Comparative evaluation of outcomes amongst different radiosurgery management paradigms for patients with large brain metastasis.

INTRODUCTION: This study compares four management paradigms for large brain metastasis (LMB): fractionated SRS (FSRS), staged SRS (SSRS), resection and postoperative-FSRS (postop-FSRS) or preoperative-SRS (preop-SRS). METHODS: Patients with LBM (≥ 2 cm) between July 2017 and January 2022 at a single tertiary institution were evaluated. Primary endpoints were local failure (LF), radiation necrosis (RN), leptomeningeal disease (LMD), a composite of these variables, and distant intracranial failure (DIF). Gray's test compared cumulative incidence, treating death as a competing risk with a random survival forests (RSF) machine-learning model also used to evaluate the data. RESULTS: 183 patients were treated to 234 LBMs: 31.6% for postop-FSRS, 28.2% for SSRS, 20.1% for FSRS, and 20.1% for preop-SRS. The overall 1-year composite endpoint rates were comparable (21 vs 20%) between nonoperative and operative strategies, but 1-year RN rate was 8 vs 4% (p = 0.012), 1-year overall survival (OS) was 48 vs. 69% (p = 0.001), and 1-year LMD rate was 5 vs 10% (p = 0.052). There were differences in the 1-year RN rates (7% FSRS, 3% postop-FSRS, 5% preop-SRS, 10% SSRS, p = 0.037). With RSF analysis, the out-of-bag error rate for the composite endpoint was 47%, with identified top-risk factors including widespread extracranial disease, > 5 total lesions, and breast cancer histology. CONCLUSION: This is the first study to conduct a head-to-head retrospective comparison of four SRS methods, addressing the lack of randomized data in LBM literature amongst treatment paradigms. Despite patient characteristic trends, no significant differences were found in LF, composite endpoint, and DIF rates between non-operative and operative approaches.

Vitamin D Metabolites: Analytical Challenges and Clinical Relevance.

Recent research activities have provided new insights in vitamin D metabolism in various conditions. Furthermore, substantial progress has been made in the analysis of vitamin D metabolites and related biomarkers, such as vitamin D binding protein. Liquid chromatography tandem mass spectrometric (LC-MS/MS) methods are capable of accurately measuring multiple vitamin D metabolites in parallel. Nevertheless, only 25(OH)D and the biologically active form 1,25(OH)2D are routinely measured in clinical practice. While 25(OH)D remains the analyte of choice for the diagnosis of vitamin D deficiency, 1,25(OH)2D is only recommended in a few conditions with a dysregulated D metabolism. 24,25(OH)2D, free and bioavailable 25(OH)D, and the vitamin D metabolite ratio (VMR) have shown promising results, but technical pitfalls in their quantification, limited clinical data and the lack of reference values, impede their use in clinical practice. LC-MS/MS is the preferred method for the measurement of all vitamin D related analytes as it offers high sensitivity and specificity. In particular, 25(OH)D and 24,25(OH)2D can accurately be measured with this technology. When interpreted together, they seem to provide a functional measure of vitamin D metabolism beyond the analysis of 25(OH)D alone. The determination of VDBP, free and bioavailable 25(OH)D is compromised by unresolved analytical issues, lacking reference intervals and insufficient clinical data. Therefore, future research activities should focus on analytical standardization and exploration of their clinical value. This review provides an overview on established and new vitamin D related biomarkers including their pathophysiological role, preanalytical and analytical aspects, expected values, indications and influencing conditions.

Role of Vitamin K in Bone and Muscle Metabolism.

Vitamin K, a cofactor for the γ-glutamyl carboxylase enzyme, is required for the post-translational activation of osteocalcin and matrix Gla protein, which play a key role in bone and muscle homeostasis. In vivo and in vitro models for osteoporosis and sarcopenia suggest the vitamin K could exert a positive effect in both conditions. In bone, it increases osteoblastogenesis, whilst decreases osteoclast formation and function. In muscle, it is associated with increased satellite cell proliferation and migration and might play a role in energy metabolism. Observational trials suggest that high levels of vitamin K are associated with increased bone mineral density and reduced fracture risk. However, interventional studies for vitamin K supplementation yielded conflicting results. Clinical trials in sarcopenia suggest that vitamin K supplementation could improve muscle mass and function. One of the main limitations on the vitamin K studies are the technical challenges to measure its levels in serum. Thus, they are obtained from indirect sources like food questionnaires, or levels of undercarboxylated proteins, which can be affected by other environmental or biological processes. Although current research appoints to a beneficial effect of vitamin K in bone and muscle, further studies overcoming the current limitations are required in order to incorporate this supplementation in the clinical management of patients with osteosarcopenia.

Experiences of water immersion during childbirth: a qualitative thematic synthesis.

BACKGROUND: The increasing demand for childbirth care based on physiological principles has led official bodies to encourage health centers to provide evidence-based care aimed at promoting women's participation in informed decision-making and avoiding excessive medical intervention during childbirth. One of the goals is to reduce pain and find alternative measures to epidural anesthesia to enhance women's autonomy and well-being during childbirth. Currently, water immersion is used as a non-pharmacological method for pain relief. This review aimed to identify and synthesize evidence on women's and midwives' experiences, values, and preferences regarding water immersion during childbirth. METHODS: A systematic review and thematic synthesis of qualitative evidence were conducted. Databases were searched and references were checked according to specific criteria. Studies that used qualitative data collection and analysis methods to examine the opinions of women or midwives in the hospital setting were included. Non-qualitative studies, mixed-methods studies that did not separately report qualitative results, and studies in languages other than English or Spanish were excluded. The Critical Appraisal Skills Program Qualitative Research Checklist was used to assess study quality, and results were synthesized using thematic synthesis. RESULTS: Thirteen studies met the inclusion criteria and were included in this review. The qualitative studies yielded three key themes: 1) reasons identified by women and midwives for choosing a water birth, 2) benefits experienced in water births, and 3) barriers and facilitators of water immersion during childbirth. CONCLUSIONS: The evidence from qualitative studies indicates that women report benefits associated with water birth. From the perspective of midwives, ensuring safe water births requires adequate resources, midwives training, and rigorous standardized protocols to ensure that all pregnant women can safely opt for water immersion during childbirth with satisfactory results.

Implementation of superficial radiation therapy (SRT) using SRT-100 Vision™ for non-melanoma skin cancer in a Radiation Oncology clinic.

PURPOSE: This article describes our experience in implementation of superficial radiation therapy (SRT) using SRT-100 Vision™ for non-melanoma skin cancer. METHODS: Following the American Association of Physicists in Medicine Task Group-61 protocol, absolute output (absorbed dose to water at surface (cGy/min)) was measured for three energies (50, 70, and 100 kV) and for six applicators (1.5-5.0 cm in diameter). Percent depth dose (PDD) and profiles were also measured. Timer testing and ultrasound testing were performed. A treatment time calculation worksheet was created. Quality assurance (QA) of SRT-100 Vision was implemented. After treatment workflow for our clinic was developed, end-to-end (E2E) testing was performed using a Rando phantom. Considerations for treatment using SRT-100 Vision were made. RESULTS: Absolute output (cGy/min) decreases as energy increases and applicator size decreases. Due to scatter from the applicator, PDD at depths ≤5 mm does not follow conventional trends but PDD at depths ≥15 mm increases with increasing applicator size. Profiles for the 5 cm applicator do not have strong dependence on depth except profiles at 5 mm for 50 kV. Timer/end errors are negligible for all three energies. Ultrasound images confirm allowed field of view and depth as well as no image artifacts and spatial integrity. Daily, monthly and annual QA of SRT-100 Vision implemented in our clinic is listed in a table format. E2E testing results (<1%) demonstrate the functionality and performance of our treatment workflow. Our considerations for SRT treatment include patient, applicator size and energy selections, patient setup, and shields. CONCLUSIONS: This article is expected to serve as guidance for Radiation Oncology and/or Dermatology clinics aspiring to initiate an SRT program in their clinics.

OptImal Gamma kNife lIghTnIng sOlutioN (IGNITION) score to characterize the solution space of the Gamma Knife FIP optimizer for stereotactic radiosurgery.

OBJECTIVES: The objective of this study is to evaluate the user-defined optimization settings in the Fast Inverse Planning (FIP) optimizer in Leksell GammaPlan® and determine the parameters that result in the best stereotactic radiosurgery (SRS) plan quality for brain metastases, benign tumors, and arteriovenous malformations (AVMs). METHODS: Thirty patients with metastases and 30 with benign lesions-vestibular schwannoma, AVMs, pituitary adenoma, and meningioma-treated with SRS were evaluated. Each target was planned by varying the low dose (LD) and beam-on-time (BOT) penalties in increments of 0.1, from 0 to 1. The following plan quality metrics were recorded for each plan: Paddick conformity index (PCI), gradient index (GI), BOT, and maximum organ-at-risk (OAR) doses. A novel objective score matrix was calculated for each target using a linearly weighted combination of the aforementioned metrics. A histogram of optimal solutions containing the five best scores was extracted. RESULTS: A total of 7260 plans were analyzed with 121 plans per patient for the range of LD/BOT penalties. The ranges of PCI, GI, and BOT across all metastatic lesions were 0.58-0.97, 2.1-3.8, and 8.8-238 min, respectively, and were 0.13-0.97, 2.1-3.8, and 8.8-238 min, respectively, for benign lesions. The objective score matrix showed unique optimal solutions for metastatic lesions and benign lesions. Additionally, the plan metrics of the optimal solutions were significantly improved compared to the clinical plans for metastatic lesions with equivalent metrics for all other cases. CONCLUSION: In this study, FIP optimizer was evaluated to determine the optimal solution space to maximize PCI and minimize GI, BOT and OAR doses simultaneously for single metastatic/benign/non-neoplastic targets. The optimal solution chart was determined using a novel objective score which provides novice and expert planners a roadmap to generate the most optimal plans efficiently using FIP.

A study on inter-planner plan quality variability using a manual planning- or Lightning dose optimizer-approach for single brain lesions treated with the Gamma Knife® Icon™.

PURPOSE: The purpose of this study is to investigate inter-planner plan quality variability using a manual forward planning (MFP)- or fast inverse planning (FIP, Lightning)-approach for single brain lesions treated with the Gamma Knife® (GK) Icon™. METHODS: Thirty patients who were previously treated with GK stereotactic radiosurgery or radiotherapy were selected and divided into three groups (post-operative resection cavity, intact brain metastasis, and vestibular schwannoma [10 patients per group]). Clinical plans for the 30 patients were generated by multiple planners using FIP only (1), a combination of FIP and MFP (12), and MFP only (17). Three planners (Senior, Junior, and Novice) with varying experience levels re-planned the 30 patients using MFP and FIP (two plans per patient) with planning time limit of 60 min. Statistical analysis was performed to compare plan quality metrics (Paddick conformity index, gradient index, number of shots, prescription isodose line, target coverage, beam-on-time (BOT), and organs-at-risk doses) of MFP or FIP plans among three planners and to compare plan quality metrics between each planner's MFP/FIP plans and clinical plans. Variability in FIP parameter settings (BOT, low dose, and target max dose) and in planning time among the planners was also evaluated. RESULTS: Variations in plan quality metrics of FIP plans among three planners were smaller than those of MFP plans for all three groups. Junior's MFP plans were the most comparable to the clinical plans, whereas Senior's and Novice's MFP plans were superior and inferior, respectively. All three planners' FIP plans were comparable or superior to the clinical plans. Differences in FIP parameter settings among the planners were observed. Planning time was shorter and variations in planning time among the planners were smaller for FIP plans in all three groups. CONCLUSIONS: The FIP approach is less planner dependent and more time-honored than the MFP approach.

Mandibular Dysmorphology and Clinical Presentation in Treacher Collins Syndrome.

INTRODUCTION: Treacher Collins syndrome is a rare congenital disease characterized by the multiple craniofacial malformations. Although the deformities affecting patients with Treacher Collins syndrome have been well characterized, the effects of these malformations to clinical severity of the syndrome are not well understood. OBJECTIVE: To determine the association of specific Treacher Collins mandibular malformations with clinical severity. DESIGN: A retrospective radiographic observational study. SETTING: Study conducted at a single institution, a quaternary craniofacial care center. PATIENTS: 54 patients with Treacher Collins syndrome. INTERVENTIONS: Computed tomography (CT), clinical photographs and medical history were included in this analysis. Mandibles were isolated from CT data and reconstructed in three dimensions using Mimics software. Cephalometric measurements were performed on CT data. Clinical severity was determined by Teber and Vincent scores. Association of craniofacial dysmorphology to clinical severity was determined by Spearman rank coefficient. MAIN OUTCOME MEASURES: The main results obtained were the measurements of the mandibles and the quantification of the malformations of the evaluated patients. RESULTS: Among the most frequent findings in the sample are hypoplasia of the zygomatic complex, descending palpebral cleft and mandibular hypoplasia. Patients with a lower ramus/corpus ratio had a higher (more severe) Teber and Vincent classification. CONCLUSION: Patients with the most compromised mandible are also the patients with the highest number of malformations, thus, the most severe patients.

Impact of magnetic field regulation in conjunction with the volumetric repainting technique on the spot positions and beam range in pencil beam scanning proton therapy.

PURPOSE: The objective of this study was to evaluate the impact of the magnetic field regulation in conjunction with the volumetric repainting technique on the spot positions and range in pencil beam scanning proton therapy. METHODS: "Field regulation" - a feature to reduce the switching time between layers by applying a magnetic field setpoint (instead of a current setpoint) has been implemented on the proton beam delivery system at the Miami Cancer Institute. To investigate the impact of field regulation for the volumetric repainting technique, several spot maps were generated with beam delivery sequence in both directions, that is, irradiating from the deepest layer to the most proximal layer ("down" direction) as well as irradiating from the most proximal layer to the deepest layer ("up" direction). Range measurements were performed using a multi-layer ionization chamber array. Spot positions were measured using two-dimensional and three-dimensional scintillation detectors. For range and central-axis spot position, spot maps were delivered for energies ranging from 70-225 MeV. For off-axis spot positions, the maps were delivered for high-, medium, and low-energies at eight different gantry angles. The results were then compared between the "up" and "down" directions. RESULTS: The average difference in range for given energy between "up" and "down" directions was 0.0 ± 0.1 mm. The off-axis spot position results showed that 846/864 of the spots were within ±1 mm, and all off-axis spot positions were within ±1.2 mm. For spots (n = 126) at the isocenter, the evaluation between "up" and "down" directions for given energy showed the spot position difference within ±0.25 mm. At the nozzle entrance, the average differences in X and Y positions for given energy were 0.0 ± 0.2 mm and -0.0 ± 0.4 mm, respectively. At the nozzle exit, the average differences in X and Y positions for given energy were 0.0 ± 0.1 mm and -0.1 ± 0.1 mm, respectively. CONCLUSION: The volumetric repainting technique in magnetic field regulation mode resulted in acceptable spot position and range differences for our beam delivery system. The range differences were found to be within ±1 mm (TG224). For the spot positions (TG224: ±1 mm), the central axis measurements were within ±1 mm, whereas for the off-axis measurements, 97.9% of the spots were within ±1 mm, and all spots were within ±1.2 mm.

Proteomic investigations into hypertension: what's new and how might it affect clinical practice?

Introduction: Hypertension is a multifactorial disease that has, thus far, proven to be a difficult target for pharmacological intervention. The application of proteomic strategies may help to identify new biomarkers for the early diagnosis and prompt treatment of hypertension, in order to control blood pressure and prevent organ damage. Areas covered: Advances in proteomics have led to the discovery of new biomarkers to help track the pathophysiological processes implicated in hypertension. These findings not only help to better understand the nature of the disease, but will also contribute to the clinical needs for a timely diagnosis and more precise treatment. In this review, we provide an overview of new biomarkers identified in hypertension through the application of proteomic techniques, and we also discuss the difficulties and challenges in identifying biomarkers in this clinical setting. We performed a literature search in PubMed with the key words 'hypertension' and 'proteomics', and focused specifically on the most recent literature on the utility of proteomics in hypertension research. Expert opinion: There have been several promising biomarkers of hypertension identified by proteomics, but too few have been introduced to the clinic. Thus, further investigations in larger cohorts are necessary to test the feasibility of this strategy for patients. Also, this emerging field would profit from more collaboration between clinicians and researchers.

Development and long-term stability of a comprehensive daily QA program for a modern pencil beam scanning (PBS) proton therapy delivery system.

PURPOSE: The main purpose of this study is to demonstrate the clinical implementation of a comprehensive pencil beam scanning (PBS) daily quality assurance (QA) program involving a number of novel QA devices including the Sphinx/Lynx/parallel-plate (PPC05) ion chamber and HexaCheck/multiple imaging modality isocentricity (MIMI) imaging phantoms. Additionally, the study highlights the importance of testing the connectivity among oncology information system (OIS), beam delivery/imaging systems, and patient position system at a proton center with multi-vendor equipment and software. METHODS: For dosimetry, a daily QA plan with spot map of four different energies (106, 145, 172, and 221 MeV) is delivered on the delivery system through the OIS. The delivery assesses the dose output, field homogeneity, beam coincidence, beam energy, width, distal-fall-off (DFO), and spot characteristics - for example, position, size, and skewness. As a part of mechanical and imaging QA, a treatment plan with the MIMI phantom serving as the patient is transferred from OIS to imaging system. The HexaCheck/MIMI phantoms are used to assess daily laser accuracy, imaging isocenter accuracy, image registration accuracy, and six-dimensional (6D) positional correction accuracy for the kV imaging system and robotic couch. RESULTS: The daily QA results presented herein are based on 202 daily sets of measurements over a period of 10 months. Total time to perform daily QA tasks at our center is under 30 min. The relative difference (Δrel ) of daily measurements with respect to baseline was within ± 1% for field homogeneity, ±0.5 mm for range, width and DFO, ±1 mm for spots positions, ±10% for in-air spot sigma, ±0.5 spot skewness, and ±1 mm for beam coincidence (except 1 case: Δrel  = 1.3 mm). The average Δrel in dose output was -0.2% (range: -1.1% to 1.5%). For 6D IGRT QA, the average absolute difference (Δabs ) was ≤0.6 ± 0.4 mm for translational and ≤0.5° for rotational shifts. CONCLUSION: The use of novel QA devices such as the Sphinx in conjunction with the Lynx, PPC05 ion chamber, HexaCheck/MIMI phantoms, and myQA software was shown to provide a comprehensive and efficient method for performing daily QA of a number of system parameters for a modern proton PBS-dedicated treatment delivery unit.

Novel clinical and molecular findings in Spanish patients with naevoid basal cell carcinoma syndrome.

BACKGROUND: Naevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by developmental alterations and multiple basal cell carcinomas. Mutations in PTCH1, which encodes a membrane receptor for Sonic Hedgehog, are associated with the development of the disease. Most of them produce a truncated protein, which is unable to suppress Smoothened protein and continuously activates the downstream pathway. OBJECTIVES: We aimed to characterize 22 unrelated Spanish patients with NBCCS, the largest cohort with Gorlin syndrome reported to date in Spain. METHODS: Genomic analysis of PTCH1 was performed in patients with NBCCS and controls, and mutations were analysed using bioinformatics tools. RESULTS: We report for the first time two young patients, one each with uterus didelphys and ganglioneuroma, within the context of NBCCS. One patient showing a severe phenotype of the disease had developed basal cell carcinomas since childhood. Sanger sequencing of PTCH1 in this cohort identified 17 novel truncating mutations (11 frameshift, five nonsense and one mutation affecting an exon-intron splice site) and two novel missense mutations that were predicted to be pathogenic. The patients showed great clinical variability and inconsistent genotype-phenotype correlation, as seen in relatives carrying similar mutations. CONCLUSIONS: This study contributes to increase the pool of clinical manifestations of NBCCS, as well as increasing the number of pathogenic mutations identified in PTCH1 predisposing to the condition. The inconsistencies found between phenotype and genotype suggest the involvement of other modifying factors, genetic, epigenetic or environmental.

Albedo and atmospheric constraints of dwarf planet Makemake from a stellar occultation.

Pluto and Eris are icy dwarf planets with nearly identical sizes, comparable densities and similar surface compositions as revealed by spectroscopic studies. Pluto possesses an atmosphere whereas Eris does not; the difference probably arises from their differing distances from the Sun, and explains their different albedos. Makemake is another icy dwarf planet with a spectrum similar to Eris and Pluto, and is currently at a distance to the Sun intermediate between the two. Although Makemake's size (1,420 ± 60 km) and albedo are roughly known, there has been no constraint on its density and there were expectations that it could have a Pluto-like atmosphere. Here we report the results from a stellar occultation by Makemake on 2011 April 23. Our preferred solution that fits the occultation chords corresponds to a body with projected axes of 1,430 ± 9 km (1σ) and 1,502 ± 45 km, implying a V-band geometric albedo p(V) = 0.77 ± 0.03. This albedo is larger than that of Pluto, but smaller than that of Eris. The disappearances and reappearances of the star were abrupt, showing that Makemake has no global Pluto-like atmosphere at an upper limit of 4-12 nanobar (1σ) for the surface pressure, although a localized atmosphere is possible. A density of 1.7 ± 0.3 g cm(-3) is inferred from the data.

An evaluation of the stability of image quality parameters of Elekta X-ray volume imager and iViewGT imaging systems.

INTRODUCTION: A robust image quality assurance and analysis methodology for image-guided localization systems is crucial to ensure the accurate localization and visualization of target tumors. In this study, the long-term stability of selected image parameters was assessed and evaluated for the cone-beam computed tomography (CBCT) mode, planar radiographic kV mode, and the radiographic MV mode of an Elekta VersaHD. MATERIALS AND METHODS: The CATPHAN, QckV-1, and QC-3 phantoms were used to evaluate the image quality parameters. The planar radiographic images were analyzed in PIPSpro™ with spatial resolution (f30, f40, f50), contrast to noise ratio (CNR) and noise being recorded. For XVI CBCT, Head and Neck Small20 (S20) and Pelvis Medium20 (M20) standard acquisition modes were evaluated for uniformity, noise, spatial resolution, and HU constancy. Dose and kVp for the XVI were recorded using the Unfors RaySafe Xi system with the R/F low detector for the kV planar radiographic mode. For each metric, values were normalized to the mean and the standard deviations were recorded. RESULTS: A total of 30 measurements were performed on a single Elekta VersaHD linear accelerator over an 18-month period without significant adjustment or recalibration to the XVI or iViewGT systems during the evaluated time frame. For the planar radiographic spatial resolution, the normalized standard deviation values of the f30, f40, and f50 were 0.004, 0.003, and 0.003 and 0.015, 0.009, and 0.017 for kV and MV, respectively. The average recorded dose for kV was 67.96 µGy. The standard deviations of the evaluated metrics for the S20 acquisition were 0.083(f30), 0.058(f40), 0.056(f50), 0.021(Water/poly-HU constancy), 0.029(uniformity) and 0.028(noise). The standard deviations for the M20 acquisition were 0.093(f30), 0.043(f40), 0.037(f50), 0.016(Water/poly-HU constancy), 0.010(uniformity) and 0.011(Noise). CONCLUSION: A study was performed to assess the stability of the basic image quality parameters recommended by TG-142 for the Elekta XVI and iViewGT imaging systems. The two systems show consistent imaging and dosimetric properties over the evaluated time frame.

Association between dental hygiene, gingivitis and overweight or the risk of overweight in primary teeth of 4- and 5-year-old preschoolers in México.

OBJECTIVE: To determine the association between dental hygiene, gingivitis and overweight or the risk of overweight according to body mass index (BMI). METHODS: A cross-sectional study was performed with 1527 preschoolers. The children were divided into 4 groups: (i) absence of visible plaque and normal weight; (ii) absence of visible plaque and risk of overweight or overweight; (iii) presence of visible plaque and normal weight; and (iv) presence of visible plaque and risk of overweight or overweight. The clinical parameters evaluated were as follows: body mass index, degree of urban marginalization, dental caries, the simplified oral hygiene index and gingival status. Bivariate analysis and multivariate binary logistic regression models were used to identify associations between variables. RESULTS: The highest mean of gingivitis (0.28) was observed in the groups with visible plaque with normal weight and with overweight and risk of overweight. The presence of visible plaque and risk of overweight or overweight were positively associated (P = .0001) with the mean of gingivitis (OR = 8.28, 95% CI = 3.30-19.8). The absence of visible plaque and risk of overweight or overweight (P = .0001) were also positively associated with the presence of gingivitis (OR = 2.44, 95% CI = 0.68-8.06). This is after both models were adjusted by gender and degree of marginalization. CONCLUSIONS: The professionals should develop interdisciplinary approaches to (i) propose appropriate interventions to improve oral health in overweight preschoolers; and (ii) propose interventions to decrease the overweight with the possibility of also reducing its association with gingivitis.

Comparison of initial patient setup accuracy between surface imaging and three point localization: A retrospective analysis.

PURPOSE: Historically, the process of positioning a patient prior to imaging verification used a set of permanent patient marks, or tattoos, placed subcutaneously. After aligning to these tattoos, plan specific shifts are applied and the position is verified with imaging, such as cone-beam computed tomography (CBCT). Due to a variety of factors, these marks may deviate from the desired position or it may be hard to align the patient to these marks. Surface-based imaging systems are an alternative method of verifying initial positioning with the entire skin surface instead of tattoos. The aim of this study was to retrospectively compare the CBCT-based 3D corrections of patients initially positioned with tattoos against those positioned with the C-RAD CatalystHD surface imager system. METHODS: A total of 6000 individual fractions (600-900 per site per method) were randomly selected and the post-CBCT 3D corrections were calculated and recorded. For both positioning methods, four common treatment site combinations were evaluated: pelvis/lower extremities, abdomen, chest/upper extremities, and breast. Statistical differences were evaluated using a paired sample Wilcoxon signed-rank test with significance level of <0.01. RESULTS: The average magnitudes of the 3D shift vectors for tattoos were 0.9 ± 0.4 cm, 1.0 ± 0.5 cm, 0.9 ± 0.6 cm and 1.4 ± 0.7 cm for the pelvis/lower extremities, abdomen, chest/upper extremities and breast, respectively. For the CatalystHD, the average magnitude of the 3D shifts for the pelvis/lower extremities, abdomen, chest/upper extremities and breast were 0.6 ± 0.3 cm, 0.5 ± 0.3 cm, 0.5 ± 0.3 cm and 0.6 ± 0.2 cm, respectively. Statistically significant differences (P < 0.01) in the 3D shift vectors were found for all four sites. CONCLUSION: This study shows that the overall 3D shift corrections for patients initially aligned with the C-RAD CatalystHD were significantly smaller than those aligned with subcutaneous tattoos. Surface imaging systems can be considered a viable option for initial patient setup and may be preferable to permanent marks for specific clinics and patients.

Clinical and Genetic Advances in Paget's Disease of Bone: a Review.

Paget's disease of bone (PDB) is the second most common metabolic bone disorder, after osteoporosis. It is characterised by focal areas of increased and disorganised bone turnover, coupled with increased bone formation. This disease usually appears in the late stages of life, being slightly more frequent in men than in women. It has been reported worldwide, but primarily affects individuals of British descent. Majority of PDB patients are asymptomatic, but clinical manifestations include pain, bone deformity and complications, like pathological fractures and deafness. The causes of the disease are poorly understood and it is considered as a complex trait, combining genetic predisposition with environmental factors. Linkage analysis identified SQSTM1, at chromosome 5q35, as directly related to the disease. A number of mutations in this gene have been reported, pP392L being the most common variant among different populations. Most of these variants affect the ubiquitin-associated (UBA) domain of the protein, which is involved in autophagy processes. Genome-wide association studies enlarged the number of loci associated with PDB, and further fine-mapping studies, combined with functional analysis, identified OPTN and RIN3 as causal genes for Paget's disease. A combination of risk alleles identified by genome-wide association studies led to the development of a score to predict disease severity, which could improve the management of the disease. Further studies need to be conducted to elucidate other important aspects of the trait, such as its focal nature and the epidemiological changes found in some populations. In this review, we summarize the clinical characteristics of the disease and the latest genetic advances to identify susceptibility genes. We also list current available treatments and prospective options.

Bloodstream infections caused by Escherichia coli producing AmpC ß-lactamases: epidemiology and clinical features.

The aim of the study was to investigate the epidemiology and clinical features of bloodstream infections due to Escherichia coli producing AmpC ß-lactamases (AmpC-Ec-BSI). In a multi-centre case-control study, all third-generation-cephalosporin-resistant Escherichia coli BSI (3GC-Ec-BSI) isolates were analysed. Acquired bla AmpC (bla ac-AmpC) detection was done by polymerase chain reaction (PCR) and sequencing. Chromosomal bla AmpC (bla c-AmpC) expression was quantified by real-time PCR. Cases were patients with AmpC-Ec-BSI. Controls were patients with cephalosporin-susceptible E. coli BSI, matched 1:1 by sex and age. Demographics, comorbidities, intrinsic and extrinsic risk factors for antimicrobial resistance, clinical presentation and outcomes were investigated. Among 841 E. coli BSI, 17 were caused by AmpC-Ec (2 %). Eleven isolates (58.8 %) had bla ac-AmpC and six were bla c-AmpC overproducers. The mean age of cases was 66.2 years and 71 % were men. Cases were more frequently healthcare-related (82 vs. 52 % controls, p < 0.05) and presented more intrinsic and extrinsic risk factors. At least one risk factor was present in 94.1 % of cases vs. 41.7 % of controls (p = 0.002). Severity and length of stay (LOS) were higher among cases (mean Pitt Score 2.6 vs. 0.38 in controls, p = 0.03; LOS 17.5 days vs. 6 in controls, p = 0.02). Inappropriate empirical therapy (IET) was administered to 70.6 % of cases and 23.5 % of controls (p < 0.003). No differences were found in terms of cure rate at the 14th day and mortality. Bloodstream infections due to AmpC-Ec (mostly plasmid-mediated) are infrequent in our area. AmpC-Ec-BSI affects mainly patients with intrinsic risk factors and those with previous antibiotic exposure. A high proportion received IET.

Relationship between calcium mobilization and platelet α- and δ-granule secretion. A role for TRPC6 in thrombin-evoked δ-granule exocytosis.

Changes in cytosolic Ca(2+) concentration ([Ca(2+)]c) regulate granule secretion in different cell types. Thrombin activates PAR1 and PAR4 receptors and promotes release of Ca(2+) from distinct intracellular stores, which, in turn, activates store-operated Ca(2+) entry (SOCE). A crucial step during platelet function is the release of physiological agonists stored in secretory granules to the extracellular compartment during activation. We aim to study the role of Ca(2+) mobilization from the extracellular compartment or from different intracellular stores in platelet granule secretion. By using flow cytometry, we have found that α- and δ-granules are secreted in thrombin-stimulated platelets in the absence of extracellular Ca(2+), and in a concentration-dependent manner. Our findings show that thrombin-stimulated granule secretion depends on Ca(2+) mobilization from intracellular stores. Analysis of the kinetics of granule secretion reveals that platelet stimulation with thrombin results in rapid release of α-granules which precedes the secretion of δ-granules. Incubation of platelets with a specific antibody, which recognizes the extracellular amino acid sequence 573-586 of TRPC6, inhibited thrombin-evoked δ-granule exocytosis. Our results indicate that the mechanisms underlying thrombin-induced α- and δ-granule secretion show differences in dependency on Ca(2+) mobilization.

An evaluation of the stability of image-quality parameters of Varian on-board imaging (OBI) and EPID imaging systems.

Quality assurance (QA) of the image quality for image-guided localization systems is crucial to ensure accurate visualization and localization of regions of interest within the patient. In this study, the temporal stability of selected image parameters was assessed and evaluated for kV CBCT mode, planar radiographic kV, and MV modes. The motivation of the study was to better characterize the temporal variability in specific image-quality parameters. The CATPHAN, QckV-1, and QC-3 phantoms were used to evaluate the image-quality parameters of the imaging systems on a Varian Novalis Tx linear accelerator. The planar radiographic images were analyzed in PIPSpro with high-contrast spatial resolution (f30, f40,f50 lp/mm) being recorded. For OBI kV CBCT, high-quality head full-fan acquisition and pelvis half-fan acquisition modes were evaluated for uniformity, noise, spatial resolution, HU constancy, and geometric distortion. Dose and X-ray energy for the OBI were recorded using the Unfors RaySafe Xi system with the R/F High Detector for kV planar radiographic and the CT detector for kV CBCT. Dose for the MV EPID was recorded using a PTW975 Semiflex ion chamber, PTW UNIDOS electrometer, and CNMC Plastic Water. For each image-quality parameter, values were normalized to the mean, and the normalized standard deviations were recorded to evaluate the parameter's temporal variability. For planar radiographic modes, the normalized standard deviations of the spatial resolution (f30, f40, & f50) were 0.015, 0.008, 0.004 lp/mm and 0.006, 0.009, 0.018 lp/mm for the kV and MV, respectively. The normalized standard deviation of dose for kV and MV were 0.010 mGy and 0.005mGy, respectively. The standard deviations for full- and half-fan kV CBCT modes were averaged together. The following normalized standard deviations for each kV CBCT parameter were: 0.075 HU (uniformity), 0.071 HU (noise), 0.006mm (AP-geometric distortion), 0.005 mm (LAT-geometric distortion), 0.058mm (slice thickness), 0.124 (f50), 0.031 (HU constancy - Lung), 0.063 (HU constancy- Water), 0.020 (HU constancy - Bone), 0.006 mGy (Dose - Center), 0.004 mGy (Dose -Periphery). Using control chart analysis, institutional QA tolerances were reported as warning and action thresholds based on 1σ and 2σ thresholds. A study was performed to characterize the stability of image-quality parameters recommended by AAPM Task Group-142 for the Varian OBI and EPID imaging systems. Both imaging systems show consistent imaging and dosimetric properties over the evaluated time frame.