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Brainstem metastases are challenging to manage owing to the critical neurological structures involved. Although stereotactic radiotherapy (SRT) offers targeted high doses while minimizing damage to adjacent normal tissues, the optimal dose fractionation remains undefined. This study evaluated the efficacy and safety of multifraction SRT with an inhomogeneous dose distribution. This retrospective study included 31 patients who underwent 33 treatments for 35 brainstem lesions using linear accelerator-based multifraction SRT (30 Gy in five fractions, 35 Gy in five fractions or 42 Gy in 10 fractions) with an inhomogeneous dose distribution (median isodose, 51.9%). The outcomes of interest were local failure, toxicity and symptomatic failure. The median follow-up time after brainstem SRT for a lesion was 18.6 months (interquartile range, 10.0-24.3 months; range, 1.8-39.0 months). Grade 2 toxicities were observed in two lesions, and local failure occurred in three lesions. No grade 3 or higher toxicities were observed. The 1-year local and symptomatic failure rates were 8.8 and 16.7%, respectively. Toxicity was observed in two of seven treatments with a gross tumor volume (GTV) greater than 1 cc, whereas no toxicity was observed in treatments with a GTV less than 1 cc. No clear association was observed between the biologically effective dose of the maximum brainstem dose and the occurrence of toxicity. Our findings indicate that multifraction SRT with an inhomogeneous dose distribution offers a favorable balance between local control and toxicity in brainstem metastases. Larger multicenter studies are needed to validate these results and determine the optimal dose fractionation., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Uterine atony is a major contributor to postpartum hemorrhage. We previously proposed the novel histological concept of postpartum acute myometritis (PAM) to elucidate the pathophysiology of uterine atony. This concept involves the infiltration of macrophages and neutrophils, as well as mast cell and complement activation in the myometrium. However, the pathological mechanism underlying uterine atony in the context of PAM remains unclear. Herein, we focused on uterine contraction-associated proteins (CAPs) including connexin 43 (Cx43), oxytocin receptors (OXR), prostaglandin receptors EP1, EP3, FP, and protease-activated receptor (PAR)-1. This follow-up study aimed to compare CAP expression between PAM and control groups. We selected 38 PAM subjects from the cases enrolled in our amniotic fluid embolism registry between 2011 and 2018. Control tissues from 10 parturients were collected during cesarean section. We stained the myometrial tissues with the following CAP markers, inflammatory cell markers, and other markers: Cx43, OXR, EP1, EP3, FP, PAR-1, C5a receptor, tryptase, neutrophil elastase, CD68, β-actin, and Na + /K + -ATPase. The immunostaining-positive areas of Cx43, OXR, EP1, EP3, and FP standardized by β-actin in the PAM tissue were significantly smaller than in the control group, whereas those of PAR-1 and Na + /K + -ATPase increased significantly in the PAM group. The Cx43- and OXR-positive areas correlated negatively with the immunostaining-positive cell numbers of CD68 and tryptase with halo, respectively. PAM may impair individual and synchronized myocyte contraction, leading to uterine atony refractory to uterotonics. Further cell-based studies are needed to elucidate the molecular mechanism by which inflammatory cells suppress CAP expression., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Tomoaki Oda, Naoaki Tamura, Naomi Furuta-Isomura, Naohiro Kanayama, and Hiroaki Itoh report financial support was provided by Japan Society for the Promotion of Science. Hiroaki Itoh reports financial support was provided by Japan Agency for Medical Research and Development. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Fractionated stereotactic radiosurgery (fSRS) is an important treatment strategy for unresected brain metastases. We previously reported that a good volumetric response 6 months after fSRS can be the first step for local control. Few studies have reported the association between gross tumor volume (GTV) dose, volumetric response, and local control in patients treated with the same number of fractions. Therefore, in this study, we aimed to investigate the GTV dose and volumetric response 6 months after fSRS in five daily fractions and identify the predictive GTV dose for local failure (LF) for unresected brain metastasis., Methods: This retrospective study included 115 patients with 241 unresected brain metastases treated using fSRS in five daily fractions at our hospital between January 2013 and April 2022. The median prescription dose was 35 Gy (range, 30-35 Gy) in five fractions. The median follow-up time after fSRS was 16 months (range, 7-66 months)., Results: GTV D80 > 42 Gy and GTV D98 > 39 Gy were prognostic factors for over 65% volume reduction (odds ratio, 3.68, p < 0.01; odds ratio, 4.68, p < 0.01, respectively). GTV D80 > 42 Gy was also a prognostic factor for LF (hazard ratio, 0.37; p = 0.01)., Conclusions: GTV D80 > 42 Gy in five fractions led to better volume reduction and local control. The goal of planning an inhomogeneous dose distribution for fSRS in brain metastases may be to increase the GTV D80 and GTV D98. Further studies on inhomogeneous dose distributions are required., (© 2024. The Author(s).)

Aim: In Japan, unlike Western countries, tocolytic agents are administered in long-term protocols to treat threatened preterm labor. Evaluating the side effects of this practice is crucial. We examined whether ritodrine hydrochloride had been administered in cases of maternal death, aiming to investigate any relationship between ritodrine administration and maternal death., Methods: This retrospective cohort study used reports of maternal deaths from multiple institutions in Japan between 2010 and 2020. Data on the reported cases were retrospectively analyzed, and data on the route of administration, administered dose, and clinical findings, including causes of maternal death, were extracted. The amount of tocolytic agents was compared between maternal deaths with ritodrine administration and those without., Results: A total of 390 maternal deaths were reported to the Maternal Death Exploratory Committee in Japan during the study period. Ritodrine hydrochloride was administered in 32 of these cases. The frequencies (n) and median doses (range) of oral or intravenous ritodrine hydrochloride were 34.4% (11) and 945 (5-2100) mg and 84.4% (27) and 4032 (50-18 680) mg, respectively. Frequencies of perinatal cardiomyopathy, cerebral hemorrhage, diabetic ketoacidosis, and pulmonary edema as causes of maternal death were significantly higher with ritodrine administration than without it., Conclusions: Our results suggest a relationship between long-term administration of ritodrine hydrochloride and an increased risk of maternal death due to perinatal cardiomyopathy, cerebral hemorrhage, diabetic ketoacidosis, and pulmonary edema. In cases where ritodrine should be administered to prevent preterm labor, careful management and monitoring of maternal symptoms are required., (© 2024 Japan Society of Obstetrics and Gynecology.)

Background/aim: Intensity-modulated radiation therapy can deliver a highly conformal dose to a target while minimizing the dose to the organs at risk (OARs). Delineating the contours of OARs is time-consuming, and various automatic contouring software programs have been employed to reduce the delineation time. However, some software operations are manual, and further reduction in time is possible. This study aimed to automate running atlas-based auto-segmentation (ABAS) and software operations using a scripting function, thereby reducing work time., Materials and Methods: Dice coefficient and Hausdorff distance were used to determine geometric accuracy. The manual delineation, automatic delineation, and modification times were measured. While modifying the contours, the degree of subjective correction was rated on a four-point scale., Results: The model exhibited generally good geometric accuracy. However, some OARs, such as the chiasm, optic nerve, retina, lens, and brain require improvement. The average contour delineation time was reduced from 57 to 29 min (p<0.05). The subjective revision degree results indicated that all OARs required minor modifications; only the submandibular gland, thyroid, and esophagus were rated as modified from scratch., Conclusion: The ABAS model and scripted automation in head and neck cancer reduced the work time and software operations. The time can be further reduced by improving contour accuracy., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: The study aimed to investigate the optimal isodose line (IDL) in linear accelerator-based stereotactic radiotherapy for single brain metastasis, using HyperArc. We compared the dosimetric parameters for target and normal brain tissue among six plans with different IDLs., Methods: This study included 30 patients with single brain metastasis. We retrospectively generated six plans for each tumor with different IDLs (80%, 70%, 60%, 50%, 40%, and 33%) using HyperArc. All treatment plans were normalized to the prescription dose of 35 Gy in five fractions which was covered by 95% of the planning target volume (PTV), defined by adding a 1.0 mm margin to the gross tumor volume (GTV). The dosimetric parameters were compared among the six plans., Results: For GTV > 0.1 cm 3 , the ratio of brain-GTV volumes receiving 25 Gy to PTV (V 25Gy /PTV) was significantly lower at IDL 40%-70% than at IDL 80% and 33% (p < 0.01, retrospectively). For GTV < 0.1 cm 3 , V 25Gy /PTV decreased continuously as IDL decreased. The values of D 99% and D 80% for GTV increased with decreasing IDL. An IDL of 50% or less was required to achieve D 99% of greater than 43 Gy and D 80% of greater than 50 Gy. The mean values of D 99% and D 80% for IDL 50% were 44.3 and 51.9 Gy., Conclusion: The optimal IDL is 40%-50% for GTV > 0.1 cm 3 . These lower IDLs could increase D 99% and D 80% of GTV while lowering V 25Gy of normal brain tissue, which may help reduce the risk of radiation necrosis and improve local control., (© 2024 The Author(s). Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

In linear accelerator-based stereotactic irradiation (STI) for brain metastasis, cone-beam computed tomography (CBCT) image quality is essential for ensuring precise patient setup and tumor localization. However, CBCT images may be degraded by the deviation of the CBCT isocenter from the brain center. This study aims to investigate the effects of the distance from the brain center to the CBCT isocenter (DBI) on the image quality in STI. An anthropomorphic phantom was scanned with varying DBI in right, anterior, superior, and inferior directions. Thirty patients undergoing STI were prospectively recruited. Objective metrics, utilizing regions of interest included contrast-to-noise ratio (CNR) at the centrum semiovale, lateral ventricle, and basal ganglia levels, gray and white matter noise at the basal ganglia level, artifact index (AI), and nonuniformity (NU). Two radiation oncologists assessed subjective metrics. In this phantom study, objective measures indicated a degradation in image quality for non-zero DBI. In this patient study, there were significant correlations between the CNR at the centrum semiovale and lateral ventricle levels (r s = - 0.79 and - 0.77, respectively), gray matter noise (r s = 0.52), AI (r s = 0.72), and NU (r s = 0.91) and DBI. However, no significant correlations were observed between the CNR at the basal ganglia level, white matter noise, and subjective metrics and DBI (r s  < ± 0.3). Our results demonstrate the effects of DBI on contrast, noise, artifacts in the posterior fossa, and uniformity of CBCT images in STI. Aligning the CBCT isocenter with the brain center can aid in improving image quality., (© 2024. Australasian College of Physical Scientists and Engineers in Medicine.)

Postoperative radiotherapy for breast cancer reportedly increases the risk of thoracic soft tissue sarcomas, particularly angiosarcomas; however, the risk in the Japanese population remains unknown. Therefore, this study aimed to investigate the incidence of thoracic soft tissue sarcoma among patients with breast cancer in Japan and determine its association with radiotherapy. This retrospective cohort study used data from the population-based cancer registry of the Osaka Prefecture. The inclusion criteria were female sex, age 20-84 years, diagnosis of breast cancer between 1990 and 2010, no supraclavicular lymph node or distant metastasis, underwent surgery and survived for at least 1 year. The primary outcome was the occurrence of thoracic soft tissue sarcomas 1 year or later after breast cancer diagnosis. Among the 13 762 patients who received radiotherapy, 15 developed thoracic soft tissue sarcomas (nine angiosarcomas and six other sarcomas), with a median time of 7.7 years (interquartile range, 4.0-8.6 years) after breast cancer diagnosis. Among the 27 658 patients who did not receive radiotherapy, four developed thoracic soft tissue sarcomas (three angiosarcomas and one other sarcoma), with a median time of 11.6 years after diagnosis. The 10-year cumulative incidence was higher in the radiotherapy cohort than in the non-radiotherapy cohort (0.087 vs. 0.0036%, P < 0.001). Poisson regression analysis revealed that radiotherapy increased the risk of thoracic soft tissue sarcoma (relative risk, 6.8; 95% confidence interval, 2.4-24.4). Thus, although rare, breast cancer radiotherapy is associated with an increased risk of thoracic soft tissue sarcoma in the Japanese population., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Rationale: Amniotic fluid embolism (AFE) is a fatal obstetric condition that often rapidly leads to severe respiratory and circulatory failure. It is complicated by obstetric disseminated intravascular coagulation (DIC) with bleeding tendency; therefore, the introduction of venoarterial extracorporeal membrane oxygenation (VA-ECMO) is challenging. We report the case of a patient with AFE requiring massive blood transfusion, rescued using VA-ECMO without initial anticoagulation., Patients Concerns: A 39-year-old pregnant patient was admitted with a complaint of abdominal pain. An emergency cesarean section was performed because a sudden decrease in fetal heart rate was detected in addition to DIC with hyperfibrinolysis. Intra- and post-operatively, the patient had a bleeding tendency and required massive blood transfusions. After surgery, the patient developed lethal respiratory and circulatory failure, and VA-ECMO was introduced., Diagnosis: Based on the course of the illness and imaging findings, the patient was diagnosed with AFE., Interventions: By controlling the bleeding tendency with a massive transfusion and tranexamic acid administration, using an antithrombotic ECMO circuit, and delaying the initiation of anticoagulation and anti-DIC medication until the bleeding tendency settled, the patient was managed safely on ECMO without complications., Outcomes: By day 5, both respiration and circulation were stable, and the patient was weaned off VA-ECMO. Mechanical ventilation was discontinued on day 6. Finally, she was discharged home without sequelae., Lessons: VA-ECMO may be effective to save the lives of patients who have AFE with lethal circulatory and respiratory failure. For safe management without bleeding complications, it is important to start VA-ECMO without initial anticoagulants and to administer anticoagulants and anti-DIC drugs after the bleeding tendency has resolved., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The aim of this study was to evaluate the effectiveness of intensity-modulated radiation therapy in combination with long-term androgen deprivation therapy for high-risk and very high-risk localized prostate cancer while also investigating factors associated with the therapeutic effect., Methods: Men who fulfilled criteria for the National Comprehensive Cancer Network high-risk or very high-risk localized prostate cancer and were treated with definitive intensity-modulated radiation therapy (74-78 Gy) of the prostate and the seminal vesicle combined with androgen deprivation therapy in our institution from 2007 to 2016 were identified (n = 197). In principle, patients received androgen deprivation therapy for 3-6 months before radiation, concurrently, and for 2 years after completion of intensity-modulated radiation therapy., Results: The median follow-up period was 96 months. The 5-year and 10-year overall survival rates in the overall population were 96.9% and 89.3%, respectively. The 5-year and 10-year cumulative incidence rates of biochemical failure were 2.5% and 16.3% in the high-risk group, and 8.6% and 32.0% in the very high-risk group, respectively, indicating a significant difference between the two groups (P = 0.023). Grade Group 5 and younger age (cutoff: 70 years old) were independent predictors of recurrence (P = 0.016 and 0.017, respectively). Patients exhibiting biochemical failure within <18 months after completion of androgen deprivation therapy displayed an increased risk of cancer-specific mortality (P = 0.039) when contrasted with those who had a longer interval to biochemical failure., Conclusions: Patients with the National Comprehensive Cancer Network very high-risk prostate cancer, particularly those with Grade Group 5 and younger age, showed worse outcomes following intensity-modulated radiation therapy and long-term androgen deprivation therapy., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The involvement of the human amygdala in facial mimicry remains a matter of debate. We investigated neural activity in the human amygdala during a task in which an imitation task was separated in time from an observation task involving facial expressions. Neural activity in the amygdala was measured using functional magnetic resonance imaging in 18 healthy individuals and using intracranial electroencephalogram in six medically refractory patients with epilepsy. The results of functional magnetic resonance imaging experiment showed that mimicry of negative and positive expressions activated the amygdala more than mimicry of non-emotional facial movements. In intracranial electroencephalogram experiment and time-frequency analysis, emotion-related activity of the amygdala during mimicry was observed as a significant neural oscillation in the high gamma band range. Furthermore, spectral event analysis of individual trial intracranial electroencephalogram data revealed that sustained oscillation of gamma band activity originated from an increased number and longer duration of neural events in the amygdala. Based on these findings, we conclude that during facial mimicry, visual information of expressions and feedback from facial movements are combined in the amygdalar nuclei. Considering the time difference of information approaching the amygdala, responses to facial movements are likely to modulate rather than initiate affective processing in human participants., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Amniotic fluid embolism (AFE) and placental abruption (PA) are typical obstetric diseases associated with disseminated intravascular coagulation (DIC). AFE is more likely to be complicated with enhanced fibrinolysis than PA. AFE may have an additional mechanism activating fibrinolytic cascade. We aimed to compare the coagulation/fibrinolysis factors among AFE, PA, and peripartum controls. We assessed AFE cases registered in the Japanese AFE Registry, and PA cases complicated with DIC (severe PA) and peripartum controls recruited at our hospital. The following factors in plasma were compared: prothrombin fragment 1 + 2 (PF1 + 2), plasmin α2-plasmin inhibitor complex (PIC), tissue factor (TF), tissue plasminogen activator (tPA), annexin A2 (AnnA2), total thrombin activatable fibrinolysis inhibitor (TAFI) including its activated form (TAFIa), and plasminogen activator inhibitor-type 1 (PAI-1). PF1 + 2 and PIC were markedly increased in both AFE (n = 27) and severe PA (n = 12) compared to controls (n = 23), without significant difference between those disease groups; however, PIC in AFE showed a tendency to elevate relative to PF1 + 2, compared with severe PA. AFE had significantly increased tPA and decreased total TAFI levels compared with severe PA and controls, which might be associated with further plasmin production in AFE and underlie its specific fibrinolytic activation pathway., (© 2024. The Author(s).)

Purpose: The geometric distortion related to magnetic resonance (MR) imaging in a diagnostic radiology (MR DR ) and radiotherapy (MR RT ) setup is evaluated, and the dosimetric impact of MR distortion on fractionated stereotactic radiotherapy (FSRT) in patients with brain metastases is simulated., Materials and Methods: An anthropomorphic skull phantom was scanned using a 1.5‑T MR scanner, and the magnitude of MR distortion was calculated with (MR DR -DC and MR RT -DC) and without (MR DR -nDC and MR RT -nDC) distortion-correction algorithms. Automated noncoplanar volumetric modulated arc therapy (HyperArc, HA; Varian Medical Systems, Palo Alto, CA, USA) plans were generated for 53 patients with 186 brain metastases. The MR distortion at each gross tumor volume (GTV) was calculated using the distance between the center of the GTV and the MR image isocenter (MIC) and the quadratic regression curve derived from the phantom study (MR RT -DC and MR RT -nDC). Subsequently, the radiation isocenter of the HA plans was shifted according to the MR distortion at each GTV (HA DC and HA nDC )., Results: The median MR distortions were approximately 0.1 mm when the distance from the MIC was < 30 mm, whereas the median distortion varied widely when the distance was > 60 mm (0.23, 0.47, 0.37, and 0.57 mm in MR DR -DC, MR DR -nDC, MR RT -DC, and MR RT -nDC, respectively). The dose to the 98% of the GTV volume (D 98% ) decreased as the distance from the MIC increased. In the HA DC plans, the relative dose difference of D 98% was less than 5% when the GTV was located within 70 mm from the MIC, whereas the underdose of GTV exceeded 5% when it was 48 mm (-26.5% at maximum) away from the MIC in the HA nDC plans., Conclusion: Use of a distortion-correction algorithm in the studied MR diagnoses is essential, and the dosimetric impact of MR distortion is not negligible, particularly for tumors located far away from the MIC., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Independent component analysis (ICA) is widely used today for scalp-recorded EEG analysis. One of the limitations of ICA-based analysis is polarity indeterminacy. It is not easy to find detailed documentations that explains engineering solutions of how the polarity indeterminacy is addressed in a given implementation. We investigated how it is implemented in the case of EEGLAB and also the relation between the outcome of the polarity determination and classification of independent components (ICs) in terms of the estimated nature of the sources (brain, muscle, eye, etc.) using an open database of n = 212 EEG dataset of resting state recordings. We found that (1) about 91% of ICs showed positive-dominant IC scalp topographies; (2) positive-dominant ICs were more associated with brain-originated signals; (3) positive-dominant ICs showed more radial (peaked at 10-30 degrees deviations from the radial axis) dipolar projection pattern with less residual variance from fitting the equivalent current dipole. In conclusion, using the EEGLAB's default ICA algorithm, one out of 10 ICs results in flipping its polarity to negative, which is associated with non-radial dipole orientation with higher residual variance. Thus, we determined EEGLAB biases toward positive polarity in decomposing high-quality brain ICs., (© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)