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The aim of this research was to study and compare the mechanism of action of interleukin (IL)-8, IL-1beta dehydroepiandrosterone sulphate (DHEA-S) and prostaglandin (PG)E2 on the cervix. Five equal groups of pregnant rabbits (n = 45) were tested by either placebo or tested drugs in the form of vaginal suppositories once daily for 3 days. The suppositories contained human recombinant IL-8 (100 ng), IL-1beta (200 ng), DHEA-S (10 mg) or PGE2 (1 mg). All rabbits were tested by one dose, two doses or three doses. Consistency, dilatation and water contents were estimated 24 h after the last dose of treatment. Leukocyte infiltration of the cervices was studied after staining the cervical tissue sections with antirabbit RT2 monoclonal antibodies. Relative collagen concentration was assessed after staining with Picrosirius Red. Collagenase, gelatinase and elastase activities were measured in 100 mg of homogenized cervical connective tissue. Water contents were significantly increased in all tested cervices. Neutrophil numbers were increased in IL-8 and IL-1beta groups after the second dose of treatment (P < 0.0005 and 0.001 respectively). In the PGE2 group, neutrophils were increased after the third dose of treatment, whereas in DHEA-S group no significant changes were observed. Collagen content was significantly decreased in IL-8, IL-1beta and PGE2 groups after the first dose of treatment (P < 0.004, and 0.005 and 0.03 respectively). In the DHEA-S group, the decrease in collagen content occurred after the third dose (P < 0.05). Collagenase activity was markedly increased in IL-8, IL-1, and DHEA-S groups after the second dose of treatment (P < 0.001, 0.003 and 0.007 respectively). No significant increase in collagenase activity was found in PGE2 group. Gelatinase activity was significantly increased in IL-8, IL-1beta, PGE2 and DHEA-S groups after the second dose of treatment (P < 0.008, 0.01, 0.003 and 0.05 respectively). Also, elastase activity was increased after the second dose of treatment in all groups (P < 0.001, 0.001, 0.001 and 0.006 respectively). Our data suggest that ripening of the cervix in rabbit can be initiated by different mechanisms. Cytokines play a vital role in cervical ripening, especially IL-8 and IL-1. IL-8 is one of the factors which could ripen the cervix in a manner similar to the physiological process at term. [ABSTRACT FROM AUTHOR]

Objective Steroid pulse therapy is a regimen involving the intravenous administration of supra-pharmacological doses of corticosteroids in the short term. It is used to treat various inflammatory and autoimmune conditions. However, the strengths and limitations of steroid pulse therapy for induction of remission in type 1 autoimmune pancreatitis (AIP) are unknown. Methods Depending on the steroid therapy regimen administered, the 104 patients with type 1 AIP included in this retrospective study were divided into three groups: conventional oral prednisolone (PSL) regimen (PSL group), intravenous methylprednisolone (IVMP) pulse followed by oral PSL regimen (Pulse+PSL group), and IVMP pulse-alone regimen (Pulse-alone group). We then examined the relapse rate and adverse events among the three groups. Results The Kaplan-Meier estimates of the relapse rate at 36 months after steroid therapy were 13.6% in the PSL group, 13.3% in the Pulse+PSL group, and 46.2% in the Pulse-alone group. The log-rank test revealed that the relapse-free survival in the Pulse-alone group was significantly shorter than that in the PSL (p=0.024) and Pulse+PSL groups (p=0.014). The exacerbation of glucose tolerance after steroid therapy was less frequently observed in the Pulse-alone group (0%) than in the PSL group (17%, p=0.050) and Pulse+PSL groups (26%, p=0.011). Conclusion Although treatment with IVMP pulse alone resulted in unsatisfactory relapse prevention outcomes compared with conventional steroid therapy, the IVMP pulse-alone regimen might be an alternative treatment strategy for type 1 AIP from the perspective of avoiding adverse events from steroids.

Background: Global longitudinal strain (GLS) is reportedly a sensitive marker for early subtle abnormalities in left ventricular (LV) performance of asymptomatic patients with severe aortic stenosis (AS) and preserved LV ejection fraction (LVEF). For symptomatic patients with severe AS and preserved LVEF, however, the association of immediate improvement in GLS after transcatheter aortic valve implantation (TAVI) with long-term outcomes remains uncertain., Methods: This study concerned 151 symptomatic patients with severe AS and preserved LVEF who had undergone TAVI. Echocardiography was performed before TAVI and 7 (7-9) days after TAVI. GLS was determined by means of a two-dimensional speckle-tracking strain using current guidelines. The primary endpoint was defined as a composite endpoint comprising cardiovascular death or re-hospitalization for HF after TAVI over a median follow-up period of 27.7 (11.9-51.4) months., Results: Mean LVEF and GLS were 65 ± 7 % and 12.8 ± 3.4 %, respectively. The Kaplan-Meier curve indicated that patients with acute improvement in GLS after TAVI experienced fewer cardiovascular events than those without such improvement (log-rank P = 0.02). Multivariate analysis showed that non-acute improvement in GLS after TAVI was independently associated with worse outcomes as well as deterioration of the mean transaortic pressure gradient., Conclusion: Assessment of GLS immediately after TAVI is a valuable additional parameter for better management of symptomatic patients with severe AS and preserved LVEF who are scheduled for TAVI., Competing Interests: Conflict of interest H.T. is a consultant for AstraZeneca plc, Ono Pharmaceutical Company, Limited. Pfizer Inc., Otsuka Pharmaceutical Co., Ltd., Daiichi Sankyo Company, Limited, and Novartis International AG. H.O is a consultant for Abbott Vascular Japan and Terumo Co. K.H. has received research funding from Daiichi Sankyo Company, Limited, Actelion Pharmaceuticals Japan, Terumo Corporation, Abbott Vascular Japan, Otsuka Pharmaceutical Company, Limited, Kowa Company, Limited, Takeda Pharmaceutical Company Limited, Nihon Medi-Physics Company Limited, Novartis Pharma Company Limited, Bayer Company Limited, Biotronic Japan Company Limited, FUJIFILM Toyama Chemical Company Limited, Medtronic Japan Company Limited, Sysmex Company Limited. The remaining authors have no conflicts of interest to declare., (Copyright © 2023. Published by Elsevier Ltd.)

Endoscopic resection for GIST has become more widespread in recent years because it is less invasive than surgery. However, when endoscopic resection is performed, a full-layer resection of the gastric wall is often necessary, and extensive suturing is required if perforation occurs, which is a technically challenging procedure. Recently, we reported a new method called endoscopic inversion and strangulation of the muscle layer and resection (EISMR), which consists of endoscopically inverting the muscle layer into the gastric lumen and strangulating the muscle layer with a detachable snare, followed by resection. The study comprised five consecutive patients with gastric GIST ≤50 mm in diameter who underwent EISMR procedures. The main outcomes of the study were en bloc resection rate, R0 resection rate, procedure time, and complications. The results showed that all five patients successfully underwent complete resection without perforation, and the en bloc resection and R0 resection rates were 100%. The median procedure time was 93 min (range, 58-120 min), and there were no major complications. We concluded that EISMR would be a safe and effective technique for endoscopic resection of gastric GISTs and may be an alternative to surgery or endoscopic submucosal dissection., Competing Interests: Conflict of Interest 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/).)

Left ventricular (LV) longitudinal myocardial dysfunction can be observed even in type 2 diabetes mellitus (DM) (T2DM) patients with preserved LV ejection fraction (LVEF), and is considered the earliest marker of DM-related cardiac dysfunction. Furthermore, diabetic nephropathy (DN), a common complication in DM, is strongly associated with LV longitudinal myocardial function in T2DM patients, but its association with type 1 DM (T1DM) has not been fully investigated. We studied 125 asymptomatic T1DM patients with preserved LVEF, and 75 age-, gender-, LVEF-matched non-diabetic healthy controls. Two-dimensional speckle-tracking strain LV was used to assess longitudinal myocardial function as global longitudinal strain (GLS). GLS of T1DM patients was significantly lower than that of normal controls (19.7 ± 3.6% vs. 20.6 ± 1.8%, P = 0.049). GLS of T1DM patients with DN was significantly lower that of T1DM patients without DN (17.3 ± 3.7% vs. 20.2 ± 3.5%, P < 0.001), but that of T1DM patients without DN was similar compared to normal controls (20.6 ± 1.8% vs. 20.2 ± 3.5%, P = 0.37). Moreover, multiple regression analysis identified DN the independent determinant parameters for GLS of T1DM patients also correlated significantly with duration of T1DM. Impaired LV longitudinal myocardial function was observed in asymptomatic T1DM patients with preserved LVEF, and DN was associated with LV longitudinal myocardial dysfunction. These findings are clinically useful for better management of T1DM patients to prevent impending development of cardiovascular disease., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

The human gastrointestinal tract, which constitutes the digestive system, contains a large number of virus particles that maintain organizational homeostasis and health. Conversely, viral pathogens have also attracted attention for their involvement in the pathogenesis of certain cancers, including gastrointestinal cancers. To aid prevention and treatment of these cancers, the relevance of gastrointestinal viral factors as potential risk factors needs to be carefully investigated. This review summarizes and discusses the available literature on the relationship between the development of esophageal, gastric, and colorectal cancers and their corresponding viruses. This review reveals that research on the association between colorectal cancer and viruses, in particular, is still in its infancy compared to the association between HPV and esophageal cancer and between EBV and gastric cancer.

Materials and Methods: This was a retrospective cohort study conducted in two municipal hospitals. We identified 24 patients with SNADETs of 3-18 mm in diameter who underwent UEMR or GIEMR. One lesion was excluded from the analysis because it was found to be in the stomach after surgery. The primary outcome was procedure time., Results: GIEMR significantly reduced the procedure time compared with UEMR (5 min vs. 10 min, P = 0.016). There was no significant difference between the UEMR and GIEMR groups for en bloc resection rate (93% vs. 100%, P = 1.0) and R0 resection rate (57% vs. 80%, P = 0.39). No serious complications were observed in either group., Conclusions: GIEMR of SNADET has the potential to reduce procedure time compared with UEMR and may be particularly effective in areas where immersion in water is difficult., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Takeshi Yamashina et al.)

Background and Aim: To clarify the clinicoepidemiological characteristics of immunoglobulin G4 (IgG4)-related disease (IgG4-RD) with malignancy, a nationwide epidemiological survey was conducted., Methods: Immunoglobulin G4-related disease patients with malignancy who had visited selected hospitals in Japan were surveyed. The study consisted of two stages: the number of IgG4-RD patients with malignancy was estimated by the first questionnaire and their clinicoepidemiological characteristics were assessed by the second questionnaire., Results: The frequencies of autoimmune pancreatitis (AIP), IgG4-related sialadenitis, IgG4-related eye disease, IgG4-related kidney disease, and IgG4-related retroperitoneal fibrosis were 44.7%, 20.8%, 14.0%, 5.16%, and 5.12%, respectively. The overall prevalence of malignant disease in IgG4-RD cases was estimated to be 10 900 per 100 000 cases, which was significantly higher than that of malignant disease in the general population. The prevalence of malignant lymphoma in IgG4-RD cases was the highest and was estimated to be 1985 per 100 000 cases. IgG4-related kidney disease had the highest frequency of malignant disease (17.1%). In data from 200 patients, 61 (30.5%) cases of cancer were found 2 years or more before the IgG4-RD diagnosis, 92 cases (46%) during the 1 year preceding or following IgG4-RD diagnosis, and 62 cases of cancer (31%) 2 or more years following IgG4-RD diagnosis., Conclusions: The nationwide survey for IgG4-RD with malignancy in Japan showed that IgG4-RD may be related with malignant diseases., (© 2022 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

We investigated the characteristics of patients with non-valvular atrial fibrillation (NVAF) and left atrial (LA) appendage (LAA) thrombus who had been given appropriate oral anticoagulation therapy. We studied 737 NVAF patients who were scheduled for catheter ablation or electrical cardioversion. All patients received appropriate oral anticoagulation therapy for at least 3 weeks prior to echocardiography in accordance with the guidelines. Whether LAA thrombus was present or absent on transesophageal echocardiography (TEE) was determined by at least three senior echocardiologists. LAA thrombi were observed in 22 patients (3.0%). Multivariate logistic regression analysis showed that LAA flow and LA volume index were both independent predictors of LAA thrombus formation; however, LAA flow (≤ 18 cm/s) was indicated as a more powerful predictor. Moreover, the prevalence of LAA thrombus formation in patients with NVAF without LA enlargement (LA volume index ≤ 34 mL/m 2 ) was extremely rare (0.4%). LAA thrombus formation in patients with a mildly dilated LA volume index of 34-49.9 mL/m 2 and paroxysmal AF was also extremely rare (0.0%). LAA flow is strongly associated with LAA thrombus formation, even in NVAF patients treated with appropriate oral anticoagulation therapy. Augmented oral anticoagulation therapy or transcatheter or surgical LAA closure should be considered for such patients, especially for those with an LAA flow < 18 cm/s. Furthermore, TEE for evaluating LAA thrombus before catheter ablation or electrical cardioversion may be unnecessary for NVAF patients who are undergoing appropriate oral anticoagulation therapy, depending on LA size., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

The most serious adverse effect of anthracycline chemotherapy is progressive dose-dependent left ventricular (LV) dysfunction, and a total cumulative doxorubicin dose ≥ 240 mg/m 2 has been classified as putting patients at high risk for developing cardiac dysfunction. Hypertension is the single most important risk factor for heart failure and chemotherapy-induced LV dysfunction, but the effect of hypertension on the total cumulative doxorubicin dose to prevent the development of LV dysfunction in patients scheduled for anthracycline chemotherapy remains uncertain. The aim of this study was to investigate the effect of hypertension on the optimal total cumulative anthracycline dose to prevent the development of LV dysfunction in patients with malignant lymphoma. We retrospectively studied 92 patients with malignant lymphoma and preserved LV ejection fraction (LVEF) who underwent anthracycline chemotherapy. Echocardiography was performed before and 2 months after anthracycline chemotherapy. LV hypertrophy (LVH) was defined as concentric hypertrophy, and LV dysfunction after chemotherapy as a relative decrease in LVEF ≥ 5%. The cutoff value of the total cumulative doxorubicin dose for the development of LV dysfunction was lower for hypertensive patients (n = 23) than for non-hypertensive patients (n = 69) (259.3 mg/m 2 vs. 358.9 mg/m 2 ). Importantly, the cutoff value of the total cumulative doxorubicin dose to prevent the development of LV dysfunction in hypertensive patients with LVH was even lower at 40.1 mg/m 2 . A lower cumulative anthracycline dose can cause LV dysfunction in hypertensive patients with malignant lymphoma, especially when complicated by LVH. Our findings can thus be expected to have clinical implications for better management of such patients., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Background and Aim: Diagnostic support using artificial intelligence may contribute to the equalization of endoscopic diagnosis of colorectal lesions. We developed computer-aided diagnosis (CADx) support system for diagnosing colorectal lesions using the NBI International Colorectal Endoscopic (NICE) classification and the Japan NBI Expert Team (JNET) classification., Methods: Using Residual Network as the classifier and NBI images as training images, we developed a CADx based on the NICE classification (CADx-N) and a CADx based on the JNET classification (CADx-J). For validation, 480 non-magnifying and magnifying NBI images were used for the CADx-N and 320 magnifying NBI images were used for the CADx-J. The diagnostic performance of the CADx-N was evaluated using the magnification rate., Results: The accuracy of the CADx-N for Types 1, 2, and 3 was 97.5%, 91.2%, and 93.8%, respectively. The diagnostic performance for each magnification level was good (no statistically significant difference). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the CADx-J were 100%, 96.3%, 82.8%, 100%, and 96.9% for Type 1; 80.3%, 93.7%, 94.1%, 79.2%, and 86.3% for Type 2A; 80.4%, 84.7%, 46.8%, 96.3%, and 84.1% for Type 2B; and 62.5%, 99.6%, 96.8%, 93.8%, and 94.1% for Type 3, respectively., Conclusions: The multi-class CADx systems had good diagnostic performance with both the NICE and JNET classifications and may aid in educating non-expert endoscopists and assist in diagnosing colorectal lesions., (© 2021 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Left ventricular (LV) involvement in diabetic cardiomyopathy has been reported; however, only limited data exist on right ventricular (RV) involvement. Therefore, our purpose was to investigate RV systolic dysfunction and its association with LV longitudinal myocardial dysfunction in patients with type 2 diabetes mellitus (T2DM) and preserved LV ejection fraction (LVEF)., Methods: We studied 177 T2DM patients with preserved LVEF and 79 age-, sex-, and LVEF-matched healthy volunteers. LV longitudinal myocardial function was assessed as global longitudinal strain (GLS), and RV systolic function was assessed as RV free-wall strain, and predefined cutoff values for subclinical dysfunction were set at GLS < 18% and RV free-wall strain < 20%, respectively., Results: RV free-wall strain in T2DM patients was significantly lower than that in normal controls (19.3% ± 4.8% vs. 24.4% ± 5.1%; P < 0.0001). RV free-wall strain in T2DM patients and LV longitudinal dysfunction was similar compared to that in T2DM patients without (19.0 ± 4.5% vs. 19.6 ± 5.0%, P = 0.40). Furthermore, multivariate logistic regression analyses showed that GLS was independently associated with RV systolic dysfunction as well as mitral inflow E and mitral e' annular velocities ratio (odds ratio, 1.16; 95% confidence interval: 1.03-1.31; P < 0.05). Sequential logistic models evaluating the association of RV systolic dysfunction in T2DM patients showed an improvement in clinical variables (χ 2  = 6.2) with the addition of conventional echocardiographic parameters (χ 2  = 13.4, P < 0.001) and a further improvement with the addition of GLS (χ 2  = 20.8, P < 0.001)., Conclusion: RV subclinical systolic dysfunction was observed in T2DM patients with preserved LVEF and was associated with LV longitudinal myocardial dysfunction. Our findings may provide additional findings for the management of T2DM patients., (© 2021. The Author(s).)

Purposes: The closure of atrial septal defect (ASD) is associated with a significant reduction in right ventricular (RV) overload and an improvement in functional capacity in most adults with ASD. However, a subset of patients remains symptomatic even after closure due to therapeutic delay. To date, no clinically robust preoperative predictor of postoperative residual symptoms has been clearly identified., Methods: In this study, 120 adult patients with ASD and 39 controls were investigated. As an index of RV myocardial deformation, RV global longitudinal strain (RV-GLS) was evaluated. The degree of coupling between RV and pulmonary artery (PA) was quantified by the tricuspid annular plane systolic excursion (TAPSE) divided by the PA systolic pressure (PASP)., Results: Compared to controls, baseline RV-GLS was significantly greater (- 27 ± 7 vs. - 23 ± 5%, P = 0.02) and TAPSE/PASP ratio was severely impaired (0.8 ± 0.3 vs. 2.1 ± 1.6 mm/mmHg, P < 0.01) in ASD patients. At 6 months after closure, 15 patients (12.5%) remained symptomatic. In patients without residual symptoms, TAPSE/PASP ratio significantly improved from 0.9 ± 0.3 to 1.0 ± 0.6 mm/mmHg (P = 0.02), and RV-GLS normalized (from - 28 ± 11 to - 24 ± 7%, P < 0.01) after closure. However, RV-GLS and TAPSE/PASP ratio showed no significant change in ASD patients with residual symptoms. On multivariate analysis, preoperative TAPSE/PASP ratio (odds ratio [OR] 0.034, 95% confidence interval [CI] 0.000-0.604, P = 0.03) and pulmonary vascular resistance index ([PVRI], OR 1.011, 95% CI 1.000-1.021, P < 0.05) were associated with the postoperative symptomatic status., Conclusion: In terms of integrated assessment of the RV-PA unit, preoperative TAPSE/PASP ratio and PVRI were important determinants of residual symptoms after ASD closure., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Objectives: A single-balloon overtube (SBO) can improve poor scope operability during colonic endoscopic submucosal dissection (ESD). We aimed to evaluate the clinical usefulness of SBO for ESD in the proximal colon and the predictive factors for cases in which SBO is useful., Methods: A total of 88 tumors located in the proximal colon resected by balloon-assisted ESD (BA-ESD) using SBO and 461 tumors resected by conventional ESD (C-ESD) between June 2015 and November 2020 were considered. Seventy-eight tumors each in the BA-ESD and C-ESD groups were matched by propensity score matching. ESD outcomes were compared between the groups, and a decision tree analysis was performed to explore the predictive factors for cases in which SBO is useful., Results: There were no significant differences between the groups in the major outcomes such as en bloc resection rate (95% vs. 99%, p = 0.17), R0 resection rate (92% vs. 96%, p = 0.30), mean dissection speed (16 mm 2 /min vs. 16 mm 2 /min, p = 0.53), and intraoperative perforation rate (5% vs. 6%, p = 0.73). Even when considering cases with poor preoperative scope operability, there were no significant differences between the groups. Comparison of tumors ≥40 mm in diameter between the groups confirmed that the intraoperative perforation rate was significantly lower in the BA-ESD group than in the C-ESD group (0% vs. 24%, p = 0.0188)., Conclusion: SBO is useful for ESD of tumors ≥40 mm in diameter in the proximal colon to prevent intraoperative perforation, which usually has a long procedure time., Competing Interests: The authors declare no conflict of interest for this article., (© 2021 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)