Yasunori Sato

The role of endoscopic submucosal dissection (ESD) in treating superficial non-ampullary duodenal epithelial tumors (SNADETs) remains controversial. This study aimed to evaluate the role of ESD for SNADETs by lesion size. A systematic review and meta-analysis were conducted to compare outcomes between ESD and endoscopic mucosal resection (EMR). For duplicate publications, the study with the largest sample was included. Key outcomes included rates of en bloc resection, intraoperative perforation, and delayed adverse events (AEs) (bleeding, perforation). Data were analyzed according to lesion size categories (< 20 mm and ≥ 20 mm). Corresponding authors were contacted for data clarification when necessary. Fifteen retrospective observational studies met the inclusion criteria. For lesions < 20 mm, there was no significant difference in the en bloc resection rates between both groups (OR: 1.12 [95% CI 0.50–2.51]); however, the intraoperative perforation (OR: 9.74 [95% CI 5.07–18.69]) and delayed AEs rates (OR: 4.21 [95% CI 2.54–6.98]) were significantly higher for the ESD group. For lesions ≥ 20 mm, ESD was associated with a significantly higher en bloc resection rate (OR: 6.17 [95% CI 3.52–10.80]) and intraoperative perforation rate (OR: 5.33 [95% CI 2.23–12.76]), whereas the rate of delayed AEs was not significantly different from that of EMR (OR: 1.34 [95% CI 0.58–3.11]). For SNADETs ≥ 20 mm, ESD demonstrates a higher en bloc resection rate while maintaining a comparable rate of delayed AEs compared to EMR. These findings suggest that ESD may be considered a potential treatment option for large SNADETs, with careful patient selection and risk assessment.

Background: The long-term immune implications of administering more than four doses of COVID-19 vaccine and the impact of breakthrough infections are not fully understood. Research Design and Methods: We conducted a follow-up cohort study on Japanese healthcare workers who received more than three doses of the BNT162b2 vaccine. We assessed both the anti-SARS-CoV-2 antibody titer and cellular immunity in 429 participants and investigated the numbers, types, and brands of COVID-19 vaccines administered, as well as the episodes of COVID-19 infections after the third dose. Results: Individuals who received three total doses of vaccines with BTI episodes demonstrated higher antibody titers than those who received four total doses of vaccines with no BTIs. The cellular immune responses between these two groups were comparable. Conclusions: These findings suggest that BTIs occurring after the primary series of COVID-19 vaccinations (first to third dose) induced humoral immunity to the spike protein that is greater than that induced by booster doses (fourth or fifth dose) and elicit cellular immunity to the spike protein comparable to that of booster doses.

Background: Liver resection for colorectal liver metastases (CRLM) with concurrent extrahepatic disease (EHD) has demonstrated potential benefits for long-term prognosis; however, its effectiveness remains controversial. Additionally, the prognostic impact of different EHD sites is not well elucidated. This study aimed to assess the significance of liver resection in patients with CRLM with concurrent EHD and evaluate how different EHD sites influence prognosis. Methods: A nationwide multicenter database was used for a retrospective analysis of patients diagnosed during two periods: 2005–2007 and 2013–2015. EHD was classified into the following five subgroups: lung, peritoneum, lymph nodes, local, and others. The inverse probability of treatment weighting (IPTW) method was applied to minimize selection bias. Kaplan–Meier survival curves and Cox proportional hazards models were used to compare the overall survival (OS) between the different treatment groups and EHD subgroups. Results: Among 3787 patients, 874 (23.1%) underwent liver resection. Following IPTW adjustment, the hepatectomy (HT) group demonstrated significantly better OS than the non-hepatectomy (non-HT) group (5-year hazard ratio, 0.322; 95% confidence interval, 0.273–0.379; P < 0.001). Analysis by the EHD site subgroup demonstrated that liver resection was associated with a better prognosis across all sites. However, the prognostic impact differed by EHD site, with peritoneal metastasis associated with poorer outcomes in both the HT (5-year OS rates, 30.1% vs. 45.0%) and non-HT (5-year OS rates, 4.4% vs. 8.6%) groups. Conclusions: Regardless of the EHD site, liver resection was associated with a significantly better OS in patients with CRLM with concurrent EHD. The prognostic impact varies across EHD sites, underscoring the significance of considering differential prognostic risks when selecting treatment strategies.

Objectives: Severe acute respiratory syndrome coronavirus 2 significantly impacts Japan with a high number of infections and deaths reported. Long coronavirus disease (COVID) characterised by persistent symptoms after COVID-19 has gained recognition but varies across studies. This study aimed to investigate the differences in long COVID among patients hospitalised during Japan’s first three waves of the pandemic. Design: Multicentre prospective cohort study. Setting: 26 medical facilities across Japan between February 2020 and February 2021. Participants: In total, 1066 hospitalised patients diagnosed with COVID-19 were included with 206, 301 and 559 patients in the first, second and third waves, respectively. Data were collected using electronic data capture and patient-reported outcome forms. Primary and secondary outcome measures: Long COVID was assessed at 3, 6 and 12 months after COVID-19 diagnosis. Results: Significant differences were observed between the waves in various baseline and clinical characteristics such as age, body mass index (BMI), comorbidities, the severity of COVID-19, complications and treatment during hospitalisation. Long COVID, particularly dyspnoea, was most prevalent in the first wave. Multivariate logistic regression analysis confirmed a significant positive association between the first wave and long COVID including dyspnoea after adjusting for age, sex, BMI, smoking status and COVID-19 severity. Conclusions: Patients hospitalised during the first wave had a higher risk of experiencing long COVID, especially dyspnoea, than those hospitalised during the other waves. These findings underscore the need for continued monitoring and managing long COVID in COVID-19 survivors, particularly in those hospitalised during the first wave. Trial registration number: UMIN000042299.

Primary angle closure glaucoma (PACG) is a major cause of visual impairment, particularly in Asia. Although effective screening tools are necessary, the current gold standard is complex and time-consuming, requiring extensive expertise. Artificial intelligence has introduced new opportunities for innovation in ophthalmic imaging. Anterior chamber depth (ACD) is a key risk factor for angle closure and has been suggested as a quick screening parameter for PACG. This study aims to develop an AI algorithm to quantitatively predict ACD from anterior segment photographs captured using a portable smartphone slit-lamp microscope. We retrospectively collected 204,639 frames from 1586 eyes, with ACD values obtained by anterior-segment OCT. We developed two models, (Model 1) diagnosable frame extraction and (Model 2) ACD estimation, using SWSL ResNet as the machine learning model. Model 1 achieved an accuracy of 0.994. Model 2 achieved an MAE of 0.093 ± 0.082 mm, an MSE of 0.123 ± 0.170 mm, and a correlation of R = 0.953. Furthermore, our model’s estimation of the risk for angle closure showed a sensitivity of 0.943, specificity of 0.902, and an area under the curve (AUC) of 0.923 (95%CI: 0.878–0.968). We successfully developed a high-performance ACD estimation model, laying the groundwork for predicting other quantitative measurements relevant to PACG screening.

Objective: Available treatment for chronic neuropathic pain is still limited, and the positive effects are modest. Thus, clinicians aim to improve activity and quality of life despite pain. The objective monitoring of activity is attracting attention in chronic pain assessments. Therefore, we objectively evaluated daytime activity and sleep in patients with postherpetic neuralgia (PHN), using actigraphy to determine risk factors for decreased activity. Methods: Participants with PHN wore an actigraph (a wristwatch-like accelerometer) on the nondominant hand. The actigraph measured day-time activity and sleep, which were compared with participant-reported subjective pain and sleep assessments. Results: Fifty-four individuals with PHN who visited our outpatient clinic completed questionnaires and a week of actigraph monitoring. Subjective scores of pain intensity, neuropathic pain, disability in daily life, pain-catastrophizing thoughts, and insomnia were all well correlated. However, the actigraph-monitored activity levels, using 2 equations, and sleep quality were not associated with any pain or sleep-related subjective scores. Conclusion: The discrepancy between the subjective and objective scores in this study may be due to (1) features of PHN, an archetype of peripheral neuropathic pain affecting no motor nerves, (2) actigraph measurement limitations regarding the sedentary life of the elderly, or (3) activity misperception, a new proposition explaining the discrepancy between subjective and objective measures of activity, similar to the sleep state misperception. In patients with PHN, high pain intensity may be reported in those with highly maintained activity, in which treatment must be selected cautiously to prevent interruption of their physical abilities.

Tear film instability is a major cause of dry eye disease. In order to treat patients with short tear film breakup time (TBUT)-type dry eye, the development of tear film stabilizing agents is essential. However, the lack of an appropriate animal model of tear film instability has made drug development difficult. Although rabbit dry eye models have been reported in the past, there are only a few reports that focus on tear film instability. Herein, we assessed the tear film stability of a rabbit dry eye model induced by dacryoadenectomy. A clinical evaluation of the ocular surface, interferometry, and histological assessments of the cornea and conjunctiva were performed. Following the removal of the lacrimal glands, TBUT was shortened significantly, with dimple and random breakup patterns prominently observed. Furthermore, the blink rate in this model increased after dacryoadenectomy, suggesting that this model partially captured the phenotypes of human short TBUT-type dry eye and may be useful as an animal model for investigating potential drug candidates.

Background: This study aimed to assess the long-term effects of tofogliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, on atherosclerosis progression and major clinical parameters in patients with type 2 diabetes lacking an apparent history of cardiovascular disease. Methods: This was a prospective observational 2-year extension study of the “Using TOfogliflozin for Possible better Intervention against Atherosclerosis for type 2 diabetes patients (UTOPIA)” trial, a 2-year randomized intervention study. The primary endpoints represented changes in the carotid intima-media thickness (IMT). Secondary endpoints included brachial-ankle pulse wave velocity (baPWV) and biomarkers for glucose metabolism, lipid metabolism, renal function, and cardiovascular risks. Results: The mean IMT of the common carotid artery (IMT-CCA) significantly decreased in both the tofogliflozin (− 0.067 mm, standard error 0.009, p < 0.001) and conventional treatment groups (− 0.080 mm, SE 0.009, p < 0.001) throughout the follow-up period; however, no significant intergroup differences in the changes (0.013 mm, 95% confidence interval (CI) − 0.012 to 0.037, p = 0.32) were observed in a mixed-effects model for repeated measures. baPWV significantly increased in the conventional treatment group (82.7 ± 210.3 cm/s, p = 0.008) but not in the tofogliflozin group (− 17.5 ± 221.3 cm/s, p = 0.54), resulting in a significant intergroup difference in changes (− 100.2 cm/s, 95% CI − 182.8 to − 17.5, p = 0.018). Compared to the conventional treatment group, tofogliflozin significantly improved the hemoglobin A1c and high-density lipoprotein cholesterol levels, body mass index, abdominal circumference, and systolic blood pressure. The frequencies of total and serious adverse events did not vary significantly between the groups. Conclusions: Tofogliflozin was not associated with improved inhibition of carotid wall thickening but exerted long-term positive effects on various cardiovascular risk factors and baPWV while showing a good safety profile.

Tools that can be used to estimate antibody waning following COVID-19 vaccinations can facilitate an understanding of the current immune status of the population. In this study, a two-compartment-based mathematical model is formulated to describe the dynamics of the anti-SARS-CoV-2 antibody in healthy adults using serially measured waning antibody concentration data obtained in a prospective cohort study of 673 healthcare providers vaccinated with two doses of BNT162b2 vaccine. The datasets of 165 healthcare providers and 292 elderly patients with or without hemodialysis were used for external validation. Internal validation of the model demonstrated 97.0% accuracy, and external validation of the datasets of healthcare workers, hemodialysis patients, and nondialysis patients demonstrated 98.2%, 83.3%, and 83.8% accuracy, respectively. The internal and external validations demonstrated that this model also fits the data of various populations with or without underlying illnesses. Furthermore, using this model, we developed a smart device application that can rapidly calculate the timing of negative seroconversion.