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Simple Summary: In this phase II trial, patients with advanced hepatocellular carcinoma (HCC) previously treated with lenvatinib were enrolled to receive atezolizumab and bevacizumab every 3 weeks. The primary endpoint was progression-free survival. A total of 26 eligible patients were enrolled. The median progression-free survival from the start of treatment was 9.70 [90% confidence interval, 5.10–14.24] months, with the lower limit above the predefined threshold. The median overall survival was 17.23 [90% confidence interval, 13.18–27.85] months and the objective response rate was 34.6%. Sixteen patients (61.5%) received subsequent therapies. Severe adverse events, adverse events leading to treatment delays, and adverse events leading to treatment discontinuation occurred in eight (30.8%), fourteen (53.8%), and five (19.2%) patients, respectively, and no treatment-related death occurred. This combination therapy is suggested to be effective and safely administered for patients with advanced HCC previously treated with lenvatinib. Background/Objectives: Atezolizumab and bevacizumab combination therapy has been established as a standard of care for first-line treatment; however, its efficacy and safety have not been fully evaluated for patients previously treated with systemic therapy. Methods: In this phase II trial, patients with advanced hepatocellular carcinoma previously treated with lenvatinib were enrolled to receive a dose of 1,200 mg of atezolizumab and 15 mg/kg of bevacizumab every 3 weeks. The primary endpoint was progression-free survival. The secondary endpoints included overall survival, objective response rate, disease control rate, subsequent therapy, and frequency of adverse events. The threshold and expected progression-free survival were 3 and 6.8 months, respectively. Considering a one-sided significance level of 0.05 and a statistical power of 80%, the minimum required sample size was 26 patients. Results: The median progression-free survival from the start of treatment was 9.70 [90% confidence interval, 5.10–14.24] months, and the lower limit of the 90% CI was above the predefined threshold. The objective response and disease control rates were 34.6% and 73.1%, respectively. Sixteen patients (61.5%) received subsequent therapies, and the median overall survival was 17.23 [90% confidence interval, 13.18–27.85] months. Severe adverse events, adverse events leading to treatment delays, and adverse events leading to treatment discontinuation occurred in eight (30.8%), fourteen (53.8%), and five (19.2%) patients, respectively, and no treatment-related deaths occurred. Conclusions: Atezolizumab and bevacizumab combination therapy is effective and can safely be administered to patients with advanced HCC previously treated with lenvatinib. [ABSTRACT FROM AUTHOR]

Purpose: The prevalence of migraine headache is higher in women. Low barometric pressure is a factor in headache triggering, but sex-related differences have not been identified. The purpose of this study was to examine sex-related differences in headache triggered by low barometric pressure. Methods: Study subjects aged 20–49 years were randomly selected from a research company's (Macromill, Inc.) web panel. Those with chronic migraine or tension-type headache invited to complete a web-based self-administered questionnaire. Logistic regression analysis was performed with the objective variable as the Headache Impact Test-6 (HIT-6) high scores (56 or more) or headache triggered by low barometric pressure. Results: Participants were 332 women and 337 men in the headache population. HIT-6 high scores were associated with age at headache occurrence 20 years or younger (OR: odds ratio 1.85, 95% CI: confidence interval 1.15–2.99, p = 0.012) and headache triggered by low barometric pressure (OR 2.11, 95%CI 1.51–2.94, p < 0.001). Headache triggered by low barometric pressure was significantly associated with women (OR 2.92, 95%CI 2.12–4.02, p < 0.001). Conclusions: Headache triggered by low barometric pressure were related to sex-related differences. It was suggested that a sex-specific treatment approach for headache triggering is needed. [ABSTRACT FROM AUTHOR]

Simple Summary: Although sarcopenia-related factors, including decreased skeletal muscle index (SMI), have been reported to affect therapeutic efficacy and the occurrence of adverse events in sorafenib or lenvatinib treatment for hepatocellular carcinoma (HCC), there is considerably less evidence regarding the relationship between SMI and prognosis in the HCC patients treated with atezolizumab plus bevacizumab (atezo/bev) therapy. Furthermore, there are no reports of muscle strength, including grip strength (GS), which is essential for an accurate diagnosis of sarcopenia. This is the first study to show the relationship between sarcopenia, diagnosed by decreased GS and SMI, and clinical outcomes in atezo/bev therapy, with novel evidence having a strong impact. The presence of sarcopenia is significantly associated with shorter overall survival with the occurrence of adverse events and decreased liver function. Monitoring of both GS and SMI is useful for assessing the general condition and predicting prognosis in HCC patients treated with atezo/bev therapy. Although there have been advances in the prevention and diagnosis of hepatocellular carcinoma (HCC) in recent years, many HCC patients are still diagnosed with advanced stage. Systemic therapy is indicated for unresectable HCC (uHCC) with major vascular invasion and/or extrahepatic metastases, and the atezolizumab plus bevacizumab (atezo/bev) combination is currently recommended as first-line treatment for uHCC. Recently, sarcopenia-related factors, including decreased skeletal muscle index (SMI), have been reportedly associated with prognosis in uHCC patients treated with sorafenib or lenvatinib. There are few reports on muscle strength assessments, including grip strength (GS), despite their importance in accurate sarcopenia diagnosis, and furthermore, there is no evidence regarding atezo/bev therapy. In this study, we investigated whether sarcopenia affects the clinical outcome of atezo/bev therapy. This study included 64 uHCC patients on atezo/bev therapy and assessed their GS and SMI, and SMI was measured using bioelectrical impedance analysis (BIA). We diagnosed sarcopenia based on GS and BIA-SMI and compared the clinical outcomes in the sarcopenia and non-sarcopenia groups. Of these patients, 28 had sarcopenia, and 36 had non-sarcopenia. Adverse events (AEs) frequently occurred, and the albumin-bilirubin score significantly decreased after atezo/bev therapy in the sarcopenia group than in the non-sarcopenia group. The median progression-free survival was 4.7 (0.4–26.4) and 10.6 (1.1–24.5) months in the sarcopenia and non-sarcopenia groups, respectively. The median overall survival (OS) was 12.6 (1.4–27.7) months in the sarcopenia group and was not reached in the non-sarcopenia group, indicating a significant difference in the Kaplan-Meier survival curves for both groups (p < 0.01). In multivariate analysis, sarcopenia was significantly associated with OS. In conclusion, sarcopenia was significantly associated with poor clinical outcomes based on the occurrence of AEs and decreased liver function in uHCC patients on atezo/bev therapy. GS and SMI are important parameters for accurately diagnosing sarcopenia. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship between weather and headache occurrence using big data from an electronic headache diary smartphone application with recent statistical and deep learning (DL)‐based methods. Background: The relationship between weather and headache occurrence remains unknown. Methods: From a database of 1 million users, data from 4375 users with 336,951 hourly headache events and weather data from December 2020 to November 2021 were analyzed. We developed statistical and DL‐based models to predict the number of hourly headache occurrences mainly from weather factors. Temporal validation was performed using data from December 2019 to November 2020. Apart from the user dataset used in this model development, the physician‐diagnosed headache prevalence was gathered. Results: Of the 40,617 respondents, 15,127/40,617 (37.2%) users experienced physician‐diagnosed migraine, and 2458/40,617 (6.1%) users had physician‐diagnosed non‐migraine headaches. The mean (standard deviation) age of the 4375 filtered users was 34 (11.2) years, and 89.2% were female (3902/4375). Lower barometric pressure (p < 0.001, gain = 3.9), higher humidity (p < 0.001, gain = 7.1), more rainfall (p < 0.001, gain = 3.1), a significant decrease in barometric pressure 6 h before (p < 0.001, gain = 11.7), higher barometric pressure at 6:00 a.m. on the day (p < 0.001, gain = 4.6), lower barometric pressure on the next day (p < 0.001, gain = 6.7), and raw time‐series barometric type I (remaining low around headache attack, p < 0.001, gain = 10.1) and type II (decreasing around headache attack, p < 0.001, gain = 10.1) changes over 6 days, were significantly associated with headache occurrences in both the statistical and DL‐based models. For temporal validation, the root mean squared error (RMSE) was 13.4, and the determination coefficient (R2) was 52.9% for the statistical model. The RMSE was 10.2, and the R2 was 53.7% for the DL‐based model. Conclusions: Using big data, we found that low barometric pressure, barometric pressure changes, higher humidity, and rainfall were associated with an increased number of headache occurrences. [ABSTRACT FROM AUTHOR]

Aim: The prognosis of patients with acute liver failure has improved dramatically in the past three decades due to advances in medical critical care and use of liver transplantation (LT) in Western countries, where the etiology of acute liver failure is different from that in Japan. We analyzed patients with fulminant hepatitis (FH) and late‐onset hepatic failure (LOHF) admitted to our unit over a 32‐year period to clarify the nature of Japanese patients with FH and LOHF. Methods: A total of 137 Japanese patients with FH and LOHF between 1986 and 2017 were analyzed for etiologies, disease types, treatment protocols, and outcome. Results: Of 137 patients, 124 were FH (53 acute type and 71 subacute type) and 13 LOHF. The major etiology was due to viral infections in 48% of patients. A total of 23.4% of patients recovered without LT, 7.3% received LT, and 69.3% died without LT. The number of patients showed rise and fall without an evident decrease during the period. Patients with autoimmune hepatitis increased after the establishment of autoimmune hepatitis criteria in 1999 (p < 0.001), and that with indeterminate cause decreased (p < 0.01). The mean age was older in the last decade than in the first decade (p = 0.036). Spontaneous and overall survival rates were not different during the period. Conclusions: The prognosis of our patients with FH and LOHF has not improved, probably because of aging and the increasing proportion of etiologies with poor prognosis and difficult‐to‐treat patients without response to medications regardless of advancement of clinical management, including artificial liver support devices and LT. [ABSTRACT FROM AUTHOR]

In the course of screening for antioxidant agricultural products in Shizuoka Prefecture, Japan, we found that Akebia trifoliata Koidz fruit had a high activity. Furthermore, we found that the peel of A. trifoliata showed remarkable antioxidant activity compared to other parts of the fruit. We isolated seven known phenylpropanoids, including caffeoylquinic acids from the peel of A. trifoliata: 5-O-caffeoylquinic acid (1), 4-O-caffeoylquinic acid (2), 3-O-caffeoylquinic acid (3), 4,5-di-O-caffeoylquinic acid (4), 3,5-di-Ocaffeoylquinic acid (5), calceolarioside B (6), and (4-hydroxyphenyl)-ethyl-6-O-(E)-caffeoyl-β-Dglucopyranoside (7). These isolated compounds were found to contribute to the antioxidant activity of the peel, with 6 exhibiting the strongest activity amongst them. Quantitative analyses showed that 6 is abundant in the peel of A. trifoliata. Therefore, the peel of A. trifoliata can be effectively used as a functional material with antioxidant activity. [ABSTRACT FROM AUTHOR]

Simple Summary: Ramucirumab has been shown to be effective as a second-line agent after sorafenib in hepatocellular carcinoma (HCC) patients whose α-fetoprotein was ≥400 ng/mL. We performed a retrospective cohort study to investigate ramucirumab efficacy in a real-world setting. Progression-free survival (PFS) was consistent through treatment lines, modified albumin–bilirubin (mALBI) grade, Barcelona Clinic for Liver Cancer (BCLC) stage, and α-fetoprotein (AFP) level. By contrast, ascites was more frequently seen in mALBI 2b/3 patients and, therefore, should be carefully monitored. Background: The present study aimed to clarify the efficacy and safety of ramucirumab in a real-world setting, including patients who experienced two or more systemic treatments or whose hepatic reserve was deteriorated. Methods: In total, 79 patients with hepatocellular carcinoma (HCC) from 14 institutes throughout Japan were retrospectively analyzed. The response was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, and AEs were recorded according to the Common Terminology Criteria for AEs (CTCAE) version 5.0. Results: Median overall survival (OS) in the total cohort was 7.5 months (m). Median OS was 8.8 m in patients who were administered ramucirumab as a second-line treatment, while it was 7.3 m in third- or later-line treatment. Progression-free survival rates in the second- and third- or later-line therapies were 3.2 m and 3.2 m, respectively. The disease control rate (DCR) in the study was 43%. There were no statistically significant differences in DCR between the treatment courses. Regarding adverse events (AEs), the development of ascites was observed significantly more frequently in modified albumin–bilirubin (mALBI) 2b/3 patients than in mALBI 1/2a patients (54.5% vs. 25.0%, p = 0.03). Conclusions: Ramucirumab is useful as a second-line therapy and feasible as a third- or later-line treatment for HCC. [ABSTRACT FROM AUTHOR]

Objective: This study prospectively observed the incidence of all malignancies and the prognosis of all patients in a population of patients who achieved Sustained Virological Response (SVR) with a 100% capture rate., Design: A prospective study of 651 SVR cases was conducted from July 2013 to December 2021. The primary endpoint was the occurrence of all malignancies, and the secondary endpoint was overall survival. The cancer incidence during the follow-up period was calculated using the man-year method, and risk factors were analyzed. In addition, sex- and age-matched standardized mortality ratio (SMR) was used to compare the general population with the study population., Results: The overall median follow-up was 5.44 years. 107 malignancies occurred in 99 patients during the follow-up. The incidence of all malignancies was 3.94/100 person-years. The cumulative incidence was 3.6% at 1 year, 11.1% at 3 years, and 17.9% at 5 years, and continued to increase almost linearly. The incidence of liver cancer and non-liver cancer was 1.94/100 patient-years vs. 1.81%/100 patient-years. The 1-year, 3-year, and 5-year survival rates were 99.3%, 96.5%, and 94.4%, respectively. This life expectancy was compared to the standardized mortality ratio of the Japanese population, which proved non-inferior., Conclusion: It was found that malignancies of other organs occur as frequently as hepatocellular carcinoma (HCC). Therefore, follow-up of patients who have achieved SVR should focus not only on HCC but also on malignant tumors of other organs, and lifelong follow could contribute prolonged life expectancy for the previously short-lived., (© 2023. Asian Pacific Association for the Study of the Liver.)