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Experimental fission studies for reaction physics or nuclear spectroscopy can profit from fast, efficient, and radiation-resistant fission fragment (FF) detectors. When such experiments are performed in-beam in intense thermal neutron beams, additional constraints arise in terms of target-detector interface, beam-induced background, etc. Therefore, wide gap semi-conductor detectors were tested with the aim of developing innovative instrumentation for such applications. The detector characterization was performed with mass- and energy-separated fission fragment beams at the ILL (Institut Laue Langevin) LOHENGRIN spectrometer. Two single crystal diamonds, three polycrystalline and one diamond-on-iridium as well as a silicon carbide detector were characterized as solid state ionization chamber for FF detection. Timing measurements were performed with a 500-µm thick single crystal diamond detector read out by a broadband amplifier. A timing resolution of ∼10.2 ps RMS was obtained for FF with mass A = 98 at 90 MeV kinetic energy. Using a spectroscopic preamplifier developed at INFN-Milano, the energy resolution measured for the same FF was found to be slightly better for a ∼50-µm thin single crystal diamond detector (∼1.4% RMS) than for the 500-µm thick one (∼1.6% RMS), while a value of 3.4% RMS was obtained with the 400-µm silicon carbide detector. The Pulse Height Defect (PHD), which is significant in silicon detectors, was also investigated with the two single crystal diamond detectors. The comparison with results from α and triton measurements enabled us to conclude that PHD leads to ∼50% loss of the initial generated charge carriers for FF. In view of these results, a possible detector configuration and integration for in-beam experiments has been discussed.

Measurement of specific loss power (SLP) of magnetic nanoparticles is crucial to assert the heating potential in magnetic hyperthermia. There has been a significant improvement in characterizing magnetic nanoparticles’ heat-triggered functions by many research groups. However, optimal experimental conditions along with notable determination methods of the SLP in magnetic hyperthermia have not been widely proposed until now. Despite the remarkable progress in this field, the evaluation process of SLP suffers from uncertainties and errors imposed not only by experimental parameters (depending on the particles, the conditions and the measurement) but by the estimation methodology, as well. In this work, we propose a step by step standardization protocol, starting from definition and recording of potential uncertainty and error sources, present during a typical magnetic hyperthermia experimental protocol. The error of each specific parameter is estimated and translated to ultimate heating efficiency evaluation. According to our analysis, magnetic hyperthermia experiment and its corresponding estimation, under non-adiabatic conditions, may lead to a propagated uncertainty up to 14% on the SLP value. Meanwhile, different heating evaluation methods were assessed under a wide range of experimental conditions, with the ‘modified law of cooling’ proving to be the most accurate one—limiting the SLP uncertainty to values under 5%—compared to the ‘initial slope’ and ‘Box–Lucas’ methods, which show a remarkable uncertainty of over 15%. All parameters involved in the heating efficiency evaluation and their associated uncertainties analysis presented in this work, are included in a standardisation protocol, a handy guideline for determining accurate, reliable and reproducible SLP values, thus adequately evaluating its impact in potential bioapplications. [ABSTRACT FROM AUTHOR]

Objective: To investigate fear of hypoglycemia (FoH) in parents of children with type 1 diabetes (T1D) before and after undergoing training to learn intranasal (IN) glucagon administration., Method: In this pre-test/post-test uncontrolled study 364 caregivers of patients with T1D (6-18 years) completed questionnaires measuring sociodemographic characteristics, diabetes-related factors (e.g., type of insulin therapy, glycemic control), and parents' trait anxiety. Parents' FoH was assessed at baseline (T0, training) and after nine months (T1). Two repeated-measure mixed analyses of covariance (ANCOVA) compared the FoH at T0 and at T1 and analyzed the moderating roles of anxiety proneness and type of insulin therapy, as well as of anxiety proneness and use of sensor. Age, T1D duration, HbA1c values, and SES were included as covariates., Results: Parental FoH at T1 (M = 1.72; SE = 0.06/M = 1.57; SE = 0.09) was significantly lower than parental FoH at T0 (M = 1.89; SE = 0.06/M = 1.77; SE = 0.09). The group with high trait-anxiety had a higher level of FoH (M = 2.05; SE = 0.08/M = 1.89; SE = 0.12) than the group with low trait-anxiety (M = 1.57; SE = 0.08/M = 1.46; SE = 0.09) at both time points. SES was negatively associated with FoH at T0 (t = -2.87; p = .004/t = -2.87; p = .005). No other significant effects were found., Conclusions: Training and educating parents on IN glucagon use can help them effectively manage hypoglycemic episodes and alleviate the fear that generally accompany such events., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The relationship between Helicobacter-pylori(Hp)infection and inflammatory-bowel-disease(IBD) in pediatric-patients remains controversial. We aimed to assess the Hp-infection occurrence in newly-diagnosed pediatric-patients with IBD compared to no-IBD patients. Additionally, we aimed to examine differences in clinical-activity-index(CAI) and endoscopic-severity-score(ESS)between IBD-patients with and without Hp-infection, at baseline and at 1-year-follow-up(FU), after eradication-therapy(ET)., Methods: IBD diagnosis was based on Porto-criteria, and all patients underwent gastroscopy at baseline and 1-year FU. For Crohn's-disease(CD) and ulcerative colitis(UC), IBD-CAI and -ESS were classified using PCDAI/SES-CD and PUCAI/UCEIS, respectively., Results: 76 IBD-patients were included in the study[35 F(46.1%),median-age 12(range 2-17)]. CD and UC were diagnosed in 29(38.2%) and 45(59.2%)patients, respectively, and unclassified-IBD in two(2.6%)patients. Non-IBD patients were 148[71 F(48.0%),median-age 12(range 1-17)]. Hp-infection at baseline was reported in 7(9.2%) and 18(12.2%)IBD and non-IBD patients, respectively(p = 0.5065). The 7 IBD patients with Hp infection were compared to 69 IBD patients without Hp-infection at baseline evaluation, and no significant differences were reported considering CAI and ESS in these two groups. At 1-year FU, after ET, IBD patients with Hp infection improved, both for CAI and ESS, but statistical significance was not reached., Conclusion: The occurrence of Hp-infection did not differ between IBD and no-IBD patients. No differences in CAI or ESS were observed at the diagnosis, and after ET no worsening of CAI or ESS was noted at one-year FU, between Hp-positive and -negative IBD patients., (© 2024. The Author(s).)

Background and Purpose: Integrating simultaneous interstitial hyperthermia in high-dose-rate brachytherapy treatments (HDR-BT) is expected to lead to enhanced therapeutic effect. However, there is currently no device available for such an integration. In this study, we presented and validated the thermobrachytherapy (TBT) preclinical prototype system that is able to seamlessly integrate into the HDR-BT workflow., Materials and Methods: The TBT system consisted of an advanced radiofrequency power delivery and control system, dual-function interstitial applicators, and integrated connection and impedance matching system. The efficiency and minimum heating ability of the system was calculated performing calorimetric experiments. The effective-heating-length and heating pattern was evaluated using single-applicator split phantom experiments. The heating independence between applicators, the ability of the system to adaptable and predictable temperature steering was evaluated using multi-applicator split phantom experiments., Results: The system satisfied interstitial hyperthermia requirements. It demonstrated 50 % efficiency and ability to reach 6 °C temperature increase in 6 min. Effective-heating-length of the applicator was 43.7 mm, following the initial design. Heating pattern interference between applicators was lower than recommended. The system showed its ability to generate diverse heating patterns by adjusting the phase and amplitude settings of each electrode, aligning well with simulations (minimum agreement of 88 %)., Conclusions: The TBT preclinical prototype system complied with IHT requirements, and agreed well with design criteria and simulations, hence performing as expected. The preclinical prototype TBT system can now be scaled to an in-vivo validation prototype, including an adaptable impedance matching solution, appropriate number of channels, and ensuring biocompatibility and regulatory compliance., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: I. Androulakis, R.M.C. Mestrom, I.K.K. Kolkman-Deurloo, and G.C. van Rhoon are inventors of a pending patent on an interstitial hyperthermia device (WO2022235155A1). S. Curto declares no conflict of interest., (© 2024 The Author(s).)

Introduction: Hyperthermia efficacy depends on the temperatures achieved in the target area. Therefore, hyperthermia systems must deliver both controlled and conformal heating. This study presents a comprehensive multi-institutional quality assurance (QA) evaluation of deep hyperthermia devices., Methods: Six European institutions equipped with BSD- Sigma 60 and Sigma Eye deep hyperthermia applicators participated in the study. Up to six measurements per applicator were performed in each institution. The thermal distribution in cylindrical homogeneous phantoms after 10 minutes of heating with a total power delivered of 1000 watts was assessed using the applicator's integrated mapping thermometry system. Evaluated quality parameters included temperature increase, focus location, and focus symmetry., Results: A total of 54 measurements were conducted, with 43 included in the analysis. All applicators, except one, achieved a temperature increase of 6 °C in 10 minutes. Central heating capabilities were demonstrated, with mean deviations from the intended location of -1.4 ± 1.6 cm for Sigma 60 and 1.5 ± 1.4 cm for Sigma Eye. Symmetry evaluations showed differences in radial temperature profiles of 6.2 ± 4.5 % for the Sigma 60 and 5.9 ± 4.4 % for the Sigma Eye. We propose minimum acceptable values for each quality parameter based on these results., Conclusion: The measurements were reproducible with acceptable values for the various quality parameters. Potential deviations might be attributed to inaccuracies in the mapping thermometry system rather than the heating system. The presented protocol and practical recommendations should be applied for future QA measurements in deep hyperthermia.

Background: Phantoms accurately mimicking the electromagnetic and thermal properties of human tissues are essential for the development, characterization, and quality assurance (QA) of clinically used equipment for Hyperthermia Treatment (HT). Currently, a viable recipe for a fat equivalent phantom is not available, mainly due to challenges in the fabrication process and fast deterioration., Materials and Methods: We propose to employ a glycerol-in-oil emulsion stabilized with ethylcellulose to develop a fat-mimicking material. The dielectric, rheological, and thermal properties of the phantom have been assessed by state-of-the-art measurement techniques. The full-size phantom was then verified in compliance with QA guidelines for superficial HT, both numerically and experimentally, considering the properties variability., Results: Dielectric and thermal properties were proven equivalent to fat tissue, with an acceptable variability, in the 8 MHz to 1 GHz range. The rheology measurements highlighted enhanced mechanical stability over a large temperature range. Both numerical and experimental evaluations proved the suitability of the phantom for QA procedures. The impact of the dielectric property variations on the temperature distribution has been numerically proven to be limited (around 5%), even if higher for capacitive devices (up to 20%)., Conclusions: The proposed fat-mimicking phantom is a good candidate for hyperthermia technology assessment processes, adequately representing both dielectric and thermal properties of the human fat tissue while maintaining structural stability even at elevated temperatures. However, further experimental investigations on capacitive heating devices are necessary to better assess the impact of the low electrical conductivity values on the thermal distribution.

Purpose: This study aimed to assess the quality of the lucite cone applicator (LCA), the standard applicator for superficial hyperthermia at the Erasmus MC Cancer Institute, using the most recent quality assurance guidelines, thus verifying their feasibility., Materials and Methods: The assessment was conducted on each of the six LCAs available for clinical treatments. The temperature distribution was evaluated using an infrared camera across different layers of a fat-muscle mimicking phantom. The maximum temperature increase, thermal effective penetration depth (TEPD), and thermal effective field size (TEFS) were used as quality metrics. The experimental results were validated through comparison with simulated results, using a canonical phantom model and a realistic phantom model segmented from CT imaging., Results: A maximum temperature increase above 6 °C at 2 cm depth in the fat-muscle phantom for all the experiments was found. A mean negative difference between simulated and experimental data was of 1.3 °C when using the canonical phantom model. This value decreased to a mean negative difference of 0.4 °C when using the realistic model. Simulated and measured TEPD showed good agreement for both in silico scenarios, while discrepancies were present for TEFS., Conclusions: The LCAs passed all QA guidelines requirements for superficial hyperthermia delivery when used singularly or in an array configuration. A further characterization of parameters such as antenna efficiency and heat transfer coefficients would be beneficial for translating experimental results to simulated values. Implementing the QA guidelines was time-consuming and demanding, requiring careful preparation and correct setup of antenna elements.

The challenge to explain the diffuse and unconclusive message reported by hyperthermia studies investigating the thermal dose parameter is still to be unravelled. In the present review, we investigated a wide range of technical and clinical parameters characterising hyperthermia treatment to better understand and improve the probability of detecting a thermal dose effect relationship in clinical studies. We performed a systematic literature review to obtain hyperthermia clinical studies investigating the associations of temperature and thermal dose parameters with treatment outcome or acute toxicity. Different hyperthermia characteristics were retrieved, and their influence on temperature and thermal dose parameters was assessed. In the literature, we found forty-eight articles investigating thermal dose effect relationships. These comprised a total of 4107 patients with different tumour pathologies. The association between thermal dose and treatment outcome was the investigated endpoint in 90% of the articles, while the correlation between thermal dose and toxicity was investigated in 50% of the articles. Significant associations between temperature-related parameters and treatment outcome were reported in 63% of the studies, while those between temperature-related parameters and toxicity were reported in 15% of the studies. One clear difficulty for advancement is that studies often omitted fundamental information regarding the clinical treatment, and among the different characteristics investigated, thermometry details were seldom and divergently reported. To overcome this, we propose a clear definition of the terms and characteristics that should be reported in clinical hyperthermia treatments. A consistent report of data will allow their use to further continue the quest for thermal dose effect relationships.

[This corrects the article .]., (Copyright © 2022 Cherubini, Marino, Scaramuzza, Tiberi, Bobbio, Delvecchio, Piccinno, Ortolani, Innaurato, Felappi, Gallo, Ripoli, Ricciardi, Pascarella, Stamati, Citriniti, Arnaldi, Monti, Graziani, De Berardinis, Giannini, Chiarelli, Zampolli, De Marco, Bracciolini, Grosso, De Donno, Piccini, Toni, Coccioli, Cardinale, Bassi, Minuto, D’Annunzio, Maffeis, Marigliano, Zanfardino, Iafusco, Rollato, Piscopo, Curto, Lombardo, Bombaci, Sordelli, Mameli, Macedoni, Rigamonti, Bonfanti, Frontino, Predieri, Bruzzi, Mozzillo, Rosanio, Franzese, Piredda, Cardella, Iovane, Calcaterra, Berioli, Lasagni, Pampanini, Patera, Schiaffini, Rutigliano, Meloni, De Sanctis, Tinti, Trada, Guerraggio, Franceschi, Cauvin, Tornese, Franco, Musolino, Maltoni, Talarico, Iannilli, Lenzi, Matteoli, Pozzi, Moretti, Zucchini, Rabbone and Gesuita.)

Background: During resonance frequency (RF) hyperthermia treatment, the temperature of the tumor tissue is elevated to the range of 39-44°C. Accurate temperature monitoring is essential to guide treatments and ensure precise heat delivery and treatment quality. Magnetic resonance (MR) thermometry is currently the only clinical method to measure temperature noninvasively in a volume during treatment. However, several studies have shown that this approach is not always sufficiently accurate for thermal dosimetry in areas with motion, such as the pelvic region. Model-based temperature estimation is a promising approach to correct and supplement 3D online temperature estimation in regions where MR thermometry is unreliable or cannot be measured. However, complete 3D temperature modeling of the pelvic region is too complex for online usage., Purpose: This study aimed to evaluate the use of proper orthogonal decomposition (POD) model reduction combined with Kalman filtering to improve temperature estimation using MR thermometry. Furthermore, we assessed the benefit of this method using data from hyperthermia treatment where there were limited and unreliable MR thermometry measurements., Methods: The performance of POD-Kalman filtering was evaluated in several heating experiments and for data from patients treated for locally advanced cervical cancer. For each method, we evaluated the mean absolute error (MAE) concerning the temperature measurements acquired by the thermal probes, and we assessed the reproducibility and consistency using the standard deviation of error (SDE). Furthermore, three patient groups were defined according to susceptibility artifacts caused by the level of intestinal gas motion to assess if the POD-Kalman filtering could compensate for missing and unreliable MR thermometry measurements., Results: First, we showed that this method is beneficial and reproducible in phantom experiments. Second, we demonstrated that the combined method improved the match between temperature prediction and temperature acquired by intraluminal thermometry for patients treated for locally advanced cervical cancer. Considering all patients, the POD-Kalman filter improved MAE by 43% (filtered MR thermometry = 1.29°C, POD-Kalman filtered temperature = 0.74°C). Moreover, the SDE was improved by 47% (filtered MR thermometry = 1.16°C, POD-Kalman filtered temperature = 0.61°C). Specifically, the POD-Kalman filter reduced the MAE by approximately 60% in patients whose MR thermometry was unreliable because of the great amount of susceptibilities caused by the high level of intestinal gas motion., Conclusions: We showed that the POD-Kalman filter significantly improved the accuracy of temperature monitoring compared to MR thermometry in heating experiments and hyperthermia treatments. The results demonstrated that POD-Kalman filtering can improve thermal dosimetry during RF hyperthermia treatment, especially when MR thermometry is inaccurate., (© 2022 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Aim/hypothesis: To compare the frequency of diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes in Italy during the COVID-19 pandemic in 2020 with the frequency of DKA during 2017-2019., Methods: Forty-seven pediatric diabetes centers caring for >90% of young people with diabetes in Italy recruited 4,237 newly diagnosed children with type 1 diabetes between 2017 and 2020 in a longitudinal study. Four subperiods in 2020 were defined based on government-imposed containment measures for COVID-19, and the frequencies of DKA and severe DKA compared with the same periods in 2017-2019., Results: Overall, the frequency of DKA increased from 35.7% (95%CI, 33.5-36.9) in 2017-2019 to 39.6% (95%CI, 36.7-42.4) in 2020 (p=0.008), while the frequency of severe DKA increased from 10.4% in 2017-2019 (95%CI, 9.4-11.5) to 14.2% in 2020 (95%CI, 12.3-16.4, p<0.001). DKA and severe DKA increased during the early pandemic period by 10.4% (p=0.004) and 8% (p=0.002), respectively, and the increase continued throughout 2020. Immigrant background increased and high household income decreased the probability of presenting with DKA (OR: 1.55; 95%CI, 1.24-1.94; p<0.001 and OR: 0.60; 95 CI, 0.41-0.88; p=0.010, respectively)., Conclusions/interpretation: There was an increase in the frequency of DKA and severe DKA in children newly diagnosed with type 1 diabetes during the COVID-19 pandemic in 2020, with no apparent association with the severity of COVID-19 infection severity or containment measures. There has been a silent outbreak of DKA in children during the pandemic, and preventive action is required to prevent this phenomenon in the event of further generalized lockdowns or future outbreaks., Competing Interests: No author reported any conflict of interest as regards this study. The following conflicts of interest pointed out are referred to a period from January 2020 to the submission of this manuscript. VCh’s institution has received research grants from AstraZeneca, Novonordisk, Eli Lilly, Movi, Dompè, and Menarini, and VCh received honoraria from Eli Lilly, Tandem, and Insulet for participating on speakers’ bureaus and scientific advisory boards. CR, DT, IRa, BPr, BPi, SZ, ST, and AR has received support Eli Lilly. In addition, SZ’s institution has received support from Pfeizer, ST, BPi, and DT have received support from Abbott and Theras. MM and AR have received support from Menarini. BPr and PB received honoraria for participating on speakers’ bureaus and scientific advisory boards for Sandoz. Lastly, RS has received research grants by Sanofi and received honoraria for participating on speakers’ bureaus and scientific advisory boards for Movi. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cherubini, Marino, Scaramuzza, Tiberi, Bobbio, Delvecchio, Piccinno, Ortolani, Innaurato, Felappi, Gallo, Ripoli, Ricciardi, Pascarella, Stamati, Citriniti, Arnaldi, Monti, Graziani, De Berardinis, Giannini, Chiarelli, Zampolli, De Marco, Bracciolini, Grosso, De Donno, Piccini, Toni, Coccioli, Cardinale, Bassi, Minuto, D’Annunzio, Maffeis, Marigliano, Zanfardino, Iafusco, Rollato, Piscopo, Curto, Lombardo, Bombaci, Sordelli, Mameli, Macedoni, Rigamonti, Bonfanti, Frontino, Predieri, Bruzzi, Mozzillo, Rosanio, Franzese, Piredda, Cardella, Iovane, Calcaterra, Berioli, Lasagni, Pampanini, Patera, Schiaffini, Rutigliano, Meloni, De Sanctis, Tinti, Trada, Guerraggio, Franceschi, Cauvin, Tornese, Franco, Musolino, Maltoni, Talarico, Iannilli, Lenzi, Matteoli, Pozzi, Moretti, Zucchini, Rabbone and Gesuita.)

Electromagnetic thermal therapies for cancer treatment, such as microwave hyperthermia, aim to heat up a targeted tumour site to temperatures within 40 and 44 °C. Computational simulations used to investigate such heating systems employ the Pennes' bioheat equation to model the heat exchange within the tissue, which accounts for several tissue properties: density, specific heat capacity, thermal conductivity, metabolic heat generation rate, and blood perfusion rate. We present a review of these thermal and physiological properties relevant for hyperthermia treatments of breast including fibroglandular breast, fatty breast, and breast tumours. The data included in this review were obtained from both experimental measurement studies and estimated properties of human breast tissues. The latter were used in computational studies of breast thermal treatments. The measurement methods, where available, are discussed together with the estimations and approximations considered for values where measurements were unavailable. The review concludes that measurement data for the thermal and physiological properties of breast and tumour tissue are limited. Fibroglandular and fatty breast tissue properties are often approximated from those of generic muscle or fat tissue. Tumour tissue properties are mostly obtained from approximating equations or assumed to be the same as those of glandular tissue. We also present a set of reliable data, which can be used for more accurate modelling and simulation studies to better treat breast cancer using thermal therapies.

Wolfram Syndrome (WS) is a very rare genetic disorder characterized by several symptoms that occur from childhood to adulthood. Usually, the first clinical sign is non-autoimmune diabetes even if other clinical features (optic subatrophy, neurosensorial deafness, diabetes insipidus) may be present in an early state and may be diagnosed after diabetes' onset. Prognosis is poor, and the death occurs at the median age of 39 years as a consequence of progressive respiratory impairment, secondary to brain atrophy and neurological failure. The aim of this paper is the description of the metabolic treatment of the WS. We reported the experience of long treatment in patients with this syndrome diagnosed in pediatric age and followed also in adult age. It is known that there is a correlation between metabolic control of diabetes, the onset of other associated symptoms, and the progression of the neurodegenerative alterations. Therefore, a multidisciplinary approach is necessary in order to prevent, treat and carefully monitor all the comorbidities that may occur. An extensive understanding of WS from pathophysiology to novel possible therapy is fundamental and further studies are needed to better manage this devastating disease and to guarantee to patients a better quality of life and a longer life expectancy.

Objective: The addition of hyperthermia in the treatment of intact breast cancer with the aim to improve local response is currently in a research phase. First, optimal hyperthermia devices need to be developed, for which a diverse, anatomically and pathologically accurate set of patient models is necessary., Methods: To investigate the effects of inter-subject variations on hyperthermia treatment plans, we generated a repository of 22 anatomically and pathologically diverse patient models based on MR images of breast cancer patients. Hyperthermia treatment plans were generated for the 22 models using a generic theoretical phased array hyperthermia applicator., Results: Good temperature coverage was achieved in the vast majority of the models, with median values for T 10 = 43.5°C (41.9-43.8°C), T 50 = 42.5°C (41.3-43.3°C), and T 90 = 41.3°C (39.8-42.6°C) under the condition that the maximum temperature increase in the patient is limited to 44°C., Conclusions: For future development of hyperthermia devices and treatment methods, a repository with a sufficiently large number of representative patient models, such as the one provided in this study, should be used to ensure applicability to a wide variety of patients. This repository is therefore made publicly available.

This paper presents three devices suitable for the preclinical application of hyperthermia via the simultaneous high-resolution imaging of intratumoral events. (Pre)clinical studies have confirmed that the tumor micro-environment is sensitive to the application of local mild hyperthermia. Therefore, heating is a promising adjuvant to aid the efficacy of radiotherapy or chemotherapy. More so, the application of mild hyperthermia is a useful stimulus for triggered drug release from heat-sensitive nanocarriers. The response of thermosensitive nanoparticles to hyperthermia and ensuing intratumoral kinetics are considerably complex in both space and time. To obtain better insight into intratumoral processes, longitudinal imaging (preferable in high spatial and temporal resolution) is highly informative. Our devices are based on (i) an external electric heating adaptor for the dorsal skinfold model, (ii) targeted radiofrequency application, and (iii) a microwave antenna for heating of internal tumors. These models, while of some technical complexity, significantly add to the understanding of effects of mild hyperthermia warranting implementation in research on hyperthermia.

Preclinical studies have shown that application of mild hyperthermia (40-43 °C) is a promising adjuvant to solid tumor treatment. To improve preclinical testing, enhance reproducibility, and allow comparison of the obtained results, it is crucial to have standardization of the available methods. Reproducibility of methods in and between research groups on the same techniques is crucial to have a better prediction of the clinical outcome and to improve new treatment strategies (for instance with heat-sensitive nanoparticles). Here we provide a preclinically oriented review on the use and applicability of basic hyperthermia systems available for solid tumor thermal treatment in small animals. The complexity of these techniques ranges from a simple, low-cost water bath approach, irradiation with light or lasers, to advanced ultrasound and capacitive heating devices.

The efficacy of a hyperthermia treatment depends on the delivery of well-controlled heating; hence, accurate temperature monitoring is essential for ensuring effective treatment. For deep pelvic hyperthermia, there are no comprehensive and systematic reports on MR thermometry. Moreover, data inclusion generally lacks objective selection criteria leading to a high probability of bias when comparing results. Herein, we studied whether imaging-based data inclusion predicts accuracy and could serve as a tool for prospective patient selection. The accuracy of the MR thermometry in patients with locally advanced cervical cancer was benchmarked against intraluminal temperature. We found that gastrointestinal air motion at the start of the treatment, quantified by the Jaccard similarity coefficient, was a good predictor for MR thermometry accuracy. The results for the group that was selected for low gastrointestinal air motion improved compared to the results for all patients by 50% (accuracy), 26% (precision), and 80% (bias). We found an average MR thermometry accuracy of 2.0 °C when all patients were considered and 1.0 °C for the selected group. These results serve as the basis for comprehensive benchmarking of novel technologies. The Jaccard similarity coefficient also has good potential to prospectively determine in which patients the MR thermometry will be valuable.

Background: The success of cancer hyperthermia (HT) treatments is strongly dependent on the temperatures achieved in the tumor and healthy tissues as it correlates with treatment efficacy and safety, respectively. Hyperthermia treatment planning (HTP) simulations have become pivotal for treatment optimization due to the possibility for pretreatment planning, optimization and decision making, as well as real-time treatment guidance., Materials and Methods: The same computational methods deployed in HTP are also used for in silico studies. These are of great relevance for the development of new HT devices and treatment approaches. To aid this work, 3 D patient models have been recently developed and made available for the HT community. Unfortunately, there is no consensus regarding tissue properties, simulation settings, and benchmark applicators, which significantly influence the clinical relevance of computational outcomes., Results and Discussion: Herein, we propose a comprehensive set of applicator benchmarks, efficacy and safety optimization algorithms, simulation settings and clinical parameters, to establish benchmarks for method comparison and code verification, to provide guidance, and in view of the 2021 ESHO Grand Challenge (Details on the ESHO grand challenge on HTP will be provided at https://www.esho.info/)., Conclusion: We aim to establish guidelines to promote standardization within the hyperthermia community such that novel approaches can quickly prove their benefit as quickly as possible in clinically relevant simulation scenarios. This paper is primarily focused on radiofrequency and microwave hyperthermia but, since 3 D simulation studies on heating with ultrasound are now a reality, guidance as well as a benchmark for ultrasound-based hyperthermia are also included.

Tissue mimicking phantoms are frequently used in hyperthermia applications for device and protocol optimization. Unfortunately, a commonly experienced limitation is that their precise thermal properties are not available. Therefore, in this study, the thermal properties of three currently used QA phantoms for deep hyperthermia are measured with an "off-shelf" commercial thermal property analyzer. We have measured averaged values of thermal conductivity ( k = 0.59 ± 0.07 Wm -1 K -1 ), volumetric heat capacity ( C = 3.85 ± 0.45 MJm -3 K -1 ) and thermal diffusivity ( D = 0.16 ± 0.02 mm 2 s -1 ). These values are comparable with reported values of internal organs, such as liver, kidney and muscle. In addition, a sensitivity study of the performance of the commercial sensor is conducted. To ensure correct thermal measurements, the sample under test should entirely cover the length of the sensor, and a minimum of 4 mm of material parallel to the sensor in all directions should be guaranteed.

Infections caused by Campylobacter jejuni are rarely associated with extraintestinal complications. C. jejuni bacteremia is difficult to detect in patients with hematological malignancies undergoing chemotherapy where the choice of appropriate antibiotic treatment is extremely important. We report two cases of C. jejuni bacteremia in Italian pediatric patients affected by acute lymphoblastic leukemia (ALL). Agreeing with the most recent epidemiological data, both clinical isolates showed a typical phenotypic antimicrobial resistance patterns with combined resistance to ciprofloxacin and tetracycline. To our knowledge, this is the first report of C. jejuni isolation from the blood of ALL pediatric patients in Italy, and it provides important epidemiological information on this rare infection.

Clinical trials have demonstrated the therapeutic benefits of adding radiofrequency (RF) hyperthermia (HT) as an adjuvant to radio- and chemotherapy. However, maximum utilization of these benefits is hampered by the current inability to maintain the temperature within the desired range. RF HT treatment quality is usually monitored by invasive temperature sensors, which provide limited data sampling and are prone to infection risks. Magnetic resonance (MR) temperature imaging has been developed to overcome these hurdles by allowing noninvasive 3D temperature monitoring in the target and normal tissues. To exploit this feature, several approaches for inserting the RF heating devices into the MR scanner have been proposed over the years. In this review, we summarize the status quo in MR-guided RF HT devices and analyze trends in these hybrid hardware configurations. In addition, we discuss the various approaches, extract best practices and identify gaps regarding the experimental validation procedures for MR - RF HT, aimed at converging to a common standard in this process.

Introduction: Within the hyperthermia community, consensus exists that clinical outcome of the treatment radiotherapy and/or chemotherapy plus hyperthermia (i.e. elevating tumor temperature to 40 - 44 °C) is related to the applied thermal dose; hence, treatment quality is crucial for the success of prospective multi-institution clinical trials. Currently, applicator quality assurance (QA) measurements are implemented independently at each institution using basic cylindrical phantoms. A multi-institution comparison of heating quality using magnetic resonance thermometry (MRT) and anatomical representative anthropomorphic phantoms provides a unique opportunity to obtain novel QA insights to facilitate multi-institution trial evaluation., Objective: Perform a systematic QA procedure to compare the performance of MR-compatible hyperthermia systems in five institutions., Methods and Materials: Anthropomorphic phantoms, including pelvic and spinal bones, were produced. Clinically relevant power of 600 watts was applied for ∼12 min to allow for 8 sequential MR-scans. The 3D-heating distribution, steering capabilities, and presence of off-target heating were analyzed., Results: The evaluated devices show comparable heating profiles for centric and eccentric targets. The differences observed in the 3D-heating profiles are the result of variations in the exact phantom positioning and applicator characteristics, whereby positioning of the phantom followed current ESHO-QA guidelines., Conclusion: Anthropomorphic phantoms were used to perform QA-measurements of MR-guided hyperthermia systems operating in MR-scanners of different brands. Comparable heating profiles are shown for the five evaluated institutions. Subcentimeter differences in position substantially affected the results when evaluating the heating patterns. Integration of advanced phantoms and precise positioning in QA-guidelines should be evaluated to guarantee the best quality patient care.

Purpose: To compare the size of the coagulation (CZ) and periablational (PZ) zones created with two commercially available devices in clinical use for radiofrequency (RFA) and microwave ablation (MWA), respectively., Methods: Computer models were used to simulate RFA with a 3-cm Cool-tip applicator and MWA with an Amica-Gen applicator. The Arrhenius model was used to compute the damage index ( Ω ). CZ was considered when Ω  > 4.6 (>99% of damaged cells). Regions with 0.6< Ω  < 2.1 were considered as the PZ (tissue that has undergone moderate sub-ablative hyperthermia). The ratio of PZ volume to CZ volume (PZ/CZ) was regarded as a measure of performance, since a low value implies achieving a large CZ while keeping the PZ small., Results: Ten-min RFA (51 W) created smaller periablational zones than 10-min MWA (11.3 cm 3 vs. 17.2-22.9 cm 3 , for 60-100 W MWA, respectively). Prolonging duration from 5 to 10 min increased the PZ in MWA more than in RFA (2.7 cm 3 for RFA vs. 8.3-11.9 cm 3 for 60-100 W MWA, respectively). PZ/CZ for RFA were relatively high (65-69%), regardless of ablation time, while those for MWA were highly dependent on the duration (increase of up to 25% between 5 and 10 min) and on the applied power (smaller values as power was raised, 102% for 60 W vs. 81% for 100 W, both for 10 min). The lowest PZ/CZ across all settings was 56%, obtained with 100 W-5 min MWA., Conclusions: Although RFA creates smaller periablational zones than MWA, 100 W-5 min MWA provides the lowest PZ/CZ.

Hyperthermia therapy is a potent enhancer of chemotherapy and radiotherapy. In particular, microwave (MW) and radiofrequency (RF) hyperthermia devices provide a variety of heating approaches that can treat most cancers regardless the size. This review introduces the physics of MW/RF hyperthermia, the current state-of-the-art systems for both localized and regional heating, and recent advancements in hyperthermia treatment guidance using real-time computational simulations and magnetic resonance thermometry. Clinical trials involving RF/MW hyperthermia as adjuvant for chemotherapy are also presented per anatomical site. These studies favor the use of adjuvant hyperthermia since it significantly improves curative and palliative clinical outcomes. The main challenge of hyperthermia is the distribution of state-of-the-art heating systems. Nevertheless, we anticipate that recent technology advances will expand the use of hyperthermia to chemotherapy centers for enhanced drug delivery. These new technologies hold great promise not only for (image-guided) perfusion modulation and sensitization for cytotoxic drugs, but also for local delivery of various compounds using thermosensitive liposomes., (Copyright © 2020. Published by Elsevier B.V.)

Purpose: Thermal dose-effect relations have demonstrated that clinical effectiveness of hyperthermia would benefit from more controlled heating of the tumor. Hyperthermia treatment planning (HTP) is a potent tool to study strategies enabling target conformal heating, but its accuracy is affected by patient modeling approximations. Homogeneous phantoms models are being used that do not match the body shape of patients in treatment position and often have unrealistic target volumes. As a consequence, simulation accuracy is affected, and performance comparisons are difficult. The aim of this study is to provide the first step toward standardization of HTP simulation studies in terms of patient modeling by introducing the Erasmus Virtual Patient Repository (EVPR): a virtual patient model database. Methods: Four patients with a tumor in the head and neck or the pelvis region were selected, and corresponding models were created using a clinical segmentation procedure. Using the Erasmus University Medical Center standard procedure, HTP was applied to these models and compared to HTP for commonly used surrogate models. Results: Although this study was aimed at presenting the EVPR database, our study illustrates that there is a non-negligible difference in the predicted SAR patterns between patient models and homogeneous phantom-based surrogate models. We further demonstrate the difference between actual and simplified target volumes being used today. Conclusion: Our study describes the EVPR for the research community as a first step toward standardization of hyperthermia simulation studies.

Background: Glycemia following pizza consumption is typically managed with a dual-wave insulin bolus. This study evaluated the effect of a simple bolus on glycemia following consumption of traditionally prepared pizzas with long (24 h) or short (8 h) dough fermentation periods. Research Design and Methods: On two separate evenings, children with type 1 diabetes ( n  = 38) receiving sensor-integrated pump therapy consumed traditionally prepared pizza with either short (pizza A) or long (pizza B) dough fermentation, and blood glucose was monitored over 11 h. A simple insulin bolus was administered 15 min preprandially. The carbohydrate and amino acid contents of the two types of pizza were analyzed by liquid chromatography and high-resolution mass spectrometry (LC-HRMS). Results: The mean (±standard deviation) time in range 3.9-10.0 mmol/L was 73.2% ± 23.2%, and 50.8% ± 26.7% of glucose measurements were within the range 3.9-7.8 mmol/L. However, during the 2 h after bolus administration, the mean time in range 3.9-7.8 mmol/L was significantly greater with pizza B than with pizza A (73.3% ± 31.5% vs. 51.8% ± 37.4%, respectively, P  = 0.009), and the time in hyperglycemia (>10 mmol/L) was significantly shorter (mean percentage 6.1% ± 19.0% vs. 17.7% ± 29.8%, respectively, P  = 0.019). LC-HRMS analysis showed that long fermentation was associated with a lower carbohydrate content in the pizza, and a higher amino acid content. Conclusions: Glycemia following consumption of traditionally prepared pizza can be managed using a simple bolus 15 min before eating. Glycemic control can be further improved by increasing the dough fermentation time. Study registration: NCT03748251, Clinicaltrials.gov.

Clinical outcome of hyperthermia depends on the achieved target temperature, therefore target conformal heating is essential. Currently, invasive temperature probe measurements are the gold standard for temperature monitoring, however, they only provide limited sparse data. In contrast, magnetic resonance thermometry (MRT) provides unique capabilities to non-invasively measure the 3D-temperature. This study investigates MRT accuracy for MR-hyperthermia hybrid systems located at five European institutions while heating a centric or eccentric target in anthropomorphic phantoms with pelvic and spine structures. Scatter plots, root mean square error (RMSE) and Bland-Altman analysis were used to quantify accuracy of MRT compared to high resistance thermistor probe measurements. For all institutions, a linear relation between MRT and thermistor probes measurements was found with R 2 (mean ± standard deviation) of 0.97 ± 0.03 and 0.97 ± 0.02, respectively for centric and eccentric heating targets. The RMSE was found to be 0.52 ± 0.31 °C and 0.30 ± 0.20 °C, respectively. The Bland-Altman evaluation showed a mean difference of 0.46 ± 0.20 °C and 0.13 ± 0.08 °C, respectively. This first multi-institutional evaluation of MR-hyperthermia hybrid systems indicates comparable device performance and good agreement between MRT and thermistor probes measurements. This forms the basis to standardize treatments in multi-institution studies of MR-guided hyperthermia and to elucidate thermal dose-effect relations., Competing Interests: Dr. Curto reports grants from Pyrexar Medical Corp., grants from COST, during the conduct of the study; Mr. Mulder reports grants from Dutch Cancer Society, during the conduct of the study; Mr. Lamprecht reports grants from Sennewald, during the conduct of the study; grants from Elekta, grants from Siemens, outside the submitted work; Dr. Peller reports grants from Dr. Sennewald Medizintechnik GmbH, outside the submitted work; Dr. Lindner reports grants from Sennewald Medizintechnik GmbH, during the conduct of the study; Dr. Fietkau reports personal fees from Sennewald GmbH, during the conduct of the study; grants and personal fees from Merck Serono, grants and personal fees from Astra Zenica, grants and personal fees from MSD, personal fees from Novocure, personal fees from Brainlab, personal fees from Fresenius Kabi, personal fees from Bristol Byers Squibb, outside the submitted work; Dr. Zips reports financial support from Dr. Sennewald for educational events, during the conduct of the study; grants from Elekta, grants from Siemens, outside the submitted work; Dr. Paulides reports grants from Dutch Cancer Society, during the conduct of the study; Dr. van Rhoon reports grants from Dutch Cancer Society grant KWF-DDHK 2013-6072, grants from Pyrexar Medical Corp., during the conduct of the study; grants from Sensius BV, outside the submitted work. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.