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Objective The characteristics of gastric cancer in patients with atrophic mucosa and no apparent history of Helicobacter pylori eradication have not been thoroughly investigated. Therefore, this study examined the clinicopathological characteristics of gastric cancer in these patients. Methods We retrospectively examined the endoscopic and pathological characteristics of gastric cancer in patients who underwent endoscopic submucosal dissection. Patients We divided the patients into 2 groups: those with gastric atrophy and no history of eradication (group A; n=102) and those with a history of eradication (group B; n=161). In group A, patients were further divided into mild atrophy (group C) and severe atrophy (group D) groups, while group B was further divided into those who underwent eradication treatment >5 years ago (group E) and those who underwent eradication 1-5 years ago (group F). Results Group A comprised significantly older individuals (75±8.0 vs. 71±7.5 years old, p<0.001) with a higher frequency of elevated gastric cancer than group B (32.4% vs. 17.4%, p=0.006). Compared with group E, group A was older and had a greater incidence of elevated gastric cancer. The incidence of gastric cancer in the U or M region was lower in group C than in group D. Conclusion Gastric cancer in patients with gastric atrophy and no history of eradication was associated with an older age and higher frequency of elevated-type morphology than in those with a history of eradication.

Objectives: Endoscopic ultrasonography (EUS)-guided radiofrequency ablation has recently been introduced as one of the management strategies for small pancreatic neuroendocrine neoplasms (PNENs). However, prospective data on its safety and efficacy remain limited., Methods: This prospective pilot study was conducted at Okayama University Hospital from May 2023 to December 2024. Patients with grade 1 PNENs ≤15 mm, confirmed by EUS-guided fine-needle aspiration, were included. The primary endpoint was safety (adverse events [AEs] evaluated according to the 2010 guidelines of the American Society for Gastrointestinal Endoscopy. Severe AEs were defined as moderate or higher in American Society for Gastrointestinal Endoscopy grading and grade ≥3. Secondary endpoints included efficacy (complete response on contrast-enhanced computed tomography at 1 and 6 months), treatment details, device failure, diabetes mellitus exacerbation, and overall survival at 6 months., Results: Five patients with non-functional PNENs (median age: 64 years; median tumor size: 10 mm) were treated. AEs occurred in two patients (40%, 2/5), although none was severe. Both patients developed asymptomatic pseudocysts, one experienced mild pancreatitis, and both resolved with conservative treatment. The complete response rates on contrast-enhanced computed tomography at one and 6 months were 100%. The median procedure time was 16 min without any device failure, and the median hospitalization was 5 days. None of the patients developed new-onset or worsening diabetes mellitus. The 6-month overall survival rate was 100%., Conclusion: EUS-guided radiofrequency ablation demonstrated a high complete response rate with no severe AEs in this pilot study, suggesting a minimally invasive option for small, low-grade PNENs (jRCTs062230014)., Competing Interests: This study received a free supply of the EUSRA RF Electrode and VIVA Combo RF System from TaeWoong Medical., (© 2025 The Author(s). DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Individuals diagnosed with Castleman disease (CD) and TAFRO syndrome (characterized by thrombocytopenia, anasarca, fever, bone marrow fibrosis, and organomegaly) displays a wide range of clinical symptoms, including varying patterns of lymph node enlargement, systemic inflammation, and impaired organ function. Some patients may present with both CD and TAFRO syndrome concurrently. A retrospective study conducted across multiple centers in Japan examined 321 cases to determine if the quantity and position of swollen lymph nodes could forecast the clinical progression and intensity of these conditions. Interestingly, the study revealed that patients with TAFRO syndrome exhibited lymphadenopathy across all ranges of lymph node region counts. Moreover, no specific clinical patterns were associated with the number of affected lymph node regions in CD patients, regardless of whether they also had TAFRO syndrome. These results enhance our understanding of the clinical variability in CD and TAFRO syndrome, suggesting that a comprehensive clinical evaluation, rather than relying solely on lymph node count, is crucial for effectively managing these conditions. Additional studies are required to establish reliable diagnostic markers and to predict disease severity at the time of diagnosis, ultimately improving patient outcomes., (© 2025 The Author(s). American Journal of Hematology published by Wiley Periodicals LLC.)

In Japan, as elsewhere, the coronavirus disease 2019 (COVID-19) pandemic has affected notification trends of respiratory syncytial virus (RSV) infection. Here, we describe the epidemiological trends of cases of RSV infection among children reported during 2018-2021 in Japan based on the national surveillance system. Compared with 2018 and 2019, 2020 saw an unprecedented decrease in notifications of RSV infection per sentinel site. However, 2021 experienced an unseasonably early and high peak at week 28 (peak week in 2018 and 2019 was week 37), with a large resurgence in notifications nationwide and across regions. Regarding age, compared with 2018 and 2019, the number and proportion of case-patients aged 2, 3, and ≥4-years increased substantially in 2021, but the number of case-patients aged <1 year decreased slightly. Furthermore, in 2021, the ratio of notifications per site from outpatient clinics to notifications per site from hospitals increased, suggesting a proportionate increase in diagnoses of clinically milder cases. Notably, RSV-attributed deaths from vital statistics also dropped substantially in 2020 and rebounded in 2021 but were fewer than in 2018 or 2019. While the incidence of RSV infections likely declined in 2020 (possibly owing to COVID-19 countermeasures) and increased in 2021, notifications in 2021 appeared to be associated with milder presentations. Given the unpredictable epidemiology of RSV, continuous monitoring and pluralistic assessments are imperative.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

Endoscopic ultrasound-guided biliary drainage (EUS-BD) is performed as a second drainage method when endoscopic retrograde cholangiopancreatography-guided biliary drainage fails. There are several severe adverse events in EUS-BD, and avoiding technical failure is desirable. Although EUS-BD is a skilled endoscopic treatment, the appropriate conditions for EUS-BD beginners are not well known. The present study aimed to clarify the appropriate cases for EUS-BD beginners. The present retrospective cohort study included patients with malignant biliary obstruction who underwent EUS-BD, which was performed by beginners between March 2005 and June 2024. Factors associated with successful EUS-BD performed by beginners were evaluated by multivariate logistic regression analysis. The performance of each factor was evaluated via a receiver operating characteristic (ROC) curve. According to multivariate analysis, the diameter of the punctured bile duct was associated with successful EUS-BD performed by beginners (odds ratio, 1.34; 95% CI, 1.03-1.75; P=0.031). The area under the ROC curve for the diameter of the punctured bile duct was 0.79, and the cutoff value was 6.7 mm (71% sensitivity and 81.8% specificity). The diameter of the punctured bile duct might be associated with successful EUS-BD procedures performed by beginners. When a beginner performs EUS-BD, a diameter of the targeted bile duct >6.7 mm might be desirable for successful procedures., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2025, Spandidos Publications.)

Competing Interests: Declarations. Conflict of interest: Tomoharu Yoshizumi is Editor-in-Chief, and Soichiro Ishihara, Shigeru Imoto, Tomoki Ebata and Aya Saito are editorial board members of Surgery Today. Arata Takahashi is affiliated with the Department of Healthcare Quality Assessment at the University of Tokyo that is a social collaboration department supported by grants from the National Clinical Database. Ethical standards: No applicable.

Endoscopic ultrasonography (EUS)-guided ethanol injection (EI) has recently been introduced as one of the management strategies for pancreatic neuroendocrine neoplasms (PNENs); however, its role as a surgical alternative is unclear. We evaluated the efficacy and safety of EUS-EI in treating small PNENs through a prospective multicenter study.Patients with grade 1 tumors of ≤15 mm confirmed by pathology were included. The primary end point assessed efficacy and safety, measuring complete ablation using computed tomography at 1 and 6 months, prevention of adverse events (AEs) within 1 month, severe pancreatic fistula at 1 month, and incidence/worsening of diabetes mellitus (DM) at 6 months. The composite end point of EUS-EI was compared with that of historical results of a study based on surgical treatment.25 patients with PNENs, with a median tumor size of 10.1 mm, were treated using EUS-EI. The composite primary end point was achieved by 76.0% of patients (19/25; 95%CI 54.9%-90.6%), a proportion significantly higher than that of surgical treatment ( P = 0.008). Regarding efficacy, 88.0% (22/25) of patients achieved complete ablation at 1 and 6 months (95%CI 68.8%-97.5%). Regarding safety, 96.0% (24/25) of patients had no severe AEs within 1 month (95%CI 79.7%-99.9%). No patients had severe pancreatic fistulas at 1 month, and 84.0% (21/25) had no incidence or exacerbation, or both, of DM at 6 months (95%CI 63.9%-95.5%).EUS-EI is safe and could be a potent treatment option for patients with small PNENs., Competing Interests: The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Introduction: Compared to platinum-based therapies, a combination of ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) has demonstrated improved outcomes in advanced non-small cell lung cancer (NSCLC), albeit with higher rates of immune-related adverse events (irAEs). This multicenter retrospective study evaluated the efficacy and safety of nivolumab and ipilimumab with or without chemotherapy (NI and NICT) in real-world clinical settings., Methods: We enrolled 215 treatment-naïve NSCLC patients who received NI or NICT between December 2020 and May 2023 at 14 institutions in Japan. Severe irAEs (Grade ≥ 3) were assessed using the Common Terminology Criteria for Adverse Events. Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan-Meier methods and propensity score matching., Results: Of 215 patients, 104 and 111 received NI and NICT, respectively. The median PFS was 5.3 and 5.9 months for NI and NICT, respectively. The median OS was 22.1 and 19.2 months for NI and NICT, respectively. High fever within 3 weeks of treatment initiation and high tumor burden were indicators of severe irAEs. Grade 3 or higher irAEs occurred in 36.5% patients in the NI group and 50.5% patients in the NICT group, with higher treatment-related mortality in the NICT group (5.4% vs. 1.9% in NI)., Conclusions: NI and NICT showed comparable efficacies in PFS and OS. However, NICT had a higher incidence of severe irAEs and treatment-related mortality. High tumor burden and early high fever were predictors of severe irAEs. Further research is warranted to optimize the efficacy and safety of NICT for NSCLC treatment., Competing Interests: Declarations. Conflict of interest: Financial Interests: Dr Toshiyuki Sumi reported personal fee from Ono Pharmaceutical and AstraZeneca outside the submitted work. Other authors declare they have no financial interests. Ethics approval: This study was conducted with the approval of the Institutional Review Board of Sapporo Medical University Hospital (352–103) and was performed in accordance with the provisions of the Declaration of Helsinki. Consent to participate: Informed consent was not obtained from all patients; instead, the opt-out method was used. Comprehensive information about the research was made available at the hospital facility and website. Consent to publish: Not applicable., (© 2024. The Author(s).)

Background and aims Endoscopic mucosal resection (EMR) is a standard preventive method for colorectal cancer. Managing patients on anticoagulants during EMR is challenging because of balancing bleeding and thrombotic risks. Updated guidelines recommend continuing anticoagulants over heparin bridging; however, data on bleeding risks with continuing anticoagulants remain limited. This multicenter prospective study evaluated bleeding rates in patients who continued oral anticoagulants during EMR. Methods Patients on warfarin or direct oral anticoagulants (DOACs) undergoing EMR were enrolled from 12 tertiary hospitals. Warfarin was maintained on the day of EMR, while DOACs were paused on the day of EMR and resumed afterward. Post-EMR mucosal defects were closed with clips per protocol. Adverse events were monitored for 30 days. The primary endpoint was the major bleeding rate, defined as immediate bleeding requiring difficult hemostasis or delayed bleeding necessitating endoscopic intervention. The secondary endpoints were minor bleeding, other adverse events, and differences in bleeding rates between warfarin and DOACs. Results Among 107 patients (341 polyps; mean size = 6.7 mm), major bleeding occurred in five (4.7%) patients (95% confidence interval: 2.0%-10.5%), and all cases were managed endoscopically. Minor bleeding and thromboembolism events occurred in eight (7.5%) patients and one (0.9%) patient, respectively. No significant differences in bleeding rates were observed between warfarin and DOACs. Major bleeding rates were lower than those reported for heparin bridging. Conclusions Continuing anticoagulant therapy during EMR was associated with a low major bleeding rate (4.7%) and minimal thrombotic events, supporting its safety as an alternative to heparin bridging., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Institutional Review Board of Okayama University Hospital issued approval 1611-004. The study was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN) under the identifier UMIN 00021416. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2025, Kobayashi et al.)

Endoscopic ultrasound (EUS) was developed in the 1990s and has significantly transformed pancreatic tumor diagnosis. Subsequently, EUS has rapidly shifted from being a purely diagnostic procedure to being used in a wide range of interventional procedures. Recently, new therapeutic techniques, such as EUS-guided fine needle injection (EUS-FNI) or radiofrequency ablation (RFA), have been developed to deliver various antitumor agents. Despite technological advancements, pancreatic cancer (PC) has a poor prognosis and improvements in treatment outcomes are urgently required. One of the reasons for the limited response to antitumor agents in PC is the abundant desmoplasia and hypovascular nature of the tumor, complicating drug delivery into the tumor. Thus, changing the tumor microenvironment may be important to enhance the effectiveness of chemotherapy, and direct injection of antitumor agents into the tumor under EUS guidance can help overcome treatment challenges in PC. Treatment approaches using the EUS-FNI or RFA technique are expected to further improve the prognosis of PC. Therefore, this study reviewed the existing literature on EUS-guided antitumor therapy, specifically highlighting its application in PC to address the current challenges and to identify potential advancements in the field., (© 2024 The Authors. Digestive Endoscopy published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

"Wound, Pressure Ulcer, and Burn Guidelines-5: Guidelines for the management of lower leg ulcers and varicose veins, second edition" is revised from the first edition, which was published in the Japanese Journal of Dermatology in 2011. The guidelines were drafted by the Wound, Pressure Ulcer, and Burn Guidelines Drafting Committee delegated by the Japanese Dermatological Association and intend to facilitate physicians' clinical decisions in preventing, diagnosing and management of lower leg ulcers and varicose veins. We updated all sections by collecting documents published since the publication of the first edition. In particular, we added clinical question 8 (CQ8), which addresses endovenous laser ablation for varicose veins, a procedure that became covered by the Japanese national health insurance after the writing of the first edition, and endovenous radiofrequency ablation, which became covered by national health insurance in 2014. We also rearranged the subsequent clinical question (CQs) for easier reading. While the addition of these new techniques has increased the number of options available within the treatment algorithm, differences have arisen in the indication for surgery depending on the facility performing the treatment. Therefore, these have been abbreviated., (© 2024 Japanese Dermatological Association.)

Background: A bipartite atlas is a rare congenital anomaly characterized by incomplete fusion of the anterior and posterior arches of the first cervical vertebra (C1). While typically asymptomatic, this condition can result in cervical myelopathy when accompanied by degenerative changes. This report presents a rare case of cervical myelopathy caused by a bipartite atlas in an older patient that required surgical intervention., Observations: A 63-year-old male presented with progressive neurological symptoms, including impaired fine motor skills, pain, and paresthesias in both the upper and lower extremities. Imaging revealed a bipartite atlas accompanied by degenerative changes, resulting in significant spinal cord compression. The patient underwent a posterior decompression via C1 laminectomy and duraplasty, resulting in significant clinical improvement and a resolution of symptoms., Lessons: This case highlights the importance of recognizing a bipartite atlas as a potential cause of cervical myelopathy, particularly in older patients with degenerative changes. This is a rare case in which congenital and degenerative factors are intertwined, underscoring the importance of a comprehensive pathological analysis and the development of a personalized treatment strategy. Prompt diagnosis and appropriate surgical intervention are essential for favorable outcomes. https://thejns.org/doi/10.3171/CASE24688.

Background and Purpose: Radiation-induced lymphopenia (RIL) may be associated with a worse prognosis in pancreatic cancer. This study aimed to develop a normal tissue complication probability (NTCP) model to predict severe RIL in patients with pancreatic cancer undergoing concurrent chemoradiotherapy (CCRT)., Materials and Methods: We reviewed pancreatic cancer patients treated at our facility for model training and internal validation. Subsequently, we reviewed data from three other facilities to validate model fit externally. An absolute lymphocyte count (ALC) of ＜0.5 × 10 3 /μL during CCRT was defined as severe RIL. An NTCP model was trained using a least absolute shrinkage and selection operator (LASSO)-based logistic model. The model's predictive performance was evaluated using the receiver operating characteristic area under the curve (AUC), scaled Brier score, and calibration plots., Results: Among the 114 patients in the training set, 78 had severe RIL. LASSO showed that low baseline ALC, large planning target volume, and high percentage of bilateral kidneys receiving ≥ 5Gy were selected as parameters of the NTCP model for severe RIL. The AUC and scaled Brier score were 0.91 and 0.49, respectively. Internal validation yielded an average AUC of 0.92. In the external validation with 68 patients, the AUC and scaled Brier score was 0.83 and 0.30, respectively. Calibration plots showed good conformity., Conclusions: The NTCP model for severe RIL during CCRT for pancreatic cancer, developed and validated in this study, demonstrated good predictive performance. This model can be used to evaluate and compare the risk of RIL., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: HA reports grants from Hitachi Ltd., outside of the submitted work. KK was an employee of Hitachi Ltd. until January 2024, but worked for Hokkaido University under a secondary agreement. IY reports grants from KAKENHI, AMED, and Health, Labour and Welfare Policy Research Grants, research fund by Nihon Medi-Physics, and speaker fees from Chugai Pharmaceutical Co, AstraZeneca, and Pfizer outside the submitted work. The other authors have no conflicts of interest to declare., (© 2024 The Author(s).)

Myeloid sarcoma is a rare extramedullary tumor of immature myeloid cells that is often associated with acute myeloid leukemia (AML). We herein report an 81-year-old man who presented with intestinal obstruction due to myeloid sarcoma of the small intestine. Diagnostic challenges were overcome using double-balloon enteroscopy and a biopsy, which confirmed the diagnosis of myeloid sarcoma. The patient subsequently developed AML but responded well to chemotherapy. This case underscores the importance of considering myeloid sarcoma in the differential diagnosis of small-bowel tumors. Highlighting the significance of a histological analysis, even in patients presenting with small bowel obstruction, the early diagnosis and treatment are crucial for improving outcomes, particularly in patients without a history of hematologic malignancies.

Background and Aim: Lymphatic involvement is sometimes detected during routine examination of intramucosal (pT1a) gastric cancer resected endoscopically. However, its clinical significance and association with the risk of metastasis remain unknown., Methods: This was a retrospective cohort study of 6797 consecutive patients with pT1a gastric cancers treated by endoscopic submucosal dissection (ESD) at three institutions in Japan from January 2005 to August 2023. Patients with 49 uncommon-type gastric cancer types were excluded. The risk of metastasis for pT1a cancers with lymphatic involvement was quantified by comparing lymph node metastasis and/or metastatic recurrence in patient groups who underwent additional surgery post-ESD or did not undergo surgery but were followed up for > 3 years., Results: Among the 6748 pT1a cancers treated by ESD, 41 lesions (0.6%) had histologically confirmed lymphatic involvement. Among the 41 patients, 1 was excluded from the analysis of metastasis risk because the follow-up period after ESD without additional surgery was ≤ 3 years. Metastasis was identified in 1 of 40 patients analyzed (2.5%; 95% confidence interval [CI] 0.4%-12.9%), and was not detected in any of the 25 patients with pure differentiated-type lesions (0.0%; 95% CI 0.0%-13.7%)., Conclusions: The low prevalence of metastasis after ESD for pT1a gastric cancer with lymphatic involvement, particularly in patients with pure differentiated-type lesions, suggests a low risk of metastatic recurrence., (© 2024 The Author(s). Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: The proto-oncogene WWP1 is overexpressed in various cancers and contributes to tumor growth and poor prognosis. Recently, WWP1 inhibition was reported to suppress tumor development and cell proliferation by activating the PTEN function. However, the expression profiles and clinical significance of WWP1 in pancreatic ductal adenocarcinoma (PDAC) tissues remain undetermined. Therefore, this study aimed to evaluate the WWP1 expression in PDAC and investigate the therapeutic potential of WWP1 inhibition., Methods: Cellular proliferation assays were performed using a doxycycline-inducible shWWP1 expression system. Transcriptome analyses were conducted to identify the altered pathways in WWP1-depleted cells. PTEN ubiquitination by WWP1 was confirmed using immunoprecipitation assays. In vivo xenograft and drug screening assays were performed to evaluate the clinical significance of WWP1 inhibition., Results: WWP1 was significantly upregulated in PDAC tissues and associated with poor prognosis. WWP1 depletion significantly reduced the proliferation of PDAC cell lines, correlating with the suppression of the PI3K-AKT pathway. Mechanistically, as reported in other cancer types, PTEN is a target of WWP1 in PDAC cells. PTEN silencing abrogated the growth-inhibitory effects in WWP1-depleted cells, suggesting that the anti-tumor effects of WWP1 inhibition are mediated through PTEN activation. In vivo xenograft studies confirmed that WWP1 depletion substantially inhibited tumor growth. Moreover, drug screening assays revealed that WWP1 depletion had an additive effect with the PI3K-AKT pathway inhibitors on hindering tumor growth., Conclusion: WWP1 inhibition enhances the anti-tumor effects of PI3K-AKT pathway inhibitors through PTEN activation. Thus, WWP1 could be a potential therapeutic target in PDAC., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests. Ethical approval: All the animal experiments were approved by the Internal Ethics Committee for Animal Experimentation (approval numbers #H21-113 and #P21-047) and conducted in accordance with the guidelines for the Care and Use of Laboratory Animals of the Graduate School of Medicine, University of Tokyo (Tokyo, Japan)., (© 2024. The Author(s).)

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a therapeutic strategy for managing cardiogenic shock. However, it carries the risk of cardiogenic pulmonary edema, potentially leading to differential hypoxia. Although IMPELLA can mitigate pulmonary congestion, the combination of VA-ECMO and IMPELLA has frequently resulted in differential hypoxia, requiring a transition from VA-ECMO to veno-arteriovenous extracorporeal membrane oxygenation (VAV-ECMO). Therefore, this study aimed to examine the influence of IMPELLA on the incidence of differential hypoxia, necessitating a shift to VAV-ECMO. This single-center, retrospective, observational study included patients who experienced cardiopulmonary arrest and received treatment with VA-ECMO combined with an intra-aortic balloon pump (IABP) or IMPELLA between 2017 and 2022. The primary endpoint assessed the incidence of differential hypoxia, necessitating a switch to VAV-ECMO. Patients with cardiopulmonary arrest received treatment with VA-ECMO in combination with IABP (N = 28) or IMPELLA (N = 29). There was a significant increase in differential hypoxia 96 hours post-VA-ECMO initiation in the IMPELLA group, necessitating a transition to VAV-ECMO. The combination of VA-ECMO and IMPELLA in patients experiencing cardiopulmonary arrest may significantly increase the risk of differential hypoxia. A multidisciplinary approach employing mechanical circulatory support is crucial, with ongoing consideration of the potential risks associated with differential hypoxia., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2024.)

In Asia-Pacific region, hepatocellular carcinoma is a serious health threat attributing to over 600,000 deaths each year and account for over 70% of global cases. Clinically, the major unmet needs are recurrence after curative-intent surgery, liver transplantation or local ablation and disease progression in those with hepatocellular carcinoma not eligible for resection or failed locoregional therapy. In the recent few years, new targeted therapy and immune-checkpoint inhibitors have been registered as systemic therapy to address these issues. Notably, new forms of systemic therapy, either as first-line or second-line therapy for unresectable hepatocellular or those not eligible for locoregional therapy, are now available. New data is also emerging with the use of systemic therapy to prevent hepatocellular carcinoma recurrence after curative-intent resection or local ablation therapy and to retard disease progression after locoregional therapy. In the future, further implementation of immune-checkpoint inhibitors and other forms of immunotherapy are expected to bring a new paradigm to the management of hepatocellular carcinoma. New insight related to immune-related adverse events with the use of immunotherapy has allso enabled optimization of the therapeutic approach to patients with hepatocellular carcinoma. The purpose of this clinical practice guideline is to provide an up-to-date recommendation based on clinical evidence and experience from expert Asia-Pacific key opinion leaders in the field of hepatocellular carcinoma. Three key questions will be addressed, namely: (1) Which patients with hepatocellular carcinoma should be considered for systemic therapy? (2) Which systemic therapy should be used? (3) How should a patient planned for immune checkpoint-based systemic therapy be managed and monitored?, Competing Interests: Declarations. Conflict of interest: George LAU reported lecture fees from AstraZeneca. Shuntaro OBI reported research grants from Eisai, Otsuka pharmaceutical, and Mochida pharmaceutical. Ryosuke TATEISHI reported lecture fees from Abbvie, AstraZeneca, Chugai, Eisai, Gilead Sciences, MSD and Takeda. Sadahisa OGASAWARA reported honoraria from Bayer, Eisai, Eli Lilly, consulting or advisory fees from Bayer, Eisai, Merck & Co. Inc., Chugai Pharma, Eli Lilly, and research grants from Bayer and Eisai. Naoya KATO reported honoraria payment from Bayer and Chugai; research funding from Bayer, Chugai, and Roche. Stephen L CHAN reported consulting or advisory board fees from AstraZeneca, Eisai, and MSD; reports being an invited speaker for AstraZeneca, Bayer, Bristol Myers Squibb, Eisai, IPSEN, MSD, and Roche; and research funding from Bayer, Eisai, IPSEN, MSD, and Sirtex Medical. Yoshiyuki UENO reported honoraria payment from Chugai and Eisai. Ann-Lii CHENG reported consulting or advisory board fees from AstraZeneca, Bayer, BeiGene, Bristol Myers Squibb, Eisai, Genentech/Roche, Ipsen, IQVIA, MSD, Ono Pharmaceutical, and Roche; and honoraria from AstraZeneca, Bayer, Eisai, and Genentech/Roche. Yock Young DAN reported consulting or advisory board fees from Boehringer Ingelheim, MSD, Norvo Nordisk, Roche, and research grants from MSD, Norvo Nordisk, Perspectum, Siemens. Jeong Min LEE reported lecture fees from Samsung Medison, GE Healthcare, Philips Healthcare, Starmed, and research grants from Samsung Medison, Siemens Healthineers, Philips Healthcare, GE Healthcare, Bayer, Guerbet, CMS, Canon Healthcare, Dongkuk Pharma. Diana A. Payawal reported lecture, consulting or advisory board fees from Gilead Sciences, Mylan Pharmaceuticals, Echosense, Getz and Abbott. Ekaphop SIRACHAINAN reported honoraria payment from MSD, Sanofi/Aventis, Merck, Amgen, Roche, Mundipharma, AstraZeneca, LF Asia, Diethelm Keller Group, Bristol Myers Squibb, Boehringer Ingelheim, Taiho Pharmaceutical, Dr Reddy's Laboratories, Zuellig Pharma, Meda Pharmaceuticals, Pfizer, Novo Nordisk, Novartis. Tawesak Tanwandee reported research grants from Bristol Myers Squibb and Merck. Masao Omata reported lecture, consulting or advisory board fees from Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Otsuka, Astellas, Gilead Sciences, Chugai, Mitsubishi Tanabe, Kyorin, Merck Sharp and Dohme, Dainippon Sumitomo, Vertex Pharmaceuticals, Takeda, Merck Serono, and Zeria. Jian ZHOU, Shukui QIN, Haitao ZHAO, Motoyuki OTSUKA, Jacob GEORGE, Pierce KH CHOW, Jianqiang CAI, Shuichiro SHIINA, Osamu YOKOSUKA, Kyoko OURA, Thomas YAU, Ming KUANG, Minshan CHEN, Gregory CHENG, Wan-Long CHUANG, Oidov BAATARKHUU, Feng BI, Rino A GANI, Atsushi TANAKA, Wasim JAFRI, Ji-Dong JIA, Jia-Horng KAO, Kiyoshi HASEGAWA, Patrick LAU, Jun LIANG, Zhenwen LIU, Yinying LU, Hongming PAN, Salimur RAHMAN, Jinsil SEONG, Feng SHEN, Gamal SHIHA, Tianqiang SONG, Hui-Chuan SUN, Tsutomu MASAKI, Lai WEI, Jin Mo YANG, Jose D SALLANO, Yanqiao ZHANG,, A Kadir DOKMECI, Shu-sen ZHENG, Jia FAN, Sheung-Tat FAN and Shiv Kumar Sarin reported that they have no conflict of interest. Ethical approval: Not applicable. Informed consent: Not applicable., (© 2024. Asian Pacific Association for the Study of the Liver.)

Background and Aim: As the population ages, the number of elderly patients with superficial esophageal squamous cell carcinoma (ESCC) is increasing. We aimed to clarify the indications for endoscopic resection (ER) in late-elderly patients with ESCC in terms of life expectancy., Methods: Patients aged ≥75 years who underwent ER for ESCC at our institution from January 2005 to December 2018 were enrolled. Clinical data, including the Eastern Cooperative Oncology Group performance status, American Society of Anesthesiologists physical status (ASA-PS), Charlson comorbidity index, and prognostic nutritional index (PNI), were collected at the time of ER. The main outcome measure was overall survival (OS)., Results: Two hundred eight consecutive patients were enrolled. The patients' median age was 78 years (range, 75-89 years). The 5-year follow-up rate was 88.5% (median follow-up period, 6.6 years). The 5-year OS rate was 79.2% (95% confidence interval [CI], 72.2-84.8), and 5-year net survival standardized for age, sex, and calendar year was 1.04 (95% CI, 0.98-1.09). In the multivariate analysis, an ASA-PS of 3 (hazard ratio, 2.45; 95% CI, 1.16-5.17) and PNI of <44.0 (hazard ratio, 2.73; 95% CI, 1.38-5.40) were independent prognostic factors. When neither of these factors was met, the 5-year OS rate was 87.8% (95% CI, 80.0-92.9), and 5-year net survival was 1.08 (95% CI, 1.02-1.14)., Conclusions: ER for ESCC in late-elderly patients may improve life expectancy. ER is recommended in patients with a good ASA-PS and PNI., (© 2024 The Author(s). Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aim: The 2017 Japanese guidelines recommend continuing warfarin therapy during the perioperative period or discontinuing direct oral anticoagulants (DOACs) only on the day of endoscopic submucosal dissection for early gastric cancer. However, their safety has not been sufficiently explored. This study aimed to validate this management method., Methods: This retrospective, multicenter study analyzed the characteristics and outcomes of patients who underwent gastric endoscopic submucosal dissection between July 2017 and June 2019. The patients were categorized according to the use of warfarin or DOACs., Results: Among the 62 eligible patients, 53 (85%) were male (median age, 76 years). Warfarin was used in 10 patients (16%) and DOACs in 52 patients (84%). Fourteen patients taking DOACs (27%) used concomitant antiplatelet agents, with seven patients (13%) continuing treatment at the time of the endoscopic procedure. No postprocedural bleeding occurred in patients receiving warfarin (0%), whereas 10 cases (19%) of bleeding occurred in patients receiving DOACs: rivaroxaban, 0% (0/22); dabigatran, 0% (0/2); edoxaban, 43% (6/14); and apixaban, 29% (4/14). The type of anticoagulant (P < 0.01) and continuation of antiplatelet therapy (P = 0.02) were risk factors for postprocedural bleeding in patients receiving DOACs. Intraprocedural bleeding requiring transfusion or symptomatic thromboembolic events were not reported., Conclusions: Continuous warfarin therapy is preferred. DOAC withdrawal 1 day before a procedure is associated with a high bleeding rate, which may differ for different types of anticoagulants. The continuation of antiplatelet medications in patients receiving DOACs carries a high risk of bleeding and is a future challenge., (© 2024 The Author(s). Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Objective: Because vascular endothelial growth factor inhibition has been suggested to improve immune cell function in the cancer microenvironment, we examined whether using ramucirumab (RAM) before nivolumab usage is more effective in advanced gastric cancer., Methods: This was a multicenter retrospective observational study. We analyzed patients who received nivolumab monotherapy as the third-line regimen for unresectable advanced or recurrent gastric cancer between October 2017 and December 2022. They were divided into the RAM (RAM-treated) group and the non-RAM (non-treated) group according to the RAM usage in the second-line regimen. The primary outcome was to compare the overall survival after nivolumab administration in the third-line regimen between the RAM and non-RAM groups., Results: Fifty-two patients were included in the present study: 42 patients in the RAM group and ten patients in the non-RAM group. The median overall survival was significantly longer in the RAM group than in the non-RAM group (8.5 months vs 6.9 months, p < 0.05). In the RAM group, patients without peritoneal metastasis had significantly better median overall survival than those with peritoneal metastasis (23.8 months vs 7.7 months, p = 0.0033). Multivariate Cox-proportional hazards analyses showed that the presence of peritoneal metastasis (hazard ratio, 2.4; 95% confidence interval 1.0-5.7) alone was significantly associated with overall survival in the RAM group., Conclusions: The use of RAM prior to nivolumab monotherapy may contribute to prolonged survival in patients with gastric cancer, especially those without peritoneal metastasis., Competing Interests: Declarations. Funding: This work was supported in part by Grants-in-Aid from the Japan Society for the Promotion of Science (#22H02828 to Motoyuki Otsuka). Conflicts of interest/competing interests: Yuka Obayashi, Shoichiro Hirata, Yoshiyasu Kono, Makoto Abe, Koji Miyahara, Masahiro Nakagawa, Michihiro Ishida, Yasuhiro Choda, Kenta Hamada, Masaya Iwamuro, Seiji Kawano, Yoshiro Kawahara, and Motoyuki Otsuka have no conflicts of interest that are directly relevant to the content of this article. Ethics approval: This retrospective chart review study involving human participants was in accordance with the ethical standards of the institutional and national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. The Human Investigation Committee (Institutional Review Board) of Okayama University Hospital approved this study (approval number 2307-031). Consent to participate: Informed consent was acquired by the opt-out method. Consent for publication: Not applicable. Availability of data and material: The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request. Code availability: Not applicable. Authors’ contributions: Writing (original draft preparation): YO, SH, and YK; conceptualization and methodology: YK; formal analysis and investigation: MA, KM, MN, MI, YC, KH, MI, SK, and YK; writing (review and editing): MO. All authors read and approved the final version., (© 2024. The Author(s).)

Black hairy tongue, also known as lingua villosa nigra , is a benign oral condition characterized by a dark discoloration and "hairy" appearance on the tongue's dorsal surface, resulting from elongated filiform papillae. This condition is associated with risk factors such as smoking, poor oral hygiene, and diabetes, which increase susceptibility to microbial colonization, particularly by Candida species. Although commonly diagnosed by visual inspection, black hairy tongue is infrequently observed during endoscopic procedures. We report a case of a 69-year-old Japanese man with poorly controlled type 2 diabetes (hemoglobin A1c of 9.7%) and a significant smoking history of 49 pack-years. During a routine esophagogastroduodenoscopy, a dark lesion was detected on the dorsal surface of the tongue. Detailed imaging and biopsy revealed elongated papillae with fungal hyphae, confirming a diagnosis of candidiasis. This case underscores the value of esophagogastroduodenoscopy and histopathological examination in diagnosing black hairy tongue and distinguishing it from other pigmented lesions. Recognizing black hairy tongue as a potential finding during endoscopy may aid in prompt diagnosis, especially in patients with predisposing factors like smoking and diabetes., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Iwamuro et al.)

Diabetes mellitus disturbs kisspeptin-neurokinin B-dynorphin A (KNDy) neurons in the arcuate nucleus (ARC), which regulate pulsatile luteinizing hormone (LH) secretion in both sexes. However, it remains unclear whether a sex-specific association with the negative effects of diabetes on KNDy neurons exists. Therefore, we examined mRNA expression in KNDy neurons of diabetic male and female rats 7 weeks after streptozotocin (STZ) injection using histochemistry. In gonad-intact rats, the numbers of Kiss1 and Pdyn mRNA-expressing cells in the ARC decreased in an STZ-dose-dependent manner; moreover, no sex-dependent association with STZ treatment was observed. In males, plasma LH and sex steroid levels decreased in diabetic rats. Conversely, those of females did not vary significantly between the control and diabetic rats. Kiss1 expression in the anteroventral periventricular nucleus was slightly affected in diabetic animals but did not exhibit sex-dependent differences. In gonadectomized rats, the numbers of KNDy mRNA-expressing cells in the ARC and plasma LH levels decreased in diabetic male and female rats; however, sex-dependent differences did not exist. These results demonstrated that a sex-specific association with the negative effects of diabetes on KNDy neurons did not exist. Therefore, the stage of diabetes that induces the suppression of the hypothalamus may not vary according to sex.

The epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2), pioneer members of the receptor tyrosine kinase subfamily, are frequently mutated and/or overexpressed in several types of human cancers, including nonsmall cell lung cancer (NSCLC) and breast cancer, which are leading causes of cancer-related deaths worldwide. EGFR and HER2-focused anti-NSCLC and antibreast cancer studies encouraged us to search for new potential agents. For this purpose, in the current work, naphthalene-linked pyrazoline-thiazole hybrids ( BTT-1 - 10 and BTP-1 - 10 ) were synthesized and examined for their antiproliferative effects on A549 NSCLC and MCF-7 breast cancer cell lines. According to the results, the MTT assay showed that BTT-5 induced strong toxicity in A549 cells with an IC 50 value of 9.51 ± 3.35 μM compared to lapatinib (IC 50 = 16.44 ± 3.92 μM). BTT-5 also presented a high selectivity profile between the Jurkat cell line and PBMCs (healthy) (SI = 65.65). Furthermore, BTT-5 augmented apoptosis significantly in A549 cells (18.40%). BTT-5 displayed significant EGFR inhibition (58.32%) and no significant HER2 inhibition at 10 μM concentration, showing its selective kinase inhibitory effects. The molecular docking assessment indicated that BTT-5 showed high affinity with a different binding profile than lapatinib in the ATP binding cleft of EGFR. Consequently, BTT-5 can serve as a lead for future anti-NSCLC studies., (© TÜBİTAK.)

Purpose: We investigated the effect of enhanced monofocal intraocular lenses (IOL) (TECNIS Eyhance DIB00V) on retinal sensitivity in glaucoma patients after cataract surgery by comparing results with of such patients implanted with non-enhanced monofocal intraocular lenses (TECNIS ZCB00V)., Patients and Methods: This was a multi-facility retrospective study of glaucoma patients who had undergone cataract surgery. We measured the value of the foveal threshold with a Humphrey visual field analyzer before and after cataract surgery and considered this value to represent the sensitivity of the retina. As a sub-analysis, we also compared the mean deviation (MD), pattern standard deviation (PSD), thickness of ganglion cell complex (GCC), and best corrected visual acuity (BCVA) before and after surgery. We used t-tests to determine statistical differences between lens groups., Results: We included 60 glaucoma patients (104 eyes) who underwent cataract surgery: enhanced group, n = 58 eyes; non-enhanced group, n = 46 eyes. In both groups, cataract surgery improved the retinal sensitivity (p < 0.001), MD (p < 0.001) and BCVA (p < 0.001). The postoperative foveal thresholds did not significantly differ by lens type (p = 0.673), at 34.41 ± 2.44 dB in the enhanced group and 34.61 ± 2.19 dB in the non-enhanced group. Likewise, there was no significant difference (p = 0.942) among advanced glaucoma patients, with postoperative foveal thresholds of 33.08 ± 2.35 dB and 33.17 ± 3.45 dB in the enhanced and non-enhanced, respectively., Conclusions: Implantation of enhanced monofocal IOLs in glaucoma patients did not result in any apparent loss of sensitivity compared with non-enhanced monofocal lens implantation., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background and study aims Although esophagogastroduodenoscopy (EGD) is a widely used technique, the procedure is often associated with discomfort. This study aimed to analyze painful situations, their frequency, and factors associated with patient discomfort during EGD. Patients and methods This prospective observational study included patients scheduled to undergo EGD. Seven endoscopists recruited patients scheduled for EGD screening or surveillance. Each endoscopist enrolled 20 patients, performing 10 EGD procedures using ultraslim endoscopes and 10 with standard-sized endoscopes. Data regarding painful situations and frequency were collected using specialized buttons pressed by the patients during EGD. A survey about overall discomfort was conducted after the procedure. Results We analyzed data from 140 patients. Esophageal insertion and duodenal observation were associated with the highest incidence of pressing the pain button, accounting for 59.3% and 40.7% of the cases, respectively. The factor associated with pressing the pain button during esophageal insertion was endoscopist experience (< 10 years). In contrast, younger age and female sex were the factors associated with pressing the pain button during duodenal observation. In the post-procedure survey, 63.6% of patients reported discomfort. Factors associated with patient discomfort included pressing the pain button during esophageal insertion (odds ratio [OR]: 2.84, P = 0.01) and previous painful EGD experience (OR: 2.41, P = 0.03). Concusions This study provides objective data on painful situations, their frequency, and related factors during EGD. Further research and interventions focusing on pain reduction during endoscopic procedures are warranted. The results of this study will help endoscopists manage painful situations and potentially improve skills., Competing Interests: Conflict of Interest This research was conducted with funding provided by Fujifilm Corporation., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Impaired hepatic and renal function influence Alzheimer's disease (AD) progression; however, whether AD progression affects these important organ functions remains unclear. Here, we investigated the impact of AD progression, characterized by brain amyloid-beta (Aβ) accumulation, on liver and kidney function of App NL-G-F/NL-G-F (APP-KI) mice using quantitative proteomics. SWATH-based quantitative proteomics revealed changes in mitochondrial, drug metabolism, and pharmacokinetic-related proteins in mouse liver and kidneys during the early (2-month-old) and intermediate (5-month-old) stages of Aβ accumulation. Notably, in 5-month-old APP-KI mouse liver, 25 phase I/II metabolizing enzymes (8 CYPs, 7 UGTs, 7 CESs, and 3 SLCs) and five transporters (2 ABCs and 3 SLCs) were significantly altered; specifically, Ugt1a9 and Slc33a1 protein abundances increased, whereas Ugt1a1 and Abcc3 protein abundances decreased. In the kidneys, 13 phase I/II metabolizing enzymes and 10 ABC-SLC transporters were altered, including Ugt1a6, Ugt1a7, Slc22a7, and Abcb1a. Additionally, plasma proteins, such as albumin and alpha-1-acid glycoprotein, which are critical for drug binding and distribution, were also altered. These results underscore the significant role of progressive brain Aβ accumulation in modifying hepatic and renal protein abundances, potentially influencing drug metabolism and disposition in AD. Our findings provide novel insights into the complex relationship between AD progression and organ dysfunction., 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 © 2024. Published by Elsevier Inc.)

Background and Aims: Accurately diagnosing biliary strictures is crucial for surgical decisions, and although peroral cholangioscopy (POCS) aids in visual diagnosis, diagnosing malignancies or determining lesion margins via this route remains challenging. Indigo carmine is commonly used to evaluate lesions during GI endoscopy. We aimed to establish the utility of virtual indigo carmine chromoendoscopy (VICI) converted from POCS images using artificial intelligence., Methods: This single-center, retrospective study analyzed 40 patients with biliary strictures who underwent POCS using white-light imaging (WLI) and narrow-band imaging (NBI). A cycle-consistent adversarial network was used to convert the WLI into VICI of POCS images. Three experienced endoscopists evaluated WLI, NBI, and VICI via POCS in all patients. The primary outcome was the visualization quality of surface structures, surface microvessels, and lesion margins. The secondary outcome was diagnostic accuracy., Results: VICI showed superior visualization of the surface structures and lesion margins compared with WLI (P < .001) and NBI (P < .001). The diagnostic accuracies were 72.5%, 87.5%, and 90.0% in WLI alone, WLI and VICI simultaneously, and WLI and NBI simultaneously, respectively. WLI and VICI simultaneously tended to result in higher accuracy than WLI alone (P = .083), and the results were not significantly different from WLI and NBI simultaneously (P = .65)., Conclusions: VICI in POCS proved valuable for visualizing surface structures and lesion margins and contributed to higher diagnostic accuracy comparable to NBI. In addition to NBI, VICI may be a novel supportive modality for POCS., Competing Interests: Disclosure All authors disclosed no financial relationships., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Aims/hypothesis: Appropriate management of blood glucose levels and the prevention of complications are important in the treatment of diabetes. We have previously reported on a compound named HPH-15 that is not only antifibrotic but also AMP-activated protein kinase (AMPK)-activating. In this study, we evaluated whether HPH-15 is useful as a therapeutic medication for diabetes., Methods: We examined the effects of HPH-15 on AMPK activation, glucose uptake, fat accumulation and lactic acid production in L6-GLUT4, HepG2 and 3T3-L1 cells, as a model of muscle, liver and fat tissue, respectively. Additionally, we investigated the glucose-lowering, fat-accumulation-suppressing, antifibrotic and AMPK-activating effect of HPH-15 in mice fed a high-fat diet (HFD)., Results: HPH-15 at a concentration of 10 µmol/l increased AMPK activation, glucose uptake and membrane translocation of GLUT4 in each cell model to the same extent as metformin at 2 mmol/l. The production of lactic acid (which causes lactic acidosis) in HPH-15-treated cells was equal to or less than that observed in metformin-treated cells. In HFD-fed mice, HPH-15 lowered blood glucose from 11.1±0.3 mmol/l to 8.2±0.4 mmol/l (10 mg/kg) and 7.9±0.4 mmol/l (100 mg/kg) and improved insulin resistance. The HPH-15 (10 mg/kg) group showed the same level of AMPK activation as the metformin (300 mg/kg) group in all organs. The HPH-15-treated HFD-fed mice also showed suppression of fat accumulation and fibrosis in the liver and fat tissue; these effects were more significant than those obtained with metformin. Mice treated with high doses of HPH-15 also exhibited a 44% reduction in subcutaneous fat., Conclusions/interpretation: HPH-15 activated AMPK at lower concentrations than metformin in vitro and in vivo and improved blood glucose levels and insulin resistance in vivo. In addition, HPH-15 was more effective than metformin at ameliorating fatty liver and adipocyte hypertrophy in HFD-fed mice. HPH-15 could be effective in preventing fatty liver, a common complication in diabetic individuals. Additionally, in contrast to metformin, high doses of HPH-15 reduced subcutaneous fat in HFD-fed mice. Presumably, HPH-15 has a stronger inhibitory effect on fat accumulation and fibrosis than metformin, accounting for the reduction of subcutaneous fat. Therefore, HPH-15 is potentially a glucose-lowering medication that can lower blood glucose, inhibit fat accumulation and ameliorate liver fibrosis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The Roberts linkage is recognized for enabling long-period pendulum motion in a compact format. Utilizing this characteristic, we are developing a three-point Roberts linkage for vibration isolation systems, with an eye toward its potential contribution to the development of next-generation interferometric gravitational wave antennas. In this article, we derived the equations to determine the essential parameters when using this linkage as a vibration isolation system, namely, the equivalent pendulum length and the relationship between translational motion of the center of mass and rigid body rotation, from size parameters. In addition, we analyzed the behavior in response to various errors., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Background and Aims: Accurate assessment of colorectal polyp size is crucial for determining treatment and surveillance policies. However, visual estimation of lesion diameter is often inaccurate, making simple and effective educational tools essential. We aimed to evaluate the learning effects of virtual scale endoscopy (VSE)., Methods: Thirty-three endoscopists first watched prelearning videos for SET1. They then estimated the diameters of 20 lesions and referred to instructional videos with VSE for self-study. Subsequently, they watched the postlearning videos for SET2 and estimated the lesion diameters. The error between the estimated and correct lesion sizes of both sets was compared. To evaluate longer-term learning effects, participants answered SET3 and SET4, which consisted of the same questions as SET2 and SET1, respectively, but 2 to 3 months later without watching the instructional video for SET2., Results: The error in the participants' estimation of the correct lesion diameter improved from SET1 to SET2 (34.7 ± 6.6 mm vs 30.7 ± 7.7 mm, P = .048), with a significant learning effect and error improvement specifically among nonexperts (35.2 ± 5.3 mm vs 30 ± 6.8 mm, P = .028). In SET3 and SET4, participants' errors indicated that the learning effect was well maintained (SET2 vs SET3: 30.7 ± 7.7 mm vs 28.6 ± 7.2 mm [P = .1]; SET1 vs SET4: 34.7 ± 6.6 mm vs 31.7 ± 7.1 mm [P = .025])., Conclusions: VSE videos are a valuable learning tool for estimating lesion diameter, particularly for novice endoscopists, both in the short and longer term., Competing Interests: Disclosure All authors disclosed no financial relationships., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Purpose: We compared the corneal endothelial cell loss between trabeculectomy (Trab) and Ex-Press ® surgery (EXP) for low-intraocular pressure (IOP) glaucoma patients., Patients and Methods: This was a single-facility retrospective study. We analyzed the cases of patients with primary open-angle glaucoma (POAG) and pre-operative IOP ≤ 21 mmHg who had undergone Trab or EXP surgery and were followed for >3 years. Noncontact specular microscopy was used to determine the corneal endothelial cell density (CED) before and after Trab or EXP surgery. We measured the CED at 12, 24, and 36 months post-surgery. We compared the CED values and CED survival ratio after both surgeries using paired t-tests., Results: We included 39 eyes that underwent Trab and 36 eyes that underwent EXP surgery. In the Trab group, the mean CED value had decreased from 2333 ± 399 at baseline to 2066 ± 587 cells/mm2 after 3 years. In the EXP group, the mean CED value had decreased from 2320 ± 393 at baseline to 2229 ± 460 cells/mm 2 after 3 years. The survival ratio of CED at >3 years was 89.3 ± 14.2% (Trab group) and 95.6 ± 11.1% (EXP group); compared to the Trab surgery, the EXP surgery thus significantly decreased the CED loss (p = 0.037). No case resulted in bullous keratopathy., Conclusion: Compared to trabeculectomy, Ex-Press ® surgery appears to be a safer surgical method with regard to the endothelial cell loss risk., Competing Interests: No potential conflict of interest was reported by the authors., (© 2024 Otsuka et al.)

Aim: Type 2 diabetes mellitus (T2DM) is a well-known risk factor for hepatocellular carcinoma (HCC). However, HCC is often diagnosed at an advanced stage in patients with diabetes because of the lack of the best criteria for surveillance candidates. The aim of this study was to identify risk factors for HCC development in patients with diabetes with nonviral chronic liver disease., Method: Three hundred thirty T2DM patients with nonviral chronic liver disease who underwent surveillance for HCC by imaging techniques between 2009 and 2020 were enrolled in this multicenter cross-sectional retrospective study. The clinical and laboratory parameters of patients with and without HCC were compared., Results: Age ≥65 years, alcohol intake, lack of hepatic steatosis, triglyceride level <111 mg/dL, Mac2 binding protein glycosylation isomer (M2BPGi) ≥0.9 cut-off index (COI), α-fetoprotein concentration ≥5 ng/mL, and des-γ-carboxy prothrombin concentration ≥26 mAU/mL were independently associated with HCC development. When stratified by age, only alcohol intake (odds ratio [OR] 114.19, p < 0.001) was associated with HCC development in patients aged <65 years, and medication for diabetes mellitus (OR 5.72, p = 0.001), lack of hepatic steatosis (OR 4.47, p = 0.002), lactate dehydrogenase ≥198 IU/L (OR 2.751, p = 0.031), M2BPGi ≥1.18 COI (OR 9.05, p < 0.001), and FIB-4 index ≥2.59 (OR 3.22, p = 0.017) were associated with HCC development in patients aged ≥65 years., Conclusions: In addition to age and advanced liver fibrosis, alcohol intake in younger T2DM patients and medication for DM and lack of hepatic steatosis in older T2DM patients should be considered for HCC surveillance by imaging., (© 2024 Japan Society of Hepatology.)

Achalasia, a chronic esophageal motility disorder, increases the risk of esophageal squamous cell carcinoma. Despite effective treatment with peroral endoscopic myotomy (POEM), patients remain at risk of malignancy. We present the case of a 75-year-old Japanese woman diagnosed with achalasia who was found to have esophageal squamous cell carcinoma three months after POEM. Early detection through endoscopic surveillance and biopsy led to successful endoscopic submucosal dissection. This case underscores the need for ongoing surveillance of patients with achalasia post-POEM to ensure early identification and treatment of potential malignancies., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kamio et al.)

Low birthweight (LBW) increases the risk of adult-onset diseases, including kidney diseases, with intergenerational consequences; however, the underlying mechanisms and effective interventions are unclear. To examine the cross-generational effects of LBW, we established an LBW mouse model through reduced uterine perfusion pressure (RUPP) and investigated the therapeutic potential of tadalafil, a phosphodiesterase 5 inhibitor, on LBW-associated consequences. RUPP-pups (R1) had lower fetal and birth weights, delayed renal development, and fewer glomeruli than Sham-pups. In adulthood, R1 mice exhibited persistently fewer glomeruli and elevated blood pressure, while Tadalafil-R1 mice showed reduced hypertension in both sexes and improved renal pathological changes in males. Additionally, pregnant R1 mice displayed inadequate gestational liver hypertrophy, impaired hepatic purine metabolism, and diminished placental angiogenesis, resulting in fetal growth restriction in the subsequent generation. These findings underscore the lasting impact of LBW on adult health and future generations and suggest tadalafil's potential to mitigate LBW-associated risks., Competing Interests: The authors declare that they have no conflicts of interest., (© 2024 The Author(s).)

This case report presents a 34-year-old Japanese man with hematemesis who was ultimately diagnosed with gingival bleeding due to periodontitis via esophagogastroduodenoscopy. Although endoscopic examination revealed no gastrointestinal lesions, persistent bleeding from the gums was observed, highlighting the need to consider non-gastrointestinal sources of bleeding in such scenarios. Heavy alcohol consumption likely contributed to poor oral health and increased the risk of oral bleeding. This case emphasizes the importance of thorough endoscopic evaluation of the oral and pharyngolaryngeal regions, particularly when common gastrointestinal sources of bleeding are excluded. A comprehensive diagnostic approach is essential to avoid overlooking less common causes of bleeding., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Iwamuro et al.)

Rapid on-site cytopathology evaluation (ROSE) has been considered an effective method to increase the diagnostic ability of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA); however, ROSE is unavailable in most institutes worldwide due to the shortage of cytopathologists. To overcome this situation, we created an artificial intelligence (AI)-based system (the ROSE-AI system), which was trained with the augmented data to evaluate the slide images acquired by EUS-FNA. This study aimed to clarify the effects of such data-augmentation on establishing an effective ROSE-AI system by comparing the efficacy of various data-augmentation techniques. The ROSE-AI system was trained with increased data obtained by the various data-augmentation techniques, including geometric transformation, color space transformation, and kernel filtering. By performing five-fold cross-validation, we compared the efficacy of each data-augmentation technique on the increasing diagnostic abilities of the ROSE-AI system. We collected 4059 divided EUS-FNA slide images from 36 patients with pancreatic cancer and nine patients with non-pancreatic cancer. The diagnostic ability of the ROSE-AI system without data augmentation had a sensitivity, specificity, and accuracy of 87.5%, 79.7%, and 83.7%, respectively. While, some data-augmentation techniques decreased diagnostic ability, the ROSE-AI system trained only with the augmented data using the geometric transformation technique had the highest diagnostic accuracy (88.2%). We successfully developed a prototype ROSE-AI system with high diagnostic ability. Each data-augmentation technique may have various compatibilities with AI-mediated diagnostics, and the geometric transformation was the most effective for the ROSE-AI system., (© 2024. The Author(s).)

Durvalumab plus tremelimumab (Durva/Treme) combined immunotherapy is the first-line therapy recommended for unresectable hepatocellular carcinoma (HCC). Since sequential therapy is more effective in improving prognosis, tumor markers have been used as predictive biomarkers for response to systemic therapy. This study aimed to investigate the predictive ability of objective response (OR) by tumor markers for Durva/Treme therapy against HCC. In this multicenter study, 110 patients with HCC who received Durva/Treme therapy were retrospectively enrolled. The OR rate was 15.5%. To aid early decision-making regarding OR, we evaluated the predictors contributing to OR in two steps: before (first step) and 4 weeks after (second step) treatment induction. Changes in tumor markers (alpha-fetoprotein [AFP] and des-gamma-carboxy prothrombin [DCP]) from baseline to 4 weeks after treatment (ΔAFP/ΔDCP) were included as the input factors. In the first step, multivariable analysis identified only the baseline AFP level (odds ratio 3.497, p = 0.029) as a predictor of OR. Patients with AFP ≥ 400 ng/mL had a significantly higher OR rate than those with < 400 ng/mL (28.2 vs. 8.5%, p = 0.011), and there was no significant difference in progression-free survival (PFS) between the two groups. When AFP/DCP response was defined as a ≥10% reduction from baseline, multivariable analysis showed that AFP response (odds ratio 6.023, p = 0.042) and DCP response (odds ratio 11.657, p = 0.006) were both independent predictors of OR in the second step. The PFS of patients with AFP or DCP response was significantly longer than that of patients without AFP or DCP response. The study demonstrated that the use of AFP and DCP can predict the OR of patients with HCC receiving Durva/Treme therapy., Competing Interests: I.S.: Lecture fees from AstraZeneca, and Eisai Co. Ltd., S.S.: Lecture fees from AstraZeneca, Eisai Co. Ltd., T.I.: Lecture fees from AstraZeneca, and Chugai Pharmaceutical Co., Ltd., and research funding from Chugai Pharmaceutical Co., Ltd., H.K.: Research funding from Chugai Pharmaceutical Co., Ltd. T.K.: Lecture fees from ASKA Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Kowa Company, Ltd., AbbVie GK., Eisai Co., Ltd., Novo Nordisk Pharma Ltd., Janssen Pharmaceutical K.K., Otsuka Pharmaceutical Co., Ltd., EA Pharma Co., Ltd. T.T.: Lecture fee from Gilead Sciences, Inc., AbbVie GK., Otsuka Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd. The remaining authors have no conflicts of interest., (Copyright: © 2024 Saeki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Eczema is the most common category of inflammatory skin disorders as dermatologists see many patients with eczematous diseases in daily practice. It is characterized by the three major morphological features: multiple-pinpoint condition, polymorphism, and itch. To describe polymorphism, "eczema triangle" has been used in German/Japanese dermatology. The multiple pinpoints correspond to numerous tiny foci from which individual papules/vesicles arise. The polymorphism betrays composition of erythema, papule, seropapule, vesicle, pustule, scale, and crust, which are seen in acute eczema. Meanwhile, chronic eczema is represented by lichenification and hyperpigmentation, and possibly by hypopigmentation. In acute eczema, spongiosis is associated with overproduction of hyaluronic acid, secretion of self-protective galectin-7, and decreased expression of E-cadherin. In the upper dermis, Th1/Tc1 or Th2/Tc2, and additional Th17, Th22, and/or Tc22 infiltrate, depending on each eczematous disease. Innate lymphoid cells are also involved in the formation of eczema. In chronic eczema, periostin contributes to remodeling of inflammatory skin with dermal fibrosis, and epidermal melanogenesis and dermal pigment deposition result in hyperpigmentation. Finally, eczematous diseases are potentially associated with increased risk of comorbidities, including not only other allergic diseases but also coronary heart disease and mental problems such as depression. Although the original word for eczema is derived from old Greek "ekzein," eczema remains a major target of modern science and novel therapies., (© 2024 Japanese Dermatological Association.)

Purpose: Several studies investigated endometrial patterns, with respect to pregnancy rates following the transfer of embryos but did not distinguish between single- and multiple-blastocyst procedures. We clarified how the endometrial pattern imaged to transfer a frozen embryo is associated with pregnancy outcomes in single-blastocyst frozen-embryo transfer (sbFET)., Methods: Patients ≤35 years who underwent sbFET on the hormone replacement protocol. We analyzed endometrial patterns' associations with pregnancy outcomes in relation to blastocyst grade and pregnancy-related factors., Results: Of the 1383 cycles, 483 were Lf, 840 were partial-Lf, and 60 were non-Lf. Leaf pattern (Lf): central echogenic line present and continuous. Overall, decreasing distinctness of the central echogenic line was associated with significantly lower rates of clinical pregnancy (Lf: 70.4%; partial-Lf: 58.1%; non-Lf: 28.3%) and live birth (56.3%, 45.5%, and 15.0%) and a higher miscarriage rate (20.0%, 21.7%, and 47.1%). Logistic regressions showed pregnancy and live birth to be significantly more likely and miscarriage less likely in Lf than non-Lf: OR (95% CI): 6.07 (3.24-11.37), 7.43 (3.47-15.39), and 0.20 (0.07-0.57)., Conclusions: Non-Lf presentation was associated with lower rates of pregnancy and live birth, suggesting it signals unsuitable conditions for embryo transfer. We provide information on the pregnancy outcomes of sbFET for endometrial patterns., Competing Interests: The authors declare that there are no conflicts of interest., (© 2024 The Author(s). Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.)

Background and Aims: The difficulty in radiographic confirmation of the presence of stones remains challenging in the treatment of intrahepatic bile duct (IHBD) stones in patients after hepaticojejunostomy (HJ). Peroral direct cholangioscopy (PDCS) enables direct observation of the bile duct and is useful for detecting and removing residual stones; however, its effectiveness is not clearly established in this clinical context., Methods: This single-center, single-arm, prospective study included 44 patients with IHBD who underwent bowel reconstruction with HJ during the study period. Stone removal was performed by using short-type double-balloon enteroscopy. After balloon-occluded cholangiography, the double-balloon enteroscopy was exchanged for an ultra-slim endoscope through the balloon overtube for PDCS. The primary end point was the rate of residual stones detected by PDCS. Secondary end points were success rate of PDCS, residual stone removal with PDCS, procedure time for PDCS, procedure-related adverse events, and stone recurrence rate., Results: PDCS was successful in 39 (89%) of 44 patients, among whom residual stones were detected in 16 (41%) (95% CI, 28%-54%). Twelve patients (75%) had residual stones <5 mm. Stone removal was successful in 15 (94%) patients, and median procedure time for PDCS was 16 minutes (interquartile range, 10-26 minutes). The rate of procedure-related adverse events was 7% (3 of 44); all adverse events improved with conservative treatment. During the median follow-up of 2.1 years (interquartile range, 1.4-3.3 years), the overall probability of recurrence-free status at 1, 2, and 3 years was 100%, 92%, and 86%, respectively., Conclusions: PDCS is a safe and effective procedure for complete stone removal in patients with IHBD stones after HJ., Competing Interests: Disclosure All authors disclosed no financial relationships., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

The introduction of combined antiretroviral therapy (cART) has greatly improved the quality of life of human immunodeficiency virus type 1 (HIV-1)-infected individuals. Nonetheless, the ever-present desire to seek out a full remedy for HIV-1 infections makes the discovery of novel antiviral medication compelling. Owing to this, a new late-stage inhibitor, Lenacapavir/Sunlenca, an HIV multi-phase suppressor, was clinically authorized in 2022. Besides unveiling cutting-edge antivirals inhibiting late-stage proteins or processes, newer therapeutics targeting host restriction factors hold promise for the curative care of HIV-1 infections. Notwithstanding, bone marrow stromal antigen 2 (BST2)/Tetherin/CD317/HM1.24, which entraps progeny virions is an appealing HIV-1 therapeutic candidate. In this study, a novel drug screening system was established, using the Jurkat/Vpr-HiBiT T cells, to identify drugs that could obstruct HIV-1 release; the candidate compounds were selected from the Ono Pharmaceutical compound library. Jurkat T cells expressing Vpr-HiBiT were infected with NL4-3, and the amount of virus release was quantified indirectly by the amount of Vpr-HiBiT incorporated into the progeny virions. Subsequently, the candidate compounds that suppressed viral release were used to synthesize the heterocyclic compound, HT-7, which reduces HIV-1 release with less cellular toxicity. Notably, HT-7 increased cell surface BST2 coupled with HIV-1 release reduction in Jurkat cells but not Jurkat/KO-BST2 cells. Seemingly, HT-7 impeded simian immunodeficiency virus (SIV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) release. Concisely, these results suggest that the reduction in viral release, following HT-7 treatment, resulted from the modulation of cell surface expression of BST2 by HT-7., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Methods for predicting therapeutic response to immune checkpoint inhibitors in cancer therapy are in high demand. In patients with advanced hepatocellular carcinoma (HCC), atezolizumab (anti-programmed cell death-ligand 1 [PD-L1]) and bevacizumab (anti-vascular endothelial growth factor) combination therapy (Atezo/Bev therapy) is a first-line treatment. However, no reliable biomarkers are currently available to predict its efficacy. Here, we examined serum anti-PD-1 autoantibody levels as candidate biomarkers., Methods: We prospectively enrolled 63 patients with advanced HCC who received Atezo/Bev therapy. Serum anti-PD-1 autoantibody levels were measured before treatment using an indirect enzyme-linked immunosorbent assay. The correlation between the titers and response to therapy was statistically examined., Results: Serum anti-PD-1 autoantibody levels were not significantly associated with the treatment response in any patient. However, when examining only patients who received the Atezo/Bev as their first-line therapy, higher anti-PD-1 autoantibody levels were significantly associated with worse overall survival rates. The titer was an independent risk factor for poor prognosis (odds ratio [OR] = 7.8, P  = .013), in addition to a higher neutrophil-to-lymphocyte ratio (OR = 7.1, P  = .009) and lower albumin levels (OR = 14.2, P  = .003)., Conclusion: Serum anti-PD-1 autoantibody levels correlated with the overall survival rate in patients who received Atezo/Bev as first-line therapy. Serum anti-PD-1 autoantibody levels may serve as new biomarkers for predicting the efficacy of immune checkpoint inhibitors in patients with HCC., (© 2024 The Authors.)

In this study, we examined the usefulness of a simpler and more feasible method for determining the optimal timing of artificial insemination and the conditions for its success in six female common bottlenose dolphins. Pregnancy was successfully achieved in five dolphins by performing intrauterine insemination, using chilled semen stored for less than 3 days or frozen semen within 24 hr of exhibiting a peak serum estradiol (E 2 ) level of 100 pg/mL or higher or on the day with a serum E 2 level of approximately 100 pg/mL, measured with a simple measuring device. We concluded that the determining the optimal timing of intrauterine insemination by measuring serum E 2 levels is a simpler and more useful method compared with the conventional approach.

Competing Interests: Disclosure All authors disclosed no financial relationships. Commentary Gastric syphilis is rare and presents in 1% of patients with syphilis. The most common presenting symptom is abdominal pain and fullness (92%), followed by nausea/vomiting (71%), weight loss (60%), and gastric bleeding (35%). Multisystem involvement may be seen, as with our patients who presented with a rash and chancre, but in up to two-thirds of patients, there may be no concurrent extraintestinal manifestation of syphilis. The endoscopic appearance typically consists of multiple annular ulcerations and erosions, sometimes with a purple/brown hue at the ulcer margin, as well as nodular mucosa, thickened gastric folds, and nondistensibility of the stomach. This presentation leaves the clinician with a broad differential diagnosis, including lymphoma, infiltrative tumors, Crohn’s disease, and tuberculosis, to name a few. Histologic examination can demonstrate a chronic gastritis with dense plasmacytic and lymphocytic infiltrate, proliferative endarteritis or endophlebitis, and perivascular cuffing. A high index of suspicion for T pallidum is needed to appropriately diagnose gastric syphilis with serologic testing and to detect spirochetes on gastric biopsy specimens with immunostaining, silver staining, dark field microscopy, or polymerase chain reaction. Treatment is prescribed based on the clinical stage of syphilis and results in full resolution of symptoms. The nonspecific clinical and endoscopic presentation of gastric syphilis indeed makes it “the great imitator” of other gastric diseases. Therefore, as highlighted in these cases, gastric syphilis should be suspected in high-risk patients who present with abdominal symptoms and unusual endoscopic findings. Early diagnosis can lead to prompt treatment and a significant decrease in syphilis-associated morbidity. Deepika Satish, MD, Assistant Professor of Medicine, Baylor College of Medicine, Houston, Texas, USA Amy Tyberg, MD, FASGE, FACG, Associate Editor for Focal Points

Purpose: We compared corneal endothelial cell (CED) loss after Ex-Press (EXP) surgery between patients with primary open-angle glaucoma (POAG) and pseudo-exfoliation glaucoma (PEX)., Patients and Methods: This was a single-facility retrospective study. We included glaucoma patients who had undergone EXP surgery and were followed up > 3 years. We measured the CED before and after (at 12, 24, and 36 months) EXP surgery by noncontact specular microscopy and compared the means of the CED values and CED survival ratios after EXP surgery by paired t-test., Results: We included 119 eyes that underwent EXP surgery, including 60 POAG eyes and 59 PEX eyes. In the POAG group, the mean CED decreased from 2389 ± 321 at baseline to 2230 ± 424 cells/mm 2 after 3 years. In the PEX group, the mean CED decreased from 2111 ± 510 at baseline to 1845 ± 628 cells/mm 2 after 3 years. At the 3-year follow-up, the CED survival ratio was 93.3 ± 12.5% in the POAG group and significantly lower, at 85.0 ± 19.5%, in the PEX group (p = 0.0064). Two cases in the PEX group developed bullous keratopathy., Conclusions: EXP surgery decreased the corneal endothelial cell populations in PEX patients faster than POAG patients., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Some RNAs such as 28S rRNA, U1 small nuclear RNA (snRNA), and Y RNAs are known to be cleaved during apoptosis. The underlying mechanism, functions, and biological significance of RNA degradation in apoptosis remain elusive. Y RNAs are non-coding RNAs widely conserved from bacteria to mammals, and are major components of Ro ribonucleoprotein (RNP) complexes which contain the 60 kDa Ro protein (SS-A) and the 50 kDa La protein (SS-B). The autoantigenic Ro and La proteins were identified by autoantibodies present in the sera from patients with Systemic lupus erythematosus (SLE) and Sjögren's syndrome (SjS). We previously identified novel, functional small RNAs named AGO-taxis small RNAs (ASRs) that are specifically bound to Argonaute protein 1 (AGO1), which are processed from Y RNAs. Cell-free analysis combined with fractionation methods revealed that the apoptosis-specific biogenesis of ASRs or cleavage of Y RNA was induced by truncation of polypyrimidine tract-binding protein 1 (PTBP1), which is an endoribonuclease inhibitor of Y RNAs by caspase 3. Caspase 3-resistant PTBP1 mutant protected cleavage of Y RNAs in apoptosis induced by staurosporine. Furthermore, caspase 3-resistant PTBP1 mutant knock-in mice showed elevated cytokines, dysregulation of the germinal center formation compared to the wild-type mice at LPS stimulation, and high positivity of antinuclear antibody. Those results suggest that cleavage of Y RNAs or biogenesis of ASR during apoptosis has critical biological functions and their deregulation result in immune dysregulation and the formation of autoantibody, possibly leading to the development of autoimmune diseases., (© 2024. The Author(s).)