Search

This is the English version of the guidelines for the diagnosis and treatment of idiopathic portal hypertension, extrahepatic portal obstruction, and Budd-Chiari syndrome, which were established and revised in 2018 by the Aberrant Portal Hemodynamics Study Group under the jurisdiction of the Ministry of Health, Labor, and Welfare in Japan. These guidelines are excerpts, and the full version consists of 86 clinical questions and explanations, totaling 183 pages in Japanese., (© 2024 Japan Society of Hepatology.)

Aim: An association between hepatitis B core-related antigen (HBcrAg) kinetics and hepatocarcinogenesis during nucleoside (t)id analog (NA) treatment has recently been reported. HBcrAg kinetics and factors associated with HBcrAg response during tenofovir alafenamide (TAF) administration remain unclear. In this multicenter retrospective study, we aimed to clarify the efficacy and safety of TAF in treatment-naïve patients with chronic hepatitis B, focusing on the reduction in HBcrAg levels., Methods: Patients were treated with TAF monotherapy for 96 weeks, and the kinetics of HBcrAg during treatment and the factors associated with HBcrAg response (defined as a change in HBcrAg of -1 log IU/mL from baseline) were evaluated., Results: The study population comprised 241 patients, 36.9% of whom were HBeAg-positive. The median baseline HBcrAg level was 4.7 log IU/mL. The median change in HBcrAg from baseline was -1.1 log IU/mL at 96 weeks after treatment. The HBcrAg response rate at 96 weeks was 56.6% (43/76). Multivariate analysis revealed high alanine transaminase level as an independent baseline factor associated with HBcrAg response at 96 weeks of treatment (p = 4.53 × 10 -6 ). No correlation was found between the HBcrAg and hepatitis B surface antigen kinetics in patients treated with TAF monotherapy., Conclusions: In TAF monotherapy for patients with chronic hepatitis B, HBcrAg levels were significantly decreased and baseline alanine transaminase level is an important factor associated with HBcrAg reduction. As no correlation was found between HBcrAg and reduced hepatitis B surface antigen levels in this study, HBcrAg kinetics in addition to hepatitis B surface antigen may need to be monitored during TAF treatment., (© 2024 The Authors. Hepatology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Hepatology.)

Hemosuccus pancreaticus (HP) is characterized by gastrointestinal bleeding from the papilla of Vater via the pancreatic duct. In this report, we describe a case of HP due to arterial perforation in a pancreatic pseudocyst and discuss the computed tomography (CT) findings and efficacy of stent graft placement. A 64-year-old man with a history of heavy alcohol use, situs inversus totalis, and total gastrectomy was hospitalized with hematochezia. Enhanced CT revealed a pseudoaneurysm in the common hepatic artery (CHA) with mildly high density in the main pancreatic duct. Subsequent CT revealed an enlarged cystic lesion with inflow of contrast medium. Angiography confirmed blood flow from the CHA into the pancreatic pseudocyst, and the patient was diagnosed with HP due to intrapancreatic pseudocyst perforation of the CHA pseudoaneurysm. Coil packing into the pseudocyst failed to block the blood flow, and a covered stent graft was placed into the CHA. The patient had an uneventful clinical course. The identification of a pseudoaneurysm and a high-density area in the main pancreatic duct on enhanced CT and changes in the pancreatic cyst diameter may indicate the acute phase of HP, and stent grafting is an effective treatment for intracystic arterial perforation., (© 2024. Japanese Society of Gastroenterology.)

Background: Little is known about the relationship of healthy diets, which are widely recommended to prevent diseases in general populations, with the risk of hypertensive disorders of pregnancy (HDP), particular among non-Western populations with different dietary habits. We aimed to investigate the association between periconceptional diet quality and the risk of HDP among pregnant Japanese women., Methods and Results: Dietary intake over 1 year before the first trimester of pregnancy was assessed using a validated, self-administered food frequency questionnaire among 81 113 pregnant Japanese women who participated in a prospective cohort of the Japan Environment and Children's Study. Overall diet quality was assessed by the Balanced Diet Score (BDS) based on adherence to the country-specific dietary guidelines and the Dietary Approaches to Stop Hypertension (DASH) score. Cases of HDP were identified by medical record transcription. The association between diet quality and HDP risk was examined using Bayesian logistic regression models with monotonic effects. We identified 2383 (2.9%) cases of HDP. A higher BDS was associated with a lower risk of HDP. When comparing the highest with the lowest quintile of the BDS, the adjusted odds ratio (aOR) of HDP was 0.83 (95% credible interval [CrI], 0.73-0.94). The DASH score and HDP risk were inversely associated in a monotonic dose-response manner (aOR per 1-quintile increase in the DASH score, 0.92 [95% CrI, 0.89-0.95])., Conclusions: A high-quality diet, which is recommended for disease prevention in general populations, before conception may also reduce the risk of HDP among pregnant Japanese women.

Aim: To investigate the outcomes of cabozantinib in patients with unresectable hepatocellular carcinoma (uHCC), focusing on dose setting and modification., Methods: We retrospectively analyzed 34 Japanese patients who received cabozantinib for uHCC. Trough concentrations (C trough ) of cabozantinib were also measured weekly for 6 weeks in the 18 patients., Results: Sixteen patients received ≥40 mg (high-dose group), and 18 patients received 20 mg (low-dose group). Dose escalations were performed in 27.8% of the patients in the low-dose group. Although median duration of the first dose reduction or interruption in the low-dose group was twice that in the high-dose group (28 vs. 14 days, p < 0.001), there were no significant differences in the relative dose intensity (RDI) during 6 weeks, progression free survival (PFS), and overall survival (p = 0.162, p = 0.950, p = 0.817, respectively) between the two groups. Patients who received RDI during 6 weeks ≥33.4% showed a trend toward longer median PFS (p = 0.054). Each serum aldolase value during the 6 weeks was significantly correlated with the C trough at any point (r = 0.500, p < 0.001). In multivariate analyses, aldolase ≥8.7 U/L within 2 weeks was significantly associated with the very early dose reduction or interruption (odds ratio 20.0, p = 0.002)., Conclusions: An initial dose of 20 mg cabozantinib could be a safe option in Japanese patients. The serum aldolase value could be useful for making appropriate dose modifications of cabozantinib., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

The current prebirth cohort study investigated the association between maternal intake of specific types of fatty acids during pregnancy and adolescent depressive symptoms based on the Center for Epidemiologic Studies Depression Scale. Subjects were 873 mother-child pairs. Dietary intake during the preceding month was assessed using a self-administered diet history questionnaire. The risk of depressive symptoms was 23.3% among the 873 adolescents at 13 years of age. Higher maternal saturated fatty acid intake during pregnancy was independently associated with a reduced risk of depressive symptoms in adolescents. Maternal intake of total fat, monounsaturated fatty acids, n-3 polyunsaturated fatty acids, α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, n-6 polyunsaturated fatty acids, linoleic acid, arachidonic acid and cholesterol during pregnancy was not significantly related to depressive symptoms in adolescents. Higher maternal intake of saturated fatty acids during pregnancy may be inversely associated with adolescent depressive symptoms.

Background: This study aimed to clarify the morphological changes in esophageal varices after achieving sustained virological response (SVR) with direct-acting antivirals (DAAs) in patients with cirrhosis., Methods: A total of 243 patients underwent esophagogastroduodenoscopy before DAA treatment and after achieving SVR. Morphological changes in esophageal varices were investigated using esophagogastroduodenoscopy., Results: This study comprised 125 males and 118 females with a median age of 68 years. Esophageal varices at baseline were classified into no varix in 155 (63.8%), F1 in 59 (24.3%), F2 in 25 (10.3%) and F3 in 4 (1.6%) patients. The improvement, unchanged, and aggravation rates of esophageal varices after SVR were 11.9%, 73.3%, and 14.8%, respectively. High ALBI score at SVR12 was an independent factor associated with post-SVR esophageal varices aggravation (p = 0.045). Time-dependent receiver operating characteristic (ROC) curve analysis revealed a cut-off value of - 2.33 for ALBI score at SVR12 in predicting post-SVR esophageal varices aggravation. Of the 155 patients without esophageal varices at baseline, 17 developed de novo post-SVR esophageal varices. High ALBI score at SVR12 was a significant independent factor associated with de novo post-SVR esophageal varices (p = 0.046). ROC curve analysis revealed a cut-off value of - 2.65 for ALBI score at SVR12 in predicting de novo post-SVR esophageal varices., Conclusions: Patients with cirrhosis can experience esophageal varices aggravation or de novo esophageal varices, despite achieving SVR. In particular, patients with high ALBI score at SVR12 have a high likelihood of developing post-SVR esophageal varices aggravation or de novo post-SVR esophageal varices., (© 2024. Japanese Society of Gastroenterology.)

Purpose: Individuals with impaired masticatory function tend to prefer soft foods, which results in decreased masticatory muscle activity. This study examined the association between the oral condition (number of teeth, occlusal force, and occlusal contact area) and dietary hardness using a daily dietary questionnaire., Methods: This cross-sectional study evaluated 1841 participants aged 69-71 and 79-81 years. Registered dentists examined the number of teeth, occlusal force, and occlusal contact area. Dietary hardness was defined as the estimated masticatory muscle activity required for a habitual diet. Habitual diet during the preceding month was assessed using a brief self-administered diet history questionnaire. Confounding factors, such as age, sex, socioeconomic status, smoking habits, history of chronic diseases (hypertension, hyperlipidemia, and diabetes), and cognitive function were also evaluated. Multivariate linear regression analyses were performed to assess the association between dietary hardness and each oral condition., Results: Occlusal force (standardized regression coefficients [β]=0.08, P < 0.01) and occlusal contact area (β=0.06, P < 0.01) were significantly associated with dietary hardness after adjusting for the confounding factors. Number of teeth was not significantly associated with dietary hardness. In addition, the associations between dietary hardness, sex, and a history of diabetes were stronger than those between dietary hardness and oral factors., Conclusions: Occlusal force and contact area were significantly associated with dietary hardness as estimated from the masticatory muscle activity using a daily diet questionnaire.

Introduction: Platinum-based chemotherapy is the mainstay of first-line therapy for advanced-stage non-small cell lung cancer (NSCLC). Although carboplatin-induced hypersensitivity reactions (HSRs) commonly occur following multiple cycles of therapy, they are rarely observed during the first cycle of the treatment., Case Report: Here, we report the case of a 70-year-old man with advanced-stage NSCLC who developed HSR possibly caused by carboplatin during the first cycle of induction with platinum-doublet chemotherapy plus pembrolizumab. The patient presented with bronchial obstruction due to a centrally located tumor. No driver mutations were detected, and the programmed death-ligand 1 expression ranged from 1% to 24%. Consequently, the patient was treated with pembrolizumab combined with carboplatin and paclitaxel. However, immediately after the start of carboplatin, the blood pressure and oxygen levels of the patient dropped and he began exhibiting an altered level of consciousness. These findings indicated carboplatin-induced anaphylaxis. Hypotension and oxygen desaturation improved following carboplatin discontinuation and normal saline administration., Management and Outcome: The basophil activation test for both carboplatin and cisplatin was negative. Thus, the risk of anaphylaxis owing to both drugs was ruled out, and carboplatin was believed to have induced grade 3 HSR. Subsequently, carboplatin-based chemotherapy was switched to cisplatin-based chemotherapy. HSR was not observed during the four treatment cycles with pembrolizumab, cisplatin, and pemetrexed, and best response was partial response., Discussion: Cisplatin-based chemotherapy could be used as an alternate treatment in patients with NSCLC who develop severe carboplatin-induced HSR., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Herein, we present a case of mosaic trisomy 6 detected by amniocentesis., Case Report: Amniocentesis (G-banding) was performed at 17 weeks of gestation; the results were 47,XY,+6[3]/46,XY[12]. Fetal screening ultrasonography showed no morphological abnormalities, and the parents desired to continue the pregnancy. The infant was delivered vaginally at 39 weeks' gestation. The male infant weighed 3002 g at birth with no morphological abnormalities. G-banding karyotype analysis performed on the infant's peripheral blood revealed 46,XY[20]. FISH analysis revealed trisomy signals on chromosome 6 in 1-4 out of 100 cells from the placenta. The single nucleotide polymorphism microarray of the umbilical cord blood revealed no abnormalities. Methylation analysis of umbilical cord blood revealed no abnormalities in PLAGL1. No disorders were observed at one year of age., Conclusion: When amniocentesis reveals chromosomal mosaicism, it is essential to provide a thorough fetal ultrasound examination and careful genetic counseling to support the couples' decision-making., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interests., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a member of the coronavirus family that also includes endemic human coronaviruses (HCoVs) types OC43, HKU1, 229E, and NL63. HCoVs share extensive sequence homology with SARS-CoV-2. It has been assumed that HCoV infection occur primarily in winter and spring in Japan before the coronavirus disease 2019 (COVID-19) pandemic and that its frequency is the same for all age groups., Methods: Nasopharyngeal swab samples were collected for HCoVs and SARS-CoV-2. All medical data were retrospectively analyzed. Our primary objective was to describe the epidemiology of HCoV in the Furano, Japan during the COVID-19 pandemic. Our secondary objective was to compare the prevalence of HCoV with that of SARS-CoV-2., Results: From September 2020 to August 2022, 113 (6.2 %) of 1823 cases were positive for any HCoV. The HCoV-NL63 activity peaked in January-March 2021. The HCoV-OC43 activity peaked in June-August 2021. HCoVs were mostly detected at age ≤11 years and most frequently at age ≤2 years. HCoVs showed high detection in 2021, while SARS-CoV-2 showed moderate detection in 2020-2021, but significantly increased in 2022., Conclusions: During the COVID-19 pandemic, HCoV-OC43 activity peaked in the summer. The frequency of HCoV infection varied widely by age group and was higher among those aged ≤11 years. These were different from those reported before the COVID-19 pandemic. These findings suggest that the disease dynamics of HCoVs remain unclear and that continued surveillance is essential in the post-COVID-19 pandemic., Competing Interests: Declaration of competing interest There are no conflicts of interest., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Objectives: Nuts are nutrient-dense foods rich in unsaturated fatty acids, protein, dietary fiber, vitamins, and minerals. The present prebirth cohort study examined the association between maternal nut intake during pregnancy and the risk of childhood behavioral problems in 5-year-old Japanese children., Methods: Study subjects were 1199 mother-child pairs. Dietary intake was assessed using a diet history questionnaire. Emotional problems, conduct problems, hyperactivity problems, peer problems, and low prosocial behavior were assessed using the parent-reported version of the Strengths and Difficulties Questionnaire. Adjustments were made for a priori-selected nondietary confounders and potentially related dietary factors., Results: Compared with mothers who had not eaten nuts during pregnancy, mothers who had eaten nuts had a significantly reduced risk of peer problems in children; the adjusted odds ratio was 0.64 (95% confidence interval: 0.42-0.97). There were no measurable associations between maternal consumption of nuts during pregnancy and the risk of childhood emotional problems, conduct problems, hyperactivity problems, and low prosocial behavior., Conclusions: Maternal consumption of nuts during pregnancy may be associated with a decreased risk of peer problems in 5-year-old children., (© 2024 The Authors. Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background and Aim: Although diet is one of the potential environmental factors affecting ulcerative colitis (UC), evidence is not sufficient to draw definitive conclusions. This Japanese case-control study examined the association between the consumption of coffee, other caffeine-containing beverages and food, and total caffeine and the risk of UC., Methods: The study involved 384 UC cases and 665 control subjects. Intake of coffee, decaffeinated coffee, black tea, green tea, oolong tea, carbonated soft drinks, and chocolate snacks was measured with a semiquantitative food-frequency questionnaire. Adjustments were made for sex, age, pack-years of smoking, alcohol consumption, history of appendicitis, family history of UC, education level, body mass index, and intake of vitamin C, retinol, and total energy., Results: Higher consumption of coffee and carbonated soft drinks was associated with a reduced risk of UC with a significant dose-response relationship (P for trend for coffee and carbonated soft drinks were <0.0001 and 0.01, respectively), whereas higher consumption of chocolate snacks was significantly associated with an increased risk of UC. No association was observed between consumption of decaffeinated coffee, black tea, green tea, or oolong tea and the risk of UC. Total caffeine intake was inversely associated with the risk of UC; the adjusted odds ratio between extreme quartiles was 0.44 (95% confidence interval: 0.29-0.67; P for trend <0.0001)., Conclusions: We confirmed that intake of coffee and caffeine is also associated with a reduced risk of UC in Japan where people consume relatively low quantities of coffee compared with Western countries., (© 2023 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: The role of prenatal diet on childhood wheezing and subsequent risk of asthma is inconclusive, which may be partly due to the heterogeneity in wheezing phenotypes. We aimed to identify wheeze trajectories in early childhood and to examine their associations with periconceptional maternal diet quality., Methods: Data from 70,530 mother-child pairs of liveborn singletons from the Japan Environment and Children's Study were analysed. Wheezing was reported by caregivers using a modified International Study of Asthma and Allergies in Childhood questionnaire yearly from 1 to 4 years of age, from which trajectories were derived using group-based trajectory modelling. Maternal diet in the year preceding the first trimester of pregnancy was assessed using a validated food frequency questionnaire; overall diet quality was determined using the balanced diet score based on the Japanese Food Guide Spinning Top. Bayesian inference of multinomial logistic regression models was performed to examine the association between maternal diet quality and wheeze trajectory in early childhood., Results: We identified four wheeze trajectories: 'never/infrequent' (69.1%; reference group), 'early-childhood onset' (6.2%), 'transient early' (16.5%) and 'persistent' (8.2%). After adjustment for confounders, a higher quartile of maternal balanced diet score was associated with a lower risk of belonging to the 'transient early' and 'persistent' wheeze trajectories compared with the 'never/infrequent' wheeze trajectory by 10% of both. Maternal balanced diet score was not associated with belonging to the 'early-childhood onset' wheeze trajectory., Conclusion: Improving maternal diet quality prior to conception may reduce certain wheeze phenotypes in early childhood., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: While research has explored the risk of periodontal disease in various eye conditions, the link between dry eye and periodontal disease remains underexplored, especially in Japanese adults. This study aims to investigate the association between dry eye and periodontal disease in community-dwelling Japanese adults., Methods: This study is a subset of the Uonuma cohort study, which includes Japanese adults aged 40 years and older residing in the Uonuma area of Niigata Prefecture, Japan. Participants completed a self-administered, paper-based questionnaire. Statistical analyses, including the chi-square test, independent t test, ANOVA test, and logistic regressions, were employed to assess the association of periodontal disease with independent variables., Results: Among 36,488 participants (average age 63.3 years, 47.4% men), 39.3% had a history of periodontal disease, and gender differences were statistically significant (p < 0.001). Significant associations were found between periodontal disease and dry eye diagnosis or symptoms. Univariable logistic regression revealed links between periodontal disease and age, gender, living status, alcohol consumption, remaining teeth, bite molar availability, and history of dry eye disease or symptoms. Multiple-adjusted regression found that doctor-diagnosed dry eye was associated with a higher likelihood of periodontal disease (odds ratio, 1.12; 95% confidence interval, 1.03-1.22). Participants who never experienced dryness or foreign body sensation had lower ORs of periodontal disease than those who always experienced such symptoms across all models., Conclusion: A significant correlation was found between dry eye and periodontal disease in Japanese adults. Regular check-ups, early detection, and effective management of both conditions are strongly recommended., (© 2023. The Author(s).)

Introduction: Constipation is one of the most common gastrointestinal symptoms. It may compromise quality of life and social functioning and result in increased healthcare use and costs. We aimed to evaluate the prevalence and risk factors of constipation symptoms, as well as those of refractory constipation symptoms among patients who underwent colonoscopy., Methods: Over 4.5 years, patients who underwent colonoscopy and completed questionnaires were analyzed. Patients' symptoms were evaluated using the Gastrointestinal Symptoms Rating Scale., Results: Among 8,621 eligible patients, the prevalence of constipation symptoms was 33.3%. Multivariate analysis revealed female sex (odds ratio [OR] 1.7, p &lt; 0.001), older age (OR 1.3, p &lt; 0.001), cerebral stroke with paralysis (OR 1.7, p = 0.009), chronic renal failure (OR 2.6, p &lt; 0.001), ischemic heart disease (OR 1.3, p = 0.008), diabetes (OR 1.4, p &lt; 0.001), chronic obstructive pulmonary disease (OR 1.5, p = 0.002), benzodiazepine use (OR 1.7, p &lt; 0.001), antiparkinsonian medications use (OR 1.9, p = 0.030), and opioid use (OR 2.1, p = 0.002) as independent risk factors for constipation symptoms. The number of patients taking any medication for constipation was 1,134 (13.2%); however, refractory symptoms of constipation were still present in 61.4% of these patients. Diabetes (OR 1.5, p = 0.028) and irritable bowel syndrome (OR 3.1, p &lt; 0.001) were identified as predictors for refractory constipation symptoms., Conclusions: Constipation occurred in one-third of patients, and more than half of patients still exhibited refractory symptoms of constipation despite taking laxatives. Multiple medications and concurrent diseases seem to be associated with constipation symptoms., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Concentrated polymer brushes (CPBs), which are significantly denser and thicker than conventional semidilute polymer brushes, have received increasing attention in the field of tribology because of their superlow friction properties. However, despite numerous studies aimed at enhancing CPBs for mechanical applications, the relationship between the specific layered structure and lubrication mechanisms of CPBs is still not completely understood. In this study, to reveal the relationship, simultaneous time-resolved measurements of the interfacial gap, static mechanical response, and dynamic mechanical response of the CPB at the contact interface were conducted using optical interference and precise force measuring methods. Two types of tests (i.e., the "indentation" and "sliding" tests) were alternately performed on a glass substrate coated with the CPB against a steel ball immersed in an ionic liquid. The indentation tests measuring the time-resolved interfacial gap and changes in static and dynamic mechanical responses quantitatively confirmed the presence of dilute, middle, and concentrated layers in the CPB. In the sliding tests, the wear of the CPB was detected by observing a decrease in the interfacial gap at the contact interface. Moreover, the thickness of the dilute layer remained constant with sliding, whereas the thicknesses of the other layers decreased, indicating that the dilute layer was continuously formed due to sliding. Therefore, CPB wear occurs randomly at the friction interface alongside the formation of a dilute layer with low density and stiffness on the surface.

Background: The present study was carried out to answer three questions: 1) How much forearm rotation can be expected after mobilization of congenital radioulnar synostosis (CRUS)? 2) Does preoperative radius head dislocation affect forearm rotation after mobilization? 3) What factors other than radius head dislocation affect postoperative forearm rotation?, Methods: We performed mobilization of CRUS with a free vascularized fascio-fat graft and a radius osteotomy (Kanaya's procedure) on 26 forearms of 25 patients. The age at the surgery ranged from 5.3 to 13.4 years. The follow-up duration ranged 24-111 months. We classified CRUS into 3 groups according to the dislocation of the radius head: posterior dislocation (N = 13), anterior dislocation (N = 9) and no dislocation (N = 4). Since major complaints of patients and parents were poor forearm rotation and lack of supination, they were evaluated separately., Results: Mean preoperative forearm ankylosis angle was 34.8° (range; neutral to 90° pronation). Preoperative pronation ankylosis angle was higher in the posterior dislocation group (mean 55.3°) than the anterior dislocation (mean 11.6°) and no dislocation groups (mean 5.0°). There was no re-ankylosis after mobilization and the mean postoperative active range of motion (ROM) was 86.5°. The mean active ROM was 75.7° in the posterior dislocation group, 96.1° in anterior dislocation group and 100.0° in no dislocation group. The mean active supination was 6.9, 33.9 and 47.5° respectively. The posterior dislocation group showed less ROM and less supination than other groups. Preoperative pronation ankylosis angle showed negative correlation with postoperative ROM (ρ = - 0.59) and postoperative supination (ρ = - 0.73)., Conclusion: The mean postoperative active ROM of this mobilization was 86.5°. Posterior dislocation group showed higher pronation ankylosis angle preoperatively, and less postoperative ROM and less supination than anterior and no dislocation groups. Preoperative pronation ankylosis angle showed negative correlation with postoperative ROM and supination., Competing Interests: Declaration of competing interest Each author certifies that neither he nor she, nor any member of his or her immediate family, has funding or commercial associations (consultancies, stock ownership, equity interest, patient/licensing arrangement, etc.) that might pose a conflict of interest in connection with the submitted article., (Copyright © 2022 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

RNA aptamersare nucleic acids that are obtained using the systematic evolution of ligands by exponential enrichment (SELEX) method. When using conventional selection methods to immobilize target proteins on matrix beads using protein tags, sequences are obtained that bind not only to the target proteins but also to the protein tags and matrix beads. In this study, we performed SELEX using β-1,3-glucan recognition protein (GRP)-tags and curdlan beads to immobilize the acute myeloid leukaemia 1 (AML1) Runt domain (RD) and analysed the enrichment of aptamers using high-throughput sequencing. Comparison of aptamer enrichment using the GRP-tag and His-tag suggested that aptamers were enriched using the GRP-tag as well as using the His-tag. Furthermore, surface plasmon resonance analysis revealed that the aptamer did not bind to the GRP-tag and that the conjugation of the GRP-tag to RD weakened the interaction between the aptamer and RD. The GRP-tag could have acted as a competitor to reduce weakly bound RNAs. Therefore, the affinity system of the GRP-tagged proteins and curdlan beads is suitable for obtaining specific aptamers using SELEX., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.)

Chemotherapeutic nucleoside analogs, such as cytarabine (Ara-C), are incorporated into genomic DNA during replication. Incorporated Ara-CMP (Ara-cytidine monophosphate) serves as a chain terminator and inhibits DNA synthesis by replicative polymerase epsilon (Polε). The proofreading exonuclease activity of Polε removes the misincorporated Ara-CMP, thereby contributing to the cellular tolerance to Ara-C. Purified Polε performs proofreading, and it is generally believed that proofreading in vivo does not need additional factors. In this study, we demonstrated that the proofreading by Polε in vivo requires CTF18, a component of the leading-strand replisome. We found that loss of CTF18 in chicken DT40 cells and human TK6 cells results in hypersensitivity to Ara-C, indicating the conserved function of CTF18 in the cellular tolerance of Ara-C. Strikingly, we found that proofreading-deficient POLE1 D269A/- , CTF18 -/- , and POLE1 D269A/- /CTF18 -/- cells showed indistinguishable phenotypes, including the extent of hypersensitivity to Ara-C and decreased replication rate with Ara-C. This observed epistatic relationship between POLE1 D269A/- and CTF18 -/- suggests that they are interdependent in removing mis-incorporated Ara-CMP from the 3' end of primers. Mechanistically, we found that CTF18 -/- cells have reduced levels of chromatin-bound Polε upon Ara-C treatment, suggesting that CTF18 contributes to the tethering of Polε on fork at the stalled end and thereby facilitating the removal of inserted Ara-C. Collectively, these data reveal the previously unappreciated role of CTF18 in Polε-exonuclease-mediated maintenance of the replication fork upon Ara-C incorporation., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Diets contain toxic chemical contaminants as well as essential nutrients, both of which influence the intrauterine environment for foetal growth. However, whether a high-quality diet that is nutritionally healthy also results in lower exposure to chemical contaminants is unknown., Objective: We examined associations between periconceptional maternal diet quality and circulating concentrations of heavy metals during pregnancy., Design: Dietary intake over the year prior to the first trimester of pregnancy was assessed using a validated, self-administered food frequency questionnaire among 81,104 pregnant Japanese women who participated in the Japan Environment and Children's Study. Overall diet quality was determined using the Balanced Diet Score (BDS) based on the Japanese Food Guide Spinning Top, the Healthy Eating Index-2015 (HEI-2015), the Dietary Approaches to Stop Hypertension (DASH) score and the Mediterranean diet score (MDS). We measured whole-blood concentrations of mercury (Hg), lead (Pb) and cadmium (Cd) during the second or third trimester of pregnancy., Results: After controlling for confounders, all diet quality scores were positively associated with blood Hg concentrations. By contrast, higher BDS, HEI-2015 and DASH scores were associated with lower concentrations of Pb and Cd. Although the MDS was positively associated with concentrations of Pb and Cd, when dairy products were classified as a beneficial (rather than detrimental) food component, these associations were attenuated., Conclusion: A high-quality diet may reduce exposure to Pb and Cd but not Hg. Further studies are required to determine the optimal balance between mercury exposure risk and nutritional benefits of high-quality diets prior to pregnancy., 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 Authors. Published by Elsevier Inc. All rights reserved.)

Background: mRNA vaccination is an effective, safe, and widespread strategy for protecting pregnant women against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, information on factors such as perinatal outcomes, safety, and coverage of mRNA vaccinations among pregnant women is limited in Japan. Therefore, this study aimed to investigate the perinatal outcomes, coverage, adverse effects, and short-term safety of mRNA vaccination as well as vaccine hesitancy among pregnant women., Methods: We conducted a multicenter online survey of postpartum women who delivered their offspring at 15 institutions around Tokyo from October 2021 to March 2022. Postpartum women were divided into vaccinated and unvaccinated groups. Perinatal outcomes, COVID-19 prevalence, and disease severity were compared between the two groups. Adverse reactions in the vaccinated group and the reasons for being unvaccinated were also investigated retrospectively., Results: A total of 1,051 eligible postpartum women were included. Of these, 834 (79.4%) had received an mRNA vaccine, while 217 (20.6%) had not, mainly due to concerns about the effect of vaccination on the fetus. Vaccination did not increase the incidence of adverse perinatal outcomes, including fetal morphological abnormalities. The vaccinated group demonstrated low COVID-19 morbidity and severity. In the vaccinated group, the preterm birth rate, cesarean section rate, and COVID-19 incidence were 7.2%, 33.2%, and 3.3%, respectively, compared with the 13.7%, 42.2%, and 7.8% in the unvaccinated group, respectively. Almost no serious adverse reactions were associated with vaccination., Conclusions: mRNA vaccines did not demonstrate any adverse effects pertaining to short-term perinatal outcomes and might have prevented SARS-CoV-2 infection or reduced COVID-19 severity. Concerns regarding the safety of the vaccine in relation to the fetus and the mother were the main reasons that prevented pregnant women from being vaccinated. To resolve concerns, it is necessary to conduct further research to confirm not only the short-term safety but also the long-term safety of mRNA vaccines., (© 2023. The Author(s).)

Purpose: There are various analysis methods for CT perfusion (CTP). Although the advantages of Bayesian estimation algorithms have been newly suggested, comparisons with other analysis methods on clinical data are still limited. In this study, we compared the Bayesian estimation method with the singular value decomposition (SVD) method in the evaluation of patients with acute cerebral infarction and examined its usefulness., Methods: CTP data from 13 patients with acute stroke were analyzed using the SVD and Bayesian estimation methods implemented in Vitrea. Evaluation of visual clarity of the ischemic area and quantitative values of the healthy side-affected side ratio using the mean values of the left and right region of interest (ROI) on the images were compared using the SVD and Bayesian estimation methods., Results: In visual evaluation, there were significant differences in CBV in four cases, and in CBF, MTT, and TTP in many cases. The healthy side-affected side ratio of the SVD and Bayesian estimation methods were as follows: CBF 1.19, 1.84; CBV 1.09, 1.02; MTT 1.12, 1.79; and TTP 1.48, 1.19. For CBF and MTT, the Bayesian estimation method had a larger ratio of the healthy side to the affected side, and for TTP, the SVD method had a larger ratio of the test side to the affected side., Conclusion: We suggest that the Bayesian estimation method is more useful than the SVD method for assessing CBF and MTT in CTP analysis of patients with acute stroke.

Lenvatinib is an oral tyrosine kinase inhibitor that acts on multiple receptors involved in angiogenesis. Lenvatinib is a standard agent for the treatment of several types of advanced cancers; however, it frequently causes muscle-related adverse reactions. Our previous study revealed that lenvatinib treatment reduced carnitine content and the expression of carnitine-related and oxidative phosphorylation (OXPHOS) proteins in the skeletal muscle of rats. Therefore, this study aimed to evaluate the effects of L-carnitine on myotoxic and anti-angiogenic actions of lenvatinib. Co-administration of L-carnitine in rats treated with lenvatinib for 2 weeks completely prevented the decrease in carnitine content and expression levels of carnitine-related and OXPHOS proteins, including carnitine/organic cation transporter 2, in the skeletal muscle. Moreover, L-carnitine counteracted lenvatinib-induced protein synthesis inhibition, mitochondrial dysfunction, and cell toxicity in C2C12 myocytes. In contrast, L-carnitine had no influence on either lenvatinib-induced inhibition of vascular endothelial growth factor receptor 2 phosphorylation in human umbilical vein endothelial cells or angiogenesis in endothelial tube formation and mouse aortic ring assays. These results suggest that L-carnitine supplementation could prevent lenvatinib-induced muscle toxicity without diminishing its antineoplastic activity, although further clinical studies are needed to validate these findings., 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 Jing, Iba, Naito, Xu, Morishige, Nagata, Okubo and Ando.)

This study investigated the impact of partial splenic embolization (PSE) on portal hypertensive gastropathy (PHG). We retrospectively analyzed endoscopic findings and the portal venous system of 31 cirrhotic patients with PHG. The improved group was defined as the amelioration of PHG findings using the McCormack classification. Child-Pugh scores of the improved group (18 of 31 patients) were significantly lower compared with those of the non-improved group ( p = 0.018). The changes in the diameters of the portal trunk and those of the spleno-portal junction and spleen hilum in the splenic vein of the improved group were significantly larger than those of the non-improved group ( p = 0.007, p = 0.025, and p = 0.003, respectively). The changes in the diameters of the portal vein and splenic hilum of the splenic vein showed significant correlations with Child-Pugh score (r = 0.386, p = 0.039; r = 0.510, p = 0.004). In a multivariate analysis of baseline factors related to the improved group, Child-Pugh grade A was significantly associated with the improvement of PHG (odds ratio 6.875, p = 0.033). PSE could be useful for PHG, especially in patients with Child-Pugh grade A, at least in the short term.

A bronchobiliary fistula (BBF) is an uncommon but severe complication after radiofrequency ablation (RFA). However, the definitive salvage methods are controversial. We herein report a patient with hepatocellular carcinoma with hepatic abscess and BBF following RFA. We also review previous reports of BBF after RFA. The patient was a man in his 70s who underwent RFA for recurrent hepatocellular carcinoma in the subphrenic area. Despite percutaneous transhepatic abscess drainage, bilioptysis persisted. Finally, the BBF was occluded with an endobronchial Watanabe spigot under fiber-optic bronchoscopy. Placing an endobronchial Watanabe spigot should be considered as a salvage therapy for refractory BBF following RFA.

Background: Both poor maternal nutrition and toxic heavy metal exposure influence foetal growth and development. However, whether consumption of a variety of healthy foods modifies the association between prenatal heavy metal exposure and foetal growth is unknown., Objective: We examined whether long-term maternal diet quality in periconception modifies the associations between maternal circulating concentrations of heavy metals and foetal growth., Design: Data of 72,317 Japanese women who delivered singleton infants was extracted from the Japan Environment and Children's Study. Maternal diet over a 1-year before the first trimester of pregnancy was assessed using a validated food frequency questionnaire, and overall diet quality was determined using the balanced diet score based on the Japanese Food Guide Spinning Top. Maternal whole-blood concentrations of mercury (Hg), lead (Pb) and cadmium (Cd) were measured during the second/third trimester of pregnancy. Bayesian inference of multiple linear regression analysis was performed to evaluate the relationships between maternal diet quality and the blood concentrations of heavy metals; Bayesian logistic regression was used to analyse the risk of low birth weight (LBW; <2,500 g)., Results: After controlling for confounders, a high maternal balanced diet score was associated with low concentrations of blood Pb and Cd and high Hg. While all heavy metals assessed were positively associated with LBW risk, a higher maternal balanced diet score was negatively associated with LBW risk. A high-quality maternal diet attenuated the effect of Pb on LBW, an effect that was more marked at high blood Pb concentrations., Conclusion: A high-quality, 'well-balanced' diet prior to conception may reduce exposure to some heavy metals and mitigate the elevated risk of LBW associated with prenatal Pb exposure in Japanese mother-child pairs., 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 Ltd.. All rights reserved.)

Background: Tricuspid regurgitation pressure gradient (TRPG) measurement by echocardiography is recommended as the most objective examination to detect portopulmonary hypertension (PoPH). This study aimed to identify factors associated with a high TRPG in patients with cirrhosis and develop a scoring model for identifying patients who are most likely to benefit from echocardiography investigations., Results: A total of 486 patients who underwent echocardiography were randomly allocated to the derivation and validation sets at a ratio of 2:1. Of the patients, 51 (10.5%) had TRPG ≥ 35 mmHg. The median brain natriuretic peptide (BNP) was 39.5 pg/mL. Shortness of breath (SOB) was reported by 91 (18.7%) patients. In the derivation set, multivariate analysis identified female gender, shortness of breath, and BNP ≥ 48.9 pg/mL as independent factors for TRPG ≥ 35 mmHg. The risk score for predicting TRPG ≥ 35 mmHg was calculated as follows: - 3.596 + 1.250 × gender (female: 1, male: 0) + 1.093 × SOB (presence: 1, absence: 0) + 0.953 × BNP (≥ 48.9 pg/mL: 1, < 48.9 pg/mL: 0). The risk score yielded sensitivity of 66.7%, specificity of 75.3%, positive predictive value of 25.5%, negative predict value of 94.3%, and predictive accuracy of 74.4% for predicting TRPG ≥ 35 mmHg. These results were almost similar in the validation set, indicating the reproducibility and validity of the risk score., Conclusions: This study clarified the characteristics of patients with suspected PoPH and developed a scoring model for identifying patients at high risk of PoPH, which may be used in selecting patients that may benefit from echocardiography., (© 2022. Asian Pacific Association for the Study of the Liver.)

(1) Background: The aim of this study is to review the benefits of the 8020 Campaign since its inception. (2) Methods: We followed the PRISMA guideline and collected information regarding the 8020 Campaign through online database searches. (3) Results: Twenty-five studies met the inclusion criteria and were eligible for analysis. The main outcomes of the 25 included studies were reviewed. The quality evaluation demonstrated a range of studies showing a credible relationship between masticatory function, number of teeth, salivary secretion, frequent dental check-ups, and general health concerns. Due to the risk of bias, publication bias, and indirectness, 22 studies were considered that only had "fair" quality. (4) Conclusions: The 8020 Foundation funded several of the studies, and other research papers noted the 8020 Campaign in their papers, however there were no clear explanations for any direct relationship between their findings and the 8020 Campaign. As a result, evidence for the direct effectiveness and benefits assessment of the 8020 Campaign positive outcomes were compromised by confounding social and economic variables over the 30-year period. To fully elucidate how improvement in Japan's oral health was directly related to the 8020 Campaign, a more informed and systematic explanation of the campaign's structure and activities is required., Competing Interests: The authors declare no conflict of interest.

Aim: The association between thrombolytic therapy and the outcome in patients with portal vein thrombosis (PVT) remains controversial. This study aimed to evaluate the outcome in patients with PVT who received antithrombin III-based therapy., Methods: This study was a retrospective, multicenter study to investigate the liver-related events and the survival rates in 240 patients with PVT who received the therapy., Results: The patients comprised 151 men and 89 women, with a median age of 69 years. The rate of favorable response, defined as maximum area of PVT changed to ≤75%, was 67.5% (162/240). The cumulative rates of liver-related events at 1, 2, and 3 years were 38.2%, 53.9%, and 68.5%, respectively. The multivariate analysis showed that viable hepatocellular carcinoma, absence of maintenance therapy, non-responder, and PVT progression were significantly associated with liver-related events. The PVT progression was observed in 23.3% (56/240). The multivariate analysis identified older age, absence of maintenance therapy, and non-responder as independent factors associated with PVT progression. The multivariate analysis revealed that younger age, no hepatocellular carcinoma, presence of maintenance therapy, and lower Model for End-stage Liver Disease-Sodium score significantly contributed to 3-year survival. Of the 240 patients, 13 (8.9%) prematurely discontinued treatment due to any adverse events., Conclusions: This study suggests that maintenance therapy, favorable response, and absence of PVT progression may suppress or control liver-related events in antithrombin III-based therapy for patients with PVT. Specifically, maintenance therapy could suppress not only liver-related events, but also PVT progression and improve the prognosis., (© 2022 The Japan Society of Hepatology.)

In April 2011, the International Commission on Radiological Protection recommended reducing the occupational equivalent dose limit for the lens. Such a new occupational lens dose limit has thus far been implemented in many countries, and there are extensive discussions toward its regulatory implementation in other countries. In Japan, discussions in the Japan Health Physics Society (JHPS) began in April 2013 and in Radiation Council in July 2017, and the new occupational lens dose limit was implemented into regulation in April 2021. To share our experience, we have published a series of papers summarizing situations in Japan: the first paper based on information available by early 2017, and the second paper by early 2019. This paper (our third paper of this series) aims to review updated information available by mid-2022, such as regarding regulatory implementation of the new occupational lens dose limit, recent discussions by relevant ministries based on the opinion from the council, establishment process of safety and health management systems, the JHPS guidelines on lens dose monitoring and radiation safety, voluntary countermeasures of the licensees, development of lens dose calibration method, and recent studies on exposure of the lens in nuclear workers and biological effect on the lens.

A future sustainable dietary pattern for Japanese is yet undefined. This study aimed to explore more sustainable Japanese diets that are nutritious, affordable and with low greenhouse gas emissions (GHGE) and particular emphasis on cultural acceptability. A newly developed data envelopment analysis (DEA) diet model was applied to 4-d dietary record data among 184 healthy Japanese men and 185 women volunteers aged 21-69 years. Alternative diets were calculated as the linear combinations of observed diets. Firstly, for each individual, four modelled diets were calculated that maximised cultural acceptability (i.e. minimise dietary change from observed diet), maximised nutritional quality assessed by the Nutrient-Rich Food Index (NRF), minimised monetary diet costs or minimised diet-related GHGE. The final modelled diet combined all four indicators. In the first four models, the largest improvement was obtained for each targeted indicator separately, while relatively small improvements or unwanted changes were observed for other indicator. When all indicators were aimed to optimise, the NRF score and diet-related GHGE were improved by 8-13 % with the lower monetary cost than observed diets, although the percentage improvement was a bit smaller than the separate models. The final modelled diets demanded increased intakes for whole grains, fruits, milk/cream/yogurt, legumes/nuts, and decreased intakes for red and processed meat, sugar/confectioneries, alcoholic and sweetened beverages, and seasonings in both sexes. In conclusion, more sustainable dietary patterns considering several indicators are possible for Japanese, while total improvement is moderate due to trade-offs between indicators and methodological limitation of DEA diet model.

Objective: Tryptophan is an essential amino acid wholly derived from diet. While the majority of tryptophan is degraded through the kynurenine pathway into neuroactive metabolites like quinolinic acid and kynurenic acid, a small proportion of ingested tryptophan is metabolized into the neurotransmitter serotonin. The current cross-sectional study in Japan examined the association between tryptophan intake and depressive symptoms during pregnancy., Methods: Study subjects were 1744 pregnant women. Dietary intake during the preceding month was assessed using a self-administered diet history questionnaire. Depressive symptoms were defined as a score ≥ 16 on the Center for Epidemiologic Studies Depression Scale. Adjustment was made for age, gestation, region of residence, number of children, family structure, history of depression, family history of depression, smoking, secondhand smoke exposure at home and at work, employment, household income, education, body mass index, and intake of saturated fatty acids, eicosapentaenoic acid plus docosahexaenoic acid, calcium, vitamin D, and isoflavones., Results: The prevalence of depressive symptoms during pregnancy was 19.2%. After adjustment for confounding factors, higher tryptophan intake was independently inversely associated with the prevalence of depressive symptoms during pregnancy: the adjusted prevalence ratios (95% confidence intervals) for depressive symptoms during pregnancy in the first, second, third, and fourth quartiles of tryptophan intake were 1 (reference), 0.99 (0.76-1.28), 0.94 (0.71-1.25), and 0.64 (0.44-0.93), respectively (p for trend = 0.04)., Conclusions: Higher estimated tryptophan intake was cross-sectionally independently associated with a lower prevalence of depressive symptoms during pregnancy in Japanese women., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Swallow or deglutition syncope is an unusual disorder. We herein report an 80-year-old man with paroxysmal atrial tachycardia induced by swallowing, causing syncope. Initially, we suspected a digestive disorder and found no significant findings. Finally, a swallowing test with monitoring of the heart rate and blood pressure helped in the diagnosis. The patient was treated with antiarrhythmic drugs and catheter ablation. The mechanism underlying swallowing-induced tachycardia presumably involves mechanical stimulation of the esophagus and autonomic nervous system effects. However, few cases have been reported, and the exact mechanism remains unclear.

This prospective study investigated the impact of cabozantinib exposure on proteinuria and muscle toxicity, in a cohort of 14 Japanese patients with unresectable hepatocellular carcinoma (uHCC). We measured the trough concentration of cabozantinib (Ctrough) weekly for 6 weeks after starting treatment. Although the initial dose was less than 60 mg in most cases, dose interruption occurred in 79%, primarily because of proteinuria and/or malaise. The median and coefficient of variation of maximum Ctrough at 7−42 d were 929.0 ng/mL and 59.2%, respectively. The urinary protein-to-creatinine ratio (UPCR), serum creatine kinase, and serum aldolase values were all significantly elevated following treatment. Moreover, maximum changes in serum creatine kinase and aldolase were significantly associated with maximum Ctrough (r = 0.736, p < 0.01; r = 0.798, p < 0.001; respectively). Receiver operating characteristic (ROC) curve analysis showed that changes in serum creatine kinase ≥70.5 U/L and aldolase ≥6.1 U/L from baseline relatively accurately predicted inclusion in the high-maximum Ctrough (≥929.0 ng/mL) group, with an area under the ROC of 0.929 and 0.833, respectively. Measurement of serum creatine kinase and aldolase may increase the clinical usefulness of cabozantinib treatment for uHCC and help alleviate difficulties with dose adjustments.

Milk is a good source of fats, minerals, and vitamins. The present prebirth cohort study examined the association between maternal dairy product intake during pregnancy and the risk of childhood behavioral problems in 5-year-old Japanese children. Study subjects were 1199 mother-child pairs. Dietary intake was assessed using a diet history questionnaire. Emotional problems, conduct problems, hyperactivity problems, peer problems, and low prosocial behavior were assessed using the parent-reported version of the Strengths and Difficulties Questionnaire. Adjustments were made for a priori selected non-dietary confounders and potentially related dietary factors. A significant inverse exposure-response association was observed between maternal total dairy intake during pregnancy and the risk of childhood emotional problems (adjusted odds ratio [OR] between extreme quartiles, 0.62; 95% confidence interval [CI]: 0.36-1.03, p for trend, 0.04). The greater maternal consumption of cow's milk, but not yogurt or cheese, during pregnancy was independently related to a reduced risk of emotional problems in children (adjusted OR between extreme quartiles, 0.41; 95% CI: 0.23-0.70, p for trend, 0.003). Higher maternal consumption levels of total dairy products, especially cow's milk, during pregnancy may be associated with a decreased risk of emotional problems in 5-year-old children.

Background: Due to the coronavirus disease 2019 (COVID-19) pandemic, hygienic behaviors became a new norm since January 2020. The hygiene hypothesis predicts that an excessively hygienic environment may adversely affect human health., Objective: We quantified the effect of COVID-19 on immunological parameters linked to the hygiene hypothesis., Methods: We examined age-specific levels of total nonspecific immunoglobulin G (IgG) and IgE in individuals who visited Fukuoka Tokushukai Hospital between 2010 and 2021. Pre-COVID (2010-2019) and COVID (2020-2021) periods were compared., Results: IgG levels steadily decreased throughout Pre-COVID period. IgG levels fell abruptly from the pre-COVID period to the COVID period in all age groups (P = 0.0271, < 0.3 years; P = 0.0096, 0.3-5 years; P = 0.0074, ≥ 5 years). The declines in IgG in < 0.3 years and that in ≥ 5 years accelerated during the COVID period. IgE levels were seasonal, but did not change noticeably from the pre-COVID to COVID period. IgG levels recorded for patients with Kawasaki disease (KD) (mean 709 mg/dL) were significantly lower than for matched control subjects (826 mg/dL) (P<0.0001)., Discussion: Hygienic behaviors during the COVID-19 outbreak decreased the chance of infection, which may explain the decreases in IgG levels in children and adults. Neonatal IgG declined, possibly because of the decrease in maternal IgG., Conclusion: Hygienic behaviors decreased the IgG levels in all age groups, from neonates to adults. This downturn in IgG may lead to vulnerability to infections as well as to KD., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Evidence regarding the relationship between maternal calcium intake during pregnancy and childhood blood pressure is limited and inconsistent. The present prebirth cohort study examined this issue in Japanese children aged 6 years., Methods: Subjects were 854 mother-child pairs. Maternal intake during pregnancy was assessed with a validated diet history questionnaire. A research technician measured systolic and diastolic blood pressures at home in children aged 6 years using an electronic sphygmomanometer. Analysis of covariance was used to calculate adjusted means of systolic and diastolic blood pressures according to maternal calcium intake during pregnancy., Results: Maternal calcium intake during pregnancy was not related to systolic blood pressure in children. On the other hand, compared with children of mothers whose calcium intake during pregnancy was in the lowest quartile, those of mothers whose calcium intake during pregnancy was in the highest quartile had 2.8 mmHg lower adjusted mean diastolic blood pressure (95% confidence interval: 0.3-5.3 mmHg, P for trend = .009)., Conclusions: Higher maternal calcium intake during pregnancy may be associated with a decrease in diastolic, but not systolic, blood pressure in Japanese children aged 6 years., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Soft tissue defects following wide excision of malignant soft tissue tumors (STTs) are sometimes too large for primary closure, especially in the lower legs where available soft tissue is limited. This study aimed to determine the clinical outcomes of reconstruction of a defect after wide excision of an STT with a veno-accompanying artery fasciocutaneous (VAF) flap in the lower leg., Methods: This study comprised 9 patients with malignant STTs who had undergone reconstructive surgeries using VAF flaps after wide excisions, between October 2010 and September 2017. We retrospectively reviewed and collected data involving age, sex, follow-up period, histological diagnosis, surgical procedures, size and location of defects, size and location of the flaps, venous source of the flaps, direction of the pedicles, closing of donor sites, perioperative chemotherapies, postoperative complications, and the presence of postoperative local recurrence and metastasis., Results: The median follow-up period was 91.5 (range, 15.5-189.0) months. Four patients had defects located around the knee, 3 patients had defects located on the calf, and 2 patients had defects located around the ankle. The mean flap size was 95.6 × 119.4 (range, 50 × 100-130 × 140) mm. Six patients had venous sources from the small saphenous vein and 3 patients had venous sources from the great saphenous vein. The pedicles were proximally based in 4 patients and distally based in 5 patients. All flaps remained viable without any complications., Conclusions: Our findings showed that the VAF flap was easily elevated and reliable. Furthermore, it was effective in reconstructing soft tissue defects following wide excisions of STTs in the lower leg., Competing Interests: Declaration of competing interest The author(s) declare no potential conflicts of interest., (Copyright © 2021 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Objectives: Lower maternal metal intake during pregnancy might affect childhood development. The current prebirth cohort study investigated the relationship between maternal intake of zinc, magnesium, iron, copper, and manganese during pregnancy and behavioral problems in Japanese children aged five years., Methods: Subjects were 1199 mother-child pairs. Dietary intake during the preceding month was assessed using a diet history questionnaire. Emotional, conduct, hyperactivity, and peer problems and low prosocial behavior were assessed using the Strengths and Difficulties Questionnaire. Maternal age, gestation at baseline, region of residence, number of children, maternal and paternal education, household income, maternal depressive symptoms during pregnancy, maternal alcohol intake during pregnancy, maternal smoking during pregnancy, child's birth weight, child's sex, breastfeeding duration, smoking in the household during the first year of life, and some dietary confounders that were associated with outcomes under study in this population were adjusted for., Results: Compared with maternal magnesium intake during pregnancy in the first quartile, magnesium intake in the second, third, and fourth quartiles was independently inversely related to childhood hyperactivity problems, but not to emotional, conduct, or peer problems or low prosocial behavior: the adjusted odds ratio between extreme quartiles was 0.48 (95% confidence interval: 0.23-0.99, P for trend = 0.04). No evident associations were observed between maternal intake of zinc, iron, copper, or manganese during pregnancy and childhood emotional, conduct, hyperactivity, or peer problems or low prosocial behavior., Conclusions: The present study suggests that higher maternal magnesium intake during pregnancy is inversely associated with hyperactivity problems in Japanese children.

Lenvatinib, an oral tyrosine kinase inhibitor, is widely used to treat several types of advanced cancers but often causes muscular adverse reactions. Although carnitine supplementation may prevent these effects, the mechanism underlying lenvatinib-induced skeletal muscle impairment remains poorly understood. To this end, we aimed to investigate the impact of lenvatinib on carnitine disposition in rats. Once-daily administration of lenvatinib repeated for two weeks did not affect urinary excretion or serum concentration of carnitines throughout the treatment period but ultimately decreased the L-carnitine content in the skeletal muscle. The treatment decreased the expression of carnitine/organic cation transporter (OCTN) 2, a key transporter of carnitine, in skeletal muscle at the protein level but not at the mRNA level. In cultured C2C12 myocytes, lenvatinib inhibited OCTN2 expression in a dose-dependent manner at the protein level. Furthermore, lenvatinib dose-dependently decreased the protein levels of carnitine-related genes, adenosine triphosphate content, mitochondrial membrane potential, and markers of mitochondrial function in vitro. These results reveal the deleterious effects of lenvatinib on OCTN2 expression, carnitine content, and mitochondrial function in skeletal muscle that may be associated with muscle toxicity., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Positive ulnar variance (UV) may be associated with a higher incidence of ulnar impaction syndrome (UIS). However, neutral and/or negative UV has also been associated with the development of UIS; therefore, other risk factors may be involved. The purpose of this study was to compare radiological bone morphology in patients with UIS and asymptomatic controls. Methods: Between 2009 and 2018, posteroanterior wrist radiographs of 47 wrists in 45 patients diagnosed with UIS were compared with those of 163 wrists in 93 asymptomatic patients from the control group. The following parameters were obtained: ulnar variance (UV); ulnar head top-fovea distance (UTFD); capitate-triquetrum distance (CTD); radio-lunate distance (RLD) and lunate coverage ratio (LCR). The morphology of the lunate was classified based on the absence (type I) or presence (type II) of a medial facet that articulates with the hamate. The radiographic parameters and lunate types were compared between the two groups. We then divided the groups into two subgroups: the positive UV subgroup and the neutral/negative UV subgroup. In each subgroup, the radiographic parameters and lunate types were compared between the UIS and control groups. Results: In the UIS group, the UV and UTFD were significantly increased compared to those in the control group. The proportion of type II lunates was significantly higher in the UIS group than in the control group. In addition, the type II lunate was more common in the UIS group in both the positive UV and negative UV groups. Conclusions: Our study suggests that in addition to positive UV, ulnar head morphology with an increased UTFD and type II lunate morphology may be associated with the development of ulnar impaction syndrome. Level of Evidence: Level III (Diagnostic).

Glecaprevir is a substrate for organic anion-transporting polypeptide (OATP) 1B1/1B3, which transports bilirubin. Hyperbilirubinemia is an adverse event during anti-hepatitis C virus treatment with glecaprevir and pibrentasvir. Gadoxetic acid is also transported by OATP1B1/1B3, and we aimed to evaluate whether gadoxetic acid-enhanced magnetic resonance (MR) imaging was associated with glecaprevir trough concentrations (C trough ). We further determined whether this was predictive of hyperbilirubinemia development in a cohort of 33 patients. The contrast enhancement index (CEI), a measure of hepatic enhancement effect on the hepatobiliary image, was assessed. Glecaprevir C trough was determined 7 days after administration. Five of the 33 patients (15%) developed Common Terminology Criteria for Adverse Events grade ≥ 2 hyperbilirubinemia. We found a negative relationship between CEI and C trough (r = - 0.726, p < 0.001). The partial correlation coefficient between CEI and C trough was - 0.654 (p < 0.001), while excluding the effects of albumin, FIB-4 index, and indirect bilirubin at baseline. The C trough was significantly higher in patients with hyperbilirubinemia than in those without (p = 0.008). In multivariate analysis, CEI ≤ 1.71 was an independent factor influencing the development of hyperbilirubinemia (p = 0.046). Our findings indicate that gadoxetic acid MR imaging can help predict glecaprevir concentration and development of hyperbilirubinemia., (© 2022. The Author(s).)

Nalfurafine hydrochloride, a selective κ-opioid receptor agonist has been approved for pruritus in patients with chronic liver disease. However, not all patients respond to nalfurafine hydrochloride. The aim of this study was to clarify the efficacy of nalfurafine hydrochloride. The subjects were patients with chronic liver disease complicated by pruritus who were treated with nalfurafine hydrochloride between May, 2015, and May, 2021. The degree of pruritus was evaluated based on the Visual Analog Scale (VAS) score and the Kawashima's pruritus score. Nalfurafine hydrochloride 2.5 μg was orally administered once a day for 12 weeks. A decrease in the VAS score of ≥ 25 mm or the Kawashima's pruritus score of ≥ 1 scores was designated as relevant response. The former of ≥ 50 mm or the latter of ≥ 2 scores as remarkable response. The 326 patients who were evaluated the efficacy at 12 weeks. The median time suffering from pruritus to administration of nalfurafine hydrochloride was 4 months. The median VAS score improved from 70.0 mm before administration to 40.0 and 30.0 mm at 4 and 12 weeks of treatment, respectively. On multivariate analysis, shorter itching period and lower FIB-4 index value were extracted as the independent factors related to remarkable responder. On multivariate analysis, shorter itching period was extracted as the only independent factor related to relevant responder. In conclusion, this study suggested nalfurafine hydrochloride treatment markedly improves pruritus in patients with chronic liver disease. A short pruritus period and less-advanced fibrosis were associated with response to nalfurafine hydrochloride., (© 2022. The Author(s).)

Aim: Direct-acting antivirals (DAAs) are currently available even for patients with decompensated cirrhosis. Reportedly, hepatic functional reserve improved in the short term after achievement of sustained virologic response (SVR). We aimed to clarify the outcomes after achievement of SVR in patients with decompensated cirrhosis who were treated by DAAs in real-world clinical practice., Methods: A prospective, multicenter study of 12-week sofosbuvir/velpatasvir was conducted in 86 patients with decompensated cirrhosis, who were evaluated for 48 weeks post-treatment., Results: The cohort included 8 patients with Child-Pugh class A, 56 with B, and 22 with C. The proportion of Child-Pugh class A patients increased from 9.1% at baseline to 44.1% at 48 weeks post-treatment, while that of class B and C patients decreased from 66.2% to 35.1% and from 24.7% to 14.3%, respectively. Among the patients with Child-Pugh class B and C, univariate analysis identified low total bilirubin, Child-Pugh score, Child-Pugh class B, ALBI score, and high serum albumin as factors associated with improvement to Child-Pugh class A. The optimal cut-off value of the factors for predicting improvement to Child-Pugh class A were 1.4 mg/dl for total bilirubin, 2.9 g/dl for serum albumin, 8 points for Child-Pugh score, and -1.88 for ALBI score., Conclusion: Achievement of SVR with sofosbuvir/velpatasvir improved the liver functional reserve at 12 weeks post-treatment and maintained the stable effects until 48 weeks post-treatment in patients with decompensated cirrhosis. Specifically, the patients with less advanced conditions had the likelihood of improving to Child-Pugh class A at 48 weeks post-treatment., (© 2021 Japan Society of Hepatology.)

This prospective study examined the impact of genetic polymorphisms on the pharmacokinetics and clinical efficacy and safety of lenvatinib, a substrate of ATP-binding transporters, in a cohort of 48 Japanese patients with hepatocellular carcinoma (HCC). Pharmacokinetic studies were performed at the start of lenvatinib therapy (day 1) and on day 15. The coefficients of variation in AUC 0-24h of lenvatinib on days 1 and 15 were 44.0% and 52.4%, respectively. Although the ABCB1 3435C > A, 1236C > T, and 2677G>T/A polymorphisms did not influence pharmacokinetic parameters, the AUC 0-24h values on days 1 and 15 of the ABCG2 C/A or A/A group were approximately 1.1-fold and 1.4-fold that in the ABCG2 C/C group (P = 0.164 and 0.024). There were no significant differences in AUC 0-24h on days 1 and 15 between the responders (complete or partial response) and non-responders (stable or progressive disease). The AUC 0-24h on day 15 in those developing anorexia of any grade was significantly higher than that without such development (P = 0.017). In multivariate analysis, ABCG2 421C > A C/A or A/A was significantly associated with the development of anorexia (odds ratio 9.009, P = 0.009). ABCG2 421C > A polymorphism could affect exposure to lenvatinib and the development of anorexia., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2021 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Background: Previous reports have not clarified the difference in clinical efficacy between baloxavir and oseltamivir against influenza., Methods: A prospective observational study was performed during 2017-2018, 2018-2019, and 2019-2020 influenza seasons. The primary endpoint of this study was to compare the duration of fever between patients who received baloxavir and those who received oseltamivir., Results: A total of 235 influenza-infected patients (3-18 years of age), including 91 who received oseltamivir and 144 who received baloxavir, were enrolled. The proportions of influenza A(H3N2) virus, influenza A(H1N1)pdm09 virus, and influenza B virus-infected patients were 31.5%, 42.6%, and 26.0%, respectively. Patients who received oseltamivir were significantly younger than those who received baloxavir. Univariate analyses showed that the duration of fever was shorter with baloxavir than with oseltamivir against influenza virus overall, influenza A virus, influenza B virus, and influenza A(H1N1)pdm09 virus, but not for influenza A(H3N2) virus. In multivariate analyses, hazard ratios for influenza virus overall (0.53 [95% CI, 0.38-0.73]), influenza B virus (0.16 [95% CI, 0.07-0.41]), and influenza A(H1N1)pdm09 virus (0.55 [95% CI, 0.32-0.93]) were significantly lower in the patients who received baloxavir than those who received oseltamivir. However, the differences between influenza A virus and influenza A(H3N2) virus were not significant between the two groups., Conclusion: For influenza virus overall, influenza B virus, and influenza A(H1N1)pdm09 virus, baloxavir treatment resulted in shorter duration of fever than oseltamivir treatment, but not for influenza A virus and influenza A(H3N2) virus., (© 2022 Japan Pediatric Society.)

This study investigated the inhibitory effect of levocarnitine supplementation on sarcopenia progression in hepatocellular carcinoma (HCC) patients treated with lenvatinib. We evaluated the skeletal muscle index (SMI). After propensity score matching for age, sex, modified albumin-bilirubin grade, baseline presence of sarcopenia, and branched-chain amino acid administration, we selected 17 patients who received levocarnitine supplementation after starting lenvatinib therapy and 17 propensity-score-matched patients who did not receive levocarnitine. Sarcopenia was present in 76% of the patients at baseline. Changes in baseline SMI at 6 and 12 weeks of treatment were significantly suppressed in the group with levocarnitine supplementation compared with those without ( p = 0.009 and p = 0.018, respectively). While there were no significant differences in serum free carnitine levels in cases without levocarnitine supplementation between baseline and after 6 weeks of treatment ( p = 0.193), free carnitine levels were significantly higher after 6 weeks of treatment compared with baseline in cases with levocarnitine supplementation ( p < 0.001). Baseline SMI and changes in baseline SMI after 6 weeks of treatment were significantly correlated with free carnitine levels (r = 0.359, p = 0.037; and r = 0.345, p = 0.045, respectively). Levocarnitine supplementation can suppress sarcopenia progression during lenvatinib therapy.