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Objectives: In our previous functional magnetic resonance imaging (fMRI) study, we determined that there was distinct left hemispheric dominance for lexical-semantic processing without the influence of human voice perception in right-handed healthy subjects. However, the degree of right-handedness in the right-handed subjects ranged from 52 to 100 according to the Edinburgh Handedness Inventory (EHI) score. In the present study, we aimed to clarify the correlation between the degree of right-handedness and language dominance in the fronto-temporo-parietal cortices by examining cerebral activation for lexical-semantic processing.Methods: Twenty-seven normal right-handed healthy subjects were scanned by fMRI while listening to sentences (SEN), reverse sentences (rSEN), and identifiable non-vocal sounds (SND). Fronto-temporo-parietal activation was observed in the left hemisphere under the SEN - rSEN contrast, which included lexical-semantic processing without the influence of human voice perception. Laterality Index was calculated as LI = (L - R)/(L + R) x 100, L: left, R: right.Results: Laterality Index in the fronto-temporo-parietal cortices did not correlate with the degree of right-handedness in EHI score.Conclusions: The present study indicated that the degree of right-handedness from 52 to 100 in EHI score had no effect on the degree of left hemispheric dominance for lexical-semantic processing in right-handed healthy subjects. [ABSTRACT FROM AUTHOR]

Objective Although language and culture are different in each area in the world, how does culture affect the recognition of nonverbal emotional vocalisations? A previous study on non-verbal emotional vocalisations has shown a cross-cultural effect in Western and African participants. However, nobody has ever investigated the cross-cultural differences between Japanese and Caucasian participants in their emotional response to non-verbal vocal sounds. In the present study, we aimed to investigate cross-cultural effect between Caucasian subjects and Japanese subjects when the subjects listen to nonverbal affect bursts. Method 30 Japanese subjects (15 males) participated in this study. The data of Japanese subjects were compared with data from 30 Canadian subjects (15 males). Subjects listened to the Montreal Affective Voices (MAVs), which consist of a database of nonverbal affect bursts portrayed by Canadian actors. Each voice was evaluated using three criteria: perceived emotional intensity in each of the eight emotions (Anger, Disgust, Fear, Pain, Sadness, Surprise, Happiness, and Pleasure), perceived valence, and perceived arousal. To investigate cross-cultural differences between Japanese and Canadian participants, mixed 238 ANOVAs with Group (Japanese, Canadian) and Emotion (eight emotions) as factors were calculated on ratings of Intensity, Valence, and Arousal. Results Significant Group 3 Emotion interactions were observed for ratings of intensity, valence and arousal (intensity: F(5.5, 313.5) = 9.137, p<0.001, valence: F(4.3, 244.3) = 25.101, p<0.001, arousal: F(4.4, 250.5) = 8.955, p<0.001). Post-hoc tests showed that intensity ratings from Japanese listeners were significantly higher than ratings from Caucasian listeners for angry, disgusted, fearful, surprise, and pleased (p<0.05/8). Further, valence ratings from Japanese listeners were significantly higher than ratings from Caucasian listeners for angry, disgusted, fearful, painful, surprised (p<0.05/9), whereas valence rating of pleased in Japanese listener was significantly lower than in Caucasian listener (p<0.05/9). Arousal ratings of sad vocalisations by Japanese listeners were significantly higher than by Caucasian listeners (p<0.05/9). Conclusion This study demonstrates important cross-cultural differences in the perception of non-verbal affect bursts and extends recent observations by showing that these cross-cultural differences are also found for negative emotions. [ABSTRACT FROM AUTHOR]

Background: Concerns surrounding long-term proton pump inhibitor use have prompted the exploration of alternative treatments for reflux esophagitis (RE). We previously demonstrated that 24 weeks of on-demand treatment with vonoprazan, a potassium-competitive acid blocker, effectively managed mild RE (Los Angeles classification grade A/B) in more than 80% of patients. However, its long-term efficacy remains unknown. Therefore, the present study investigated sustained effectiveness., Methods: We conducted a retrospective observational study on 30 participants with mild RE from our previous research. Participants with recurrent RE or symptom exacerbation were excluded and considered as treatment failure. Participants with the remission of RE and reflux symptoms under on-demand treatment until the clinic visit between October 2023 and February 2024 were regarded as treatment success. Predictors of treatment failure were analyzed., Results: During the observation period, 5 participants failed treatment due to symptom exacerbation and 6 due to recurrent RE. Five participants were excluded from analyses due to non-GERD causes. Fourteen participants (56.0%) successfully continued on-demand treatment for 91.5 months [89.3-92.8]. Age > 67 years significantly predicted treatment failure with a sensitivity of 72.7% and specificity of 85.7%. Although none of the patients with RE grade A had recurrent RE, it was not a significant difference., Conclusions: Approximately 50% of patients with mild RE successfully continued on-demand treatment for more than 7 years. Age > 67 years was identified as a predictor of treatment failure. Prospective multi-center studies are warranted to validate these results., Competing Interests: Declarations. Conflict of interest: Katsuhiko Iwakiri received lecture fees from Takeda Pharmaceutical Company Limited., (© 2024. The Author(s) under exclusive licence to The Japan Esophageal Society.)

Background: Eosinophilic esophagitis (EoE) presents with various esophageal motility disorders, and some cases of hypercontractile esophagus (HE) are associated with eosinophilic esophageal myositis (EoEM). This study aimed to compare the clinical characteristics of patients with EoE and EoEM according to their esophageal motility., Methods: The 28 patients with EoE and 2 patients with EoEM were divided into three groups based on esophageal motility: normal motility group, hypomotility group, and spastic contraction group. The clinical characteristics of the three groups were retrospectively compared., Results: Among the 28 patients with EoE, there were 15 with normal esophageal motility, 9 with hypomotility (2 with absent contractility, 7 with ineffective esophageal motility), and 4 with spastic contractions (1 with type III achalasia, 1 with HE, 2 with unclassifiable multipeak contractions). The two patients with EoEM had HE. Most patients in the normal and hypomotility groups had typical endoscopic findings of EoE, whereas these typical findings were less common in the spastic contraction group (P < 0.001). Four of the five patients with esophageal stricture were in the hypomotility group (P = 0.036). The therapy method significantly differed between the three groups: the normal group had more patients that responded to a proton pump inhibitor or potassium-competitive acid blocker, the hypomotility group had more patients that responded to steroids, and the spastic contraction group contained two patients treated with per-oral endoscopic myotomy (P = 0.021)., Conclusions: The endoscopic findings and therapy methods differ between patients with EoE and EoEM based on the esophageal motility., (© 2024. The Author(s) under exclusive licence to The Japan Esophageal Society.)

Introduction: Mental rotation (MR) tasks of body parts involve anatomically interconnected brain systems. The systems are implicated in sensorimotor information integration and activate cortical motor-related areas, corresponding to the execution of similar motor tasks. In this study, we aimed to investigate the effect of varying the angle in the hand MR task on cerebral activation of the motor-related areas., Methods: Twenty healthy right-handed participants were recruited. We investigated cerebral activation while each participant decided whether a hand-palm image, rotated by 0°, 90°, 180°, and 270°, was a right or left hand., Results and Discussion: A significant negative correlation between the angle and brain activity was observed in the right and left supplementary motor area (SMA) and right posterior anterior cingulate gyrus. The SMA was inactivated with 180°- or 270°-rotated images in the regions of interest analysis. 180°- and 270°-rotated palms would be biomechanically difficult to position; thus, SMA deactivation may be closely associated with biomechanical constraints. This study provided novel findings regarding the neurophysiological mechanisms of motor imagery and may be useful in developing treatment plans using MR tasks during patient rehabilitation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Nomura, Koeda, Ikeda, Tateno, Arakawa and Aoyagi.)

Background: Extrinsic factors for erosive tooth wear (ETW) have been widely reported, but the intrinsic factors for wear remain unclear., Objectives: The aim of this study was to evaluate the factors associated with the prevalence of ETW in patients with reflux oesophagitis (RO). To prevent severe ETW with RO, factors associated with severity of ETW were also evaluated., Methods: A total of 270 patients with RO were recruited. A modified tooth wear index was used to evaluate the prevalence and severity of ETW. Salivary secretion and buffering capacity were assessed prior to endoscopy. Subjects were asked to complete a medical condition and oral self-care questionnaire. Univariate and multivariate analyses were employed to identify factors collectively associated with the prevalence and severity of ETW., Results: A total of 212 cases were categorized as patients with ETW (148 with mild ETW and 64 with severe ETW). Multivariate analyses indicated that saliva secretion, severity of RO and proton pump inhibitor (PPI) resistance were associated with the prevalence of ETW, whereas age, BMI and severity of RO were associated with the severity of ETW. The odds ratio of saliva secretion and BMI were less than 1, meaning that higher saliva secretion resulted in a lower prevalence of ETW and lower BMI was associated with severe ETW., Conclusion: Saliva secretion, severity of RO and PPI resistance were associated with the prevalence of ETW, whereas age, BMI and severity of RO were associated with the severity of ETW. Lower saliva secretion and BMI were significant factors for ETW., (© 2024 John Wiley & Sons Ltd.)

Background: The salivary secretion in patients with mild reflux esophagitis (RE) and non-erosive reflux disease is significantly lower in females, but not in males. However, sex differences in salivary secretion in patients with severe RE remain unknown. Therefore, the present study investigated sex differences in saliva secretion in patients with severe RE., Methods: Subjects consisted of 23 male patients with severe RE, 24 male healthy controls (HCs), 26 female patients with severe RE, and 25 female HCs. Saliva secretion was assessed as follows: each patient chewed sugarless gum for 3 min prior to endoscopy, and the amount and pH of saliva secreted before and after acid loading as an index of the acid-buffering capacity were measured., Results: In males, no significant differences were observed in the amount of saliva secretion, salivary pH, or the acid-buffering capacity between severe RE patients and HCs. In females, the amount of saliva secretion (severe RE: 2.4 [1.8-4.1], HCs: 5.3 [3.4-7.5], p = 0.0017), salivary pH (severe RE: 7.0 [6.7-7.3], HCs: 7.2 [7.1-7.3], p = 0.0455), and the acid-buffering capacity (severe RE: 5.9 [5.3-6.2], HCs: 6.2 [6.1-6.5], p = 0.0024) were significantly lower in severe RE patients than in HCs., Conclusion: Among females, the salivary secretion was significantly lower in severe RE patients than in HCs. This reduction in salivary secretion may contribute to the pathophysiology of severe RE in females., (© 2024. The Author(s), under exclusive licence to The Author(s) under exclusive licence to The Japan Esophageal Society.)

Dental drilling sounds can induce anxiety in some patients. This study aimed to use functional magnetic resonance imaging (fMRI) to assess the relationship between dental fear and auditory stimuli. Thirty-four right-handed individuals (21 women and 13 men; average age, 31.2 years) were selected. The level of dental fear was assessed using the dental fear survey (DFS). Based on a threshold DFS score > 52, participants were categorized into two groups: dental fear (DF) group (n = 12) and control group (n = 22). Two types of stimuli were presented in a single session: dental and neutral sounds. Cerebral activation during the presentation of these sounds was evaluated using contrast-enhanced blood oxygenation level-dependent fMRI. In the DF group, dental sounds induced significantly stronger activation in the left inferior frontal gyrus and left caudate nucleus (one-sample t test, P < 0.001). In contrast, in the control group, significantly stronger activation was observed in the bilateral Heschl's gyri and left middle frontal gyrus (one-sample t test, P < 0.001). Additionally, a two-sample t test revealed that dental sounds induced a significantly stronger activation in the left caudate nucleus in the DF group than in the control group (P < 0.005). These findings suggest that the cerebral activation pattern in individuals with DF differs from that in controls. Increased activation of subcortical regions may be associated with sound memory during dental treatment., (© 2024. The Author(s).)

Background: The prevalence between erosive tooth wear (ETW) in association with reflux oesophagitis (RO) has been reported. However, the severity of both diseases and the relationship between ETW and non-erosive reflux disease (NERD) is unclear., Objectives: The prevalence and severity of ETW were investigated in RO, NERD and healthy controls., Methods: 135 patients with RO, 65 with NERD and 40 healthy controls were recruited for this case-control study. A modified tooth wear index was used to evaluate the prevalence and severity of ETW. Salivary secretion and buffer capacity were assessed prior to endoscopy. The prevalence and severity of ETW, saliva properties among each group were analysed using Pearson's chi-squared test., Results: A total of 135 cases (56.3%) were categorised as the patient with ETW (55 with mild RO, 49 with severe RO and 31 with NERD). There was a significant relationship between the prevalence of RO and ETW, while there was no significant correlation between the prevalence of NERD and ETW. There was a significant difference related to the severity between RO and ETW. For salivary secretion, there was a significant difference between with and without ETW in patients with mild RO, severe RO and NERD. There was a significant difference between with and without ETW for salivary buffer capacity in patients with mild and severe RO., Conclusion: There was a significant association of the prevalence and severity between RO and ETW. Clinical signs such as ETW and salivary buffer capacity depended on the severity of RO., (© 2023 John Wiley & Sons Ltd.)

Background: Saliva secretion is significantly lower in patients with non-erosive reflux disease (NERD) than in healthy controls (HC). A previous study on HC showed that saliva secretion was lower in females than in males. Saliva secretion may be lower in female patients with NERD than in male patients. Therefore, the present study investigated sex differences in saliva secretion in patients with NERD., Methods: Subjects older than 50 years were included in the present study and consisted of 20 male patients with NERD, 19 male HC, 25 female patients with NERD, and 23 female HC. Saliva secretion was assessed as follows: each patient chewed sugar-free gum for 3 min prior to endoscopy, and the amount and pH of saliva before and after acid loading as an index of the acid-buffering capacity were measured., Results: In males, no significant differences were observed in the amount of stimulated saliva secretion or salivary pH between NERD patients and HC. However, the acid-buffering capacity (NERD: 6.1 [5.9-6.5], HC: 6.4 [6.2-6.6]) was significantly lower in NERD patients than in HC. In females, the amount of stimulated saliva secretion (NERD: 2.6 [2.0-4.1], HC: 5.8 [3.7-7.5]), salivary pH (NERD: 7.0 [6.8-7.2], HC: 7.2 [7.0-7.2]), and the acid-buffering capacity (NERD: 5.8 [5.4-6.2], HC: 6.2 [6.0-6.5]) were significantly lower in NERD patients than in HC., Conclusion: Among females older than 50 years, saliva secretion was significantly lower in NERD patients than in HC. This reduction in saliva secretion may contribute to the pathophysiology of NERD in females., (© 2023. The Author(s) under exclusive licence to The Japan Esophageal Society.)

Background: The primary mechanism of diurnal gastroesophageal reflux (GER) is transient lower esophageal sphincter relaxation (TLESR) in both healthy persons and patients with gastroesophageal reflux disease (GERD). However, few studies have examined nocturnal GER. Using portable high-resolution manometry (HRM), esophageal pH, and electroencephalography (EEG), we investigated the association of onset of nocturnal GER with sleep depth in healthy Japanese adults., Methods: We recruited ten healthy men (mean age 33.5 ± 4.2 years) with no reflux symptoms, no history of surgery, and no current medication use. HRM and an esophageal pH catheter were inserted in the evening. The participants returned home after consuming a test meal, and EEG was placed at home before bedtime to measure sleep depth., Results: The main mechanism underlying nocturnal GER was TLESR (15/17 episodes: 88.2%). The rate of TLESR with nocturnal GER during sleep was high (51.9%, 27/52 episodes). Sleep depth during TLESR was 44.2% (23/52 times) awake and 34.6% (18/52 times) shallow sleep (N1-2). Sleep depth during TLESR with nocturnal GER was 74.0% (20/27 time) awake and 18.5% (5/27 times) shallow sleep (N1-2)., Conclusion: The primary mechanism underlying nocturnal GER was TLESR in healthy Japanese men. TLESR and TLESR with nocturnal GER were more frequent during awakenings and shallow sleep.

Introduction: Humans mainly utilize visual and auditory information as a cue to infer others' emotions. Previous neuroimaging studies have shown the neural basis of memory processing based on facial expression, but few studies have examined it based on vocal cues. Thus, we aimed to investigate brain regions associated with emotional judgment based on vocal cues using an N-back task paradigm., Methods: Thirty participants performed N-back tasks requiring them to judge emotion or gender from voices that contained both emotion and gender information. During these tasks, cerebral hemodynamic response was measured using functional near-infrared spectroscopy (fNIRS)., Results: The results revealed that during the Emotion 2-back task there was significant activation in the frontal area, including the right precentral and inferior frontal gyri, possibly reflecting the function of an attentional network with auditory top-down processing. In addition, there was significant activation in the ventrolateral prefrontal cortex, which is known to be a major part of the working memory center., Discussion: These results suggest that, compared to judging the gender of voice stimuli, when judging emotional information, attention is directed more deeply and demands for higher-order cognition, including working memory, are greater. We have revealed for the first time the specific neural basis for emotional judgments based on vocal cues compared to that for gender judgments based on vocal cues., 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 Ohshima, Koeda, Kawai, Saito, Niioka, Okuno, Naganawa, Hama, Kyutoku and Dan.)

Background and Aim: Previous studies on age differences in proton pump inhibitor (PPI)-resistant reflux esophagitis (RE) have found that stenosis and bleeding complications were significantly more common in the elderly than in the non-elderly. We sought to examine differences between two groups of elderly (75 years or older) and non-elderly (<75 years) patients with (PPI)-resistant severe RE and also the efficacy of vonoprazan (VPZ) in these patients., Methods: There were 14 patients in the elderly group and 15 in the non-elderly group. Information was obtained on patient background (sex, body mass index [BMI], gastric mucosal atrophy, and the presence of hernia and collagen disease), and all patients underwent the saliva secretion test and esophagogastroduodenoscopy (EGD). The saliva secretion test (amount of saliva secreted, salivary pH, and the acid-buffering capacity) was performed by chewing sugar-free gum for 3 min before EGD. The efficacy of VPZ in both groups was also assessed., Results: Saliva secretion, sex, BMI, and the presence of gastric mucosal atrophy did not significantly differ between the two groups. The number of hernias larger than 4 cm was significantly higher in the elderly PPI-resistant group, and significantly more patients had collagen disease in the non-elderly group. The efficacy of VPZ was not significantly different between the two groups; however, 10 patients in the non-elderly group had collagen disease, and 4 did not achieve esophageal mucosal healing even with VPZ 20 mg., Conclusion: The number of large hernias (>4 cm) was significantly higher in the elderly group, while significantly more non-elderly patients had collagen disease. In the non-elderly group with scleroderma, the efficacy of VPZ 20 mg may not be sufficient., (© 2023 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Differential diagnosis is sometimes difficult in practical psychiatric settings, in terms of using the current diagnostic system based on presenting symptoms and signs. The creation of a novel diagnostic system using objective biomarkers is expected to take place. Neuroimaging studies and others reported that subcortical brain structures are the hubs for various psycho-behavioral functions, while there are so far no neuroimaging data-driven clinical criteria overcoming limitations of the current diagnostic system, which would reflect cognitive/social functioning. Prior to the main analysis, we conducted a large-scale multisite study of subcortical volumetric and lateralization alterations in schizophrenia, bipolar disorder, major depressive disorder, and autism spectrum disorder using T1-weighted images of 5604 subjects (3078 controls and 2526 patients). We demonstrated larger lateral ventricles volume in schizophrenia, bipolar disorder, and major depressive disorder, smaller hippocampus volume in schizophrenia and bipolar disorder, and schizophrenia-specific smaller amygdala, thalamus, and accumbens volumes and larger caudate, putamen, and pallidum volumes. In addition, we observed a leftward alteration of lateralization for pallidum volume specifically in schizophrenia. Moreover, as our main objective, we clustered the 5,604 subjects based on subcortical volumes, and explored whether data-driven clustering results can explain cognitive/social functioning in the subcohorts. We showed a four-biotype classification, namely extremely (Brain Biotype [BB] 1) and moderately smaller limbic regions (BB2), larger basal ganglia (BB3), and normal volumes (BB4), being associated with cognitive/social functioning. Specifically, BB1 and BB2-3 were associated with severe and mild cognitive/social impairment, respectively, while BB4 was characterized by normal cognitive/social functioning. Our results may lead to the future creation of novel biological data-driven psychiatric diagnostic criteria, which may be expected to be useful for prediction or therapeutic selection., (© 2023. The Author(s).)

According to the operational diagnostic criteria, psychiatric disorders such as schizophrenia (SZ), bipolar disorder (BD), major depressive disorder (MDD), and autism spectrum disorder (ASD) are classified based on symptoms. While its cluster of symptoms defines each of these psychiatric disorders, there is also an overlap in symptoms between the disorders. We hypothesized that there are also similarities and differences in cortical structural neuroimaging features among these psychiatric disorders. T1-weighted magnetic resonance imaging scans were performed for 5,549 subjects recruited from 14 sites. Effect sizes were determined using a linear regression model within each protocol, and these effect sizes were meta-analyzed. The similarity of the differences in cortical thickness and surface area of each disorder group was calculated using cosine similarity, which was calculated from the effect sizes of each cortical regions. The thinnest cortex was found in SZ, followed by BD and MDD. The cosine similarity values between disorders were 0.943 for SZ and BD, 0.959 for SZ and MDD, and 0.943 for BD and MDD, which indicated that a common pattern of cortical thickness alterations was found among SZ, BD, and MDD. Additionally, a generally smaller cortical surface area was found in SZ and MDD than in BD, and the effect was larger in SZ. The cosine similarity values between disorders were 0.945 for SZ and MDD, 0.867 for SZ and ASD, and 0.811 for MDD and ASD, which indicated a common pattern of cortical surface area alterations among SZ, MDD, and ASD. Patterns of alterations in cortical thickness and surface area were revealed in the four major psychiatric disorders. To our knowledge, this is the first report of a cross-disorder analysis conducted on four major psychiatric disorders. Cross-disorder brain imaging research can help to advance our understanding of the pathogenesis of psychiatric disorders and common symptoms., (© 2023. The Author(s).)

Background: Emotional cognitive impairment is a core phenotype of the clinical symptoms of psychiatric disorders. The ability to measure emotional cognition is useful for assessing neurodegenerative conditions and treatment responses. However, certain factors such as culture, gender, and generation influence emotional recognition, and these differences require examination. We investigated the characteristics of healthy young Japanese adults with respect to facial expression recognition., Methods: We generated 17 models of facial expressions for each of the six basic emotions (happiness, sadness, anger, fear, disgust, and surprise) at three levels of emotional intensity using the Facial Acting Coding System (FACS). Thirty healthy Japanese young adults evaluated the type of emotion and emotional intensity the models represented to them., Results: Assessment accuracy for all emotions, except fear, exceeded 60% in approximately half of the videos. Most facial expressions of fear were rarely accurately recognized. Gender differences were observed with respect to both faces and participants, indicating that expressions on female faces were more recognizable than those on male faces, and female participants had more accurate perceptions of facial emotions than males., Conclusion: The videos used may constitute a dataset, with the possible exception of those that represent fear. The subject's ability to recognize the type and intensity of emotions was affected by the gender of the portrayed face and the evaluator's gender. These gender differences must be considered when developing a scale of facial expression recognition., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: This study was performed to evaluate the orientation of lower esophageal sphincter (LES) pressure in patients with untreated achalasia using three-dimensional high-resolution manometry (3D-HRM)., Methods: The study involved 20 patients with untreated achalasia (10 men, 60 [47-74] years of age). The 3D-HRM assembly had 32 standard channels and 12 3D channels. During basal LES pressure measurements, the orientations of the LES high- and low-pressure zones were evaluated at end-expiration. The directional relationships between the orientation of the LES high- and low-pressure zones were also evaluated., Results: The LES high-pressure zones were located on the greater curvature side in nine (45%) patients, from the greater curvature to posterior wall side in six (30%), and from the greater curvature to anterior wall side in five (25%). The LES high-pressure zones were located mainly on the greater curvature side, but there were some variations of the orientation among the patients. The LES low-pressure zones were most frequently located from the lesser curvature to the posterior wall side in 11 (55%) patients, from the lesser curvature to anterior wall side in 6 (30%), on the posterior wall side in 2 (10%), and on the anterior wall side in 1 (5%). Significant differences were found in the directional relationships between the orientation of the LES high- and low-pressure zones (P = 0.0053)., Conclusions: This is the first report from Japan focusing on the LES pressure orientation using 3D-HRM. Such evaluation may be useful for clarifying the pathophysiology of achalasia.

Objective: Saliva secretion in healthy subjects is lower in females than in males. The present study investigated sex differences in saliva secretion in patients with gastroesophageal reflux disease (GERD) and healthy controls., Methods: This case-control study included 39 (male/female: 16/23) with non-erosive reflux disease (NERD), 49 (25/24) patients with mild reflux esophagitis, 45 (23/22) with severe reflux esophagitis (A1), and 46 (24/22) healthy controls. Saliva secretion was examined as follows: before endoscopy, patients chewed sugar-free gum for three minutes, and the amount and pH of saliva before and after acid loading as an index of acid-buffering capacity were evaluated. The relationships between saliva secretion and body mass index, height, and weight were also examined., Results: The amount of saliva secreted was significantly lower in females than in males in all four groups (NERD, mild reflux esophagitis, severe reflux esophagitis, and healthy controls). Salivary pH and acid-buffering capacity were similar in all groups. The amount of saliva secreted positively correlated with height and body weight, albeit more strongly with height., Conclusion: A sex difference in saliva secretion exists in GERD patients, similar to healthy controls. Saliva secretion was significantly lower in female GERD patients than in male GERD patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Momma et al.)

Background: Sex differences in salivary secretion have been reported among healthy subjects. In the present study, salivary secretion and salivary epidermal growth factor (EGF) concentrations were investigated in mild reflux esophagitis patients, non-erosive reflux disease (NERD) patients, and healthy controls by matching the sex ratio., Methods: Thirty-three (male:female = 11:22) patients with NERD, 33 (11:22) with mild reflux esophagitis, and 33 (11:22) healthy controls were recruited for this case-control study. Salivary secretion was assessed as follows: each patient chewed sugar-free gum for 3 min prior to endoscopy, and the amount of saliva secretion, salivary pH, and salivary pH after acid loading as an index of the acid-buffering capacity were measured. Salivary EGF concentrations were measured by ELISA., Results: No significant differences were observed in the amount of saliva secretion, salivary pH, or the acid-buffering capacity between the mild reflux esophagitis and NERD groups. However, the amount of saliva secretion and the acid-buffering capacity in the mild reflux esophagitis group and the amount of saliva secretion, salivary pH, and the acid-buffering capacity in the NERD group were significantly lower than those in the healthy control group. No significant differences were noted in salivary EGF concentrations between the mild reflux esophagitis and NERD groups., Conclusion: After matching the sex ratio, the saliva secretion was significantly lower in patients with mild reflux esophagitis and NERD than in healthy controls. However, no significant differences were observed in the amount of saliva secretion or salivary EGF concentrations between both groups., (© 2022. The Author(s) under exclusive licence to The Japan Esophageal Society.)

Introduction: Saliva secretion is significantly lower in patients with mild reflux esophagitis than in healthy controls. A previous study on healthy controls showed that stimulated saliva secretion was lower in females than in males. Saliva secretion may be lower in female patients with mild reflux esophagitis than in male patients. Therefore, the present study investigated sex differences in saliva secretion in patients with mild reflux esophagitis., Methods: Twenty-five male patients with mild reflux esophagitis, 25 male healthy controls, 24 female patients with mild reflux esophagitis, and 24 female healthy controls were recruited for this case-control study. Saliva secretion was assessed as follows: each patient chewed sugar-free gum for 3 minutes prior to endoscopy, and the volume and pH of saliva before and after acid loading as an index of the acid-buffering capacity were measured., Results: No significant differences were observed in the amount of stimulated saliva secretion, salivary pH, or the acid-buffering capacity between male patients with mild reflux esophagitis and healthy controls. No significant differences were noted in salivary pH between female patients with mild reflux esophagitis and healthy controls; however, the amount of stimulated saliva secretion was significantly lower (p = 0.0023) in the former (2.5 [1.9-4.1]) than in the latter (4.6 [3.2-6.6]), while the acid-buffering capacity was slightly lower (p = 0.0578) in the former (5.9 [5.7-6.2]) than in the latter (6.2 [6.0-6.5])., Conclusion: The amount of stimulated saliva secretion was significantly lower in female patients with mild reflux esophagitis than in female healthy controls. This reduction in saliva secretion may affect the pathophysiology of mild reflux esophagitis in females., (© 2023 S. Karger AG, Basel.)

Background and Aim: Discrepancies have been reported in the circumferential locations of mild mucosal breaks. We investigated their locations using a new method., Methods: This is a retrospective study. Eighty patients (Grade A/B: 53/27) with mild mucosal breaks in the lower esophagus were examined. Since the 3 o'clock position corresponded to the right wall of the lower esophagus using our method with sufficient accuracy, the circumferential locations of mucosal breaks were identified as times on a clock face, which were changed to circular data to calculate the mean direction. The circumferential distribution of mucosal breaks was evaluated in the single lesion group (single group) and multiple lesion group (multiple group)., Results: Forty-eight of 80 patients had 1 mucosal break, while 32 had ≥2 mucosal breaks. Circumferential locations markedly differed between the single and multiple groups. In the single group, mucosal breaks were exclusively distributed between 2 and 7 o'clock, with 50% in the 3 o'clock direction (right wall). In the multiple group, 81 mucosal breaks were distributed circumferentially, not uniformly; however, at least 1 lesion was located between 2 and 7 o'clock in 91% of subjects. Therefore, a factor for the development of mucosal breaks from the right to posterior wall was present in both groups., Conclusion: In the single group, mucosal breaks were localized from the right to posterior wall, mainly in the right wall. In the multiple group, mucosal breaks were located circumferentially, but often between the right lateral and posterior wall. These two distributions significantly differed.Clinical trial registration: This is a retrospective study, so it was not registered., (© 2022 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: The relationship between bothersome symptoms and gastric pressure or CO2 injection volumes in drug-resistant functional dyspepsia (FD) patients remains unknown; therefore, this relationship was examined in drug-resistant FD and non-FD patients., Methods: Thirty drug-resistant FD patients and 30 non-FD patients were recruited. Gastric pressure was assessed using an external pressure transducer, and the CO2 injection volume was measured using an endoscopic CO2-supplied device and flow meter. The following variables were examined: gastric pressure at baseline and gastric pressure and the CO2 injection volume when patients initially felt abdominal tension and bothersome symptoms following the CO2 injection. The relationship between belching and bothersome symptoms was also investigated., Results: No significant differences were observed in basal gastric pressure between the groups. Initial and bothersome symptoms in the upper abdomen in drug-resistant FD patients developed at a significantly lower gastric pressure and significantly smaller CO2 injection volume than in non-FD patients. The frequency of belching was significantly lower in the drug-resistant FD group than in the non-FD group., Conclusion: Bothersome symptoms in drug-resistant FD patients develop at a lower gastric pressure and smaller CO2 injection volume than in non-FD patients. These patients also had difficulties with belching., Competing Interests: The authors have declared that no competing interests exist.

Background: Cognitive impairment is common in people with mental disorders, leading to transdiagnostic classification based on cognitive characteristics. However, few studies have used this approach for intellectual abilities and functional outcomes., Aims: The present study aimed to classify people with mental disorders based on intellectual abilities and functional outcomes in a data-driven manner., Method: Seven hundred and forty-nine patients diagnosed with schizophrenia, bipolar disorder, major depression disorder or autism spectrum disorder and 1030 healthy control subjects were recruited from facilities in various regions of Japan. Two independent k -means cluster analyses were performed. First, intelligence variables (current estimated IQ, premorbid IQ, and IQ discrepancy) were included. Second, number of work hours per week was included instead of premorbid IQ., Results: Four clusters were identified in the two analyses. These clusters were specifically characterised in terms of IQ discrepancy in the first cluster analysis, whereas the work variable was the most salient feature in the second cluster analysis. Distributions of clinical diagnoses in the two cluster analyses showed that all diagnoses were unevenly represented across the clusters., Conclusions: Intellectual abilities and work outcomes are effective classifiers in transdiagnostic approaches. The results of our study also suggest the importance of diagnosis-specific strategies to support functional recovery in people with mental disorders.

Background: Salivary secretion in patients with mild reflux esophagitis has not been examined. In this study, saliva secretion and salivary epidermal growth factor (EGF) in patients with mild reflux esophagitis were investigated., Methods: Thirty-eight mild reflux esophagitis patients and 38 control subjects were recruited for this case-control study. Saliva secretion testing was performed. Saliva secretion was assessed as follows: each patient chewed sugar-free gum for 3 min prior to endoscopy, and the volume and pH of saliva before and after acid loading as an index of the acid-buffering capacity were measured. The salivary EGF concentration was assessed by ELISA., Results: The volume of saliva secreted was significantly (p = 0.0412) lower in the mild reflux esophagitis group than in the control group, with medians (25th-75th percentile) of 4.2 mL/3 min [2.6-6.2] and 6.0 [3.9-8.0], respectively. No significant differences were observed in salivary pH (the mild reflux esophagitis group: 7.1 [6.9-7.2], the control group 7.2 [7.1-7.3]). Salivary pH after acid loading was significantly (p = 0.0009) lower in the mild reflux esophagitis group (5.9 [5.5-6.3]) than in the control group (6.3 [6.2-6.5]). No significant differences were noted in salivary EGF concentrations (the mild reflux esophagitis group: 1739.0 pg/mL [1142.3-3329.0], the control group: 1678.0 [1091.8-2122.5]., Conclusion: The secretion volume and acid-buffering capacity of stimulated saliva were reduced in patients with mild reflux esophagitis., (© 2021. The Japan Esophageal Society.)

Background: This study investigated potential determinants of reflux perception in patients with non-erosive reflux disease (NERD) who had reflux-related symptoms on potassium-competitive acid blocker (P-CAB) therapy., Methods: This study included 23 patients with reflux-related symptoms despite P-CAB therapy. Esophageal impedance-pH monitoring was performed on P-CAB and the following potential determinants of reflux perception were investigated: reflux nadir pH value; change in pH (baseline-nadir); bolus clearance time; reflux extent; proportions of acid, weakly acidic, and weakly alkaline reflux episodes; and proportions of liquid and mixed reflux episodes., Results: Overall, ≥ 90% of all and symptomatic reflux episodes were weakly acidic reflux and 63% of symptomatic reflux episodes were reflux episodes with pH ≥ 5. There were no significant differences regarding potential determinants between symptomatic and asymptomatic reflux episodes. However, the proportion of symptomatic reflux episodes was significantly greater with pH < 5 (13.8%) than with pH ≥ 5 (9.5%) (P = 0.0431). In reflux episodes with pH < 5, the proportion of symptomatic reflux episodes was significantly greater in proximal sites (20.6%) than in distal sites (10.6%) (P = 0.0178). Conversely, in reflux episodes with pH ≥ 5, there was no significant difference regarding reflux perception according to reflux extent (proximal: 9.6% vs. distal: 9.0%, P = 0.9337)., Conclusions: In patients with P-CAB-resistant NERD, reflux symptoms were mainly caused by reflux episodes with pH ≥ 5 on P-CAB therapy. The proportions of symptomatic reflux episodes among reflux sites differed according to reflux pH value; thus, the mechanisms of reflux perception may differ according to reflux pH value., (© 2021. The Japan Esophageal Society.)

Background: Although rikkunshito was reported to be effective for treatment-resistant nonerosive gastroesophageal reflux disease (NERD), it is unclear which Rome IV subgroups of NERD patients benefit fromrikkunshito. This study investigated the efficacy of rikkunshito in patients with functional heartburn., Methods: Ten patients with functional heartburn who experienced symptoms of dyspepsia were enrolled and received rikkunshito for 8 weeks. The Frequency Scale for Symptoms of GERD (FSSG), the Japanese translation of the Quality of Life in Reflux and Dyspepsia (QOLRAD-J) questionnaire, and the Hospital Anxiety and Depression Scale (HADS) before, and 4 and 8 weeks after, administration were evaluated. Overall treatment efficacy (OTE) was evaluated at 8 weeks after administration., Results: One patient voluntarily withdrew from treatment at 4 weeks. Total FSSG score was significantly (P = 0.039) lower 8 weeks after treatment or at discontinuation (13.2 ± 8.0) than before treatment (18.3 ± 10.7). Although QOLRAD-J score was higher 8 weeks after treatment or at discontinuation than before treatment, the difference was not significant different. HADS score was not significantly lower 8 weeks after treatment or at discontinuation, as compared with before treatment. However, total FSSG and HADS anxiety scores were positively correlated (correlation coefficient: 0.684, P = 0.027)., Conclusions: The findings from this first study of the efficacy of rikkunshito for functional heartburn suggest that it might be effective in such patients.

The underlying pathologies of psychiatric disorders, which cause substantial personal and social losses, remain unknown, and their elucidation is an urgent issue. To clarify the core pathological mechanisms underlying psychiatric disorders, in addition to laboratory-based research that incorporates the latest findings, it is necessary to conduct large-sample-size research and verify reproducibility. For this purpose, it is critical to conduct multicenter collaborative research across various fields, such as psychiatry, neuroscience, molecular biology, genomics, neuroimaging, cognitive science, neurophysiology, psychology, and pharmacology. Moreover, collaborative research plays an important role in the development of young researchers. In this respect, the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium and Cognitive Genetics Collaborative Research Organization (COCORO) have played important roles. In this review, we first overview the importance of multicenter collaborative research and our target psychiatric disorders. Then, we introduce research findings on the pathophysiology of psychiatric disorders from neurocognitive, neurophysiological, neuroimaging, genetic, and basic neuroscience perspectives, focusing mainly on the findings obtained by COCORO. It is our hope that multicenter collaborative research will contribute to the elucidation of the pathological basis of psychiatric disorders., (© 2021 The Authors Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

Background: Modafinil improves wakefulness and attention, is approved in Japan for treatment of narcolepsy, and was reported to be effective for attention-deficit/hyperactivity disorder. However, it was reported to induce emotional instability, including mania, depression, and suicidal ideation. Such side effects may be related to changes in cognitive behavior caused by the effects of modafinil on emotional recognition. However, the effects of modafinil on the neural basis of emotional processing have not been fully verified. We used functional magnetic resonance imaging to investigate the effects of modafinil on the neural basis of auditory emotional processing., Methods: This study adopted a placebo-controlled within-subject crossover design. Data from 14 participants were analyzed. The effects of modafinil on cerebral activation and task performance during an emotional judgement task were analyzed., Results: Task accuracy decreased significantly and response time of emotional judgement was significantly delayed by modafinil, as compared with placebo. Right thalamic activation in auditory emotional processing was significantly less in the modafinil condition than in the placebo condition. In addition, reduction of right thalamic activation by modafinil was positively correlated with accuracy of emotional judgement., Conclusions: Our findings suggest that modafinil acts on the right thalamus and changes behavior and brain function associated with auditory emotional processing. These results indicate that modafinil might change emotional recognition by reducing emotional activation related to social communication.

Background: There is no consensus on the relationship between saliva secretion and non-erosive reflux disease (NERD). In this study, saliva secretion and salivary epidermal growth factor (EGF) in patients with NERD were examined., Methods: Thirty-one PPI-responsive NERD patients and 31 control subjects were recruited for this case-control study. Saliva secretion testing was performed. Saliva secretion was assessed as follows: each patient chewed sugar-free gum for 3 min prior to endoscopy, and the amount and pH of saliva before and after acid loading as an index of the acid-buffering capacity were measured. The salivary EGF concentration was assessed by ELISA., Results: The amount of saliva secreted was significantly lower in the NERD group than in the control group, with medians (25th-75th percentile) of 4.0 mL/3 min (2.0-6.0) and 6.0 (3.9-8.0), respectively (p = 0.0131). Salivary pH was significantly lower in the NERD group (7.0 [6.8-7.2]) than in the control group (7.2 [7.0-7.3], p = 0.0100). Salivary pH after acid loading was significantly lower in the NERD group (5.8 [5.4-6.2]) than in the control group (6.3 [6.1-6.5], p = 0.0002). The difference in pH of stimulated saliva after acid loading (1.2 [0.9-1.5], p = 0.0021) was significantly higher in the NERD group than in the control group (0.8 [0.7-1.1]). The salivary EGF concentration was significantly higher in the NERD group (2513.0 pg/mL [1497.5-5005.0] than in the PPI-responsive group (1641.0 [1139.8-2092.0], p = 0.0032)., Conclusion: Stimulated saliva secretion was reduced in PPI-responsive NERD patients., (© 2021. The Japan Esophageal Society.)

Background: Salivary secretion in patients with proton-pump inhibitor (PPI)-resistant severe reflux esophagitis has not been examined. In this study, saliva secretion and salivary epidermal growth factor (EGF) in patients with PPI-resistant severe reflux esophagitis were investigated., Methods: We recruited 22 PPI-resistant and 22 PPI-responsive severe reflux esophagitis patients who were not infected with Helicobacter pylori. Saliva secretion testing and esophageal manometry using high-resolution manometry were performed. Saliva secretion was assessed as follows: each patient chewed sugar-free gum for 3 min prior to endoscopy and the amount and pH of saliva as well as the pH of saliva after acid loading as an index of the acid-buffering capacity were measured. The salivary EGF concentration was assessed by ELISA., Results: The amount of saliva secreted was significantly lower in the PPI-resistant group than in the PPI-responsive group, with medians (25th-75th percentile) of 3.7 (2.2-6.8) and 4.9 (4.0-7.8) mL, respectively (p = 0.029). Salivary pH was significantly lower in the PPI-resistant group [6.9 (6.7-7.2)] than in the PPI-responsive group [7.2 (7.1-7.4), p = 0.001]. Salivary pH after acid loading was significantly lower in the PPI-resistant group [5.6 (5.3-5.9)] than in the PPI-responsive group [6.4 (6.1-6.5), p = 0.002]. The salivary EGF concentration was significantly higher in the PPI-resistant group [3211.5 (1865.0-4121.5)] than in the PPI-responsive group [1816.0 (1123.5-2792.3), p = 0.041]. No significant differences were observed in the proportion of esophageal motility abnormalities., Conclusion: Stimulated saliva secretion was reduced in PPI-resistant severe reflux esophagitis patients.

Aim: Anodal transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (DLPFC) is known as a useful application for improving depressive symptoms or cognitive performance. Antidepressive effects by anodal tDCS over the left DLPFC are expected, but the neural mechanisms of these effects are still unclear. Further, in depression, reduced performance and left prefrontal hypofunction during the verbal fluency task (VFT) are generally known. However, few studies have examined the effect of tDCS on the language-related cerebral network. We aimed to investigate whether anodal tDCS at the left DLPFC affects cognitive performance and the neural basis of verbal fluency., Methods: Nineteen healthy volunteers participated in this study. The effects of tDCS on cognitive behavior and cerebral function were evaluated by (i) performance and accuracy of implicit/explicit motor learning task (serial reaction time task/sequential finger-tapping task), and (ii) cerebral activation while the subjects were performing the VFT by using a functional MRI protocol of a randomized sham-controlled, within-subjects crossover design., Results: Reaction times of the implicit motor learning task were significantly faster with tDCS in comparison with the sham. Further, language-related left prefrontal-parahippocampal-parietal activation was significantly less with tDCS compared with the sham. Significant correlation was observed between shortened response time in serial reaction time task and decreased cerebral activation during VFT with tDCS., Conclusion: Anodal tDCS over the left DLPFC could improve cognitive behavior of implicit motor learning by improving brain function of the frontoparietal-parahippocampal region related to motor learning, as well as language-related regions., (© 2021 The Authors Psychiatry and Clinical Neurosciences © 2021 Japanese Society of Psychiatry and Neurology.)

Background and Aim: Although one of the causes of dyspeptic symptoms in functional dyspepsia patients is gastric hypersensitivity, there is currently no routine endoscopic gastric hypersensitivity test. We developed a new endoscopic method for gastric hypersensitivity testing. The aim of the present study was to investigate whether this method is useful for evaluating gastric hypersensitivity in drug-resistant functional dyspepsia patients who were strongly suspected of having gastric hypersensitivity., Methods: Twenty-seven drug-resistant functional dyspepsia patients and 27 nonfunctional dyspepsia patients were recruited. Gastric pressure was assessed using an external pressure transducer, and the CO 2 insufflation volume was measured using an endoscopic CO 2 -supplied device and flow meter. The following variables were examined: gastric pressure at baseline and gastric pressure, the CO 2 insufflation volume, and compliance of the stomach when patients initially felt abdominal tension following CO 2 insufflation., Results: No significant differences were observed in baseline gastric pressure or compliance of the stomach between the groups. Drug-resistant functional dyspepsia patients had a significantly smaller CO 2 insufflation volume and lower gastric pressure when symptoms developed than nonfunctional dyspepsia patients. Based on a cutoff value of 1.25 L by receiver operating characteristic curves, sensitivity and specificity for gastric pressure were 85.0 and 96.3%, respectively. Similarly, based on a cutoff value of 12.7 mmHg, sensitivity and specificity for the CO 2 insufflation volume were 81.5 and 81.5%, respectively., Conclusion: This endoscopic gastric hypersensitivity testing is a useful tool for evaluating the presence of gastric hypersensitivity., (© 2021 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Introduction: Bupropion is an antidepressant with less possibility to give rise to emotional blunting as side effect, and it also acts on improving negative self-recognition in a depressive state. Previous neuroimaging studies indicated a change in brain function by facial expression as an effect of antidepressants. As well as facial expression, vocal affective processing is essential for accurately recognizing another's feelings, but to our knowledge, no study has investigated whether bupropion affects the cerebral function of recognition of auditory affective processing. In this study, we aimed to investigate the acute effect of bupropion on cerebral response to vocal affective processing., Methods: Sixteen healthy volunteers (male = 8) participated in this study. With a randomized placebo-controlled within-subject trial, two series of fMRI scans, using either placebo or bupropion (150 mg), were examined. An auditory emotional valence judgement task was performed during fMRI scanning. The acute effects of bupropion on cerebral activation in the emotional circuit and behavioral performance during emotional processing were analyzed., Results: Compared with placebo, bupropion caused a significantly greater activation of emotional voices in the left insula and right superior temporal gyrus, whereas the amygdala was not activated. By bupropion, a significantly greater activation of the positive emotional circuit was observed at the superior temporal gyrus and middle frontal gyrus. As for behavioral performance, no significant difference was observed between placebo and bupropion., Conclusions: Our findings suggest that bupropion enhances the cerebral response to affective processing, especially positive emotional vocalizations, indicating a possible mechanism underlying the therapeutic effects for patients with depression., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Jackhammer esophagus (JE) is a rare disease with unclear clinical features. The objective of this study was to retrospectively compare the clinical characteristics of patients with JE whose symptoms were controlled with conservative treatment, such as observation or medication, versus those who were required surgical treatment, such as surgical myotomy or per oral endoscopic myotomy., Methods: Eighteen patients with JE were included in this study. The patients were divided into two groups: patients who responded to conservative treatment (C group) and patients who were refractory to conservative treatment and underwent surgery (S group). Patient age, sex, disease duration before treatment, symptoms, esophagogastroduodenoscopic (EGD) findings, esophagographic findings, esophageal wall thickness on computed tomography, number of swallows with hypercontractile peristalsis in 10 water swallows, and maximum distal contractile integral (DCI) were compared between the groups., Results: Thirteen of 18 patients (72%) were in the C group and five of 18 (28%) were in the S group. There were no significant differences in age, sex, disease duration before treatment, symptoms, EGD findings, esophagographic findings, esophageal wall thickness, or number of swallows with hypercontractile peristalsis between the groups. On Starlet high-resolution manometry, the median maximum DCI value was significantly higher in the S group (32,651 mmHg-s-cm) than in the C group (17,926 mmHg-s-cm) (P = 0.0136)., Conclusions: JE treatment should be carefully considered because some patients require surgery, whereas others are controlled with conservative treatment alone. A higher DCI value in patients with JE may predict resistance to conservative treatment.

Objective Pegylated-interferon monotherapy is the standard treatment for patients with chronic hepatitis B; however, the factors associated with its therapeutic effects remain unclear. Methods Patients with chronic hepatitis B were treated with pegylated interferon α-2a for 48 weeks. We evaluated the kinetics of hepatitis B surface antigen (HBsAg) during treatment and follow-up periods and the factors associated with an HBsAg response (defined as a change in HBsAg of ≥-1 log IU/mL from baseline). Results The study population comprised 50 patients. The median baseline levels of hepatitis B virus DNA and HBsAg were 5.00 and 3.40 log IU/mL. The median values of HBsAg reduction from baseline were -0.44 (n=48), -0.41 (n=40), and -0.68 (n=11) log IU/mL at the end of treatment and at 48 and 144 weeks post-treatment, respectively. The rates of HBsAg response were 24.0% and 22.5% at the end of treatment and at 48 weeks post-treatment, respectively. A multivariate analysis identified HBsAg <3.00 log IU/mL as an independent baseline factor contributing to the HBsAg response at the end of treatment and 48 weeks post-treatment (p=1.07×10 -2 and 4.42×10 -2 , respectively). There were significant differences in the reduction of the HBsAg levels at 12 weeks of treatment and in the incidence of serum ALT increase during treatment between patients with and without an HBsAg response. Conclusion These findings suggest that the baseline HBsAg level, HBsAg kinetics at 12 weeks of treatment, and ALT increase during treatment are important factors contributing to the HBsAg response in pegylated interferon α-2a monotherapy for patients with chronic hepatitis B.

Background: The relationship between gastroesophageal reflux disease (GERD) and constipation has not yet been examined in Japan. We herein analyzed the use of laxatives by GERD and non-GERD patients to clarify the relationship between GERD and constipation., Methods: This was a retrospective observational study designed to examine the use of laxatives by GERD and non-GERD patients. A total of 118 patients (mean age 69.7 years, 50 males) with reflux esophagitis (RE) and non-erosive reflux disease (NERD) who received maintenance acid-suppressive therapy for more than 1 year were included in the GERD group (83 RE patients, 35NERD patients). Similarly, 61 patients (mean age 69.4 years, 28 males) who received regular acid-suppressive therapy for reasons other than GERD were included in the non-GERD group. We also investigated demographic factors associated with the onset of GERD, including body mass index (BMI), age, and sex., Results: The frequency of laxative use was significantly higher in the GERD group (38.1%) than in the non-GERD group (21.3%). No significant differences were observed in dose frequencies between the groups. The type of laxative used also did not significantly differ between the groups. Furthermore, no significant differences were noted in sex, age, or BMI between the groups., Conclusions: The use of laxatives was significantly more common in GERD patients than in non-GERD patients. The present results suggest that a relationship exists between GERD and constipation.

Background and Aim: Although tenofovir alafenamide (TAF), as well as entecavir (ETV), is widely used as first-line treatment for patients with chronic hepatitis B, there are only a few studies comparing sequential therapy from ETV to TAF and continuous ETV monotherapy in patients with maintained virologic response to ETV., Methods: In a retrospective multicenter study, we investigated the efficacy and safety of sequential therapy from ETV to TAF (ETV-TAF group) and compared them with continuous ETV monotherapy (ETV group), using propensity score matching, in chronic hepatitis B patients., Results: From 442 patients, we analyzed 142 patients from each group comprising 71 patients matched for several data, including age, HBV genotype, hepatitis B envelope antigen, cirrhosis, alanine aminotransferase, platelet count, prior ETV monotherapy period, and hepatitis B surface antigen (HBsAg) change during prior ETV monotherapy. In the ETV-TAF group, HBsAg levels significantly decreased from baseline to 48 weeks after switching to TAF (-0.02 log IU/mL, P = 0.038). HBcrAg levels also significantly decreased after switching to TAF (-0.1 log IU/mL, P = 0.004). However, there were no significant differences in the reduction of HBsAg and HBcrAg levels between the ETV-TAF and ETV groups. There was no significant difference in the change of estimated glomerular filtration rate levels from baseline to 48 weeks between the two groups., Conclusions: The present study indicated that the efficacy, especially of the HBsAg-reducing action, and safety of sequential therapy from ETV to TAF were similar to those of continuous ETV monotherapy among chronic hepatitis B patients with maintained virologic response to ETV., (© 2020 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Portopulmonary hypertension (PoPH) is a well-known complication of liver cirrhosis. The aim of this study was to clarify the pulmonary hemodynamics and the prevalence and characteristics of PoPH in patients with portal hypertension., Methods: The subjects were 335 patients with portal hypertension diagnosed by hepatic vein pressure gradient (HVPG). Among them, 186 patients received measurements of pulmonary artery pressure (PAP), pulmonary artery wedge pressure (PAWP) and pulmonary vascular resistance (PVR). PoPH was diagnosed by PAP >20 mmHg, PVR ≥3 Wood units (WU) and PAWP ≤15 mmHg., Results: The Child-Pugh classification was class A in 53, B in 92 and C in 41 patients. Median (range) values of HVPG, PAP, PVR and PAWP were 18.4 (5.5-39.0) mmHg, 12.9 (6.6-40.8) mmHg, 0.8 (0.1-4.5) WU and 7.5 (2.2-15.4) mmHg, respectively. Of six patients with PAP >20 mmHg, four had autoimmune hepatitis or primary biliary cholangitis, with the prevalence being significantly higher than that in patients with PAP ≤20 mmHg. Meanwhile, no significant difference was noted in the hepatic functional reserve or HVPG between patients with PAP >20 mmHg and ≤20 mmHg. Only two patients met the diagnostic criteria of PoPH and both patients were Child-Pugh B. The Child-Pugh score and HVPG were not associated with PoPH., Conclusions: Our study demonstrated that only two patients were complicated by PoPH. High PAP values were noted in patients with primary biliary cholangitis or autoimmune hepatitis. However, the presence of PoPH and high PAP were not associated with the degree of hepatic functional reserve or HVPG., (© 2020 The Japan Society of Hepatology.)

Background: To examine the clinical characteristics, including complications, of patients older than 75 years of age with proton pump inhibitor-resistant reflux esophagitis., Methods: Patients who were resistant to standard-dose proton pump inhibitors were enrolled in the present study. Eligible patients (n = 26) were divided into those who were older (n = 11) and younger (n = 15) than 75 years of age. Clinical characteristics including complications (hemorrhage and stricture), body mass index, the severity of reflux esophagitis, Helicobactor pylori infection, gastric mucosal atrophy, hiatal hernia, kyphosis, and the use of antithrombotic agents were examined. The efficacy of 20 mg vonoprazan for proton pump inhibitor-resistant reflux esophagitis was also investigated., Results: The severity of reflux esophagitis was significantly higher in the elderly group than in the non-elderly group. No other significant differences were observed between the groups. The proportion of patients with hemorrhage was significantly larger in the elderly group than in the non-elderly group. Similarly, the proportion of patients with stricture was significantly larger in the elderly group than in the non-elderly group. Nine out of 10 patients in the elderly group and all patients in the non-elderly group achieved healing after the 4-week administration of 20 mg vonoprazan. No significant differences were observed in healing rates between the groups., Conclusion: Among patients with proton pump inhibitor-resistant reflux esophagitis, the rates of severe reflux esophagitis and complications (hemorrhage and/or stricture) were significantly higher in elderly patients than in non-elderly patients. Regardless of age, 20 mg vonoprazan was effective for proton pump inhibitor-resistant reflux esophagitis.