Radiotherapy (RT) aims to deliver a spatially conformal dose of radiation to tumours while maximizing the dose sparing to healthy tissues. However, the internal patient anatomy is constantly moving ...due to respiratory, cardiac, gastrointestinal and urinary activity. The long term goal of the RT community to 'see what we treat, as we treat' and to act on this information instantaneously has resulted in rapid technological innovation. Specialized treatment machines, such as robotic or gimbal-steered linear accelerators (linac) with in-room imaging suites, have been developed specifically for real-time treatment adaptation. Additional equipment, such as stereoscopic kilovoltage (kV) imaging, ultrasound transducers and electromagnetic transponders, has been developed for intrafraction motion monitoring on conventional linacs. Magnetic resonance imaging (MRI) has been integrated with cobalt treatment units and more recently with linacs. In addition to hardware innovation, software development has played a substantial role in the development of motion monitoring methods based on respiratory motion surrogates and planar kV or Megavoltage (MV) imaging that is available on standard equipped linacs. In this paper, we review and compare the different intrafraction motion monitoring methods proposed in the literature and demonstrated in real-time on clinical data as well as their possible future developments. We then discuss general considerations on validation and quality assurance for clinical implementation. Besides photon RT, particle therapy is increasingly used to treat moving targets. However, transferring motion monitoring technologies from linacs to particle beam lines presents substantial challenges. Lessons learned from the implementation of real-time intrafraction monitoring for photon RT will be used as a basis to discuss the implementation of these methods for particle RT.
BACKGROUND:Guidelines recommend routine preoperative frailty assessment for older people. However, the degree to which frailty instruments improve predictive accuracy when added to traditional risk ...factors is poorly described. Our objective was to measure the accuracy gained in predicting outcomes important to older patients when adding the Clinical Frailty Scale (CFS), Fried Phenotype (FP), or Frailty Index (FI) to traditional risk factors.
METHODS:This was an analysis of a multicenter prospective cohort of elective noncardiac surgery patients ≥65 years of age. Each frailty instrument was prospectively collected. The added predictive performance of each frailty instrument beyond the baseline model (age, sex, American Society of Anesthesiologists’ score, procedural risk) was estimated using likelihood ratio test, discrimination, calibration, explained variance, and reclassification. Outcomes analyzed included death or new disability, prolonged length of stay (LoS, >75th percentile), and adverse discharge (death or non-home discharge).
RESULTS:We included 645 participants (mean age, 74 standard deviation, 6); 72 (11.2%) participants died or experienced a new disability, 164 (25.4%) had prolonged LoS, and 60 (9.2%) had adverse discharge. Compared to the baseline model predicting death or new disability (area under the curve AUC, 0.67; R, 0.08, good calibration), prolonged LoS (AUC, 0.73; R, 0.18, good calibration), and adverse discharge (AUC, 0.78; R, 0.16, poor calibration), the CFS improved fit per the likelihood ratio test (P < .02 for death or new disability, <.001 for LoS, <.001 for discharge), discrimination (AUC = 0.71 for death or new disability, 0.76 for LoS, 0.82 for discharge), calibration (good for death or new disability, LoS, and discharge), explained variance (R = 0.11 for death or new disability, 0.22 for LoS, 0.25 for discharge), and reclassification (appropriate directional reclassification) for all outcomes. The FP improved discrimination and R for all outcomes, but to a lesser degree than the CFS. The FI improved discrimination for death or new disability and R for all outcomes, but to a lesser degree than the CFS and the FP. These results were consistent in internal validation.
CONCLUSIONS:Frailty instruments provide meaningful increases in accuracy when predicting postoperative outcomes for older people. Compared to the FP and FI, the CFS appears to improve all measures of predictive performance to the greatest extent and across outcomes. Combined with previous research demonstrating that the CFS is easy to use and requires less time than the FP, clinicians should consider its use in preoperative practice.
Colorado tick fever virus is an understudied tick-borne virus of medical importance that is primarily transmitted in the western United States and southwestern Canada. The virus is the type species ...of the genus Coltivirus (Spinareoviridae) and consists of 12 segments that remain largely uncharacterized. Patterns of viral distribution are driven by the presence of the primary vector, the Rocky Mountain wood tick, Dermacentor andersoni. Infection prevalence in D. andersoni can range from 3% to 58% across the geographic distribution of the tick. Infection in humans can be severe and often presents with fever relapses but is rarely fatal. Here, we review the literature from primary characterizations in the early 20th century to current virus/vector research being conducted and identify vacancies in current research.
Imaging has become an essential tool in modern radiotherapy (RT), being used to plan dose delivery prior to treatment and verify target position before and during treatment. Ultrasound (US) imaging ...is cost-effective in providing excellent contrast at high resolution for depicting soft tissue targets apart from those shielded by the lungs or cranium. As a result, it is increasingly used in RT setup verification for the measurement of inter-fraction motion, the subject of Part I of this review (Fontanarosa et al 2015 Phys. Med. Biol. 60 R77-114). The combination of rapid imaging and zero ionising radiation dose makes US highly suitable for estimating intra-fraction motion. The current paper (Part II of the review) covers this topic. The basic technology for US motion estimation, and its current clinical application to the prostate, is described here, along with recent developments in robust motion-estimation algorithms, and three dimensional (3D) imaging. Together, these are likely to drive an increase in the number of future clinical studies and the range of cancer sites in which US motion management is applied. Also reviewed are selections of existing and proposed novel applications of US imaging to RT. These are driven by exciting developments in structural, functional and molecular US imaging and analytical techniques such as backscatter tissue analysis, elastography, photoacoustography, contrast-specific imaging, dynamic contrast analysis, microvascular and super-resolution imaging, and targeted microbubbles. Such techniques show promise for predicting and measuring the outcome of RT, quantifying normal tissue toxicity, improving tumour definition and defining a biological target volume that describes radiation sensitive regions of the tumour. US offers easy, low cost and efficient integration of these techniques into the RT workflow. US contrast technology also has potential to be used actively to assist RT by manipulating the tumour cell environment and by improving the delivery of radiosensitising agents. Finally, US imaging offers various ways to measure dose in 3D. If technical problems can be overcome, these hold potential for wide-dissemination of cost-effective pre-treatment dose verification and in vivo dose monitoring methods. It is concluded that US imaging could eventually contribute to all aspects of the RT workflow.
Our purpose was to perform an in vivo validation of ultrasound imaging for intrafraction motion estimation using the Elekta Clarity Autoscan system during prostate radiation therapy. The study was ...conducted as part of the Clarity-Pro trial (NCT02388308).
Initial locations of intraprostatic fiducial markers were identified from cone beam computed tomography scans. Marker positions were translated according to Clarity intrafraction 3-dimensional prostate motion estimates. The updated locations were projected onto the 2-dimensional electronic portal imager plane. These Clarity-based estimates were compared with the actual portal-imaged 2-dimensional marker positions. Images from 16 patients encompassing 80 fractions were analyzed. To investigate the influence of intraprostatic markers and image quality on ultrasound motion estimation, 3 observers rated image quality, and the marker visibility on ultrasound images was assessed.
The median difference between Clarity-defined intrafraction marker locations and portal-imaged marker locations was 0.6 mm (with 95% limit of agreement at 2.5 mm). Markers were identified on ultrasound in only 3 of a possible 240 instances. No linear relationship between image quality and Clarity motion estimation confidence was identified. The difference between Clarity-based motion estimates and electronic portal–imaged marker location was also independent of image quality. Clarity estimation confidence was degraded in a single fraction owing to poor probe placement.
The accuracy of Clarity intrafraction prostate motion estimation is comparable with that of other motion-monitoring systems in radiation therapy. The effect of fiducial markers in the study was deemed negligible as they were rarely visible on ultrasound images compared with intrinsic anatomic features. Clarity motion estimation confidence was robust to variations in image quality and the number of ultrasound-imaged anatomic features; however, it was degraded as a result of poor probe placement.
ObjectivesTo determine whether whole-body MRI defines clinically relevant subgroups within polymyalgia rheumatica (PMR) including glucocorticoid responsiveness.Methods22 patients with PMR and 16 with ...rheumatoid arthritis (RA), untreated and diagnosed by consultant rheumatologists, underwent whole-body, multiple-joint MRI, scored by two experts. Patients with PMR reported whether they felt ‘back to normal’ on glucocorticoid therapy and were followed for a median of 2 years.ResultsAll patients with PMR were deemed to respond to glucocorticoids clinically. A characteristic pattern of symmetrical, extracapsular inflammation, adjacent to greater trochanter, acetabulum, ischial tuberosity and/or symphysis pubis, was observed in 14/22 of the PMR cases. In PMR, this pattern was associated with complete glucocorticoid response (p=0.01), higher pretreatment C-reactive protein (CRP) and serum interleukin-6 (IL-6), and better post-treatment fatigue and function. Only 1/14 in the extracapsular group could stop glucocorticoids within 1 year, compared with 4/7 of the others. A score derived from the five sites discriminating best between PMR and RA correlated with IL-6 (p<0.002). IL-6 levels ≥16.8 pg/mL had 86% sensitivity and 86% specificity for the extracapsular MRI pattern.ConclusionsA subset of patients with rheumatologist-diagnosed PMR had a characteristic, extracapsular pattern of MRI inflammation, associated with elevated IL-6/CRP and with complete patient-reported glucocorticoid responsiveness.
Tick vectors are capable of transmitting several rickettsial species to vertebrate hosts, resulting in various levels of disease. Studies have demonstrated the transmissibility of both rickettsial ...pathogens and novel
species or strains with unknown pathogenicity to vertebrate hosts during tick blood meal acquisition; however, the quantitative nature of transmission remains unknown. We tested the hypothesis that if infection severity is a function of the rickettsial load delivered during tick transmission, then a more virulent spotted fever group (SFG)
species is transmitted at higher levels during tick feeding. Using
cohorts infected with
or "
Rickettsia andeanae," a quantitative PCR (qPCR) assay was employed to quantify rickettsiae in tick salivary glands and saliva, as well as in the vertebrate hosts at the tick attachment site over the duration of tick feeding. Significantly greater numbers of
than of "
Rickettsia andeanae" rickettsiae were present in tick saliva and salivary glands and in the vertebrate hosts at the feeding site during tick feeding. Microscopy demonstrated the presence of both rickettsial species in tick salivary glands, and immunohistochemical analysis of the attachment site identified localized
, but not "
Rickettsia andeanae," in the vertebrate host. Lesions were also distinct and more severe in vertebrate hosts exposed to
than in those exposed to "
Rickettsia andeanae." The specific factors that contribute to the generation of a sustained rickettsial infection and subsequent disease have yet to be elucidated, but the results of this study suggest that the rickettsial load in ticks and during transmission may be an important element.
Background
Personalized medicine aims to improve outcomes through application of therapy directed by individualized risk profiles. Whether personalized risk assessment is routinely applied in ...practice is unclear; the impact of personalized preoperative risk prediction and communication on outcomes has not been synthesized. Our objective was to perform a scoping review to examine the extent, range, and nature of studies where personalized risk was evaluated preoperatively and communicated to the patient and/or healthcare professional.
Methods
A systematic search was developed, peer-reviewed, and applied to Embase, Medline, CINAHL, and Cochrane databases to identify studies of individuals having or considering surgery, where a process to assess personalized risk was applied and where these estimates were communicated to a patient and/or healthcare professional. All stages of the review were completed in duplicate. We narratively synthesized and described identified themes.
Results
We identified 796 studies; 24 underwent full-text review. Seven studies were included; one communicated personalized risk to patients, four to a healthcare professional, and two to both. Cardiac (
n
= 2) and orthopedic surgery (
n
= 2) were the most common surgical specialties. Four studies used electronic risk calculators, and three used paper-based tools. Personalized preoperative risk assessment and communication may improve accuracy of information provided to patients, improve consent processes, and influence length of stay. Methodologic weaknesses in study design were common.
Conclusions
Personalized preoperative risk assessment and communication may improve patient and system outcomes. This evidence is limited, however, by weaknesses in study design. Appropriately powered, low risk of bias evaluation of personalized risk communication before surgery is needed.
Abstract The concept of radiation dose–volume effect has been exploited in breast cancer as boost treatment for high risk patients and more recently in trials of Partial Breast Irradiation for low ...risk patients. However, there appears to be paucity of published data on the dose–volume effect of irradiation on breast tissue including the recently published report on Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC). This systematic review looks at the current literature for relationship between irradiated breast volume and normal tissue complications and introduces the concept of dose modulation.
A minority of individuals with eating disorders report being asked about their eating by health care professionals; delayed detection of eating disorders may contribute to poorer outcomes. The ...current study investigated common meal-related gastrointestinal symptoms (i.e., elevated fullness and bloating) as correlates of eating pathology that may be more readily disclosed to health professionals and indicate the need to assess for eating pathology. The current study also tested the hypothesis that elevated fullness and bloating are more strongly linked to eating pathology among those with higher body dissatisfaction. 281 university students (70.1% female, 84.3% white) completed gastrointestinal symptom and eating pathology assessments. Elevated fullness and bloating were each associated with increased purging, restrictive eating behaviors, and likelihood of having an eating disorder. Elevated fullness and bloating were more strongly linked to purging and probable eating disorder diagnosis with higher, relative to lower, body dissatisfaction. However, body dissatisfaction did not moderate the relationship between gastrointestinal symptoms and restrictive eating behaviors. Results indicate that elevated fullness and bloating are correlates of eating pathology. Healthcare professionals should consider and/or assess for eating pathology when elevated fullness and bloating are reported; further assessment of body dissatisfaction may be helpful in identifying purging behaviors.
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