Design, construction, and dosimetry of 3D printed heterogeneous phantoms for synchrotron brain cancer radiation therapy quality assurance.

Objective.This study aims to design, manufacture, and test 3D printed quality assurance (QA) dosimetry phantoms for synchrotron brain cancer radiation therapy at the Australian synchrotron.Approach.Fabricated 3D printed phantoms from simple slab phantoms, a preclinical rat phantom, and an anthropomorphic head phantom were fabricated and characterized. Attenuation measurements of various polymers, ceramics and metals were acquired using synchrotron monochromatic micro-computed tomography (CT) imaging. Polylactic acid plus, VeroClear, Durable resin, and tricalcium phosphate were used in constructing the phantoms. Furthermore, 3D printed bone equivalent materials were compared relative to ICRU bone and hemihydrate plaster. Homogeneous and heterogeneous rat phantoms were designed and fabricated using tissue-equivalent materials. Geometric accuracy, CT imaging, and consistency were considered. Moreover, synchrotron broad-beam x-rays were delivered using a 3 Tesla superconducting multipole wiggler field for four sets of synchrotron radiation beam qualities. Dose measurements were acquired using a PinPoint ionization chamber and compared relative to a water phantom and a RMI457 Solid Water phantom. Experimental depth doses were compared relative to calculated doses using a Geant4 Monte Carlo simulation.Main results.Polylactic acid (PLA+) shows to have a good match with the attenuation coefficient of ICRU water, while both tricalcium phosphate and hydroxyapatite have good attenuation similarity with ICRU bone cortical. PLA+ material can be used as substitute to RMI457 slabs for reference dosimetry with a maximum difference of 1.84%. Percent depth dose measurement also shows that PLA+ has the best match with water and RMI457 within ±2.2% and ±1.6%, respectively. Overall, PLA+ phantoms match with RMI457 phantoms within ±3%.Significance and conclusion.The fabricated phantoms are excellent tissue equivalent equipment for synchrotron radiation dosimetry QA measurement. Both the rat and the anthropomorphic head phantoms are useful in synchrotron brain cancer radiotherapy dosimetry, experiments, and future clinical translation of synchrotron radiotherapy and imaging.

Characterization of selected additive manufacturing materials for synchrotron monochromatic imaging and broad-beam radiotherapy at the Australian synchrotron-imaging and medical beamline.

Objective.This study aims to characterize radiological properties of selected additive manufacturing (AM) materials utilizing both material extrusion and vat photopolymerization technologies. Monochromatic synchrotron x-ray images and synchrotron treatment beam dosimetry were acquired at the hutch 3B and 2B of the Australian Synchrotron-Imaging and Medical Beamline.Approach.Eight energies from 30 keV up to 65 keV were used to acquire the attenuation coefficients of the AM materials. Comparison of theoretical, and experimental attenuation data of AM materials and standard solid water for MV linac was performed. Broad-beam dosimetry experiment through attenuated dose measurement and a Geant4 Monte Carlo simulation were done for the studied materials to investigate its attenuation properties specific for a 4 tesla wiggler field with varying synchrotron radiation beam qualities.Main results.Polylactic acid (PLA) plus matches attenuation coefficients of both soft tissue and brain tissue, while acrylonitrile butadiene styrene, Acrylonitrile styrene acrylate, and Draft resin have close equivalence to adipose tissue. Lastly, PLA, co-polyester plus, thermoplastic polyurethane, and White resins are promising substitute materials for breast tissue. For broad-beam experiment and simulation, many of the studied materials were able to simulate RMI457 Solid Water and bolus within ±10% for the three synchrotron beam qualities. These results are useful in fabricating phantoms for synchrotron and other related medical radiation applications such as orthovoltage treatments.Significance and conclusion.These 3D printing materials were studied as potential substitutes for selected tissues such as breast tissue, adipose tissue, soft-tissue, and brain tissue useful in fabricating 3D printed phantoms for synchrotron imaging, therapy, and orthovoltage applications. Fabricating customizable heterogeneous anthropomorphic phantoms (e.g. breast, head, thorax) and pre-clinical animal phantoms (e.g. rodents, canine) for synchrotron imaging and radiotherapy using AM can be done based on the results of this study.

Superficial parasternal intercostal plane blocks in cardiac surgery: a systematic review and meta-analysis.

PURPOSE: Traditional multimodal analgesic strategies have several contraindications in cardiac surgery patients, forcing clinicians to use alternative options. Superficial parasternal intercostal plane blocks, anesthetizing the anterior cutaneous branches of the thoracic intercostal nerves, are being explored as a straightforward method to treat pain after sternotomy. We sought to evaluate the literature on the effects of superficial parasternal blocks on pain control after cardiac surgery. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). We searched MEDLINE, Embase, CENTRAL, and Web of Science databases for RCTs evaluating superficial parasternal intercostal plane blocks in adult patients undergoing cardiac surgery via midline sternotomy published from inception to 11 March 2022. The prespecified primary outcome was opioid consumption at 12 hr. The risk of bias was assessed with the Cochrane Collaboration Risk of Bias Tool, and the quality of evidence was evaluated using the grading of recommendations, assessments, development, and evaluations. Outcomes were analyzed with a random-effects model. All subgroups were prespecified. RESULTS: We reviewed 1,275 citations. Eleven RCTs, comprising 756 patients, fulfilled the inclusion criteria. Only one study reported the prespecified primary outcome, precluding the possibility of meta-analysis. This study reported a reduction in opioid consumption (-11.2 mg iv morphine equivalents; 95% confidence interval [CI], -8.2 to -14.1) There was a reduction in opioid consumption at 24 hr (-7.2 mg iv morphine equivalents; 95% CI, -5.6 to -8.7; five trials; 436 participants; moderate certainty evidence). All five studies measuring complications reported that none were detected, which included a sample of 196 blocks. CONCLUSION: The literature suggests a potential benefit of using superficial parasternal blocks to improve acute postoperative pain control after cardiac surgery via midline sternotomy. Future studies specifying dosing regimens and adjuncts are required. STUDY REGISTRATION: PROSPERO (CRD42022306914); first submitted 22 March 2022.

RéSUMé: OBJECTIF: Il existe plusieurs contre-indications aux stratégies analgésiques multimodales traditionnelles chez la patientèle de chirurgie cardiaque, ce qui oblige les clinicien·nes à se tourner vers d'autres options. Les blocs des plans intercostaux parasternaux superficiels, anesthésiant les branches cutanées antérieures des nerfs intercostaux thoraciques, sont l'une des méthodes simples actuellement explorées pour traiter la douleur après une sternotomie. Nous avons cherché à évaluer la littérature sur les effets des blocs parasternaux superficiels sur le contrôle de la douleur après une chirurgie cardiaque. MéTHODE: Nous avons réalisé une revue systématique et une méta-analyse des études randomisées contrôlées (ERC). Nous avons fait des recherches dans les bases de données MEDLINE, Embase, CENTRAL et Web of Science pour en tirer les ERC évaluant les blocs des plans intercostaux parasternaux superficiels chez les patient·es adultes bénéficiant d'une chirurgie cardiaque par sternotomie médiane publiées depuis leur création jusqu'au 11 mars 2022. Le critère d'évaluation principal préspécifié était la consommation d'opioïdes à 12 heures. Le risque de biais a été évalué à l'aide de l'outil Cochrane Collaboration Risk of Bias, et la qualité des données probantes à l'aide de l'outil GRADE. Les résultats ont été analysés à l'aide d'un modèle à effets aléatoires. Tous les sous-groupes étaient préspécifiés. RéSULTATS: Nous avons examiné 1275 citations. Onze ERC, comprenant 756 patient·es, remplissaient les critères d'inclusion. Une seule étude a rapporté le critère d'évaluation principal préspécifié, ce qui a exclu la possibilité d'une méta-analyse. Cette étude a rapporté une réduction de la consommation d'opioïdes (−11,2 mg équivalents de morphine iv; intervalle de confiance [IC] à 95 %, −8,2 à −14,1). Il y a eu une réduction de la consommation d'opioïdes à 24 heures (−7,2 mg équivalents de morphine iv; IC 95 %, −5,6 à −8,7; cinq études; 436 participant·es; données probantes de certitude modérée). Les cinq études mesurant les complications ont rapporté qu'aucune complication n'avait été détectée, en incluant un échantillon de 196 blocs. CONCLUSION: La littérature suggère un avantage potentiel de l'utilisation de blocs parasternaux superficiels pour améliorer le contrôle de la douleur postopératoire aiguë après une chirurgie cardiaque par sternotomie médiane. Des études futures précisant les schémas posologiques et les adjuvants sont nécessaires. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42022306914); soumis pour la première fois le 22 mars 2022.

Benzodiazepine-Free Cardiac Anesthesia for Reduction of Postoperative Delirium (B-Free): A Protocol for a Multi-centre Randomized Cluster Crossover Trial.

Delirium is common after cardiac surgery and is associated with adverse outcomes. Administration of benzodiazepines before and after cardiac surgery is associated with delirium; guidelines recommend minimizing their use. Benzodiazepine administration during cardiac surgery remains common because of its recognized benefits. The Benzodiazepine-Free Cardiac Anesthesia for Reduction of Postoperative Delirium (B-Free) trial is a randomized cluster crossover trial evaluating whether an institutional policy of restricting intraoperative benzodiazepine administration (ie, ≥ 90% of patients do not receive benzodiazepines during cardiac surgery), as compared with a policy of liberal intraoperative benzodiazepine administration (ie, ≥ 90% of patients receive ≥ 0.03 mg/kg midazolam equivalent), reduces delirium. Hospitals performing ≥ 250 cardiac surgeries a year are included if their cardiac anesthesia group agrees to apply both benzodiazepine policies per their randomization, and patients are assessed for postoperative delirium every 12 hours in routine clinical care. Hospitals apply the restricted or liberal benzodiazepine policy during 12 to 18 crossover periods of 4 weeks each. Randomization for all periods takes place in advance of site startup; sites are notified of their allocated policy during the last week of each crossover period. Policies are applied to all patients undergoing cardiac surgery during the trial period. The primary outcome is the incidence of delirium at up to 72 hours after surgery. The B-Free trial will enroll ≥ 18,000 patients undergoing cardiac surgery at 20 hospitals across North America. Delirium is common after cardiac surgery, and benzodiazepines are associated with the occurrence of delirium. The B-Free trial will determine whether an institutional policy restricting the administration of benzodiazepines during cardiac surgery reduces the incidence of delirium after cardiac surgery. Clinicaltrials.gov registration number: NCT03928236 (First registered April 26, 2019).

L'état confusionnel est fréquent après une chirurgie cardiaque et il est associé à des complications. L'administration de benzodiazépines avant et après une chirurgie cardiaque est associée à l'état confusionnel; dans les lignes directrices, on recommande de réduire leur utilisation au minimum. L'administration de benzodiazépines pendant une chirurgie cardiaque demeure fréquente, en raison des leurs bienfaits reconnus. L'essai B-Free (Benzodiazepine-Free Cardiac Anesthesia for Reduction of Postoperative Delirium ou l'anesthésie sans benzodiazépine en contexte de chirurgie cardiaque pour la réduction de l'état confusionnel postopératoire) est un essai à répartition aléatoire par grappes et avec permutation, visant à évaluer si une politique institutionnelle de restriction de l'administration peropératoire de benzodiazépines (c.-à-d. que ≥ 90 % des patients ne reçoivent pas de benzodiazépines durant une chirurgie cardiaque) réduit l'état confusionnel, comparativement à une politique d'administration peropératoire libérale de benzodiazépines (c.-à-d. que ≥ 90 % des patients reçoivent ≥ 0,03 mg/kg d'équivalent du midazolam). Des hôpitaux effectuant au moins 250 chirurgies cardiaques par année sont inclus dans l'essai si leurs équipes d'anesthésie cardiaque acceptent d'appliquer les deux politiques relatives aux benzodiazépines en vertu de la répartition aléatoire et si les patients sont évalués toutes les 12 heures, en ce qui a trait à l'état confusionnel postopératoire, dans le cadre des soins cliniques habituels. Les hôpitaux mettent en œuvre la politique d'administration restreinte ou libérale de benzodiazépines durant 12 à 18 périodes de permutation de 4 semaines chacune. La répartition aléatoire de l'ensemble des périodes a lieu avant le début de l'essai à l'hôpital; les établissements sont avisés de la politique qui leur est attribuée au cours de la dernière semaine de chaque période de permutation. Les politiques sont appliquées à tous les patients qui subissent une chirurgie cardiaque durant la période de l'essai. Le critère d'évaluation principal est l'incidence de l'état confusionnel dans les 72 heures suivant l'intervention chirurgicale. L'étude B-Free inclura au moins 18 000 patients qui subiront une chirurgie cardiaque dans 20 hôpitaux en l'Amérique du Nord. L'état confusionnel est fréquent après une chirurgie cardiaque, et les benzodiazépines sont associées à la survenue de l'état confusionnel. L'essai B-Free permettra de déterminer si une politique institutionnelle de restriction de l'administration de benzodiazépines durant une chirurgie cardiaque réduit l'incidence de l'état confusionnel après une telle chirurgie.Clinicaltrials.gov registration number: NCT03928236 (First registered April 26, 2019).

The design and characterization of a novel dynamic collimator system for synchrotron radiotherapy applications.

BACKGROUND: Novel synchrotron radiotherapy techniques are currently limited to using prefabricated beam-limiting blocks for field definition. For large experiments, a single square tungsten block is often used for every treatment since conformal blocks are both patient and field specific, and require long lead times for fabrication. Future synchrotron radiotherapy treatments would benefit from a dynamic collimator system. PURPOSE: We developed and tested a novel collimator design for use on the Imaging and Medical Beamline (IMBL) at the ANSTO Australian Synchrotron. METHODS: The maximum usable beam size on IMBL is 50-mm wide by 3-mm tall. Given the beam shape, targets must be vertically scanned through the synchrotron beam to cover the target volume. To shape the beam, a novel collimator design was developed, consisting of two semi-circular leaves made from 4-mm thick tungsten sheets, with each leaf capable of both vertical and horizontal movement. A software model was created to optimize motor trajectories and generate deliverable treatment fields. A series of geometric field shapes and clinical target volumes were delivered using the collimator and imaged with a digital imaging detector. Four similarity metrics (volumetric similarity, DICE, and the average and maximum Hausdorff distances) were used to measure differences between the input and planned fields, and the planned and delivered fields. RESULTS: Differences between input and planned fields increased with delivery speed, and were worse for rectangular and square fields compared to circular fields. However, the differences between planned and delivered fields were small, where the maximum average deviation between the fields was 0.25 mm (one pixel). Field repeatability was consistent with no difference (σ = 0 for all metrics) observed in consecutively delivered fields. CONCLUSIONS: We have successfully built and demonstrated a novel collimator for synchrotron radiotherapy applications on IMBL. Several design improvements have been highlighted and will be addressed in future revisions the collimator. However, in its current state, the collimator enables dynamically delivered conformal treatment fields to be utilized on IMBL, and is ready to support the forthcoming canine treatments on IMBL.

A Novel Anthropomorphic Phantom Composed of Tissue-Equivalent Materials for Use in Experimental Radiotherapy: Design, Dosimetry and Biological Pilot Study.

The production of anthropomorphic phantoms generated from tissue-equivalent materials is challenging but offers an excellent copy of the typical environment encountered in typical patients. High-quality dosimetry measurements and the correlation of the measured dose with the biological effects elicited by it are a prerequisite in preparation of clinical trials with novel radiotherapy approaches. We designed and produced a partial upper arm phantom from tissue-equivalent materials for use in experimental high-dose-rate radiotherapy. The phantom was compared to original patient data using density values and Hounsfield units obtained from CT scans. Dose simulations were conducted for broad-beam irradiation and microbeam radiotherapy (MRT) and compared to values measured in a synchrotron radiation experiment. Finally, we validated the phantom in a pilot experiment with human primary melanoma cells.

Accurate and Fast Deep Learning Dose Prediction for a Preclinical Microbeam Radiation Therapy Study Using Low-Statistics Monte Carlo Simulations.

Microbeam radiation therapy (MRT) utilizes coplanar synchrotron radiation beamlets and is a proposed treatment approach for several tumor diagnoses that currently have poor clinical treatment outcomes, such as gliosarcomas. Monte Carlo (MC) simulations are one of the most used methods at the Imaging and Medical Beamline, Australian Synchrotron to calculate the dose in MRT preclinical studies. The steep dose gradients associated with the 50µm-wide coplanar beamlets present a significant challenge for precise MC simulation of the dose deposition of an MRT irradiation treatment field in a short time frame. The long computation times inhibit the ability to perform dose optimization in treatment planning or apply online image-adaptive radiotherapy techniques to MRT. Much research has been conducted on fast dose estimation methods for clinically available treatments. However, such methods, including GPU Monte Carlo implementations and machine learning (ML) models, are unavailable for novel and emerging cancer radiotherapy options such as MRT. In this work, the successful application of a fast and accurate ML dose prediction model for a preclinical MRT rodent study is presented for the first time. The ML model predicts the peak doses in the path of the microbeams and the valley doses between them, delivered to the tumor target in rat patients. A CT imaging dataset is used to generate digital phantoms for each patient. Augmented variations of the digital phantoms are used to simulate with Geant4 the energy depositions of an MRT beam inside the phantoms with 15% (high-noise) and 2% (low-noise) statistical uncertainty. The high-noise MC simulation data are used to train the ML model to predict the energy depositions in the digital phantoms. The low-noise MC simulations data are used to test the predictive power of the ML model. The predictions of the ML model show an agreement within 3% with low-noise MC simulations for at least 77.6% of all predicted voxels (at least 95.9% of voxels containing tumor) in the case of the valley dose prediction and for at least 93.9% of all predicted voxels (100.0% of voxels containing tumor) in the case of the peak dose prediction. The successful use of high-noise MC simulations for the training, which are much faster to produce, accelerates the production of the training data of the ML model and encourages transfer of the ML model to different treatment modalities for other future applications in novel radiation cancer therapies.

Effect of High-Dose Selenium on Postoperative Organ Dysfunction and Mortality in Cardiac Surgery Patients: The SUSTAIN CSX Randomized Clinical Trial.

Importance: Selenium contributes to antioxidative, anti-inflammatory, and immunomodulatory pathways, which may improve outcomes in patients at high risk of organ dysfunctions after cardiac surgery. Objective: To assess the ability of high-dose intravenous sodium selenite treatment to reduce postoperative organ dysfunction and mortality in cardiac surgery patients. Design, Setting, and Participants: This multicenter, randomized, double-blind, placebo-controlled trial took place at 23 sites in Germany and Canada from January 2015 to January 2021. Adult cardiac surgery patients with a European System for Cardiac Operative Risk Evaluation II score-predicted mortality of 5% or more or planned combined surgical procedures were randomized. Interventions: Patients were randomly assigned (1:1) by a web-based system to receive either perioperative intravenous high-dose selenium supplementation of 2000 µg/L of sodium selenite prior to cardiopulmonary bypass, 2000 µg/L immediately postoperatively, and 1000 µg/L each day in intensive care for a maximum of 10 days or placebo. Main Outcomes and Measures: The primary end point was a composite of the numbers of days alive and free from organ dysfunction during the first 30 days following cardiac surgery. Results: A total of 1416 adult cardiac surgery patients were analyzed (mean [SD] age, 68.2 [10.4] years; 1043 [74.8%] male). The median (IQR) predicted 30-day mortality by European System for Cardiac Operative Risk Evaluation II score was 8.7% (5.6%-14.9%), and most patients had combined coronary revascularization and valvular procedures. Selenium did not increase the number of persistent organ dysfunction-free and alive days over the first 30 postoperative days (median [IQR], 29 [28-30] vs 29 [28-30]; P = .45). The 30-day mortality rates were 4.2% in the selenium and 5.0% in the placebo group (odds ratio, 0.82; 95% CI, 0.50-1.36; P = .44). Safety outcomes did not differ between the groups. Conclusions and Relevance: In high-risk cardiac surgery patients, perioperative administration of high-dose intravenous sodium selenite did not reduce morbidity or mortality. The present data do not support the routine perioperative use of selenium for patients undergoing cardiac surgery. Trial Registration: ClinicalTrials.gov Identifier: NCT02002247.

Evaluation of silicon strip detectors in transmission mode for online beam monitoring in microbeam radiation therapy at the Australian Synchrotron.

Successful transition of synchrotron-based microbeam radiation therapy (MRT) from pre-clinical animal studies to human trials is dependent upon ensuring that there are sufficient and adequate measures in place for quality assurance purposes. Transmission detectors provide researchers and clinicians with a real-time quality assurance and beam-monitoring instrument to ensure safe and accurate dose delivery. In this work, the effect of transmission detectors of different thicknesses (10 and 375 µm) upon the photon energy spectra and dose deposition of spatially fractionated synchrotron radiation is quantified experimentally and by means of a dedicated Geant4 simulation study. The simulation and experimental results confirm that the presence of the 375 µm thick transmission detector results in an approximately 1-6% decrease in broad-beam and microbeam peak dose. The capability to account for the reduction in dose and change to the peak-to-valley dose ratio justifies the use of transmission detectors as thick as 375 µm in MRT provided that treatment planning systems are able to account for their presence. The simulation and experimental results confirm that the presence of the 10 µm thick transmission detector shows a negligible impact (<0.5%) on the photon energy spectra, dose delivery and microbeam structure for both broad-beam and microbeam cases. Whilst the use of 375 µm thick detectors would certainly be appropriate, based upon the idea of best practice the authors recommend that 10 µm thick transmission detectors of this sort be utilized as a real-time quality assurance and beam-monitoring tool during MRT.

Iron supplementation for patients undergoing cardiac surgery: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: Iron supplementation has been evaluated in several randomized controlled trials (RCTs) for its potential to increase baseline hemoglobin and decrease red blood cell transfusion during cardiac surgery. This study's main objective was to evaluate the current evidence for iron administration in cardiac surgery patients. METHODS: We searched MEDLINE, EMBASE, CENTRAL, Web of Science databases, and Google Scholar from inception to 19 November 2020 for RCTs evaluating perioperative iron administration in adult patients undergoing cardiac surgery. The RCTs were assessed using a risk of bias assessment and the quality of evidence was assessed using the grading of recommendations, assessments, development, and evaluations. RESULTS: We reviewed 1,767 citations, and five studies (n = 554) met the inclusion criteria. The use of iron showed no statistical difference in incidence of transfusion (risk ratio, 0.86; 95% confidence interval, 0.65 to 1.13). Trial sequential analysis suggested an optimal information size of 1,132 participants, which the accrued information size did not reach. CONCLUSION: The current literature does not support or refute the routine use of iron therapy in cardiac surgery patients. TRIAL REGISTRATION: PROSPERO (CRD42020161927); registered 19 December 2019.

RéSUMé: OBJECTIF: La supplémentation en fer a été évaluée dans plusieurs études randomisées contrôlées (ERC) pour son potentiel à augmenter l'hémoglobine de base et à diminuer la transfusion d'érythrocytes pendant la chirurgie cardiaque. L'objectif principal de cette étude était d'évaluer les données probantes actuelles soutenant l'administration de fer chez les patients de chirurgie cardiaque. MéTHODE: Nous avons effectué des recherches dans les bases de données MEDLINE, EMBASE, CENTRAL, Web of Science et Google Scholar de leur création jusqu'au 19 novembre 2020 pour en extraire les ERC évaluant l'administration périopératoire de fer chez les patients adultes bénéficiant d'une chirurgie cardiaque. Les ERC ont été évaluées à l'aide d'une évaluation du risque de biais et la qualité des données probantes a été évaluée à l'aide du système de notation GRADE. RéSULTATS: Nous avons examiné 1767 citations et cinq études (n = 554) répondaient aux critères d'inclusion. L'administration de fer n'a montré aucune différence statistique dans l'incidence des transfusions (risque relatif, 0,86; intervalle de confiance à 95 %, 0,65 à 1,13). Selon l'analyse séquentielle des études, la taille d'information optimale serait de 1132 participants, une taille que l'information accumulée n'a pas atteint. CONCLUSION: La littérature actuelle ne soutient ni ne réfute l'utilisation systématique d'une thérapie à base de fer chez les patients de chirurgie cardiaque. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42020161927); enregistrée le 19 décembre 2019.

Iron supplementation for patients undergoing cardiac surgery: a protocol for a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Iron administration has been evaluated in several randomized controlled trials for the potential of increasing baseline hemoglobin values and decreasing the incidence of red blood cell transfusion during cardiac surgery. We describe the protocol for a study aiming to evaluate the efficacy and safety of perioperative iron administration in patients undergoing cardiac surgery. METHODS: We will search MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and the Web of Science, from inception to Nov. 19, 2020, for randomized controlled trials in any language evaluating the perioperative administration of iron in adult patients undergoing cardiac surgery; we will also include the first 50 results from Google Scholar. The primary outcome will be the incidence of red blood cell transfusion from the study intervention time until 8 weeks postoperatively. The secondary outcomes will be the number of red blood cell units transfused; change in ferritin level, reticulocyte count and hemoglobin concentration after iron administration; and adverse events. We will assess the risk of bias with the Cochrane Collaboration Risk of Bias Tool, and will analyze the primary and secondary outcomes using a random-effects model. INTERPRETATION: This study will summarize the current evidence about perioperative iron administration in patients undergoing cardiac surgery, help determine whether this intervention should be included in enhanced-recovery protocols, and shape future research if needed. The final manuscript will be submitted to a peer-reviewed journal. TRIAL REGISTRATION: PROSPERO no. CRD42020161927.

Toward personalized synchrotron microbeam radiation therapy.

Synchrotron facilities produce ultra-high dose rate X-rays that can be used for selective cancer treatment when combined with micron-sized beams. Synchrotron microbeam radiation therapy (MRT) has been shown to inhibit cancer growth in small animals, whilst preserving healthy tissue function. However, the underlying mechanisms that produce successful MRT outcomes are not well understood, either in vitro or in vivo. This study provides new insights into the relationships between dosimetry, radiation transport simulations, in vitro cell response, and pre-clinical brain cancer survival using intracerebral gliosarcoma (9LGS) bearing rats. As part of this ground-breaking research, a new image-guided MRT technique was implemented for accurate tumor targeting combined with a pioneering assessment of tumor dose-coverage; an essential parameter for clinical radiotherapy. Based on the results of our study, we can now (for the first time) present clear and reproducible relationships between the in vitro cell response, tumor dose-volume coverage and survival post MRT irradiation of an aggressive and radioresistant brain cancer in a rodent model. Our innovative and interdisciplinary approach is illustrated by the results of the first long-term MRT pre-clinical trial in Australia. Implementing personalized synchrotron MRT for brain cancer treatment will advance this international research effort towards clinical trials.

Intraoperative Ketamine for Analgesia Post-Coronary Artery Bypass Surgery: A Randomized, Controlled, Double-Blind Clinical Trial.

OBJECTIVES: To determine whether the administration of ketamine during coronary artery bypass grafting (CABG) surgery leads to a reduction in the quantity of opioids required over the first 48 hours after surgery. DESIGN: Randomized, controlled, double-blind clinical trial. SETTING: Single university academic center. PARTICIPANTS: Patients undergoing CABG surgery with a normal left ventricular ejection fraction. INTERVENTIONS: Ketamine administered intravenously as a bolus dose of 0.5 mg/kg before skin incision, followed by an infusion of 0.5 mg/kg/h until the end of surgery. MEASUREMENTS AND MAIN RESULTS: One hundred eighty-three patients were screened, and 80 patients were randomized. Baseline characteristics were similar between the 2 groups. The intervention group received 53.6 mg (95% confidence interval [CI] 47.1-60.1 mg) of morphine equivalents in the first 48 hours after surgery, whereas the placebo group received 55.7 mg (95% CI 48.4-63.1 mg) over the same time period (p = 0.66). No significant difference was noted in morphine equivalents over the first 6, 12, or 24 hours postoperatively or in maximum, minimum, or average pain scores on postoperative days 1 or 2. CONCLUSIONS: The administration of ketamine during CABG surgery did not result in reduced opioid consumption or pain scores postoperatively.

Validation of a Monte Carlo simulation for Microbeam Radiation Therapy on the Imaging and Medical Beamline at the Australian Synchrotron.

Microbeam Radiation Therapy (MRT) is an emerging cancer treatment modality characterised by the use of high-intensity synchrotron-generated x-rays, spatially fractionated by a multi-slit collimator (MSC), to ablate target tumours. The implementation of an accurate treatment planning system, coupled with simulation tools that allow for independent verification of calculated dose distributions are required to ensure optimal treatment outcomes via reliable dose delivery. In this article we present data from the first Geant4 Monte Carlo radiation transport model of the Imaging and Medical Beamline at the Australian Synchrotron. We have developed the model for use as an independent verification tool for experiments in one of three MRT delivery rooms and therefore compare simulation results with equivalent experimental data. The normalised x-ray spectra produced by the Geant4 model and a previously validated analytical model, SPEC, showed very good agreement using wiggler magnetic field strengths of 2 and 3 T. However, the validity of absolute photon flux at the plane of the Phase Space File (PSF) for a fixed number of simulated electrons was unable to be established. This work shows a possible limitation of the G4SynchrotronRadiation process to model synchrotron radiation when using a variable magnetic field. To account for this limitation, experimentally derived normalisation factors for each wiggler field strength determined under reference conditions were implemented. Experimentally measured broadbeam and microbeam dose distributions within a Gammex RMI457 Solid Water® phantom were compared to simulated distributions generated by the Geant4 model. Simulated and measured broadbeam dose distributions agreed within 3% for all investigated configurations and measured depths. Agreement between the simulated and measured microbeam dose distributions agreed within 5% for all investigated configurations and measured depths.

High spatial resolution scintillator dosimetry of synchrotron microbeams.

Microbeam radiation therapy is a novel pre-clinical external beam therapy that uses high-brilliance synchrotron X-rays to deliver the necessary high dose rates. The unique conditions of high dose rate and high spatial fractionation demand a new class of detector to experimentally measure important beam quality parameters. Here we demonstrate the highest spatial resolution plastic scintillator fibre-optic dosimeter found in the literature to date and tested it on the Imaging and Medical Beam-Line at the Australian Synchrotron in a X-ray beam where the irradiation dose rate was 4435 Gy/s. With a one-dimensional spatial resolution of 10 µm the detector is able to resolve the individual microbeams (53.7 ± 0.4 µm wide), and measure the peak-to-valley dose ratio to be 55 ± 17. We also investigate the role of radioluminescence in the optical fibre used to transport the scintillation photons, and conclude that it creates a significant contribution to the total light detected.

Prospective External Validation of Three Preoperative Risk Scores for Prediction of New Onset Atrial Fibrillation After Cardiac Surgery.

BACKGROUND: Postoperative atrial fibrillation (POAF) is associated with early and late morbidity and mortality of cardiac surgical patients. Prophylactic treatment of atrial fibrillation (AF) has been recommended to improve outcome in cardiac surgical patients at high risk of developing POAF. Reliable models for prediction of POAF are needed to achieve that goal. This study attempted to externally validate 3 risk models proposed for preoperative prediction of POAF in cardiac surgical patients: the POAF score, the CHA2DS2-VASc score, and the Atrial Fibrillation Risk Index. METHODS: This was a prospective cohort study of 1416 adult patients who underwent nonemergent coronary artery bypass graft and/or valve surgery in a single cardiac surgical center between February 2014 and September 2015. A risk score for each of the 3 prediction models was calculated in each patient. All patients were followed for up to 2 weeks, or until hospital discharge, to observe the primary outcome of new onset AF requiring treatment. Discrimination was assessed using receiver operating characteristic curves. Calibration was assessed using the Pearson χ goodness-of-fit test and calibration plots. Utility of the score to implement AF prophylaxis based on the risk of POAF, in comparison to strategies of treating all patients, or not treating any patients, was assessed via a net benefit analysis. RESULTS: Of the 1416 patients included in this study, 478 had the primary outcome (33.8%). The areas under the receiver operating characteristic curve for prediction of POAF in the population subsets for which the scores were validated were as follows: 0.651 (95% confidence interval [CI], 0.621-0.681) for the POAF score, 0.593 (95% CI, 0.557-0.629) for the CHA2DS2-VASc score (P < .001 versus POAF score, P < .222 versus Atrial Fibrillation Risk Index), and 0.563 (95% CI, 0.522-0.604) for the Atrial Fibrillation Risk Index (P < .001 versus POAF score). The calibration analysis showed that the predictive models had a poor fit between the observed and expected rates of POAF. Net benefit analysis showed that AF preventive strategies based on these scores, and targeting patients with moderate or high risk of POAF, improve decision-making in comparison to preventive strategies of treating all patients. CONCLUSIONS: The 3 prediction scores evaluated in this study have limited ability to predict POAF in cardiac surgical patients. Despite this, they may be useful in preventive strategies targeting patients with moderate or high risk of PAOF in comparison with preventive strategies applied to all patients.

X-ray microbeam measurements with a high resolution scintillator fibre-optic dosimeter.

Synchrotron microbeam radiation therapy is a novel external beam therapy under investigation, that uses highly brilliant synchrotron x-rays in microbeams 50 µm width, with separation of 400 µm, as implemented here. Due to the fine spatial fractionation dosimetry of these beams is a challenging and complicated problem. In this proof-of-concept work, we present a fibre optic dosimeter that uses plastic scintillator as the radiation conversion material. We claim an ideal one-dimensional resolution of 50 µm. Using plastic scintillator and fibre optic makes this dosimeter water-equivalent, a very desirable dosimetric property. The dosimeter was tested at the Australian Synchrotron, on the Imaging and Medical Beam-Line. The individual microbeams were able to be resolved and the peak-to-valley dose ratio and the full width at half maximum of the microbeams was measured. These results are compared to a semiconductor strip detector of the same spatial resolution. A percent depth dose was measured and compared to data acquired by an ionisation chamber. The results presented demonstrate significant steps towards the development of an optical dosimeter with the potential to be applied in quality assurance of microbeam radiation therapy, which is vital if clinical trials are to be performed on human patients.