bone reference, the differences between fiducials and liver contour and bone reference were calculated. Data from 88 CBCT were analyzed. The correlation between the displacements found with fiducials and those performed based on the liver contour and the nearest bone structure as references was determined. The mean, median, variance, range and standard deviation of the displacements with each of the fusion methods were obtained. µ, Æ©, and σ values and margins were obtained. Results: Lateral displacements of less than 3 mm with respect to the gold standard in 92% vs. 62.5% of cases using liver contour and bone references, respectively, with 93.2% vs. 65.9% in the AP axis and SI movement in 69.3% vs. 51.1%. The errors µ, σ and Æ© of the fusions with hepatic contour and bone reference in SI were 0.26 mm, 4 mm and 3 mm, and 0.8 mm, 5 mm and 3 mm respectively. Conclusion: Our study showed that displacements were smaller with the use of hepatic contour compared to bone reference and comparable to those obtained with the use of fiducials in the lateral, AP and SI motion axes. This would justify that hepatic contouring can be a guide in the treatment of patients in the absence of fiducials.

Prediction of clinical diagnosis of Alzheimer's disease, vascular, mixed, and all-cause dementia by a polygenic risk score and APOE status in a community-based cohort prospectively followed over 17 years.

The strongest genetic risk factor for Alzheimer's disease (AD) is the ε4 allele of Apolipoprotein E (APOE) and recent genome-wide association meta-analyses have confirmed additional associated genetic loci with smaller effects. The aim of this study was to investigate the ability of an AD polygenic risk score (PRS) and APOE status to predict clinical diagnosis of AD, vascular (VD), mixed (MD), and all-cause dementia in a community-based cohort prospectively followed over 17 years and secondarily across age, sex, and education strata. A PRS encompassing genetic variants reaching genome-wide significant associations to AD (excluding APOE) from the most recent genome-wide association meta-analysis data was calculated and APOE status was determined in 5203 participants. During follow-up, 103, 111, 58, and 359 participants were diagnosed with AD, VD, MD, and all-cause dementia, respectively. Prediction ability of AD, VD, MD, and all-cause dementia by the PRS and APOE was assessed by multiple logistic regression and receiver operating characteristic curve analyses. The PRS per standard deviation increase in score and APOE4 positivity (≥1 ε4 allele) were significantly associated with greater odds of AD (OR, 95% CI: PRS: 1.70, 1.45-1.99; APOE4: 3.34, 2.24-4.99) and AD prediction accuracy was significantly improved when adding the PRS to a base model of age, sex, and education (ASE) (c-statistics: ASE, 0.772; ASE + PRS, 0.810). The PRS enriched the ability of APOE to discern AD with stronger associations than to VD, MD, or all-cause dementia in a prospective community-based cohort.

Alzheimer's disease medication and outcomes of hospitalisation among patients with dementia.

AIMS: The use of Alzheimer disease medication for the treatment of dementia symptoms has shown significant benefits with regards to functional and cognitive outcomes as well as nursing home placement (NHP) and mortality. Hospitalisations in these patient groups are characterised by extended length of stays (LOS), frequent readmissions, frequent NHP and high-mortality rates. The impact of Alzheimer disease medication on the aforementioned outcomes remains still unknown. This study assessed the association of Alzheimer disease medication with outcomes of hospitalisation among patients with Alzheimer disease and other forms of dementia. METHODS: A dynamic retrospective cohort study from 2004 to 2015 was conducted which claims data from a German health insurance company. People with dementia (PWD) were identified using ICD-10 codes and diagnostic measures. The main predictor of interest was the use of Alzheimer disease medication. Hospitalisation outcomes included LOS, readmissions, NHP and mortality during and after hospitalisation across four hospitalisations. Confounding was addressed using a propensity score throughout all analyses. RESULTS: A total of 1380 users of Alzheimer disease medication and 6730 non-users were identified. The use of Alzheimer disease medication was associated with significantly shorter LOS during the first hospitalisations with estimates for the second, third and fourth showed a tendency towards shorter hospital stays. In addition, current users of Alzheimer disease medication had a lower risk of hospital readmission after the first two hospitalisations. These associations were not significant for the third and fourth hospitalisations. Post-hospitalisation NHP and mortality rates also tended to be lower among current users than among non-users but differences did not reach statistical significance. CONCLUSIONS: Our results indicate that Alzheimer disease medication might contribute to a reduction of the LOS and the number of readmissions in PWD.

Nonlinear diffusion and thermo-electric coupling in a two-variable model of cardiac action potential.

This work reports the results of the theoretical investigation of nonlinear dynamics and spiral wave breakup in a generalized two-variable model of cardiac action potential accounting for thermo-electric coupling and diffusion nonlinearities. As customary in excitable media, the common Q10 and Moore factors are used to describe thermo-electric feedback in a 10° range. Motivated by the porous nature of the cardiac tissue, in this study we also propose a nonlinear Fickian flux formulated by Taylor expanding the voltage dependent diffusion coefficient up to quadratic terms. A fine tuning of the diffusive parameters is performed a priori to match the conduction velocity of the equivalent cable model. The resulting combined effects are then studied by numerically simulating different stimulation protocols on a one-dimensional cable. Model features are compared in terms of action potential morphology, restitution curves, frequency spectra, and spatio-temporal phase differences. Two-dimensional long-run simulations are finally performed to characterize spiral breakup during sustained fibrillation at different thermal states. Temperature and nonlinear diffusion effects are found to impact the repolarization phase of the action potential wave with non-monotone patterns and to increase the propensity of arrhythmogenesis.

Validation of a method for "dose of the day" calculation in head-neck tomotherapy by using planning ct-to-MVCT deformable image registration.

PURPOSE: The aim of this study was to test the feasibility and dosimetric accuracy of a method that employs planning CT-to-MVCT deformable image registration (DIR) for calculation of the daily dose for head and neck (HN) patients treated with Helical Tomotherapy (HT). METHODS: For each patient, the planning kVCT (CTplan) was deformably registered to the MVCT acquired at the 15th therapy session (MV15) with a B-Spline Free Form algorithm using Mattes mutual information (open-source software 3D Slicer), resulting in a deformed CT (CTdef). On the same day as MVCT15, a kVCT was acquired with the patient in the same treatment position (CT15). The original HT plans were recalculated both on CTdef and CT15, and the corresponding dose distributions were compared; local dose differences <2% of the prescribed dose (DD2%) and 2D/3D gamma-index values (2%-2mm) were assessed respectively with Mapcheck SNC Patient software (Sun Nuclear) and with 3D-Slicer. RESULTS: On average, 87.9%±1.2% of voxels were found for DD2% (on average 27 slices available for each patient) and 94.6%±0.8% of points passed the 2D gamma analysis test while the 3D gamma test was satisfied in 94.8%±0.8% of body's voxels. CONCLUSIONS: This study represents the first demonstration of the dosimetric accuracy of kVCT-to-MVCT DIR for dose of the day computations. The suggested method is sufficiently fast and reliable to be used for daily delivered dose evaluations in clinical strategies for adaptive Tomotherapy of HN cancer.

Deformable registration-based segmentation of the bowel on Megavoltage CT during pelvic radiotherapy.

During pelvic radiotherapy bowel loops (BL) are subject to inter-fraction changes. MVCT images have the potential to provide daily bowel segmentation. We assess the feasibility of deformable registration and contour propagation in replacing manual BL segmentation on MVCT. Four observers delineated BL on the planning kVCT and on one therapy MVCT in eight patients. Inter-observer variations in BLs contouring were quantified using DICE index. BLs were then automatically propagated onto MVCT by a commercial software for image deformation and subsequently manually corrected. The agreement between propagated BL/propagated+manually corrected BL vs manual were quantified using the DICE. Contouring times were also compared. The impact on DVH of using the deformable-registration method was assessed. The same procedures were repeated on high-resolution planning-kVCT and therapy-kVCT. MVCTs are adequate to visualize BL (average DICE: 0.815), although worse than kVCT (average DICE:0.889). When comparing propagated vs manual BL, a poor agreement was found (average DICE: 0.564/0.646 for MVCT/KVCT). After manual correction, average DICE indexes increased to 0.810/0.897. The contouring time was reduced to 15min with the semi-automatic approach from 30min with manual contouring. DVH parameters of propagated BL were significantly different from manual BL (p<0.0001); after manual correction, no significant differences were seen. MVCT are suitable for BL visualization. The use of a software to segment BL on MVCT starting from BL-kVCT contours was feasible if followed by manual correction. The method resulted in a substantial reduction of contouring time without detrimental effect on the quality of bowel segmentation and DVH estimates.

Quality assurance of rapid arc treatments: performances and pre-clinical verifications of a planar detector (MapCHECK2).

The purpose of this study is to evaluate the use of MapCHECK2 in a patient-specific quality assurance (QA) procedure for Rapid Arc (RA) radiotherapy and to obtain reference values of gamma index (γ) for different irradiation geometries. Dose distributions of 386 patients, optimized with Eclipse treatment planning system for RA on Varian Clinac 2300IX were exported and measured with MapCHECK2 detector array inserted in a MapPHAN dedicated phantom. Gamma index analysis was used to evaluate differences between calculated and delivered doses; collected data were analysed on the basis of complexity of plans and type of disease. Angular dependence and dose drift of detectors were estimated. The overall mean passing rate (percentage of points with γ < 1) was equal to 97.0% ± 3.1%; plan-specific evaluation of %γ < 1 showed significant differences among different treatment protocols (pancreas 98.6% ± 1.5%, prostate 96.6% ± 2.8% and rectum 92.8% ± 5.7%). MapCHECK2 demonstrated a strong angular dependence over a restricted range of angles (90° ± 5° and 270° ± 5°); this condition affected the result of pre-treatment QA only for plans with intense lateral fluence. The drift of diode array response due to the accumulated dose was found to be comparable with the manufacturer's declaration (0.5% per 1000 Gy). MapCHECK2 proved to be a useful and accurate tool in the process of patient-specific QA for RA treatment. Excluding the irradiation geometries with a high contribution of lateral fluence, the mean percentage of cases with γ-index > 95% equal to 90.3% was obtained instead of 81.7% including all plans.

Serum 25-hydroxyvitamin D and incidence of fatal and nonfatal cardiovascular events: a prospective study with repeated measurements.

CONTEXT: Several studies suggested that low serum concentrations of 25-hydroxyvitamin D (25(OH)D) are associated with an increased risk of cardiovascular disease (CVD). However, the evidence is still inconclusive, mostly based on CVD mortality and studies with single 25(OH)D measurements. OBJECTIVE: We aimed to assess the association of 25(OH)D with fatal and nonfatal CVD in the same study population, using repeated 25(OH)D measurements and competing risks analysis. DESIGN: This was a population-based cohort study (ESTHER study, baseline 2000-2002). Follow-up data, including survival status, were collected after 2, 5, and 8 years. The response rate for survival was 99.9%. SETTING: Participants were recruited during a health screening examination by their general practitioners. 25(OH)D was measured in blood samples collected at baseline and the 5-year follow-up visit. PATIENTS OR OTHER PARTICIPANTS: A total of 9949 men and women, aged 50 to 74 years at baseline, with sufficient knowledge of the German language and resident in the German state of Saarland were included in the study. MAIN OUTCOME MEASURES: Outcomes included CVD, coronary heart disease (CHD), and stroke, in total and differentiated into fatal and nonfatal events. RESULTS: Overall, 854 study participants had a nonfatal and 176 a fatal CVD event during 8 years of follow-up. Comparing subjects with 25(OH)D levels below 30 nmol/L and above 50 nmol/L resulted in a hazard ratio of 1.27 (95% confidence interval = 1.05-1.54) for total CVD and 1.62 (95% confidence interval = 1.07-2.48) for fatal CVD in a model adjusted for important potential confounders. No significant association for nonfatal CVD was observed. In dose-response analysis, we observed an increased cardiovascular risk at 25(OH)D levels below 75 nmol/L. Results for CHD and stroke were comparable to the results obtained for the composite outcome CVD. CONCLUSIONS: Our results support evidence that low 25(OH)D levels are associated with moderately increased risk of CVD and indicate that the observed association is much stronger for fatal than for nonfatal events.

Sample cleanup by on-line chromatography for the determination of Am in sediments and soils by alpha-spectrometry.

A novel sample cleanup procedure for the Am determination in environmental samples by alpha-spectrometry is described. The method is based on the use of three analytical chromatographic columns. TEVA-Spec. from Eichrom has been packed in an analytical chromatographic column to carry out the lanthanide/actinide separation. A CS5A mixed-bed column from Dionex was used to separate Am from lanthanide impurities and other actinides. A TCC-II column from Dionex was used to connect the TEVA to the CS5A and act as a preconcentrator column for the trivalent ions. The behavior of the columns was studied by coupling the chromatograph to an ICPMS detector. A chromatographic fraction has been used for sample preparation for alpha-spectrometric determination of 241Am. The analytical procedure has been validated with certified reference materials (sediment and soil) and was applied to sediment core samples from the Irish Sea and compared with the classical radiochemical separation of Am.

Ultrasound-guided thrombin injection for the treatment of postcatheterization pseudoaneurysms.

BACKGROUND: This prospective study was designed to assess the safety and efficacy of using bovine thrombin injection to treat pseudoaneurysms. METHODS AND RESULTS: From April 1998 through December 1999, 70 pseudoaneurysm were injected with bovine thrombin under the guidance of color duplex ultrasound. The most superficial pseudoaneurysm chamber was entered with a 1.5-inch, 19- to 22-gauge or spinal needle. Bovine thrombin, in a 1000 U/cc solution, was injected into the chamber. A total of 36 women and 34 men underwent ultrasound-guided thrombin injection (UGTI). Their mean age was 69.5 years. Most pseudoaneurysms were associated with diagnostic cardiac catheterization or percutaneous coronary intervention (80%). Two pseudoaneurysms arose from the brachial artery; the remainder were in the groin. Twenty-one patients were being treated with either heparin or warfarin, and the majority of the others were on antiplatelet therapy with aspirin or clopidogrel. UGTI was successful in 66 of the 70 patients (94%). The first patient in the series had 2 attempts at thrombin injection and refused further attempts. Two patients had undergone stent graft placement and had short, wide tracts. Both of these patients required surgical repair of their pseudoaneurysms. The fourth patient had a nearly complete pseudoaneurysm thrombosis and was lost to follow-up on discharge. No arterial thrombotic events occurred. One patient had a soleal vein thrombosis in the ipsilateral leg. CONCLUSIONS: UGTI was safe and effective in 94% of patients with postcatheterization pseudoaneurysms. Anticoagulant use did not hinder successful thrombosis. UGTI should be the initial treatment of choice for patients with postcatheterization pseudoaneurysms.

Radiotherapy treatment verification.

During a radiotherapy treatment, a dosimetric verification or a geometric localization can be done, in order to assess the quality of the treatment. The dosimetric verification is generally performed measuring the dose at some points inside (natural cavities) or outside the patient, and comparing it to the dose at the same points calculated and predicted by the treatment planning system. This can be done either with thermoluminescent or diodes dosimeters or with ionization chambers. The geometric localization can be done acquiring a portal image of the patient. Portal imaging can be performed either with films placed between metallic screens, or with an electronic portal imaging device such as fluoroscopic systems, solid state devices or matrix ionization chamber systems. In order to assess possible field placement errors, the portal images have to be compared with images obtained with the simulator in the same geometric conditions and/or with the digitally reconstructed radiograph (DRR) obtained with the treatment planning system. In particular, when using matrix ionization chamber systems, the portal images contain also information regarding the exit dose. This means that this kind of imaging device can be used both for geometric localization and for dosimetric verification. In this case, the exit dose measured by the portal image can be compared with the exit dose calculated and predicted by the treatment planning system. Some "in-vivo" applications of this methodology are presented.

Clinical relapse in systemic lupus erythematosus: correlation with antecedent elevation of urinary free light-chain immunoglobulin.

This paper reports preliminary evidence suggesting that measurements of free light-chain Ig (FLIg) in urine may represent quantitative markers of in vivo polyclonal B-cell activation. Thus, longitudinal levels of urinary FLIg in patients with systemic lupus erythematosus (SLE) may be used to track or monitor the in vivo immunopathologic B-cell activity of SLE and be helpful in predicting a disease relapse. Our findings showed that dramatic rises in urinary FLIg occurred during asymptomatic intervals that preceded by 4-8 weeks the first symptomatic signs of acute SLE relapse. These results suggest that a sizable lead time may exist between the occurrence of immunopathologic B-cell stimulation and the resultant symptoms and tissue damage of immune complex-induced acute inflammation. In these studies the measurement of urinary FLIg was accomplished by an indirect method using ng-sensitive radioimmunoassays (RIAs) that measured isotypic IgG, IgA, IgM, total kappa-Ig, and total lambda-Ig. As a control for the assessment of renal tubular function and the excretion of low molecular weight proteins in SLE patients, longitudinal measurements of beta-2-microglobulin (B2M) and lysozyme were made using a novel solid-phase 3H-biotin RIA technique.

[Short-term and average-term automatic control of re-entry arrhythmias]. / Controllo automatico a breve e medio termine delle aritmie da rientro.

The AA. described an external stimulator to be utilized instead of invasive pharmacological treatment, as a short and middle-time therapeutic approach to re-entry tachycardia, in Departments of cardiology. The device must be connected with an electrode placed in atrium or in coronary sinus or in ventricle, according to individual request. A frequency discriminant device recognizes tachycardia and activates automatic scanning stimulator, synchronized on R or P waves, with progressive 5 msec stop delay; tachycardia interruption zone is automatically individuated. Stimulation has an automatic stop when tachycardia is interrupted; in case of persistent tachycardia scanning-function cycle will star again automatically. The device, which can be programmed for a simple or a double impulse emission, is equipped with a demand stimulator working if post-tachycardia asystole is present. Frequency discriminant device activates the scanning function beyond a defined threshold which can be varied within a wide range of frequencies.