From Pancytopenia to Hyperleukocytosis, an Unexpected Presentation of Immune Reconstitution Inflammatory Syndrome in an Infant with Methylmalonic Acidemia.

A 2.5-month-old girl admitted for failure to thrive and severe pancytopenia was diagnosed with methylmalonic acidemia (MMA) secondary to transcobalamin II deficiency, an inborn error of vitamin B12 metabolism. Opportunistic Cytomegalovirus and Pneumocystis jirovecii pneumonia led to severe acute respiratory distress syndrome (ARDS) and immune reconstitution inflammatory syndrome (IRIS) after treatment initiation with vitamin B12 supplementation. In children with interstitial pneumonia-related ARDS, normal lymphocyte count should not delay invasive procedures required to document opportunistic infections. MMA can be associated with underlying lymphocyte dysfunction and vitamin B12 supplementation can fully reverse the associated immunodeficiency. IRIS may appear in highly treatment-responsive forms of pancytopenia in children and prompt treatment of dysregulated inflammation with high-dose corticosteroids should be initiated.

The effectiveness of cervical rehabilitation interventions for pain in adults with myogenic temporomandibular disorders: A systematic review and meta-analysis.

OBJECTIVE: Little evidence exists for the most effective conservative treatment approach for adults with myogenic temporomandibular disorders (MTMD). We aim to assess the effectiveness of cervical rehabilitation interventions on pain intensity and sensitivity in adults with MTMD compared to comparison intervention such as placebo, sham treatment, education or no intervention. METHODS: For this systematic review and meta-analysis, we searched PubMed, EMBASE, Medline, PEDro databases, forward and backward citations and grey literature studies through PROSPERO, clinical trials and data registries without language or date restrictions between inception and 1 December 2021. We selected randomised controlled trials (RCTs) based on adult populations with MTMD who had a cervical rehabilitation intervention which was defined as any conservative intervention targeting the anatomical structures of the cervical spine. The primary outcome measures for pain were self-reported pain intensity and pain sensitivity through the pressure pain threshold (PPT) of the masseter and temporalis muscles. Secondary outcome measures of maximal mouth opening (on MMO) were included. Included studies were assessed for bias with the Cochrane risk of bias tool for randomised trials. Evidence from RCTs was synthesised to determine treatment effect size as differences between standardised mean difference (SMD) for changes in pain intensity, PPT and MMO comparing adults with MTMD who were treated with cervical rehabilitation interventions compared to a control group. This study is registered on Prospero, number CRD 42021289299. RESULTS: Our general search yielded 2647 studies where seven RCTs met eligibility criteria with low to some concerns in their risk of bias. Pain intensity (five studies, n = 223, SMD -0.98, 95% CI -1.67 to -0.28, I2 = 79%), PPT of the masseter muscle (six studies, n = 395, SMD 0.64, 95% CI 0.43 to 0.86, I2 = 90%) and the temporalis muscles (five studies, n = 295, SMD 0.76, 95% CI 0.07 to 1.45, I2 = 84%) showed large treatment effect estimates favouring cervical rehabilitation interventions compared to no treatment, sham cervical treatment, patient education or non-cervical neuromuscular techniques. Compared to control interventions, one type of cervical rehabilitation intervention, cervical manual therapy alone or in combination with a neck exercise program was associated with statistically significant, large treatment effect estimates on pain intensity (four studies, n = 203, SMD -1.52, 95% CI -2.50 to -0.55). CONCLUSIONS: This review found that in the short-term, cervical rehabilitation interventions especially upper cervical MT alone or in combination with a neck exercise program are effective in improving multiple pain outcomes in adults with MTMD. However, further research is needed to measure the long-term effects of this type of intervention.

Performance characterization of a novel hybrid dosimetry insert for simultaneous spatial, temporal, and motion-included dosimetry for MR-linac.

BACKGROUND: Several (online) adaptive radiotherapy procedures are available to maximize healthy tissue sparing in the presence of inter/intrafractional motion during stereotactic body radiotherapy (SBRT) on an MR-linac. The increased treatment complexity and the motion-delivery interplay during these treatments require MR-compatible motion phantoms with time-resolved dosimeters to validate end-to-end workflows. This is not possible with currently available phantoms. PURPOSE: Here, we demonstrate a new commercial hybrid film-scintillator cassette, combining high spatial resolution radiochromic film with four time-resolved plastic scintillator dosimeters (PSDs) in an MRI-compatible motion phantom. METHODS: First, the PSD's performance for consistency, dose linearity, and pulse repetition frequency (PRF) dependence was evaluated using an RW3 solid water slab phantom. We then demonstrated the MRI4D scintillator cassette's suitability for time-resolved and motion-included quality assurance for adapt-to-shape (ATS), trailing, gating, and multileaf collimator (MLC) tracking adaptations on a 1.5 T MR-linac. To do this, the cassette was inserted into the Quasar MRI4D phantom, which we used statically or programmed with artificial and patient-derived motion. Simultaneously with dose measurements, the beam-gating latency was estimated from the time difference between the target entering/leaving the gating window and the beam-on/off times derived from the time-resolved dose measurements. RESULTS: Experiments revealed excellent detector consistency (standard deviation ≤ $\le$ 0.6%), dose linearity (R2 = 1), and only very low PRF dependence ( ≤ $\le$ 0.4%). The dosimetry cassette demonstrated a near-perfect agreement during an ATS workflow between the time-resolved PSD and treatment planning system (TPS) dose (0%-2%). The high spatial resolution film measurements confirmed this with a 1%/1-mm local gamma pass-rate of 90%. When trailing patient-derived prostate motion for a prostate SBRT delivery, the time-resolved cassette measurements demonstrated how trailing mitigated the motion-induced dose reductions from 1%-17% to 1%-2% compared to TPS dose. The cassette's simultaneously measured spatial dose distribution highlighted the dosimetric gain of trailing by improving the 3%/3-mm local gamma pass-rates from 80% to 97% compared to the static dose. Similarly, the cassette demonstrated the benefit of real-time adaptations when compensating patient-derived respiratory motion by showing how the TPS dose was restored from 2%-56% to 0%-12% (gating) and 1%-26% to 1%-7% (MLC tracking) differences. Larger differences are explainable by TPS-PSD coregistration uncertainty combined with a steep dose gradient outside the PTV. The cassette also demonstrated how the spatial dose distributions were drastically improved by the real-time adaptations with 1%/1-mm local gamma pass-rates that were increased from 8 to 79% (gating) and from 35 to 89% (MLC tracking). The cassette-determined beam-gating latency agreed within ≤ $\le$ 12 ms with the ground truth latency measurement. Film and PSD dose agreed well for most cases (differences relative to TPS dose < $<$ 4%), while film-PSD coregistration uncertainty caused relative differences of 5%-8%. CONCLUSIONS: This study demonstrates the excellent suitability of a new commercial hybrid film-scintillator cassette for simultaneous spatial, temporal, and motion-included dosimetry.

Full-scale multisampling and empirical modeling of DBPs in water and air of indoor pools.

Disinfection by-products (DBPs) are formed in the water in swimming pools due to reactions between disinfectants (chlorine, bromine, ozone) and the organic matter introduced by bathers and supply water. High concentrations of DBPs are also reported in the air of indoor swimming pools. Based on a robust multisampling program, the levels and variations of DBPs in the air (trichloramine [TCAM] and trihalomethanes [THMs]) and water (THM) were assessed, as well as their precursors (total organic carbon, water temperature, pH, free, and total chlorine) and proxies (CO2 and relative humidity) in four indoor chlorinated swimming pools. High-frequency sampling was conducted during one high-attendance day for each pool. This study focused on parameters that are easy to measure in order to develop models for predicting levels of THMs and TCAM in the air. The results showed that the number of bathers had an important impact on the levels of THMs and TCAM, with a two-to-three-fold increase in air chloroform (up to 110 µg/m3) and a two-to-four-fold increase in TCAM (up to 0.52 mg/m3) shortly after pools opened. The results of this study for the first time showed that CO2 and relative humidity can serve as proxies for monitoring variations in airborne THMs and TCAM. Our results highlight the good predictive capacity of the developed models and their potential for use in day-to-day monitoring. This could help optimize and control DBPs formation in the air of indoor swimming pools and reduce contaminant exposure for both pool employees and users.

Performance of the HYPERSCINT scintillation dosimetry research platform for the 1.5 T MR-linac.

Objective.Adaptive radiotherapy techniques available on the MR-linac, such as daily plan adaptation, gating, and dynamic tracking, require versatile dosimetric detectors to validate end-to-end workflows. Plastic scintillator detectors (PSDs) offer great potential with features including: water equivalency, MRI-compatibility, and time-resolved dose measurements. Here, we characterize the performance of the HYPERSCINT RP-200 PSD (MedScint, Quebec, CA) in a 1.5 T MR-linac, and we demonstrate its suitability for dosimetry, including in a moving target.Approach.Standard techniques of detector testing were performed using a Beamscan water tank (PTW, Freiburg, DE) and compared to microDiamond (PTW, Freiburg, DE) readings. Orientation dependency was tested using the same phantom. An RW3 solid water phantom was used to evaluate detector consistency, dose linearity, and dose rate dependence. To determine the sensitivity to motion and to MRI scanning, the Quasar MRI4Dphantom (Modus, London, ON) was used statically or with sinusoidal motion (A= 10 mm,T= 4 s) to compare PSD and Semiflex ionization chamber (PTW, Freiburg, DE) readings. Conformal beams from gantry 0° and 90° were used as well as a 15-beam 8 × 7.5 Gy lung IMRT plan.Main results.Measured profiles, PDD curves and field-size dependence were consistent with the microDiamond readings with differences well within our clinical tolerances. The angular dependence gave variations up to 0.8% when not irradiating directly from behind the scintillation point. Experiments revealed excellent detector consistency between repeated measurements (SD = 0.06%), near-perfect dose linearity (R2= 1) and a dose rate dependence <0.3%. Dosimetric effects of MRI scanning (≤0.3%) and motion (≤1.3%) were minimal. Measurements were consistent with the Semiflex (differences ≤1%), and with the treatment planning system with differences of 0.8% and 0.4%, with and without motion.Significance.This study demonstrates the suitability of the HYPERSCINT PSD for accurate time-resolved dosimetry measurements in the 1.5 T MR-linac, including during MR scanning and target motion.

Hybrid Cerenkov-scintillation detector validation using Monte Carlo simulations.

Objective.This study aimed at investigating through Monte Carlo simulations the limitations of a novel hybrid Cerenkov-scintillation detector and the associated method for irradiation angle measurements.Approach.Using Monte Carlo simulations, previous experimental irradiations of the hybrid detector with a linear accelerator were replicated to evaluate its general performances and limitations. Cerenkov angular calibration curves and irradiation angle measurements were then compared. Furthermore, the impact of the Cerenkov light energy dependency on the detector accuracy was investigated using the energy spectra of electrons travelling through the detector.Main results.Monte Carlo simulations were found to be in good agreement with experimental values. The irradiation angle absolute mean error was found to be less than what was obtained experimentally, with a maximum value of 1.12° for the 9 MeV beam. A 0.4% increase of the ratio of electrons having an energy below 1 MeV to the total electrons was found to impact the Cerenkov light intensity collected as a function of the incident angle. The effect of the Cerenkov intensity variation on the measured angle was determined to vary according to the slope of the angular calibration curve. While the contribution of scattered electrons with a lower energy affects the detector accuracy, the greatest discrepancies result from the limitations of the calculation method and the calibration curve itself.Significance.A precise knowledge of the limitations of the hybrid detector and the irradiation angle calculation method is crucial for a clinical implementation. Moreover, the simulations performed in this study also corroborate hypotheses made regarding the relations between multiple Cerenkov dependencies and observations from the experimental measurements.

Spatial and temporal variability of contaminants of emerging concern in a drinking water source.

The spatial-temporal behaviour of contaminants of emerging concern (CECs) are not well-documented in drinking water sources, including in Quebec, Canada. In this study, a set of seven contaminants, which are more frequently reported in water sources, were monitored from May 2016 to August 2017 at ten locations within an urbanized watershed (lakes and rivers) in Quebec, Canada. Samples were collected between a wastewater plant discharge (upstream) and the intake of a drinking water plant (downstream). The results showed that three (acetaminophen, salicylic acid, caffeine) out of seven CECs were consistently detected at a range of up to a few hundred ng L-1 at all sampling stations throughout the sampling period with a detection frequency between 51% and 94%. Upstream of two wastewater plant discharge locations, six CECs were measured above the detection limit compared to other locations where only three CECs (acetaminophen, salicylic acid, caffeine) were detected. Most of the CEC concentrations were higher (a few ng L-1) during late winter in comparison with the summer, in both years 2016 and 2017. The results highlight that the wastewater effluents and septic system effluents are significant sources of CECs that are released into the surface water. Moreover, the results help to identify the spatio-temporal patterns, which is a crucial element to understand the fate of CECs in water sources submitted to extreme weather conditions during the year. This research also provides baseline data for CEC occurrence at different points across lakes, rivers, and tributaries which will be useful for future ecotoxicological studies.

External beam irradiation angle measurement using a hybrid Cerenkov-scintillation detector.

Objective.In this study, we propose a novel approach designed to take advantage of the Cerenkov light angular dependency to perform a direct measurement of an external beam irradiation angle.Approach.A Cerenkov probe composed of a 10 mm long filtered sensitive volume of clear PMMA optical fibre was built. Both filtered and raw Cerenkov signals from the transport fibre were collected through a single 1 mm diameter transport fibre. An independent plastic scintillation detector composed of 10 mm BCF12 scintillating fibre was also used for simultaneous dose measurements. A first series of measurements aimed at validating the ability to account for the Cerenkov electron energy spectrum dependency by simultaneously measuring the deposited dose, thus isolating signal variations resulting from the angular dependency. Angular calibration curve for fixed dose irradiations and incident angle measurements using electron and photon beams where also achieved.Main results.The beam nominal energy was found to have a significant impact on the shapes of the angular calibration curves. This can be linked to the electron energy spectrum dependency of the Cerenkov emission cone. Irradiation angle measurements exhibit an absolute mean error of 1.86° and 1.02° at 6 and 18 MV, respectively. Similar results were obtained with electron beams and the absolute mean error reaches 1.97°, 1.66°, 1.45° and 0.95° at 9, 12, 16 and 20 MeV, respectively. Reducing the numerical aperture of the Cerenkov probe leads to an increased angular dependency for the lowest energy while no major changes were observed at higher energy. This allowed irradiation angle measurements at 6 MeV with a mean absolute error of 4.82°.Significance.The detector offers promising perspectives as a potential tool for future quality assurance applications in radiotherapy, especially for stereotactic radiosurgery (SRS), magnetic resonance image-guided radiotherapy (MRgRT) and brachytherapy applications.

Lead-doped scintillator dosimeters for detection of ultrahigh dose-rate x-rays.

Objective.Lead-doped scintillator dosimeters may be well suited for the dosimetry of FLASH-capable x-ray radiotherapy beams. Our study explores the dose rate dependence and temporal resolution of scintillators that makes them promising in the accurate detection of ultrahigh dose-rate (UHDR) x-rays.Approach.We investigated the response of scintillators with four material compositions to UHDR x-rays produced by a conventional x-ray tube. Scintillator output was measured using the HYPERSCINT-RP100 dosimetry research platform. Measurements were acquired at high frame rates (400 fps) which allowed for accurate dose measurements of sub-second radiation exposures from 1 to 100 ms. Dose-rate dependence was assessed by scaling tube current of the x-ray tube. Scintillator measurements were validated against Monte Carlo simulations of the probe geometries and UHDR x-ray system. Calibration factors converting dose-to-medium to dose-to-water were obtained from simulation data of plastic and lead-doped scintillator materials.Main Results.The results of this work suggest that lead-doped scintillators were dose-rate independent for UHDR x-rays from 1.1 to 40.1 Gy s-1and capable of measuring conventional radiotherapy dose-rates (0.1 Gy s-1) at extended distance from the x-ray focal spot. Dose-to-water measured with a 5% lead-doped scintillator detector agreed with simulations within 0.6%.Significance.Lead-doped scintillators may be a valuable tool for the accurate real-time dosimetry of FLASH-capable UHDR x-ray beams.

Technical note: Characterization and practical applications of a novel plastic scintillator for online dosimetry for an ultrahigh dose rate (FLASH).

PURPOSE: Although flash radiation therapy (FLASH-RT) is a promising novel technique that has the potential to achieve a better therapeutic ratio between tumor control and normal tissue complications, the ultrahigh pulsed dose rates (UHPDR) mean that experimental dosimetry is very challenging. There is a need for real-time dosimeters in the development and implementation of FLASH-RT. In this work, we characterize a novel plastic scintillator capable of temporal resolution short enough (2.5 ms) to resolve individual pulses. METHODS: We characterized a novel plastic dosimeter for use in a linac converter to deliver 16-MeV electrons at 100-Gy/s UHPDR average dose rates. The linearity and reproducibility were established by comparing relative measurements with a pinpoint ionization chamber placed at 10-cm water-equivalent depth where the electrometer is not saturated by the high dose per pulse. The accuracy was established by comparing the plastic scintillator dose measurements with EBT-XD Gafchromic radiochromic films, the current reference dosimeter for UHPDR. Finally, the plastic scintillator was compared against EBT-XD films for online dosimetry of two in vitro experiments performed at UHPDR. RESULTS: Relative ion chamber measurements were linear with plastic scintillator response within ≤1% over 4-20 Gy and pulse frequencies (18-180 Hz). When characterized under reference conditions with NIST-traceability, the plastic scintillator maintained its dose response under UHPDR conditions and agreed with EBT-XD film dose measurements within 4% under reference conditions and 6% for experimental online dosimetry. CONCLUSION: The plastic scintillator shows a linear and reproducible response and is able to accurately measure the radiation absorbed dose delivered by 16-MeV electrons at UHPDR. The dose is measured accurately in real time with a greater level of precision than that achieved with a radiochromic film.