Citations

Abstract Background Rescanning is a common technique used in proton pencil beam scanning to mitigate the interplay effect. Advances in machine operating parameters across different generations of particle therapy systems have led to improvements in beam delivery time (BDT). However, the potential impact of these improvements on the effectiveness of rescanning remains an underexplored area in the existing research. Methods We systematically investigated the impact of proton machine operating parameters on the effectiveness of layer rescanning in mitigating interplay effect during lung SBRT treatment, using the CIRS phantom. Focused on the Hitachi synchrotron particle therapy system, we explored machine operating parameters from our institution's current (2015) and upcoming systems (2025A and 2025B). Accumulated dynamic 4D dose were reconstructed to assess the interplay effect and layer rescanning effectiveness. Results Achieving target coverage and dose homogeneity within 2% deviation required 6, 6, and 20 times layer rescanning for the 2015, 2025A, and 2025B machine parameters, respectively. Beyond this point, further increasing the number of layer rescanning did not further improve the dose distribution. BDTs without rescanning were 50.4, 24.4, and 11.4 s for 2015, 2025A, and 2025B, respectively. However, after incorporating proper number of layer rescanning (six for 2015 and 2025A, 20 for 2025B), BDTs increased to 67.0, 39.6, and 42.3 s for 2015, 2025A, and 2025B machine parameters. Our data also demonstrated the potential problem of false negative and false positive if the randomness of the respiratory phase at which the beam is initiated is not considered in the evaluation of interplay effect. Conclusion The effectiveness of layer rescanning for mitigating interplay effect is affected by machine operating parameters. Therefore, past clinical experiences may not be applicable to modern machines.

Abstract Interstitial nephritis associated with multiple myeloma (LCTIN) is a rare histological finding defined as an abundant inflammatory infiltrate of polyclonal lymphocytes and plasma cells in the interstitium, not related to secondary causes other than a coexistent malignant plasma cell dyscrasia. The present case report illustrates an LCTIN associated with a light chain proximal tubulopathy, secondary to a kappa light chain MM, previously addressed as steroid-resistant drug-induced interstitial nephritis.

AbstractBackgroundThe detectability performance of a CT scanner is difficult to precisely quantify when nonlinearities are present in reconstruction. An efficient detectability assessment method that is sensitive to small effects of dose and scanner settings is desirable. We previously proposed a method using a search challenge instrument: a phantom is embedded with hundreds of lesions at random locations, and a model observer is used to detect lesions. Preliminary tests in simulation and a prototype showed promising results.PurposeIn this work, we fabricated a full‐size search challenge phantom with design updates, including changes to lesion size, contrast, and number, and studied our implementation by comparing the lesion detectability from a nonprewhitening (NPW) model observer between different reconstructions at different exposure levels, and by estimating the instrument sensitivity to detect changes in dose.MethodsDesigned to fit into QRM anthropomorphic phantoms, our search challenge phantom is a cylindrical insert 10 cm wide and 4 cm thick, embedded with 12 000 lesions (nominal width of 0.6 mm, height of 0.8 mm, and contrast of −350 HU), and was fabricated using PixelPrint, a 3D printing technique. The insert was scanned alone at a high dose to assess printing accuracy. To evaluate lesion detectability, the insert was placed in a QRM thorax phantom and scanned from 50 to 625 mAs with increments of 25 mAs, once per exposure level, and the average of all exposure levels was used as high‐dose reference. Scans were reconstructed with three different settings: filtered‐backprojection (FBP) with Br40 and Br59, and Sinogram Affirmed Iterative Reconstruction (SAFIRE) with strength level 5 and Br59 kernel. An NPW model observer was used to search for lesions, and detection performance of different settings were compared using area under the exponential transform of free response ROC curve (AUC). Using propagation of uncertainty, the sensitivity to changes in dose was estimated by the percent change in exposure due to one standard deviation of AUC, measured from 5 repeat scans at 100, 200, 300, and 400 mAs.ResultsThe printed insert lesions had an average position error of 0.20 mm compared to printing reference. As the exposure level increases from 50 mAs to 625 mAs, the lesion detectability AUCs increase from 0.38 to 0.92, 0.42 to 0.98, and 0.41 to 0.97 for FBP Br40, FBP Br59, and SAFIRE Br59, respectively, with a lower rate of increase at higher exposure level. FBP Br59 performed best with AUC 0.01 higher than SAFIRE Br59 on average and 0.07 higher than FBP Br40 (all P < 0.001). The standard deviation of AUC was less than 0.006, and the sensitivity to detect changes in mAs was within 2% for FBP Br59.ConclusionsOur 3D‐printed search challenge phantom with 12 000 submillimeter lesions, together with an NPW model observer, provide an efficient CT detectability assessment method that is sensitive to subtle effects in reconstruction and is sensitive to small changes in dose.

AbstractBackgroundSimulated error training is a method to practice error detection in situations where the occurrence of error is low. Such is the case for the physics plan and chart review where a physicist may check several plans before encountering a significant problem. By simulating potentially hazardous errors, physicists can become familiar with how they manifest and learn from mistakes made during a simulated plan review.PurposeThe purpose of this project was to develop a series of training datasets that allows medical physicists and trainees to practice plan and chart reviews in a way that is familiar and accessible, and to provide exposure to the various failure modes (FMs) encountered in clinical scenarios.MethodsA series of training datasets have been developed that include a variety of embedded errors based on the risk‐assessment performed by American Association of Physicists in Medicine (AAPM) Task Group 275 for the physics plan and chart review. The training datasets comprise documentation, screen shots, and digital content derived from common treatment planning and radiation oncology information systems and are available via the Cloud‐based platform ProKnow.ResultsOverall, 20 datasets have been created incorporating various software systems (Mosaiq, ARIA, Eclipse, RayStation, Pinnacle) and delivery techniques. A total of 110 errors representing 50 different FMs were embedded with the 20 datasets. The project was piloted at the 2021 AAPM Annual Meeting in a workshop where participants had the opportunity to review cases and answer survey questions related to errors they detected and their perception of the project's efficacy. In general, attendees detected higher‐priority FMs at a higher rate, though no correlation was found between detection rate and the detectability of the FMs. Familiarity with a given system appeared to play a role in detecting errors, specifically when related to missing information at different locations within a given software system. Overall, 96% of respondents either agreed or strongly agreed that the ProKnow portal and training datasets were effective as a training tool, and 75% of respondents agreed or strongly agreed that they planned to use the tool at their local institution.ConclusionsThe datasets and digital platform provide a standardized and accessible tool for training, performance assessment, and continuing education regarding the physics plan and chart review. Work is ongoing to expand the project to include more modalities, radiation oncology treatment planning and information systems, and FMs based on emerging techniques such as auto‐contouring and auto‐planning.

This cohort study characterizes heterogeneity in cardiac function prior to sepsis and describes associations with hospitalization outcomes and mortality.

Pores through ion channels rapidly transport small inorganic ions along their electrochemical gradients. Here, applying single-channel electrophysiology and mutagenesis to the archetypal muscle nicotinic acetylcholine receptor (AChR) channel, we show that a conserved pore-peripheral salt bridge partners with those in the other subunits to regulate ion transport. Disrupting the salt bridges in all five receptor subunits greatly decreases the amplitude of the unitary current and increases its fluctuations. However, disrupting individual salt bridges has unequal effects that depend on the structural status of the other salt bridges. The AChR ε- and δ-subunits are structurally unique in harboring a putative palmitoylation site near each salt bridge and bordering the lipid membrane. The effects of disrupting the palmitoylation sites mirror those of disrupting the salt bridges, but the effect of disrupting either of these structures depends on the structural status of the other. Thus, rapid ion transport through the AChR channel is maintained by functionally interdependent salt bridges linking the pore to the lipid membrane.

Introduction: Biomarkers are often used in conjunction with MRI to improve the specificity of prostate cancer screening. Our objective was to evaluate the real-world utility of the 4Kscore test in the setting of MRI. We explored the association of the 4Kscore test with the decision to pursue prostate biopsy and its contribution to the accurate detection of clinically significant prostate cancer. Methods: We retrospectively analyzed patients undergoing the 4Kscore test and MRI for consideration of prostate biopsy. Multivariable logistic regression was used to model the association of 4Kscore with the decision to pursue biopsy. Receiver-operating characteristic curves were used to calculate the AUC of 4Kscore alone, PSA with MRI, and 4Kscore with MRI for detection of Gleason Grade Group ≥ 2 (GG ≥ 2) prostate cancer. Results: Of 442 patients, 311 (70%) proceeded to biopsy. 4Kscore was associated with the decision to pursue biopsy for continuous (odds ratio [OR] 1.05 per 1-point increase in 4Kscore, 95% confidence interval [CI] 1.02-1.07; P < .001) and categorical (high-risk 4Kscore: OR 16.1, 6.62-39.3, P < .001; intermediate-risk 4Kscore: OR 6.89, 95% CI 3.15-15.1; P < .01) models. For the detection of GG ≥ 2 prostate cancer, the AUC of 4Kscore with MRI (AUC = 0.866) was superior to 4Kscore alone (AUC = 0.800, P < .001) and PSA with MRI (AUC = 0.792, P < .001). Conclusions: In patients with MRI, the 4Kscore is associated with the decision to pursue prostate biopsy and augments the accurate prediction of GG ≥ 2 prostate cancer. Our findings suggest 4Kscore provides independent information as an adjunct to MRI for real-world clinical decision making.

BACKGROUND: Associations of early changes in vasoactive support with cardiogenic shock (CS) mortality remain incompletely defined. METHODS: The Critical Care Cardiology Trials Network is a multicenter registry of cardiac intensive care units. Patients admitted with CS (2018–2023) had vasoactive dosing assessed at 4 and 24 hours from cardiac intensive care unit admission and quantified by the vasoactive-inotropic score (VIS). Prognostic associations of VIS at both time points, as well as change in VIS from 4 to 24 hours, were examined. Interaction testing was performed based on mechanical circulatory support status. RESULTS: Among 3665 patients, 82% had a change in VIS <10, with 7% and 11% having a ≥10-point increase and decrease from 4 to 24 hours, respectively. The 4 and 24-hour VIS were each associated with cardiac intensive care unit mortality (13%–45% and 11%–73% for VIS <10 to ≥40, respectively; P trend <0.0001 for each). Stratifying by the 4-hour VIS, changes in VIS from 4 to 24 hours had a graded association with mortality, ranging from a 2- to >4-fold difference in mortality comparing those with a ≥10-point increase to ≥10-point decrease in VIS ( P trend <0.0001). The change in VIS alone provided good discrimination of cardiac intensive care unit mortality (C-statistic, 0.72 [95% CI, 0.70–0.75]) and improved discrimination of the 24-hour Sequential Organ Failure Assessment score (0.72 [95% CI, 0.69–0.74] to 0.76 [95% CI, 0.74–0.78]) and the clinician-assessed Society for Cardiovascular Angiography and Interventions shock stage (0.72 [95% CI, 0.70–0.74] to 0.77 [95% CI, 0.75–0.79]). Although present in both groups, the mortality risk associated with VIS was attenuated in patients managed with versus without mechanical circulatory support (odds ratio per 10-point higher 24-hour VIS, 1.36 [95% CI, 1.23–1.49] versus 1.84 [95% CI, 1.69–2.01]; P interaction <0.0001). CONCLUSIONS: Early changes in the magnitude of vasoactive support in CS are associated with a gradient of risk for mortality. These data suggest that early VIS trajectory may improve CS prognostication, with the potential to be leveraged for clinical decision-making and research applications in CS.