A vanguard randomised feasibility trial comparing three regimens of peri-operative oxygen therapy on recovery after major surgery.

International recommendations encourage liberal administration of oxygen to patients having surgery under general anaesthesia, ostensibly to reduce surgical site infection. However, the optimal oxygen regimen to minimise postoperative complications and enhance recovery from surgery remains uncertain. The hospital operating theatre randomised oxygen (HOT-ROX) trial is a multicentre, patient- and assessor-blinded, parallel-group, randomised clinical trial designed to assess the effect of a restricted, standard care, or liberal peri-operative oxygen therapy regimen on days alive and at home after surgery in adults undergoing prolonged non-cardiac surgery under general anaesthesia. Here, we report the findings of the internal vanguard feasibility phase of the trial undertaken in four large metropolitan hospitals in Australia and New Zealand that included the first 210 patients of a planned overall 2640 trial sample, with eight pre-specified endpoints evaluating protocol implementation and safety. We screened a total of 956 participants between 1 September 2019 and 26 January 2021, with data from 210 participants included in the analysis. Median (IQR [range]) time-weighted average intra-operative Fi O2 was 0.30 (0.26-0.35 [0.20-0.59]) and 0.47 (0.44-0.51 [0.37-0.68]) for restricted and standard care, respectively (mean difference (95%CI) 0.17 (0.14-0.20), p < 0.001). Median time-weighted average intra-operative Fi O2 was 0.83 (0.80-0.85 [0.70-0.91]) for liberal oxygen therapy (mean difference (95%CI) compared with standard care 0.36 (0.33-0.39), p < 0.001). All feasibility endpoints were met. There were no significant patient adverse events. These data support the feasibility of proceeding with the HOT-ROX trial without major protocol modifications.

MALDI-TOF MS for identification of porcine Brachyspira species.

UNLABELLED: The aim of this study consisted in evaluating MALDI-TOF MS as a tool for the identification of the genus Brachyspira (B.) and its relevant species for the pig industry. First, a database was created with 30 control strains, and superspectra for five different porcine Brachyspira species were calculated. In a second step, 67 field isolates were investigated using MALDI-TOF MS, and results were compared to those obtained using nox gene-based RFLP (reference method) and biochemical tests. Among the 67 field isolates, five different Brachyspira species were detected using nox gene-based RFLP analysis. MALDI-TOF MS analysis correctly assigned all isolates to the genus Brachyspira and identified all isolates from B. hyodysenteriae (29/29), B. pilosicoli (11/11), B. intermedia (4/4) and B. innocens (11/11). In terms of B. murdochii, MALDI-TOF MS assigned one of 12 isolates ambiguously as B. innocens/B. murdochii. The results of this study indicate that MALDI-TOF MS facilitates the diagnosis of swine dysentery and porcine intestinal spirochaetosis. SIGNIFICANCE AND IMPACT OF THE STUDY: Current methods for the discrimination of pathogenic Brachyspira hyodysenteriae and Brachyspira pilosicoli from Brachyspira species with low pathogenic potential have proven to be laborious and time-consuming and are therefore not suitable for routine diagnostics. This study describes the evaluation of MALDI-TOF MS for the identification of different porcine Brachyspira species in routine diagnostic laboratories. The results suggest that MALDI-TOF MS is an effective method for the identification of porcine Brachyspira spp. and accelerates diagnosis of swine dysentery and porcine intestinal spirochaetosis.

Auto-commissioning of a Monte Carlo electron beam model with application to photon MLC shaped electron fields.

Objective.Presently electron beam treatments are delivered using dedicated applicators. An alternative is the usage of the already installed photon multileaf collimator (pMLC) enabling efficient electron treatments. Currently, the commissioning of beam models is a manual and time-consuming process. In this work an auto-commissioning procedure for the Monte Carlo (MC) beam model part representing the beam above the pMLC is developed for TrueBeam systems with electron energies from 6 to 22 MeV.Approach.The analytical part of the electron beam model includes a main source representing the primary beam and a jaw source representing the head scatter contribution each consisting of an electron and a photon component, while MC radiation transport is performed for the pMLC. The auto-commissioning of this analytical part relies on information pre-determined from MC simulations, in-air dose profiles and absolute dose measurements in water for different field sizes and source to surface distances (SSDs). For validation calculated and measured dose distributions in water were compared for different field sizes, SSDs and beam energies for eight TrueBeam systems. Furthermore, a sternum case in an anthropomorphic phantom was considered and calculated and measured dose distributions were compared at different SSDs.Main results.Instead of the manual commissioning taking up to several days of calculation time and several hours of user time, the auto-commissioning is carried out in a few minutes. Measured and calculated dose distributions agree generally within 3% of maximum dose or 2 mm. The gamma passing rates for the sternum case ranged from 96% to 99% (3% (global)/2 mm criteria, 10% threshold).Significance.The auto-commissioning procedure was successfully implemented and applied to eight TrueBeam systems. The newly developed user-friendly auto-commissioning procedure allows an efficient commissioning of an MC electron beam model and eases the usage of advanced electron radiotherapy utilizing the pMLC for beam shaping.

Efficiency enhancements of a Monte Carlo beamlet based treatment planning process: implementation and parameter study.

Objective.The computational effort to perform beamlet calculation, plan optimization and final dose calculation of a treatment planning process (TPP) generating intensity modulated treatment plans is enormous, especially if Monte Carlo (MC) simulations are used for dose calculation. The goal of this work is to improve the computational efficiency of a fully MC based TPP for static and dynamic photon, electron and mixed photon-electron treatment techniques by implementing multiple methods and studying the influence of their parameters.Approach.A framework is implemented calculating MC beamlets efficiently in parallel on each available CPU core. The user can specify the desired statistical uncertainty of the beamlets, a fractional sparse dose threshold to save beamlets in a sparse format and minimal distances to the PTV surface from which 2 × 2 × 2 = 8 (medium) or even 4 × 4 × 4 = 64 (large) voxels are merged. The compromise between final plan quality and computational efficiency of beamlet calculation and optimization is studied for several parameter values to find a reasonable trade-off. For this purpose, four clinical and one academic case are considered with different treatment techniques.Main results.Setting the statistical uncertainty to 5% (photon beamlets) and 15% (electron beamlets), the fractional sparse dose threshold relative to the maximal beamlet dose to 0.1% and minimal distances for medium and large voxels to the PTV to 1 cm and 2 cm, respectively, does not lead to substantial degradation in final plan quality compared to using 2.5% (photon beamlets) and 5% (electron beamlets) statistical uncertainty and no sparse format nor voxel merging. Only OAR sparing is slightly degraded. Furthermore, computation times are reduced by about 58% (photon beamlets), 88% (electron beamlets) and 96% (optimization).Significance.Several methods are implemented improving computational efficiency of beamlet calculation and plan optimization of a fully MC based TPP without substantial degradation in final plan quality.

Enabling non-isocentric dynamic trajectory radiotherapy by integration of dynamic table translations.

Objective.The purpose of this study is to develop a treatment planning process (TPP) for non-isocentric dynamic trajectory radiotherapy (DTRT) using dynamic gantry rotation, collimator rotation, table rotation, longitudinal, vertical and lateral table translations and intensity modulation and to validate the dosimetric accuracy.Approach.The TPP consists of two steps. First, a path describing the dynamic gantry rotation, collimator rotation and dynamic table rotation and translations is determined. Second, an optimization of the intensity modulation along the path is performed. We demonstrate the TPP for three use cases. First, a non-isocentric DTRT plan for a brain case is compared to an isocentric DTRT plan in terms of dosimetric plan quality and delivery time. Second, a non-isocentric DTRT plan for a craniospinal irradiation (CSI) case is compared to a multi-isocentric intensity modulated radiotherapy (IMRT) plan. Third, a non-isocentric DTRT plan for a bilateral breast case is compared to a multi-isocentric volumetric modulated arc therapy (VMAT) plan. The non-isocentric DTRT plans are delivered on a TrueBeam in developer mode and their dosimetric accuracy is validated using radiochromic films.Main results.The non-isocentric DTRT plan for the brain case is similar in dosimetric plan quality and delivery time to the isocentric DTRT plan but is expected to reduce the risk of collisions. The DTRT plan for the CSI case shows similar dosimetric plan quality while reducing the delivery time by 45% in comparison with the IMRT plan. The DTRT plan for the breast case showed better treatment plan quality in comparison with the VMAT plan. The gamma passing rates between the measured and calculated dose distributions are higher than 95% for all three plans.Significance.The versatile benefits of non-isocentric DTRT are demonstrated with three use cases, namely reduction of collision risk, reduced setup and delivery time and improved dosimetric plan quality.

A virtual source model for kilo-voltage cone beam CT: source characteristics and model validation.

PURPOSE: The purpose of this investigation was to study the source characteristics of a clinical kilo-voltage cone beam CT unit and to develop and validate a virtual source model that could be used for treatment planning purposes. METHODS: We used a previously commissioned full Monte Carlo model and new bespoke software to study the source characteristics of a clinical kilo-voltage cone beam CT (CBCT) unit. We identified the main particle sources, their spatial, energy and angular distribution for all the image acquisition presets currently used in our clinical practice. This includes a combination of two energies (100 and 120 kVp), two filters (neutral and bowtie), and eight different x-ray beam apertures. We subsequently built a virtual source model which we validated against full Monte Carlo calculations. RESULTS: We found that the radiation output of the clinical kilo-voltage cone beam CT unit investigated in this study could be reproduced with a virtual model comprising of two sources (target and filtration cone) or three sources (target, filtration cone and bowtie filter) when additional filtration was used. With this model, we accounted for more than 97% of the photons exiting the unit. Each source in our model was characterised by a origin distribution in both X and Y directions, a fluence map, a single energy spectrum for unfiltered beams and a two dimensional energy spectrum for bowtie filtered beams. The percentage dose difference between full Monte Carlo and virtual source model based dose distributions was well within the statistical uncertainty associated with the calculations ( ± 2%, one standard deviation) in all cases studied. CONCLUSIONS: The virtual source that we developed is accurate in calculating the dose delivered from a commercial kilo-voltage cone beam CT unit operating with routine clinical image acquisition settings. Our data have also shown that target, filtration cone, and bowtie filter sources needed to be all included in the model in order to accurately replicate the dose distribution from the clinical radiation beam.

TriB-RT: Simultaneous optimization of photon, electron and proton beams.

PURPOSE: To develop a novel treatment planning process (TPP) with simultaneous optimization of modulated photon, electron and proton beams for improved treatment plan quality in radiotherapy. METHODS: A framework for fluence map optimization of Monte Carlo (MC) calculated beamlet dose distributions is developed to generate treatment plans consisting of photon, electron and spot scanning proton fields. Initially, in-house intensity modulated proton therapy (IMPT) plans are compared to proton plans created by a commercial treatment planning system (TPS). A triple beam radiotherapy (TriB-RT) plan is generated for an exemplary academic case and the dose contributions of the three particle types are investigated. To investigate the dosimetric potential, a TriB-RT plan is compared to an in-house IMPT plan for two clinically motivated cases. Benefits of TriB-RT for a fixed proton beam line with a single proton field are investigated. RESULTS: In-house optimized IMPT are of at least equal or better quality than TPS-generated proton plans, and MC-based optimization shows dosimetric advantages for inhomogeneous situations. Concerning TriB-RT, for the academic case, the resulting plan shows substantial contribution of all particle types. For the clinically motivated case, improved sparing of organs at risk close to the target volume is achieved compared to IMPT (e.g. myelon and brainstem [Formula: see text] -37%) at cost of an increased low dose bath (healthy tissue V 10% +22%). In the scenario of a fixed proton beam line, TriB-RT plans are able to compensate the loss in degrees of freedom to substantially improve plan quality compared to a single field proton plan. CONCLUSION: A novel TPP which simultaneously optimizes photon, electron and proton beams was successfully developed. TriB-RT shows the potential for improved treatment plan quality and is especially promising for cost-effective single-room proton solutions with a fixed beamline in combination with a conventional linac delivering photon and electron fields.

Two independent receptors allow selective target lysis by T cell clones.

Dimethylbenzanthracene-induced P1 sarcoma cells induce P1-specific antibodies in syngeneic DA rats. Antiidiotypic antibodies of specificity DA anti-(DA anti-P1) were induced against the tumor-specific antibodies and used to restimulate P1-primed DA T cells in vitro. Using antiidiotypic antibodies and T cell growth factor, P1-specific cytotoxic DA T cell clones were established by limiting dilution and kept in vitro. Two of these clones acquired during culture periods in addition to the P1 specificity lytic activity towards natural killer (NK) targets YAC-1 or K562. Cold target inhibition experiments showed that the very same cytotoxic T cells kill P1 and NK targets. Antiidiotypic antibodies of specificity DA anti-(DA anti-P1) inhibited cytotoxicity against P1 but not against YAC-1 or K562. We conclude that two independent receptors are located on these double-reactive T cell clones, one that is idiotypic and antigen-specific, and another displaying the binding profile of NK cells.

Comparison of monte carlo collimator transport methods for photon treatment planning in radiotherapy.

PURPOSE: The aim of this work was a Monte Carlo (MC) based investigation of the impact of different radiation transport methods in collimators of a linear accelerator on photon beam characteristics, dose distributions, and efficiency. Thereby it is investigated if it is possible to use different simplifications in the radiation transport for some clinical situations in order to save calculation time. METHODS: Within the Swiss Monte Carlo Plan, a GUI-based framework for photon MC treatment planning, different MC methods are available for the radiation transport through the collimators [secondary jaws and multileaf collimator (MLC)]: EGSnrc (reference), VMC++, and Pin (an in-house developed MC code). Additional nonfull transport methods were implemented in order to provide different complexity levels for the MC simulation: Considering collimator attenuation only, considering Compton scatter only or just the firstCompton process, and considering the collimators as totally absorbing. Furthermore, either a simple or an exact geometry of the collimators can be selected for the absorbing or attenuation method. Phasespaces directly above and dose distributions in a water phantom are analyzed for academic and clinical treatment fields using 6 and 15 MV beams, including intensity modulated radiation therapy with dynamic MLC. RESULTS: For all MC transport methods, differences in the radial mean energy and radial energy fluence are within 1% inside the geometric field. Below the collimators, the energy fluence is underestimated for nonfull MC transport methods ranging from 5% for Compton to 100% for Absorbing. Gamma analysis using EGSnrc calculated doses as reference shows that the percentage of voxels fulfilling a 1% /1 mm criterion is at least 98% when using VMC++, Compton, or firstCompton transport methods. When using the methods Pin, Transmission, Flat-Transmission, Flat-Absorbing or Absorbing, the mean value of points fulfilling this criterion over all tested cases is 97%, 88%, 74%, 68%, or 65%, respectively. However, compared to EGSnrc calculations, the gain in efficiency is a factor of up to 10 for VMC++ and up to 48 for the absorbing method. CONCLUSIONS: The results of this investigation suggest that it is an option to use a simple transport technique in the initial treatment planning process and use more accurate transport methods for the final dose calculation accepting longer calculation times.

Development of an extended Macro Monte Carlo method for efficient and accurate dose calculation in magnetic fields.

MOTIVATION: Progress in the field of magnetic resonance (MR)-guided radiotherapy has triggered the need for fast and accurate dose calculation in presence of magnetic fields. The aim of this work is to satisfy this need by extending the macro Monte Carlo (MMC) method to enable dose calculation for photon, electron, and proton beams in a magnetic field. METHODS: The MMC method is based on the transport of particles in macroscopic steps through an absorber by sampling the relevant physical quantities from a precalculated database containing probability distribution functions. To enable MMC particle transport in a magnetic field, a transformation accounting for the Lorentz force is applied for each macro step by rotating the sampled position and direction around the magnetic field vector. The transformed position and direction distributions on local geometries are validated against full MC for electron and proton pencil beams. To enable photon dose calculation, an in-house MC algorithm is used for photon transport and interaction. Emerging secondary charged particles are passed to MMC for transport and energy deposition. The extended MMC dose calculation accuracy and efficiency is assessed by comparison with EGSnrc (photon and electron beams) and Geant4 (proton beam) calculated dose distributions of different energies and homogeneous magnetic fields for broad beams impinging on water phantoms with bone and lung inhomogeneities. RESULTS: The geometric transformation on the local geometries is able to reproduce the results of full MC for all investigated settings (difference in mean value and standard deviation <1%). Macro Monte Carlo calculated dose distributions in a homogeneous magnetic field are in agreement with EGSnrc and Geant4, respectively, with gamma passing rates >99.6% (global 2%, 2 mm and 10% threshold criteria) for all situations. MMC achieves a substantial efficiency gain of up to a factor of 21 (photon beam), 66 (electron beam), and 356 (proton beam) compared to EGSnrc or Geant4. CONCLUSION: Efficient and accurate dose calculation in magnetic fields was successfully enabled by utilizing the developed extended MMC transport method for photon, electron, and proton beams.

Benchmarking Monte-Carlo dose calculation for MLC CyberKnife treatments.

BACKGROUND: Vendor-independent Monte Carlo (MC) dose calculation (IDC) for patient-specific quality assurance of multi-leaf collimator (MLC) based CyberKnife treatments is used to benchmark and validate the commercial MC dose calculation engine for MLC based treatments built into the CyberKnife treatment planning system (Precision MC). METHODS: The benchmark included dose profiles in water in 15 mm depth and depth dose curves of rectangular MLC shaped fields ranging from 7.6 mm × 7.7 mm to 115.0 mm × 100.1 mm, which were compared between IDC, Precision MC and measurements in terms of dose difference and distance to agreement. Dose distributions of three phantom cases and seven clinical lung cases were calculated using both IDC and Precision MC. The lung PTVs ranged from 14 cm3 to 93 cm3. Quantitative comparison of these dose distributions was performed using dose-volume parameters and 3D gamma analysis with 2% global dose difference and 1 mm distance criteria and a global 10% dose threshold. Time to calculate dose distributions was recorded and efficiency was assessed. RESULTS: Absolute dose profiles in 15 mm depth in water showed agreement between Precision MC and IDC within 3.1% or 1 mm. Depth dose curves agreed within 2.3% / 1 mm. For the phantom and clinical lung cases, mean PTV doses differed from - 1.0 to + 2.3% between IDC and Precision MC and gamma passing rates were > =98.1% for all multiple beam treatment plans. For the lung cases, lung V20 agreed within ±1.5%. Calculation times ranged from 2.2 min (for 39 cm3 PTV at 1.0 × 1.0 × 2.5 mm3 native CT resolution) to 8.1 min (93 cm3 at 1.1 × 1.1 × 1.0 mm3), at 2% uncertainty for Precision MC for the 7 examined lung cases and 4-6 h for IDC, which, however, is not optimized for efficiency but used as a gold standard for accuracy. CONCLUSIONS: Both accuracy and efficiency of Precision MC in the context of MLC based planning for the CyberKnife M6 system were benchmarked against MC based IDC framework. Precision MC is used in clinical practice at our institute.

Imaging of Patients with Suspected Large-Vessel Occlusion at Primary Stroke Centers: Available Modalities and a Suggested Approach.

The overwhelming benefit of endovascular therapy in patients with large-vessel occlusions suggests that more patients will be screened than treated. Some of those patients will be evaluated first at primary stroke centers; this type of evaluation calls for standardizing the imaging approach to minimize delays in assessing, transferring, and treating these patients. Here, we propose that CT angiography (performed at the same time as head CT) should be the minimum imaging approach for all patients with stroke with suspected large-vessel occlusion presenting to primary stroke centers. We discuss some of the implications of this approach and how to facilitate them.

EXPOSURE OF A SERVICE TECHNICIAN REPAIRING A BIPLANE X-RAY SYSTEM.

While repairing a biplane cardiovascular X-ray system in a hospital, a service technician accidentally activated the system's floor pedal. He continued his work under unnoticed exposure for about 5 min until the system alarm was automatically activated. About 2 h after the exposure, the technician developed an erythema on parts of his left face and neck. The next day, he reported his incident to the competent authorities and was hospitalised in a unit specialised in treating heavily irradiated patients. Frequent blood analysis did not show any signs for a significant exposure to radiation. The Federal Office of Public Health then conducted extensive dose estimations. It could be shown that the dismounted collimator was always in front of the lateral X-ray tube, shielding the technician from the direct beam. The dose estimations came to the following conservative results: an effective dose of 5 mSv, a skin dose of 200 mSv, an eye lens dose of 100 mSv and an extremity dose (arm) of 700 mSv. The cause of the erythema remains unclear since the estimated doses are thought to be too low to induce any visible effect on the skin.

Electron beam collimation with a photon MLC for standard electron treatments.

Standard electron treatments are currently still performed using standard or molded patient-specific cut-outs placed in the electron applicator. Replacing cut-outs and electron applicators with a photon multileaf collimator (pMLC) for electron beam collimation would make standard electron treatments more efficient and would facilitate advanced treatment techniques like modulated electron radiotherapy (MERT) and mixed beam radiotherapy (MBRT). In this work, a multiple source Monte Carlo beam model for pMLC shaped electron beams commissioned at a source-to-surface distance (SSD) of 70 cm is extended for SSDs of up to 100 cm and validated for several Varian treatment units with field sizes typically used for standard electron treatments. Measurements and dose calculations agree generally within 3% of the maximal dose or 2 mm distance to agreement. To evaluate the dosimetric consequences of using pMLC collimated electron beams for standard electron treatments, pMLC-based and cut-out-based treatment plans are created for a left and a right breast boost, a sternum, a testis and a parotid gland case. The treatment plans consist of a single electron field, either alone (1E) or in combination with two 3D conformal tangential photon fields (1E2X). For each case, a pMLC plan with similar treatment plan quality in terms of dose homogeneity to the target and absolute mean dose values to the organs at risk (OARs) compared to a cut-out plan is found. The absolute mean dose to an OAR is slightly increased for pMLC-based compared to cut-out-based 1E plans if the OAR is located laterally close to the target with respect to beam direction, or if a 6 MeV electron beam is used at an extended SSD. In conclusion, treatment plans using cut-out collimation can be replaced by plans of similar treatment plan quality using pMLC collimation with accurately calculated dose distributions.

Part 2: Dynamic mixed beam radiotherapy (DYMBER): Photon dynamic trajectories combined with modulated electron beams.

PURPOSE: The purpose of this study was to develop a treatment technique for dynamic mixed beam radiotherapy (DYMBER) utilizing increased degrees of freedom (DoF) of a conventional treatment unit including different particle types (photons and electrons), intensity and energy modulation and dynamic gantry, table, and collimator rotations. METHODS: A treatment planning process has been developed to create DYMBER plans combining photon dynamic trajectories (DTs) and step and shoot electron apertures collimated with the photon multileaf collimator (pMLC). A gantry-table path is determined for the photon DTs with minimized overlap of the organs at risk (OARs) with the target. In addition, an associated dynamic collimator rotation is established with minimized area between the pMLC leaves and the target contour. pMLC sequences of photon DTs and electron pMLC apertures are then simultaneously optimized using direct aperture optimization (DAO). Subsequently, the final dose distribution of the electron pMLC apertures is calculated using the Swiss Monte Carlo Plan (SMCP). The pMLC sequences of the photon DTs are then re-optimized with a finer control point resolution and with the final electron dose distribution taken into account. Afterwards, the final photon dose distribution is calculated also using the SMCP and summed together with the one of the electrons. This process is applied for a brain and two head and neck cases. The resulting DYMBER dose distributions are compared to those of dynamic trajectory radiotherapy (DTRT) plans consisting only of photon DTs and clinically applied VMAT plans. Furthermore, the deliverability of the DYMBER plans is verified in terms of dosimetric accuracy, delivery time and collision avoidance. For this purpose, The DYMBER plans are delivered to Gafchromic EBT3 films placed in an anthropomorphic head phantom on a Varian TrueBeam linear accelerator. RESULTS: For each case, the dose homogeneity in the target is similar or better for DYMBER compared to DTRT and VMAT. Averaged over all three cases, the mean dose to the parallel OARs is 16% and 28% lower, D2% to the serial OARs is 17% and 37% lower and V10% to normal tissue is 12% and 4% lower for the DYMBER plans compared to the DTRT and VMAT plans, respectively. The DYMBER plans are delivered without collision and with a 4-5 min longer delivery time than the VMAT plans. The absolute dose measurements are compared to calculation by gamma analysis using 2% (global)/2 mm criteria with passing rates of at least 99%. CONCLUSIONS: A treatment technique for DYMBER has been successfully developed and verified for its deliverability. The dosimetric superiority of DYMBER over DTRT and VMAT indicates utilizing increased DoF to be the key to improve brain and head and neck radiation treatments in future.

Time for a Time Window Extension: Insights from Late Presenters in the ESCAPE Trial.

BACKGROUND AND PURPOSE: The safety and efficacy of endovascular therapy for large-artery stroke in the extended time window is not yet well-established. We performed a subgroup analysis on subjects enrolled within an extended time window in the Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke (ESCAPE) trial. MATERIALS AND METHODS: Fifty-nine of 315 subjects (33 in the intervention group and 26 in the control group) were randomized in the ESCAPE trial between 5.5 and 12 hours after last seen healthy (likely to have groin puncture administered 6 hours after that). Treatment effect sizes for all relevant outcomes (90-day mRS shift, mRS 0-2, mRS 0-1, and 24-hour NIHSS scores and intracerebral hemorrhage) were reported using unadjusted and adjusted analyses. RESULTS: There was no evidence of treatment heterogeneity between subjects in the early and late windows. Treatment effect favoring intervention was seen across all clinical outcomes in the extended time window (absolute risk difference of 19.3% for mRS 0-2 at 90 days). There were more asymptomatic intracerebral hemorrhage events within the intervention arm (48.5% versus 11.5%, P = .004) but no difference in symptomatic intracerebral hemorrhage. CONCLUSIONS: Patients with an extended time window could potentially benefit from endovascular treatment. Ongoing randomized controlled trials using imaging to identify late presenters with favorable brain physiology will help cement the paradigm of using time windows to select the population for acute imaging and imaging to select individual patients for therapy.

Integration of external and internal dosimetry in Switzerland.

Individual monitoring regulations in Switzerland are based on the ICRP60 recommendations. The annual limit of 20 mSv for the effective dose applies to the sum of external and internal radiation. External radiation is monitored monthly or quarterly with TLD, DIS or CR-39 dosemeters by 10 approved external dosimetry services and reported as Hp(10) and Hp(0.07). Internal monitoring is done in two steps. At the workplace, simple screening measurements are done frequently in order to recognise a possible incorporation. If a nuclide dependent activity threshold is exceeded then one of the seven approved dosimetry services for internal radiation does an incorporation measurement to assess the committed effective dose E50. The dosimetry services report all the measured or assessed dose values to the employer and to the National Dose Registry. The employer records the annually accumulated dose values into the individual dose certificate of the occupationally exposed person, both the external dose Hp(10) and the internal dose E50 as well as the total effective dose E=Hp(10)+E50. Based on the national dose registry an annual report on the dosimetry in Switzerland is published which contains the statistics for the total effective dose, as well as separate statistics for external and internal exposure.

Administration of anaesthetic triggering agents to patients tested malignant hyperthermia normal and their relatives in New Zealand: an update.

Testing for malignant hyperthermia in New Zealand involves two tests-in vitro contracture testing of excised lateral quadriceps muscle and DNA analysis. In vitro contracture testing is regarded as the gold standard in malignant hyperthermia diagnosis but several publications have questioned the reliability of a normal result. Analysis of 479 anaesthetic records in 280 patients or their descendants throughout New Zealand who had tested negative for malignant hyperthermia, demonstrated there was no evidence of malignant hyperthermia episodes in this group who had been administered anaesthetic triggering agents. A wide range of anaesthetics were used over the study period. Analysis of each anaesthetic record was undertaken using the malignant hyperthermia grading scale which determines the likelihood that an anaesthetic event represents a malignant hyperthermia episode. Confirmation of the negative results was further supported by normal DNA analysis of patients in 48% of anaesthetics. There are advantages to using inhalational agents in certain situations and although demonstrating a zero risk of a malignant hyperthermia episode is not statistically possible, evidence in this large series suggests that the risk of an episode in these patients is extremely low and may be negligible. We suggest that anaesthetic triggering agents can be used safely in patients with normal in vitro contracture tests, and in their descendants.

Simultaneous optimization of photons and electrons for mixed beam radiotherapy.

The aim of this work is to develop and investigate an inverse treatment planning process (TPP) for mixed beam radiotherapy (MBRT) capable of performing simultaneous optimization of photon and electron apertures. A simulated annealing based direct aperture optimization (DAO) is implemented to perform simultaneous optimization of photon and electron apertures, both shaped with the photon multileaf collimator (pMLC). Validated beam models are used as input for Monte Carlo dose calculations. Consideration of photon pMLC transmission during DAO and a weight re-optimization of the apertures after deliverable dose calculation are utilized to efficiently reduce the differences between optimized and deliverable dose distributions. The TPP for MBRT is evaluated for an academic situation with a superficial and an enlarged PTV in the depth, a left chest wall case including the internal mammary chain and a squamous cell carcinoma case. Deliverable dose distributions of MBRT plans are compared to those of modulated electron radiotherapy (MERT), photon IMRT and if available to those of clinical VMAT plans. The generated MBRT plans dosimetrically outperform the MERT, photon IMRT and VMAT plans for all investigated situations. For the clinical cases of the left chest wall and the squamous cell carcinoma, the MBRT plans cover the PTV similarly or more homogeneously than the VMAT plans, while OARs are spared considerably better with average reductions of the mean dose to parallel OARs and D 2% to serial OARs by 54% and 26%, respectively. Moreover, the low dose bath expressed as V 10% to normal tissue is substantially reduced by up to 45% compared to the VMAT plans. A TPP for MBRT including simultaneous optimization is successfully implemented and the dosimetric superiority of MBRT plans over MERT, photon IMRT and VMAT plans is demonstrated for academic and clinical situations including superficial targets with and without deep-seated part.

Telestroke-the promise and the challenge. Part one: growth and current practice.

Acute ischemic stroke remains a major public health concern, with low national treatment rates for the condition, demonstrating a disconnection between the evidence of treatment benefit and delivery of this treatment. Intravenous thrombolysis and endovascular thrombectomy are both strongly evidence supported and exquisitely time sensitive therapies. The mismatch between the distribution and incidence of stroke presentations and the availability of specialist care significantly affects access to care. Telestroke, the use of telemedicine for stroke, aims to surmount this hurdle by distributing stroke expertise more effectively, through video consultation with and examination of patients in locations removed from specialist care. This is the first of a detailed two part review, and explores the growth and current practice of telestroke, including the specific role it plays in the assessment and management of patients after emergent large vessel occlusion.