Decompensated metabolic acidosis in the emergency department: Epidemiology, sodium bicarbonate therapy, and clinical outcomes.

Objective: This article aims to describe the epidemiology of decompensated metabolic acidosis, the characteristics of sodium bicarbonate (SB) administration and outcomes in emergency department (ED) patients. Design: This is a retrospective cohort study. Setting: ED of a tertiary referral hospital in Melbourne, Australia. Participants: Adult patients presenting to the ED between 1 July 2011 and 20 September 2020 with decompensated metabolic acidosis diagnosed on arterial blood gas (ABG). Main outcome measures: We compared characteristics between those treated with or without SB. We studied SB administration characteristics, change in laboratory variables, factors associated with use and dose, and clinical outcomes. Results: Among 753,613 ED patients, 314 had decompensated metabolic acidosis on ABG, with 17.8% receiving SB. Patients in the SB group had lower median pH, CO2, bicarbonate, and base excess (BE) levels compared with the No SB group (P < 0.01). The median number of SB doses in the SB group was one treatment. This was given at a median total dose of 100 mmol and at a median of 2.8 h after the diagnostic blood gas results. Only 42% of patients in the SB group had a subsequent blood gas measured. In such patients, there was no significant change in pH, bicarbonate, or BE. SB therapy was not independently associated with mortality. Conclusions: ABG-confirmed decompensated metabolic acidosis was rare but associated with a high mortality. SB administration occurred in a minority of patients and in more acidaemic patients. However, SB dose was stereotypical and not tailored to acidosis severity. Assessment of SB effect was infrequent and showed no correction of acidosis. Systematic studies of titrated SB therapy are required to inform current practice.

Shallow kinetics induced by a metronome (SKIM): A novel contactless respiratory motion management.

OBJECTIVES: As an alternative to conventional compression amidst the COVID-19 pandemic, we developed a contactless motion management strategy. By increasing the patient's breathing rate to induce shallow breathing with the aid of a metronome, our hypothesis is that the motion magnitude of the target may be minimized without physical contact or compression. METHODS: Fourteen lung stereotactic body radiation therapy (SBRT) patients treated under fast shallow-breathing (FSB) were selected for inclusion in this retrospective study. Our proposed method is called shallow kinetics induced by a metronome (SKIM). We induce FSB by setting the beats-per-minute (BPM) high (typically in the range of 50-60). This corresponded to a patient breathing rate of 25-30 (breathing) cycles per minute. The magnitude of target motion in 3D under SKIM was evaluated using 4DCT datasets. Comparison with free breathing (FB) 4DCT was also made for a subset for which FB data available. RESULTS: The overall effectiveness of SKIM was evaluated with 18 targets (14 patients). Direct comparison with FB was performed with 12 targets (10 patients). The vector norm mean ± SD value of motion magnitude under SKIM for 18 targets was 8.2 ± 4.1 mm. The mean ± SD metronome BPM was 54.9 ± 4.0 in this group. The vector norm means ± SD values of target motion for FB and SKIM in the 12 target sub-group were 14.6 ± 8.5 mm and 9.3 ± 3.7 mm, respectively. The mean ± SD metronome BPM for this sub-group was 56.3 ± 2.5. CONCLUSION: Compared with FB, SKIM can significantly reduce respiratory motion magnitude of thoracic targets. The difference in maximum motion reduction in the overall vector norm, S-I, and A-P directions was significant (p = 0.033, 0.042, 0.011). Our proposed method can be an excellent practical alternative to conventional compression due to its flexibility and ease of implementation.

Landscape diversity promotes stable food-web architectures in large rivers.

Uncovering relationships between landscape diversity and species interactions is crucial for predicting how ongoing land-use change and homogenization will impact the stability and persistence of communities. However, such connections have rarely been quantified in nature. We coupled high-resolution river sonar imaging with annualized energetic food webs to quantify relationships among habitat diversity, energy flux, and trophic interaction strengths in large-river food-web modules that support the endangered Pallid Sturgeon. Our results demonstrate a clear relationship between habitat diversity and species interaction strengths, with more diverse foraging landscapes containing higher production of prey and a greater proportion of weak and potentially stabilizing interactions. Additionally, rare patches of large and relatively stable river sediments intensified these effects and further reduced interaction strengths by increasing prey diversity. Our findings highlight the importance of landscape characteristics in promoting stabilizing food-web architectures and provide direct relevance for future management of imperilled species in a simplified and rapidly changing world.

Invasive predator diet plasticity has implications for native fish conservation and invasive species suppression.

Diet plasticity is a common behavior exhibited by piscivores to sustain predator biomass when preferred prey biomass is reduced. Invasive piscivore diet plasticity could complicate suppression success; thus, understanding invasive predator consumption is insightful to meeting conservation targets. Here, we determine if diet plasticity exists in an invasive apex piscivore and whether plasticity could influence native species recovery benchmarks and invasive species suppression goals. We compared diet and stable isotope signatures of invasive lake trout and native Yellowstone cutthroat trout (cutthroat trout) from Yellowstone Lake, Wyoming, U.S.A. as a function of no, low-, moderate-, and high-lake trout density states. Lake trout exhibited plasticity in relation to their density; consumption of cutthroat trout decreased 5-fold (diet proportion from 0.89 to 0.18) from low- to high-density state. During the high-density state, lake trout switched to amphipods, which were also consumed by cutthroat trout, resulting in high diet overlap (Schoener's index value, D = 0.68) between the species. As suppression reduced lake trout densities (moderate-density state), more cutthroat trout were consumed (proportion of cutthroat trout = 0.42), and diet overlap was released between the species (D = 0.30). A shift in lake trout δ13C signatures from the high- to the moderate-density state also corroborated increased consumption of cutthroat trout and lake trout diet plasticity. Observed declines in lake trout are not commensurate with expected cutthroat trout recovery due to lake trout diet plasticity. The abundance of the native species in need of conservation may take longer to recover due to the diet plasticity of the invasive species. The changes observed in diet, diet overlap, and isotopes associated with predator suppression provides more insight into conservation and suppression dynamics than using predator and prey biomass alone. By understanding these dynamics, we can better prepare conservation programs for potential feedbacks caused by invasive species suppression.

Reconstructing the history of helminth prevalence in the UK.

Intestinal helminth parasites (worms) have afflicted humans throughout history and their eggs are readily detected in archaeological deposits including at locations where intestinal parasites are no longer considered endemic (e.g. the UK). Parasites provide valuable archaeological insights into historical health, sanitation, hygiene, dietary and culinary practices, as well as other factors. Differences in the prevalence of helminths over time may help us understand factors that affected the rate of infection of these parasites in past populations. While communal deposits often contain relatively high numbers of parasite eggs, these cannot be used to calculate prevalence rates, which are a key epidemiological measure of infection. The prevalence of intestinal helminths was investigated through time in England, based on analysis of 464 human burials from 17 sites, dating from the Prehistoric to Industrial periods. Eggs from two faecal-oral transmitted nematodes (Ascaris sp. and Trichuris sp.) and the food-derived cestodes (Taenia spp. and Diphyllobothrium latum syn Dibothriocephalus latus) were identified, although only Ascaris was detected at a high frequency. The changing prevalence of nematode infections can be attributed to changes in effective sanitation or other factors that affect these faecal-oral transmitted parasites and the presence of cestode infections reflect dietary and culinary preferences. These results indicate that the impact of helminth infections on past populations varied over time, and that some locations witnessed a dramatic reduction in parasite prevalence during the industrial era (18th-19th century), whereas other locations continued to experience high prevalence levels. The factors underlying these reductions and the variation in prevalence provide a key historical context for modern anthelmintic programs.

The design of a novel direction modulated brachytherapy vaginal cylinder applicator for optimizing coverage of the apex.

PURPOSE: High-dose-rate (HDR) vaginal cuff brachytherapy is an effective adjuvant therapy for women with stage I endometrial cancer. Although infrequent, failures do occur, most frequently at the vaginal vault. A potential cause of failure is insufficient dosimetric coverage at the vaginal apex due to cold spots from the anisotropic dose distribution of the source. Here, we propose a novel direction modulated brachytherapy (DMBT)-concept vaginal cylinder (VC) applicator that resolves this dosimetric issue. METHODS AND MATERIALS: The novel DMBT-VC applicator was designed and simulated with the GEANT4 Monte Carlo code. The outer cylinder material chosen was polyphenylsulfone (PPSU) plastic, and the central part was a detachable rod, housing a single lumen made of either polyether ether ketone (PEEK) plastic or an MR-compatible tungsten alloy. The PPSU-based outer cylinder, together with the inner PEEK rod provides the dose distribution of a conventional VC applicator. The PEEK rod is then replaced with an MR-compatible tungsten alloy rod of the same dimensions to generate directional "pencil-like" beams to compensate for the anisotropic cold spots. Two widely used 192 Ir HDR sources, VS2000 and GammaMedPlus, were also simulated. RESULTS: The novel DMBT-VC applicator was able to remove the underdosage at the apex due to the anisotropy effect regardless of the HDR sources without unnecessarily increasing the dose to the periphery of the applicator. Also, further directional modulation to reach deeper in the apex by up to 14 mm beyond the VC surface was achievable, again without increasing the peripheral doses. Total treatment dwell times increased only by 7-13%. CONCLUSIONS: The novel DMBT-VC applicator provides improved dose coverage at the vaginal apex by overcoming the classical anisotropy issue ubiquitous to all HDR brachytherapy sources. The next step in development of the device is manufacturing a prototype for clinical testing.

A paradoxical knowledge gap in science for critically endangered fishes and game fishes during the sixth mass extinction.

Despite unprecedented scientific productivity, Earth is undergoing a sixth mass extinction. The disconnect between scientific output and species conservation may be related to scientists studying the wrong species. Given fishes have a high extinction rate, we assessed the paradox between scientific productivity and science needed for conservation by comparing scientific output created for critically endangered fishes and game fishes. We searched 197,866 articles (1964-2018) in 112 journals for articles on 460 critically endangered fishes, 297 game fishes, and 35 fishes classified as critically endangered and game fish-our analysis included freshwater and marine species. Only 3% of the articles in the final database were on critically endangered fishes; 82% of critically endangered fishes had zero articles. The difference between the number of articles on game fishes and critically endangered fishes increased temporally with more articles on game fishes during the extinction crisis. Countries with 10 or more critically endangered fishes averaged only 17 articles from 1964 to 2018. Countries with the most critically endangered fishes are most in need of science. More scientific knowledge is needed on critically endangered fishes to meet the challenges of conserving fishes during the sixth mass extinction.

Epidemiological insights from a large-scale investigation of intestinal helminths in Medieval Europe.

Helminth infections are among the World Health Organization's top neglected diseases with significant impact in many Less Economically Developed Countries. Despite no longer being endemic in Europe, the widespread presence of helminth eggs in archaeological deposits indicates that helminths represented a considerable burden in past European populations. Prevalence of infection is a key epidemiological feature that would influence the elimination of endemic intestinal helminths, for example, low prevalence rates may have made it easier to eliminate these infections in Europe without the use of modern anthelminthic drugs. To determine historical prevalence rates we analysed 589 grave samples from 7 European sites dated between 680 and 1700 CE, identifying two soil transmitted nematodes (Ascaris spp. and Trichuris trichiura) at all locations, and two food derived cestodes (Diphyllobothrium latum and Taenia spp.) at 4 sites. The rates of nematode infection in the medieval populations (1.5 to 25.6% for T. trichiura; 9.3-42.9% for Ascaris spp.) were comparable to those reported within modern endemically infected populations. There was some evidence of higher levels of nematode infection in younger individuals but not at all sites. The genetic diversity of T. trichiura ITS-1 in single graves was variable but much lower than with communal medieval latrine deposits. The prevalence of food derived cestodes was much lower (1.0-9.9%) than the prevalence of nematodes. Interestingly, sites that contained Taenia spp. eggs also contained D. latum which may reflect local culinary practices. These data demonstrate the importance of helminth infections in Medieval Europe and provide a baseline for studies on the epidemiology of infection in historical and modern contexts. Since the prevalence of medieval STH infections mirror those in modern endemic countries the factors affecting STH decline in Europe may also inform modern intervention campaigns.

Characterization of Respiration-Induced Motion in Prone Versus Supine Patient Positioning for Thoracic Radiation Therapy.

PURPOSE: Variations in the breathing characteristics, both on short term (intrafraction) and long term (interfraction) time scales, may adversely affect the radiation therapy process at all stages when treating lung tumors. Prone position has been shown to improve consistency (ie, reduced intrafraction variability) and reproducibility (ie, reduced interfraction variability) of the respiratory pattern with respect to breathing amplitude and period as a result of natural abdominal compression, with no active involvement required from the patient. The next natural step in investigating breathing-induced changes is to evaluate motion amplitude changes between prone and supine targets or organs at risk, which is the purpose of the present study. METHODS AND MATERIALS: Patients with lung cancer received repeat helical 4-dimensional computed tomography scans, one prone and one supine, during the same radiation therapy simulation session. In the maximum-inhale and maximum-exhale phases, all thoracic structures were delineated by an expert radiation oncologist. Geometric centroid trajectories of delineated structures were compared between patient orientations. Motion amplitude was measured as the magnitude of difference in structure centroid position between inhale and exhale. RESULTS: Amplitude of organ motion was larger when the patient was in the prone position compared with supine for all structures except the lower left lobe and left lung as a whole. Across all 12 patients, significant differences in mean motion amplitude between orientations were identified for the right lung (3.0 mm, P = .01), T2 (0.5 mm, P = .01) and T12 (2.1 mm, P < .001) vertebrae, the middle third of the esophagus (4.0 mm, P = .03), and the lung tumor (1.7 mm, P = .02). CONCLUSIONS: Respiration-induced thoracic organ motion was quantified in the prone position and compared with that of the supine position for 12 patients with thoracic lesions. The prone position induced larger organ motion compared with supine, particularly for the lung tumor, likely requiring increases in planning margins compared with supine.

Fatal Radiation Pneumonitis: Literature Review and Case Series.

PURPOSE: Fatal radiation pneumonitis is a rare event. In recent years, higher incidences of grade 5 pneumonitis have been reported. Based on 3 cases in our clinic, a literature review was performed to assess specific clinical features and risk factors for fatal pneumonitis. METHODS AND MATERIALS: Three patients with nonsmall cell lung cancer were treated with conventionally fractionated radiation therapy, 2 with volumetric modulated arc therapy and one with intensity modulated radiation therapy. All 3 patients had high volumes of 5 Gy in the total lung and contralateral lungs. Patients died of pneumonitis between 2 and 5 months after the end of radiation therapy. A literature review focused on grade 5 pneumonitis was performed for conventionally fractioned and stereotactic radiation therapy for lung cancer. RESULTS: Patients with grade 5 pneumonitis develop symptoms sooner than lower grade pneumonitis. Symptoms often do not respond to steroid treatment or return after steroid taper. Imaging features extend beyond the high dose area and involve the contralateral lung. Dosimetric risk factors include both low dose and high dose lung volumes. For patients undergoing stereotactic radiation therapy interstitial lung disease has been described as a risk factor. CONCLUSIONS: Despite decades of investigating radiation pneumonitis, the question of the optimum dose distribution in the lung, a large dose to a small volume versus a small dose to a large volume, is still unresolved. When both low and high dose lung volume constraints are followed, the risk for grade 5 pneumonitis has been shown to be low even with intensity modulated radiation therapy and concurrent chemotherapy. In addition to dose factors, underlying clinical and radiographic parameters play an important role for the development of grade 5 pneumonitis.

A fast and scalable method for quality assurance of deformable image registration on lung CT scans using convolutional neural networks.

PURPOSE: To develop and evaluate a method to automatically identify and quantify deformable image registration (DIR) errors between lung computed tomography (CT) scans for quality assurance (QA) purposes. METHODS: We propose a deep learning method to flag registration errors. The method involves preparation of a dataset for machine learning model training and testing, design of a three-dimensional (3D) convolutional neural network architecture that classifies registrations into good or poor classes, and evaluation of a metric called registration error index (REI) which provides a quantitative measure of registration error. RESULTS: Our study shows that, despite having limited number of training images available (10 CT scan pairs for training and 17 CT scan pairs for testing), the method achieves 0.882 AUC-ROC on the test dataset. Furthermore, the combined standard uncertainty of the estimated REI by our model lies within ± 0.11 (± 11% of true REI value), with a confidence level of approximately 68%. CONCLUSIONS: We have developed and evaluated our method using original clinical registrations without generating any synthetic/simulated data. Moreover, test data were acquired from a different environment than that of training data, so that the method was validated robustly. The results of this study showed that our algorithm performs reasonably well in challenging scenarios.

The vaginal cylinder: Misunderstood, misused, or trivial? An in-depth dosimetric and multiinstitutional outcome investigation.

PURPOSE: The purpose of the study was to investigate the impact on dose distribution and radiobiological metrics of common high-dose-rate vaginal brachytherapy treatment parameters and to analyze multiinstitutional data for clinically significant impact on outcomes in early-stage endometrial cancer. METHODS AND MATERIALS: Treatment plans were created for all combinations of prescription parameters and used to quantify the dosimetric impact of each parameter and to estimate the dose delivered using common voxel-integrated radiobiological metrics. A rating system, based on risk grouping from GOG and PORTEC trials, was used to consolidate staging information into a cancer "aggressiveness" measure. Correlations between the rating, toxicity, disease recurrence, and plan parameters were investigated. RESULTS: When prescribing to 5 mm depth, the variation caused by the diameter was very large across all dose metrics, ranging from 51% to 175% increase with the most divergence in BEDmax. For surface prescription, changing the cylinder diameter from 4 cm to 2 cm caused the dose metrics of BEDmin, Dmin, and gBEUD (a = -3) to increase by 117%, 67%, and 52%, respectively. Prescription to 5-mm depth caused changes across all dose metrics of 260% compared with surface prescription for a 2-cm cylinder. Deeper prescription point (p = 0.005) and longer treatment length (p = 0.01) were correlated with increased stenosis rates. No correlation between recurrence and any plan parameter was found. CONCLUSIONS: Dramatic differences in dose distributions arise by small variations of plan parameters, with large impact on rates of vaginal stenosis, but no clear relation with local recurrence. To help radiation oncologists interpret the magnitude of these effects for their patients, we created a tool that allows comparison between dose and fractionation parameters.

Dynamic Modulated Brachytherapy (DMBT) Balloon Applicator for Accelerated Partial Breast Irradiation.

PURPOSE: To propose a novel high-dose-rate brachytherapy applicator for balloon-based dynamic modulated brachytherapy (DMBT) for accelerated partial breast irradiation (APBI) and to demonstrate its dosimetric advantage compared to the widely used Contura applicator. METHODS AND MATERIALS: The DMBT balloon device consists of a fixed central channel enabling real-time, in vivo dosimetry and an outer motion-dynamic, adjustable-radius channel capable of moving to any angular position within the balloon. This design allows placement of dwell positions anywhere within the balloon volume, guaranteeing optimal placement and generation of the applicator and treatment plan, respectively. Thirteen clinical treatment plans for patients with early-stage breast cancer receiving APBI after lumpectomy using Contura were retrospectively obtained under institutional review board approval. New treatment plans were created by replacing the Contura with the DMBT device. DMBT plans were limited to 4 angular positions and an outer channel radius of 1.5 cm. The new plans were optimized to limit dose to ribs and skin while maintaining target coverage similar to that of the clinical plan. RESULTS: Similar target coverage was obtained for the DMBT plans compared with clinical Contura plans. Across all patients the mean (standard deviation) reductions in D0.1 cc to the ribs and skin were 6.70% (6.28%) and 5.13% (6.54%), respectively. A threshold separation distance between the balloon surface and the organ at risk (OAR), below which dosimetric changes of greater than 5% were obtained, was observed to be 12 mm for ribs and skin. When both OARs were far from the balloon, DMBT plans were of similar quality to Contura plans, as expected. CONCLUSIONS: This study demonstrates the superior ability of the APBI DMBT applicator to spare OARs while achieving target coverage comparable to current treatment plans, especially when in close proximity. The DMBT balloon may enable new modes of dynamic high-dose-rate treatment delivery and allow for ultrahypofractionated dose regimens to be safely used.

Evaluation of Image Registration Accuracy for Tumor and Organs at Risk in the Thorax for Compliance With TG 132 Recommendations.

PURPOSE: To evaluate accuracy for 2 deformable image registration methods (in-house B-spline and MIM freeform) using image pairs exhibiting changes in patient orientation and lung volume and to assess the appropriateness of registration accuracy tolerances proposed by the American Association of Physicists in Medicine Task Group 132 under such challenging conditions via assessment by expert observers. METHODS AND MATERIALS: Four-dimensional computed tomography scans for 12 patients with lung cancer were acquired with patients in prone and supine positions. Tumor and organs at risk were delineated by a physician on all data sets: supine inhale (SI), supine exhale, prone inhale, and prone exhale. The SI image was registered to the other images using both registration methods. All SI contours were propagated using the resulting transformations and compared with physician delineations using Dice similarity coefficient, mean distance to agreement, and Hausdorff distance. Additionally, propagated contours were anonymized along with ground-truth contours and rated for quality by physician-observers. RESULTS: Averaged across all patients, the accuracy metrics investigated remained within tolerances recommended by Task Group 132 (Dice similarity coefficient >0.8, mean distance to agreement <3 mm). MIM performed better with both complex (vertebrae) and low-contrast (esophagus) structures, whereas the in-house method performed better with lungs (whole and individual lobes). Accuracy metrics worsened but remained within tolerances when propagating from supine to prone; however, the Jacobian determinant contained regions with negative values, indicating localized nonphysiologic deformations. For MIM and in-house registrations, 50% and 43.8%, respectively, of propagated contours were rated acceptable as is and 8.2% and 11.0% as clinically unacceptable. CONCLUSIONS: The deformable image registration methods performed reliably and met recommended tolerances despite anatomically challenging cases exceeding typical interfraction variability. However, additional quality assurance measures are necessary for complex applications (eg, dose propagation). Human review rather than unsupervised implementation should always be part of the clinical registration workflow.

Technical Note: A method for quality assurance of landmark sets for use in evaluation of deformable image registration accuracy of lung parenchyma.

PURPOSE: To develop a quality control method to improve the accuracy of corresponding landmark sets used for deformable image registration (DIR) evaluation in the lung parenchyma. METHODS: An iterative workflow was developed as a method for quality assurance of landmark sets. Starting with the initial landmark set for a given image pair, a landmark-based deformation was applied to one of the images. A difference image and a color overlay were generated using the deformed image and the other image of the pair. Inspection of these generated images at locations of landmarks allowed for the identification of misplaced landmarks. The observer responsible for creating the initial landmark set was tasked with review and revision of points flagged by the quality assurance procedure. Using the updated landmark sets, the process was repeated until all points were acceptable to the reviewer. RESULTS: Eighteen landmark sets, containing a mean (SD) of 170 (31) landmarks, were created using CT images from non-small cell lung cancer patients exhibiting large geometric changes and atelectasis resolution, making landmark specification challenging. Following the quality assurance procedure, the final landmark sets contained a mean (SD) of 165 (25) landmarks, as points too difficult to match were removed and points were added to regions deficient in landmarks. For landmark sets in which changes were made, maximum and mean differences in landmark positions before and after quality assurance ranged between 8.7-81.5 mm and 0.3-9.6 mm, respectively. CONCLUSIONS: An effective method for improving the accuracy of landmark correspondence was presented. This quality assurance approach enables more accurate evaluation of DIR for lung parenchyma in clinical image pairs in the absence of a ground truth deformation and may be applicable to other feature-rich anatomical sites.

Laboratory alerts to guide early intensive care team review in surgical patients: A feasibility, safety, and efficacy pilot randomized controlled trial.

AIM: Common blood tests can help identify patients at risk of death, unplanned intensive care unit (ICU) admission, or rapid response team (RRT) call. We aimed to test whether early ICU-team review triggered by such laboratory tests (lab alert) is feasible, safe, and can alter physiological variables, clinical management, and clinical outcomes. METHODS: In prospective pilot randomized controlled trial in surgical wards of a tertiary hospital, we studied patients admitted for >24 h. We applied a previously validated risk assessment tool to each set of common laboratory tests to identify patients at risk and generate a "lab-alert". We randomly allocated such lab-alert patients to receive early ICU-team review (intervention) or usual care (control). RESULTS: We studied 205 patients (males 54.1%; average age 79 years; 103 randomized to intervention and 102 to usual care). Intervention patients were more likely to trigger RRT activation during their first lab-alert (10.7 vs. 2.0%; P < 0.001) but less likely to receive an allied health referral (18.0% vs. 24.5%; p = 0.007). They were less likely to trigger RRT activation in the 24-h before subsequent alerts (18.4 vs. 22.4%; p = 0.008) and less likely to generate further alerts (204 vs. 320; p < 0.001), but more likely to receive a not for resuscitation or endotracheal intubation status in the 24-h before subsequent alerts (26.6 vs. 17.3%; p = 0.05). Mortality at 24 h was 1.9% for the intervention group vs. 2.9% in the control group (p = 0.63). Finally, overall mortality was 19.4% for intervention patients vs. 23.5% for control patients (p = 0.50). CONCLUSION: Among surgical patients, lab alerts identify patients with a high mortality. Lab alert-triggered interventions are associated with more first alert-associated RRT activations; more changes in resuscitation status toward a more conservative approach; fewer subsequent alert-associated RRT activations; fewer subsequent alerts, and decreased allied health interventions (ANZCTRN12615000146594).

CALIPER: A deformable image registration algorithm for large geometric changes during radiotherapy for locally advanced non-small cell lung cancer.

PURPOSE: Locally advanced non-small cell lung cancer (NSCLC) patients may experience dramatic changes in anatomy during radiotherapy and could benefit from adaptive radiotherapy (ART). Deformable image registration (DIR) is necessary to accurately accumulate dose during plan adaptation, but current algorithms perform poorly in the presence of large geometric changes, namely atelectasis resolution. The goal of this work was to develop a DIR framework, named Consistent Anatomy in Lung Parametric imagE Registration (CALIPER), to handle large geometric changes in the thorax. METHODS: Registrations were performed on pairs of baseline and mid-treatment CT datasets of NSCLC patients presenting with atelectasis at the start of treatment. Pairs were classified based on atelectasis volume change as either full, partial, or no resolution. The evaluated registration algorithms consisted of several combinations of a hybrid intensity- and feature-based similarity cost function to investigate the ability to simultaneously match healthy lung parenchyma and adjacent atelectasis. These components of the cost function included a mass-preserving intensity cost in the lung parenchyma, use of filters to enhance vascular structures in the lung parenchyma, manually delineated lung lobes as labels, and several intensity cost functions to model atelectasis change. Registration error was quantified with landmark-based target registration error and post-registration alignment of atelectatic lobes. RESULTS: The registrations using both lobe labels and vasculature enhancement in addition to intensity of the CT images were found to have the highest accuracy. Of these registrations, the mean (SD) of mean landmark error across patients was 2.50 (1.16) mm, 2.80 (0.70) mm, and 2.04 (0.13) mm for no change, partial resolution, and full atelectasis resolution, respectively. The mean (SD) atelectatic lobe Dice similarity coefficient was 0.91 (0.08), 0.90 (0.08), and 0.89 (0.04), respectively, for the same groups. Registration accuracy was comparable to healthy lung registrations of current state-of-the-art algorithms reported in literature. CONCLUSIONS: The CALIPER algorithm developed in this work achieves accurate image registration for challenging cases involving large geometric and topological changes in NSCLC patients, a requirement for enabling ART in this patient group.

Lung and Heart Dose Variability During Radiation Therapy of Non-Small Cell Lung Cancer.

PURPOSE: To investigate the hypothesis that positional and anatomic variations during radiation therapy induce changes in lung and heart volumes and associated radiation doses. METHODS AND MATERIALS: In this longitudinal investigation, variations in lung and heart volumes and standard dose parameters of mean lung dose, lung V20Gy, mean heart dose, and heart V40Gy were analyzed on weekly 4-dimensional CT scans of 15 lung cancer patients during conventionally fractionated radiochemotherapy. Tumor, individual lung lobes, and heart were delineated on the mid-ventilation phase of weekly 4-dimensional CT scans. Lung lobes and heart were also contoured on individual breathing phases of pre-, mid-, and end-of-treatment scans. Planning dose was transferred to consecutive scans via rigid registration. Volume and dose variations were assessed relative to the initial planning scan. RESULTS: Interfraction lung volume variability relative to week 0 was twice as large as tidal volume variability (8.0% ± 5.3% vs 4.0% ± 3.3%, P=.003). Interfraction lung volume variation ranged between 0.8% and 17.1% for individual patient means. Lower lung lobes had larger volume variability compared with upper lobes (13.5% ± 8.1% vs 7.0% ± 5.0%, P<.00001). Average mean lung dose variation was 0.5 Gy (range, 0.2-1.0 Gy for individual patient means) and average lung V20Gy variation 0.9% (range, 0.2%-1.6%). Average heart volume variation was 7.2% (range, 3.4%-12.6%). Average mean heart dose variation was 1.2 Gy (range, 0.1-3.0 Gy) and average heart V40Gy variation 1.4% (range, 0%-4.2%). CONCLUSIONS: Anatomic and positional variations during radiation therapy induce changes in radiation doses to lung and heart. Repeated lung and heart dose assessment will provide a better estimate of the actual delivered dose and will improve prediction models for normal tissue toxicity, if assessed in larger cohorts.

Clinically relevant investigation of flattening filter-free skin dose.

As flattening filter-free (FFF) photon beams become readily available for treat-ment delivery in techniques such as SBRT, thorough investigation of skin dose from FFF photon beams is necessary under clinically relevant conditions. Using a parallel-plate PTW Markus chamber placed in a custom water-equivalent phantom, surface-dose measurements were taken at 2 × 2, 3 × 3, 4 × 4, 6 × 6, 8 × 8, 10 × 10, 20 × 20, and 30 × 30 cm2 field sizes, at 80, 90, and 100 cm source-to-surface distances (SSDs), and with fields defined by jaws and multileaf collimator (MLC) using multiple beam energies (6X, 6XFFF, 10X, and 10XFFF). The same set of measurements was repeated with the chamber at a reference depth of 10cm. Each surface measurement was normalized by its corresponding reference depth measurement for analysis. The FFF surface doses at 100 cm SSD were higher than flattened surface doses by 45% at 2 × 2 cm2 to 13% at 20 × 20 cm2 for 6MV energy. These surface dose differences varied to a greater degree as energy increased, ranging from +63% at 2 × 2 cm2 to -2% at 20 × 20 cm2 for 10 MV. At small field sizes, higher energy increased FFF surface dose relative to flattened surface dose; while at larger field sizes, relative FFF surface dose was higher for lower energies. At both energies investigated, decreasing SSD caused a decrease in the ratios of FFF-to-flattened surface dose. Variability with SSD of FFF-to-flattened surface dose differences increased with field size and ranged from 0% to 6%. The field size at which FFF and flattened beams gave the same skin dose increased with decreasing beam energy. Surface dose was higher with MLC fields compared to jaw fields under most conditions, with the difference reaching its maximum at a field size between 4 × 4 cm2 and 6 × 6 cm2 for a given energy and SSD. This study conveyed the magnitude of surface dose in a clinically meaning-ful manner by reporting results normalized to 10 cm depth dose instead of depth of dose maximum.

Effect of atelectasis changes on tissue mass and dose during lung radiotherapy.

PURPOSE: To characterize mass and density changes of lung parenchyma in non-small cell lung cancer (NSCLC) patients following midtreatment resolution of atelectasis and to quantify the impact this large geometric change has on normal tissue dose. METHODS: Baseline and midtreatment CT images and contours were obtained for 18 NSCLC patients with atelectasis. Patients were classified based on atelectasis volume reduction between the two scans as having either full, partial, or no resolution. Relative mass and density changes from baseline to midtreatment were calculated based on voxel intensity and volume for each lung lobe. Patients also had clinical treatment plans available which were used to assess changes in normal tissue dose constraints from baseline to midtreatment. The midtreatment image was rigidly aligned with the baseline scan in two ways: (1) bony anatomy and (2) carina. Treatment parameters (beam apertures, weights, angles, monitor units, etc.) were transferred to each image. Then, dose was recalculated. Typical IMRT dose constraints were evaluated on all images, and the changes from baseline to each midtreatment image were investigated. RESULTS: Atelectatic lobes experienced mean (stdev) mass changes of -2.8% (36.6%), -24.4% (33.0%), and -9.2% (17.5%) and density changes of -66.0% (6.4%), -25.6% (13.6%), and -17.0% (21.1%) for full, partial, and no resolution, respectively. Means (stdev) of dose changes to spinal cord Dmax, esophagus Dmean, and lungs Dmean were 0.67 (2.99), 0.99 (2.69), and 0.50 Gy (2.05 Gy), respectively, for bone alignment and 0.14 (1.80), 0.77 (2.95), and 0.06 Gy (1.71 Gy) for carina alignment. Dose increases with bone alignment up to 10.93, 7.92, and 5.69 Gy were found for maximum spinal cord, mean esophagus, and mean lung doses, respectively, with carina alignment yielding similar values. 44% and 22% of patients had at least one metric change by at least 5 Gy (dose metrics) or 5% (volume metrics) for bone and carina alignments, respectively. Investigation of GTV coverage showed mean (stdev) changes in VRx, Dmax, and Dmin of -5.5% (13.5%), 2.5% (4.2%), and 0.8% (8.9%), respectively, for bone alignment with similar results for carina alignment. CONCLUSIONS: Resolution of atelectasis caused mass and density decreases, on average, and introduced substantial changes in normal tissue dose metrics in a subset of the patient cohort.