The influence of different sub-bandage pressure values in the prevention of recurrence of venous ulceration-A ten year follow-up.

OBJECTIVE: The aim of this study was to establish the efficacy of three different strengths of compression systems in the prevention of venous leg ulcer (VLU) recurrences during a 10-year follow up period. METHODS: An open, prospective, randomized, single-center study included 477 patients (240 men, 237 women; mean age 59 years). Patients were randomized into three groups: Group A) 149 patients (allocated to wear elastic stocking 18-25 mmHg). Group B) 167 patients (wearing compression device exerting 25-35 mmHg), and Group C) 161 patients (treated with multilayer compression system exerting 35-50 mmHg). RESULTS: Overall, 65% (234/360) of patients had recurrent VLU within 10 years. Recurrence occurred in 120 (96%) of 125 in group A, in 89 (66.9%) of 133 patients in group B and in 25 (24.5%) of 102 patients in group C (p < 0.05). CONCLUSION: Compression systems with the higher compression class provide lower recurrence rate.

Platelet thrombus formation in patients with end-stage renal disease before and after hemodialysis as measured by the total thrombus-formation analysis system.

BACKGROUND: Patients with end-stage renal disease (ESRD) receiving hemodialysis (HD) often experience bleeding. However, mechanisms behind this bleeding tendency are incompletely understood but may involve platelet dysfunction. We, therefore, studied platelet-dependent thrombus formation in flowing whole blood inside a microchip coated with collagen, and its association with circulating von Willebrand factor (VWF). METHODS: Blood samples were obtained in 22 patients before and after HD. The area under the 10 min flow pressure curve in a microchip (AUC10) reflecting total platelet thrombogenicity was measured, using the Total Thrombus-formation Analysis System (T-TAS01). AUC10 < 260 indicates platelet dysfunction. VWF activity and antigen in plasma were also assayed. RESULTS: VWF levels were moderately elevated and increased further after HD (P < 0.01 or lower). In contrast, AUC10 before and after HD was < 260 in 17/22 patients and < 130 in 15/22 patients, with no statistically significant difference in pre- vs post-HD measurements, indicating reduced platelet thrombogenicity, but with some variability as 5/22 patients showed normal platelet responsiveness. AUC10 and VWF activity or antigen levels in plasma were not correlated, either before or after HD. CONCLUSIONS: Most ESRD patients display moderate-to-severe platelet dysfunction as assessed by shear-induced platelet-dependent thrombus formation with T-TAS01. HD does not influence platelet function despite HD-induced elevations in VWF. T-TAS01 should be further evaluated as a tool in the assessment of bleeding risk in patients on HD.

Characterizing Sensitive Cardiac Substructure Excursion Due to Respiration.

PURPOSE: Whole-heart dose metrics are not as strongly linked to late cardiac morbidities as radiation doses to individual cardiac substructures. Our aim was to characterize the excursion and dosimetric variation throughout respiration of sensitive cardiac substructures for future robust safety margin design. METHODS AND MATERIALS: Eleven patients with cancer treatments in the thorax underwent 4-phase noncontrast 4-dimensional computed tomography (4DCT) with T2-weighted magnetic resonance imaging in end-exhale. The end-exhale phase of the 4DCT was rigidly registered with the magnetic resonance imaging and refined with an assisted alignment surrounding the heart from which 13 substructures (chambers, great vessels, coronary arteries, etc) were contoured by a radiation oncologist on the 4DCT. Contours were deformed to the other respiratory phases via an intensity-based deformable registration for radiation oncologist verification. Measurements of centroid and volume were evaluated between phases. Mean and maximum dose to substructures were evaluated across respiratory phases for the breast (n = 8) and thoracic cancer (n = 3) cohorts. RESULTS: Paired t tests revealed reasonable maintenance of geometric and anatomic properties (P < .05 for 4/39 volume comparisons). Maximum displacements >5 mm were found for 24.8%, 8.5%, and 64.5% of the cases in the left-right, anterior-posterior, and superior-inferior axes, respectively. Vector displacements were largest for the inferior vena cava and the right coronary artery, with displacements up to 17.9 mm. In breast, the left anterior descending artery Dmean varied 3.03 ± 1.75 Gy (range, 0.53-5.18 Gy) throughout respiration whereas lung showed patient-specific results. Across all patients, whole heart metrics were insensitive to breathing phase (mean and maximum dose variations <0.5 Gy). CONCLUSIONS: This study characterized the intrafraction displacement of the cardiac substructures through the respiratory cycle and highlighted their increased dosimetric sensitivity to local dose changes not captured by whole heart metrics. Results suggest value of cardiac substructure margin generation to enable more robust cardiac sparing and to reduce the effect of respiration on overall treatment plan quality.

Identification and Characterization of Downy Mildew-Responsive microRNAs in Indian Vitis vinifera by High-Throughput Sequencing.

Downy mildew (DM) is one of the most devastating diseases disturbing viticulture, mainly during temperate and humid climates. The DM pathogen can attack grapevine leaves and berries differentially, and the disease is managed with recurring applications of fungicides that direct pathogen pressure, develop of resistant strains, and lead to residual soil toxicity and increased pollution effects. Plant microRNAs (miRNAs) are important candidates in physiological regulatory roles in response to biotic stress in plants. In this study, high-throughput sequencing and MiRDeep-P were employed to identify miRNAs in Vitis vinifera. Altogether, 22,492,910, 25,476,471, and 22,448,438 clean reads from the sterile distilled water (SDW)-control, bio-pesticide Trichoderma harzianum (TriH_JSB36)-treated, and downy mildew Plasmopara viticola pathogen libraries, respectively, were obtained. On the basis of the sequencing results and analysis (differential expression analysis), we observed significant differences in 15 miRNAs (5 novel upregulated, and 10 known downregulated) in the pathogen-infected sample (Test) in comparison to the SDW-control sample, with majority of the reads beingin the range of 20-24 bp. This study involves the identification and characterization of vvi-miRNAs that are involved in resistance against downy mildew disease in grapes.

Predictive potential of biomarkers and risk scores for major adverse cardiac events in elderly patients undergoing major elective vascular surgery.

Elderly patients scheduled for major elective vascular surgery are at high risk for a major adverse cardiac events (MACE). The objectives of the study were: (1) To determine the individual discriminatory ability of four risk prediction models and four biomarkers in predicting MACEs in elderly patients undergoing major elective vascular surgery; (2) to find a prognostic model with the best characteristics; (3) to examine the significance of all preoperative parameters; and (4) to determine optimal cut-off values for biomarkers with best predictor capabilities. We enrolled 144 geriatric patients, aged 69.97 ± 3.73 years, with a 2:1 male to female ratio. Essential inclusion criteria were open major vascular surgery and age >65 years. The primary outcome was the appearance of MACEs within 6 months. These were noted in 33 (22.9%) patients. The most frequent cardiac event was decompensated heart failure, which occurred in 22 patients (15.3%). New onset atrial fibrillation was registered in 13 patients (9%), and both myocardial infarction and ventricular arrhythmias occurred in eight patients each (5.5%). Excellent discriminatory ability (AUC >0.8) was observed for all biomarker combinations that included the N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP). The most predictive two-variable combination was the Geriatric-Sensitive Cardiac Risk Index (GSCRI) + NT-proBNP (AUC of 0.830 with a 95% confidence interval). Female gender, previous coronary artery disease, and NT-proBNP were three independent predictors in a multivariate model of binary logistic regression. The Cox regression multivariate model identified high-sensitivity C-reactive protein and NT-proBNP as the only two independent predictors.

Quantifying inter-fraction cardiac substructure displacement during radiotherapy via magnetic resonance imaging guidance.

PURPOSE: Emerging evidence suggests cardiac substructures are highly radiosensitive during radiation therapy for cancer treatment. However, variability in substructure position after tumor localization has not been well characterized. This study quantifies inter-fraction displacement and planning organ at risk volumes (PRVs) of substructures by leveraging the excellent soft tissue contrast of magnetic resonance imaging (MRI). METHODS: Eighteen retrospectively evaluated patients underwent radiotherapy for intrathoracic tumors with a 0.35 T MRI-guided linear accelerator. Imaging was acquired at a 17-25 s breath-hold (resolution 1.5 × 1.5 × 3 mm3). Three to four daily MRIs per patient (n = 71) were rigidly registered to the planning MRI-simulation based on tumor matching. Deep learning or atlas-based segmentation propagated 13 substructures (e.g., chambers, coronary arteries, great vessels) to daily MRIs and were verified by two radiation oncologists. Daily centroid displacements from MRI-simulation were quantified and PRVs were calculated. RESULTS: Across substructures, inter-fraction displacements for 14% in the left-right, 18% in the anterior-posterior, and 21% of fractions in the superior-inferior were > 5 mm. Due to lack of breath-hold compliance, ~4% of all structures shifted > 10 mm in any axis. For the chambers, median displacements were 1.8, 1.9, and 2.2 mm in the left-right, anterior-posterior, and superior-inferior axis, respectively. Great vessels demonstrated larger displacements (> 3 mm) in the superior-inferior axis (43% of shifts) and were only 25% (left-right) and 29% (anterior-posterior) elsewhere. PRVs from 3 to 5 mm were determined as anisotropic substructure-specific margins. CONCLUSIONS: This exploratory work derived substructure-specific safety margins to ensure highly effective cardiac sparing. Findings require validation in a larger cohort for robust margin derivation and for applications in prospective clinical trials.

Synthesis and Biological Screening of New 4-Hydroxycoumarin Derivatives and Their Palladium(II) Complexes.

Two newly synthesized 4-hydroxycoumarin bidentate ligands (L1 and L2) and their palladium(II) complexes (C1 and C2) were screened for their biological activities, in vitro and in vivo. Structures of new compounds were established based on elemental analysis, 1H NMR, 13C NMR, and IR spectroscopic techniques. The obtained compounds were tested for their antioxidative and cytotoxic activities and results pointed to selective antiradical activity of palladium(II) complexes towards •OH and -•OOH radicals and anti-ABTS (2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) cation radical) activity comparable to that of ascorbate. Results indicated the effect of C1 and C2 on the enzymatic activity of the antioxidative defense system. In vitro cytotoxicity assay performed on different carcinoma cell lines (HCT166, A375, and MIA PaCa-2), and one healthy fibroblast cell line (MRC-5) showed a cytotoxic effect of both C1 and C2, expressed as a decrease in carcinoma cells' viability, mostly by induction of apoptosis. In vivo toxicity tests performed on zebrafish embryos indicated different effects of C1 and C2, ranging from adverse developmental effect to no toxicity, depending on tested concentration. According to docking studies, both complexes (C1 and C2) showed better inhibitory activity in comparison to other palladium(II) complexes.

Liquid chromatography-tandem mass spectrometry glycoproteomic study of porcine IgG and detection of subtypes.

RATIONALE: While high-throughput proteomic methods have been widely applied to monoclonal antibodies and human immunoglobulin gamma (IgG) samples, less information is available on porcine IgG. As pigs are considered one of the most suitable species for xenotransplantation, it is important to characterize IgG amino acid sequences and glycosylation profiles, which is the focus of this study. METHODS: Three different purified porcine IgG samples, including wild-type and knockout species, were digested with trypsin and enriched for glycopeptides. Digestion mixtures were spiked with a mixture of six standard peptides. Analysis was performed using electrospray ionization liquid chromatography-tandem mass spectrometry (MS/MS) in standard MS/MS data-dependent acquisition mode on a hybrid triple quadrupole time-of-flight mass spectrometer. RESULTS: To facilitate the classification of subtypes detected experimentally, UniprotKB database entries were organized using comparative alignment scores. Sequences were grouped based on 11 different subtypes as translated from GenBank entries. Proteomic searches were accomplished automatically using specialized software, whereas glycoprotein searches were performed manually by monitoring the extracted chromatograms of diagnostic MS/MS glycan fragments and studying their corresponding mass spectra; 40-50 non-glycosylated peptides and 4-5 glycosylated peptides were detected in each sample, with several glycoforms per sequence. CONCLUSIONS: Proteomic analysis of porcine IgG is complicated by factors such as the presence of several subtypes, redundant heavy chain (HC) sequences in protein databases, and the lack of consistent cross-referencing between databases. Aligning and comparing HC sequences were necessary to eliminate redundancy. This study highlights the complexity of pig IgG and shows the importance of MS in proteomics and glycoproteomics.

A deep dive into understanding tumor foci classification using multiparametric MRI based on convolutional neural network.

PURPOSE: Deep learning models have had a great success in disease classifications using large data pools of skin cancer images or lung X-rays. However, data scarcity has been the roadblock of applying deep learning models directly on prostate multiparametric MRI (mpMRI). Although model interpretation has been heavily studied for natural images for the past few years, there has been a lack of interpretation of deep learning models trained on medical images. In this paper, an efficient convolutional neural network (CNN) was developed and the model interpretation at various convolutional layers was systematically analyzed to improve the understanding of how CNN interprets multimodality medical images and the predictive powers of features at each layer. The problem of small sample size was addressed by feeding the intermediate features into a traditional classification algorithm known as weighted extreme learning machine (wELM), with imbalanced distribution among output categories taken into consideration. METHODS: The training data collection used a retrospective set of prostate MR studies, from SPIE-AAPM-NCI PROSTATEx Challenges held in 2017. Three hundred twenty biopsy samples of lesions from 201 prostate cancer patients were diagnosed and identified as clinically significant (malignant) or not significant (benign). All studies included T2-weighted (T2W), proton density-weighted (PD-W), dynamic contrast enhanced (DCE) and diffusion-weighted (DW) imaging. After registration and lesion-based normalization, a CNN with four convolutional layers were developed and trained on tenfold cross validation. The features from intermediate layers were then extracted as input to wELM to test the discriminative power of each individual layer. The best performing model from the tenfolds was chosen to be tested on the holdout cohort from two sources. Feature maps after each convolutional layer were then visualized to monitor the trend, as the layer propagated. Scatter plotting was used to visualize the transformation of data distribution. Finally, a class activation map was generated to highlight the region of interest based on the model perspective. RESULTS: Experimental trials indicated that the best input for CNN was a modality combination of T2W, apparent diffusion coefficient (ADC) and DWIb50 . The convolutional features from CNN paired with a weighted extreme learning classifier showed substantial performance compared to a CNN end-to-end training model. The feature map visualization reveals similar findings on natural images where lower layers tend to learn lower level features such as edges, intensity changes, etc, while higher layers learn more abstract and task-related concept such as the lesion region. The generated saliency map revealed that the model was able to focus on the region of interest where the lesion resided and filter out background information, including prostate boundary, rectum, etc. CONCLUSIONS: This work designs a customized workflow for the small and imbalanced dataset of prostate mpMRI where features were extracted from a deep learning model and then analyzed by a traditional machine learning classifier. In addition, this work contributes to revealing how deep learning models interpret mpMRI for prostate cancer patient stratification.

Aminoalcoholate-driven tetracopper(II) cores as dual acetyl and butyrylcholinesterase inhibitors: Experimental and theoretical elucidation of mechanism of action.

Three coordination compounds featuring different types of tetracopper(II) cores, namely [O ⊂ Cu4{N(CH2CH2O)3}4(BOH)4][BF4]2 (1), [Cu4(µ4-H2edte)(µ5-H2edte)(sal)2]n·7nH2O, (H4edte = N,N,N',N'-tetrakis(2-hydroxyethyl)ethylenediamine, H2sal = salicylic acid) (2), and [{Cu4(µ3-Hbes)4(µ-hba)}K(H2O)3]n, H3bes = N,N-bis(2-hydroxyethyl)-2-aminoethanesulfonic acid (3), were assayed for their potency to inhibit the acetyl (AChE) and butyrylcholinesterase (BuChE) enzymes aiming to test these compounds as potential dual inhibitors in the treatment of Alzheimer's disease. All the investigated compounds showed a strong inhibitory potency toward both enzymes with IC50 values in micromolar range of concentration; compound 1 displayed the most potent inhibitory behaviour toward both enzymes. The mechanism of the AChE and BuChE inhibition was examined by enzyme kinetic measurements. The obtained kinetic parameters, Vmax and Km indicated an uncompetitive type of inhibition of both enzymes by compound 1. For the other two compounds a non-competitive inhibition mode was observed. To get further insight into the mechanism of action and to elucidate binding modes in details we examined the interactions of 1-3 with acetylcholinesterase, using molecular docking approach. Grid based docking studies indicated that these compounds can bind to peripheral anionic site (PAS) of the AChE with Ki values in micromolar range. Moreover, blind docking revealed the capability of investigated compounds to bind to new allosteric site (i.e. binding site II) distinct from PAS. Showing that these Cu-based compounds can act as new allosteric inhibitors of AChE and identifying novel allosteric binding site on AChE represents a significant contribution toward the design of novel and more effective inhibitors of AChE.

Cardiac substructure segmentation with deep learning for improved cardiac sparing.

PURPOSE: Radiation dose to cardiac substructures is related to radiation-induced heart disease. However, substructures are not considered in radiation therapy planning (RTP) due to poor visualization on CT. Therefore, we developed a novel deep learning (DL) pipeline leveraging MRI's soft tissue contrast coupled with CT for state-of-the-art cardiac substructure segmentation requiring a single, non-contrast CT input. MATERIALS/METHODS: Thirty-two left-sided whole-breast cancer patients underwent cardiac T2 MRI and CT-simulation. A rigid cardiac-confined MR/CT registration enabled ground truth delineations of 12 substructures (chambers, great vessels (GVs), coronary arteries (CAs), etc.). Paired MRI/CT data (25 patients) were placed into separate image channels to train a three-dimensional (3D) neural network using the entire 3D image. Deep supervision and a Dice-weighted multi-class loss function were applied. Results were assessed pre/post augmentation and post-processing (3D conditional random field (CRF)). Results for 11 test CTs (seven unique patients) were compared to ground truth and a multi-atlas method (MA) via Dice similarity coefficient (DSC), mean distance to agreement (MDA), and Wilcoxon signed-ranks tests. Three physicians evaluated clinical acceptance via consensus scoring (5-point scale). RESULTS: The model stabilized in ~19 h (200 epochs, training error <0.001). Augmentation and CRF increased DSC 5.0 ± 7.9% and 1.2 ± 2.5%, across substructures, respectively. DL provided accurate segmentations for chambers (DSC = 0.88 ± 0.03), GVs (DSC = 0.85 ± 0.03), and pulmonary veins (DSC = 0.77 ± 0.04). Combined DSC for CAs was 0.50 ± 0.14. MDA across substructures was <2.0 mm (GV MDA = 1.24 ± 0.31 mm). No substructures had statistical volume differences (P > 0.05) to ground truth. In four cases, DL yielded left main CA contours, whereas MA segmentation failed, and provided improved consensus scores in 44/60 comparisons to MA. DL provided clinically acceptable segmentations for all graded patients for 3/4 chambers. DL contour generation took ~14 s per patient. CONCLUSIONS: These promising results suggest DL poses major efficiency and accuracy gains for cardiac substructure segmentation offering high potential for rapid implementation into RTP for improved cardiac sparing.

Volumetric and Voxel-Wise Analysis of Dominant Intraprostatic Lesions on Multiparametric MRI.

Introduction: Multiparametric MR imaging (mpMRI) has shown promising results in the diagnosis and localization of prostate cancer. Furthermore, mpMRI may play an important role in identifying the dominant intraprostatic lesion (DIL) for radiotherapy boost. We sought to investigate the level of correlation between dominant tumor foci contoured on various mpMRI sequences. Methods: mpMRI data from 90 patients with MR-guided biopsy-proven prostate cancer were obtained from the SPIE-AAPM-NCI Prostate MR Classification Challenge. Each case consisted of T2-weighted (T2W), apparent diffusion coefficient (ADC), and Ktrans images computed from dynamic contrast-enhanced sequences. All image sets were rigidly co-registered, and the dominant tumor foci were identified and contoured for each MRI sequence. Hausdorff distance (HD), mean distance to agreement (MDA), and Dice and Jaccard coefficients were calculated between the contours for each pair of MRI sequences (i.e., T2 vs. ADC, T2 vs. Ktrans, and ADC vs. Ktrans). The voxel wise spearman correlation was also obtained between these image pairs. Results: The DILs were located in the anterior fibromuscular stroma, central zone, peripheral zone, and transition zone in 35.2, 5.6, 32.4, and 25.4% of patients, respectively. Gleason grade groups 1-5 represented 29.6, 40.8, 15.5, and 14.1% of the study population, respectively (with group grades 4 and 5 analyzed together). The mean contour volumes for the T2W images, and the ADC and Ktrans maps were 2.14 ± 2.1, 2.22 ± 2.2, and 1.84 ± 1.5 mL, respectively. Ktrans values were indistinguishable between cancerous regions and the rest of prostatic regions for 19 patients. The Dice coefficient and Jaccard index were 0.74 ± 0.13, 0.60 ± 0.15 for T2W-ADC and 0.61 ± 0.16, 0.46 ± 0.16 for T2W-Ktrans. The voxel-based Spearman correlations were 0.20 ± 0.20 for T2W-ADC and 0.13 ± 0.25 for T2W-Ktrans. Conclusions: The DIL contoured on T2W images had a high level of agreement with those contoured on ADC maps, but there was little to no quantitative correlation of these results with tumor location and Gleason grade group. Technical hurdles are yet to be solved for precision radiotherapy to target the DILs based on physiological imaging. A Boolean sum volume (BSV) incorporating all available MR sequences may be reasonable in delineating the DIL boost volume.

Influence of triazole pesticides on tillage soil microbial populations and metabolic changes.

Pesticides are generally applied to agricultural soil to control crop diseases, with the critical goal of preventing yield loss and optimizing economic returns. However, the excessive utilization of pesticides in agriculture is a severe environmental and human health problem. In the present study, effect of triazole based fungicide, propiconazole on soil physicochemical properties, stimulatory impact of propiconazole residue on soil microbial communities and soil enzyme activities (phosphatise and urease) in contaminated red sandy loam and deep black soils of paddy (Oryza sativa L.) fields at different concentrations were evaluated. The liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) analysis showed high levels of propiconazole residues of 434 and 426 ng g-1 in red sandy loam and deep black soils, respectively. A total of 27 bacterial and 18 fungal strains were isolated from propiconazole-contaminated soils, identified by molecular markers and had their sequences deposited in the GenBank. We observed a pronounced increase in soil microbial growth, and urease and phosphatase activities at lower propiconazole concentrations up to 2 weeks post-treatment. On the contrary, the microbial growth and urease and phosphatase activities were relentlessly reduced at higher propiconazole concentrations and a long incubation period after 2 to 4 weeks of post-treatment. Overall, it was concluded that the concentration-dependency and incubation period of propiconazole would enhance the growth and activity of soil microbes and enzymes respectively and the higher application will be detrimental to the soil health.

Cardiac Substructure Segmentation and Dosimetry Using a Novel Hybrid Magnetic Resonance and Computed Tomography Cardiac Atlas.

PURPOSE: Radiation dose to the heart and cardiac substructures has been linked to cardiotoxicities. Because cardiac substructures are poorly visualized on treatment-planning computed tomography (CT) scans, we used the superior soft-tissue contrast of magnetic resonance (MR) imaging to optimize a hybrid MR/CT atlas for substructure dose assessment using CT. METHODS AND MATERIALS: Thirty-one patients with left-sided breast cancer underwent a T2-weighted MR imaging scan and noncontrast simulation CT scans. A radiation oncologist delineated 13 substructures (chambers, great vessels, coronary arteries, etc) using MR/CT information via cardiac-confined rigid registration. Ground-truth contours for 20 patients were inputted into an intensity-based deformable registration atlas and applied to 11 validation patients. Automatic segmentations involved using majority vote and Simultaneous Truth and Performance Level Estimation (STAPLE) strategies with 1 to 15 atlas matches. Performance was evaluated via Dice similarity coefficient (DSC), mean distance to agreement, and centroid displacement. Three physicians evaluated segmentation performance via consensus scoring by using a 5-point scale. Dosimetric assessment included measurements of mean heart dose, left ventricular volume receiving 5 Gy, and left anterior descending artery mean and maximum doses. RESULTS: Atlas approaches performed similarly well, with 7 of 13 substructures (heart, chambers, ascending aorta, and pulmonary artery) having DSC >0.75 when averaged over 11 validation patients. Coronary artery segmentations were not successful with the atlas-based approach (mean DSC <0.3). The STAPLE method with 10 matches yielded the highest DSC and the lowest mean distance to agreement for all high-performing substructures (omitting coronary arteries). For the STAPLE method with 10 matches, >50% of all validation contours had centroid displacements <3.0 mm, with the largest shifts in the coronary arteries. Atlas-generated contours had no statistical difference from ground truth for left anterior descending artery maximum dose, mean heart dose, and left ventricular volume receiving 5 Gy (P > .05). Qualitative contour grading showed that 8 substructures required minor modifications. CONCLUSIONS: The hybrid MR/CT atlas provided reliable segmentations of chambers, heart, and great vessels for patients undergoing noncontrast CT, suggesting potential widespread applicability for routine treatment planning.

A randomized trial of class 2 and class 3 elastic compression in the prevention of recurrence of venous ulceration.

BACKGROUND: Venous leg ulcers (VLUs) are a major health problem because of their high prevalence and associated high cost of care. Despite the widespread use of compression, treatment recurrence rates remain high. Numerous studies have suggested that regular use of compression stockings reduces VLU recurrences. However, there are limited data concerning how long compression hosiery should be worn after ulcer healing and which class of compression hosiery achieves better results in the prevention of VLU recurrences. METHODS: An open, prospective, randomized, single-center study with a 5-year follow-up was performed to establish the efficacy of two different strengths of knee-high compression hosiery (class 2 and class 3) in the prevention of VLU recurrences. The study included patients with recently healed venous ulcers and no significant arterial disease, rheumatoid disease, diabetes mellitus, and restriction in range of ankle movement. Overall, 361 patients were randomized, and 308 patients (170 men, 138 women; mean age, 59 years) completed the study. Patients were randomized into two groups: group A, 186 patients who wore a heel-less open-toed elastic class 3 compression device knitted in tubular form (Tubulcus; Laboratoires Innothera, Arcueil, France); and group B, 175 patients who wore a class 2 elastic stocking (Rudo, Nis, Serbia). All patients were instructed to wear compression stockings continuously for the first 2 years of follow-up (both during the day and at night). In the third, fourth, and fifth years of follow-up, patients were instructed to wear elastic stockings during the day only. The main outcome measures were recurrence of leg ulceration and compliance with the treatment. RESULTS: Rates of ulcer recurrence after the 5 years of follow-up were 28.98% for the compression class 3 group and 60% for the compression class 2 group (P < .001, log-rank test). Patients in the compression class 3 group experienced significantly longer absolute (46 vs 40 months; P < .001, Mann-Whitney U test) and proportional (77% vs 67%; P < .001, Mann-Whitney U test) ulcer-free time after 5 years than those in the compression class 2 group. Rates of noncompliance after 5 years were 10.23% for the compression class 3 group and 6.25% for the compression class 2 group (P = .188, χ2 test). CONCLUSIONS: The results obtained in this study suggest that class 3 compression stockings provide a statistically significant lower recurrence rate compared with the class 2 compression stockings.

MEASUREMENTS OF THE PARASITIC NEUTRON DOSE AT ORGANS FROM MEDICAL LINACS AT DIFFERENT ENERGIES BY USING BUBBLE DETECTORS.

Conventional linear accelerators (LINACs) for radiotherapy produce fast secondary neutrons due to photonuclear processes. The neutron presence is considered as an extra undesired dose during the radiotherapy treatment, which could cause secondary radio-induced tumors and malfunctions to cardiological implantable devices. It is thus important to measure the neutron dose contribution to patients during radiotherapy, not only at high-energy LINACs, but also at lower energies, near the giant dipole resonance reaction threshold. In this work, the full body neutron dose equivalent has been measured during single-field radiotherapy sessions carried out at different LINAC energies (15, 10 and 6 MV) by using a tissue equivalent (for neutrons) anthropomorphic phantom together with bubble dosemeters. Results have shown that some neutron photoproduction is still present also at lower energies. As a consequence, emitted photoneutrons cannot be ignored and represent a risk contribution for patients undergoing radiotherapy.

Evolution of Symptom Burden of Advanced Lung Cancer Over a Decade.

INTRODUCTION: Lung cancer is associated with higher levels of symptom distress and unmet needs than other cancer types. We assessed changes in symptoms, function, understanding, and preferences of patients with advanced lung cancer over a 10-year period. MATERIALS AND METHODS: A 26-item self-administered questionnaire was used to assess symptom burden, functional impairment, knowledge of disease and treatment, and information preferences. The survey was administered to consecutive outpatients with advanced lung cancer first in 2002 and a second cohort in 2012. RESULTS: A total of 108 patients with advanced lung cancer were surveyed in 2002, and 100 in 2012. Rates of severe physical symptoms were similar over the 10-year period. The most common symptoms remained fatigue, cough, and dyspnea. One-third perceived major impairment of daily activities from lung cancer. Significant anxiety was reported by at least 20%; nearly a quarter reported being unable to meet family needs. More patients in 2012 received information on treatment benefits, side effects, and clinical trials. Only 40% reported having end-of-life wishes, and fewer than half had discussed these with their oncologist. Over time, more patients expressed a preference for treatment associated with increased survival even if it compromised quality of life. Half were interested in Internet-based resources, most in print media, and a growing number in telephone support. CONCLUSION: Patients with advanced lung cancer continue to experience significant symptom distress and unmet needs despite advances in treatment. Comprehensive assessment and symptom, psychological, financial, and information support remain key areas for improvement in the care of patients with advanced lung cancer.

Single-stage Reconstruction of Elbow Flexion Associated with Massive Soft-Tissue Defect Using the Latissimus Dorsi Muscle Bipolar Rotational Transfer.

In the upper extremity, the latissimus dorsi muscle can be used as an ipsilateral rotational muscle flap for soft-tissue coverage or functional reconstruction of arm and elbow. Patients who have both major soft-tissue loss and functional deficits can be successfully treated with a single-stage functional latissimus dorsi rotational muscle transfer that provides simultaneous soft-tissue coverage and functional reconstruction. METHODS: Our data base was queried for all patients undergoing a rotational latissimus dorsi muscle transfer for simultaneous soft-tissue coverage and functional reconstruction of elbow flexion. Four patients were identified. A chart review documented the mechanism of injury, associated injuries, soft-tissue defect size, number of surgical procedures, length of follow-up, last elbow range of motion, and flexion strength. RESULTS: Four patients with loss of elbow flexion due to traumatic loss of the anterior compartment muscles and the overlying soft tissue underwent simultaneous soft-tissue coverage and elbow flexorplasty using the ipsilateral latissimus dorsi as a bipolar muscle rotational tissue transfer. All flaps survived and had a recovery of Medical Research Council Grade 4/5 elbow flexion strength. No additional procedures were required for elbow flexion. The surgical technique is described and supplemented with surgical technique video and patient outcome. CONCLUSIONS: This patient series augments the data provided in other series supporting the safety and efficacy of this procedure which provides both soft-tissue coverage and functional restoration of elbow flexion as a single-stage procedure in the setting of massive traumatic soft-tissue loss of the arm.

Pronator-sparing technique for volar plating of distal radius fractures.

Acute distal radius fractures are commonly treated by volar locking plate fixation and typically involve reflection of the pronator quadratus for adequate exposure of the fracture. Recently, attention has been centered on the role and repair of the pronator quadratus. This article presents an alternative approach to fixation of distal radius fractures with a pronator-sparing technique that offers similar short-term radiographic outcomes to the conventional volar plating approach.