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Masanori Yasuo,* Yoshiaki Kitaguchi,* Yayoi Tokoro, Makoto Kosaka, Yosuke Wada, Takumi Kinjo, Atsuhito Ushiki, Hiroshi Yamamoto, Masayuki Hanaoka The First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan*These authors contributed equally to this workCorrespondence: Masanori YasuoThe First Department of Internal Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, JapanTel +81 263 37 2631Fax +81 263 36 3722Email yasumasa@shinshu-u.ac.jpBackground: Obstructive ventilatory disturbances occur in both chronic obstructive pulmonary disease (COPD), a typical disease representative of peripheral airway obstruction, and central airway obstruction (CAO). Pulmonary function tests (PFTs), which depend on patient effort, are traditionally used to evaluate lung function. The forced oscillation technique (FOT) is an effort-independent method for examining lung function during tidal breathing. The FOT is used universally to assess respiratory function in patients with COPD. Several studies have measured FOT to assess ventilatory disturbances in CAO. The results showed that FOT measurements in patients with CAO were similar to those reported in patients with COPD. However, no studies have compared FOT measurements directly between CAO and COPD. The aim of this study was to identify differences in ventilatory disturbances between peripheral and central airway obstructions in COPD and CAO, before patients received pharmacological therapy or bronchoscopic interventions, respectively.Patients and Methods: We retrospectively included 16 patients with CAO (10 cases of tracheal obstruction and 6 cases of bronchial obstruction) and 75 treatment-naïve patients with COPD (60 cases in Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage II and 15 cases in GOLD stage III) that were admitted from December 2013 to May 2017. Prior to treatment, patients were examined with the FOT and PFTs.Results: All parameters measured with the FOT in the inspiratory phase were significantly worse in patients with CAO than in patients with COPD. The PFTs showed that the CAO group had a significantly lower peak expiratory flow rate. In the airway wall thickening phenotype of COPD, a difference between the inspiratory and expiratory phases of the resonance frequency (ΔFres) was the best indicator for distinguishing between peripheral and central airway obstructions.Conclusion: This study compared differences between CAO and COPD (mainly GOLD stage II). We found that the FOT measurement, ΔFres, was the optimal indicator of the difference between the airway wall thickening COPD phenotype and CAO. Thus, the difference might be due to mechanical changes that occur in COPD with airway wall thickening.Keywords: forced oscillation technique, pulmonary function test, quality of life, central airway obstruction, COPD

The specific heat of Mn3−xFexSi was measured over a wide temperature range. Aside from the lattice and electronic specific heat components, another component had a significant contribution to the specific heat at low temperatures in the case of x = 0.2; however, its contribution decreased when x = 1.0. It is observed that the net component was retained at temperatures significantly higher than TN for both x. The XAFS spectra of the Mn K-edge for x = 0 not only indicated a smooth structure near the edge, but also an unusually small amplitude in the extended high energy region; however, these features disappeared with Fe doping. The specific heat and XAFS data were discussed in terms of the charge degree of freedom or electronic inhomogeneity. [ABSTRACT FROM AUTHOR]

Background: In the first-line treatment of elderly patients with advanced-stage non-small cell lung cancer (NSCLC) with high programmed death-ligand 1 (PD-L1) expression (tumor proportion score ≥ 50%), this study aimed to determine whether pembrolizumab monotherapy (MONO) or pembrolizumab plus platinum-based chemotherapy (COMB) should be selected., Methods: We performed a retrospective multicenter study (sub-analysis of the HOT/NJLCG2001 trial) of 299 patients with NSCLC with high PD-L1 expression who received MONO or COMB as the first-line treatment between December 2018 and January 2020. We selected patients aged 75 years and older and assessed the clinical efficacy and toxicity., Results: In total, 81 (median age: 79 years) and 19 (median age: 76 years) patients received MONO and COMB, respectively. Twenty patients with a performance status (PS) score of 2-3 were enrolled in the MONO group. The median progression-free survival (PFS) was 7.8 and 8.9 months in the MONO and COMB groups, respectively. The median overall survival (OS) was 14.6 and 20.3 months, and the 2-year survival rates were 38.8 and 49.9%, respectively. Furthermore, 29.6% and 26.3% of patients discontinued treatment due to adverse events, respectively. In MONO, patients with PS 0-1 had a longer PFS (10.5 months) and OS (21.7 months) than those with PS 2-3 (0.7 and 1.6 months, respectively)., Conclusion: Some elderly patients with NSCLC and high PD-L1 expression might benefit from COMB; however, MONO is considered the preferred treatment. MONO may not be an effective or feasible treatment for patients with PS 2-3, even with high PD-L1 expression., (© The Author(s) 2024. Published by Oxford University Press.)

Efficient formation of excited triplet states on metal-free photosensitizer dyads, bodipy-phenoxazine (BDP-PXZ) and tetramethylbodipy-phenoxazine (TMBDP-PXZ), was investigated using ab initio calculations. We revealed the reason why two different triplet transient species, 3 CT and 3 BDP, can co-exist only for BDP-PXZ as observed in the previous study with the TR-EPR measurements. It was found that the state mixing of 3 CT enables the transition from 1 CT to 3 CT and 3 BDP states only for BDP-PXZ. This mixing effect is commonly seen in the singlet states of twisted intermolecular charge transfer molecules, though the key factor that determines the mixing of the excited states of the dyes was found to be the electron-donating ability of the substituents rather than their steric hindrance. This mechanism was corroborated by comparing the spin polarization ratio of the triplet spin-sublevels measured by TR-EPR with the theoretical predictions. The spin polarization ratio of the triplets should contain information about the transition via intersystem crossing, e.g. the twisted angle of two chromophores of the dyad, and thus it can be a powerful tool to analyze the molecular mechanism of photochemical processes at the electronic structure level. These insights on the molecular structures' effect provided by this theoretical study would be a compass to molecular design of metal-free triplet photosensitizers.

Background: We have been able to use molecular targeted agents for unresectable hepatocellular carcinoma since 2009, and immune checkpoint inhibitors have been approved in recent years. We assessed the efficacy of systemic therapy in Hiroshima University Hospital by each era., Methods: A total of 357 patients who were treated with sorafenib, lenvatinib, atezolizumab plus bevacizumab combination therapy, or durvalumab plus tremeliumab combination therapy as first-line systemic therapy in our hospital from November 2009 to December 2023 were enrolled in this retrospective cohort study. We divided the years from 2009 to 2023 into the following three periods: cohort I, 2009-2016, the single-molecular targeted agent era; cohort II, 2017-2020, the multi-molecular targeted agent era; and cohort III, 2020-2023, the immuno-oncology era., Results: The median survival time was 9.5 months in cohort I, 15.8 months in cohort II, and 20.2 months in cohort III. The median survival time in cohort III was significantly (p < 0.01) longer than in the other cohorts. The overall response rate by mRECIST was 4.1% in cohort I, 28.7% in cohort II, and 47.2% in cohort III. The disease control rate was 41.6% in cohort I, 61.2% in cohort II, and 73.6% in cohort III. Both overall response rate and disease control rate significantly increased by era., Conclusions: We consider that advancements in systemic therapy, along with changes in treatment strategies, such as sequential therapy after progression, contribute to the prolonged prognosis across different eras., (© 2024 The Author(s). Hepatology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Hepatology.)

Aim: When evaluating response to immune checkpoint inhibitor therapy, the tumor sometimes initially swells before shrinking and ultimately responding, also called pseudo-progression. In this study, we analyzed whether tumor markers were useful for reflecting the treatment response., Methods: Thirty-three patients who were treated with durvalumab plus tremelimumab combination therapy (Dur + Tre) were enrolled. Their functional reserve was Child-Pugh grade A. Their tumor markers α-fetoprotein (AFP), des-γ-carboxy prothrombin (DCP), or AFP-Lectin 3 fraction (AFP-L3) were positive. Tumor markers were evaluated before treatment and at 1, 4, and 8 weeks after the start of treatment. The first radiological evaluation was carried out at 4 weeks and the second evaluation at 8-12 weeks. The responders included those with complete response and partial response and the nonresponders included those with stable disease (SD) and progression disease at best response evaluated by Response Evaluation Criteria in Solid Tumors., Results: In the responder group, the change ratio of AFP, DCP, and AFP-L3 specifically decreased at 8 weeks. In the nonresponder group, the change ratio of DCP specifically increased at 4 weeks. The optimal cut-off value to divide responders and nonresponders at 4 weeks was approximately -40%. The ratio of responders was 72.7% in the patients whose AFP or DCP decreased over 40% at 4 weeks., Conclusions: The change in tumor markers is a more useful predicter of tumor response to Dur + Tre than imaging evaluation alone., (© 2024 The Author(s). Hepatology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Hepatology.)

It is crucial to anticipate nuclear emergency scenarios and implement effective measures. Japan's climate and topography make it vulnerable to natural disasters; thus, it is necessary to address compounding and cascading disaster scenarios involving the simultaneous occurrence of natural and nuclear disasters. On 1 January 2024, an earthquake hit the Noto region of Ishikawa Prefecture, resulting in damage to the area around the Shika Nuclear Power Plant, located 90 km from the epicenter. This earthquake revealed that, in the event of a complex disaster, it is possible that residents living within 30 km of the Shika Nuclear Power Plant will be completely unprepared for a nuclear disaster. In the event of a complex disaster, it is crucial to implement appropriate countermeasures while balancing responses to both nuclear and natural disasters and optimizing radiation disaster prevention measures., (Creative Commons Attribution license.)

In Japan, a considerable number of foreigners encounter challenges in accessing appropriate healthcare services due to the lack of insurance coverage. However, the absence of a public database on these individuals makes it difficult to assess their health problems and healthcare access status. This study aims to investigate the characteristics of vulnerable Thai patients in Japan and to shed light on the specific challenges they face within Japan's healthcare system. A retrospective analysis was conducted using records of patients who required emergency healthcare support from the Royal Thai Embassy in Tokyo between 2004 and 2020. Descriptive statistical analyses were performed to examine the general characteristics, insurance status, and diseases of the patients. Additionally, patients were classified as either prolonged residents or brief residents based on their duration of stay in Japan until hospital admission (1 year or more or less than 1 year). A total of 74 patients were identified, with the majority (91.9%) lacking insurance coverage. Notably, there was an increase in the number of brief residents, including tourists, during the 2010s. Prolonged residents were more likely to experience chronic diseases, whereas brief residents were more prone to sustaining injuries. The patient records from the Thai Embassy consistently highlight the urgent requirement for emergency healthcare support within this population. However, the existing policies in Japan fall short in adequately addressing the healthcare access needs of this vulnerable population. Therefore, it is crucial to provide additional support and interventions to enhance their healthcare access., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: Atezolizumab plus bevacizumab combination therapy (Atezo + Beva) is used as the first-line therapy for unresectable hepatocellular carcinoma (u-HCC). Serious adverse events (AEs), including rupture of esophagogastric varices, have been seen during treatment. Therefore, the relationships of efficacy, safety, and portal hypertension (PH) were analyzed., Methods: A total of 146 patients with u-HCC and Child-Pugh Scores of 5-7 received Atezo + Beva. Prophylactic treatment for varices was performed for patients with the risk of rupture of varices before the start of Atezo + Beva. A propensity score-matched cohort was created to minimize the risk of potential confounders. Efficacy was assessed in 41 propensity score-matched pairs. AEs were assessed between patients without PH (n = 80) and with PH (n = 66)., Results: In patients without PH and with PH, median overall survival was 18.4 months and 18.8 months (p = 0.71), and median progression-free survival was 8.6 months and 5.8 months (p = 0.92), respectively. On the best radiological response evaluation for Response Evaluation Criteria in Solid Tumors, the objective response rate was 31.7% and 26.8% (p = 0.81), respectively. Variceal rupture occurred in three patients with PH, but there were no significant differences in the occurrence of variceal rupture (p = 0.090) and Grade 3-4 AEs between patients without and with PH., Conclusions: No significant differences in efficacy and safety were observed with PH. Prophylactic treatment for varices before the start of Atezo + Beva would allow treatment to continue relatively safely., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Introduction : Clinical pathways (CPWs) are patient management tools based on a standardized treatment plan aimed at improving quality of care. This study aimed to investigate whether CPW-guided treatment has a favorable impact on the outcomes of hospitalized older patients with aspiration pneumonia. Method : This retrospective study included patients with aspiration pneumonia, aged ≥ 65 years, and hospitalized at a community hospital in Japan. CPW implementation was arbitrarily determined by the attending physician upon admission. Outcomes were compared according to with or without the CPW (CPW-group and non-CPW groups). Propensity score (PS)-based analyses were used to control for confounding factors. Logistic regression analyses were conducted to evaluate the impact of CPW on the clinical course and outcomes. Results : Of 596 included patients, 167 (28%) received the CPW-guided treatment. The mortality rate was 16.4%. In multivariable model, CPW implementation did not increase the risk for total and 30-day mortality, and resulted in shorter antibiotic therapy duration (≤9 days) (PS matching (PSM): odds ratio (OR) 0.50, p = 0.001; inverse provability of treatment weighting (IPTW): OR 0.48, p < 0.001) and length of hospital stay (≤21 days) (PSM: OR 0.67, p = 0.05; IPTW: OR 0.66, p = 0.03). Conclusions : This study support CPW utility in this population.

Introduction Foreign residents in Japan often face challenges accessing healthcare due to language barriers, potentially leading to health inequities. This study aimed to assess the utilization and impact of human-mediated translation services in a specific medical setting in Tokyo. Methods A retrospective investigation was conducted on medical records of foreign patients who utilized human-mediated translation services at Navitas Clinic Tachikawa (Tachikawa, Tokyo, Japan) from November 2017 to December 2021. Data on age, gender, language used, department visited, diagnosis, insurance status, and booking methods were analyzed. Results Out of the 124 foreign patients who utilized the human-mediated translation services during the study period, 69 (56%) were male, and 55 (44%) were female. The median age was 35 years, with a range from 3 to 61 years. English was the predominant language used by 34 patients (59%), followed by Chinese for nine patients (16%) and Spanish for four patients (7%). The majority, 107 patients (86%) visited the internal medicine department, nine patients (7%) consulted dermatology, and six patients (5%) visited pediatrics. Regarding insurance status, 47 patients (81%) were insured, three patients (5%) were uninsured by the Japanese national health insurance system, and eight patients (14%) were self-pay. The primary mode of appointment booking was at the reception desk, with 112 patients (90%) using this method, while 12 patients (10%) made reservations online. Conclusions The findings of this study underscore the importance of human-mediated translation services for improving healthcare accessibility for foreign residents in Japan, emphasizing the need to address language barriers and promote health equity in clinical settings. Future studies should also explore challenges faced in patient-physician interactions from a linguistic perspective and potential technological solutions to enhance these services., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2023, Kaneda et al.)

Background: Elbow valgus instability is a risk factor for elbow medial collateral ligament injury. This study aimed to investigate the relationship between shoulder range of motion and elbow valgus instability using an ultrasound imaging system. A questionnaire and ultrasound examination were used for the study., Methods: Thirty-seven high school baseball players (15-18 years) with no history of shoulder or elbow disorders were included. Shoulder range of motion was measured at 90° of adduction, 10° of horizontal adduction, and 90° of elbow flexion in the supine resting position. To evaluate elbow valgus instability, an ultrasound imaging system was used to measure the shortest distance from the apex of the ulnar capitulum to the humeral glenoid with 2.5 kg of valgus stress applied to the ulnohumeral joint. The presence of elbow valgus instability was determined by the value obtained by subtracting the joint space distance on the non-throwing side from that on the throwing side. Student's t-test was applied for the range of shoulder rotation between the two groups, and Pearson's correlation coefficient was used for the relationship between the range of shoulder rotation and elbow instability. Statistical significance was set at 5%., Results: The range of internal and total shoulder rotation was significantly lower in participants with elbow valgus instability than those without elbow valgus instability (P<0.001). In addition, a significant moderate correlation was found in the range of internal (r=0.608, P<0.001) and total shoulder (r=0.479, P<0.001) rotations., Conclusions: Decreased shoulder range of motion may affect elbow valgus instability.

A total of 137 HCC patients treated with atezolizumab plus bevacizumab from October 2020 to September 2022 were enrolled. The median overall survival (OS) and progression-free survival (PFS) from the beginning of atezolizumab plus bevacizumab were 21.1 months (range, 18.8 months-not reached) and 10.5 months (range, 8.2-12.1 months), respectively. Fifty patients were diagnosed with progressive disease after atezolizumab plus bevacizumab. Of this group, 24 patients were administered lenvatinib, and the median OS and PFS from the beginning of lenvatinib were 15.3 months (range, 10.5 months-not reached) and 4.0 months (range, 2.5-6.4 months), respectively. The objective response rates based on the response evaluation criteria in solid tumors (RECISTs) criteria version 1.1 and modified RECISTs were 33.3% and 54.2%, respectively. There was no significant difference in the median serum alpha-fetoprotein level between before and after lenvatinib. In the multivariate analysis, Child-Pugh class A (hazard ratio 0.02, 95% confidence interval (CI) 0.02-0.76, p = 0.02) and intrahepatic tumor occupancy rate < 50% (hazard ratio < 0.01, 95% CI 0.003-0.35, p < 0.01) were the significant factors for OS. There were some frequent adverse events (AEs) in patients treated with lenvatinib such as hypertension, fatigue, anorexia, proteinuria, and so on, but none directly caused death. In conclusion, lenvatinib after atezolizumab plus bevacizumab for unresectable HCC should be considered an effective treatment option.

Background: Zoledronic acid reduces the risk of bone metastasis, but denosumab is a better option for treating bone metastases. However, few studies have evaluated the use of denosumab to treat bone metastasis originating from hepatocellular carcinoma. This study aimed to assess the clinical outcomes of switching from zoledronic acid to denosumab for treating bone metastasis in patients with hepatocellular carcinoma., Methods: This prospective study enrolled 10 patients with HCC and bone metastases. The levels of type 1 collagen cross-linked N-telopeptide (NTx) and tumor growth remained abnormal in these patients despite administration of zoledronic acid for over 3 months. We switched from zoledronic acid to 120 mg denosumab every 4 weeks and evaluated the clinical outcomes, including changes in the NTx level, pain level, and activities of daily living, as well as adverse events, after each administration., Results: Urinary NTx clearance was normal in all patients. The average urinary NTx clearance increased from 13.2 to 21.2 nmol BCE/nmol · Cre ( P = 0.54) after the switch to denosumab. Serum NTx levels were abnormal in all cases. The serum NTx level decreased from 142 nmol BCE/L to 126 nmol BCE/L ( P = 0.56). The answers to questionnaires on pain and activities of daily living did not change significantly. Some patients showed elevated transaminase levels, but this was not due to the drug switch., Conclusion: Switching to denosumab did not show a significant change of the pain and activity of daily living for the patients with severe bone metastasis from hepatocellular carcinoma, in whom the efficacy of zoledronic acid was limited., Competing Interests: The authors declare no conflict of interest., (©2023 Tottori University Medical Press.)

In breast cancer surgery, some medical facilities lack the necessary resources to conduct sentinel lymph node biopsy and its intraoperative frozen section consultation. In the coastal rural area of Fukushima, Japan, which has suffered from physician undersupply following the 2011 triple disaster of earthquake, tsunami and nuclear disaster, we explored the feasibility of telepathology by evaluating the diagnostic accuracy in remote intraoperative frozen section consultation of sentinel lymph node biopsy and its required time. Although examination time has room for improvement, telepathology can be one possible solution in resource-limited areas.

An 81-year-old woman was admitted to our hospital because of an abnormal opacity on the chest radiograph. She was diagnosed with cT3N3M1a, Stage ⅣA left lower lung lobe adenocarcinoma, and the PD-L1(22C3)expression was high (tumor proportion score[TPS]: 100%). She was administered with pembrolizumab monotherapy because her performance status(PS)was PS 1. After 4 courses, she had a partial response(PR), but her treatment had to be discontinued because of cutaneous adverse effects. After 6 months, the tumor regrew, and atezolizumab monotherapy was provided. Another cutaneous adverse event occurred, and treatment was discontinued again. However, a complete response(CR)was maintained for approximately 2 years and 6 months after discontinuation of treatments.

Warts, caused by human papillomavirus (HPV) infection, have various clinical presentations, making them difficult to differentiate from clavus, callus, and sometimes, squamous cell carcinoma. Although skin biopsies are the gold standard, a less-invasive method of examining these lesions is desired. Ninety patients with warts and related diseases, such as clavus and callus, were recruited to explore new differentiation methods using the surface of the warts. DNA was extracted from three types of specimens in each case: surface swab, shaved hyperkeratotic scale, and post-shaved surface swab. Total DNA was successfully extracted from these three specimens and was sufficient for subsequent HPV DNA detection. We analyzed samples for the HPV type and HPV viral load using polymerase chain reaction (PCR). Fifty-five cases were PCR-positive, and HPV1a, 2a, 4, 27, 57, and 65 were detected. The amount of HPV1a DNA produced was significantly greater than that of other HPV types. Regarding the correlation between the clinical diagnosis and HPV detection, the positive agreement rate was 90.9%, the negative agreement rate was 40.0%, and the overall agreement rate was 71.1%. Ten of the 21 cases clinically diagnosed as plantar warts were PCR-negative, especially in elderly patients. This suggests that it is difficult to distinguish plantar warts from clavus and callus in clinical practice. Although the amount of HPV DNA in the removed keratinization scale was highest for all HPV types, HPV detection by swabbing before and after shaving is also useful for follow-up as well as for differential diagnosis., (© 2023 Japanese Dermatological Association.)

Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) represents a new classification system for fatty liver disease. In this study, we investigated the clinical characteristics of patients with MAFLD-hepatocellular carcinoma (HCC) in comparison with those with nonalcoholic fatty liver disease (NAFLD) and considered the validity and challenges of the new criteria., Methods: This study included 237 untreated non-B, non-C HCC patients with hepatic steatosis. We examined the profile and laboratory findings of patients with MAFLD-HCC and NAFLD-HCC. We also classified MAFLD-HCC patients according to the factors on which the diagnosis was based and compared their clinical characteristics., Results: A total of 222 (94%) and 101 (43%) patients were diagnosed with MAFLD and NAFLD, respectively. MAFLD-HCC patients were more likely to be male than NAFLD-HCC, but there were no significant differences in metabolic indices, noninvasive liver fibrosis score or HCC status. In a study of MAFLD-HCC patients by diagnostic factor, those with overweight only were younger and had advanced liver fibrosis histologically, and when limited to patients younger than 70 years, the majority were overweight. Redefinition of overweight as BMI ≥ 25 reduced the number of MAFLD-HCC patients by only 5, from 222 to 217., Conclusions: MAFLD accounted for the majority of non-B, non-C HCC cases with hepatic steatosis. Examination of additional cases and revision of the detailed criteria is needed so that it can be used to efficiently select patients with fatty liver who are at high risk of developing HCC., (© 2023. The Author(s).)

To our knowledge, there have been no reports of first-line lenvatinib (LEN) and LEN re-challenge following atezolizumab/bevacizumab (Atezo-Bev) failure in the same patient. We herein report a patient with advanced hepatocellular carcinoma who failed either 1st line LEN and 2nd line Atezo-Bev, and successfully achieved complete response to LEN rechallenge with sequencial transcatheter arterial chemoembolization (TACE). This patient had a poor response to TACE before immunotherapy and introduction of molecular-targeted drugs but showed a good response to selective TACE after LEN rechallenge. Our findings suggest the need to reconsider the use of molecular-targeted drugs and TACE with advances in immunotherapy.

Background: Sessile serrated lesions (SSLs) are precursors of colon cancer, especially in cases of large, right colon. However, they are difficult to not only detect, but only clarify the margin of the lesion, which can lead to the poor endoscopic treatment outcomes., Aims: This study evaluated the usefulness of acetic acid spray with narrow-band imaging (A-NBI) for the better visualization of the margin of SSLs., Methods: From January 2013 to March 2022, patients with superficial elevated polyps suspected of being SSLs ≥ 10 mm with an endoscopic diagnosis that had been endoscopically resected at Hiroshima City Hiroshima Citizens Hospital were enrolled. Endoscopic images with white-light imaging (WLI), narrow-band imaging (NBI), indigo-carmine (IC), and A-NBI were recorded in each lesion and were randomly arranged and assessed by 10 endoscopists. We compared the visibility score (1 to 4) and color differences (ΔE) between inside and outside of the lesions among WLI, NBI, IC, and A-NBI., Results: Forty-one lesions in 33 cases were included, and a total of 164 images were evaluated. As for the visibility score, most of the lesions were scored as 1 or 2 on WLI, whereas most were scored 4 on A-NBI. The median ΔE of A-NBI was also significantly higher than that of WLI, NBI, or IC (20.5 vs. 8.3 vs. 8.2 vs. 12.3, P < 0.01). A significant correlation was observed between the color difference and visibility score (r = 0.53, P < 0.01)., Conclusions: A-NBI may be a useful modality for identifying the margin of SSLs., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study aimed to examine the applicability of the pulp/tooth ratio (PTR) method for age estimation in Mongolian populations using panoramic radiographs and derive new regression formulae. Moreover, we aimed to assess the accuracy of these formulae in other subjects from the Mongolian population and compare them with the other formulae derived from different Asian populations. The total sample size of the study was 381. The formulae were derived from the examination of panoramic radiographs of 271 individuals aged 15-62 years. Following Cameriere's method, PTR was calculated for the upper and lower canine teeth. Linear regression analyses were performed between the actual age and that obtained from upper-lower canine PTR and established formulae for age estimation. To verify the formulae, two types of test samples were collected: 73 panoramic radiographs and 37 periapical radiographs. The estimated age was calculated using our new formulae and three other formulae derived from Asian populations. The correlation coefficient between the actual age and that obtained by PTR was significantly negative for both canines. According to our new regression formulae, the differences between the estimated age and actual age showed a bell-shaped curve distribution in both test groups. While using the other formulae derived from the Asian population, the distribution patterns obtained were significantly different in the Mongolian population. This study was the first to examine the relationship between actual age and PTR in Mongolian population, and these results advance the field of forensic science in Mongolia., 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 Elsevier B.V. All rights reserved.)

Atezolizumab plus bevacizumab combination therapy (Atezo + Beva) is currently positioned as the first-line therapy for unresectable hepatocellular carcinoma (u-HCC). It may be difficult to decide whether to continue this treatment if radiological response is assessed as stable disease (SD). Therefore, the relationship between radiological response and prognosis was analyzed. A total of 109 patients with u-HCC and Child-Pugh Score of 5-7 received this treatment. Radiological response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST at the first and second evaluations. Of SD patients (n = 71) at the first RECIST evaluation, partial response, SD, and progressive disease (PD) were seen in 10, 55, and 6 patients, respectively, at the second evaluation. On multivariate analysis, in patients with SD at the first RECIST evaluation, a 25% or greater increase in the alpha-fetoprotein (AFP) value from initiation of treatment (odds ratio, 7.38; p = 0.037) was the independent factor for PD at the second evaluation. In patients with SD (n = 59) at the second RECIST evaluation, decreased AFP from initiation of treatment (hazard ratio, 0.46; p = 0.022) was the independent factor related to progression-free survival on multivariate analysis. AFP trends could help decide the Atezo + Beva treatment strategy.

Introduction: The objective of this scoping review is to map the literature describing preventive interventions for paternal perinatal depression. Depression is a common mental disorder experienced by fathers as well as mothers around childbirth. Perinatal depression has negative consequences for men, and suicide is the most serious adverse effect. Impaired father-child relationships can also result from perinatal depression, negatively impacting child health and development. Considering its severe effects, early prevention of perinatal depression is important. However, little is known about preventive interventions for paternal perinatal depression including Asian populations., Methods and Analysis: This scoping review will consider studies of preventive interventions for perinatal depression in men with a pregnant wife or partner, and new fathers (less than 1 year post partum). Preventive intervention includes any form of intervention intended to prevent perinatal depression. Primary prevention intended to promote mental health will also be included if depression is included as an outcome. Interventions for those with a formal diagnosis of depression will be excluded. MEDLINE (EBSCOhost), CINAHL (EBSCOhost), APA PsycINFO (EBSCOhost), Cochrane Central Register of Controlled Trials and Ichushi-Web (Japan's medical literature database) will be searched for published studies, and Google Scholar and ProQuest Health and Medical Collection will be searched for grey literature. Beginning in 2012, the search will include the last 10 years of research. Screening and data extraction will be performed by two independent reviewers. Data will be extracted using a standardised data extraction tool and presented in diagrammatic or tabular form, accompanied by a narrative summary., Ethics and Dissemination: As this study involves no human participants, approval from a human research ethics committee is not required. Findings of the scoping review will be disseminated through conference presentations and publication in a peer-reviewed journal., Trial Registration Number: https://osf.io/fk2qe/., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The present study retrospectively evaluated the efficacy of stereotactic body radiation therapy (SBRT), including repeated SBRT, for hepatocellular carcinoma. Participants comprised 220 HCC patients treated with SBRT in Hiroshima University Hospital between December 2008 and December 2021. Median overall survival (OS) and disease-free survival were 52 months (range, 45-64 months) and 17 months (range, 14-23 months), respectively. The 5-year local tumor recurrence rate was 3.4% (95% confidence interval (CI), 1.3-6.9%). Fifty-three patients underwent repeated SBRT (twice, 53 cases; three times, 10 cases; four times, 4 cases; five times, 1 case). Median interval between first and second SBRT was 20 months. Median OS from first SBRT was 76 months (95% CI, 50-102 months). Among patients with repeated SBRT, only one case showed local recurrence after second SBRT. Albumin-bilirubin score increased significantly from 6 to 12 months after repeated SBRT, both in the same segment and in remote segments, but the increase was not significant in the same segment. Only one case of grade 3 bile duct stricture was observed in patients who were treated with repeated SBRT. In conclusion, repeated SBRT provides good local control and a low risk of side effects.

Background: Parents of children with medical complexity (CMC) have extra child-raising responsibilities because of the time commitments necessary for care, and their social participation is often compromised. Experiencing leisure excursions with such children may be a solution to some of these problems but the first-hand experience of excursions in regard to their psychological impact on the caregivers of CMC remains to be appraised., Methods: Semi-structured interviews were conducted, via video conference, with eight informal and eight formal caregivers of CMC who attended an excursion to Tokyo Disney Land (TDL). We investigated the psychological changes that they had experienced through the excursion, performing inductive thematic analysis., Results: Three themes were identified among parents and five were identified among medical professionals. Themes reported by the parents were: Increased trust in the public and society (Theme 1); confidence for other challenges (Theme 2), and connection with other parents in the non-medical settings (Theme 3). Themes reported by medical professionals were: Expanding the initiative to other CMC (Theme 1); feeling bonded with other caregivers within the working group (Theme 2); information exchange across different working groups (Theme 3), positive responses from CMC (Theme 4); families' confidence to go out (Theme 5)., Conclusions: This study showed that the excursion to TDL led to positive psychological changes in both medical professionals and parents of CMC, enhancing trust, connection, and confidence. The promising results of this study suggest a need for further research about the impact of an excursion on caregivers of CMC., (© 2023 Japan Pediatric Society.)

Purpose: To identify secular trends in the use of radiotherapy prostheses in the Clinic for Maxillofacial Prosthetics at Tokyo Medical and Dental University Hospital and to ascertain patient characteristics and future needs., Methods: The study included all patients who visited the clinic between January 1, 2000, and December 31, 2019. Data on numbers of cases, gender and age, numbers and types of radiotherapy prostheses, primary cancer site, and time required for prosthesis fabrication during the study period were collected from medical records and retrospectively analyzed., Results: During the 20-year study period, 1,066 prostheses were fabricated for 1,135 cases. In most years, at least 60% of cases were male. The mean age increased from 60.6 to 67.1 years during the study period, and the number of cases older than 70 years increased over time. The most common cancer site was the tongue, and the most common type of radiotherapy prosthesis was a spacer. The mean time for spacer fabrication was 11 days., Conclusion: During a recent 20-year period, mean age and the proportion of elderly patients requiring savers increased. When treating elderly patients, prosthodontists responsible for fabricating radiotherapy prostheses must collaborate effectively with radiation oncologists.

Background: With advances in medical technology, the number of children with medical complexity (CMC) has increased. Excursions with such children encourage their social participation and have been shown to have a positive impact on their caregivers. However, the first-hand experience of the excursions has not yet been evaluated regarding the difficulties faced by CMC and their caregivers during preparation, transportation, and in the local area., Methods: Semi-structured interviews were conducted with eight informal and eight formal caregivers of CMC who attended an excursion to Tokyo Disney Land (TDL) via video conference. We investigated challenges that they had experienced through the excursion, performing inductive thematic analysis., Results: Three themes were identified: the preparation stage (Theme 1), problems encountered while traveling to the theme park (Theme 2), and problems at the theme park (Theme 3). In the preparation stage, three subthemes, i.e. preparation for the trip, cooperation with related parties, and researching about the theme park and asking for help, are reported. Theme 2 includes four subthemes: activities of daily living, respiratory care, luggage, and weather changes. Theme 3 has three subthemes: activities of daily living, physical condition management, and issues for the theme parks., Conclusions: We found that securing the power supply, location, and time for daily procedures are challenges in realizing excursions for CMC, but with sufficient preparation, it is possible in Japan without major difficulty., (© 2022 Japan Pediatric Society.)

Introduction: Measurements of body composition, such as the skeletal muscle index (SMI), are useful for predicting prognosis in hepatocellular carcinoma (HCC). This study aimed to analyze the relationship between skeletal muscle changes during therapy with atezolizumab plus bevacizumab (Atezo + Beva) or lenvatinib (Len) and the association between SMI and prognosis., Methods: Patients with advanced HCC and Child-Pugh A status received Atezo + Beva or Len as first-line systemic chemotherapy. We assessed prognosis and body composition obtained by bioelectrical impedance analysis., Results: A total of 109 patients received treatment (Atezo + Beva, n = 47; Len, n = 62). During treatment, the arm SMI was reduced in the Len group and maintained in the Atezo + Beva group. The extracellular water to total body water ratio (ECW/TBW) increased significantly in both groups during treatment. In the Atezo + Beva group, no factor was associated with prognosis. Multivariate analysis showed that in the Len group, the arm SMI (hazard ratio [HR], 0.5; 95% CI: 0.26-0.89; p = 0.02), ECW/TBW (HR: 2.7; 95% CI: 1.21-6.01; p = 0.01), and Child-Pugh score (HR: 2.3; 95% CI: 1.31-6.13; p = 0.004) were associated with progression-free survival., Conclusion: Assessing body composition with BIA before Atezo + Beva and Len treatment may be useful., (© 2023 S. Karger AG, Basel.)

Background: Balloon-occluded retrograde transvenous obliteration (BRTO) is a treatment option for patients with gastric varices (GVs). This study aimed to clarify the clinical significance of portal hypertension estimated by the hepatic venous pressure gradient (HVPG), subsequent exacerbation of esophageal varices (EVs), and prognosis of patients who underwent BRTO for GVs., Methods: Thirty-six patients with GVs treated with BRTO were enrolled in this study, and their HVPG was measured before (pre-HVPG) and on the day after BRTO (post-HVPG). After BRTO, patients were followed-up for a median interval of 24.5 (3-140) months. Clinical factors related to EVs exacerbation and prognosis after BRTO were retrospectively analyzed., Results: Post-HVPG increased compared to pre-HVPG in 21 out of 36 patients (58%), and post-HVPG was overall significantly higher compared to pre-HVPG (P = 0.009). During the observation period, 19 patients (53%) developed EVs exacerbation, and the cumulative EVs exacerbation rates at 1, 3 and 5 years after BRTO were 27%, 67%, and 73%, respectively. Pre-HVPG was not related to EVs exacerbation, although elevation of post-HVPG to ≥ 13 mmHg (P < 0.01) and high level of serum aspartate aminotransferase (P < 0.05) were significant independent risk factors for EVs exacerbation after BRTO. Fourteen patients (38.9%) died during the observation period. An elevated value of liver stiffness measurement (LSM) of ≥ 21 kPa was a significant independent risk factor for poor prognosis after BRTO (P < 0.05)., Conclusions: HVPG increases after BRTO. HVPG after BRTO has greater predictive ability for subsequent EVs exacerbation than HVPG before BRTO. LSM is a potential prognostic parameter in patients who undergo BRTO., (© 2022. The Author(s).)

Introduction: Proteinuria is one of the adverse events of atezolizumab plus bevacizumab combination therapy (Atezo + Bev) and can cause interruption in the use of Bev. However, the risk factors for proteinuria in patients with hepatocellular carcinoma (HCC) who are receiving Atezo + Bev have not yet been investigated. The aim of this study was to identify the risk factors for early onset of proteinuria in Atezo + Bev for patients with unresectable HCC., Methods: Sixty-four patients with Child-Pugh scores of 5-7, an Eastern Cooperative Oncology Group performance status of 0 or 1, and low level of proteinuria (1+ or less on a dipstick test and urine protein-to-creatinine ratio (UPCR) less than 2.0 g/g Cr) at the initiation of therapy were analyzed. The level of proteinuria was evaluated based on the Common Terminology Criteria for Adverse Events version 5.0. We adopted the UPCR for the quantitative test instead of a 24-h urine collection. The incidence of proteinuria and changes in liver function were retrospectively investigated., Results: The cumulative incidence of proteinuria over a 24-week period was 34.4%. Multivariate analysis showed that a low estimated glomerular filtration rate (hazard ratio [HR], 3.807; 95% confidence interval [CI], 1.579-9.180; p = 0.003), treatment for hypertension (HR, 6.224; 95% CI, 1.614-24.010; p = 0.008), and high systolic blood pressure (SBP) (HR, 2.649; 95% CI, 1.133-6.194; p = 0.025) were risk factors for proteinuria. Serum albumin levels and albumin-bilirubin scores in patients with proteinuria worsened. In addition, a mean SBP ≥135 mm Hg during treatment was the only risk factor for the development of severe proteinuria (UPCR >2 g/g Cr)., Conclusion: Our study found that controlling blood pressure is extremely important for the management of proteinuria in patients with HCC who are receiving Atezo + Bev., Competing Interests: Michio Imamura has received honoraria and research funding from Bristol Myers Squibb., (Copyright © 2022 by The Author(s). Published by S. Karger AG, Basel.)

To reveal waning humoral immunity after second dose BNT162b2 vaccinations in a rural Japanese community and determine factors affecting antibody titers. We aimed to report Immunoglobulin G (IgG) antibody against the SARS-CoV-2 spike (S1) protein levels and neutralizing activity in a large scale community based cohort., Methods: Participants in the observational cross-sectional study received a second dose of vaccination with BNT162b2 (Pfizer/BioNTech) and were not previously infected with COVID-19. Questionnaire-collected data on sex, age, adverse vaccine reactions, and medical history was obtained., Results: Data from 2496 participants revealed that older age groups reached a low antibody titer 90-120 days after the second vaccination. Neutralizing activity decreased with age; 35 (13.3%) of those aged ≥ 80 years had neutralizing activity under the cut-off value. Neutralizing activity > 179 days from the second vaccination was 11.6% compared to that at < 60 days from the second vaccination. Significantly lower IgG antibody titers and neutralizing activity were associated with age, male sex, increased time from second vaccination, smoking, steroids, immunosuppression, and comorbidities., Conclusions: Antibody titer decreased substantially over time. Susceptible populations, older people, men, smokers, steroid users, immunosuppression users, and people with three or more comorbidities may require a special protection strategy., (© 2022. The Author(s).)