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Bone-modifying agents (BMAs) have been widely used to reduce skeletal-related events, including pathological fractures. Herein, we aimed to clarify the incidence of pathological fractures caused by high-risk femoral bone metastases after palliative radiotherapy (RT) in the BMA era and evaluate the necessity of prophylactic surgical stabilization. We assessed 90 patients with high-risk femoral bone metastases, indicated by Mirels' scores ≥ 8, without pathological fractures and surgical fixations, who received palliative RT at our institution between January 2009 and December 2018. Pathological fracture incidence was analyzed using the Kaplan-Meier method and was 22.8% and 31.0% at 2 and 6 months, respectively. Pathological fractures were caused by 17 of 65 lesions (26.2%) and 9 of 25 lesions (36.0%) in patients who received BMAs and those who did not, respectively ( p = 0.44). Additionally, 17 of 42 lesions (40.5%) and 9 of 48 lesions (18.8%) with axial cortical involvement ≥30 and <30 mm, respectively, caused pathological fractures ( p = 0.02). The incidence of pathological fractures was high among patients with high-risk femoral bone metastases treated with palliative RT, particularly those with axial cortical involvement ≥30 mm. Therefore, aggressive indications for prophylactic surgical stabilization are warranted for high-risk femoral metastases despite BMA administration.

Local failure of non-small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT) often occurs within 2 years and delayed local failure is uncommon. In the present study, features of late local failure (LLF; >2 years after SBRT) after SBRT were investigated and compared with those of early local failure (ELF; ≤2 years after SBRT) to explore whether these two local recurrence features have different prognostic implications. Patients who underwent SBRT for stage I-IIA NSCLC between July 2006 and March 2014 were retrospectively reviewed. Overall, 173 patients underwent SBRT for NSCLC. The median follow-up times after SBRT were 50 and 31 months for survival and computed tomography (CT) follow-up, respectively. LLF and ELF occurred in 7 and 13 patients, respectively. The median times to LLF and ELF were 42 months (range, 31-61 months) and 13 months (range, 4-16 months), respectively. Local-only failure occurred in 14% (1/7) of LLF cases and 77% (10/13) of ELF cases, which was significantly different (Fisher's exact test, P=0.02). Curative-intent salvage treatment was impossible in all of the LLF cases and 69% (9/13) of the ELF cases, which was significantly different (Fisher's exact test, P<0.01). The median survival times after local failure were 9 and 25 months for patients with LLF and ELF, respectively. Additionally, the 1-year overall survival rates after local failure were 29 and 83% in the LLF and ELF groups, respectively, which was significantly different (log-rank test, P<0.01 at 1-year). In summary, the prognosis after LLF was significantly unfavorable compared with after ELF. Curative-intent salvage treatment is often difficult for LLF due to metastases. Therefore, it seems reasonable to decrease the frequency of follow-up CT for detecting tumor recurrence after the first 2 years post-SBRT., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Makita et al.)

Introduction: Human alveolar echinococcosis caused by Echinococcus multilocularis is an important zoonotic disease in the northern hemisphere. The life cycle of E. multilocularis is maintained primarily in wild animals and requires an intermediate host (mainly small mammals). Human can become an intermediate host through accidental ingestion of E. multilocularis eggs. Hokkaido Prefecture is the only area of Japan in which human alveolar echinococcosis is endemic. The purposes of this study were to elucidate the land use ecological factors associated with the density of red fox feces along paved roads and the relationship between the distributions of red fox ( Vulpes vulpes ) populations and fox feces, which determine the level of hazard from eggs., Methods: A series of surveys was conducted in the central part of the Nemuro Peninsula of Hokkaido, excluding urban areas, over a total of 4 years in May-June in 2014 and 2016-2018 when red foxes remain with their cubs around the dens. Transects of 500 m were set up on paved roads, and feces within the transects were counted. Univariable and multivariable analyses were performed to examine ecological factors including the principal components (PCs) of five land use-type occupancy proportions within 500 m and 1 km, respectively, as explanatory fixed-effect variables. The number of feces in each transect was examined as the response variable using integrated nested Laplace approximation with negative binomial errors with a spatio-temporal autocorrelations structure to separate the effects of similarities of neighboring locations and annual variation. The multivariable models with the lowest widely applicable information criterion values were selected., Results: The feces density was explained by the PC of the 500- m buffer (-0.27, 2.5th and 97.5th percentiles: -0.44, -0.10) characterized by mixed forests (-0.82) and scarcity of residential areas (0.29) and the proximity to the nearest livestock farm house (-0.35, 2.5th and 97.5th percentiles: -0.53, -0.17). This suggested that foxes defecate in the areas where prey is abundant, avoiding humans., Discussion: Policy discussions regarding bait distribution design targeting these conditions should be initiated., Competing Interests: The 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 © 2024 Fukui, Uraguchi, Numa, Suzuki, Karasawa, Maita, Yokozawa, Hayama and Makita.)

Background: Shoseiryuto, a Japanese herbal medicine, is used to treat asthma exacerbation; however, the effect of Shoseiryuto in a clinical setting is yet to be elucidated. We aimed to examine the effect of Shoseiryuto for inpatients with asthma exacerbation and the reduction in the total amount of intravenous steroids administered during hospitalization, in-hospital mortality, and length of hospital stay using a national inpatient database in Japan., Methods: Using data from the Japanese Diagnosis Procedure Combination database (July 2010-March 2022), we identified patients aged ≥18 years who were admitted due to asthma exacerbation. We performed propensity score overlap weighting analyses to estimate the in-hospital outcomes between patients who received Shoseiryuto within 3 days of admission (Shoseiryuto group) and those who did not (control group). The outcomes measured were the dose of intravenous steroids administered, in-hospital mortality, and length of hospital stay for patients alive at discharge., Results: Among 51,459 eligible patients, 131 received Shoseiryuto. In the propensity score overlap weighting analyses, the use of Shoseiryuto was significantly associated with reduced amount of intravenous steroid during hospitalization (67 mg versus 149 mg, 95% confidence interval [CI]: -68 to -92), but was not associated with reduced in-hospital mortality (1.9% versus 3.5%, 95% CI: -28 to 25) or length of hospital stay (17.3 days versus 18.3 days, 95% CI: -4.2 to 2.4)., Conclusions: The use Shoseiryuto in inpatients with asthma exacerbation was significantly associated with reduced steroid use. Our results elucidated the potential role of Shoseiryuto in the treatment of asthma exacerbation., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2024 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

The purpose of the study was to explore the associations of serum non-esterified fatty acids (NEFA) and β-hydroxybutyrate (BHBA) concentrations with the body condition score (BCS) and rumen fill score (RFS) in order to predict the risk of postpartum culling, and to further investigate effective monitoring stages during the dry period. From October 2012 to March 2014, clinically healthy Holstein heifers and cows were sampled once before calving, and the occurrence of culling within 60 days in milk (DIM) was investigated. The discriminatory ability of each parameter was evaluated using receiver operating characteristic (ROC) analysis. Of the 720 cows sampled between 14 and 2 days before the actual day of calving in the study, 42 cull cows (mean DIM ± SE: 22.0 ± 2.6) were confirmed. The areas under the curve (AUC) of the ROC for predicting culling using serum NEFA concentrations were 0.6 and 0.7 at 14 to 2 and 7 to 2 days before calving, respectively. The AUC for the RFS was 0.7 for both periods, indicating the same diagnostic level as the serum NEFA concentration. Both the serum NEFA concentration and RFS were possible predictors in cows with ≥ 2 parities, but not in cows with 0-1 parity sampled even at 7 to 2 days before calving. The serum BHBA concentration and BCS were not suitable predictors of culling for any period or parity. These results indicate that RFS has a discriminatory ability comparable to the serum NEFA concentration for predicting culling within 60 DIM., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest associated with this manuscript., (Copyright © 2024. Published by Elsevier Ltd.)

Background: This study aimed to investigate the association between radiotherapy-related factors and the incidence of severe weight loss (WL) during radiotherapy in patients with head and neck squamous cell carcinoma (HNSCC) in the intensity-modulated radiation therapy (IMRT) era., Materials and Methods: Seventy-nine patients with HNSCC who received IMRT between January 2011 and December 2020 were reviewed. The 10% WL was defined as severe WL. The median prescribed doses of IMRT were 70 Gy for the high-risk planning target volume (HRPTV); 60 Gy for the intermediate-risk planning target volume (IRPTV); 54 Gy for the low-risk PTV., Results: Larger volumes of ≥ 60 Gy (PTV60Gy) had a significant impact on WL, whereas volumes of ≥ 70 Gy and ≥ 54 Gy did not. PTV60Gy to the ipsilateral level II or III necks had a significant impact on WL, whereas PTV60Gy to the ipsilateral levels I, IV, V, or VII did not. The primary site of the nasopharynx/oropharynx had a significant impact on WL, whereas the hypopharynx/larynx did not. In the stepwise regression and multivariate analyses, primary site and PTV60Gy volume were important factors for severe WL., Conclusions: Reducing the PTV60Gy volume can be useful in reducing severe WL. Because the clinical significance of IRPTV is unclear, the omission of IRPTV should be considered while balancing risks and benefits., Competing Interests: Conflict of interest: The authors declare that they have no conflict of interest., (© 2024 Greater Poland Cancer Centre.)

Pregnancy is associated with profound changes in immunity. However, pregnancy-related respiratory immune adaptations in response to influenza infection and their impact on disease severity remain unclear. Here, we describe, in a preclinical model of mid-gestation pregnancy, a mechanism of enhanced host defense against influenza A virus (IAV) localized to the nasal cavity that limits viral replication and reduces the magnitude of intrapulmonary immune responses. Consequently, the pregnant mice show reduced pulmonary pathology and preserved airway function after IAV infection. The early restriction of viral replication is independent of type I interferon (IFN) but dependent on increased antimicrobial peptides (AMPs) driven by interleukin-17 + (IL-17 + ) γδ + T cells within the nasal passages. This pathway of host defense against IAV infection in the upper airways during pregnancy restricts early viral infection and prevents virus dissemination into the lung supporting maternal fitness.

The present study investigated the prognosis of patients who received palliative radiotherapy (RT) for bone metastases (BMs) from renal cell cancer (RCC), and assessed the prognostic factors specific to BMs from RCC. A total of 109 patients with RCC and BMs who underwent RT for the first time were included in the study. Prognostic factors were evaluated using multivariate analysis and a scoring system based on regression coefficients was devised. The median follow-up time was 9 months, and the 0.5-year overall survival (OS) rate was 73.0%. In the multivariate analysis, the significant prognostic factors were higher performance status (≥2), no control of the primary site, disseminated metastasis, lymph node metastasis and multiple BMs. A score of 1 point was assigned to each risk factor. The median OS times were 19.0 and 5.0 months in patients with a total score of ≤1 (n=49) and >1 (n=60), respectively (P<0.01). In conclusion, a comprehensive prognostic assessment using these factors may be useful for predicting the prognoses of patients with BMs from RCC. In addition, this scoring system may be useful in selecting the optimal RT dose., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Makita et al.)

In 2018, classical swine fever (CSF) reemerged in Gifu Prefecture, Japan, after 26 years of absence, and vaccination of domestic pigs using a live attenuated vaccine was initiated in 2019. Because the vaccine efficacy in piglets is influenced by the maternal antibody levels, vaccination should be administered at the optimal age by assuming the antibody level in sows. In this study, the shift in the antibody titer distribution in sows due to the initiation of vaccination to naïve herds and its influence on the vaccine-induced immunity rate in fattening pigs were investigated for 3 years. The results indicated that higher antibody titers were induced in first-generation sows after vaccine initiation because they were immunologically naïve, but the distribution of antibody titers shifted to lower levels along with their replacement with second-generation sows. The average vaccination age of fattening pigs became earlier year by year, and the vaccine-induced antibody rate was almost ≥80%. Based on the estimation of the optimal age for vaccination, it was found that vaccination at a younger age may reduce the risk of CSF infection. Taken together, the risk of CSF outbreaks can be reduced by administering vaccines at the optimal age based on the sequential monitoring of the sow's immune status.

The control of digital dermatitis (DD) among cattle is crucial; however, effective and environmentally-sound control measures have yet to be identified. From the monitoring data of DD which were recorded during regular hoof trimmings in a farm in Hokkaido, Japan, we detected a decrease in the DD prevalence in a herd where an anaerobic bacterial fermentation enhancer (ABFE) was distributed. The possible effect of ABFE was analyzed using a retrospective repeated cross-sectional design. The prevalence of DD decreased over time in the ABFE-distributed group. Furthermore, a selected regression model indicated the time-dependent enhancement of the decreasing trend. While potential coincidental factors may influence, this study provides a basis for further research on the preventive effect of ABFE against DD.

Osmotic demyelination syndrome (ODS) occurs in patients with diabetes and hyponatremia. We herein report a case of ODS with chorea detected on serial magnetic resonance imaging (MRI), despite no prompt hyponatremia correction. A 74-year-old man with cirrhosis and uncontrolled type 2 diabetes developed an altered mental status and chorea during treatment for diabetic ketoacidosis (DKA). Despite no rapid sodium correction and normal initial brain MRI findings, serial MRI revealed ODS-related abnormalities. Clinicians should consider ODS in patients with DKA and a hyperosmolar hyperglycemic state displaying unconsciousness and neurological manifestations, including chorea, even without substantial changes in serum sodium levels. An MRI re-examination can help capture missing ODS complications.

The development of next-generation sequencing (NGS) has enabled the discovery of cancer-specific driver gene alternations, making precision medicine possible. However, accurate genetic testing requires a sufficient amount of tumor cells in the specimen. The evaluation of tumor content ratio (TCR) from hematoxylin and eosin (H&E)-stained images has been found to vary between pathologists, making it an important challenge to obtain an accurate TCR. In this study, three pathologists exhaustively labeled all cells in 41 regions from 41 lung cancer cases as either tumor, non-tumor or indistinguishable, thus establishing a "gold standard" TCR. We then compared the accuracy of the TCR estimated by 13 pathologists based on visual assessment and the TCR calculated by an AI model that we have developed. It is a compact and fast model that follows a fully convolutional neural network architecture and produces cell detection maps which can be efficiently post-processed to obtain tumor and non-tumor cell counts from which TCR is calculated. Its raw cell detection accuracy is 92% while its classification accuracy is 84%. The results show that the error between the gold standard TCR and the AI calculation was significantly smaller than that between the gold standard TCR and the pathologist's visual assessment (p<0.05). Additionally, the robustness of AI models across institutions is a key issue and we demonstrate that the variation in AI was smaller than that in the average of pathologists when evaluated by institution. These findings suggest that the accuracy of tumor cellularity assessments in clinical workflows is significantly improved by the introduction of robust AI models, leading to more efficient genetic testing and ultimately to better patient outcomes.

Plasma aldosterone concentration (PAC) was routinely measured using radioimmunoassay (RIA); however, the RIA kit was discontinued in March 2021 in Japan. This study examined PAC conversion in adrenal venous sampling (AVS) and AVS criteria when measured using chemiluminescent enzyme immunoassay (CLEIA). PAC of 415 adrenal venous blood samples from AVS (including segmental AVS) of 63 patients with primary aldosteronism was measured using RIA (Spac-S aldosterone kit; Fujirebio Inc.) and CLEIA (Lumipulse Presto Aldosterone; Fujirebio Inc.). PAC of 70 AVS samples was also measured using liquid chromatography-mass spectrometry (LC-MS/MS, ASKA Pharma Medical Co., Ltd.). PAC conversion formulas were determined for each AVS sample assay. PAC measured using CLEIA was significantly correlated with that measured using RIA (correlation coefficient = 0.971). The PAC conversion formula was PAC (CLEIA) = PAC (RIA) × 0.772 - 1,199 pg/mL. The PAC of 14,000 pg/mL in RIA was equivalent to 9,613 pg/mL in CLEIA. PAC measured using CLEIA was also correlated with that measured using LC-MS/MS, and the PAC conversion formula was PAC (CLEIA, pg/mL) = 0.97 × PAC (LC-MS/MS, pg/mL) + 211. The inter-assay coefficient of variability (CV) was 1.1-1.3% and intra-assay CV was 1.0-1.7%, measured using CLEIA. The PAC conversion formula for AVS samples was obtained using CLEIA and RIA, and the conversion formula was different from that for peripheral blood. PAC values measured by CLEIA showed preferable accuracy and high concordance with those measured by LC-MS/MS, even in AVS samples. The study outcomes are useful for interpreting AVS results using non-RIA measurement methods.

Livestock excrement is composted and applied to agricultural soils. If composts contain antimicrobial-resistant bacteria (ARB), they may spread to the soil and contaminate cultivated crops. Therefore, we investigated the degree of transmission of ARB and related antimicrobial resistance genes (ARGs) and, as well as clonal transmission of ARB from livestock to soil and crops through composting. This study was conducted at Rakuno Gakuen University farm in Hokkaido, Japan. Samples of cattle feces, solid and liquid composts, agricultural soil, and crops were collected. The abundance of Escherichia coli, coliforms, β-lactam-resistant E. coli, and β-lactam-resistant coliforms, as well as the copy numbers of ARG (specifically the bla gene related to β-lactam-resistant bacteria), were assessed using qPCR through colony counts on CHROMagar ECC with or without ampicillin, respectively, 160 days after compost application. After the application of the compost to the soil, there was an initial increase in E. coli and coliform numbers, followed by a subsequent decrease over time. This trend was also observed in the copy numbers of the bla gene. In the soil, 5.0 CFU g-1 E. coli was detected on day 0 (the day post-compost application), and then, E. coli was not quantified on 60 days post-application. Through phylogenetic analysis involving single nucleotide polymorphisms (SNPs) and using whole-genome sequencing, it was discovered that clonal blaCTX-M-positive E. coli and blaTEM-positive Escherichia fergusonii were present in cattle feces, liquid compost, and soil on day 0 as well as 7 days post-application. This showed that livestock-derived ARB were transmitted from compost to soil and persisted for at least 7 days in soil. These findings indicate a potential low-level transmission of livestock-associated bacteria to agricultural soil through composts was observed at low frequency, dissemination was detected. Therefore, decreasing ARB abundance during composting is important for public health., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Fukuda 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.)

Childhood maltreatment is reportedly associated with atypical gray matter structures in the primary visual cortex (V1). This study explores the hypothesis that retinal structures, the sensory organs of vision, are associated with brain atypicality and child maltreatment and examines their interrelation. General ophthalmologic examinations, visual cognitive tasks, retinal imaging, and structural magnetic resonance imaging (MRI) were conducted in children and adolescents aged 9-18 years with maltreatment experiences (CM) and typically developing (TD) children. The retinal nerve fiber layer (RNFL), the most superficial of the ten distinct retinal layers, was found to be significantly thinner in both eyes in CM. While whole-brain analysis using Voxel-based morphometry revealed a significantly larger gray matter volume (GMV) in the thalamus in CM, no significant correlation with RNFL thickness was observed. However, based on region-of-interest analysis, a thinner RNFL was associated with a larger GMV in the right V1. Although it cannot be ruled out that this outcome resulted from maltreatment alone, CM demonstrated subclinical structural atypicality in the retina, which may also correlate with the immaturity of V1 development. Examination of retinal thickness offers a novel clinical approach to capturing characteristics associated with childhood maltreatment., (© 2024. The Author(s).)

Background and Purpose: Spread-through air space (STAS) is an unfavorable factor in patients with lung cancer treated with surgery. However, the relationship between the treatment outcomes of stereotactic body radiation therapy (SBRT) for lung cancer and STAS has not been adequately investigated. This study aimed to evaluate the impact of tumor cells in the air space (TCIAS), which show a STAS burden, on treatment outcomes in patients with early-stage lung cancer treated with SBRT., Materials and Methods: Data of patients who underwent SBRT for early-stage lung cancer treated with SBRT were retrospectively reviewed. The influence of the TCIAS status on local progression-free (LPF), regional failure-free (RFF), distant failure-free (DFF), progression-free survival (PFS), and overall survival (OS) rates was assessed using univariate and multivariate analyses., Results: Overall, 68 patients were included. The median follow-up time was 24.3 months. For patients positive/negative for TCIAS, the 2-year LPF, RFF, DFF, PFS, and OS rates were 81.4 %/91.1 %, 73.7 %/96.2 %, 55.9 %/75.3 %, 55.0 %/84.6 %, and 67.8 %/92.2 %, respectively. In the multivariate analysis, TCIAS-positive was a significant unfavorable factor for RFF (hazard ratio [HR]: 4.10; 95 % confidence interval [CI]: 1.04-16.16, p = 0.04), DFF (HR: 2.61, 95 % CI: 1.03-6.57, p = 0.04), and PFS (HR: 2.36; 95 % CI: 1.05-5.30, p = 0.04). By contrast, TCIAS-positive was not a significant risk factor for LPF and OS., Conclusion: TCIAS-positive is an unfavorable factor for regional and distant failure after SBRT. TCIAS status may be useful in predicting the treatment outcome of SBRT for early-stage lung cancer., Competing Interests: Toshiyuki Kozuki received honorarium from MSD, Ono, Kyowa Hakko Kirin, AstraZeneca, Boehringer Ingelheim, Chugai, TAIHO, Eli Lilly, Bristol Myers Squibb, Pfizer, Merck Biopharma, Nippon Kayaku, Novartis, Bayer, Sawai and AMGEN, consulting fee from Chugai, AstraZeneca, Ono, Pfizer, Daiichi-Sankyo, Bayer, and Abbvie, and received research funding MSD, Kyowa Hakko Kirin, AstraZeneca, Eli Lilly, Pfizer, Chugai, TAIHO, Ono, Bristol-Myers, Merck Biopharma, Daiichi-Sankyo, AbbVie, AMGEN, Sanofi, Eisai, Labcorp Development, IQVIA Services, Gilead Sciences, Pfizer, and Bayer. All other authors declare that they have no conflict of interest., (© 2024 The Author(s).)

Child maltreatment can adversely affect brain development, leading to vulnerabilities in brain structure and function and various psychiatric disorders. Among the various types of child maltreatment, neglect has the highest incidence rate (76.0%); however, data on its sole adverse influence on the brain remain limited. This case-control brain magnetic resonance imaging (MRI) study identified the changes in gray matter structure and function that distinguish neglected children with no other type of maltreatment (Neglect group, n = 23) from typically developing children (TD group, n = 140), and investigated the association between these structural and functional differences and specific psychosocial phenotypes observed in neglected children. Our results showed that the Neglect group had a larger right and left anterior cingulate cortex (R/L.ACC) and smaller left angular gyrus (L.AG) gray matter volume. The larger R/L.ACC was associated with hyperactivity and inattention. Resting-state functional analysis showed increased functional connectivity (FC) between the left supramarginal gyrus (L.SMG) in the salience network (SN) and the right middle frontal gyrus (R.MFG) simultaneously with a decrease in FC with the L.ACC for the same seed. The increased FC for the R.MFG was associated with difficulty in peer problems and depressive symptoms; a mediating effect was evident for depressive symptoms. These results suggest that the structural atypicality of the R/L.ACC indirectly contributes to the disturbed FCs within the SN, thereby exacerbating depressive symptoms in neglected children. In conclusion, exposure to neglect in childhood may lead to maladaptive brain development, particularly neural changes associated with depressive symptoms., Competing Interests: Declaration of competing interest The authors 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 The Authors. Published by Elsevier Inc. All rights reserved.)

In asthma, CD4 + T-cell interaction with airway smooth muscle (ASM) may enhance its contractile properties and promote its proliferation. However, less is known about the effects of this interaction on T cells. To explore the consequences of interaction of CD4 + T cells with ASM we placed the cells in co-culture and analyzed the phenotypic and functional changes in the T cells. Effector status as well as cytokine expression was assessed by flow cytometry. An increase in CD45RA - CD45RO + memory T cells was observed after co-culture; however, these cells were not more responsive to CD3/28 restimulation. A reduction in mitochondrial coupling and an increase in the production of mitochondrial reactive oxygen species by CD4 + T cells post-restimulation suggested altered mitochondrial metabolism after co-culture. RNA sequencing analysis of the T cells revealed characteristic downregulation of effector T-cell-associated genes, but a lack of upregulation of memory T-cell-associated genes. The results of this study demonstrate that ASM cells can induce a phenotypic shift in CD4 + T cells into memory-like T cells but with reduced capacity for activation., (© 2024 The Authors. European Journal of Immunology published by Wiley‐VCH GmbH.)

This study aimed to investigate the changes in dose distribution in the heart and left anterior descending coronary artery region (LADR) during intensity-modulated radiation therapy (IMRT) in patients with esophageal cancer (EC) treated at our institution. The heart and LADR were delineated on the initial and off-cord boost planning computed tomography (CT) images. Cardiac volume reduction (CVR) was defined as the reduction in cardiac volume between the initial CT and off-cord boost CT at the dose of 36 Gy irradiated. The involved field IMRT plan was created based on each initial and off-cord boost CT image and was analyzed based on the relationship between CVR and heart and LADR dose-volume parameters (Heart-Dmax, Heart-Dmean, Heart-V20, Heart-V30, Heart-V40, LADR-Dmax, LADR-Dmean, LADR-V15 and LADR-V30). Forty patients with EC were investigated between January 2016 and January 2022. The median CVR ratio during radiation therapy (RT) was 5.57% (range, -7.79 to 18.26%). Simple linear regression analysis revealed significant correlations between CVR during RT and changes in the heart and LADR dose-volume parameters. Some patients (>10%) experienced severe changes in the heart and LADR dose distribution. In three cases with reduced heart volume and primary tumor mass, the changes in LADR-V15 and LADR-V30 showed outliers. In conclusion, CVR during RT correlated with an increase in the heart and LADR dose. When both CVR and tumor volume reduction are large, a potential overdose of LADR during RT should be noted in the IMRT era., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

The clinical significance of mild internal mammary node (IMN) enlargement (Mild-IMN) is uncertain. This study aimed to evaluate the relationship between treatment outcomes and IMN status in patients with breast cancer who underwent postmastectomy radiation therapy between January 2010 and December 2018. Overall, 250 patients were categorized based on IMN status: Clinically normal IMN (Normal-IMN; n=172), Mild-IMN (n=39) and clinically metastatic IMN (cMet-IMN; n=39). None of the patients in the Normal- or Mild-IMN groups received IMN irradiation. In the cMet-IMN group, 25 patients underwent IMN irradiation with an IMN boost (10 Gy in 5 fractions), while 14 patients did not. The median follow-up time was 80.0 months (range, 7.2-147.6 months). The 7-year overall survival (OS), disease-free survival (DFS) and IMN recurrence-free survival (IRF) rates were 80.2, 73.0 and 93.4%, respectively. Multivariate analyses indicated that only cMet-IMN had a significant impact on OS [hazard ratio (HR), 1.66; 95% CI, 1.01-3.68; P=0.05] and DFS (HR, 1.91; 95% CI, 1.08-3.39; P=0.03), while cMet-IMN did not have a significant impact on IRF (HR, 1.66; 95% CI, 0.41-6.78; P=0.48). Additionally, receiving an IMN boost had no influence on OS (HR, 1.11; 95% CI, 0.37-2.34; P=0.84), DFS (HR, 1.28; 95% CI, 0.51-3.22; P=0.60) or IRF (HR, 1.94; 95% CI, 0.22-17.47; P=0.55). In conclusion, the impact of Mild-IMN on clinical outcomes was small. Although irradiation for cMet-IMN is important, the impact of the cMet-IMN boost with 10 Gy in 5 fractions on clinical outcomes may also be limited., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Makita et al.)

Objective: This study aimed to identify the relationship between bovine brucellosis prevalence, farmers' knowledge, attitude, practice (KAP), and social factors on migratory draft cattle and smallholder dairy farms in the central dry zone of Myanmar., Methods: This cross-sectional study was conducted on 54 migratory and 38 dairy cattle farms between August 2020 and February 2021. A structured questionnaire was used to identify farmers' behaviors. Bulk milk was sampled and tested using indirect enzyme-linked immunosorbent assay (I-ELISA). STATA 17 was used for all the analyses., Results: Migratory cattle farms had a higher farm level brucellosis prevalence (14.8%) than dairy farms (2.6%; χ2 = 3.75; df = 1; p = 0.05). Only 2.8% of the farmers had knowledge about brucellosis, while 39.1% and 41.6% had attitudes and farm practices with respect to brucellosis, respectively in the study area. Socio-economic attribute of training in animal husbandry (p<0.01), raising system (p<0.01), practice of separating the aborted cow (p<0.01) were negatively associated to brucellosis. The overall farm level brucellosis prevalence was strongly associated with cattle herd size (p = 0.01), free movement grazing practices (p<0.01), practice of self-removal of placental debris without using personal protective equipment (p<0.01) and farmers' attitudes towards eating cow placenta debris (p<0.01)., Conclusion: Farmers had little knowledge of brucellosis. Attitudes and practices differed significantly between migratory and dairy farmers. Training and extension programs are necessary to make farmers aware of their KAP situation since livestock migration and the custom of eating cow placental debris contribute to the spread of brucellosis. Persistent efforts are required to reduce the adverse effects of brucellosis. Therefore, the study suggests that a feasible control intervention and public awareness campaigns need to be conducted regarding methods of preventing human exposure to brucellosis.

Rabies is endemic in South Africa and rabies cycles are maintained in both domestic and wildlife species. The significant number of canine rabies cases reported by the World Organization for Animal Health Reference Laboratory for Rabies at Onderstepoort suggests the need for increased research and mass dog vaccinations on specific targeted foci in the country. This study aimed to investigate the spatiotemporal distribution of animal rabies cases from 1998 to 2017 in northern South Africa and environmental factors associated with highly enzootic municipalities. A descriptive analysis was used to investigate temporal patterns. The Getis-Ord Gi statistical tool was used to exhibit low and high clusters. Logistic regression was used to examine the association between the predictor variables and highly enzootic municipalities. A total of 9580 specimens were submitted for rabies diagnosis between 1998 and 2022. The highest positive case rates were from companion animals (1733 cases, 59.71%), followed by livestock (635 cases, 21.88%) and wildlife (621 cases, 21.39%). Rabies cases were reported throughout the year, with the majority occurring in the mid-dry season. Hot spots were frequently in the northern and eastern parts of Limpopo and Mpumalanga. Thicket bush and grassland were associated with rabies between 1998 and 2002. However, between 2008 and 2012, cultivated commercial crops and waterbodies were associated with rabies occurrence. In the last period, plantations and woodlands were associated with animal rabies. Of the total number of municipalities, five consistently and repeatedly had the highest rabies prevalence rates. These findings suggest that authorities should prioritize resources for those municipalities for rabies elimination and management.

The present study investigated the factors contributing to cardiac volume reduction (CVR) during radiotherapy (RT) in patients with esophageal carcinoma (EC). This retrospective study included patients with EC treated at National Hospital Organization Shikoku Cancer Center (Matsuyama, Japan). Cardiac delineation was based on initial and off-cord boost (spinal cord-sparing approach) planning computed tomography images. The relationship between CVR and other relevant parameters was analyzed. A total of 58 patients with EC were investigated between January 2016 and January 2022. Univariate and multiple regression analyses revealed a statistically significant association between CVR during RT and the change ratio of the inferior vena cava (IVC) volume and body mass index (BMI) loss. In multivariate analysis of CVR of >10%, only the change in IVC volume exhibited a significant association. Conversely, CVR during RT displayed no association with heart dose-volume parameters, laboratory data, or changes in blood pressure and pulse rate. Among the 12 cases with CVR of >10%, the median movement of the left anterior descending coronary artery region (LADR) was 1.35 cm (range, 0.0-2.7 cm). In conclusion, CVR during RT was most strongly associated with changes in IVC volume, suggesting dehydration as the primary cause, rather than radiation-induced heart damage. LADR movement due to a CVR of >10% may lead to LADR radiation overdose., Competing Interests: Not applicable., (Copyright: © Makita et al.)

The present study investigated the differences between digital [18F]-Fluorodeoxyglucose (FDG) positron emission tomography [PET]/computed tomography [CT] (dPET/CT) and conventional PET/CT (cPET/CT) in delineating the clinical target volume (CTV) in patients with advanced lung cancer in the involved field radiation therapy (IFRT) era. Patients with advanced lung cancer were scanned using two dual-imaging protocols (dPET/CT and cPET/CT). Two virtual delineations contoured with reference to dPET/CT and cPET/CT images were created for each patient by five radiation oncologists. Changes in the delineation of target volumes in each patient were examined. A total of 10 patients [male/female, 9/1; median age, 65 years (range, 58-80 years)] were enrolled between April 2020 and September 2020. Significant changes in the delineation of CTVs were uncommon between dPET/CT and cPET/CT. A notable increase in CTVn was observed in 10% of the patients (1/10; P<0.05; Smirnov-Grubbs analysis). In this patient, a node that was not assessed as lymph node metastasis when cPET/CT was used was assessed as lymph node metastasis when dPET/CT was used and was included in the CTVn by all five radiation oncologists. In patients with advanced lung cancer, notable changes in CTV delineations are uncommon, regardless of whether dPET/CT or cPET/CT is used. However, in some cases, CTVn delineation with reference to dPET/CT may improve the treatment outcomes of IFRT for advanced lung cancer., Competing Interests: TKo received an honorarium from MSD, Ono, Kyowa Hakko Kirin, AstraZeneca, Boehringer Ingelheim, Chugai, TAIHO, Eli Lilly, Bristol Myers Squibb, Pfizer, Merck Biopharma, Nippon Kayaku, Novartis, Bayer, Sawai, and AMGEN; consulting fee from Chugai, AstraZeneca, Ono, Pfizer, Daiichi-Sankyo, Bayer, and Abbvie; and received research funding from MSD, Kyowa Hakko Kirin, AstraZeneca, Eli Lilly, Pfizer, Chugai, TAIHO, Ono, Bristol-Myers, Merck Biopharma, Daiichi-Sankyo, AbbVie, AMGEN, Sanofi, Eisai, LabCorp Development, IQVIA Services, Gilead Sciences, Pfizer, and Bayer. All other authors declare that they have no competing interests., (Copyright: © Makita et al.)

Objectives: To clarify the differences between two left sampling sites (left adrenal central vein [LCV] and common trunk [CMT], conjunction with LCV and inferior phrenic vein) and their impact on adrenal venous sampling (AVS) in primary aldosteronism by analyzing the results of segmental AVS (sAVS)., Methods: We retrospectively analyzed a final cohort of 432 patients who underwent cosyntropin-stimulated sAVS from 2017 to 2020. Hormone levels in the LCV and the CMT were compared. Subtype diagnosis was based on the lateralization index with LCV and CMT sampling (a cutoff value of 4) and sAVS after excluding patients with a selectivity index (SI) <3., Results: Compared with the LCV, CMT sampling showed significantly lower aldosterone and cortisol levels and a higher proportion of cases with an SI of <3 (2.8% vs 0.5%, p = 0.025) and <5 (6.9% vs 0.5%, p < 0.001), while the aldosterone-to-cortisol ratio and the lateralization index were not significantly different. Subtyping of both sites was concordant in 94.7% (393/415) and discordant in the remainder, which included left and right aldosterone-producing adenoma and idiopathic hyperaldosteronism cases referring to the sAVS. There was no significant difference between the concordance rate of the two sampling sites based on the sAVS diagnosis., Conclusions: LCV sampling meets the SI criteria for successful AVS more frequently compared with CMT sampling, but neither was better than the other in terms of diagnosis under conditions of meeting the criteria., Advances in Knowledge: LCV sampling would decrease the number of cases judged as AVS failure.

Background Aims: With the aim of strengthening the scientific evidence of immune-cell therapy for cancer and further examining its safety, in October 2015, our hospital jointly established the Cancer Immune-Cell Therapy Evaluation Group (CITEG) with 39 medical facilities nationwide., Methods: Medical information, such as patients' background characteristics, clinical efficacy and therapeutic cell types obtained from each facility, has been accumulated, analyzed and evaluated by CITEG. In this prospective study, we analyzed the adverse events associated with immune-cell therapy until the end of September 2022, and we presented our interim safety evaluation., Results: A total of 3839 patients with malignant tumor were treated with immune-cell therapy, with a median age of 64 years (range, 13-97 years) and a male-to-female ratio of 1:1.08 (1846:1993). Most patients' performance status was 0 or 1 (86.8%) at the first visit, and 3234 cases (84.2%) were advanced or recurrent cases, which accounted for the majority. The total number of administrations reported in CITEG was 31890, of which 960 (3.0%) showed adverse events. The numbers of adverse events caused by treatment were 363 (1.8%) of 19661 administrations of αβT cell therapy, 9 of 845 administrations of γδT-cell therapy (1.1%) and 10 of 626 administrations of natural killer cell therapy (1.6%). The number of adverse events caused by dendritic cell (DC) vaccine therapy was 578 of 10748 administrations (5.4%), which was significantly larger than those for other treatments. Multivariate analysis revealed that αβT cell therapy had a significantly greater risk of adverse events at performance status 1 or higher, and patients younger than 64 years, women or adjuvant immune-cell therapy had a greater risk of adverse events in DC vaccine therapy. Injection-site reactions were the most frequently reported adverse events, with 449 events, the majority of which were associated with DC vaccine therapy. Among all other adverse events, fever (228 events), fatigue (141 events) and itching (131 events) were frequently reported. In contrast, three patients had adverse events (fever, abdominal pain and interstitial pneumonia) that required hospitalization, although they were weakly related to this therapy; rather, it was considered to be the effect of treatment for the primary disease., Conclusions: Immune-cell therapy for cancer was considered to be a safe treatment without serious adverse events., (Copyright © 2023 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Co-selection is thought to occur when resistance genes are located on the same mobile genetic element. However, this mechanism is currently poorly understood. In this study, complete circular plasmids from swine-derived Escherichia coli were sequenced with short and long reads to confirm that resistance genes involved in co-resistance were co-transferred by the same plasmid. Conjugative transfer tests were performed, and multiple resistance genes were transmitted. The genes possessed by the donor, transconjugant, and plasmid of the donor were highly similar. In addition, the sequences of the plasmid of the donor and the plasmid of the transconjugant were almost identical. Resistance genes associated with statistically significant combinations of antimicrobial use and resistance were co-transmitted by the same plasmid. These results suggest that resistance genes may be involved in co-selection by their transfer between bacteria on the same plasmid.

Introduction: Infant stimuli attract caregiver attention and motivate parenting behavior. Studies have confirmed the existence of attentional bias toward infant face stimuli; however, relatively little is known about whether attentional bias exists for infant cry stimuli, which are as important as faces in child-rearing situations. Furthermore, scarce longitudinal evidence exists on how attentional bias toward infant crying changes through the postpartum period., Methods: In the present study, we conducted an experiment to assess bias toward infant crying at two postpartum time points: at Time 1 (Mean = 75.24 days), 45 first-time mothers participated and at Time 2 (Mean = 274.33 days), 30 mothers participated. At both time points, the mothers participated in a Stroop task with infant crying and white noise as the stimuli. They were instructed to answer the color out loud as quickly and accurately as possible, while ignoring the sound. Four types of audio stimuli were used in this task (the cry of the mother's own infant, the cry of an unfamiliar infant, white noise matched to the cry of the mother's own infant, and white noise matched to the cry of an unfamiliar infant), one of which was presented randomly before each trial. Response time and the correct response rate for each condition were the dependent variables., Results: For response time, the main effect of familiarity was significant, with longer response times when the participant's infant's cry was presented. In addition, response times were lower at Time 2 than at Time 1 in some conditions in which crying was presented., Discussion: The results suggest that mothers may be less disturbed by infant crying as they gain more experience. Elucidating the characteristics of postpartum mothers' changes in cognitive performance related to infants' cries would be useful in fundamental and applied research to understand the process of parents' adaptation to parenting., Competing Interests: The 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 © 2023 Hiraoka, Makita, Sakakibara, Morioka, Orisaka, Yoshida and Tomoda.)

The influence of a hydrogel spacer (HS) on seminal vesicle (SV) displacement in prostate radiotherapy was examined in the present study. A total of 20 patients with prostate cancer, who received intensity-modulated radiation therapy (IMRT), were enrolled. Computed tomography and magnetic resonance imaging were performed before and after HS insertion within the peripheral space for IMRT planning. Before and after HS insertion, The SV was delineated, and the amount of SV displacement was evaluated. Large SV cranial displacements (≥0.50 cm) were observed in 25% of patients. A HS lateral distribution of ≥1.00 cm in the upper two slices (midgland + superior) influenced the SV cranial displacements (P<0.01) and was associated with large SV cranial displacements (≥0.5 cm) (P<0.01). The HS cranial distribution in the upper slices did not influence SV cranial displacements (P=0.16). In addition, any HS lateral distribution of ≥1.00 cm in all slices did not induce the SV lateral and anterior-posterior displacements (P=0.50 and 0.70, respectively). In conclusion, SV cranial displacement was influenced by HS lateral distribution of ≥1.00 cm in the upper two slices. Therefore, when the sigmoid colon or small bowel is depressed in rectovesical excavation and SV needs to be included in the target volume, HS insertion should be performed carefully., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Makita et al.)

Summary: A 42-year-old female patient was referred to our hospital with hypertension and hypokalemia and was diagnosed with primary aldosteronism. Dynamic contrast-enhanced computed tomography images revealed a 13-mm nodule on the lateral segment of the left adrenal gland and a fine venous connection between the nodule and the prominent renal capsular vein running nearby. The venograms in the left lateral tributary with a microcatheter confirmed alternative drainage to the left renal capsular vein during adrenal venous sampling, and the left renal capsular vein sampling was added. The patient was diagnosed with a left aldosterone-producing adenoma (APA) using the lateralization index (48.3) and a higher plasma aldosterone concentration (PAC) of the left lateral tributary (66 700 pg/mL) than other tributary samples after adrenocorticotropic hormone stimulation. Furthermore, markedly higher PAC (224 000 pg/mL) was observed in the left renal capsular vein blood than in the left adrenal central vein (45 000 pg/mL) and tributaries, confirming the diagnosis. Laparoscopic left partial adrenalectomy and following histopathological analysis revealed a CYP11B2-positive adrenocortical adenoma. Complete clinical and biochemical success for primary aldosteronism was achieved after 6 months. Direct evidence of APA blood venous drainage into the renal capsular vein has been demonstrated. Sampling from an alternative drainage pathway could be beneficial for APA diagnosis if such APA blood drainage is assumed., Learning Points: Aldosterone-producing adenomas may drain blood into an alternative pathway but for the adrenal vein. The presence of alternative venous drainage could be assumed by contrast-enhanced computed tomography or venogram during adrenal venous sampling. Sampling in the alternative drainage veins and demonstrating elevated aldosterone levels could help in diagnosing aldosterone-producing adenoma.

This randomized controlled study examined neurological changes in socioemotional processing skills through parent training in caregivers of children with attention-deficit/hyperactivity disorder. Thirty mothers of children with attention-deficit/hyperactivity disorder were stratified into parent training and non-parent training groups. Functional magnetic resonance imaging was performed during the "Reading the Mind in the Eyes" test, and parenting difficulties were evaluated using the Parenting Stress Index and the Parenting Scale, twice (before and after parent training). Only mothers in the parent training group showed a significant decrease in Parenting Stress Index and Parenting Scale scores. They also demonstrated increased activity in the left occipital fusiform gyrus during the task of estimating emotions from facial pictures. We presumed that these changes might reflect the potential impact of enrollment in parent training in reducing stress, which might have increased activation of the fusiform gyrus., (© 2023. The Author(s).)

The present study aimed to evaluate the optimal timing of radium-223 chloride (Ra-223) administration among patients with bone metastasis from castration-resistant prostate cancer (BmCRPC). Patients, who were diagnosed with BmCRPC and treated with Ra-223 therapy between October, 2016 and January, 2022, were reviewed. The survival time was calculated from the initiation of Ra-223 administration. The time from the diagnosis of BmCRPC to the initiation of Ra-223 administration was identified as a potential prognostic factor. A total of 51 patients were examined in the present study. Ra-223 was administered as the first- and second-line therapy (earlier Ra-223 administration) in 32 patients and as the third- to fifth-line therapy (later Ra-223 administration) in 19 patients. In the multivariate analysis, which considered the potential prognosis, the difference in survival times between patients who received early and late Ra-223 administration was not significant [hazard ratio (HR), 2.67; 95% confidence interval (CI), 0.79-9.07; P=0.11]. By contrast, an incomplete Ra-223 administration (HR, 128.03; 95% CI, 10.59-1548.42; P<0.01) and higher levels of prostate-specific antigen prior to Ra-223 administration (HR, 7.86; 95% CI, 2.7-27.24; P<0.01) were independent factors, significantly associated with a poorer prognosis. The timing of Ra-223 administration did not significantly affect the survival of patients from the initiation of treatment. Further studies are thus required to determine the optimal timing for Ra-223 administration., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Makita et al.)

Background: This study aimed to devise a simple assessment system for bone metastases (BMs) from lung cancer (LC)., Methods: A total of 368 LC patients with BMs who underwent radiotherapy (RT) were retrospectively reviewed. Prognostic factors were evaluated using multivariate analysis, and a scoring system based on regression coefficients was devised., Results: The median follow-up time for survival was 4.3 months, and the 0.5-year overall survival (OS) rate was 44.7%. In the multivariate analysis, the significant prognostic factors were performance status (PS), metastases to internal organs, and post-RT molecular-targeting therapies (MTs) (tyrosine kinase inhibitors, and/or immune checkpoint inhibitors). A scoring system aggregating points assigned to each risk factor was created (2 points; non-administration of post-RT MTs, 1 point; PS ≥3 and metastases to internal organs). The median OSs were 25.0 months, 12.8 months, and 2.5 months in patients with a total score of 0 (n = 22), 1-2 (n = 124), and 3-4 (n = 221), respectively (p < 0.01)., Conclusion: This easy-to-use scoring system is useful for selecting patients who received comparatively high-dose fractionated RT for BMs from LC. Updates are required to follow the progress of systemic therapy., (© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Purpose: To evaluate the prognostic value of human epidermal growth factor receptor 2 (HER2) status and how to use HER2-targeted therapy in breast cancer (BC) with brain metastases (BM) treated with radiotherapy., Methods: We retrospectively reviewed the data of 103 BC patients with parenchymal BM treated with radiotherapy. We collected data on the hormone receptor (HR), HER-2 amplification status, and systemic therapy after treatment for BM. The primary outcome was overall survival (OS), which was calculated from the diagnosis of BM to death., Results: The median follow-up time from the diagnosis of the first BM was 9.1 months (range, .7-88 months). The 2-year OS of the HR-positive and HER2-positive (HR+HER2+) BC (31.3 mo) was significantly better than those of the HR-HER2+ (9,5 mo, p=.002), HR+HER2- (9.9mo, p=.003), and triple-negative BC (3.9 mo, p<.001) ( . Of the 36 HER2-positive patients, 31 patients treated with HER2-targeted therapy after radiotherapy for BM had a significantly better 2-year OS than those who did not receive HER2-targeted therapy (43% vs. 0%; p < .001). Among the 31 patients treated with HER2-targeted therapy, the 2-year OS for those treated with multiple anti-HER2 agents during the entire course of treatment was significantly higher than that for patients treated with a single agent (60% vs. 24%; p = .006)., Conclusions: HR+HER2+ BC patients with BM treated with radiotherapy show a better prognosis than other subtypes. For HER2-positive patients with good prognosis, it may be important to continue HER2-targeted therapy appropriately after radiotherapy for BM., (© 2022 John Wiley & Sons Australia, Ltd.)

Background and Purpose: Acute exacerbations or acute lung injury, including radiation pneumonitis (AE-ALI/RP) of interstitial lung disease (ILD), has a fatal prognosis. We evaluated the risk of palliative-intent radiotherapy (RT), with or without lung irradiation, for AE-ALI/RP of ILD., Materials and Methods: The data of patients with ILD who received palliative-intent RT between January 2011 and January 2022 were retrospectively reviewed. Factors associated with AE-ALI/RP grade ≥ 3 were assessed using univariate and multivariate analyses., Results: One hundred and three patients were examined, with median imaging and survival follow-up times of 88 (2-1440) and 144 (8-1441) days. The median time to onset of AE-ALI/RP grade ≥ 3 was 72 (5-206) days. In multivariate analysis, a higher pulmonary fibrosis score (PFS ≥ 3) (hazard ratio, HR: 2.16; 95% confidence interval, CI: 1.36-3.43; p < 0.01) and lung irradiation (lung-RT) (HR: 3.82; 95% CI: 1.01-15.73; p = 0.04) were significant factors for AE-ALI/RP grade ≥ 3. In patients who received lung-RT, the 100-day survival rate and cumulative incidence of AE-ALI/RP grade ≥ 3 were 56.8% and 13.7%, respectively. In patients with PFS ≥ 3 and who underwent lung-RT, the 100-day cumulative incidence of AE-ALI/RP grade ≥ 3 was 37.5%; all patients with AE-ALI/RP grade ≥ 3 had grade 5. In patients with PFS ≥ 3 without lung-RT, the 100-day cumulative incidence of AE-ALI/RP grade ≥ 3 was 4.8%., Conclusion: High PFS and lung-RT are significant risk factors for AE-ALI/RP grade ≥ 3. Even with relatively low doses, palliative-intent lung-RT carries an extremely high risk of AE-ALI/RP when PFS is high., Competing Interests: Declaration of Competing Interest The authors 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 © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Bone metastasis is common in advanced lung cancer, with the incidence reported to be 30%, and radiotherapy (RT) is used for pain relief from bone metastasis. The present study aimed to identify factors affecting local control (LC) of bone metastasis from lung cancer and to assess the significance of moderate RT dose escalation. This was a retrospective cohort study, where LC of bone metastasis from lung cancer that had received palliative RT was reviewed. LC at RT sites was evaluated with follow-up computed tomography (CT). The influence of treatment-, cancer- and patient-related risk factors for LC was assessed. A total of 317 metastatic lesions in 210 patients with lung cancer were evaluated. The median RT dose (biologically effective dose calculated using an α/β of 10 Gy; BED10) was 39.0 Gy (range, 14.4-50.7 Gy). The median follow-up time for survival and median radiographic follow-up time were 8 (range, 1-127) and 4 (range, 1-124) months, respectively. The 0.5-year overall survival and LC rates were 58.9 and 87.7%, respectively. The local recurrence rate in RT sites was 11.0%, and bone metastatic progression, except in RT sites, was observed in 46.1% at the time of local recurrence or the last follow-up CT of the RT sites. According to multivariate analysis, RT sites, pre-RT neutrophil to lymphocyte ratio (NLR), post-RT non-administration of molecular-targeting agents (MTs), and non-administration of bone modifying agents (BMAs) were significant unfavorable factors for LC of bone metastasis. Moderate RT dose escalation (BED10 >39 Gy) tended to improve the LC of RT sites. In cases without MTs, moderate dose escalation of RT dose improved the LC of RT sites. In conclusion, treatment (post-RT MTs and BMAs), cancer (RT sites) and patient (pre-RT NLR)-related risk factors had a large impact on improving the LC of RT sites. Moderate RT dose escalation seemed to have a small impact on improving the LC of RT sites., Competing Interests: Toshiyuki Kozuki received an honorarium from MSD, Ono, Kyowa Hakko Kirin, AstraZeneca, Boehringer Ingelheim, Chugai, TAIHO, Eli Lilly, Bristol Myers Squibb, Pfizer, Merck Biopharma, Nippon Kayaku, Novartis, Bayer, Sawai and AMGEN, received consulting fees from Chugai, AstraZeneca, Ono, Pfizer, Daiichi-Sankyo, Bayer, and Abbvie, and received research funding from MSD, Kyowa Hakko Kirin, AstraZeneca, Eli Lilly, Pfizer, Chugai, TAIHO, Ono, Bristol-Myers, Merck Biopharma, Daiichi-Sankyo, AbbVie, AMGEN, Sanofi, Eisai and Labcorp Development. All other authors declare that they have no conflict of interest., (Copyright: © Makita et al.)

Background: This study aimed to evaluate the factors that affect the local control (LC) of bone metastases from radioresistant carcinomas (renal cell carcinoma, hepatocellular carcinoma [HCC], and colorectal carcinoma [CRC]) treated with palliative external-beam radiotherapy (EBRT)., Methods and Materials: Between January 2010 and December 2020, 211 bone metastases in 134 patients were treated with EBRT in two hospitals (a cancer center and university hospital). Based on follow-up CT, these cases were reviewed retrospectively to evaluate LC at the EBRT site., Results: The median EBRT dose (BED10) was 39.0 Gy (range, 14.4-66.3 Gy). The median follow-up time of the imaging studies was 6 months (range, 1-107 months). The 0.5-year overall survival and LC rates of the EBRT sites were 73% and 73%, respectively. Multivariate analysis revealed that the primary sites (HCC/CRC), low EBRT dose (BED10) (≤ 39.0 Gy), and non-administration of post-EBRT bone modifying agents (BMAs) and/or antineoplastic agents (ATs) were statistically significant factors that negatively affected the LC of EBRT sites. In the absence of BMAs or ATs, the EBRT dose (BED10) escalation from 39.0 Gy improved the LC of EBRT sites. Based on ATs administration, the LC of EBRT sites was significantly affected by tyrosine kinase inhibitors and/or immune checkpoint inhibitors., Conclusions: Dose escalation improves LC in bone metastases from radioresistant carcinomas. Higher EBRT doses are needed to treat patients for whom few effective systemic therapies remain available., (© 2023. The Author(s).)

We encountered a 60-year-old man who had been diagnosed with heart failure of valvular disease and infective endocarditis; he was being treated with intravenous antibiotics and diuretics. On the 12th hospital day, he suddenly lost consciousness; computed tomography showed a right-sided huge subdural hematoma (SDH) with brain herniation. He died after invasive care was discontinued. A massive SDH was noted at autopsy, and microimaging demonstrated ruptured infective arteritis, without aneurysm, on the surface of the culprit lobe. Acute SDH usually occurs after head trauma, but an area of nonsaccular aneurysmal arteritis can also result in acute SDH.

A 60-year-old male with small-cell prostate carcinoma (SCPC) received external-beam radiotherapy of 60 Gy in 30 fractions and chemotherapy (cisplatin (CDDP) 80 mg/m 2 + etoposide (VP-16) 100 mg/m 2 , six courses). Although fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) showed a complete response, local recurrence occurred in the gross tumor volume after 12 months after the end of chemoradiotherapy. Although the standard treatment for SCPC is not established because SCPC is a rare disease, radiotherapy for SCPC is necessary to study the optimal dose and irradiation area for local control., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Makita et al.)