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Anthropogenic noise negatively impacts many species. One of the more insidious effects of elevated noise levels is the reduction in area over which animals are able to acoustically communicate, often termed communication masking. This study utilizes modeling approaches to evaluate relative levels of masking for 4 baleen whale species from the combination of current ambient noise conditions and noise from discrete vessels operating in the Stellwagen Bank National Marine Sanctuary. Acoustic data were collected using bottom-mounted autonomous recorders. One day was analyzed for each of 5 different species-specific sound types, corresponding to peaks in occurrence of fin and humpback whale songs, humpback whale social sounds, minke whale pulse trains and North Atlantic right whale gunshots. Source levels for animals and 3 categories of vessels were calculated empirically; sound propagation was modeled using Bellhop ray tracing. An agent-based modeling framework was used to calculate changes in communication space (CS) in comparison to reference conditions (10 dB lower than current ambient noise). In these single-day snapshots, current ambient noise and noise from vessels for which automatic identification system (AIS) data were available contribute most heavily to loss of CS, followed by whale-watching and fishing vessels. Right whale gunshots experience the least amount of masking, while fin, humpback and minke whale signals experience masking levels of 80% or more. While these results incorporate several simplifying assumptions, this study further develops the framework by which to comparatively quantify masking, providing information on the relative degree of masking experienced between species and allowing for important insights on the relative contributions of different anthropogenic sound sources.

A quiz concerning a 69-year-old man with a two-year history of generalized weakness and a two-week history of blood-tinged sputum is presented.

Purpose: To assess a modified use of Compare software as a resource to (1) improve students' ability to self-assess their endodontic access preparations (EAPs) and (2) students' opinions of this adjunct., Methods: Sixty second-year dental students were randomly assigned to two groups (n = 30). A questionnaire was developed and validated. Both groups performed two accesses on #14 acrylic teeth, one at the course's outset and another at its conclusion, and evaluated them using a traditional method of assessment, completed the self-assessment form, and answered items 1‒4 of the questionnaire. The experimental group (G2) received training and were asked to evaluate their EAPs three-dimensionally (3D), complete the self-assessment form a second time, and answer items 5‒14 of the questionnaire. Data were analyzed statistically (significance set at 5%)., Results: Using the traditional method, G1 (control group) showed improvement in "size-shape," G2 in "encroachment," and both increased their "overall rate" (p < 0.05). Using the 3D method, G2 showed improvement in the "mesial extent" (p < 0.05). No difference was found between groups for self-assessment or opinions (items 1‒4) (p > 0.05). However, both had an increase in confidence from the first access to the second, and G1 participants believed they improved their ability to perform and assess EAPs (p < 0.05)., Conclusion: No difference was observed between the two groups when relying upon the traditional method alone. Both groups experienced an increase in confidence but only G1 believed that their ability to perform and assess EAPs improved. Notably, 96.7% of G2 believed that the 3D method should be incorporated into preclinical endodontic training., (© 2025 The Author(s). Journal of Dental Education published by Wiley Periodicals LLC on behalf of American Dental Education Association.)

Competing Interests: Dr Cihoric is a technical lead for the SmartOncology project and medical advisor for Wemedoo AG, Steinhausen AG, Switzerland. The authors declare no other conflicts of interest.

Objective: The purpose of this study was to investigate patient safety implications of transporting prone-positioned mechanically ventilated patients in the air medical environment (AME)., Methods: A retrospective health record review of patient encounters from 2019 to 2021 was conducted using British Columbia Emergency Health Services air medical electronic patient care reports., Results: A total of 633 patients were identified as intubated, mechanically ventilated, and transported by British Columbia Emergency Health Services air medical teams. Ten patients were identified as having been transported in the prone position. Oxygen saturation, arterial blood oxygen levels, and carbon dioxide measurements from 8 cases indicated that patients remained stable or improved during transport. Cardiovascular episodes including hypotension and tachycardia were observed. In 2 patients, a mean 17.5% decline in oxygen saturation was identified. It could not be determined if this was a result of prone positioning during AME or due to a deteriorating physiological condition related to the patient's underlying disease. There were no identified tube dislodgments during AME transport., Conclusion: Although proning did not compromise patient safety with respect to tube or line displacement in our study, we cannot draw definitive conclusions regarding the safety implications of proning on patient vital signs during transport., Competing Interests: Declaration of Competing Interest The author(s) have no relevant disclosures. There was no grant funding or financial support for this manuscript., (Copyright © 2023 Air Medical Journal Associates. Published by Elsevier Inc. All rights reserved.)

Purpose: Technological progress of machine learning and natural language processing has led to the development of large language models (LLMs), capable of producing well-formed text responses and providing natural language access to knowledge. Modern conversational LLMs such as ChatGPT have shown remarkable capabilities across a variety of fields, including medicine. These models may assess even highly specialized medical knowledge within specific disciplines, such as radiation therapy. We conducted an exploratory study to examine the capabilities of ChatGPT to answer questions in radiation therapy., Methods and Materials: A set of multiple-choice questions about clinical, physics, and biology general knowledge in radiation oncology as well as a set of open-ended questions were created. These were given as prompts to the LLM ChatGPT, and the answers were collected and analyzed. For the multiple-choice questions, it was checked how many of the answers of the model could be clearly assigned to one of the allowed multiple-choice-answers, and the proportion of correct answers was determined. For the open-ended questions, independent blinded radiation oncologists evaluated the quality of the answers regarding correctness and usefulness on a 5-point Likert scale. Furthermore, the evaluators were asked to provide suggestions for improving the quality of the answers., Results: For 70 multiple-choice questions, ChatGPT gave valid answers in 66 cases (94.3%). In 60.61% of the valid answers, the selected answer was correct (50.0% of clinical questions, 78.6% of physics questions, and 58.3% of biology questions). For 25 open-ended questions, 12 answers of ChatGPT were considered as "acceptable," "good," or "very good" regarding both correctness and helpfulness by all 6 participating radiation oncologists. Overall, the answers were considered "very good" in 29.3% and 28%, "good" in 28% and 29.3%, "acceptable" in 19.3% and 19.3%, "bad" in 9.3% and 9.3%, and "very bad" in 14% and 14% regarding correctness/helpfulness., Conclusions: Modern conversational LLMs such as ChatGPT can provide satisfying answers to many relevant questions in radiation therapy. As they still fall short of consistently providing correct information, it is problematic to use them for obtaining medical information. As LLMs will further improve in the future, they are expected to have an increasing impact not only on general society, but also on clinical practice, including radiation oncology., Competing Interests: Nikola Cihoric is a technical lead for the SmartOncology project and medical advisor for Wemedoo AG, Steinhausen AG, Switzerland., (© 2023 The Author(s).)

Background: For critically ill and injured patients, timely access to definitive care is associated with a reduction in avoidable mortality. Access to definitive care is significantly affected by geographic remoteness. To overcome this disparity, a robust critical care transport (CCT) or retrieval system is essential to support the equity of care and overcome the tyranny of distance. While critical care transport or retrieval systems have evolved over the years, there is no universally accepted system or standard, which has led to considerable variation in practices. The objective of this mixed-methods study was to identify and explore the current clinical, operational, and educational practices of government and charity-funded critical care transport and retrieval organizations operating across access- and weather- challenged geography., Methods: This study utilized a mixed-methods approach comprising a rapid review of the literature and semi-structured interviews with identified subject matter experts (SME)., Results: A total of 44 articles and 14 interviews with SMEs from six different countries, 12 different services/systems, and seven operational roles, including clinicians (physician, paramedic, and nurse), educator, quality improvement, clinical governance, clinical informatics and research, operations manager, and medical director were included in the narrative analysis. The study identified several themes including deployment, crew composition, selection and education, clinical governance, quality assurance and quality improvement and research., Conclusion: This mixed-methods study underscores the paucity of literature describing current clinical, operational, and educational practices of government or charity-funded CCT or retrieval programs operating across access- and weather- challenged geography. While many common themes were identified including clearly defined mission profiles, use of dedicated or specialized transport teams, central coordination, rigorous selection processes, service-sponsored graduate education, and strong clinical governance, there is little consensus and considerable variation in current practices. Further research is needed to identify and harmonize best practices within the CCT and retrieval environments., (© 2023. Norwegian Air Ambulance Foundation.)

Prior work demonstrated that Phlpp1 deficiency alters limb length and bone mass, but the cell types involved and requirement of Phlpp1 for this effect were unclear. To understand the function of Phlpp1 within bone-forming osteoblasts, we crossed Phlpp1 floxed mice with mice harboring type 1 collagen (Col1a1 2.3kb )-Cre. Mineralization of bone marrow stromal cell cultures derived from Phlpp1 cKO Col1a1 was unchanged, but levels of inflammatory genes (eg, Ifng , Il6 , Ccl8 ) and receptor activator of NF-κB ligand/osteoprotegerin (RANKL/OPG) ratios were enhanced by either Phlpp1 ablation or chemical inhibition. Micro-computed tomography of the distal femur and L 5 vertebral body of 12-week-old mice revealed no alteration in bone volume per total volume, but compromised femoral bone microarchitecture within Phlpp1 cKO Col1a1 conditional knockout females. Bone histomorphometry of the proximal tibia documented no changes in osteoblast or osteoclast number per bone surface but slight reductions in osteoclast surface per bone surface. Overall, our data show that deletion of Phlpp1 in type 1 collagen-expressing cells does not significantly alter attainment of peak bone mass of either males or females, but may enhance inflammatory gene expression and the ratio of RANKL/OPG. Future studies examining the role of Phlpp1 within models of advanced age, inflammation, or osteocytes, as well as functional redundancy with the related Phlpp2 isoform are warranted. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research., (© 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.)

Background: Early resuscitation with blood components or products is emerging as best practice in selected patients with trauma and medical patients; as a result, out-of-hospital transfusion (OHT) programs are being developed based on limited and often conflicting evidence. This study aimed to provide guidance to Canadian critical care transport organizations on the development of OHT protocols., Methods: The study period was July 2021 to June 2022. We used a modified RAND Delphi process to achieve consensus on statements created by the study team guiding various aspects of OHT in the context of critical care transport. Purposive sampling ensured representative distribution of participants in regard to geography and relevant clinical specialties. We conducted 2 written survey Delphi rounds, followed by a virtual panel discussion (round 3). Consensus was defined as a median score of at least 6 on a Likert scale ranging from 1 ("Definitely should not include") to 7 ("Definitely should include"). Statements that did not achieve consensus in the first 2 rounds were discussed and voted on during the panel discussion., Results: Seventeen subject experts participated in the study, all of whom completed the 3 Delphi rounds. After the study process was completed, a total of 39 statements were agreed on, covering the following domains: general oversight and clinical governance, storage and transport of blood components and products, initiation of OHT, types of blood components and products, delivery and monitoring of OHT, indications for and use of hemostatic adjuncts, and resuscitation targets of OHT., Interpretation: This expert consensus document provides guidance on OHT best practices. The consensus statements should support efficient and safe OHT in national and international critical care transport programs., Competing Interests: Competing interests: Brodie Nolan reports research funding from Canadian Blood Services and Physicians’ Services Incorporated Foundation. Andrew Shih reports payments for consulting on educational materials in relation to bleeding management from Octapharma Canada and payments for advisory board participation in relation to clotting factor concentrates from CSL Behring. He has received speaker honoraria from Octapharma Canada and CSL Behring. Octapharma Canada reimbursed travel expenses for attending a meeting for the FARES-II trial comparing clotting factor concentrates to plasma in cardiac surgery. He is vice-chair of the National Advisory Committee on Blood and Blood Products. No other competing interests were declared., (© 2023 CMA Impact Inc. or its licensors.)

Objectives: Patients with single-ventricle physiology have a significant risk of cardiorespiratory deterioration between their first- and second-stage palliation surgeries. Detection of deterioration episodes may allow for early intervention and improved outcomes., Methods: A prospective study was executed at Nationwide Children's Hospital, Children's Hospital of Philadelphia, and Children's Hospital Colorado to collect physiologic data of subjects with single ventricle physiology during all hospitalizations between neonatal palliation and II surgeries using the Sickbay software platform (Medical Informatics Corp). Timing of cardiorespiratory deterioration events was captured via chart review. The predictive algorithm previously developed and validated at Texas Children's Hospital was applied to these data without retraining. Standard metrics such as receiver operating curve area, positive and negative likelihood ratio, and alert rates were calculated to establish clinical performance of the predictive algorithm., Results: Our cohort consisted of 58 subjects admitted to the cardiac intensive care unit and stepdown units of participating centers over 14 months. Approximately 28,991 hours of high-resolution physiologic waveform and vital sign data were collected using the Sickbay. A total of 30 cardiorespiratory deterioration events were observed. the risk index metric generated by our algorithm was found to be both sensitive and specific for detecting impending events one to two hours in advance of overt extremis (receiver operating curve = 0.927)., Conclusions: Our algorithm can provide a 1- to 2-hour advanced warning for 53.6% of all cardiorespiratory deterioration events in children with single ventricle physiology during their initial postop course as well as interstage hospitalizations after stage I palliation with only 2.5 alarms being generated per patient per day., (© 2023 The Authors.)

Objective: To summarize the available literature on using machine learning (ML) for palliative care practice as well as research and to assess the adherence of the published studies to the most important ML best practices. Methods: The MEDLINE database was searched for the use of ML in palliative care practice or research, and the records were screened according to PRISMA guidelines. Results: In total, 22 publications using machine learning for mortality prediction (n = 15), data annotation (n = 5), predicting morbidity under palliative therapy (n = 1), and predicting response to palliative therapy (n = 1) were included. Publications used a variety of supervised or unsupervised models, but mostly tree-based classifiers and neural networks. Two publications had code uploaded to a public repository, and one publication uploaded the dataset. Conclusions: Machine learning in palliative care is mainly used to predict mortality. Similarly to other applications of ML, external test sets and prospective validations are the exception.

Scientific research increasingly relies on open source software (OSS). Funding OSS development requires intentional focus on issues of scholarly credit, unique forms of labor, maintenance, governance, and inclusive community-building. Such issues cut across different scientific disciplines that make them of interest to a variety of funders and institutions but may present challenges in understanding generalized needs. Here we present 10 simple rules for investing in scientific OSS and the teams who build and maintain it., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Strasser et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: There is limited information on treatment recommendations for glioblastoma patients with poor performance status. Here, we aim to evaluate the association of radiotherapy on survival in glioblastoma patients presenting with poor postoperative performance status in first-line setting., Methods: We retrospectively analyzed data of 93 glioblastoma patients presenting with poor postoperative performance status (ECOG 2-4) at the University Hospital Zurich, Switzerland, in the years 2005-2019. A total of 43 patients received radiotherapy with or without systemic therapy in the first-line setting, whereas 50 patients received no additive local or systemic treatment after initial biopsy or resection. Overall survival was calculated from primary diagnosis and from the end of radiotherapy. In addition, factors influencing survival were analyzed., Results: Median overall survival from primary diagnosis was 6.2 months in the radiotherapy group (95% CI 6.2-14.8 weeks, range 2-149 weeks) and 2.3 months in the group without additive treatment (95% CI 1.3-7.4 weeks, range 0-28 weeks) (p < 0.001). This survival benefit was confirmed by landmark analyses. Factors associated with overall survival were extent of resection and administration of radiotherapy with or without systemic treatment. Median survival from end of radiotherapy was 3 months (95% CI 4.3-21.7 weeks, range 0-72 weeks), with 25.6% (n = 11) early termination of treatment and 83.7% (n = 36) requiring radiotherapy as in-patients. Performance status improved in 27.9% (n = 12) of patients after radiotherapy., Conclusion: In this retrospective single-institution analysis, radiotherapy improved overall survival in patients with poor performance status, especially in patients who were amendable to neurosurgical resection., (© 2021. The Author(s).)

In this study. we aimed to detect vestibular schwannomas (VSs) in individual magnetic resonance imaging (MRI) slices by using a 2D-CNN. A pretrained CNN (ResNet-34) was retrained and internally validated using contrast-enhanced T1-weighted (T1c) MRI slices from one institution. In a second step, the model was externally validated using T1c- and T1-weighted (T1) slices from a different institution. As a substitute, bisected slices were used with and without tumors originating from whole transversal slices that contained part of the unilateral VS. The model predictions were assessed based on the categorical accuracy and confusion matrices. A total of 539, 94, and 74 patients were included for training, internal validation, and external T1c validation, respectively. This resulted in an accuracy of 0.949 (95% CI 0.935-0.963) for the internal validation and 0.912 (95% CI 0.866-0.958) for the external T1c validation. We suggest that 2D-CNNs might be a promising alternative to 2.5-/3D-CNNs for certain tasks thanks to the decreased demand for computational power and the fact that there is no need for segmentations. However, further research is needed on the difference between 2D-CNNs and more complex architectures.

(1) Background: Prostate cancer is the most common cancer in men and can be treated with radical prostatectomy (RPE) or radiotherapy in the primary setting. Stereotactic radiotherapy (SBRT) has proven to be effective and well tolerated in this setting. However, if SBRT is an equally promising treatment option if applied in the adjuvant or salvage setting after RPE remains unknown. (2) Methods: We searched the PubMed and Embase databases with the following full-text queries in August 2021 for any combination of the terms "SBRT", "prostate", "adjuvant", "postoperative", "salvage", "stereotactic radiotherapy", "prostate bed". There were no limitations regarding publication date or language. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. (3) Results: We identified 11 individual studies that were included in this systematic review. Three publications included patients without prior radiotherapy and the remaining eight patients with prior radiotherapy. In all but two publications the radiation target was the macroscopic recurrence. SBRT was overall well tolerated with acceptable rates of acute and late gastrointestinal or genitourinary toxicity. Quality of life was published for two phase I trials with good results. There was a very heterogeneous reporting on biochemical control after SBRT. (4) Conclusions: At this point, ultra-hypofractionated RT using SBRT to the prostate bed remains experimental and its use should be restricted to clinical trials. Given the biological rationale for extreme hypofractionation in patients with prostate cancer and the acceptable toxicity rates that have been reported, further exploration of this field is warranted.

Introduction : Many proposed algorithms for tumor detection rely on 2.5/3D convolutional neural networks (CNNs) and the input of segmentations for training. The purpose of this study is therefore to assess the performance of tumor detection on single MRI slices containing vestibular schwannomas (VS) as a computationally inexpensive alternative that does not require the creation of segmentations. Methods : A total of 2992 T1-weighted contrast-enhanced axial slices containing VS from the MRIs of 633 patients were labeled according to tumor location, of which 2538 slices from 539 patients were used for training a CNN (ResNet-34) to classify them according to the side of the tumor as a surrogate for detection and 454 slices from 94 patients were used for internal validation. The model was then externally validated on contrast-enhanced and non-contrast-enhanced slices from a different institution. Categorical accuracy was noted, and the results of the predictions for the validation set are provided with confusion matrices. Results : The model achieved an accuracy of 0.928 (95% CI: 0.869-0.987) on contrast-enhanced slices and 0.795 (95% CI: 0.702-0.888) on non-contrast-enhanced slices from the external validation cohorts. The implementation of Gradient-weighted Class Activation Mapping (Grad-CAM) revealed that the focus of the model was not limited to the contrast-enhancing tumor but to a larger area of the cerebellum and the cerebellopontine angle. Conclusions : Single-slice predictions might constitute a computationally inexpensive alternative to training 2.5/3D-CNNs for certain detection tasks in medical imaging even without the use of segmentations. Head-to-head comparisons between 2D and more sophisticated architectures could help to determine the difference in accuracy, especially for more difficult tasks.

Introduction: In the spring of 2020, coronavirus disease 2019 posed a substantial challenge for countries and their healthcare systems. In Germany, over 70% of all cancer patients are treated in an outpatient setting, so gynecologic oncology practices are the guarantors of optimal patient care. We developed a survey to evaluate the management of gynecologic oncology patients., Methods: The survey consisted of 38 questions and was sent to the members of the Berufsverband Niedergelassener Gynäkologischer Onkologen in Deutschland e.V. (BNGO), a professional association of gynecologic oncologists in the outpatient sector in Germany., Results: The survey was completed by 54 out of 133 (41%) gynecologic oncologists from 14 out of 15 (93%) federal states where the BNGO is represented. Facing the pandemic, popular measures were mask requirements (100%), restriction of access to practices (94%), increased number of disinfectant dispensers (85%), installment of panes of acrylic glass (76%), or spatial alterations (67%). For most patients the pandemic had no influence on prioritization of therapies (82%) or prescribed systemic treatments (87%). Despite an increase in perceived psychological burden among the staff (72%), 85% (45/54) of the practices were not offered any additional psychological support., Discussion and Conclusion: As most cancer patients in Germany are treated in an outpatient setting, a suitable reaction of oncology centers to the new circumstances was crucial to secure optimal treatment and patient care. Nevertheless, the low prioritization of mental health or distress of healthcare workers poses a serious threat to the maintenance of optimal medical care in further waves of the pandemic., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2021 by S. Karger AG, Basel.)

As multiple different treatment options are available for prostate cancer (PCa) and YouTube is commonly used as a source for medical information, we performed a systematic and comparative assessment of available videos guiding patients on their choice for the optimal treatment. An independent search for surgical therapy or radiotherapy of PCa on YouTube was performed and the 40 most viewed videos of both groups were analyzed. The validated DISCERN questionnaire and PEMAT were utilized to evaluate their quality and misinformation. The median overall quality of the videos was found to be low for surgery videos, while radiotherapy videos results reached a moderate quality. The median PEMAT understandability score was 60% (range 0-100%) for radiotherapy and 75% (range 40-100) for surgery videos. The radiotherapy videos contained less misinformation and were judged to be of higher quality. Summarized, the majority of the provided videos offer insufficient quality of content and are potentially subject to commercial bias without reports on possible conflict of interest. Thus, most of available videos on YouTube informing PCa patients about possible treatment methods are not suited for a balanced patient education or as a basis for the patient's decision.

Study Objective: Our study sought to audit our institutional practice of routine single-shot caudal epidural hydromorphone injection in children undergoing congenital cardiothoracic surgery to assess perioperative pain control and evaluate for any caudal complications., Design: Retrospective observational study of all patients that received a caudal hydromorphone injection as part of the anesthetic for their cardiac surgical operation between January 2017 and July 2019., Setting: Pediatric Cardiothoracic Operating Room (OR), Cardiac Intensive Care Unit., Patients: One hundred and twenty-seven patients that received caudal hydromorphone as part of their anesthetic for a cardiac surgical operation., Interventions: Caudal epidural injection performed immediately following induction of anesthesia utilizing only hydromorphone., Measurements: The primary outcome was well-controlled pain, defined as a score of <4/10 on rFLACC or verbal pain scoring. Secondary outcome measures included in-OR extubation, pain service duration (from first assessment to "sign-off"), complications related to the caudal block, intensive care unit (ICU) length of stay (LOS), and Hospital LOS., Main Results: One hundred and nine patients were included in the final analysis. Pain was "well-controlled" on average in 96.3% of patients (105/109). Average pain in the 24-h post-block period was 1.67 (SD = 2.37), with median pain score of 0 [0-3]. Peak pain score remained <4/10 for the entire 24-h post-block period in 22% of patients. 77.1% of caudal hydromorphone patients were extubated in the operating room. The median time to heparinization post-block was 108 min, beyond the ASRA recommendation of 60 min for neuraxial procedures. There were two caudal-related complications: one subcutaneous injection, and one instance of a time to heparinization of less than 60 min (56 min). Neither caudal complication led to patient harm., Conclusion: Caudal hydromorphone injection can safely contribute to achieving "well-controlled" pain in the pediatric cardiac surgical population when used as a component of a perioperative pain control plan., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Definitive chemoradiotherapy (CRT) is standard of care for nasopharyngeal carcinoma. Due to the tumor localization and concomitant platinum-based chemotherapy, hearing impairment is a frequent complication, without defined dose-threshold. In this study, we aimed to achieve the maximum possible cochleae sparing., Materials and Methods: Treatment plans of 20 patients, treated with CRT (6 IMRT and 14 VMAT) based on the QUANTEC organs-at-risk constraints were investigated. The cochleae were re-delineated independently by two radiation oncologists, whereas target volumes and other organs at risk (OARs) were not changed. The initial plans, aiming to a mean cochlea dose < 45 Gy, were re-optimized with VMAT, using 2-2.5 arcs without compromising the dose coverage of the target volume. Mean cochlea dose, PTV coverage, Homogeneity Index, Conformity Index and dose to other OAR were compared to the reference plans. Wilcoxon signed-rank test was used to evaluate differences, a p value < 0.05 was considered significant., Results: The re-optimized plans achieved a statistically significant lower dose for both cochleae (median dose for left and right 14.97 Gy and 18.47 Gy vs. 24.09 Gy and 26.05 Gy respectively, p < 0.001) compared to the reference plans, without compromising other plan quality parameters. The median NTCP for tinnitus of the most exposed sites was 11.3% (range 3.52-91.1%) for the original plans, compared to 4.60% (range 1.46-90.1%) for the re-optimized plans (p < 0.001). For hearing loss, the median NTCP of the most exposed sites could be improved from 0.03% (range 0-99.0%) to 0.00% (range 0-98.5%, p < 0.001)., Conclusions: A significantly improved cochlea sparing beyond current QUANTEC constraints is feasible without compromising the PTV dose coverage in nasopharyngeal carcinoma patients treated with VMAT. As there appears to be no threshold for hearing toxicity after CRT, this should be considered for future treatment planning.

Background: Radiotherapy (RT) is an established, potentially curative treatment option for all risk constellations of localized prostate cancer (PCA). Androgen deprivation therapy (ADT) and dose-escalated RT can further improve outcome in high-risk (HR) PCA. In recent years, shorter RT schedules based on hypofractionated RT have shown equal outcome. Stereotactic body radiotherapy (SBRT) is a highly conformal RT technique enabling ultra-hypofractionation which has been shown to be safe and efficient in patients with low- and intermediate-risk PCA. There is a paucity of data on the role of SBRT in HR PCA. In particular, the need for pelvic elective nodal irradiation (ENI) needs to be addressed. Therefore, we conducted a systematic review to analyze the available data on observed toxicities, ADT prescription practice, and oncological outcome to shed more light on the value of SBRT in HR PCA., Methods: We searched the PubMed and Embase electronic databases for the terms "prostate cancer" AND "stereotactic" AND "radiotherapy" in June 2020. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations., Results: After a rigorous selection process, we identified 18 individual studies meeting all selection criteria for further analyses. Five additional studies were included because their content was judged as relevant. Three trials have reported on prostate SBRT including pelvic nodes; 2 with ENI and 1 with positive pelvic nodes only. The remaining studies investigated SBRT of the prostate only. Grade 2+ acute genitourinary (GU) toxicity was between 12% and 46.7% in the studies investigating pelvic nodes irradiation and ranged from 0% to 89% in the prostate only studies. Grade 2+ chronic GU toxicity was between 7% and 60% vs. 2% and 56.7%. Acute gastrointestinal (GI) grade 2+ toxicity was between 0% to 4% and 0% to 18% for studies with and without pelvic nodes irradiation, respectively. Chronic GI grade 2+ toxicity rates were between 4% and 50.1% vs. 0% and 40%. SBRT of prostate and positive pelvic nodes only showed similar toxicity rates as SBRT for the prostate only. Among the trials that reported on ADT use, the majority of HR PCA patients underwent ADT for at least 2 months; mostly neoadjuvant and concurrent. Biochemical control rates ranged from 82% to 100% after 2 years and 56% to 100% after 3 years. Only a few studies reported longer follow-up data., Conclusion: At this point, SBRT with or without pelvic ENI cannot be considered the standard of care in HR PCA, due to missing level 1 evidence. Treatment may be offered to selected patients at specialized centers with access to high-precision RT. While concomitant ADT is the current standard of care, the necessary duration of ADT in combination with SBRT remains unclear. Ideally, all eligible patients should be enrolled in clinical trials.

Objective: To assess the impact of (low) dose irradiation to the lungs and heart on the incidence of pneumonitis and pulmonary function changes after thoracic radiotherapy (RT). Methods/Material: Data of 62 patients treated with curative thoracic radiotherapy were analyzed. Toxicity data and pulmonary function tests (PFTs) were obtained before RT and at 6 weeks, at 12 weeks, and at 6 months after RT. PFTs included ventilation (e.g., vital capacity) and diffusion parameters (e.g., diffusion capacity for carbon monoxide (DL CO )). Dosimetric data of the lung and heart were extracted to assess the impact of dose on PFT changes and radiation pneumonitis (RP)., Results: No statistically significant correlations between dose parameters and changes in ventilation parameters were found. There were statistically significant correlations between DL CO and low-dose parameters of the lungs (V 5Gy -V 30Gy (%)) and irradiation of the heart during the follow-up up to 6 months after RT, as well as a temporary correlation of the V 60Gy (%) on the blood gas parameters at 12 weeks after RT. On multivariate analysis, both heart and lung parameters had a significant impact on DL CO . There was no statistically significant influence of any patient or treatment-related (including dose parameters) factors on the incidence of ≥G2 pneumonitis., Conclusion: There seems to be a lasting impact of low dose irradiation to the lung as well as irradiation to the heart on the DL CO after thoracic radiotherapy. No influence on RP was found in this analysis.

Multiple sclerosis (MS) is a chronic, inflammatory autoimmune disease that affects the central nervous system (CNS) for which there is no cure. In MS, encephalitogenic T cells infiltrate the CNS causing demyelination and neuroinflammation; however, little is known about the role of regulatory T cells (Tregs) in CNS tissue repair. Transplantation of neural stem and progenitor cells (NSCs and NPCs) is a promising therapeutic strategy to promote repair through cell replacement, although recent findings suggest transplanted NSCs also instruct endogenous repair mechanisms. We have recently described that dampened neuroinflammation and increased remyelination is correlated with emergence of Tregs following human NPC transplantation in a murine viral model of immune-mediated demyelination. In the current study we utilized the prototypic murine autoimmune model of demyelination experimental autoimmune encephalomyelitis (EAE) to test the efficacy of hNSC transplantation. Eight-week-old, male EAE mice receiving an intraspinal transplant of hNSCs during the chronic phase of disease displayed remyelination, dampened neuroinflammation, and an increase in CNS CD4 + CD25 + FoxP3 + regulatory T cells (Tregs). Importantly, ablation of Tregs abrogated histopathological improvement. Tregs are essential for maintenance of T cell homeostasis and prevention of autoimmunity, and an emerging role for Tregs in maintenance of tissue homeostasis through interactions with stem and progenitor cells has recently been suggested. The data presented here provide direct evidence for collaboration between CNS Tregs and hNSCs promoting remyelination., Competing Interests: Declaration of Competing Interest The authors have no competing interests to disclose., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)