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We investigated the differences in displacement of the outer and inner macular retina toward the optic disc after vitrectomy with internal limiting membrane (ILM) peeling for epiretinal membrane (ERM). Foveal avascular zone (FAZ) area changes were also investigated.Retrospective observational study METHODS: This retrospective observational case series included 45 eyes of 43 patients that underwent vitrectomy with ERM and ILM peeling for ERM and 38 normal eyes. The locations of the centroid of the FAZ (C-FAZ, center of the foveal inner retina) and foveal bulge (center of the foveal outer retina) were determined using 3×3mm superficial optical coherence tomography angiography. C-FAZ and foveal bulge displacements, and the pre- and postoperative FAZ areas and their associated factors, were investigated.Postoperative C-FAZ dislocated significantly more toward the optic disc than in pre-operative or normal eyes (P0.001). C-FAZ and foveal bulge displaced toward the optic disc after surgery; C-FAZ showed significantly greater displacement than foveal bulge (P0.001). The pre- and postoperative FAZ areas were correlated (P=0.01). Preoperative FAZ areas ≧0.10mmILM peeling during vitrectomy for ERM caused larger displacement of the inner and smaller displacement of the outer retinas, towards the optic disc. Postoperative changes in the FAZ area were dependent on the baseline FAZ area, but not on the foveal displacement. ILM may physiologically exert centrifugal tractional forces on the fovea.

We aimed to clarify the prognostic factors for patients with esophageal squamous cell carcinoma (ESCC) invading into the muscularis mucosa (pT1a-MM) or submucosa (pT1b-SM) after endoscopic submucosal dissection (ESD).This retrospective study enrolled such patients at 21 institutions in Japan between 2006 and 2017. We evaluated 15 factors, including pathological risk categories for ESCC-specific mortality, six non-cancer-related indices, and treatment strategies.In the analysis of 593 patients, the 5-year overall and disease-specific survival rates were 83.0% and 97.6%, respectively. In a multivariate Cox analysis, male sex (hazard ratio [HR] 3.56), Charlson comorbidity index (CCI) ≥3 (HR 2.53), ages of 75-79 (HR 1.61) and ≥80 years (HR 2.04), prognostic nutrition index (PNI)45 (HR 1.69), and pathological intermediate-risk (HR 1.63) and high-risk (HR 1.89) were prognostic factors. Subsequently, we developed a clinical risk classification for non-ESCC-related mortality based on the number of prognostic factors (age ≥75 years, male sex, CCI ≥3, PNI45): low-risk, 0; intermediate-risk, 1-2; and high-risk, 3-4. The 5-year non-ESCC-related mortality rates for patients without additional treatment were 0.0%, 10.2%, and 45.8% in the low-, intermediate-, and high-risk groups, respectively. Meanwhile, the 5-year ESCC-specific mortality rates for the pathological low-, intermediate-, and high-risk groups were 0.3%, 5.3%, and 18.2%, respectively.We clarified prognostic factors for patients with pT1a-MM/pT1b-SM ESCC after ESD. The combined assessment of non-ESCC- and ESCC-related mortalities by the two risk classifications might help clinicians in deciding treatment strategies for such patients.

Engineering of NG34 to insert the sequence of the scFv against PD-1

Supplementary figure legends

Purpose:Glioblastoma (GBM) is resistant to standard of care. Immune checkpoints inhibitors (such as anti-PD-1 mAbs) efficiently restore antitumor T-cell activity. We engineered a new oncolytic herpes simplex virus (oHSV) expressing a single-chain antibody against PD-1 (scFvPD-1) to evaluate its efficacy in mouse models of GBM.Experimental Design:NG34scFvPD-1 expresses the human GADD34 gene transcriptionally controlled by the Nestin promoter to allow replication in GBM cells and a scFvPD-1 cDNA transcriptionally controlled by the CMV promoter. ELISA assays were performed to detect binding of scFvPD-1 to mouse and human PD-1. In vitro cytotoxicity and replication assays were performed to measure NG34scFvPD-1 oncolysis, and scFvPD-1 expression and secretion were determined. In vivo survival studies using orthotopic mouse GBM models were performed to evaluate the therapeutic potency of NG34scFvPD-1.Results:NG34scFvPD-1–infected GBM cells express and secrete scFvPD-1 that binds mouse PD-1. The introduction of the scFvPD-1 sequence in the viral backbone does not alter the oncolytic properties of NG34scFvPD-1. In situ NG34scFvPD-1 treatment improved the survival with a tail of durable survivorship in 2 syngeneic immunocompetent mouse models of GBM. Mice that survived the first GBM challenge rejected the second challenge of GBM when implanted in the contralateral hemisphere. However, this was not true when athymic mice were employed as the recipients of the second challenge, consistent with the need for an intact immune system to obtain a memory response.Conclusions:NG34scFvPD-1 treatment induces a durable antitumor response in 2 preclinical mouse models of GBM with evidence for antitumor memory.

Purification of the scFvPD-1 from HEK293 cells

In vivo comparison of scFvPD-1 production and viral gene expression in mouse and human GBM cells

Supplementary Table 1. Dose-response effects of human glioblastoma cells after treatment with NG34 or rQNestin34.5. Supplementary Figure S1. A, The dose-response curves represent cell viability assay for human astrocytes. Intracellular ATP was measured as an index of cell viability, five days after infection of human astrocyte cells with NG34 or rQNestin34.5. Data were normalized to maximum and minimum values before plotting the averaged values of six replicates with S.D. error bars and non-linear dose-response curves. Ranges of 50% effective doses (ED50) at 95% confidence intervals are 0.00094-0.0034 pfu (NG34) and 0.0011-0.0024 puf (rQNestin34.5), and values of R2 are 0.9423 (NG34) and 0.9748 (rQNestin34.5), respectively. B, viral replication in normal tissues was measured by titrating viral yields collected from cultured human astrocytes after HSV1 F strain (wild-type), rHSVQ, NG34 or rQNestin34.5 at 0.1 of their MOIs. Error bars represent S.D (n = 4). Supplementary Figure S2. The dose-response curves represent are obtained from the cell viability assay used in Table. 1. Supplementary Figure S3. NG34-gCRliFluc and rHSVQ-gCRliFluc oHSV were generated as described in the Materials and Methods section . Supplementary Figure S4. Bioluminescent imaging of xenografted human glioma indicates tumor regression upon oHSV treatment. Supplementary Figure S5. Reproducibility of therapeutic efficacy of NG34 in different models in vivo. Supplementary Figure S6. Gene expression of cytokines in mouse brains with NG34 inoculation. Supplementary Figure S7. Immunohistochemistry of the brains of athymic mice after the HSV-1 inoculation.

Purpose: Glioblastoma (GBM) is the most common primary central nervous system cancer in adults. Oncolytic HSV-1 (oHSV) is the first FDA-approved gene therapy approach for the treatment of malignant melanoma. For GBM, oHSVs need to be engineered to replicate within and be toxic to the glial tumor but not to normal brain parenchymal cells. We have thus engineered a novel oHSV to achieve these objectives.Experimental Design: NG34 is an attenuated HSV-1 with deletions in the genes encoding viral ICP6 and ICP34.5. These mutations suppress virus replication in nondividing brain neurons. NG34 expresses the human GADD34 gene under transcriptional control of a cellular Nestin gene promoter/enhancer element, whose expression occurs selectively in GBM. In vitro cytotoxicity assay and survival studies with mouse models were performed to evaluate therapeutic potency of NG34 against glioblastoma. In vivo neurotoxicity evaluation of NG34 was tested by intracerebral inoculation.Results: NG34 replicates in GBM cells in vitro with similar kinetics as those exhibited by an oHSV that is currently in clinical trials (rQNestin34.5). Dose–response cytotoxicity of NG34 in human GBM panels was equivalent to or improved compared with rQNestin34.5. The in vivo efficacy of NG34 against two human orthotopic GBM models in athymic mice was similar to that of rQNestin34.5, whereas intracerebral injection of NG34 in the brains of immunocompetent and athymic mice showed significantly better tolerability. NG34 was also effective in a syngeneic mouse glioblastoma model.Conclusions: A novel oHSV encoding GADD34 is efficacious and relatively nontoxic in mouse models of GBM. Clin Cancer Res; 24(11); 2574–84. ©2018 AACR.

Background/Purpose: With the spread of thrombus retrieval procedures, the demand for immediate diagnosis and severity assessment of ischemic stroke is increasing, but current standard method using ASPECTS is semi-quantitative, and has low consistency among physicians. We develop and validate the fully automatic machine learning-based ischemic core segmentation model based only on non-contrast-enhanced computed tomography (NCCT). Materials and Methods: This multicenter retrospective study included patients with anterior circulation acute ischemic stroke who received both CT and MRI before thrombolysis or recanalization treatment between 2013 to 2019. The ischemic core on CT was manually delineated referencing the DWI and ADC map. A deep learning-based ischemic core segmentation model was developed using the derivation cohort data from 3 institutions (n=313), and the model performance was validated on the external validation cohort data from 3 institutions (n=106). Results: On the validation cohort, the median time between CT and MRI was 18 min. The ischemic core volume calculated by the DL model was significantly correlated with the reference standard (Pearson r=0.91, p4.5hr from onset; Pearson r=0.93, p70mL) with a sensitivity of 84.2%, specificity of 97.7%, and AUC of 0.91. Conclusions: A segmentation model of cerebral ischemic core volume of the anterior circulation based on NCCT using deep learning showed good correlation with the correct labels generated with reference to MRI.

Oncolytic virus therapy can increase the immunogenicity of tumors and remodel the immunosuppressive tumor microenvironment, leading to an increased antitumor response to immune-checkpoint inhibitors. Here, we investigated the therapeutic potential of G47Δ, a third-generation oncolytic herpes simplex virus type 1, in combination with immune-checkpoint inhibitors using various syngeneic murine subcutaneous tumor models. Intratumoral inoculations with G47Δ and systemic anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody administration caused an enhanced antitumor activity when combined and worked synergistically. Conversely, the efficacy of G47Δ in combination with anti-programmed cell death protein-1 (PD-1) antibody was equivalent to that of the anti-PD-1 antibody alone in all murine models examined. The combination of intratumoral G47Δ and systemic anti-CTLA-4 antibody was shown to recruit effector T cells into the tumor efficiently while decreasing regulatory T cells. Furthermore, a wide range of gene signatures related to inflammation, lymphoid lineage, and T cell activation was highly upregulated with the combination therapy, suggesting the conversion of immune-insusceptible tumors to immune susceptible. The therapeutic effect proved tumor specific and long lasting. Immune cell subset depletion studies demonstrated that CD4+ T cells were required for synergistic curative activity. The results depict the dynamics of immune modulation of the tumor microenvironment and provide a clinical rationale for using G47Δ with immune checkpoint inhibitors., Graphical abstract, G47Δ, a third-generation oncolytic HSV-1, works synergistically with CTLA-4 inhibition, but not PD-1, in murine tumor models. The combination therapy causes increased effector T cells, decreased Tregs, and upregulated gene signatures related to immunogenicity within tumors. The therapeutic effect proved tumor specific and long lasting and requires CD4+ cells for synergy.

No prediction scores for the mortality of both inpatients and outpatients who developed nonvariceal upper gastrointestinal bleeding (UGIB) without endoscopic findings have been established. We aimed to derive and validate a novel prediction score for in-hospital mortality. We conducted a three-stage, multicenter retrospective study. In the derivation stage, patients with nonvariceal UGIB at six institutions were enrolled to derive the prediction score by logistic regression analysis. External validation of the score was performed to analyze discrimination by patients at six other institutions. Then the performance of this score was compared with that of four existing scores. We enrolled 1380 and 825 patients in the derivation and validation cohorts, respectively. A prediction score (CHAMPS-R Score) comprising seven variables (Charlson Comorbidity Index ≥ 2, in-hospital onset, albumin

Although additional treatment is considered for patients with esophageal squamous cell carcinoma (ESCC) invading into the muscularis mucosa (pT1a-MM) or submucosa (pT1b-SM) after endoscopic submucosal dissection (ESD), the actual benefits of this method remain to be elucidated.We aimed to evaluate the prognostic benefits of additional treatment in such patients.Between 2006 and 2017, we enrolled patients with pT1a-MM/pT1b-SM ESCC after ESD at 21 institutions in Japan. Overall survival (OS) and disease-specific survival (DSS) were compared between the additional treatment and follow-up groups after propensity score matching, to reduce the bias of baseline characteristics. A subgroup analysis was performed according to the pathological findings: category A, pT1a-MM but negative for lymphovascular invasion (LVI) and vertical margin (VM); category B, tumor invasion into the submucosa ≤ 200 μm but negative for LVI and VM; category C, others.Of 593 patients with pT1a-MM/pT1b-SM ESCC after ESD, 101 matched pairs were extracted after propensity score matching. The OSs were similar between the additional treatment and follow-up groups (80.6% vs. 78.6% in 5 years; P = 0.972). In a subgroup analysis, the OS in the additional treatment group was significantly lower than that in the follow-up group (65.7% vs. 95.2% in 5 years; P = 0.037) in category A, whereas OS did not significantly differ in category C (76.8% vs. 69.5% in 5 years; P = 0.360).Additional treatment after ESD in patients with pT1a-MM/pT1b-SM ESCC was not associated with an improved prognosis.

In this study, the effects of selectively yellow-cut lenses on contrast sensitivity were investigated in healthy young and middle-aged individuals and elderly patients with cataract. Contrast sensitivity in middle-aged healthy individuals and elderly patients with cataract was higher when measured while the subjects were wearing selectively yellow-cut lens (NeoContrast; Mitsui Chemicals, Inc., Tokyo, Japan) compared to no yellow-cut lens. Controlling optical wavelength could provide an improved quality of vision through improved visibility.

This paper estimates the effect of comprehensive and diverse regional childcare services on Japanese women’s labour participation and well-being. On the basis of a sequence of childcare policies in...

Background and purpose:Oscillatory shear stress could not be directly measured in consideration of direction, although cerebrospinal fluid has repetitive movements synchronized with heartbeat. Our aim was to evaluate the important of oscillatory shear stress in the cerebral aqueduct and foramen magnum in idiopathic normal pressure hydrocephalus by comparing it with wall shear stress and the oscillatory shear index in patients with idiopathic normal pressure hydrocephalus., Materials and methods:By means of the 4D flow application, oscillatory shear stress, wall shear stress, and the oscillatory shear index were measured in 41 patients with idiopathic normal pressure hydrocephalus, 23 with co-occurrence of idiopathic normal pressure hydrocephalus and Alzheimer-type dementia, and 9 age-matched controls. These shear stress parameters at the cerebral aqueduct were compared with apertures and stroke volumes at the foramen of Magendie and cerebral aqueduct., Results:Two wall shear stress magnitude peaks during a heartbeat were changed to periodic oscillation by converting oscillatory shear stress. The mean oscillatory shear stress amplitude and time-averaged wall shear stress values at the dorsal and ventral regions of the cerebral aqueduct in the idiopathic normal pressure hydrocephalus groups were significantly higher than those in controls. Furthermore, those at the ventral region of the cerebral aqueduct in the idiopathic normal pressure hydrocephalus group were also significantly higher than those in the co-occurrence of idiopathic normal pressure hydrocephalus with Alzheimer-type dementia group. The oscillatory shear stress amplitude at the dorsal region of the cerebral aqueduct was significantly associated with foramen of Magendie diameters, whereas it was strongly associated with the stroke volume at the upper end of the cerebral aqueduct rather than that at the foramen of Magendie., Conclusions:Oscillatory shear stress, which reflects wall shear stress vector changes better than the conventional wall shear stress magnitude and the oscillatory shear index, can be directly measured on 4D flow MR imaging. Oscillatory shear stress at the cerebral aqueduct was considerably higher in patients with idiopathic normal pressure hydrocephalus.

Objects Although a recent study showed the cancer incidence of Barrett's esophagus (BE) to be 1.2%/year in 251 patient-years in Japan, the long-term outcomes remain unclear. The present study estimated the cancer risk of BE in Japan using our original prospective multicenter cohort. Methods A total of 98 patients with BE of maximum length of ≥2 cm were enrolled during the period of 2010 to 2012 and received at least 1 follow-up endoscopy over 5 years thereafter. Cancer incidence rates with 95% confidence interval for occurrence of esophageal adenocarcinoma were calculated as the number of events divided by patient-years of follow-up and were expressed as %/year. Results Overall, the median endoscopic follow-up period was 59.9 (first and third quartiles: 48.5-60.8) months, constituting a total of 427 patient-years of observation. Since 2 esophageal adenocarcinoma cases developed, the cancer incidence was 0.47% (0.01%-1.81%)/year. The cancer incidence was 0.39% (-0.16%-2.44%) in 232 patient-years and 0.31% (-0.13%-1.95%)/year in 318 patient-years for 55 cases with specialized intestinal metaplasia and 70 with BE ≥3 cm (maximum), respectively. At the end of follow-up, 12 of 92 patients (13.0%) died, but none died from esophageal adenocarcinoma. Conclusion This is the largest prospective follow-up study with endoscopy to investigate the incidence of esophageal adenocarcinoma in unequivocal BE with the maximum length of ≥2 cm in Japan. Although a further large-scale study will be required to validate our results, the cancer risk of BE in Japan would be lower than previously reported (0.47% vs. 1.2%/year).

Little is known about the prognostic factors for survival after endoscopic submucosal dissection (ESD) in elderly patients with early gastric cancer (EGC). The aim of this study is to determine prognostic factors and a prediction model of 3-year survival after ESD for EGC in patients aged ≥ 85 years.We retrospectively evaluated the clinical outcomes of 740 patients with EGC aged ≥ 85 years, who were treated by ESD at 30 institutions in Japan. Overall survival (OS) and disease-specific survival (DSS) were calculated with the Kaplan-Meier method. Prediction models for 3-year OS after ESD were estimated using the Cox proportional hazards model based on Uno's C-statistics.During the follow-up period, 309 patients died of any cause and 10 patients died of gastric cancer. OS and DSS after 3 years were 82.7% and 99.2%, respectively. No significant differences in OS were found among curability categories. The Cox proportional hazards model revealed the geriatric nutritional risk index (GNRI) and the Charlson comorbidity index (CCI) to be predictors of 3-year survival. We established a final model (EGC-2 model) expressed by GNRI - (2.2×CCI) with a cutoff value of 96. The overall survival rate was significantly lower in the model value 96 group than in the model value ≥ 96 group (P 0.001).The prediction model using GNRI and CCI will be useful to support decision-making for the treatment of EGC in elderly patients aged ≥ 85 years.

This study was performed to investigate the association between changes in retinal layer thickness and perfusion status in the extramacular areas of eyes with diabetic retinopathy.Retrospective cross-sectional study.The medical records of 70 eyes from 55 patients with diabetes were reviewed. The status of retinal perfusion in extramacular areas was evaluated using swept-source optical coherence tomography angiography. Retinal layer thickness was measured in nonperfused areas (NPA) larger than 2 optic disc areas, areas of sparse capillaries (SC), and perfused areas (PA-DR) in eyes with diabetic retinopathy. Retinal layer thickness was also measured in perfused areas in eyes without diabetic retinopathy (PA-NDR), and the thicknesses were then compared. In addition, swept-source optical coherence tomography angiography images and retinal thickness maps were compared to investigate the distribution of retinal thickness changes and spatial relationships to areas of retinal perfusion.The inner retinal thickness in NPA was significantly thinner than the inner retinal thicknesses in SC, PA-DR, and PA-NDR (all P.001), and the inner retinal thickness in PA-NDR and SC was significantly thinner than that in PA-DR (P = .006 and .031, respectively). In a distribution analysis of the extramacular areas, NPA spatially overlapped with areas of severe retinal thinning in all locations. Local thickening with smooth shapes and gentle borders overlapped with areas of capillary abnormalities. Neovascularization was present at sites of local thickening with irregular shapes and unnatural clear borders.Changes in retinal layer thickness were associated with perfusion status, suggesting that retinal thickness maps can reflect perfusion status.

ObjectiveTo date, no randomised trials have compared the efficacy of vonoprazan and amoxicillin dual therapy with other standard regimens for Helicobacter pylori treatment. This study aimed to investigate the efficacy of the 7-day vonoprazan and low-dose amoxicillin dual therapy as a first-line H. pylori treatment, and compared this with vonoprazan-based triple therapy.DesignThis prospective, randomised clinical trial was performed at seven Japanese institutions. Patients with H. pylori–positive culture test and naive to treatment were randomly assigned in a 1:1 ratio to either VA-dual therapy (vonoprazan 20 mg+amoxicillin 750 mg twice/day) or VAC-triple therapy (vonoprazan 20 mg+amoxicillin 750 mg+clarithromycin 200 mg twice/day) for 7 days, with stratification by age, sex, H. pylori antimicrobial resistance and institution. Eradication success was evaluated by 13C-urea breath test at least 4 weeks after treatment.ResultsBetween October 2018 and June 2019, 629 subjects were screened and 335 were randomised. The eradication rates of VA-dual and VAC-triple therapies were 84.5% and 89.2% (p=0.203) by intention-to-treat analysis, respectively, and 87.1% and 90.2% (p=0.372) by per-protocol analysis, respectively. VA-dual was non-inferior to VAC-triple in the per-protocol analysis. The eradication rates in strains resistant to clarithromycin for VA-dual were significantly higher than those for VAC-triple (92.3% vs 76.2%; p=0.048). The incidence of adverse events was equal between groups.ConclusionThe 7-day vonoprazan and low-dose amoxicillin dual therapy provided acceptable H. pylori eradication rates and a similar effect to vonoprazan-based triple therapy in regions with high clarithromycin resistance.Trial registration numberUMIN000034140.

Piglets aged approximately 50 days exhibited diarrhea and wasting. Multiple white foci were detected in the colon of a dead piglet; histopathological findings revealed multifocal ulcers and crypt abscesses with Entamoeba trophozoites and gram-negative bacilli in the piglet. These pathogens were identified as Entamoeba polecki subtype 3 and Salmonella enterica serovar Typhimurium, respectively. Numerous E. polecki subtype 3 trophozoites were located on the edge of the ulcerative and necrotic lesions in the lamina propria. Crypt abscesses were associated with S. Typhimurium. These results suggest that E. polecki subtype 3 caused multifocal ulcerative colitis accompanied by crypt abscesses with S. Typhimurium in the piglet. This study is the first report of colitis with E. polecki subtype 3 and S. Typhimurium coinfection.

A 1-month-old rabbit, imported as a pet by a distributor, died suddenly in the quarantine period in Japan due to suppurative pleuropneumonia. A bacterial isolate from its right lung was identified as Pasteurella multocida serotype A: 11. The isolate was classified as ST204 using the RIRDC scheme of multilocus sequence typing, suggesting that the isolate was genetically related to European isolates of the same sequence type listed in the PubMLST database and not to four other isolates that originated from past imported rabbits. In the immunohistochemical assay, an antiserum recognizing the somatic serotype 11 antigen generated from chicken could specifically detect P. multocida, indicating that the antiserum for somatic serotyping was useful for immunohistochemical diagnosis of rabbit pasteurellosis.

This investigator-initiated, phase 2, single-arm trial primarily assessed the efficacy of G47∆, a triple-mutated, third-generation oncolytic herpes simplex virus type 1, in 19 adult patients with residual or recurrent, supratentorial glioblastoma after radiation therapy and temozolomide (UMIN-CTR Clinical Trial Registry UMIN000015995). G47Δ was administered intratumorally and repeatedly for up to six doses. The primary endpoint of 1-yr survival rate after G47∆ initiation was 84.2% (95% confidence interval, 60.4–96.6; 16 of 19). The prespecified endpoint was met and the trial was terminated early. Regarding secondary endpoints, the median overall survival was 20.2 (16.8–23.6) months after G47∆ initiation and 28.8 (20.1–37.5) months from the initial surgery. The most common G47∆-related adverse event was fever (17 of 19) followed by vomiting, nausea, lymphocytopenia and leukopenia. On magnetic resonance imaging, enlargement of and contrast-enhancement clearing within the target lesion repeatedly occurred after each G47∆ administration, which was characteristic to this therapy. Thus, the best overall response in 2 yr was partial response in one patient and stable disease in 18 patients. Biopsies revealed increasing numbers of tumor-infiltrating CD4+/CD8+ lymphocytes and persistent low numbers of Foxp3+ cells. This study showed a survival benefit and good safety profile, which led to the approval of G47∆ as the first oncolytic virus product in Japan.

The prompt emission of Gamma Ray Bursts (GRBs) is still an outstanding question in the study of these cataclysmic events. Part of what makes GRBs difficult to study is how unique each event seems to be. However, aggregating many GRB observations and analyzing the population allows us to obtain a better understanding of the emission mechanism that produces the observed prompt emission. In this review, we outline some of the most prevalent correlations that have emerged from GRB prompt emission observations and how these correlations are interpreted in relation to GRB physical properties and prompt emission models., Comment: Invited review for: Universe Special Issue "GRBs Phenomenology, Models and Applications: A Beginner Guide" (https://www.mdpi.com/journal/universe/special_issues/GRB). Accepted Version. 33 pages, 8 figures

BACKGROUND Although post-bulbar duodenal ulcers (PBDUs) could become a source of upper gastrointestinal bleeding, the whole picture of the disease is unknown. We compared the characteristic features and treatment outcomes after endoscopic hemostasis between PBDUs and bulbar duodenal ulcers (BDUs). METHODS Data on duodenal ulcers with evidence of endoscopically-active bleeding were extracted from the data that were retrospectively collected from 12 institutes in Japan between 2011 and 2018. Rebleeding and in-hospital mortality were compared between patients with PBDUs and those with BDUs by logistic regression analyses. RESULTS Among 468 consecutive patients with bleeding duodenal ulcers, 96 (20.5%) had endoscopically-confirmed PBDUs. PBDUs were more frequently observed in patients with a poor general condition in comparison to BDUs. The rates of rebleeding and in-hospital mortality in patients with PBDUs were approximately three times higher than those in patients with BDUs (PBDU vs. BDU: 29.2% vs. 10.2% [P